Rectal suppositories for the treatment of diseases in pediatrics

 

(57) Abstract:

The invention relates to pharmacy - suppositories with vasodilator and antispasmodic action. Suppositories contain Dibazol 0.002 g one suppository weight of 1.15-1,40, suppositories Basis - solid confectionery fat type And based on plasticized hydrogenated fat or Witepsol is a mixture of triglycerides, diglycerides and monoglycerides of fatty acids with C12- C18. The use of suppositories eliminates irritating effect on the mucous membrane of the rectum children. They can be recommended especially for the children when there is nausea and vomiting. No side reactions of the child to the drug. table 1.

The invention relates to pharmaceutical industry and medical preparations characterized by special physical forms, namely rectal suppositories with vasodilator and antispasmodic effect, used in Pediatrics.

Known rectal suppositories for the treatment of newborns and infants, containing as the active ingredient interferon, vitamin C, and the filler [1]. Data suppositories have a therapeutic effeney activity but do not exert vasodilator and antispasmodic actions. The closest in composition of the base of the present invention is effective for treatment of diseases in Pediatrics, in the form of suppositories [2].

Suppositories contain base - solid grease type A technological additive - chicken oil, and as an active ingredient sangviritrin in the following ratio of components in g on 1 suppository mass of 1.0-1.2 g:

Sangviritrin - 0,001

Chicken oil - 0,035

Tallow type A - Rest

Drug sangviritrin possesses antimicrobial activity against gram-positive and gram-negative bacteria acts on yeast-like fungi and Trichomonas, has anticholinesterase activity (suppression of the activity of biological substances) [3] . Use this drug with myopathy and polio. However, the use of sanguinarine in suppositories due to its anticholinesterase activity is contraindicated in diseases of the kidneys, liver, angina, asthma, etc. and can cause side effects such as burning, vomiting, abdominal pain.

In this regard, the use of this suppository requires great is ome, data suppositories are not fully stimulate the functions of the spinal cord and do not possess vasodilator and antispasmodic effect.

The aim of the present invention is to provide a suppositories, used in Pediatrics and has vasodilator and antispasmodic effect.

This goal is achieved by the fact that rectal suppositories for the treatment of diseases in Pediatrics, containing the active ingredient and a base in the form of solid fat type A, according to the invention, as an active ingredient contain Dibazol in the following ratio of components, g on one suppository weight of 1.15-1.40 g:

Dibazol - 0,002

Tallow type A (or Witepsol) - Rest

In addition, in the proposed suppositories as the basis can be used witepsol.

The hallmark of the proposed composition of suppositories is that as the active ingredient they contain Dibazol in the following ratio of components, g on one suppository weight of 1.15-1.40 g:

Dibazol - 0,002

Tallow type A (or Witepsol) - Rest

Dibazol white or white to slightly greyish or yellowish krisch.

Dibazol has a vasodilator, antispasmodic, hypotensive effect, as well as a stimulating effect on the function of the spinal cord, has a moderate immunostimulating activity.

It is used by spasms of blood vessels and smooth muscles of internal organs (stomach ulcer, pyloric spasms of the intestines and so on), as well as in the treatment of nervous diseases and residual effects of polio, peripheral facial paralysis and other diseases.

Dibazol assign children:

Up to 1 year of 0.001,

1-3 years of 0.002,

4-8 years of 0.003,

9-12 years - 0,004,

over 12 years of 0.005.

Dibazol when assigning the inside is not very effective, it is prescribed most often for intravenous edema hypertensive crises.

However, for infants from 1 year to 4 years difficult and uncomfortable introduction of Dibazol in the form of tablets, more difficult intravenous injection.

In this regard, arose the need to develop more convenient and easy introduction of Dibazol in the child's body. The use of Dibazol in the proposed suppositories allowed to create a new drug, possess vasodilator, antispasmodic, gin tallow type A or witepsol. Tallow type A is a confectionery tallow based on plasticized hydrogenated fat (C12-C18). Witepsol is a mixture of triglycerides, diglycerides and monoglycerides of fatty acids (C12-C18) (from coconut or palm kernel oil).

