Method for anesthesiology assistance for woman in childbirth suffering with bronchial asthma
FIELD: medicine, gynecology, anesthesiology.
SUBSTANCE: invention concerns to a method for carrying out the anesthesiology assistance for woman in childbirth with accompanying bronchial asthma. Method involves administration of atropine, dimedrol, analgin and clophelin. Method involves additional intravenous administration of transamine for 5-7 min. Transamine is administrated in doses 12-14 and 15-17 mg/kg in woman in childbirth with body mass 75 kg and above and 74 kg and less, respectively. Method provides enhancing quality and safety of anesthesia in this class of woman in childbirth.
EFFECT: improved assistance method.
7 tbl, 4 ex
The invention relates to medicine, in particular to anesthesiology, and applies to the conduct of anesthesia in parturients with concomitant bronchial asthma (BA).
BA is one of the leading causes of morbidity and mortality, with mortality rates and the prevalence continues to grow. The complexity of anesthesia (AP) in the presence of pregnancy skyrocket. Application of pregnant agonists and corticosteroids immediately before childbirth and childbirth is accompanied during AP such adverse effects as arterial hypertension, tachycardia, increased bleeding and blood loss, decrease in the level of analgesia, neuro braking (NRT), the tone of the myometrium, the worsening of uterine-placental blood flow and birth outcomes for the mother and newborn (Valley O.A. et al. Application neopytnyh funds (inderal, clonidine, transamin) for anesthesia spontaneous and prompt delivery high risk. M, 2000, N.M. Fedorovsky et al. Sat. Dokl. The 2nd Congress of mirag. ACC. anest. and reanim. Arkhangelsk. 2003, s-284, Morgan D., Michael M. Clinical anesthesiology. M SPb. 2000, 2003). The vast majority of patients suffer BA polyvalent Allergy, including local anesthetics, and the choice of the AP funds have significantly limited. the label sodium oxybutyrate does not create sufficient analgesia and leads to hypertension. The use of narcotic analgesics is accompanied by inhibition of uterine activity, consciousness, disturbance of clearing, drainage of lung function, worsening hypoxia (Abramenko CENTURIES Opioid inhibition allocation of oxytocin posterior pituitary gland and its value for obstetric anesthesiology. Anest. and reanimate. 1992. № 5-6. - P.56-58, Abramenko CENTURIES of Active management of labour. SPb. 1996., Bales V.L. Anesthesia in obstetrics. In kN. Anesthesiology and critical care medicine (Ed. by Oagree) M, 2002. S-355, N.M. Fedorovsky et al. Sat. Dokl. The 2nd Congress of mirag. ACC. anest. and reanimate. Arkhangelsk. 2003. - S-284).
With the establishment of analgesic and bronhodilatiruyuschego effects clonidine described its application to improve the quality of AP in parturients with BA (Bales V.L. Anesthesia in obstetrics. In kN. Anesthesiology and critical care medicine (Ed. by Oagree). M., 1998. S-371). However, the use of clonidine as a single drug does not provide effective analgesia, gas exchange, NRT and other components of a full AP.
The closest analogue can be considered the way up, including the application of atropine, Dimedrol, dipyrone and clonidine in a dose of 1.5 mcg/kg (Valley O.A. et al. Application neopytnyh funds (inderal, clonidine, transamin) for anesthesia spontaneous and rapid delivery of high degree p is ska. M, 2000). The disadvantages of the method, despite the additional application Dimedrol, dipyrone are saving pain, shortness of breath, feelings of shortness of breath, anxiety, fatigue, impaired expectoration, delayed sputum in the lungs, low peak exhalation rate (PSV) and forced expiratory volume in first second (FEV 1 second).
The purpose of this proposal is to improve the quality and safety of AP in parturients with BA due to the increase in the degree of analgesia, NRT, inhibition of anaphylactic reactions, inflammatory process, improving speed performance breathing, drainage of lung function, labor, state intrauterine fetal well-being of mothers, improve birth outcomes for mothers and newborn. Improving the quality and safety of AP may also be due to the persistence of consciousness mothers, active, adequate maternal behavior. Transamin has a wide range of effects on the body: brake kirino and plasminogen (reduced emissions aggressive biologically active substances), anti-allergic, anti-inflammatory, haemostatic effect. Has analgesic effect of transamine in the experiment on animals, the potentiation of the analgesic effect of funds General anesthesia in clinical practice is Kyo Valley O.A. et al. 2000). The possibility of potentiation by transamine analgesic effect of dipyrone and clonidine is not described. We have suggested the possibility of potentiation by transamine analgesic effect of dipyrone, analgesic and bronhodilatiruyuschego effects of clonidine and consequently improve the quality and safety of AP with additional application of transamin in parturients with BA. The use of transamin in combination with dipyrone, hydrochloride, atropine, Dimedrol for the AP, including women with BA, not described.
