Method for prevention of hormone resistance in endometrial hyperplasia

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely gynaecology, and is applicable for the purpose of prevention of hormone resistance in endometrial hyperplasia. That is ensured by prescribing a depot synthetic analogue of gonadotrophin releasing hormone by 1 injection on the 1st-2nd day of menstrual cycle once every 28 days. Nine injections in all. It is combined with an oestrogen-gestagen drug by 1 tablet a day starting with the 14th day after the second injection of the gonadotrophin releasing hormone analogue and up to the 28th day after the ninth injection.

EFFECT: method enables prevention of hormone resistance in endometrial hyperplasia.

3 ex

 

The invention relates to medicine, in particular to the gynecologist.

In the process of organ conservative treatment of hormone-dependent pathology of the uterus, in particular, endometrial hyperplasia, it is important to carry out prevention of the development of gormonorezistentnost tissues to estradiol and progesterone, because due to the need for further implementation of the generative functions (preserving the expression of estrogen receptor and progesterone in the endometrium for the physiological processes of proliferation and secretion for subsequent adhesion and nidali blastocyst) in women of reproductive age and a possible course of treatment with Progestogens in case of recurrence and progression of the disease at any age.

The lack of effect of therapy in case of relapse due to the insensitivity of the pathological substrate for estrogen, progesterone and their medicinal counterparts and is an indication for surgical treatment is a hysterectomy.

Therefore, the task of prevention of gormonorezistentnost in the treatment of endometrial hyperplasia.

In the available scientific literature, this method is not found.

The objective of the invention is a method for the prevention of gormonorezistentnost (insensitivity estrogen and progesterone through the downregulation of receptors) when hype is plusii endometrium during her treatment.

The problem is solved by the method lies in the fact that prescribe depo-form synthetic analogue of gonadotropin-releasing hormone 1 injection of 1-2 day of the menstrual cycle 1 every 28 days, a total of nine injections and estrogen-gestagenna the drug per 1 tablet a day, starting from 14 days after the second injection of an analogue of gonadotropin-releasing hormone and up to 28 days after the ninth injection.

As an analogue of gonadotropin-releasing hormone can be used goserelin acetate 3.6 mg, leiprorelina of 3.75 mg triptorelin 3.75 mg, buserelina acetate 3.75 mg (Kharkevich, D.A. Pharmacology: a Textbook. - 6th ed., Rev. and supplementary): GEOTAR MEDICINE, 1999. - 664 S.; radar-2002, 9th edition).

As estrogen-gestagennah drug can be used the drug for monophasic hormone replacement therapy in postmenopausal women in the continuous mode, containing estradiol valerate or 17β-estradiol 1-2 mg and gestagen without androgenic activity (dydrogesteron, drosperinone, dienoguest) 2-5 mg ("angelic", contains 1 mg 17β-estradiol and 2 mg drosperinone; "Femoston 1/5", contains 1 mg 17β-estradiol and 5 mg dydrogesterone, "Climodien", contains 2 mg estradiol valerate and 2 mg dienoguesta). (Gynecology from puberty to post-menopausal: Practical use. a guide for physicians / edited by Acad. The RAMS Alkalmazasa. - M.: Medpress-inform, 2006. - 2nd ed., extra - 496.: Il.).

Example 1.

Patient A., 37 years old, hospitalized in the gynecological Department in connection with suspected recurrence of endometrial hyperplasia by ultrasound examination of the internal genitalia. For specification of the diagnosis performed hysteroscopy, separate diagnostic curettage of the uterine mucosa, morphological examination of scrapings, immunohistochemical determination of estrogen receptor (ER) and progesterone (PR) in the endometrium using antibodies firm Dako, and quantifying the expression of receptors on the system Histo Score.

