The way to prevent pregnancy


The invention relates to a method of preventing unwanted pregnancy in an individual, comprising intravaginal administration to the individual an effective amount of a composition containing narrow or monodisperse condensation polymer of aromatic sulfonic acids and aldehyde or its pharmaceutically acceptable salt, as well as to a method of preventing unwanted pregnancy in an individual, including vaginal introduction of the gel containing the above-described condensation polymer. The technical result - the method allows the use of the above compounds in the manufacture of medicaments for the prevention of pregnancy or contraception. Compounds of the present invention little annoying or not irritate the vagina. 2 C. and 7 C.p. f-crystals, 2 tab.

Many condensation polymers of formaldehyde and aromatic sulfonic acids have been described previously. U.S. patent 4604404 and patent applications U.S. 08/467725, 08/467725, 08/245619 and 08/156443, the contents of which are incorporated into the present application by reference, disclose the nature of the use of such polymers as antiviral agents against Herpes simplex virus and HIV.

One of the possible pregnancy.

Spermicidal formulations are a popular form of reversible contraception in the United States (Forrest J. D. and R. Fordyce R. Fam. Plann. Perspect. 20:112-118 (1988)). Most intravaginal contraceptive formulations as the active ingredient contain spermicide, nonoxynol-9 (N9). These recipes usually creams, gels or foam, is usually effective immediately after application, and can be entered about an hour before sexual intercourse (R. A. Hatcher et al. , "Contraceptive Technology, 16thRevised Edition, New York, Irvington Publishers (1994)). Vaginal contraceptive film, such as "VCF" (Apothecus, Inc., Oyster Bay, NY), appeared on the market later, at least in the United States. In contrast to other intravaginal contraceptives, the film is necessary to introduce a few minutes before sexual intercourse, in order to ensure adequate dissolution and dispersion to contact with sperm.

When using a separate spermicides give the frequency of adverse outcomes, approximately 21% (i.e., usually accidental pregnancy during the first year of use occurs in 21% of partners using these products). As reported, the efficiency is greatly improved if spermicides are used in combination with barrier methods such as condoms (Hatcher, R. A. et al., "Contraceptive Technology, 16th is salonie polymers of aromatic sulfonic acids and aldehyde and their fractions, in particular, polymers of formaldehyde and naphthalenesulfonate, may prevent pregnancy or prevent it. Prevention or hindrance of pregnancy is defined as a process involving, for example, warning or barrier to fertilization, conception or implantation of a fertilized egg or embryo into the endometrium of the uterus in the female animal. It was found that the compounds of the present invention little annoying or not irritate the vagina. On the basis of these results, condensation polymers of aromatic sulfonic acids and aldehyde and their fractions can be used as contraceptives. Therefore, the invention also relates to the use of the described compounds in the manufacture of medicaments for the prevention of pregnancy or contraception.

Getting condensation polymers of aldehydes and aromatic sulfonic acids generally known in the art. Preferred polymers have the General structure:Aromatic sulfonic acids, when used here, include aromatic carbocyclic and heterocyclic rings substituted by one or more radicals were snil, naphthyl, tetrahydronaphthyl, biphenyl, phenylalkylamines, phenylacetylene, phenoxyphenyl, phenylthiophene and phenoxyacetyl. Aromatic heterocyclic ring (AG) include, for example, pyridinyl, pyrimidinyl, chinoline, thiophenyl, furanyl, pyrazolyl, imidazolyl, pyrrolyl and thiazolyl. Aldehydes (chrO), suitable for producing compounds according to this invention include, for example, paraformaldehyde or formaldehyde, substituted or unsubstituted acetaldehyde, propionic aldehyde and benzaldehyde. Preferably the aldehyde is formaldehyde. Accordingly, R in the formula may be hydrogen, substituted or unsubstituted alkyl (preferably lower alkyl), substituted or unsubstituted aryl (such as phenyl). The substituents include, for example, alkyl, alkoxygroup, aryl, alloctype, halogen, hydroxyl, amino, alkylamino, dialkylamino, carboxyl group, sulfonate and phosphonate. The polymer may be a free acid, a complex ester or a pharmaceutically acceptable salt. Therefore, M can be hydrogen, a pharmaceutically acceptable cation (e.g., alkali metal, alkaline earth metal or ammonium group) or blocking sulfonate group, Chilam). The term "polymer", when used here, includes any compound formed by combining two or more monomers or repeating elements (for example, n is an integer equal to two or more). U.S. patent 4604404 gives examples of suitable polymers suitable for use here, and the methods for their production, these data are included here by reference. Polymers are also described in application U.S. 08/467725, 08/245619 and 08/156443, the contents of which are incorporated into the present application by reference.