To solve the problem with AP in parturients with BA applied atropine, diphenhydramine, analgin, clonidine and additionally transamin, which was administered for 5-7 min at a dose of 12-14 mg/kg body weight of 75 kg and above, 15-17 mg/kg body weight of 74 kg and less. Transamin as a component of AP used in 37 women aged 17 to 39 years. Severe persistent BA had 4 mothers, moderate - 21, a light - 7, intermittently, form - 5. All mothers had other comorbidities: heart disease (mitral and aortic valve, tetralogy of Fallot with 0-1 NC Art.) - 18, disorders of heart rhythm 5 - pyelonephritis - 3, disorders of lipid metabolism - 7, polyvalent Allergy - 21, nephropathy I-III century - 16 women. Nulliparous mothers was 24, multiparous - 13. The control group consisted of 29 women with similar CNAME the pregnancy, forms of ad and other concomitant diseases. Age ranged from 18 to 37 years. Severe persistent BA had 3 mothers, moderate - 19, easy - 5, intermittently - 2 mothers. Valvular heart disease (mitral and aortic valves with 0-1 NC senior) had 13 women, heart rhythm disturbances - 4, pyelonephritis - 2, fat metabolism disorders - 5, polyvalent Allergy - 20, nephropathy I-III century in 11 women. Nulliparous was 19, multiparous - 10.
Studies have allowed us to develop a new way of AP in parturients with BA and to establish that the additional application of transamine dose of 12-14 mg/kg M.L. 75 kg or more, 15-17 mg/kg MT kg or less increases the efficiency and safety of anesthesia, improves respiration, gas exchange, course and outcome of delivery, reduces the frequency of operative delivery. However, depending on M.L. dose transamin was 1020-1200 mg. In the table. 1 shows that the task is achieved using transamin dose 12-17 mg/kg: there is a statistically significant (* p<0.05) increase in tactile and pain thresholds, threshold endurance, assessment of pain on a scale Tin, Bevsnair, PSV, FEV 1, index tiffe. At the dose of 8-11 mg/kg (8-9 mg/kg M.L. 75 kg or more, 10-11 mg/kg M.L. aged 60-74 kg) a significant increase in analgesic activity, improve breathing not about the notes (p> 0,05). At the dose of 18-22 mg/kg (18-20 mg/kg M.L. 75 kg or more, 21-22 mg/kg M.L. aged 60-74 kg), in comparison with the dose 12-17 mg/kg statistically significant increasing rate of analgesia, not breathing is observed, but develops bradycardia (decrease rhythm 20-25%), blood pressure decrease (10-15%), marked dizziness, nausea. The introduction of transamine 5-7 min substantiated by the data presented in table. 2. With the introduction of transamine dose 12-17 mg/kg over 3-4 min develops bradycardia (decrease by 20-25%, the reduction of blood pressure by 10-15%), observed phenomena discomfort (nausea, dizziness). When the speed of the introduction of transamine 8-10 min no significant increase threshold of pain sensitivity (p<0,05).
Thus, for effective and safe up in parturients with BA transamin should be entered in the dose 12-17 mg/kg for 5-7 minutes
The method is as follows. Obstetrician sets the period of confinement, the degree of opening of the fallopian throat. The anesthesiologist examines the parameters of respiration, gas exchange, circulation, sets of indications, contraindications to the AP depending on the condition of the pregnant woman. At the opening of the fallopian throat 3-5 cm, active labor activity, the presence of pain and other indications for AP, the absence of indicators of decompensation of breathing, gas exchange, circulation, maintain through natural childbirth generic p is ti. AP carried out according to the scheme, including the application of atropine (0.01 to 0.012 mg/kg), demerol (0.3 to 0.35 mg/kg), dipyrone (30-35 mg/kg), clonidine (1.5 mcg/kg). At the same time within 5-7 min/enter transamin dose of 12-14 mg/kg M.L. 75 kg and above, 15-17 mg/kg M.L. aged 60-74 kg Comes smooth, adequate analgesia, lighter mood, calm behavior, maintaining an appropriate orientation, physical activity and opportunities for effective expectoration. The degree of analgesia figures reflect thresholds of pain sensitivity. On the positive effect of the claimed method the data threshold of pain (in volts, V) sensitivity (table 3), speed indicators of respiration (table. 4), hemodynamics, gas exchange (table 5), the average duration of the genera (table 6), of course the early postnatal period (table 7). Assessment of children born after application of the developed AP, higher Apgar scale as the pregnancy 35-37 weeks and at term 38-40 weeks, as in nulliparous and multiparous: the average score when the time 35-37 weeks of 7.8 points, when the term 38-40 weeks - 8.1 score in the control group, respectively 7.4 and 7.7 points.