The onset of disease (complex endometrial hyperplasia without atypia, the receptor status of the endometrium: ER - 60% and 55% and PR - 80% and 60% in the epithelium and stroma hyperplastic endometrium, respectively) was diagnosed 23 months before relapse assigned therapy depo-form analogue of gonadotropin-releasing hormone (buserelin depot), a total of 9 injections, with subsequent morphological verification of the effectiveness of after the end of therapy (achievement atrophy of the endometrium). Menstrual function recovered after 82 days after the last injection. Recommended an ultrasound of the genital vaginal sensor every 3 months 5-8 day of the menstrual cycle.

With regular checkups detected deviation from normalnyh characteristics median uterine echo: 14 mm heterogeneous. Was admitted to hospital for diagnostic procedures (see above). The diagnosis was confirmed morphologically: focal complex endometrial hyperplasia without atypia, relapse. The expression of ER was 14% and 12%, the expression of PR 13% and 13% in the epithelium and stroma hyperplastic endometrium, respectively.

The patient has a second rate of depo-form analogue of gonadotropin-releasing hormone with subsequent morphological monitoring the effectiveness of therapy: centers of complex endometrial changes are preserved (ineffective hormonal therapy). Proposed radical surgical treatment is hysterectomy, in which the patient agreed.

Example 2.

Patient C., 36 years. According to the results of a complete clinical examination diagnosed with complex endometrial hyperplasia without atypia, the receptor status of the endometrium: ER - 80% and 60% and PR - 70% and 90% in the epithelium and stroma hyperplastic endometrium, respectively. Assigned therapy depo-form synthetic analogue of gonadotropin-releasing hormone (buserelin depot) 1 injection of 1-2 day of the menstrual cycle 1 every 28 days, a total of nine injections, and, in parallel, estrogen-gestagennye drug ("angelic") 1 tablet per day, starting from 14 days after the second injection of an analogue of gonadotropin-releasing hormone and up to 28 days after the ninth injection.

Morphol the strategic research after the end of treatment found no evidence of endometrial hyperplasia. Menstrual function recovered through 63 days after the last injection of an analogue of gonadotropin-releasing hormone. Six months after the end of therapy has come a planned pregnancy.

Example 3.

Patient S., aged 39. According to the results of a complete clinical examination diagnosed with complex endometrial hyperplasia without atypia, the receptor status of the endometrium: ER - 75% and 50% and PR - 70% and 80% in the epithelium and stroma hyperplastic endometrium, respectively. Assigned therapy depo-form synthetic analogue of gonadotropin-releasing hormone (buserelin depot) 1 injection of 1-2 day of the menstrual cycle 1 every 28 days, a total of nine injections and estrogen-gestagennye drug (Femoston 1/5") 1 tablet per day, starting from 14 days after the second injection of an analogue of gonadotropin-releasing hormone and up to 28 days after the ninth injection.

Morphological study after the course of treatment found no evidence of endometrial hyperplasia. Menstrual function recovered after 71 days after the last injection of an analogue of gonadotropin-releasing hormone.

After 19 months after the end of therapy was diagnosed with a relapse of complex endometrial hyperplasia without atypia. The expression of ER was 72% and 50% in the epithelium and stroma, respectively. Expression of PR - 75% and 55% in the epithelium and stroma, respectively the military. A refresher course of therapy by analogues of gonadotropin-releasing hormone in parallel with estrogen-gestagenna drug with full morphological effect: no evidence of endometrial hyperplasia.

The proposed method used in 12 patients. Positive effect (save to the expression of estrogen receptor and progesterone on the morphological background of healing or achieving pregnancy as an integral indicator of the physiological expression of steroid hormone receptors) was observed in 10 patients.

The way to prevent gormonorezistentnost hyperplasia of the endometrium, which is to assign depot-form synthetic analogue of gonadotropin-releasing hormone 1 injection of 1-2 day of the menstrual cycle 1 every 28 days, a total of nine injections and estrogen-gestagenna of the drug per 1 tablet per day, starting from 14 days after the second injection of an analogue of gonadotropin-releasing hormone and up to 28 days after the ninth injection.



 

Same patents:

FIELD: medicine.

