13-ethyl-gona-1,3,5( 10), 8 (9)-tetraene-3,17β-diol diacetate, having anti-implantation and antioxidant activity
SUBSTANCE: invention relates to a diacetate of racemic 18-ethyl-gona-1,3,5(10),8(9)-tetraene-3,17β-diol, having anti-implantation and antioxidant activity with low uterotropic action. Presence of antioxidant activity in said steroid is essential since compounds with such action can be agents for preventing oestrogen-dependent breast cancer.
EFFECT: compounds exhibit anti-implantation and antioxidant activity with low uterotropic action, which is an advantage over agents used in practice.
1 cl, 1 ex, 4 tbl
The invention relates to medicine and can be used in the synthesis of biologically active analogues of steroidal estrogens, in particular, upon receipt of the diacetate of racemic 18-atilgan-1,3,5(10),8(9)-tetraen-3,17β-diol with antiinflammation and antioxidant activity at low uterotrophic activity that involves its use as a contraceptive pill.
Known patent, in which a method is proposed for the synthesis of 13-Alkylgona-1,3,5(10),9(11)-tetraenes , and also reported the existence of estrogen and lipid-lowering activity, which is the closest to the claimed invention and is selected as a prototype. Later this steroid in optically active form used as an intermediate substance for other compounds, but its biological properties are not studied .
The technical result of the claimed invention to provide compounds having antiinflammation and antioxidant effect at low uterotrophic activity.
This technical result is achieved by the synthesis of diacetate 13-atilgan-1,3,5(10),8(9)-tetraen-3,17β-diol.
The scheme of synthesis of steroid given in example 1.
Example 1. To a solution of 1 g of the known compound (3-hydroxy-13-atilgan-1,3,5(10),8(9)-tetraen-17-one)  in 40 ml of THF was added when paramesh the processes in 10 ml of 1M solution of lithium aluminum hydride in THF, the mixture is boiled for 2 hours Then the reaction mixture is cooled to room temperature, the excess solvent is decomposed with ethyl acetate and poured into 1 l of 3%aqueous hydrochloric acid solution. The reduction products are extracted with three portions of ethyl acetate, 100 ml), the combined extracts washed with water until neutral, dried with anhydrous sodium sulfate. The drying agent is filtered off, the residue is dissolved in 40 ml of pyridine, add 25 ml of acetic anhydride, the reaction mixture is left for a day at room temperature. After conventional treatment  the target compound allocate crystallization from methanol. Obtain 1.03 g (78%) steroid TPL 145-146 .5°C (lit. data TPL 141-143°C ).
Mass spectrum, m/z (IRel, %): 368 (35, M+), 326 (51), 266 (19), 237 (100), 209 (27), 181 (14), 160 (37), 133 (12), 107 (16).
Range13C NMR, δ, ppm: 9.81; 18.41; 21.00; 21.15; 21.91; at 23.66; 24.44; 27.95; 28.16; 29.92; 43.88; 48.28; 82.56; 118.77; 120.21; 122.55; 125.97; 133.53; 133.76; 136.62; 148.39; 169.67; 171.10.
Found, %: C, 74.99; H, 7.70. C23H28O4. Calculated, %: C at 74.97; H, 7.66.
Mass spectra obtained by the gas chromatography-mass spectrometry instrument Aligent 6850 with mass-selective detector Aligent 5973. Chromatographic analysis was performed on a capillary column HP-5MS length 30 m, internal diameter 0.25 mm and film thickness of stationary phase 0.25. The speed of the carrier gas (helium) through a column of 1.3 ml/min was Used linear programming temperature the tours thermostat column from 220 to 230°C at 5 C/min The evaporator temperature 330°C, the division of the flow of 20:1. Mass-selective detector was provided by the scan mass spectra obtained by electron impact ionization (70 eV) in the range from 50 to 800 m/z at a rate of 2 scans per second. The information obtained was processed using the program ADMIS.
Spectra were obtained at 295 °K spectrometer DPX-300 (Bruker) with an operating frequency of 75.468 MHz. For registration used a solution of 50 mg in 0.6 ml CDCl3. Chemical shifts are measured relative to TMS by setting the signal of the solvent (CDCl3/CHCl3=99.9/0.1) standard values 76.90 M. D.
