RU2542414C2 - Medication for treating erectile dysfunctions and method of treating erectile dysfunctions - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to urology, and deals with treatment of erectile dysfunction. For this purpose pharmaceutical composition, containing activated potentiated form of antibodies to prostate-specific antigen and as additional enhancing component - activated potentiated form of antibodies to endothelial NO-synthase.

EFFECT: introduction of claimed composition provides efficient treatment of erectile dysfunction due to anti-inflammatory, antiproloferative and vascularisation-improving properties of its components.

9 cl, 1 ex

Description

The invention relates to medicine and can be used to treat erectile dysfunctions of various origins.

A medicament for the treatment of erectile dysfunctions is known which contains an activated form of ultra-low doses of antibodies to endothelial NO synthase (RU 2191601 CI, A61K 39/395, 10.27.2002). However, this drug does not in all cases provide sufficient therapeutic efficacy.

In addition, it is known to use the Impaza preparation based on the activated form of ultra-low doses of antibodies to endothelial NO synthase as an additional tool to improve the quality of erection in the treatment of patients with benign prostatic hyperplasia who were prescribed Afala based on the activated form of ultra-low doses antibodies to prostate-specific antigen (Tsybdenov A.G. Clinical efficacy of Afala and Impaz drugs in the treatment of prostatic hyperplasia in combination with e rectal dysfunction. Bulletin of the Buryat State Univeritity. 2009/12, p. 278-279 (D1); Tsybdenov GD, Tsybdenov AG and others. Clinical efficacy of Afala and Impaz drugs in the treatment of prostatic hyperplasia in combination with erectile dysfunction The Third Congress of Surgeons of Siberia and the Far East, Tomsk, October 15-16, 2009, Materials of the Congress, p.129 - 130 (D2); Kalinina SN, Shelipanov OL, etc. Diagnosis and treatment of patients with benign hyperplasia prostate gland. Actual issues of urology. Collection of scientific papers. St. Petersburg. 2007, p.125-130 (D3)).

In this case, the Afala drug was used as the main drug for the treatment of benign prostatic hyperplasia and was prescribed 2 tablets 4 times a day, the Impaza drug was used to improve the quality of the erection and was prescribed daily: 2 tablets or 1 tablet daily. 2 times a day, that is, drugs were taken in different quantities and at different times. This circumstance suggests that each of the drugs acted independently of each other and ensured its own, due to its pharmacological properties, therapeutic effect.

In addition, in D1 - D2, Afala was used to treat prostate adenoma (hyperplasia). Results were evaluated using standard questionnaires. Estimated the quality of life of patients according to the questionnaire.

Since these patients simultaneously suffered from sexual dysfunctions, they were simultaneously prescribed the drug Impaz.

From D1 - D2 it follows that the use of 2 drugs for each specific patient with erectile dysfunction was prescribed for patients in order to improve their quality of life compared with patients with BPH without erectile dysfunction. Moreover, the Afala drug containing the active substance in homeopathic doses is a safe drug that does not cause side effects and does not, in contrast to 5-a-reductose inhibitors and adrenoblockers, inhibit sexual function.

The study confirmed previously known properties inherent in each drug individually:

1. Safety, good tolerance (properties of both drugs).

2. Reduction of symptoms of BPH (properties of "Afal").

3. Improving erectile function (Impaz properties) Each of the drugs was used according to the manufacturer's recommended treatment regimens: 4 doses of Afala and 1 dose of Impaz per day - 2 tablets per dose.

In the course of the study, the interaction factors of the drugs or any new, unknown effects were not found with their simultaneous use.

Thus, we can say that this publication D1 reflects the fact of parallel administration of drugs in order to reproduce the properties known to each drug in an individual patient, but not the fact of their combined (combined, simultaneous and single dose) use for the treatment of a single disease.