Example 1. The mother A. 37 years, perforada (s/R 2743), M.L. 89 kg, with the term 38-39 weeks. ber. with severe persistent BA, MT. pyelonephritis, polyvalent Allergy samostojatelnosti in childbirth. At the opening of the fallopian shed 3-4 cm active labor activity, painful contractions, restless behavior. Deterioration of the General state is not observed. It was decided to continue the management of delivery through the birth canal. Held up, including in the application of atropine (0.8 mg), demerol (20 mg), dipyrone (2000 mg), clonidine (135 μg). Transamin put into/in the dose of 12 mg/kg (1068 mg) for 5 minutes came effective pain relief, calm behavior with preservation of effective labor. After 7 hours up at the opening of the fallopian throat 6-7 cm due to the slow pace of disclosure uterine throat to 0.6 cm/h started redistillate the prostenona at a concentration of 1.25-0.5 μg/min disclosure uterine throat increased to 0.9 cm/h, a boy was born M.L. 3370 g, length 50 cm with estimation on Apgar scale 8-8 points. The first stage of labor was 8 h 05 min, a period of 39 minutes, the total duration of 8 h 52 min Pain threshold after 1 h and 2.5 h made 58.6 V and 43.1 V (exceeding the initial level on the 135,3% 73,1%), endurance threshold, respectively 53,9 V and 50.2 V (exceeding the baseline by 50.5% to 38.8%. Throughout the birth of FEV 1 and PSV increased by 16.1%-13,4% and 21.8-19,2%. The state of health was satisfactory. After birth due to the original weight of the state was transferred to the intensive observations in the chamber it. During the first day of th the generic period took a single inhalation of salmeterol on the list. After 1 day transferred to the postpartum unit, where he received the planned treatment used during pregnancy. In the dynamics of improving the status and well-being. Discharged on day 7 with improving the status and well-being.
Example 2. The mother P. 26 years (and/R 2934), M.L. 75 kg, with a gestation 39 weeks, perforada with persistent form BA moderate, insufficiency of aortic valve (NC 0 tbsp.), polyvalent Allergy, including local anesthetics, antibiotics, in the active phase of labor, when the opening of the uterine orifice 4 see Shows labor pain relief. Held up, including in the application of atropine (0.8 mg), demerol (25 mg), dipyrone (2250 mg), clonidine (112,5 mg). Transamin put into/in the dose of 14 mg/kg (1050 mg) for 7 minutes came effective pain relief, calm behavior with preservation of effective labor. The rate of disclosure uterine throat was 1 cm/hour, the boy was Born M.L. 3120 g assessment 8-8 points. During the first days took a single inhalation of salmeterol on the list. For p/R period without complications.
Example 3. Pregnant With. 27 years, perforada (s/R 2941), M.L. 74 kg, with a term of ber. 39 weeks. with medium-severe persistent BA, mitral valve insufficiency (0-1 NC Art.) sinus tachycardia, polyvalent Allergy independently came into birth. When about is the opening of the fallopian throat 3 cm active labor activity, sharply painful contractions, restless behavior. Planned delivery through the birth canal. Shown and held up with the use of atropine (0.7 mg), demerol (20 mg), dipyrone (2000 mg), hydrochloride (105 mg) and transamine. Transamin introduced at a dose of 15 mg/kg (1110 mg) in/in for 5 minutes came effective pain relief, calm behavior with preservation of effective labor. The first stage of labor was 7 h 55 min, II - 37 minutes, the total duration of 8 h 42 min was Born a girl M.L. 3630 g, length 49 cm estimate 8-9. Pain threshold after 1 h and 2.5 h, respectively 57,3 V and 39.9 V (exceeding the initial level on the 122,1% and 54.6% at p<0.05), and the endurance threshold, respectively 57,2 V and 51.3 V (excess respectively 58% and 41.8% at p<0,05). Throughout the birth of FEV 1 and PSV increased by 18.9-20.6 per cent and 11.8 to 13.3% (p<0,05). In childbirth health was satisfactory, shortness of breath was not felt. After childbirth transferred to the postpartum unit. During the first days after birth, shortness of breath, asthma was not observed. Discharged on the 6th day.