SUBSTANCE: group of inventions relates to medicine, namely to gynecology, and can be used for syndrome of ovary hyperstimulation, as well as for its prevention in a subject who is under treatment against infertility with gonadotropic hormone. For this purpose composition, which contains quinagolide in pharmaceutically acceptable carrier, is introduced to patient.

EFFECT: introduction of quinagolide, in contrast to other dophamine agonists, ensures high therapeutic efficiency in considerably smaller doses and is quickly excreted from organism, which reduces risk of toxicity for mother and fetus.

16 cl, 3 tbl, 6 ex, 2 dwg

FIELD: chemistry.

SUBSTANCE: invention relates to 4-phenyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline derivatives of formula I

or pharmaceutically acceptable salts thereof, where R1 denotes (1-6C)alkyl; R2, R3 independently denote halogen, (1-4C)alkoxy; R4 denotes phenyl or a 5-6-member heteroaryl, having one or two heteroatoms selected from nitrogen, oxygen or sulphur, phenyl or said heteroaryl, substituted with R7 and optionally substituted on the (hetero)aromatic ring with one or two substitutes selected from halogen, nitro, trifluoromethyl and (1-4C)alkyl; R7 denotes H, (1-4C)alkylthio, (1-4C)alkylsulphonyl, R8R9-amino, R10R11-aminocarbonyl, R12R13-amino(1-4C)alkylcarbonyl-amino, R14R15-amino(1-4C)alkyl, R16-oxy, R17R18-aminocarbonyl (1-4C)alkoxy, R19-oxy(1-4C)alkyl, R19-oxycarbonyl(1-4C)alkyl, R20R21-aminosulphonyl, R20-oxysulphonyl, aminoiminomethyl, (di)(1-4C)alkylaminoiminomethyl, morpholinyliminomethyl, trifluoromethylsulphonyl; R23-oxycarbonyl, or R23R24-aminocarbonyl; R8 denotes H or (1-4C)alkyl; R9 denotes (1-4C)alkylsulphonyl, (1-6C)alkylcarbonyl, (2-6C)alkenylcarbonyl, (3-6C)cycloalkylcarbonyl, (1-4C)alkoxycarbonyl, (3-4C)alkenyloxycarbonyl, (di)(1-4C)alkylaminocarbonyl, piperazinylcarbonyl, (5-8C)alkyl, (3-6C)cycloalkyl(1-4C)alkyl or phenylcarbonyl, furylcarbonyl, thiophenylsulphonyl, 5-member heteraryl(1-4C)alkyl, having one or two nitrogen atoms, optionally substituted on the heteroaromatic ring with one, two or three substitutes selected from hydroxy, amino, halogen, nitro, trifluoromethyl, (1-4C)alkoxy; R10 denotes H or (1-4C)alkyl; R11 denotes hydroxy(2-4C)alkyl, (1-4C)alkoxy(2-4C)alkyl; R12, R13 independently denote H, (1-6C)alkyl, (3-6C)-cycloalkyl, (1-4C)alkoxy(2-4C)alkyl, (3-6C)cycloalkyl-(1-4C)alkyl, pyrrolidinyl(1-4C)alkyl, amino(2-4C)alkyl, (di)(1-4C)-alkylamino(2-4C)alkyl or phenyl(1-4C)alkyl, pyridinyl (1-4C)alkyl; or R12R13 in R12R13-amino(1-4C)alkylcarbonylamino can be bonded together with the nitrogen atom to which they are bonded into a (5-6C)heterocycloalkyl ring, having one or two nitrogen atoms, optionally substituted with hydroxy(1-4C)alkyl; R14, R15 independently denote H, (1-6C)alkyl, (1-6C)alkylcarbonyl, (1-4C)alkoxycarbonyl or pyridinyl(1-4C)alkyl, optionally substituted on the aromatic ring with one substitute selected from halogen; or R16 denotes (di)(1-4C)alkylamino(2-4C)alkyl, hydroxycarbonyl(1-4C)alkyl, (1-4C)alkoxycarbonyl(1-4C)alkyl, phenyl(1-4C)alkyl or pyridinyl(1-4C)alkyl; R17, R18 independently denote H, (1-6C)alkyl, thiophenyl(1-4C)alkyl; or R17R18 in R17R18-aminocarbonyl(1-4C)alkoxy can be bonded into a morpholine or piperazine ring, R19 denotes H or (1-6C)alkyl; R20R21 independently denote H, (1-6C)alkyl or (1-4C)alkoxy(1-4C)alkyl; or R20R21 in R20R21-aminosulphonyl can be bonded into a morpholine ring; X denotes O or N-R22; Y denotes CH2 or C(O); Z denotes CN or NO2; R22 denotes H; R23, R24 independently denotes H; (1-4C)alkyl; or R23R24 in R23R24-aminocarbonyl can be bonded into a dihydropyridine ring; provided that compounds of formula I, in which X denotes O, R4 denotes phenyl and R7 is selected from H, (1-4C)alkylthio, (1-4C)alkylsulphonyl, R23-oxycarbonyl, and R23R24-aminocarbonyl, and compounds of formula I, in which X denotes O, R4 denotes (2-5C)heteroaryl and R7 denotes H are excluded. The invention also relates to use of 4-phenyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline derivatives to prepare a medicinal agent for treating sterility.