From a wide range of foundations Dibazol soluble in the solid fat type A and witepsol. The application of these principles eliminates irritating effect on the mucous membrane of the rectum, promotes good absorption of the drug into the body of the patient.

Analysis of scientific-technical and patent documents showed that the proposed composition of the suppositories is "new" and meets the criterion of "inventive step".

In accordance with the invention were produced samples of the proposed suppositories.

Research shows formulations of suppositories showed that the reduction of Dibazol below 0.002 g reduces therapeutic effect (an increased need for treatment), and the increase of Dibazol more than 0,002 impractical.

Clinical trials of new suppositories with Dibazol was conducted by employees of the Department of prevention of childhood diseases RSMU on the basis of branches of p is the group there were 25 children aged from 7 days to 13 months (boys 12, girls 13) treated with rectal "Dibazol, and 20 children in the comparison group with the same disease treated pelletized form. The distribution of children by type of disease is reflected in the table . Candles were introduced into the rectum children up to 1 year - 1/2 candles per day, from 1 year to 3 years on one candle a day, from 4 to 8 years 1.5 candles in the night, from 9 years of age and older by 2 candles per day. The treatment course of 2-3 weeks, if necessary, treatment was repeated depending on the severity of the disease.

During oral appointment, the drug was given 2 hours before eating, and rectal administration did not depend on its reception. The duration of treatment was from 2 weeks to 4 weeks and averaged 22.4 days in a rectal and 20.7 days during oral.

The studied patients were subjected to thorough clinical assessment of neurological status. For the purpose of diagnosis and treatment monitoring of the disease, also known routine methods of examination (urinalysis; complete blood count; microscopic examination of feces; planting the stool on the Col and dysenteric group; planting urine, liquor on flora and sensitivity to antibiotics; determination of total protein and protein fractions, creatinine, CSR, enzymes, saggin herpes virus simple and antibodies to Toxoplasma; the analysis of a feces on a dysbacteriosis; conducted electrocardiography, electroencephalography, electromyography, echoencephalography; ultrasound of the brain through a large fontanel), according to the testimony - computed tomography brain imaging study of the lumbar region and lower extremities, ultrasound of the abdominal organs and kidneys, fibrogastroduodenoscopy, the study of cellular and humoral immunity. Patients were examined by an optometrist and, if necessary, the otorhinolaryngologist.

All the patients along with the purpose of study drug received and various other medicinal drugs, depending on the base and associated diseases. In treatment, we used the following drugs: 1) vitamins - thiamine, Riboflavin, pyridoxine, cyanocobalamin, ascorbic acid; 2) diuretics - dikarbina, pironolactone; 3) agents that improve cerebral circulation - Cinnarizine, Cavinton; 4) the means acting on the peripheral mediator - pharmacological, neostigmine, atropine; 5) means for regulating metabolic processes Actovegin, Cerebrolysin, lydasum, ATP, calcium gluconate, nicotinic acid, glutamic acid, cytochrome C, essenziale; 6) nootropic drugs - neutrokine - luminal, seduxen; 9) antibiotics - ampicillin, lincomycin, gentamicin, amikacin, totate, Fortum, claforan, levorin.

In the treatment patients also used human immunoglobulin, - globulin, plasma, interferon, Bromhexine, mukaltin, bronholitin, ketotifen, tavegil. Along with drug therapy patients received: massage, gymnastics, appliques oscarito, electrophoresis was performed with novocaine, syphilinum, lidazoy, sulphate of magnesium.

Comparison of the efficiency of Dibazol in rectal and oral assignment was evaluated on the background of the treatment, which was administered for the concrete patient. In assessing the effectiveness of treatment of patients used as instrumental and laboratory findings, but the main (basic) clinical indicators were: improvement of the General condition of the patient; the improvement act of sucking; the increase of body weight; the disappearance of tremor of the limbs; reducing the frequency of seizures; improved support act on her feet; the reduction or disappearance of pathological reflexes; increased muscle tone; positive dynamics of psychomotor development.