A particularly preferred polymer is the condensation product of naphthalenesulfonate and formaldehyde with the formula:where x is 1 or 2; R2is hydrogen, alkyl, alkoxygroup or anionic group, such as carboxyl and phosphonate, M is hydrogen or a pharmaceutically acceptable cation.

In some cases, one or more sulfonic groups can be irreversibly locked.

The polymers of the present invention also include copolymers, where the aldehyde and/or aromatic acid is added in the form of mixtures of different aldehydes and/or aromatic sulphonic acids (such as defined above). Also included are copolymers where bollicelli or heterocyclic group (defined above), not substituted or substituted by one or more groups such as alkyl, alkoxygroup, aryl, alloctype, halogen, hydroxyl, sulfonamidnuyu, carboxyl or phosphonate.

Preferably, the molecular weight of the polymer (MB) was less than about 50 kDa, and/or greater than about 0.7 kDa. Preferred polymers with a molecular weight of between about 1.3 and about 30 kDa, or between about 4 and about 12 kDa. Particularly favorable polymer is the condensation of 2-naphthalenesulfonate and formaldehyde with a molecular weight of 51 kDa.

Preferably, the average number of molecules sulfonic acids on the aromatic group is from about 0.5 to 2.0, most preferably about 1.0.

Polymers with narrow or monodisperse molecular weight can be obtained by fractionation methods generally known in the art (see, for example, Polymer Fractionation, Editors, Cantow and Manfred, Jr. , (Acad. Press) 1967), such as precipitation in selective solvents, gel-filtration chromatography, precipitation in saline solutions and diafiltrate. Alternatively, the polymers can be produced using sequential or managed the composition, in which its components are largely the same molecular weight. For example, oncodispensary polymer includes polymer compositions, where the polydispersity is less than about 2, preferably less than about 1.5, and more preferably less than about 1.2. "Monodisperse polymer" is defined as a polymer composition, where almost all components have the same molecular weight, such as tetramer, pentamer, hexamer, heptamer, octamer, nonamer etc.

As described above, the condensation polymer may, optionally, be introduced in the form of pharmaceutically acceptable salts. Examples of suitable salts include salts of alkali metals, alkaline earth metals and ammonium, such as salts of calcium, sodium, potassium, ammonium and alkyl - or arylamine (such as trimethylammonium salt, triethylamine and triethanolamine (trolamine)).

The drug or the polymer of the present invention can be introduced intrawaginalno (such as contraceptive formulations, suppositories or grease) in dosage formulations containing a physiologically acceptable carrier and, optionally, substances that enhance the action, and preservatives. Suitable formulations include physiologically acceptable gels, foams and creams. But the STI, can be used a solution of sodium chloride for injection, USP (0.9%), ringer's solution for injection USP, ringer's solution for injection lactate USP, the solution of sodium lactate for injection USP, dextrose injection USP (5% or 10%), bacteriostatic water for injection USP, and sterile water for injection USP. In another example embodiment of the invention, the connection form, is applied or sprayed, for example, in the form of a film on contraception, such as condoms (including male condoms and female condoms, as in the case of the female REALITY condom (Women's Health Company), U.S. patent 4735621) or aperture. The specific dose of the active ingredient will depend on many factors, including biological activity of the individual drug and the General health of the patient or individual.

Typically, the connection will be included in the formulation in the form of a gel with a concentration of from about 0.5 to about 50%, preferably from about 1 to about 10% (weight). Gelling agents for pharmaceutical formulations are well known in this field. For example, the gelling agent can be hydroxyethylcellulose (such as Hydroxyethyl Cellulose 250 NNC, (Natrosol)), guar gum, cellulose resin, cross-links is about the preferred gelling agent is a Carbomer 1382, copolymer of acrylic acid and long chain methacrylate, cross-linked with allyl ethers of pentaerythrol. The agent is usually added in an amount of from about 1 to about 5% by weight.