EFFECT: improved useful biological properties.

12 cl, 73 ex

FIELD: medicine.

SUBSTANCE: invention refers to a compound of formula I where A represents an optionally substituted aryl or heteroaryl, B - a benzene or thiophene cycle, C - a benzene or aliphatic hydrocarbon cycle, while values of other radicals are disclosed in the description. The compound according to the present invention, and the based pharmaceutical compositions exhibit a strong antagonistic effect in relation to GnRH receptor that makes them applicable for treatment of GnRH-related diseases, particularly prostate cancer, benign prostatic hyperplasia, breast cancer, endometriosis and/or uterine fibroid tumour.

EFFECT: improved clinical effectiveness.

11 cl, 70 tbl, 765 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to 2-methyl-4-phenyl-5-oxo-1,4,5,6,7,8-hexahydrochinoline derivatives of formula 1 , in which R1 represents (1-6C)alkyl; R2 represents halogen; R3 represents SO2NR5R6 or (1-4C)alkoxy; X represents O or NR7; R4 represents R8-(2-8C)alkyl, R8-(3-8C)alkenyl or R8-(2-4C)alkoxy-(2-4C)alkyl; Z represents CN or NO2; R5 and R6 independently on each other represent H or (1-4C)alkyl; or R5 together with R6 and N, to which they are bound, form 5-6-member saturated ring, optionally containing additional heteroatom, selected from O; R8 represents OH, (1-4C)alkoxy, NH2; NR9C(O)R11, NR9SO2R11 or C(O)NR9R10; R7 and R9 independently represent H or (1-4C)alkyl; R10 represents (1-4C)alkyl; R11 represents (1-4C)alkyl, (1-4C)alkoxy(1-4C)alkyl, (3-6C)cycloalkyl, (1-4C)alkoxy or phenyl, or (4-5C)heteroaryl, and (4-5C)heteroaryl stands for aromatic group, which has 4-5 carbon atoms and at least one heteroatom, selected from N and O; or to their pharmaceutically acceptable salts. Invention also relates to pharmaceutical composition, as well as to application of 2-methyl-4-phenyl-5-oxo-1,4,5,6,7,8-hexahydrochinoline derivatives.

EFFECT: obtaining novel biologically active compounds, possessing agonistic activity with respect to FSH receptor.