Example 4. Pregnant With. 31, (s/R 3341), M.L. 60 kg, with a term of ber. 38-39 weeks., powerseraya with medium-severe persistent BA, mitral valve insufficiency NC 0-1 article, polyvalent Allergy, with the opening of the fallopian shed 3-4 cm, sharply painful contractions, restless behavior is Denia, shortness of breath, odalevaut mucous sputum in moderation, in the lungs moderate amount of dry and wheezing, BP 130/90, heart rate 88 minutes Shown pharmacological analgesia in labor. Shown and held up with the use of atropine (0.75 mg), demerol (20 mg), dipyrone (2100 mg), clonidine (90 mcg), transamin dose of 17 mg/kg (1020 mg) for 7 minutes came effective pain relief, calm behavior with preservation of effective labor (the amplitude of contractions 90-110 mm RT. Art. with a frequency of 4/10 minutes) and the rate of disclosure of the uterine orifice (1.2 cm/hour). She was born full-term girl M.L. 3230 g assessment 8-8 points on the Apgar scale. For p/R period without complications.
Thus, studies carried out in 37 women were allowed to establish that effective, safe AP with favorable birth outcomes in pregnant women with asthma can be achieved using atropine (0.01 to 0.012 mg/kg), demerol (0.3 to 0.35 mg/kg), dipyrone (30-35 mg/kg), clonidine (1.5 mcg/kg) and the use of additional transamine for 5-7 min at a dose of 12-14 mg/kg in parturients with M.L. 75 kg and higher dose of 15-17 mg/kg in parturients with M.L. 74 kg and less. However, depending on M.L., dose transamin was 1020-1200 mg.
|Substantiation of the optimal dose of transamine mg/kg introduction within 5 - minutes|
|Indicators||8-11 (8-9 mg/kg M.L. 75 kg and above, 10-11 mg/kg M.L. 74 kg and less)||12-17(12-14 mg/kg M.L. 75 kg and above, 15-17 mg/kg M.L. 74 kg or less||18-22 (18-20 mg/kg M.L. 75 kg and above, 21-22 mg/kg M.L. 74 kg and less)|
|PSV, l/s||increase <10%||an increase of 15-20%*||an increase of 15-20% *|
|FEV 1C||increase<10%||the increase of 19-22%*||the increase of 19-21% *|
|index tiffe||increase <5%||an increase of 9.5 to 9.9%*||An increase of 9.6 and 9.8%*|
|Tactile threshold||an increase of 22%||an increase of 210%*||an increase of 205%*|
|the threshold of pain||an increase of 28%||an increase of 37.9%*||increased by 41.0%*|
|the endurance threshold||an increase of 19%||the increase of 35.8%*||the increase of 37.7%*|
|assessment of analgesia in points||5,1±0,3||8,3±0,5||8,4±0,9|
|dynamics of heart rate||no||no||decrease by 15-25%*|
|dynamics of blood pressure Syst.||no||no||reduced the E. by 10-15%*|
|the phenomenon of discomfort||No||no||nausea, dizziness|
|Note: *p<0.05 compared with the data in the first column|
|The justification for the introduction of transamine dose 12-17 mg/kg|
|indicators||the introduction of transamine min|
|Ceramica HR||decrease by 20-25%*||no speakers||no speakers|
|Ceramica HELL Syst.||Decrease by 10 -15%||no speakers||no speakers|
|the phenomenon of discomfort||nausea, dizziness||no||No|
|dynamics pain threshold||the increase of 9.8%||an increase of 37.9%*||the increase of 41.1%, P2-3>0,05*|
|the dynamics of the threshold endurance||an increase of 10.5%||the increase of 38.3%*||the increase of 38.3%*|
|Dynamics of thresholds is alevai sensitivity in V when the AP claimed (C) and method prototype (p)|
|the source data||5-7 min||8 -10 min||30 min||1 hour||2.5-3 hours|
|the threshold of pain||p||25,4±2,7||28,2±2,6||29,6±3,1||29,0±2,2||30,8±1,9*||27,4±1,8|
|the endurance threshold||p||36,1±3,4||40,4±4,2||41,5±3,6||42,2±3,8||42,7±2,9*||37,4±4,1|