The compound or formulation is usually administered before sexual intercourse or after intercourse (for example, not more than one hour before or within twelve hours after intercourse), such as immediately before or after sexual intercourse (for example, within 30 minutes before or one hour after sexual intercourse). Connection, you can enter the open (with the consent of the male partner) or implicitly (without the knowledge or consent of the male partner).

Primarily, the compound is administered in an amount that is effective for not only as a contraceptive, but as an antiviral or antibacterial agent (for example, in an amount that inhibits HIV infection, or infection by herpes virus or other sexually transmitted diseases). Other antiviral agents which impair the replication of the HIV virus, you can enter with this drug in accordance with the methods of the present invention with a synergistic result in some cases. CA virus optimizing thus therapeutic effect of the preparation according to this invention, reducing or eliminating the infectivity of the virus and the symptoms associated with it. For example, agents that inhibit reverse transcriptase of the HIV virus (such as azidothymidine (AZT), dideoxyinosine (ddI), lamivudine, stavudine or RMR) inhibitors integration, transcription or translation (reverse isomers oligonucleotides), other inhibitors of fusion/binding inhibitor Assembly/separation (e.g., interferon), HIV protease inhibitors (such as Saquinavir, Indinavir, Ritonavir, Nelfinavir, VX-478) or non-nucleoside reverse transcriptase inhibitors (such as delavirdine or nevirapine) may be introduced together with a condensation polymer, separately or as a separate dosage formulations containing condensation polymer and the other(s) antivirus(e) agent(s).

The preparation according to this invention can also be put together with additional contraceptive formulations, such as nonoxynol-9, octoxynol, chlorhexidine, benzalkonium chloride and menfegol.

The invention has the advantage over other methods of inhibiting conception, as it poses no risk of accidental failure at rische male and female condoms), no side effects for sexual way (as intrauterine devices), can be further effectively against sexually transmitted diseases (STDs that are not shown for the IUD and oral contraceptives), does not require daily injection for efficiency (as in the case of oral contraceptives) and mostly not absorbed into the systemic circulation, thereby preventing side effects, explain the system introduction (as in the case of oral contraceptives).

The invention will be further illustrated by the following not limiting the invention examples.

Example 1. Synthesis of condensates: polymerization.

A mixture of sodium salt of 2-naphthalenesulfonate (1,15 g, 5 mmol), 37% aqueous formaldehyde (0,65 ml, ~ 6 mmol) and sulfuric acid (0.7 g of concentrated sulfuric acid in 0.5 ml water) was heated to 98-100oC for 43 h, the Reaction mixture was then diluted with water (30 ml), neutralized with calcium carbonate to pH 7 and filtered, the filtrate evaporated to dryness to yield 1.22 g of the condensation polymer.

The above experiment was repeated, modifying the parameters of the reaction, as illustrated in the table. 1.

Example 15. The synthesis of the condensation polymer inali with ~ 3 ml of 37% formaldehyde (~43 mmol), 1.9 ml of concentrated sulfuric acid was added 5 ml of water and heated in hermetically sealed tube for ~ 24 hours at 120-130oC. the Reaction mixture was diluted with water (~ 20 ml) and neutralized to pH 7 using NaOH. The neutralized reaction mixture was concentrated to dryness to obtain ~ 11 g of the substance, which consisted of condensate and salts.

Synthesis of condensates: restaging.

Example 16. 5-Bromo-2-naphthalenesulfonate.

5-amino-2-naphthalenesulfonate (1,15 g, 50 mmol) was dissolved in 100 ml 15 0.5 N NaOH solution under stirring. Dark red solution was cooled to 0oWith the addition of ice (~ 100 g). To dissolve ice was added dropwise 20 ml of 40% aqueous solution NVG, and the resulting suspension was kept at a temperature of from -5 to 0oWith, then after 30 min was added 10 ml of an aqueous solution of NaNO2(3,65 g). The mixture was continuously stirred for 30 minutes at a temperature of -5 ~ 0oC. Unreacted NaNO2destroyed by addition of 350 mg of urea at the end of the reaction. The resulting dark diazonium suspension was kept at a temperature below 0oC and added dropwise within one hour to a solution of CuBr (7,15 g) in 40 ml of 40% Nug at 70oWith vigorous stirring (solution of CuBr nanodisperse and was treated with 200 ml of water. The precipitate was collected in a Buchner funnel and washed with about 50 ml of water. After drying under vacuum, there was obtained a 13.9 g of crude product. The crude compound was heated under reflux in 500 ml water for 2 h, cooled to room temperature and filtered. The filtrate is evaporated to dryness, and the solid was dried in vacuum to yield 8,23 g (57% yield) of pure product.