8 cl, 33 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to novel derivatives of 4-phenyl-5-oxo-1,4,5,6,7,8-hexahydrochinoline, represented by formula , where R1 represents (1-6C)alkyl; R2 represents halogen, (1-4C)alcoxy; R3 represents OH, NO2, CN, fluoridated with (1-4C)alkoxy, (1-4C)alkoxy(2-4C)alkoxy. hydroxy(2-4C)alkoxy, (1-4C)alkoxycarbonyl, R7, R8-amino, R9, R10-amino, R9, R10-aminocarbonyl, R9, R10-aminosulfonyl or phenyl(1-4C)alkoxy, where phenyl ring in composition phenyl(1-4C)alkoxy is optionally substituted with one or several substituents, selected from (1-4C)alkoxy; R4 represents R11-phenyl or R11-(4-5C)heteroaryl, which represents heteroaromatic group, containing 4-5 carbon atoms and at least one heteroatom, selected from N and S, where phenyl or heteroaryl group is optionally additionally substituted with one or several substituents, selected from nitro, (1-4C)alkyl, (1-4C)alkoxy; R7 represents H, (1-4C)alkyl; R8 represents (1-4C)alkylsulfonyl, (1-4C)alkylcarbonyl, (1-4C)alkoxycarbonyl, (1-4C)alkoxy(1-4C)alkylcarbonyl, furylcarbonyl; phenyl(1-4C)alkylcarbonyl, where phenyl ring is optionally substituted with one or several substituents, selected from (1-4C)alkoxy; R9 and R10 are not necessarily selected from H, (1-6C)alkyl and (1-4C)alkoxy(2-4C)alkyl; or R9 and R10 can be bound together with formation of morpholinyl ring; R11 represents H, R12, R13-amino, R14, R15-aminocarbonyl or R14, R15-aminosulfonyl; R12 represents H; R13 represents (1-4C)alkylsulfonyl, (1-4C)alkylcarbonyl, (1-4C)alkoxycarbonyl or pyperazinyl(1-4C)alkylcarbonyl; R14 and R15 are independently selected from H, (1-6C)alkyl, (1-4C)alkoxy(2-4C)alkyl and imidazolyl(1-4C)alkyl; X represents O or R16-N; Y represents CH2 or C(O);Z represents CN; R16 represents H, (1-4C)alkyl, (1-4C)alkylcarbonyl; or their pharmaceutically acceptable salts. Invention also relates to pharmaceutical composition, as well as to application of 4-phenyl-5-oxo-1,4,5,6,7,8-hexahydrochinoline derivatives by any of i.i. 1-10.

EFFECT: obtaining novel biologically active compounds, which possess agonistic activity with respect to FSH receptor.

13 cl, 43 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: as an active ingredient, a pharmaceutical composition contains 6β,7β; 15β; 16β-dimethylene-3-oxo-17α-preg-4-ene-21,17-carbolactone (drospirenone, DRSP) together with a pharmaceutically acceptable excipient or carrier. Said composition does not contain estrogen. Drospirenon is prepared in fast soluble dosage form. At least 70% of drospirenone are dissolved within 30 minutes. For ensuring said immediate release, drospirenone is either micronised, or in dosage form of surface area more than 10000 cm2/g, or is applied on the surface of particles of an inert carrier. The composition can be applied for endometriosis treatment and introduced in the form of a multiphase pharmaceutical preparation.

EFFECT: immediate-release drospirenone compositions under the invention exhibits high biological availability when administered orally.

23 cl, 7 ex

FIELD: medicine.

SUBSTANCE: invention refers to pharmacology. A solid pharmaceutical dispersion contains bazedoxifene acetate dispersed in a dispersant, and said dispersant contains polyvinylpyrrolidone, poloxamer, polyethylene glycol, or a mixture or copolymer of said substances. The invention refers also to the compositions containing said dispersion, to methods for making the solid pharmaceutical dispersion containing bazedoxifene acetate and the composition and a dosage form containing the solid pharmaceutical dispersion containing bazedoxifene acetate for treatment of a disease or a syndrome associated with oestrogen hunger or excess, a disease or a disorder associated with proliferation or pathological development of endometrial tissues, cholesterol reduction, bone loss inhibition and breast cancer treatment. Besides the invention covers the methods of treating mammals suffering a disease or a syndrome associated with oestrogen hunger or excess, or a disease or a disorder associated with proliferation or pathological development of endometrial tissues, or cholesterol reduction in a mammal, bone loss inhibition in a mammal or breast cancer treatment in a mammal, treatment of one or more vasomotor disorders in postmenopausal women, including the introduction of therapeutically effective amounts of the solid pharmaceutical dispersion, and also to the application of the solid pharmaceutical dispersion containing bazedoxifene acetate for preparing a drug for treatment of a disease or a syndrome associated with oestrogen hunger or excess, a disorder associated with proliferation or pathological development of endometrial tissues, cholesterol reduction, bone loss inhibition and breast cancer treatment.