Offer suppositories prepared as follows. Melt the basis of the -45oC. the resulting mixture is ground on a three-wheel rubbing the car to the dispersion of 30-40 μm. Concentrate in buttery state is injected into the base at a temperature of 38-40oC, stirred by the stirrer Ultra-Turrax" with the number of turnover 1400 per minute until a homogeneous mass. Then continue stirring with an anchor stirrer. Prepare the masses poured into candle form or blister packaging PVC film.

Analyzing the quality and validity of the developed composition suppositories, we can conclude that the use of Dibazol as the active ingredient more convenient than oral administration (drug not associated with food intake, can be used in the presence of nausea and vomiting in the patient). Were conducted clinical trials offer suppositories for children of different ages. The table gives the age of the children, their number in study groups and diagnoses of diseases.

Clinically identified irritant action of the drug on the mucous membrane of the rectum. Also it was not observed any side reactions of the child to the study drug.

Thus, the study-the study of a new dosage form also revealed the effectiveness of the studied dosage forms and safety with long-term rectal function. The obtained results allow to recommend to the widespread use of Dibazol in the form of rectal suppositories in clinical Pediatrics. The product is shown in neurology at children of early age with perinatal lesions of the nervous system encephalopathy and birth trauma, accompanied syndromes: intracranial hypertension, musculoskeletal disorders (paresis of the limbs), vegetative-visceral dysfunction and lesions of the cranial nerves.

The drug can be used in the recovery period of treatment of intrauterine infections (cytomegalovirus, toxoplasmosis), as well as polio and poliomyelitic diseases.

When conducting quality control candle set stability of a new dosage form for the action of the air, the duration of mixing, high temperature, ratio of performanec. Long-term observations showed that suppositories retain their original quality during 2 years of storage.

Given the small selection of suppositories that use the pediatricians of Russia proposed suppositories will find wide application in medical practice.

The list of references.

1. Description of the invention to paten the invention N 2026672, CL A 61 K 31/00, 9/00, publ. 20.01.95,

3. Mashkovsky, M. D. "Drug", 1984, M, "Medicine", page 420.

4. Mashkovsky, M. D. "Drug", 1984, M, "Medicine", h 1, page 517.

Rectal suppositories for the treatment of diseases in Pediatrics, characterized in that they contain Dibazol in the amount of 0.002 g per suppository weight of 1.15 - 1.40 g, and as the Foundation is solid confectionery fat type And based on plasticized hydrogenated fat or Witepsol is a mixture of triglycerides, diglycerides and mogosoaia fatty acids with C12- C18.

 

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The invention relates to new derivatives of Anthranilic acid of General formula (1) or their pharmacologically acceptable salts, where R1, R2, R3and R4- same or different and mean a hydrogen atom, halogen atom, optionally halogenated lower alkoxygroup, nitro, cyano, pyrazolidine group, a group of the formula (II), where R9and R10are the same or different and mean a hydrogen atom, a lower alkyl group and p is an integer from 0 to 6, a group of the formula (III), where R13represents a hydrogen atom, a lower alkyl group, q is an integer from 0 to 2; and R2may be 1,2,4-triazoline group; R5and R6are the same or different and represent a hydrogen atom, halogen atom, cyano, lower alkoxygroup, or R5and R6together with the carbon atoms to which they are attached, form oxolane ring, 1,3-dioxolane or 1,4-dioxane ring; W represents a group - N = or-CH=; R7and R8are the same or different and represent a hydrogen atom, a lower alkyl group, or R1and R7together with the carbon atoms and nitrogen, respectively, to which they are attached, form the second alkyl group or a group of the formula-X-(CH2)m-Z, where X represents-CO-, -CH2- or-S(O)2-; Z represents hydrogen, halogen, phenyl group which may be substituted by lower alkyl, lower alkoxygroup, carboxypropyl or lower alkoxycarbonyl group, pyridyloxy group, a group of the formula NR11R12where R11and R12together with the nitrogen atom to which they are attached, form piperidino or pyrolidine ring which may be substituted by a lower alkyl group, actigraphy, carboxypropyl, lower alkoxycarbonyl group, cycloalkyl group containing 3-8 carbon atoms which may be substituted by actigraphy, cyano, lower alkylcarboxylic, carboxypropyl or lower alkoxycarbonyl group, piperidino group, m is an integer from 0 to 6, Y is an oxygen atom; n is an integer from 0 to 6