Antiinflammation activity of racemic diacetate 3,17β-dihydroxy-18-atilgan-1,3,5(10),8(9)-tetraene investigated as follows. To the rats-females weighing 160-180 g with established estrous cycle was helping males, daily for 3 days, from the date of detection of sperm in the vaginal smears (the first day of pregnancy) were injected subcutaneously drug in an oil solution. After 20 days recorded the number of fruits. Experimental results are presented in table 1.
|Antiinflammation action diacetate 3,17β-dihydroxy-13-atilgan-1,3,5(10),8(9)-tetraene (1)|
|Injected drug the||Dose, mg/kg of body weight per day||The number of animals in the experience||Contraceptive effect, %|
In addition, the investigation revealed no pathology in the development of fruits and malformations in fetuses exposed to the drug in animals, retained pregnancy. Dimensions and weight of fetuses and placentas in this case did not differ from those in animals of the control group.
Uterotrophic effect of the drug in effective doses are considerably lower than those used in medical practice 17α-ethinyl estradiol (table 2).
|Uterotrophic action of racemic diacetate 3,17β-dihydroxy-13-atilgan-1,3,5(10),8(9)-tetraene (1)|
|Injected drug the||Dose, mg/kg of body weight per day||The number of animals in the experience||The weight of the uterus mg|
Antioxidant properties diacetate 3,17β-dihydroxy-18-methyl-östra-1,3,5(10),8(9)-tetraene investigated in accordance with the literature [5-9]. The research results presented in tables 3 and 4, processed by the Student's t - reliably indicated significant differences compared with the control experiments.
|Antioxidant properties diacetate 3,17β-Digi the Roxy-13-atilgan-1,3,5(10),8(9)-tetraene in the brain of rats (dose 1.5 mg/kg of body weight per day)|
|The group of animals||Schiff's base, $/mg lipids||Diene conjugates, nmol/mg of lipids||Tranvia conjugates cu/mg lipids||The coefficient Klein||Malonic dialdehyde, nmol/mg protein|
|Antioxidant properties diacetate 3,17β-dihydroxy-13-atilgan-1,3,5(10),8(9)-tetraene (1) in the liver of rats (dose of 1.5 mg/kg of body weight per day)|
|The group of animals||Schiff's base, $/mg lipids||Diene conjugates, nmol/mg of lipids||Tranvia conjugates, $/mg lipids||The coefficient Klein||Malonic dialdehyde, nmol/mg protein|
|rats treated erased the ID 1||P<0,01||P<0,05||P<0,05||P<0,05||P<0,01|
Thus, as shown by numerous experimental studies conducted on laboratory base of St. Petersburg state University and the research Institute of obstetrics and gynecology, steroid  used in doses is antiinflammation and antioxidant activity at low uterotrophic activity, which is an advantage compared to the actually used drugs. The presence of antioxidant activity alleged steroid is very important because of the connection with this action can be used as a means of prevention estrogenozawisimah breast cancer , which is particularly relevant today for health, given the recent tendency of this disease to a considerable increase.
1. 13-Alkylgona-1,3,5(10),9(11)-tetraenes // U.S. Pat. 3391170 (1968) - prototype
2. 8(9)-Dehydroestradiol derivatives // PCT Int. Appl. WO 98/16544.
3. Sorokin IB, Barkov TI, Saharicus AV, Chigir R.N., Ananchenko S.N., Trades IV // Estrogenic and anti-tumor activity in several transformed counterparts of estrone and estradiol. WPI. An SSSR, ser. chem. 1973, No. 5. S-670.
4. Felty Q., Singh, K., Ro D. Estrogen-induced G1/S transition to go-arrested estrogen-dependent breast cancer cells is regulated by mitochondrial oxidant signaling // Oncogene. 2005. V.24. N 31. P.4883-4893.
5. Folch, J., Less, M., Sloane-Stanly G.M. A simple method for the isolation and purification of total lipids from animal tissues // J. Biol. Chem. 1957. V.226. P.497-509.
6. Bartlet G. Phosphorus assay in colomn chromathography // J. Biol. Chem. 1959, V.23 supported. P.466-473.
7. Shvedova AA, Polanski NB // Method definition conjugates of lipid hydroperoxides in extracts of tissues. The study of synthetic and natural antioxidative (edited Ebbehoj): M. - 1992. P.74-75.
