Method of treating chronic opisthorchiasis in patients with rosacea

FIELD: medicine.

SUBSTANCE: praziquantel is administered in a single dose of 20 mc/kg for the first day of treatment in the daytime, and withdrawn; on the following day, the conducted therapy is added with introducing Gelmicide, a biologically active food supplement, in a dose of 2 capsules with meals for 21 days; the course is repeated 10 days later in a dose of 2 capsules 2 times a day with meals for 14 days.

EFFECT: reducing the rate of complications and increasing the high dishelminthisation efficacy.

1 ex

 

The invention relates to medicine, dermatology and can be used for the treatment of chronic opisthorchiasis in patients with rosacea.

The closest to the proposed is a method for the treatment of patients with combined pathology with praziquantel, which is prescribed in the usual dose 60 mg/kg of body weight over night scheme in 3 divided doses every 4 hours [Beloborodova E. I.; N. To. Bychkova Chronic opisthorchiasis. A modern view of the treatment"]. The effectiveness of deworming was 100%. However, for patients with rosacea this treatment causes a complication process of the skin in the form of appearance of new lesions, especially in the first days after deworming, accompanied by itching, which required additional detoxification gemodez within 5 days.

A new technical result - the reduction of complications in high-efficiency deworming.

To solve this problem the method of treatment of chronic opisthorchiasis in patients with rosacea, by the introduction of praziquantel in the period of the stationary stage of the process, and praziquantel administered at a dose of 20 mg/kg of body weight once in the afternoon, the following day, administered biologically active food Supplement "Helmeted" 2 capsules 2 times daily before meals for 21 days, after 10 days administered biologically active dobak� to food "Helmeted" to 2 tablet 2 times daily before meals for 14 days.

The method is as follows:

The patient undergoes a physical examination (General blood test, General urine analysis, biochemical analysis of blood), liver ultrasound, duodenal intubation.

While in the duodenal bile eggs opistorhisov patient conduct deworming on an outpatient basis.

Before treatment to relieve the acute patient with rosacea outpatient receives the following treatment: detoxification therapy (a solution of sodium thiosulfate 30% 10 ml/No. 10), antihistamines (claritin 1 tablet 1 time a day for 10 days), vitamin (Ascorbic acid 5% by 1.0 ml of 1 times a day for 10 days, Thiamine bromide 6% in 1.0 ml of 1 times a day for 10 days), sedatives (Afobazol 1 tablet 3 times a day for 10 days), antiparasitic treatment (metronidazole 0.25 mg 3 times a day for 21 days). Externally: gel Rozex.

Further, in the outpatient setting, the patient receives praziquantel in the daytime at a dose of 20 mg/kg of body weight once (after lunch). On the following day appointed for the reception of biologically active additives to food "Helmeted" 2 capsules 2 times daily before meals for 21 days, after 10 days, appoint a reception of biologically active additives to food "Helmeted" 2 capsules 2 times daily before meals for 14 days. Externally: gel Rozex.

Dietary Supplement � food "Helmeted" is a phytocomplex, consisting of herb mugwort, Cassia angustifolia, the fruit of cumin and dill and buds of the clove tree, processed by special technology.

Indications for use: Giardia, opisthorchiasis, ascariasis, chlamydia, chronic cholecystitis, cholangitis, hepatitis, biliary dyskinesia (JIT), atonic colitis, skin diseases (urticaria, skin Allergy, psoriasis) and goiter.

Method of application: adults and children over 12 years: 2 capsules during the day and 2 capsules in the evening with a glass of water (150-200 ml.). Course duration is 20 days. For preventive purpose to repeat the course in 2-3 months. For the purpose of cleansing the body of waste products of parasites in the process of taking the drug it is desirable to periodically clean the intestines via laxatives or enemas, as well as tyubazh liver after completing the course.

Contraindications: do not consume during pregnancy and when you are hypersensitive to herbs that are part of Germicide".

Release form: Hard capsule p/e of the Bank - 50 hard capsules (0.4 g).