From D3 it follows that patients for the treatment of BPH, who also complain of a decrease in erection, were prescribed complex therapy with α-adrenergic blockers and Afala in the first group, and α-adrenergic blockers and prostamolone in the second group. As a result, it was found that the combination therapy of BPH with the use of Afala is more effective than with the use of prostamol-uno.

In parallel, to increase the quality of an erection (quality of life), both groups received the Impaz drug, as well as a course of hardware vacuum treatment, which was accompanied by an increase in sexual function.

As part of the complex therapy, Afala BPH was prescribed according to the scheme recommended by the manufacturer: 2 tablets 4 times a day for a week, and then 2 tablets 2 times a day. "Impaz" is likely, also according to the recommended developed scheme, within 12 weeks (no detailed description).

Thus, as in D1 - D2, and in D3, "Afala" and "Impaza" were used in patients simultaneously for the treatment of various diseases - BPH and erectile dysfunction. There was no effect on the symptoms of BPH "Impaz" or on the symptoms of erectile dysfunction "Afala". At the same time, the combined use of Afal, α-blockers and Impaz improves the quality of life of patients, normalizes urination impaired during BPH, and increases sexual function, i.e. with the joint use of drugs according to different administration schemes, their known pharmacological properties are preserved without creating a new therapeutic effect, and, therefore, the therapeutic effect of the Impaz drug for the treatment of erectile dysfunction does not improve the administration of the Afala drug.

The invention is directed to the creation of a medicinal product in the form of a pharmaceutical composition that provides an increase in the effectiveness of the treatment of erectile dysfunction based on the activated potentiated form of antibodies to endothelial NO synthase.

The solution to this problem is provided by the fact that the drug for the treatment of erectile dysfunction, containing the activated potentiated form of antibodies to endothelial NO synthase, according to the invention, is made in the form of a pharmaceutical composition and includes an activated potentiated form of antibodies to prostate-specific antigen as an additional reinforcing component.

The activated potentiated form of antibodies to endothelial NO synthase and the activated potentiated form of antibodies to prostate-specific antigen are used in the form of an activated potentiated aqueous or hydroalcoholic solution obtained by repeated dilution in an aqueous or hydroalcoholic solvent and intermediate external mechanical action - vertical shaking .

The pharmaceutical composition of the claimed drug can be made in solid dosage form, which contains an effective amount of a neutral carrier granules saturated with a mixture of aqueous or aqueous-alcoholic solutions of an activated potentiated form of antibodies to endothelial NO synthase and an activated potentiated form of antibodies to prostate-specific antigen, and pharmaceutically acceptable additives. In addition, pharmaceutically acceptable additives include lactose, microcrystalline cellulose and magnesium stearate.

Aqueous or aqueous-alcoholic solutions of activated β-potentiated forms of antibodies to endothelial NO synthase and to prostate-specific antigen were obtained by repeated serial dilution and intermediate external exposure from matrix solutions of affinity-purified antibodies to prostate-specific antigen and to endothelial NO synthase with a concentration of 0.5+ 5.0 mg / ml.

Each of the components of ultra-low doses of affinity-purified antibodies is used in the form of a mixture of various, mainly hundred, homeopathic dilutions (super-dilutions).

Moreover, each of the active components is a mixture of various homeopathic hundred-fold dilutions.

The solution of this problem is also provided by the fact that in the method of treating erectile dysfunction by introducing into the body an activated potentiated form of antibodies to endothelial NO synthase, according to the invention, an activated potentiated form of ultralow doses of affinity-purified antibodies to prostate-specific antigen is additionally combined at the same time.

In addition, the method of treatment and prevention using the claimed drug can be used in complex therapy in men suffering from diseases of the genitourinary system, accompanied by erectile dysfunction.

In this case, the activated potentiated form of antibodies to endothelial NO synthase and the activated potentiated form of antibodies to prostate-specific antigen are used in the form of an activated potentiated aqueous or hydroalcoholic solution of each component obtained during repeated serial dilution in an aqueous or hydroalcoholic solvent and an intermediate external mechanical exposure - vertical shaking.