Product purity was checked using obetovannoi liquid chromatography high pressure and1H-NMR (250 MHz).

Example 17. 8'-Methylene-bis-5-bromo-2-naphthalenesulfonate (sodium salt).

A mixture of 5-bromo-2-naphthalenesulfonate (17,22 g), TFUK (200 ml), the resin Amberlyst-15 (17 g, Aldrich), paraformaldehyde (4.5 g) and H2O (50 ml) was heated to 130oC for 14 h in a sealed thick-walled tube. After cooling to room temperature the mixture was filtered in a Buchner funnel, and the collected solid is washed with about 10 ml TFUK, was dissolved in 250 ml of methanol/water (4/1) and filtered. The filtrate is evaporated to dryness, and the solid was suspensively in 80 ml of water and neutralized to pH ~ 8 10 M NaOH solution. The solid was filtered off, washed with 60 ml of acetone and dried in vacuum over night. Received 15.03 g (80% yield) of naphthalenesulfonate (sodium salt, 6,30 g) was slowly added to NaOH (0.32 g) in 300 ml of methanol with Pd-C (10%, 5.0 g) in an argon atmosphere. The suspension was shaken under a pressure of H2equal to 50 pounds per square inch, for 18 hours Then the mixture was filtered, and the filtrate was passed through a column filled ~ 20 g resin IR-120. The solvent was removed on a rotary evaporator, and the residue was dissolved in 200 ml of water, and then filtered. The filtrate was neutralized with 5 M NaOH solution to pH ~ 7 and concentrated to a volume of ~ 50 ml, then slowly with shaking was added 300 ml of acetone. The resulting white precipitate was collected in a Buchner funnel, washed with 20 ml of acetone and dried in vacuum with the formation of 3.51 g of dry product (sodium salt).

Examples 19 and 20. Oligomerization tetramer and hexamer respectively.

of 5.11 g of sodium salt of dimer was converted to the free acid by passing through a column of resin IR-120 in the water. Water was removed on a rotary evaporator and the residue was again dissolved in 10 ml of water and transferred into 50 ml TFUK in a thick-walled flask, then added paraformaldehyde (of € 0.195 g), and the flask is hermetically closed. The solution was stirred at 60-65oC for 15 h, the Solvent was removed, and the residue was dissolved in methanol, was applied to silica gel and pair with a solution of THF: methanol: N2About in the ratio of 16:1:1 to 5:1 ratio:1.

The solid substance of the tetramer fraction was neutralized to pH ~ 7 using 5 M NaOH in 5 ml of water was added 5 ml of methanol and 125 ml of acetone to obtain 0,94 g of precipitate. Salt was converted to the free acid by passing through the resin IR-120, and was obtained 0.73 g of dry tetramer.

From a review of the fractions was obtained 0.21 g hexamer the same way as described for the tetramer.

3.5 g of starting material dimer was allocated back from the first fraction.

Example 21. The octamer.

A mixture of tetramer (130 mg), resin Amberlyst-15 (150 mg), water (0.4 ml) and 2 ml of a solution of paraformaldehyde in TFOC (1 mg/ml) was stirred at 85oC for 15 h in a bottle for sampling closed Teflon cap. The reaction mixture was cooled to room temperature, diluted with 5 ml of water and filtered. The filtrate is evaporated to dryness, dissolved in methanol and applied on silica gel, then passed through the column, where the tetramer was suirable solution of THF:isopropanol:N2O in the ratio of 6:1:1, and the octamer was suirable solution of methanol: N2O (85:15). From the second fraction was obtained 50 mg of crude octamer.