|Dynamics of indicators of forced expirogram|
|indicators||The source data||30 min||2.5-3 hours||After giving birth|
|indec is tiffe||P||52,9±3,4||54,8±3,5||54,9±3,3||54,1±2,9|
|Hemodynamics, gas exchange at the stage of research|
|indicators||the source data||30 min||2.5-3 hours||After giving birth|
|HELL Syst.||p||130,4±3,4||RUB 127.3±4,4||126,5±2,9||uniforms, 127.6±4,6|
|HR||p||95,9±3,7||90,4 4,2||to 91.6±4,7||89,7±4,1|
|The average duration of periods of birth|
|1 period||2nd period||3 period||The total duration|
|The AP method prototype|
|pervertie||10 h 24 min||49 min||12 min||11 h 25 min|
|the who already had children||8 h 37 min||36 min||10 min||9 h 23 min|
|The AP claimed method|
|pervertie||8 h 13 min*||43 min*||9 min||9 h 05 min*|
|the who already had children||6 h 22 min*||31 min*||8 min||7 h 01 min*|
|Note: * p<0,05 in comparison with the method-prototype -|
|Evaluation of the positive effect of AP|
|C (n=37)||p (n=29)|
|1.||the rate of disclosure of the uterine orifice (cm/h)||pervertie||0,8*||0,67|
|the who already had children||1,0*||0,79|
|2.||normal delivery path||97,3%*||82.30 level%|
|4.||clinical characteristics of the flow of the postnatal period in 1 day (frequency in %)||sleep disorders||5,4*||27,6|
|coughing, shortness of breath||13,5*||27,6|
|preservation of wheezing in the lungs||13,5*||31|
|the need for AM||18,9*||of 37.9|
|need to it||8,1*||27,6|
|Note: AM - adrenoceptor agonist, it intensive therapy|
The method of anesthesia in childbirth in women with concomitant asthma, including the use of atropine, Dimedrol, analgin, clonidine, characterized in that it further intravenously within 5-7 minutes of entering transamin dose of 12-14 mg/kg in pregnant women with a body weight of 75 kg and higher dose of 15-17 mg/kg in pregnant women with a body weight of 74 kg and less.
FIELD: restorative medicine, pediatrics.
SUBSTANCE: the method deals with inhalations conducted with Hanks' solution at dispersity of particles being 0.8-2 mcm, expenditure of preparation being 1 ml/3.5 min Inhalation time corresponds to 8-10 min, daily. One should perform about 10-12 procedures per a course at the background of complex therapy including the adequate mode of motor activity, curative physical culture, carbonic acid baths. The method enables to improve sputum withdrawal and, correspondingly, bronchial permeability and the values for the function of external respiration.
EFFECT: more prolonged remission.
1 ex, 2 tbl
FIELD: organic chemistry, medicine.
SUBSTANCE: invention relates to new 2-aminopyridine derivatives of formula I , wherein R1 is cyano, carboxyl or carbamoyl; R2 is hydrogen, hydroxyl, C1-C6-alkoxy or phenyl; R3 and R4 are aromatic hydrocarbon such as phenyl or naphthyl, 5-14-membered 5-14-membered optionally substituted aromatic group, excepted cases, when (1) R1 is cyano, R2 is hydrogen, and R3 and R4 are simultaneously phenyl;(2) R1 is cyano, R2 is hydrogen, R3 is 4-pyridyl, and R4 is 1-pyridyl; (3) R1 is cyano, R2 is 4-methylphenyl, and R3 and R4 are simultaneously phenyl;(4) R1 is cyano, R2, R3 and R4 are simultaneously phenyl, or salts thereof. Derivatives of present invention have adenosine receptor antagonist activity and are useful in medicine for treatment of irritable bowel syndrome, constipation, and defecation stimulation.
EFFECT: 2-aminopyridine derivatives as adenosine receptor antagonists useful in medicine.
34 cl, 2 tbl, 179 ex
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: organic chemistry, biochemistry, medicine, pharmacy.