EFFECT: invention provides higher clinical effectiveness.

38 cl, 6 tbl, 2 dwg, 4 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to therapy and endocrinology, and concerns hypertension treatments in women in combination with hormone replacement therapy. That is ensured by introduction of Drospirenone (DRSP) in amount 0.5-3 mg/day and 17β-estradiol in amount 1-3 mg/day.

EFFECT: invention provides maximally effective arterial pressure reduction with minimum by-effects in given category of patients.

17 cl, 3 ex, 1 tbl, 8 dwg

FIELD: medicine.

SUBSTANCE: hop or hop-product is subjected to isomerisation reaction in presence of water in alkaline medium and at least one extraction, which is carried out by at least one organic solvent, selected from group of alcohols, water-containing alcohols, ketones, water-containing ketones or ethers or their mixtures or alkalised water. Reaction of isomerisation and at least one extraction is continued until obtained is extract which contains 8-prenylnaringenyl, in which (8-prenylnaringenin×100%)/(8-prenylnaringenin+6-prenylnaringenin) ratio constitutes at least 50%. By said method obtained is hop extract, which has estrogenic and anti-proliferative bioactivity. Hop extract is applied for producing medicament in which probable proliferative activity, caused by estrogenic activity of 8-prenylnaringenin, is inhibited or balanced by anti-proliferative activity of xanthogumol. Hop extract is applied for producing medicament for treatment or prevention of one of conditions, symptoms, complaints or diseases, caused by disturbance of hormonal balance of estrogenic nature.

EFFECT: invention allows realisation of said function.

25 cl, 2 tbl, 2 ex

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to ways of correction of an ovarian-menstrual cycle, and can be used in obstetrics and gynecology. Doppler and ultrasonic research is spent to an ovulation every day, since seventh day of the cycle, with gain definition of endometrium, a dominant follicle and changes of indicators of a blood flow in the arcuate arteries of a uterus and a perifollicular blood flow. Achievement of the sizes of endometrium thickness and a dominant follicle is estimated, and also change of indicators of a blood flow for 9, 11 day of a cycle and at the moment of an ovulation with individual selection of hormonal preparations. Control research through 7 and 14 days after an ovulation is carried out. Endometrium thickness, the sizes of a yellow body, blood flow indicators in arcuate arteries of a uterus and a yellow body are estimated. Individual hormonal therapy is prescribed. Further tactics of hormonal therapy at presence or absence of pregnancy is selected.

EFFECT: method allows to raise accuracy of diagnostics of disturbances of an ovarian-menstrual cycle at the women, suffering the endocrine form of sterility and to individualise selection of a dose of hormonal preparations at the expense of augmentation of controllable parametres.

4 ex, 5 tbl, 4 cl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to pharmaceutical field and deals with composition with delayed release, which does not contain gelatin, contains polymer of lactic and glycolic acids with ratio of average molecular weight and average numerical molecular weight about 1.90 or less or its salt and physiologically active substance, where polymer of lactic and glycolic acids has average molecular weight from 8000 to 15000 and molar ratio of lactic acid to glycolic acid constitutes from 70:30 to 80:20, and physiologically active substance represents peptide of formula: 5-oxo-Pro-His-Trp-Ser-Tyr-DLeu-Leu-Arg-Pro-NH-C2H5, or its acetate. In addition, invention describes method of obtaining said composition.

EFFECT: invention makes it possible to suppress high initial release of medication and, in such way, ensure stable rate of release during approximately one month.