Crude octamer was passed through the resin IR-120, cleansed help when the level of purity of 96.6 percent according to the analytical liquid chromatography high pressure), Example 22. Size-exclusion chromatography for fractionation by size/ Aliquots of solutions of synthetic polymers was fractionally size using pump Waters M625, diode detector M, system software Millenium and either two columns Waters Ultrahydrogel (7,h mm; the volumetric rate of the mobile phase, 1 ml/min) with pores of 6 µm to 250 angstroms or column TosoHaas G3000PW 17 μm (21,h mm) connected to a column TSK-Gel Guard PWH (21,h mm; the volumetric rate of 3 ml/min). The mobile phase consisted of 0.2 M solution of ammonium acetate (pH 6,2), prepared from glacial acetic acid (Baker Analysed HPLC Reagent) and ammonium hydroxide (25%, Mallinckrodt), and 35% acetonitrile (B&J Brand). Before using the mobile phase was filtered through nylon membrane with a pore diameter of 0.45 μm and sprayed in the atmosphere of helium quality 5. The solution of the synthesized samples from 2.2 to 10 mg of the substance in the volume of MilliQ water to 200 μl were injected with Ultrahydrogel columns or 40-300 mg of the substance in the mobile phase on the basis of MilliQ water up to 2 ml (50:50, by volume) were injected with columns TosoHaas, followed by sonication (Branson 2200), vortex mixing, and filtration (0.45 µm Acrodisc, Gelman Sciences). The collected fractions were combined according to the time of elution. Comparable chromatog is whether using high-speed vacuum devices Savant at high temperature (or SC200 and Vapornet VN100, or Plus SC210A). The residue was re-dissolved in water and re-dried to remove traces of solvent. The substance was weighed, dissolved in water and was normalized to the initial concentration by measuring the absorption of light at a wavelength of 290 nm in comparison with standard solutions.

The substance according to example 12, see table. 1 above, was fractionally thus to obtain fractions of the polymer, which had neveroyatnye molecular weight (NIV) 31 kDa (average molecular weight (SMW) 38 kDa); NIV 16 kDa (SMW 22 kDa); NIV 10 kDa (SMW 15 kDa); and 5,6 NIV kDa (SMW 10 kDa).

Example 23. The methodology of the light scattering.

The samples were subjected to analytical liquid chromatography high pressure pump Waters 625 and modified detector 410 RI, which contained a built-in detector of the intensity of scattered laser radiation PD2000 (Precision Detectors, Inc., Amherst, MA). This system was equipped with a column Waters Ultra-Hydrogel 250 for gel-filtration chromatography of aqueous solutions (inner diameter of 7.8 mmh mm, pore size 250 angstroms, the boundary of the exclusion 8x104, REO). The mobile phase consisted of 65% of 0.2 M ammonium acetate with pH 6.5 and 35% acetonitrile in isocratic method with a volume rate of 1 ml/min, the Elution was detected by using RI, s ranges of molecular weights.

Example 24. Fractionation of the polymer Salt formed in the neutralization process were removed from the polymer obtained in example 15, by a process of fractionation adding a polar organic solvent (acetone, ethanol or methanol). An aqueous solution of the final reaction mixture (~ 10 g/20 ml) was treated with increasing amounts of organic solvents. The initial organic solvent resulted in the formation of the lower layer of the dissolved salts.

After a large part of the salt was removed, was produced by the fractionation of the material into fractions with a more homogeneous distribution of molecular weights. Added additional amount of solvent for the formation of the lower, darker layer. The amount of added organic solvent was determined by monitoring the two phases kDa in size-exclusion liquid chromatography. Basically, a substance with higher molecular weight was moved to the bottom layer, and a substance with a lower molecular weight remained in the upper layer.

When the desired range of molecular weights was determined, it was allocated one of several ways. The first method was to simply remove all of the volatile solvent from the second method consisted in the dispersion solution in a large excess of polar organic solvent (acetone, ethanol or methanol) and collect the resulting solid by filtration.

Obtaining substances in accordance with the above description of the reaction and fractionation process gave some narrow range of molecular weights (~ 3K ~ 5K, ~ 10K, ~ 25K, EX 15/3, EX 15/5, EX 15/10 and EX 15/25 respectively).

Example 25.

Sodium salt of 2-naphthalenesulfonate (1000 g) was added to a glass reactor 8925 ml of ethyl alcohol, 3800 ml of deionized water and 10 g of carbon. The mixture was heated to about 78oC and filtered through celite. The mixture was cooled to ambient temperature and maintained for about 6 hours Wet crystals were collected by filtration and dried in a vacuum thermostat (80oC/25" of vacuum to constant weight. The average yield was equal to 59%.