SUBSTANCE: invention relates to new aminobenzophenones of the formula (I):
or their pharmaceutically acceptable salts. These compounds elicit properties of inhibitors of cytokines secretion, in particular, 1β-interleukin (IL-1β) and tumor necrosis α-factor (TNF-α) and to secretion of polymorphonuclear superoxide that are useful for treatment of inflammatory diseases, for example, skin diseases, such as psoriasis, atopic dermatitis. In the formula (I) R1 is taken among the group consisting of halogen atom, hydroxy-, mercapto-group, trifluoromethyl, amino-group, (C1-C3)-alkyl, (C2-C3)-olefinic group, (C1-C3)-alkoxy-, (C1-C3)-alkylthio-, (C1-C6)-alkylamino-group, (C1-C3)-alkoxycarbonyl, cyano-group, carbamoyl, phenyl or nitro-group under condition that when R1 means a single substitute then it at ortho-position, and when R1 means more one substitute then at least one substitute of R1 is at ortho-position; R2 means one substitute at ortho-position being indicated substitute is taken among the group consisting of (C1-C3)-alkyl, (C1-C3)-alkoxy-group; R3 means hydrogen, halogen atom, hydroxy-, mercapto-group, trifluoromethyl, amino-group, (C1-C3)-alkyl, (C2-C3)-olefinic group, (C1-C3)-alkoxy-, (C1-C3)-alkylthio-, (C1-C6)-alkylamino-group, (C1-C3)-alkoxycarbonyl, phenyl, cyano-, carboxy-group or carbamoyl; R4 means hydrogen atom or (C1-C3)-alkyl; Q means a bond or -SO2-; Y means (C1-C15)-alkyl, (C3-C10)-carbocyclic group or phenyl being each of them can be substituted optionally with one or some similar or different substitutes designated by the formula R5; R5 means halogen atom, (C1-C4)-alkyl, amino-, (C1-C3)-alkoxy-group, (C1-C3)-alkoxycarbonyl or -COOH; X means oxygen or sulfur atom. Also, invention relates to a pharmaceutical composition and to a method for treatment and/or prophylaxis of inflammatory diseases.
EFFECT: valuable medicinal properties of compounds and composition.
9 cl, 2 sch, 2 tbl, 29 ex
FIELD: organic chemistry, medicine, pharmacy.
SUBSTANCE: invention relates to new derivatives of indolylpiperidine of the formula (I): wherein A1 means (C1-C7)-alkylene, (C1-C7)-alkyleneoxy-, (C1-C7)-alkylenethio-, (C1-C7)-alkanoyl, hydroxy-(C1-C7)-alkylene; A2 means a single bond, (C1-C7)-alkylene, (C2-C5)-alkenylene; W means a single bond, phenylene, furanylene that is unsubstituted or substituted with one or more halogen atoms, (C1-C7)-alkoxy- and/or alkyl groups; R1 means hydrogen atom (H), (C1-C7)-alkyl, (C2-C7)-alkenyl, (C2-C7)-alkynyl, (C2-C5)-alkoxyalkyl, (C3-C7)-alkenyloxyalkyl, (C3-C7)-alkynyloxyalkyl, (C3-C7)-alkoxyalkoxyalkyl, phenyl-(C1-C7)-alkyl wherein phenyl is unsubstituted or substituted with one or more halogen atoms, (C1-C7)-alkyl, (C1-C7)-alkoxy- or arylalkoxy- (preferably with phenylalkoxy-) groups, or means (C3-C10)-cycloalkyl-(C1-C7)-alkyl wherein cycloalkyl is unsubstituted or substituted with one or more halogen atoms, (C1-C7)-alkyl, (C1-C7)-alkoxy-groups; R2 means hydrogen atom (H), halogen atom, (C1-C7)-alkyl, (C1-C7)-alkoxy-; R3 means carboxyl, tetrazolyl, and to their pharmaceutically acceptable salts. Compounds of the formula (I) elicit antihistaminic and anti-allergic activity that allows their using in composition used for treatment of allergic diseases including bronchial asthma, rhinitis, conjunctivitis, dermatitis and nettle rash. Also, invention describes methods for preparing compounds of the formula (I).
EFFECT: valuable medicinal properties of compounds.