8. W.R. Bidlack, Tappel A.L. Fluorescent products of phospholipids during lipid peroxidation // Lipids. 1973. P.8.
9. Andreeva LI, Kozhemyakin L.A., CASCON A.A. Modification method determination of lipid peroxides in the test with TBQ // laboratory. case. 1988. No. 11. P.41-43.
Antiinflammation and antioxidant agent representing
SUBSTANCE: disclosed is a method of producing 1,2-dehydrogenated derivatives of Δ4-3-ketosteroids of the androstane family. A 1,2-dehydrogenation reaction is carried out using cells of a microorganism having high 3-ketosteroid-1-dehydrogenase activity, in a medium containing 8-40 vol. % water miscible aprotic solvent.
EFFECT: invention enables transformation of Δ4-3-ketosteroids and ensures high selectivity of formation of 1,2-dehydrogenated Δ4-3-ketosteroids at high rates of the process.
4 cl, 1 tbl, 5 ex
SUBSTANCE: invention relates to improved methods of producing 6-methyleneandrost-4-ene-3,17-dione and 6-methyleneandrost-1,4-diene-3,17-dione (MNN exemestane) using the obtained 6-methyleneandrost-4-ene-3,17-dione. 6-methyleneandrost-4-ene-3,17-dione is obtained using a method involving preliminary enolisation of Δ4-3-ketofunction of androst-4-ene-3,17-dione with formation of 3-alkoxyandrost-3,5-dien-17-one, subsequent three-component condensation with a secondary amine and formaldehyde in the medium of a polar protonic solvent, deamination of the N,N-disubstituted amino group to form a 6-methylene group in the medium of an aprotic solvent. 6-methyleneandrost-1,4-diene-3,17-dione is obtained through 1,2-dehydrogenation of 6-methyleneandrost-4-ene-3,17-dione via microbiological transformation in a medium containing up to 40% water-miscible aprotic solvent using Nocardioides simplex cells VKM As-2033D.
EFFECT: high output and selectivity under mild conditions for carrying out the process.
11 cl, 4 ex, 1 tbl
FIELD: medicine, pharmaceutics.
SUBSTANCE: claimed invention relates to process of crystallisation, obtaining and isolation of novel crystalline form of fusidic acid, to application of said processes in production of pharmaceutical composition or medication, and to application of said form of crystalline fusidic acid in treatment of bacterial infections.
EFFECT: obtaining pharmaceutical composition for treatment of bacterial infections.
11 cl, 10 ex, 1 tbl, 10 dwg
SUBSTANCE: invention enables synthesis of 3-methoxy-2-fluoro-18ethyl-8α-gona-1,3,5(10)-trienes, having osteoprotector and hypocholesteremic activity.
EFFECT: invention has osteoprotector and hypocholesteremic activity and can be used in medicine for hormonal replacement therapy.
1 cl, 3 ex, 1 tbl, 3 dwg
SUBSTANCE: claimed invention relates to application of steroid compounds, preferably 17 α-ethinyl derivatives of androstane.
EFFECT: insuring treatment of inflammatory or autoimmune disease in subject and/or infection prevention.
7 cl, 12 ex, 18 dwg
SUBSTANCE: invention provides administration of triterpene glycosides of holothurian Cucumaria okhotensis chosen from a group consisting of Frondoside A1, Ochotoside B1, Ochotoside A1-1, Ochotoside A2-1 or Cucumarioside A2-5 or their mixtures, as an agent stimulating cell-mediated immunity in mammals, as well as for preparing a pharmaceutical composition stimulating cell-mediated immunity in mammals.
EFFECT: extended range of the agents stimulating cell-mediated immune reaction in mammals.
4 dwg, 1 tbl, 2 cl
SUBSTANCE: invention refers to a method of Δ4-3-ketosteroids 11 β-hydroxylation by a biomass Curvularia lunata strain mycelium, RNCIM No. F-988. For the transformation, Curvularia lunata strain mycelium, RNCIM No. F-988 not older than 30 h and washed of nutrient medium is used. Mycelium is taken in such amount that the relation of the biomass to the transformed steroid makes 1.5-2.5:1. The transformation is performed in a buffer solution, and a steroid substratum is added as a microcrystal suspension, or as a water-soluble methyl - β-cyclodextrine complex with steroid related thereto as 1:1-0.6:1 (mol/mol). The yield of 11β-hydroxyderivatives is 50-80 %.
EFFECT: offered invention allows for higher selectivity of 11β-hydroxylation process, concentration of the transformed steroid substratum up to 20 g/l and reduced reaction period to 24-50 h.