A mixture of various homeopathic dilutions of antibodies to endothelial NO synthase in combination with a mixture of various homeopathic dilutions of antibodies to prostate-specific antigen is preferably used as a single drug.

In addition, the drug contains active ingredients in a 1: 1 ratio, each component being used as a mixture of three appropriate matrix solutions diluted 100 ¹² , 100 ³⁰ , and ^100,200 times, which is equivalent to hundreds of homeopathic dilutions C 12, C 30 , C 200.

The claimed pharmaceutical composition is recommended to be taken, preferably, 1-2 tablets 2-4 times a day.

In the treatment of erectile dysfunction, separate but combined (simultaneous) use (administration to the body) in the form of two separately prepared preparations, both in the form of solutions and in solid dosage forms (tablets), each of which contains an activated potentiated form of ultra-low doses of affinity purified antibodies to endothelial NO synthase and, accordingly, the activated potentiated form of ultra-low doses of affinity-purified antibodies to prostate-specific antigen.

The proposed combination of activated potentiated forms of antibodies to endothelial NO synthase and prostate-specific antigen in a pharmaceutical composition (i.e., antibody forms to endothelial NO synthase and prostate-specific antigen prepared by homeopathic potentiation technology by repeated serial dilution and intermediate external exposure - vertical shaking, which are active in pharmacological models and / or clinical methods of treatment of erectile dysfunction n) provides an unexpected synergistic therapeutic effect, experimentally confirmed on an adequate model, which consists in a significant improvement in spermatological parameters (increase in the concentration of sex hormones, the number of sperm and their motility, decrease in viscosity of seminal fluid). The claimed technical solution can be used for autonomic disorders of menopause in men (weakness, fatigue, decreased physical activity, decreased libido, etc.). In addition, the claimed technical solution improves the quality of life of patients with erectile dysfunction of various origins.

This technical result is due to improved vascularization and increased endothelial protective effect of the activated potentiated forms of antibodies to endothelial NO synthase due to the antiproliferative and anti-inflammatory activity of the activated potentiated forms of antibodies to PSA when used simultaneously and in combination as a complex preparation.

Moreover, the claimed technical solution is characterized by the breadth of therapeutic effect and can be used for a wide range of indications associated with diseases of the genitourinary system, accompanied by erectile dysfunction of various origins, including as part of complex therapy.

In addition, the claimed drug expands the arsenal of drugs intended for the treatment of erectile dysfunction of various origins.

To prepare the activated potentiated form of the active components, monoclonal or, mainly, polyclonal antibodies are used, which can be obtained by known technologies - the techniques described, for example, in the book: Immunological methods, ed. G. Fremel. M., "Medicine", 1987, p. 9-33; or, for example, in an article by Laffly E., Sodoyer R. Hum. Antibodies. Monoclonal and recombinant antibodies, 30 years after. - 2005 .-- Vol.14. - N 1-2. P.33-55.

Monoclonal antibodies are obtained, for example, using hybridoma technology. Moreover, the initial stage of the process includes immunization, based on the principles already developed in the preparation of polyclonal antisera. Further stages of the work include obtaining hybrid cells producing clones of antibodies of the same specificity. Their isolation in an individual form is carried out by the same methods as in the case of polyclonal antisera.

Polyclonal antibodies can be obtained by active immunization of animals. For this purpose, according to a specially developed scheme, animals are given a series of injections with the antigens required by the invention: endothelial N0 synthase and prostate-specific antigen. As a result of this procedure, monospecific antisera with a high content of antibodies are obtained, which are used to obtain activated potentiated forms. If necessary, the antibodies present in the antiserum are purified, for example, by the method of affinity chromatography, by using fractionation by salt precipitation, or by ion exchange chromatography.