10 cl, 4 tbl, 9 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to pharmaceutical industry and concerns a prolonged release parenteral solid composition containing a parenteral implant containing: triptorelin acetate and one or more excipients containing polymer or copolymer of lactic acid and/or glycolic acid or mixed copolymers, and said implant contains 35 to 55 wt % of triptorelin acetate in total implant equivalent, and it is produced by the method involving the fusion of mixed triptorelin acetate and an excipient or excipients during the extrusion fusion of triptorelin acetate with an excipient or excipients where mixed triptorelin acetate and a polymer or copolymer excipient or excipients is dried up before the extrusion fusion so that the water level does not exceed 8 wt %.

EFFECT: specified implant provides triptorelin acetate release during at least one week after the parenteral introduction to the patient.

8 cl, 5 ex

FIELD: pharmacology.

SUBSTANCE: invention refers to medicine and can be used as an effective remedy for precise delivery of DNA complexes with molecular conjugates to certain organs and tissues in mammals. The technical effect is ensured by introduction of modified nuclear localisation signal (NLS) that shall allow for conjugates to form complexes with plasmid DNA containing a suicidal gene, and also shall provide higher conjugate concentration in tumour cell nuclei that leads to intensification of cytotoxic properties of doxorubicine.

EFFECT: higher effectiveness of tumour cell exposure.

3 cl, 5 dwg, 6 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention concerns chemical pharmaceutical industry, particularly pharmaceutical administration forms with delayed liberation, containing at least one active peptide. The invention also concerns method for obtaining such forms, a kit containing liophilised peptide and water non-organic salt or acetate solution, and application of water non-organic salt or acetate solution in obtaining a pharmaceutical administration form sustaining continuous peptide liberation for a prolonged time.

EFFECT: prolonged liberation of active peptide due to the depot effect.

42 cl, 7 ex, 4 tbl

FIELD: medicine, endocrinology, hormones.

SUBSTANCE: invention describes an aqueous injection solution of antagonist of releasing-hormone luteinizing hormone (LHRH) containing gluconic acid, a filling agent and, optionally, a surfactant. LHRH antagonist is chosen from group of substances: cetrorelix, teverelix, D-63153 (Ac-D-Nal-pCl-Z-Phe-3-D-Pal-Ser-N-Me-Tyr-D-H-Cit-Nle-Arg-Pro-D-Ala-NH2), ganipelix, abarelix, antide or azalin B wherein gluconic acid is taken as delta-lactone in the above equimolar amount with respect to the amount of LHRH antagonist, and mannitol is used a filling agent. LHRG antagonist shows significantly improved solubility and can be prepared in higher concentrations and enhanced bioavailability. Also, tendency of LHRH antagonist to aggregation is reduced significantly.

EFFECT: improved and valuable properties of antagonist.

7 cl, 1 tbl, 3 ex

FIELD: medicine.

SUBSTANCE: the present innovation deals with treating Alzheimer's disease due to introducing the antagonist of luteinizing hormone-releasing hormone (LHRH) at the dosages to provide submaximal decrease of follicle-stimulating and luteinizing hormones level up to their normal levels that correspond to those of sex hormones being above their castration level. The innovation provides the desired results of therapy without such unfavorable side effects as the blockade of sex hormones.

EFFECT: higher efficiency of therapy.

12 cl, 1 ex

FIELD: medicine, gynecology.

SUBSTANCE: additionally to histological inspection of endometrial scrapes off in which one should detect quantitative content and density of distributing the receptors of sex steroid hormones it is necessary to calculate the percentage and density in distributing estrogen-induced protein-PS2. In case of low content of sex hormones receptors and, simultaneously, at low or negative PS2 value one should carry out radical surgical therapy or endometrial ablation; in case of inflammatory process and at low or negative content of receptors against sex hormones, but at positive PS2 value one should carry out preliminary antiphlogistic therapy, after it - hormonotherapy; at normal and high content of sex hormones receptors and positive P83 it is important to specify the size and the character of myomatous nodes and at diameter being under 3 cm (except submucosal myomas) one should carry out hormonotherapy, in case of single nodes at diameter ranged 3-5 cm and submucosal myomas one should carry out conservative myomectomy followed by hormonotherapy, and at the diameter of myomatous nodes being above 5 cm and/or in case of multiple myomas it is necessary to prescribe a certain technique and conservative myomectomy followed by the course of hormonotherapy. The innovation provides the chance for pathogenetically grounded individual approach to a patient and the choice of optimal therapeutic techniques due to taking into consideration the peculiarities of its hormonal receptor background.