1 tbl, 10 ex, 2 cl
FIELD: medicine, pharmaceutics.
SUBSTANCE: there are described compounds of the following structure or their salts: where A, B, R2, R4, R6, R7, R10, R16, R17α, R17β, Z, Y, X have the values specified in the description. Some of these compounds exhibiting tissue-specific antiandrogen activity and tissue-specific androgen activity can be applied for treating or reducing risk of the diseases associated with androgen stimulation loss.
EFFECT: preparation of the compounds which reducing probability of the androgen-dependent diseases, such as prostate cancer, benign prostate hyperplasia, polycystic ovary syndrome, acne, hirsutism, seborrhoea, etc.
41 cl, 176 ex, 4 tbl
SUBSTANCE: there are described compounds of formula in a free form or in the form of salt where R1 and R2 have values specified in the description of the application which are used for treating inflammatory conditions, first of all inflammatory or obstructive respiratory tract diseases. Besides the application describes the pharmaceutical compositions containing said compounds, and methods for preparing said compounds.
EFFECT: compounds exhibits improved efficiency.
5 cl, 8 ex
SUBSTANCE: described is a 15β-substituted oestradio derivative having selective oestrogenic activity. The preferred compound is 7α-ethyl-15β-methyl-19-nor-17α-pregna-1,3,5(10)-trien-20-yne-3,17β-diol.
EFFECT: obtaining compounds which can be used in treating or preventing diseases or physiological conditions related to oestrogen receptors.
11 cl, 4 ex, 2 tbl
SUBSTANCE: invention relates to novel antibiotic oligomycin A derivatives, having anti-tumour activity and low toxicity, of formula: , where R is a methanesulphonic acid (OSO3CH3) residue or an azide group (N3) and synthesis method and use thereof.
EFFECT: obtaining novel antibiotic oligomycin A derivatives.
3 cl, 1 dwg, 1 tbl, 4 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to pyridine-3-yl derivatives of formula (I)
wherein A represents *-CONH-CH2-, *-CO-CH=CH-, *-CO-CH2CH2-, or wherein asterisks specify a link which binds with a pyridine group of formula (I); R1 represents hydrogen, C1-4alkyl or chlorine; R2 represents C1-5alkyl or C1-4alkoxy group; R4 represents hydrogen or C1-4alkyl; R4 represents hydrogen, C1-4alkyl; C1-4alkoxy group or halogen; R5 represents -CH2-(CH2)n- CONR51R52, -CO-NHR51, 1-(3-carboxyazetidinyl)-2-acetyl, hydroxy group, hydroxyC2-5alkoxy group, di-(hydroxy C1-4alkyl) C1-4alkoxy group, 2,3-dihydroxypropoxy group, 2-[(azetidine-3-carboxylic acid)-1-yl]ethoxy group, -OCH2-CH(OH)-CH2-NR51R52 or -OCH2-CH(OH)-CH2-NHCOR54; R51 represents hydrogen, C1-3alkyl, 2-hydroxyetyl, 2-hydroxy-1-hydroxymethyletyl or 2,3-dihydropropyl; R52 represents hydrogen; R54 represents hydroxymethyl; n represents 0 or 1; and R6 represents hydrogen, C1-4alkyl or halogen; and a salt of said compound. Also the invention describes a pharmaceutical composition for prevention or treatment of diseases or conditions associated with activated immune system, on the basis of the compound of formula I and application of said compounds for preparing said pharmaceutical composition.
EFFECT: there are produced and described new compounds which are especially active as immunomodulatory agents.
18 cl, 92 ex, 2 tbl
FIELD: medicine, pharmaceutics.