Recrystallized 2-naphthalenesulfonate (1000 g, obtained as described above) is then combined with water (866 g) and 99% sulfuric acid (330 ml). The reactor was tightly closed and heated with agitation to about 105oC in an oil bath with a temperature of 130oC. Formaldehyde (502 g, 37% aqueous solution) was added to the reactor over 45 minutes, the Reactor was kept in this condition for about 10 hours Over the course of the reaction was internal Dugdale and diluted with 500 g of deionized water. the pH was adjusted from values below 1 to pH approximately equal to 7 by adding about 500 g of NaOH. The reaction gave at least about 90% nefrackzionirovannam polymer.

Salts formed in the neutralization process, removed the fractionation by adding 10 l of acetone, which led to the formation of two layers. The bottom layer was discarded. The upper layer was added 2 l of acetone, which again led to the formation of two layers, the upper layer is discarded. Approximately 600 g of water was added to the lower layer together with about 1.4 l of acetone, which again led to the formation of two layers. The lower layer is discarded, the upper layer was transferred into another vessel and processed approximately 1.2 l of acetone. The resulting upper layer was discarded and the lower layer was added about 520 ml of water. The solution was concentrated, transferred into a vacuum thermostat and dried at 80oWith/24" vacuum to constant weight. Fractionation was detected using gelfiltration liquid chromatography. The process gave the yield of the condensation polymer with a molecular weight between about 4000-6000 daltons (average yield of 11%).

Example 26.

Certain amount of a substance according to example 25 (10% aqueous solution), purified water (USP) and the milk is me mixing added a set amount of Carbomer 1382 (BF Goodrich, Cleveland, OH), and agitation was continued until hydrating Carbomer. Added a 50% aqueous solution (weight percent) Trolamine (Spectrum, New Brunswick, NJ) with stirring. Recorded pH.

Gels were poured in h mm aluminum tube with an epoxy coating and polypropylene caps and a certain diameter of the neck 16 (Montebello). The amount poured gel was equal to about 3.7, the test Tube was tightly closed, and then sterilized in autoclave at 121oC for 20 minutes

Example 27. Biological activity.

Potential irritating effects of 0.1, 1, and 4% (formulation 3,5 and 6) concentration of the polymer in the formulations described above (hereinafter referred to as the gel PRO 2000), evaluated at the sheath new Zealand white rabbits. Five rabbits in each of the 5 groups were treated daily in the vaginal fornix, the dose is 1 ml, gel PRO 2000 gel carrier (formula 2) or 4% recipe with nonoxynol-9 (Conceptrol; included for comparison). The treatment was repeated for 14 consecutive days. The day after the last dose rabbits were killed and the tissue of the vagina was removed for histopathological evaluation. All rabbits remained alive during the period of the study and not obnaruzhili in weight during the study. Histopathological degree of irritation were evaluated as weak in each group exposed to processing, and were within the acceptable range for this test.

The effect of gel PRO 2000 on the outcome of pregnancy has been studied in artificially inseminated rabbits. Four groups, each of which consisted of ten female rabbits, intrawaginalno was injected gel medium (recipe 1), 4% formulation of nonoxynol-9 (Conceptrol), 0.5% gel PRO 2000 (formula 4) or 4% gel PRO 2000 (formula 7). Rabbits were injected the drug once a day (1 ml/dose), starting from the days before artificial insemination up to 7 days of pregnancy. At day 0 of pregnancy, the females were injected dose, and then 15-30 min samanali their 0.5 ml of the diluted seed obtained from fertile males. On the day of pregnancy 19 females were killed and dissected, noted the status of their pregnancy and for every pregnant female rabbits) recorded the number of yellow bodies, fruits and sites of implantation. The positive control (Conceptrolthis experiment was a contraceptive: nine out of ten rabbits in the group treated Conceptrolwere not pregnant. Gel nose is built, the share corresponding to the results obtained in this laboratory the frequency of successful conception after artificial insemination (85-90%). Compared with the group treated with the gel medium, smaller animals treated with 4% gel PRO 2000, were pregnant: three out of ten rabbits. The introduction of 0.5% gel PRO 2000 had no effect on the number of pregnant rabbits: nine out of ten rabbits were pregnant. These results were obtained on the day when rabbits were investigated to assess the condition of pregnancy.