15 cl, 2 sch, 3 tbl, 162 ex
where R1and R3designate one or more identical or different substituents selected from the group consisting of halogen, (C1-C3)-alkyl, (C1-C3)-alkoxy; provided that, if R1denotes one Deputy, he is in the ortho-position, and if R1refers to several substituents, at least one substituent R1located in the ortho-position; and R2denotes one substituent in the ortho-position, and this Deputy is selected from the group consisting of halogen, (C1-C3)-alkoxy; and R3can additionally denote hydrogen; R4represents hydrogen; X represents oxygen; Q represents -(CO)- or a bond; Y represents (C5-C15)alkyl, (C2-C15)olefinic group; and any of these groups may be optionally substituted by one or more identical or different substituents selected from the group consisting of substituents of formula R5defined below, except that when Q represents a bond, then Y appears lcil, substituted by one or more substituents selected from the group R5; or a group of formula - (Z-O)n- Z, where Z is a (C1-C3)alkyl, n is an integer >1, and the number of atoms in a continuous linear sequence of atoms in the group Y does not exceed 15; R5denotes halogen, hydroxy, amino, (C1-C6)-alkylamino, (C1-C3)alkoxycarbonyl, -COOH, -CONHR' or-COONR'R' R' means (C1-C3)alkyl; or its pharmaceutically acceptable salt
which have the properties of receptor antagonists neirokinina-1(NK-1)
where R is hydrogen, (C1-C6)alkyl, and the alkyl group optionally contains one phenyl substituent, which, in turn, optionally contains at least one Deputy, selected from the group comprising halogen, methoxy, ethoxy, (C1-C6)alkyl; R1means phenyl cycle containing at least one Deputy, selected from the group comprising (C1-C6)alkoxy, hydroxy, nitro, (C1-C6)alkoxycarbonyl one or fluorine, or R1represents the balance of the pyridine of the formula II
where the carbon atoms 2, 3 and 4 of the remaining pyridine optionally have the same or different substituents R5and R6and R5and R6denote (C1-C6)alkyl or halogen, or R1presents arylamination-2-methylprop-1-ilen group, or R and R1together with the nitrogen atom to which IGN="ABSMIDDLE">
where R7denotes phenyl or pyridinyl; R2means (C1-C6)alkyl, which optionally contains a phenyl residue, which, in turn, optionally substituted with halogen, methoxy group or ethoxypropane, or related to R2(C1-C6)alkyl group optionally substituted 2-, 3 - or 4-pyridinium residue; R3and R4are the same or different substituents and represent hydrogen, hydroxy, (C1-C6)alkoxy, (C1-C3)alkoxycarbonyl or (C1-C3)alkoxycarbonyl(C1-C3)alkyl, or R3is cyclopentanecarbonitrile; Z denotes Oh, and alkyl, alkoxy or alkylamino mean as an unbranched group, such as methyl, ethyl, n-propyl, n-butyl, n-hexyl and branched alkyl groups such as isopropyl or tert-butylene group; halogen means fluorine, chlorine, bromine or iodine and alkoxygroup means methoxy, propoxy, butoxy, isopropoxy, isobutoxy or phenoxypropan, and their pharmaceutically acceptable salts with acids
FIELD: pharmaceutical industry.
SUBSTANCE: invention is characterized by that system contains underlayer, therapeutical substance storage layer, and agent attaching the system on the person's skin and allowing access of nicotine to skin. System is transparent (opacity factor below 48.6%).
EFFECT: facilitated transcutaneous transport of nicotine.
8 cl, 1 tbl
FIELD: medicine, oncology.
SUBSTANCE: the present innovation deals with treating patients with uterine cervix cancer with relapses in parametral fiber and in case of no possibility for radical operative interference and effect of previous radiation therapy. During the 1st d of therapy one should intravenously inject 30 mg platidiam incubated for 1 h at 37 C with 150 ml autoblood, during the next 3 d comes external irradiation per 2.6 G-r. During the 5th d of therapy one should introduce the following composition into presacral space: 60 ml 0.5%-novocaine solution, 1 ml hydrocortisone suspension, 2 ml 50%-analgin solution, 1 ml 0.01%-vitamin B12 solution, 1.6 g gentamycine, 800 mg cyclophosphan, 10 mg metothrexate. These curative impacts should be repeated at mentioned sequence four times. The method enables to decrease radiation loading and toxic manifestations of anti-tumor therapy at achieving increased percent of tumor regression.
EFFECT: higher efficiency of therapy.