Manufacturer: LLC "ROS", NOVOSIBIRSK, Russia

THE 9141-001-37431838-2000

The dose of praziquantel reduced in 3 times against the commonly used by combining with a drug of plant origin. Dose and mode of application of praziquantel chosen based on�upon clinical observations. Treatment of opisthorchiasis spend in the stationary phase of psoriasis, so as not to cause exacerbation of the skin process. Praziquantel is administered in the daytime and in the outpatient setting for the patient's comfort, without compromising the quality of life, gives a high economic impact because they do not need to occupy a bed in hospital. The treatment can be carried out without interrupting the normal life of the patient. After the course of treatment carried out sensing control, according to which determined the effectiveness of deworming. The course "Helmeted" (21 days) is necessary and sufficient for treatment of this category of patients. When conducting deworming during the period of less than 21 days reduced the effectiveness of deworming and the lengthening of the course of treatment more than 21 days leads to additional side effects, undesirable for patients with rosacea. In the daytime the drug is given for the convenience of care for patients, in 2 divided doses to increase the concentration of the drug in order to more effectively carry out deworming. Dose 2 capsules 2 times a day for 21 days is necessary and sufficient for an effective deworming. Additionally in 10 days "Helmeted" is assigned to fix the achieved results. Dosage 2 capsules 2 times a day for 14 �it been selected on the basis of clinical observations.

Example

Patient Raboteau T. O., 24 years old, went to a Regional hospital in the city of Tomsk with a diagnosis of Chronic opisthorchiasis. Chronic acalculous cholecystitis in a stage of moderate exacerbation. Biliary dyskinesia hypokinetic type. Related diagnosis: Rosacea papulopustulosa form, II subtype.

Upon receipt complained of heaviness in the right hypochondrium, a constant bitter taste in the mouth, nausea, decreased appetite, anxiety.

From history revealed that the patient is suffering from rosacea for about 3 years. Last aggravation appeared 1 month ago. Associates with exposure to the sun. The following treatment was performed: detoxification therapy (a solution of sodium thiosulfate 30% 10 ml/No. 10), antihistamines (claritin 1 tablet 1 time a day for 10 days), vitamin therapy (Askorbinova acid 5% by 1.0 ml of 1 times a day for 10 days, Thiamine bromide 6% in 1.0 ml of 1 times a day for 10 days), sedatives (Afobazol 1 tablet 3 times a day for 10 days). Externally: Rozex.

The last 2 years began to disturb the heaviness in the right hypochondrium, periodic pain in this area, intolerance to fatty foods, nausea, anxiety.

Out-patient physical examination, ultrasound, duodenal intubation.

In General, the analysis of blood eosinophilia of up to 7%. In General, the analysis of mo�and - no pathological changes. Indicators of biochemical studies of blood in the normal range.

According to chromatic duodenal revealed dykinesia gallbladder hypokinetic type: gallbladder bile expired in a large volume of 80 ml (at a rate of 60 ml), time to expiration was extended to 35 minutes (at a rate of up to 21 min). Revealed hypotension sphincter of Oddi.

Microscopy bile found eggs opistorhisov (4-5 in field of view).

According to the ultrasound of the gallbladder volume was increased and amounted to 70 cm3(at a rate of 40-60 cm3).

Objective: asthenic physique. On the face, centrofacial (forehead, nose, cheeks, chin), which is the erythema with indistinct borders. On the background of erythema are small pink papules, elastic consistency. Is peeling in the nasolabial folds. On the skin of nasolabial folds are visible isolated pustules with pus.

Tongue coated yellow tinge at the base. The lungs and heart without pathology. The abdomen is soft, palpation in the right hypochondrium moderately painful. Positive symptoms of Kerala and Murphy.

For the treatment of chronic opisthorchiasis and hypotension gallbladder was appointed method of treatment according to the invention: after removal of exacerbation of rosacea was prescribed praziquantel at a dose of 20 mg/kg, � the following day, "Helmeted" 2 capsule 2 times daily with meals for 21 days.

Treatment the patient underwent right. After deworming with praziquantel side effects were noted. The appearance of lesions on the skin, itching was observed. On the 10th day of application "Helmeted" gone feeling of heaviness in the right hypochondrium, bitter taste in the mouth, by the end of treatment there was a sense of nausea and his appetite. After treatment of chronic opisthorchiasis control were conducted duodenal intubation, ultrasound. According to fractional duodenal gallbladder bile volume and the time to expiration is normalized to 65 ml (at a rate of 60 ml) and 24 min (at a rate of 21 min). When bile microscopy revealed individual eggs opistorhisov. According to the ultrasound of the gallbladder volume was 60 cm3that is the norm. During the week after treatment was achieved regression of the manifestations of rosacea. 10 days after the end of treatment was prescribed a course of drug treatment "Helmeted" 2 capsules 2 times a day for 14 days. A month after the treatment, the patient noted improvement of health, the complaints of the digestive tract did not show disappeared nausea, appetite returned to normal. Repeated duodenal intubation. Microscopic examination of eggs opistorhisov been identified. Skin process was in stage regression.