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The invention relates to pyrazole derivative of the General formula I

< / BR>
in which R1is phenyl, substituted cyclo(lower)alkyl, hydroxy(lower)alkyl, cyano, lower alkylenedioxy, carboxy, (lower alkoxy)carbonyl group, a lower alkanoyl, lower alkanoyloxy, lower alkoxy, phenoxy or carbamoyl, optionally substituted lower alkyl;

R2is halogen, halo(lower)alkyl, cyano, carboxy, (lower alkoxy)carbonyl group, carbamoyl, optionally substituted by alkyl;

R3is phenyl, substituted lower alkylthio, lower alkylsulfonyl, or lower alkylsulfonyl, provided that when R1is phenyl, substituted lower alkoxy, then R2represents halogen or halo(lower)alkyl,

or their pharmaceutically acceptable salts

The invention relates to medicine and can be used in the treatment of stress lesions of the nervous system in combustionengines, traumatic, neurological and surgical hospitals

The invention relates to new chemical substances possessing valuable properties, in particular nitrogen-containing cyclic derivative of General formula

< / BR>
where X is carbinieri, unsubstituted or substituted at the nitrogen atom by alkyl, aryl, heteroaryl or cyano, carbonyl, thiocarbonyl, sulfonyl, 1-nitroethene-2,2-diyl or 1,1-dicyano-Eten-2,2-diyl,

Y is unsubstituted or substituted Rcor Rdor Rcand Rdnonbranched alkylen or albaniles with 2 to 4 carbon atoms, which may optionally be substituted by one or two alkyl groups and in which one or two methylene groups can be replaced by a carbonyl, 1,2-cycloalkyl with 5 to 7 carbon atoms, unsubstituted or substituted Rcor Rdor Rcand Rd, 1,2 - cycloalkenyl with 5 to 7 carbon atoms, unsubstituted or substituted Rcor Rdor Rcand Rd, 1,2-Allen, 1,2-phenylene, in which one or two methine groups are replaced by nitrogen atom or one or two groups-CH=CH - replaced by a group-CO-NH - or a methine group substituted by nitrogen atom and one group-CH= CH - replaced by a group-CO-NH-, and above heterocycles or substituted Rcor Rd,

the first of the residues Ra- Rdmeans A group-B-, in which A group of the formula

< / BR>
< / BR>
or

< / BR>
where pentostatin can be monogamist the remainder R25mono - or Disaese the remainder R26or monogamist the remainder R25and additionally monogamist the remainder R26and the substituents R25and R26that may be the same or different and have the meanings stated below, in one bancoestado 1 - 3 methine group may be replaced by a nitrogen atom or a group-CH= CH - may be replaced by a group-CO-NR1or one methine group may be replaced by nitrogen atom and one group-CH=CH - may be replaced by a group-CO-NR1-, where R1means a hydrogen atom or alkyl,

G1and G4- bond or methylene which may be mono - or Disaese the alkyl, aryl or heteroaryl, and the substituents may be the same or different,

G2- bond or methylene, substituted residues R7and R8,

G3communication, methyl nitrogen atom or Metin, unsubstituted or substituted by alkyl, aryl or heteroaryl,

R2is a hydrogen atom, alkyl, aryl or heteroaryl or hydroxyl or alkoxyl if at least one of the groups G2and G3doesn't mean the relationship,

R3is a hydrogen atom, alkyl, aryl or heteroaryl or R3together with R2form an oxygen atom, if at least one of the groups G2and G3doesn't mean the relationship,