Pure drug was evaluated with respect to its ability to inhibit hyaluronidase, an enzyme that increases the permeability of the cumulative layer that is necessary for binding of sperm with the egg. The hyaluronidase activity was quantitatively assessed by measuring the level of hydrolysis of hyaluronic acid in the presence of different concentrations of polymer in example 25. The enzyme is pre-incubated with the test agent for 10 minutes, then started the reaction by addition of the substrate. Thirty-minute incubation was made at room temperature, then colorimetrically determined the reaction product. IC50polymer was determined as approximately 6 µg/ml Found that gender is does this property contraceptive effectiveness.

Gel PRO 2000 was estimated to be compatible with latex condoms. Using standard testing methods, the ability to rupture at high pressure air and physical properties of latex condoms without lubricant was evaluated directly after deployment or after processing 4% gel PRO 2000 (30 min at 37oC, relative humidity 95%). The gel does not adversely affect the properties of the condom.

Although the present invention has been shown and described in detail with reference to preferred embodiments, the experts in this field will understand that there may be various changes in form and detail without departing from the essence and scope of the invention defined in the attached formula. Specialists in this field will be able to detect, using no more than traditional experimentation, many equivalents of the specific embodiments of the invention specifically described herein. Such equivalents should be considered as covered by the claims.


1. The way to prevent unwanted pregnancy in an individual, comprising incandescing polymer of aromatic sulfonic acids and aldehyde or its pharmaceutically acceptable salt in a physiologically acceptable medium, and specified the condensation polymer has a molecular weight of less than about 50 kDa, or have an average of from about 0.5 to about 2.0 to sulfoxylate groups per aromatic group.

2. The method according to p. 1, characterized in that the condensation polymer is a condensation polymer of naphthalenesulfonate and formaldehyde.

3. The method according to p. 2, characterized in that the condensation polymer has a molecular weight of between about 0.7 kDa and about 50 kDa, more preferably between about 1.3 kDa and about 30 kDa, most preferably between about 4 kDa and 12 kDa.

4. The method according to p. 2, characterized in that the condensation polymer has on average about 1 sulfonylurea group on the aromatic group.

5. The method according to p. 1, characterized in that the composition is injected directly before sexual intercourse.

6. The method according to p. 1, characterized in that the composition is a gel, or cream, or foam.

7. The method according to p. 6, characterized in that the polymer present in the composition at a concentration of between about 1 and 10% by weight, preferably in a concentration of approximately 4% by weight.

8. The way to prevent unwanted pregnancy in an individual, including vaginal introduction of the gel, containing the 10 weight. %.

9. The method according to p. 8, characterized in that the polymer has a molecular weight approximately equal to 5 kDa.


Same patents:

The invention relates to the field of medicine and biology and relates to drugs that regulate metabolism

The invention relates to the field of medicine and AIDS, normalizes metabolic processes in the cell

The invention relates to medicine and veterinary medicine, particularly to pharmacology

The invention relates to biology and medicine and relates to remedies for pneumonia

The invention relates to biology and medicine and relates to means against radiation damage

Drug against shock // 2108790
The invention relates to biology and medicine and relates to a medicinal product that protects from shock

The invention relates to the oligoesters, method for their production and compositions on their basis, which possess significant activity against the virus of human immunodeficiency and is used for the treatment of acquired immunodeficiency syndrome (AIDS)

FIELD: medicine.

SUBSTANCE: method involves drying injured zone after having removed dental deposit and additional treating cement surface in inflammation zone with citric acid solution of 0.1 mMole/l concentration during 5 min, and then with 0.06% Chlorohexidine solution and Nikiforov mixture. Sulfacrylate is placed into periodontium pocket as glue periodontial bandage and the lesion focus is treated with ultrasound of 26.5 kHz during 3 s.

EFFECT: accelerated treatment course; activated reparative processes in periodontium; improved mechanical strength; accelerated polymerization in glue bandage.

2 tbl

FIELD: medicine.

SUBSTANCE: novel biomaterials consist of combination of sulphated hyaluronic acid and deacetylated hellane for application as highly efficient barrier for prevention of post-operation commissures in operation in abdominal, pelvic areas and, first of all, on spine.

EFFECT: increase of application efficiency.