EFFECT: higher efficiency of therapy.

2 cl, 4 ex, 1 tbl

FIELD: medicine, pharmaceutical chemistry.

SUBSTANCE: invention relates to a method for preventing formation of hydrophobic peptides gel, namely, "Teverelix". Method involves its contacting with counter-ion in the amount and in the molar ratio providing preparing liquid milk-like, microcrystalline aqueous suspension of peptide being without the gel formation. Also, invention relates to liquid, milk-like, microcrystalline aqueous suspension of "Teverelix" and counter-ion in water wherein peptide and counter-ions present in amounts and molar ratio providing formation of suspension without formation of gel in stirring. Invention provides enhancing stability of peptide.

EFFECT: improved preventing and preparing method.

35 cl, 8 ex

FIELD: chemistry of peptides, medicine, drugs, pharmacy.

SUBSTANCE: invention relates to pharmaceutical compositions containing polymer of lactic and glycolic acids with the ratio of average molecular mass and medium-numbered molecular mass about 1.90 or less, or its salt and physiologically active peptide as agonist of LH-RH of formula: 5-oxo-Pro-His-Trp-Ser-Tyr-Y-Leu-Arg-Pro-Z (I) wherein Y means D-Leu, D-Ala, D-Trp, D-Ser (tBu), D-2-Nal or D-His; Z means HN-C2H5 or Gly-NH2 or its salt, in particular, peptide of the formula: 5-oxo-Pro-His-Trp-Ser-Tyr-D-Leu-Leu-Arg-Pro-NH-C2H5 (II) or its acetate, and to polymer of lactic and glycolic acids with the ratio of average molecular mass and medium-numbered molecular mass about 1.90 or less. Also, invention relates to a method for preparing indicated polymer and to a microsphere containing indicated polymer and peptide of the formula (II), and to a medicinal agent used in prophylaxis or treatment of prostate cancer, prostatomegaly, endometriosis, uterus myoma, metrofibroma, premature sexual maturation and dysmenorrhea, or for a contraceptive agent comprising indicated microsphere, and to methods for prophylaxis or treatment of indicated diseases. Invention provides preparing compositions with delayed release and containing physiologically active substance of peptide nature and providing the stable rate of release of active substance for the prolonged period (up to 1 month) in inhibition of high initial release of indicated active substance.

EFFECT: improved preparing method, valuable medicinal properties of composition.

37 cl, 4 tbl, 9 ex

FIELD: veterinary science.

SUBSTANCE: method for increasing cow embryos survival involves a single intramuscular administration gonadoliberin surfagon in the dose 10 mcg to cows on 8-10 days after insemination followed by additional injection of thymogen in the dose 5 mcg/kg of body mass on 8, 9 and 10 days. Method provides maintenance of hormonal activity of yellow body in cows.

EFFECT: improved increasing method.

1 tbl, 1 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely oncology, and may be used in treating eyelid cancer for prevention of obliteration of the lachrymal ducts. That is ensured by irrigation of the nasolachrymal duct twice a day before each session radiation therapy and in 10-12 days after the session. A solution containing 0.1% dexamethasone min. 2.0 ml and methotrexate 5 mg is injected in the nasolachrymal duct in a lower nasal point through a blunt-ended cannula on a syringe.

EFFECT: method provides prevention of such bothersome symptom as permanent lachrymation, as well as maintenance of light-refringent, protective function of the lachrymal organs, and finally - maintenance of visual functions.

2 ex

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