R4and R14is a hydrogen atom, cycloalkyl with 3 to 7 carbon atoms, cycloalkyl with 3 to 7 carbon atoms in cycloalkyl parts, alkyl with 1 to 8 carbon atoms, alkenyl with 3 to 8 carbon atoms, which may not be linked to the nitrogen atom through the vinyl group, hydroxyalkyl, alkoxyalkyl, aminoalkyl, acylaminoalkyl, dialkylaminoalkyl, cianelli, carboxyethyl, alkoxycarbonylmethyl, aminocarbonylmethyl, N-alkylaminocarbonyl, N,N-dialkylaminoalkyl, arylalkyl, heteroallyl, alkoxycarbonyl, allmediascotland, formyl, acetyl, TRIFLUOROACETYL, allyloxycarbonyl, amidino or R11CO-0-(R12CR13)-O-CO-, where R11is alkyl with 1 to 8 carbon atoms, cycloalkyl with 5 to 7 carbon atoms, aryl or arylalkyl, R12is a hydrogen atom, alkyl, cycloalkyl with sweetlenny alkylen 2 - 4 carbon atoms or methylene, if G2doesn't mean the relationship,

R5is a hydrogen atom, alkyl, aryl or heteroaryl or hydroxyl or alkoxyl, if G1no means of communication, or R4together with R5mean an additional bond, if G1means of communication,

R6is a hydrogen atom, alkyl, aryl or heteroaryl or a chlorine atom, a hydroxyl, methoxyl, amino, alkylamino or dialkylamino, if G1means linking and R4together with R5mean an additional bond, or R6together with R5mean oxygen atom, if G1doesn't mean the relationship,

R7is a hydrogen atom, alkyl, aryl or heteroaryl,

R8is a hydrogen atom, alkyl, aryl or heteroaryl or R8together with R4mean the unbranched alkylene with 2 to 5 carbon atoms,

R9is a hydrogen atom, alkyl, aryl or heteroaryl or hydroxyl or alkoxyl, if G2doesn't mean the relationship,

R10is a hydrogen atom, alkyl, aryl or heteroaryl or R10together with R4mean the unbranched alkylene with 2 to 4 carbon atoms,

R15is a hydrogen atom or chlorine, alkyl, aryl, heteroaryl, hydroxyl, methoxyl, amino, alkylamino or dialkylamino,

R16- foelkel 1 8 carbon atoms, alkenyl with 3 to 8 carbon atoms, which may not be linked to the nitrogen atom through the vinyl group, hydroxyalkyl, alkoxyalkyl, aminoalkyl, acylaminoalkyl, dialkylaminoalkyl, cianelli, carboxyethyl, alkoxycarbonylmethyl, aminocarbonylmethyl, N-alkylaminocarbonyl, N,N-dialkylaminoalkyl or arylalkyl,

R17is a hydrogen atom or alkyl, or R16together with R17mean an additional bond, if G4means of communication,

R18is a hydrogen atom, alkyl or fluorine atom, chlorine or bromine, hydroxyl, methoxyl, amino, alkylamino or dialkylamino, if G4means linking and R16and R17together denote an additional bond,

n is the number 1 or 2,

In - line, alkylen, albaniles, Allen, peridinin, pyrimidinyl, personalen or pyridazinyl, in which one or two groups-CH=N - can be replaced by a group-CO-NH - and one of the nitrogen atoms may be associated with the remainder of A connection instead of a hydrogen atom, and these heterocyclic groups may be optionally substituted by one or two alkyl groups, cycloalkyl with 4 to 7 carbon atoms, unsubstituted or substituted by one or two alkyl groups, unsubstituted or RC="http://www.fips.ru/fullimg2/rupat3/19993/003.dwl/2126002-6t.gif" ALIGN="ABSMIDDLE">replaced by a nitrogen atom, and, in addition, in the above mentioned 5 - to 7-membered rings, one adjacent to the nitrogen atom of the methylene group may be replaced by carbonyl, the second of the residues Ra- Rdmeans a group of the formula