16 cl, 1 dwg, 2 tbl, 6 ex

FIELD: medicine.

SUBSTANCE: invention refers to high-molecular compounds for medical purposes. Water-soluble polymeric complexes of antiviral agent arbidol of general formula: are described, where: Arb - arbidol: ethyl ester 6-bromo-4-dimethyl-aminometil-1-methyl-5-oxy-2-feniltiometilindolinil-3-carboxylic acid hydrochloride monohydrate; m1=100-(m2+m3) mol %; m2=(7.6-9.8) mol %; m3=(11.5-13.6) mol %; content of Arb=26.4-32.1 wt %.

EFFECT: obtained water-soluble polymeric complexes of arbidol may find application in pharmacology, as they can serve as basis for new effective and safe antiviral drugs and their dosage forms.

1 cl, 6 ex, 4 tbl, 2 dwg

Transdermal plaster // 2445084

FIELD: medicine.

SUBSTANCE: invention refers to medicine, particularly pharmaceutical preparations, namely: plasters for transdermal application. Substance of invention consists in the fact that a transdermal plaster representing a matrix system and comprising a lining layer, a matrix layer and a lightproof protective coating in the following proportions is produced: 6.72 wt % of hypoxene substance, 15.11 wt % of sodium metabisulphite in propylene glycol with 0.067% of sodium metabisulphite, as well as 56.0 wt % of 95% ethanol and 22.17 wt % of PVP K30. The plaster aims at the transdermal introduction of hypoxene. A plaster area is 25 cm2.

EFFECT: offered plaster used for treating and preventing chronic diseases allows avoiding the problems related to oral administration, improves patient compliance, enables prolonged maintenance of the hypoxene concentration; it is suitable for purposes of combination therapy.

6 dwg, 1 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: what is presented is a group of inventions which refers to medicine, namely dermatology. The group of inventions involves the use of a known compound as an agent for preparing a composition for stimulating and/or accelerating fibroblast proliferation in vivo and ex vivo, and respectively wound healing, as a wound healing dressing containing such compound. This compound represents a copolymer of 2-methyl-2-[(1-oxo-2-propenyl)amino]-1-propane sulfonic acid salt and propenoic acid 2-hydroxyethyl ester. It may be used either separately or in a combination with the other active substances for inducing or accelerating wound healing. This compound either separately, or in a combination with the other active substance may be introduced on the wound directly and a surrounding area or mucous membranes by local application. The presents inventions also find application for making dressings on the basis of hydrogels and hydrocolloids which contain said copolymer. For the purpose of the use in vivo, the given copolymer is used in the composition or in the dressing for wound healing that promotes better improvement of wound surface regeneration and healing stimulation.

EFFECT: use of the copolymer ex vivo is effective for autologous skin or skin-epidermal transplants as that enables accelerating fibroblast proliferation.

3 tbl

FIELD: pharmacology.

SUBSTANCE: invention relates to the high-molecular weight compounds of the medical purpose, more specifically to new synthetical sulfo-containing homo- and copolymers 2-acrylamido-2-methylpropansulfoacid with its own bioactivity that can be used in pharmacology in the capacity of the future-proof antiviral agents or can serve as the basis for the new effective and harmless antiviral medicinal agents and its pharmaceutical forms. The homo- and copolymers 2-acrylamido-2-methylpropansulfoacid of the stated below formula are obtained by the radical heterophase (co)polymerization in the ethanol at 70°C within 24 hours. The homo- and copolymers 2-acrylamido-2-methylpropansulfoacid have the molecular weight MM=(40-70)⋅103.



m=100 mol. %, n=0;


m=(22.8-58.1) mol. %, n=(77.2-41.9) mol. %.

EFFECT: invention allows to get nontoxical homo- and copolymer 2-acrylamido-2-methylpropansulfoacid with its own antiviral activity against the influenza viruses H3N2, H1N1.

1 tbl, 2 ex

FIELD: medicine.

SUBSTANCE: bandages based on polysulphated oligosaccharides showing prolonged release of said active substances, and a process for their preparation are described, wherein the method comprises the step of treating with ethylene oxide. The invention relates to the use of these bandages for wound care and for the treatment and/or prevention of scar formation and skin stretch marks.

EFFECT: high release of active substances.

16 cl, 4 dwg, 2 ex