SUBSTANCE: present invention refers to quinoline derivatives of formula I
, or to its pharmaceutically acceptable salts, wherein X1 represents O; p represents 0, 1 or 2; each group R1 which can be identical or different and which can be located only in positions of 6- and/or 7-quinoline ring, specified in halogen, cyano, carboxy, (1-6C)alkoxycarbonyl, carbamoyl, (1-6C)alkoxy, N-(1-6C)alkylcarbamoyl, N,N-di-[(1-6C)alkyl]carbamoyl, or in a group of formula: Q1-X2-, wherein X2 represents CO and Q1 represents pyrrolidine, q represents 0 or 1; R2 represents (1-6C)alkoxy; R3 represents hydrogen or (1-6C)alkyl; R4 represents hydrogen; R5 represents hydrogen, methyl, ethyl, propyl, allyl, 2-propynyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 3-fluoropropyl, 3,3-difluoropropyl, 3,3,3-trifluoropropyl, 2-hydroxyethyl, 3-hydroxypropyl, 2-methoxyethyl, 3-methoxypropyl, cyanomethyl, 2-cyanoethyl or 3-cyanopropyl; the ring A represents a 5-membor monocyclic heteroaryl ring with up to three ring heteroatoms specified in oxygen, nitrogen and sulphur; r represents 0, 1 or 2; and each group R6 which can be identical or different is specified in amino, (1-6C)alkyl, (1-6C)alkylamino, di-[(1-6C)alkyl]amino, or in a group of formula: -X6-R15 wherein X6 represents a single link and R15 represents (1-6C)alkoxy-(1-6C)alkyl, di-[(1-6C)alkyl]amino-(1-6C)alkyl or in a group of formula: -X7-Q3 wherein X7 represents C(R17)2N(R17) wherein each R17 represents hydrogen and Q3 represents (3-8C)cycloalkyl, and wherein any CH2 group within the R6 group optionally carries a hydroxy group on each said group. Also, the invention refers to methods for making the compound of formula I, to a pharmaceutical composition on the basis of the compound of formula I, to applying the compound of formula I and the combinations on the basis of the compound of formula I and additional anticancer drugs.
EFFECT: there are produced new quinoline derivatives effective in treating diabetic retinopathy and disturbed cell proliferation.
15 cl, 6 tbl, 32 ex
SUBSTANCE: invention refers to medicine, concerns treating cancer. The tumour is exposed to gamma photon with a radiation source cobalt-60 at gamma photon radiation energy 1.25 MeV. A patient takes herbal infusion 400-500 ml 30-40 min before the radiation therapy session: Alexandrian laurel leaves, burdock leaves, alder blossom, dill seeds, celandine herb, nettle herb and sage herb in equal portions. The plants are pre-dried in the shade to humidity 14-16 %, then each is taken in the amount of 100 g, mixed and powdered. The herbal powder 40-50 g is filled with boiling water 500-600 ml, boiled for 3 min, and settled for 2-3 hours. Between the radiation therapy sessions, the patient takes the infusion 200-250 ml twice a day, and after the termination of the therapeutic course, the infusion 200-250 ml is prescribed once a day.
EFFECT: method provides clinical effectiveness ensured by prevented metastases formation.
SUBSTANCE: invention refers to medicine, namely oncology, and can be used for treating cervical cancer. That is ensured by radiation teletherapy and brachytherapy. Each brachytherapy session is preceded by bringing the Hydrogel Coletex-M Tissue 3-5 ml to the tumour before 12-18 hours. Before gel contact, the Coletex-M Tissue is introduced. Further,1-1,5 hours prior to the brachytherapy session, the textile tissue is removed, and Hydrogel Coletex-ADL Tissue 4-6 ml is brought to the tumour. Preliminary, the Hydrogel Coletex-ADL Tissue is added with lidocaine to achieve the gel concentration 4-6%.
EFFECT: method provides reduced total toxicity and drug load ensured by the required concentration of metronidazole maintained in the tumour before the radiation session, and also analgesia without using narcotic preparations, optimised time and geometry of centring introduction that allows intensifying the damage exposure on the tumour.
SUBSTANCE: invention concerns medicine, oncology, and is applicable for photodynamic therapy of malignant growths. That is ensured by introducing a photosensitiser and conducting light illumination of the new growth at wave length corresponding to a maximum absorption of chlorine derivatives. The photosensitiser is presented by a gelatinous capsule with powder microparticles of chlorine derivatives mixed with lyophilised spirulina platensis. Each powder microparticle is coated with a protective acid-resistant film. The gelatinous capsule is introduced orally. Each gelatinous capsule contains the ingredients in the following proportions (Mg): chlorine derivatives - 1-1.5; spirulina platensis - 100-150; protective acid-resistant film - 50-75; calcium stearate - 0.5-0.75.
EFFECT: method enables providing higher clinical and preventative effectiveness in malignant new growths.