F - E - D-,

where D is alkylene with 1 to 6 carbon atoms in which one methylene group may be replaced by oxygen atom or sulfur, sulfinil, sulfonium or the group-NR19-, where R19means a hydrogen atom, alkyl, alkylaryl, alkylsulfonyl, arylcarbamoyl or arylsulfonyl, or in which one ethylene group may be replaced by a group-CO-NR20- or-NR20-CO-, where R20means a hydrogen atom or alkyl, albaniles with 2 to 6 carbon atoms, Allen, peridinin, pyrimidinyl, personalen or pyridazinyl, in which one or two groups-CH=N - can be replaced by a group-CO-NH - and one of the nitrogen atoms, together with the hydrogen atom may also be linked with the rest of E, if the latter does not mean the connection or not connected via a heteroatom or a carbonyl with the rest of D, and these heterocyclic groups may be optionally substituted by one or two alkyl groups, indaniel, naftilan, 1,2,3,4-tetrahydronaphthalen or benzoguanamine, in which one of the be substituted by one or two alkyl groups, and the aromatic ring may be substituted by fluorine atom, chlorine, bromine or iodine, alkyl, trifluoromethyl, hydroxyl, alkoxyl, alkylsulfanyl, alkylsulfonyl, alkylsulfonyl or cyano, cycloalkyl with 4 to 7 carbon atoms, unsubstituted or substituted by one or two alkyl groups, unsubstituted or substituted by one or two alkyl groups cycloalkyl with 5 to 7 carbon atoms, in which one groupreplaced by a nitrogen atom, and, in addition, in the above mentioned 5 - to 7-membered rings, one adjacent to the nitrogen atom of the methylene group may be replaced by carbonyl, unsubstituted or substituted by one or two alkyl groups piperazinyl in which one adjacent to the nitrogen atom of the methylene group may be replaced by a carbonyl, or alkilenkarbonatov with the total number of carbon atoms 2-6, if E is a cyclic aminogroup, and a carbonyl linked to a nitrogen atom of a cyclic aminogroup group E, or a link, if E does not mean the relationship,

E - communication, alkylene with 1 to 6 carbon atoms which may be substituted by one or two alkyl groups with 1 to 8 carbon atoms, alkenyl or quinil with 2 to 4 carbon atoms, hydroxyl, is POI with the total number of carbon atoms of 2 10, the group HNR21- or N-alkyl-NR21-, where R21means alkylsulphonyl or alkylsulfonyl with 1 to 8 carbon atoms in the alkyl part, allyloxycarbonyl with the total number of carbon atoms 2 and 5 cycloalkylcarbonyl or cycloalkylcarbonyl with 5 to 7 carbon atoms in cycloalkyl part, arylalkylamines, arylalkylamines, arylethoxysilanes, arylcarbamoyl or arylsulfonyl, albaniles with 2 to 6 carbon atoms, Allen, peridinin, pyrimidinyl, personalen or pyridazinyl, unsubstituted or substituted by one or two alkyl groups, unsubstituted or substituted by one or two alkyl groups cycloalkyl with 5 to 7 carbon atoms, in which one groupreplaced by a nitrogen atom linked to the carbon atom of the residue D, cycloalkyl with 4 to 7 carbon atoms in cycloalkanones part, unsubstituted or substituted by one or two alkyl groups with 1 to 8 carbon atoms, alkenyl or quinil with 2 to 4 carbon atoms, hydroxyl, amino, aryl, heteroaryl, alkoxyl or alkylamino with 1 to 8 carbon atoms, dialkylamino with the total number of carbon atoms of 2 to 10, a group HNR21- or N-alkyl-NR21-, where R2119-, -NR20-CO - or-CO-NR20-, where R19and R20have the above meanings, with alkylene may be optionally substituted by one or two alkyl groups with 1 to 8 carbon atoms, alkenyl or quinil with 2 to 4 carbon atoms, hydroxyl, amino, aryl, heteroaryl, alkoxyl or alkylamino with 1 to 8 carbon atoms, dialkylamino with the total number of carbon atoms of 2 to 10, group-HNR21- or N-alkyl-NR21where R21have the above significance, with an additional heteroatom substituent heteroatom is separated from the remainder of W by at least two carbon atoms, if D does not mean the relationship,