This method treated 7 sick� rosacea in combination with chronic opisthorchosis. Side effects of the skin, gastrointestinal tract in the treatment of this method was observed. The effectiveness of deworming was 83.3%.

Thus, the proposed method allows to treat patients with comorbidity with optimally matched combination of highly effective antihelminthic drug with biologically active additive to food "Helmeted", derived from plant materials. This gave the opportunity to three times lower dose highly effective, but highly toxic praziquantel and more gently with a sufficiently high efficiency (83,3%) to treat patients with rosacea.

A method for the treatment of chronic opisthorchiasis in patients with rosacea, consisting in the carrying out deworming with praziquantel during remitting exacerbation, characterized in that on the first day of treatment administered praziquantel at a dose of 20 mg/kg once in the daytime, and on the following day, appoint a biologically active food Supplement “Helmeted” 2 capsules 2 times daily with food for 21 days, after 10 days, appoint a biologically active food Supplement “Helmeted” 2 capsule 2 times daily with meals for 14 days.



 

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16 cl, 4 dwg, 2 tbl, 3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to field of organic chemistry, namely to novel heterocyclic compounds of formula (1) and/or to their pharmaceutically acceptable salts, where A1 represents CH; A4and A5 independently represent CR2 or N; A2 and A3 together with ring B represent 5-membered heteroaryl or heterocycle, with said 5-membered heteroaryl or heterocycle being selected from where t represents 1 or 2; and R3 is independently selected from H, C1-C6 alkyl, C6-aryl, C3-C6-membered cycloalkyl, C(O)NRcRd, -ORb, heteroaryl, representing pyridine, and heterocycle, representing piperidine and tetrahydropyran; and each of said alkyl, aryl, cycloalkyl, heteroaryl and heterocycle can be substituted with one group, independently selected from C1-C6 alkyl, possibly substituted with one substituent, selected from -CONMe2, C3-membered cycloalkyl, -CN, -OMe, -pyridine, tetrahydropyran, -CO-morpholine, -CO-pyrrolidine, (3-methyl)oxetane; -OH; -C(O)Ra; -CN; -C(O)NRcRd; -NRcRd; -ORb; -S(O)nRe; halogen, and substituted with one group -COMe heterocycle, representing piperidine, on condition that when A4 represents CR2, A2 and A3 together with ring B are selected from structure (3), (5) or (6); represents single bond or double bond; R1 represents heteroaryl, representing 6-membered or 9-10-membered aromatic mono- or bicyclic ring, containing 1-3 heteroatoms, selected from nitrogen, oxygen and sulphur; possibly substituted with one or two groups, independently selected from C1alkyl, C2alkinyl, -NRcRd, -NRcS(O)nRe, -ORb, halogen, halogenalkyl; R2 is independently selected from H; each Ra, Rb, Rc, Rd, and Re is independently selected from H; C1-C4alkyl, possibly substituted with one substituent, selected from -OH, -OMe, -CN, -NH2, -NMe2, C3-cycloalkyl; C2-C3alkenyl; C3alkinyl; C6aryl, possibly substituted with one or more substituents, selected from fluorine or methyl group; C3-membered cycloalkyl, possibly substituted with one substituent, selected from -OH and -CN; halogenalkyl; heteroaryl, representing pyridine; and substituted with one methyl group heterocycle, representing piperidine, or Rc and Rd together with atom (atoms) which they are bound to form 5-6-membered heterocyclic ring, representing pyrrolidine or morpholine; and in each case n is independently equal 2. Invention also relates to particular compounds, pharmaceutical composition, based on claimed compounds; method of inhibiting PI3K and/or mTOR activity and to application of claimed compounds.

EFFECT: novel compounds, useful for inhibiting PI3K and/or mTOR activity have been obtained.

15 cl, 16 ex

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