8 cl, 1 dwg, 3 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: group of inventions refers to medicine, and concerns pharmaceutical compositions able to induce cancer cell apoptosis for diagnosing and treating B-cell chronic lymphocytic leukaemia. Substance of the inventions involves the pharmaceutical compositions for treating B-cell chronic lymphocytic leukaemia containing an active ingredient presented by a humanised monoclonal antibody T1h from a secreting hybridoma IOR-TIA under depositary No. ECACC 96112640, identifying a leukocyte differentiation antigen CD6. A diagnostic reagent also contains said antibody.
EFFECT: advantage of the group of inventions consists in higher specific activity.
11 cl, 4 ex, 4 dwg
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to pharmaceutics and medicine and concerns triindolyl methane derivatives of formula
and as anticancer drugs showing cytotoxic, apoptotic action on tumour cells, and also blocking NFkB transcription factor activity.
EFFECT: compounds exhibit high anticancer activity.
4 dwg, 3 tbl, 4 ex
SUBSTANCE: group of inventions refers to medicine and veterinary science. A method involves sequential intravenous introduction of a binary catalytic system (BCS): an oxidation catalyst - a metal complex and an oxidation substratum - ascorbic acid (AA). The oxidation catalyst is introduced in a maximally tolerable or lower doses, and AA - in doses related to molar ratio of the metal complex: AK=1:10. The method also involves local hyperthermia of the tumour with using near infra-red laser emission. The tumour temperature is maintained within the range of 43-45°C by adjusting laser power density. The emission is terminated after achieving the minimum power density maintaining the tumour temperature within the preset temperature range. The declared device comprises a near infra-red laser with emissive power switch-on, switch-off and adjustment systems, and optical system of laser beam formation, a tumour temperature control system with its output connected both with an input of a laser negative feedback system, a laser power density control system. The device comprises an additionally adjustable power density discriminator. An input of the laser power density discriminator is connected with an output of the laser power density control system. The output of the discriminator is connected to an input of the laser switch-off system.
EFFECT: invention provides higher clinical effectiveness.
5 cl, 1 dwg, 1 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: group of inventions refers to medicine and is applicable in the form of liposome-containing compounds for cancer therapy. A liposome contains one or more phosphatidylcholines, a first derivative of N-(ω)-dicarboxylic acid and phosphatidylethanolamine, an orientation modified derivative of N-(ω)-dicarboxylic acid and phosphatidylethanolamine, an encapsulated therapeutic agent and at least one additional lipid which represents cholesterol or a cholesterol derivative. The orientation modified derivative of N-(ω)-dicarboxylic acid and phosphatidylethanolamine contains an orientation ligand attached to a second derivative of N-(ω)-dicarboxylic acid and phosphatidylethanolamine. The first derivative of N-(ω)-dicarboxylic acid and phosphatidylethanolamine is presented by formula 1,
and the second derivative of N-(ω)-dicarboxylic acid and phosphatidylethanolamine is presented by formula 3, . The orientation ligand preferentially represents transferring, while the encapsulated therapeutic agent is oxalyplatine. The liposome is free from non-modified phosphatidylethanolamine, egg phosphatidylcholine or hydrophilic polymer used to prolong a half lifetime of the liposome in a circulatory channel, and the orientation ligand is other than an intact antibody. What is also described is a method of producing the liposome and a method of treating cancer with using it.
EFFECT: group of inventions provides better target delivery of the therapeutic substance in the tumour cells.
113 cl, 25 dwg, 4 tbl, 30 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: as a first active agent a pharmaceutical composition contains drospirenone in the amount equal to a daily dose when administering the composition and making 2 to 4 mg, and as a second active agent - ethinylestradiol in the amount equal to a daily dose and making 0.01 mg to 0.05 mg, together with one or more pharmaceutically acceptable carriers or additives. Drospirenone as a part of the pharmaceutical composition has a particle surface area more than 10000 cm2/g. Preferentially, drospirenone is fine-grained or sprayed from a drospirenone solution by inert carrier particles. The preparation contains a number of separately packed and individually taken daily dosage units in a single package used for oral administration for at least 21 days running with said daily dosage units containing a combination of drospirenone and ethinylestradiol. The preparation may additionally contain 7 and less daily dosage units containing no active agent, or containing ethinylestradiol only.
EFFECT: combination of drospirenone and ethinylestradiol provides reliable contraceptive activity ensured by the use of a maximum dose of drospirenone which causes no side effects, particularly, excess diuresis.
29 cl, 5 dwg