F - carbonyl, substituted by hydroxyl, alkoxyl with 1 to 8 carbon atoms, arialcategory or group R22O-, where R22means cycloalkyl with 4 to 8 carbon atoms and cycloalkyl with 3 to 8 carbon atoms in cycloalkyl part, in which cycloalkyl part may be substituted by alkyl, alkoxyl or dialkylamino, or alkyl and 1 to 3 methyl groups, with one methylene group in the 4 - to 8-membered cycloalkyl part may be replaced by oxygen atom or alkylaminocarbonyl, benzocyclobutene the PA R23CO-O-CHR24-O-CO-, where R23means alkyl or alkoxy with 1 to 8 carbon atoms, cycloalkyl with 5 to 7 carbon atoms, cycloalkyl with 5 to 7 carbon atoms in cycloalkyl parts, aryl, aryloxy, arylalkyl or Allakaket and R24is a hydrogen atom or alkyl,

the shortest distance between the residue of F and located at a maximum distance from the rest F the nitrogen atom of the group A-B - is at least 11 links,

the third of the residues Ra- Rdmeans a hydrogen atom, alkyl, perfluoroalkyl, alkoxy, alkylsulfanyl, alkylsulfonyl, alkylsulfonyl, amino, alkylamino, dialkylamino, aryl, heteroaryl or arylalkyl,

the fourth of the residue Ra- Rdmeans a hydrogen atom, alkyl or aryl, and if nothing else is mentioned,

under the above term "aryl" is to be understood phenyl, which can be monogamist the remainder R25mono-, di - or triamese the remainder R26or monogamist the remainder R25and additionally mono - or Disaese the remainder R26and the substituents may be the same or different, R25means cyano, carboxyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminoalkyl, alkoxycarbonyl, alkylboron, the Mino, alkylamino, dialkylamino, alkylcarboxylic, phenylalkylamine, phenylcarbonylamino, alkylsulfonyl, phenylalkylamine, phenylcarbonylamino, N-alkyl-alkylcarboxylic, N-alkyl-phenylalaninamide, N-alkyl-phenylcarbonylamino, N-alkyl-alkylsulfonyl, N-alkyl-phenylalaninamide, N-alkyl-phenylcarbonylamino, aminosulfonyl, alkylaminocarbonyl or dialkylaminoalkyl, R26- alkyl, hydroxyl or alkoxy, fluorine atom, chlorine, bromine or iodine, and two residue R26if they are linked to adjacent carbon atoms, may also be alkylene with 3 to 6 carbon atoms, 1,3-butadiene-1,4-deelen or methylendioxy group

under the above term "Allen" should be understood phenylene, which can be monogamist the remainder R25mono - or Disaese the remainder R26or monogamist the remainder R25and additionally monogamist the remainder R26and the substituents may be the same or different and have the above values,

under the above term "heteroaryl" should read 5-membered heteroaromatic ring containing one atom of oxygen, sulfur or nitrogen, one atom of nitrogen and one atom of oxygen, sulfur is certain heteroaromatic ring, in which one or two of the groups-CH= N - can be replaced by a group-CO-NR20where R20has the above value, the heteroaromatic ring can be substituted by one or two alkyl groups or by a fluorine atom, chlorine, bromine or iodine, hydroxyl or alkoxyl in the carbon skeleton,

and, if nothing else is mentioned, the above alkyl, alkylene or CNS groups can contain 1 to 4 carbon atoms and each of the carbon atoms in the above alkilinity and cycloalkenes groups associated at least one heteroatom,

mixtures of their isomers, or individual isomers or salts

The invention relates to pharmacology and describes a new tool for the treatment of irritable bowel syndrome

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.

1 ex

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