Preferred for the preparation of the claimed pharmaceutical composition is the use of polyclonal antibodies to endothelial NO synthase and to prostate-specific antigen, which are used as a matrix (primary) solution with a concentration of 0.5 ± 5.0 mg / ml

for the subsequent preparation of the activated potentiated form.

Preferred for the preparation of each component is the use of a mixture of three water-alcohol dilutions of the primary matrix solution of antibodies diluted 100 ¹² , 100 ³⁰ , and 100 ²⁰⁰ times, respectively, which corresponds to hundreds of homeopathic dilutions C 12, C30 and C 200. When performing the claimed drug in solid dosage form, a mixture of these components is applied to lactose.

Preferred for the preparation of the claimed drug is the use of polyclonal antibodies to endothelial NO synthase and prostate-specific antigen, which can be obtained by immunization of rabbits as follows.

Example 1

For experimental studies were used antibodies prepared by order of a specialized pharmaceutical company.

Polyclonal antibodies to endothelial NO synthase are prepared using the adjuvant and the whole endothelial NO synthase molecule of the following sequence as immunogen (antigen) for rabbit immunization:

1 MGNLKSVGQE PGPPCGLGLG LGLGLCGKQG PASPAPEPSR ARARATRNAR DHSPAPNSPT

61 LTRPPEGPKF PRVKNWELGS ITYDTLCAQS QQDGPCTPRR CLGSLVLPRK LQTRPSPGPP

121 PAEQLLSQAR DFINQYYSSIKRSGSQAHEE RLQEVEAEVA STGTIHLRES ELVFGAKQAW

181 RNAPRCVGRI QWGKLQVFDA RDCSSAQEMF TYICNHIKYA TNRGNLRSAITVFPQRAPGR

241 GDFRIWNSQL VRYAGYRQQD GSVRGDPANV EITELCIQHG WTPGNGRFDV LPLLLQAPDE

301 APELFVLPPE LVLEVPLGAP HTGVVRGPGL RWYALPAVSN MLLEIGGLEF SAAPFSGWYM

361 STEIGTRNLC DPHRYNILED VAVCMDLDTR TTSSLWKDKA AVEINLAVLH SFQLAKVTIV

421 DHHAATVSFM KHLDNEQKAR GGCPADWAWIVPPIYGSLPP VFHQEMVNYI LSPAFRYQPD

481 PWKGSATKGA GITRKKTFKE VANAVKISAS LMGTLMAKRV KATILYASET GRAQSYAQQL

541 GRLFRKAFDP RVLCMDEYDV VSLEHEALVL VVTSTFGNGD PPENGESFAA ALMEMSGPYN

601 SSPRPEQHKS YKIRFNSVSC SDPLVSSWRR KRKESSNTDS AGALGTLRFC VFGLGSRAYP

661 HFCAFARAVD TRLEELGGER LLQLGQGDEL CGQEEAFRGW AKAAFQASCE TFCVGEEAKA

721 AAQDIFSPKR SWKRQRYRLS AQAEGLQLLP GLIHVHRRKM FQATVLSVEN LQSSKSTRAT

781ILVRLDTAGQ EGLQYQPGDHIGISAPNRPG LVEALLSRVE DPPPPTESVA VEQLEKGSPG

841 GPPPSWVRDP RLPPCTVRQA LTFFLDITSP PSPRLLRLLS TLAEEPSEQQ ELETLSQDPR

901 RYEEWKLVRC PTLLEVLEQF PSVALPAPLL LTQLPLLQPR YYSVSSAPNA HPGEVHLTVA

961 VLAYRTQDGL GPLHYGVCST WLSQLKTGDP VPCFIRGAPS FRLPPDPYVP CILVGPGTGI

1021 APFRGFWQER LHDIESKGLQ PHPMTLVFGC RCSQLDHLYR DEVQDAQERG VFGRVLTAFS

1081 REPDSPKTYV QDILRTELAA EVHRVLCLER GHMFVCGDVT MATSVLQTVQ RILATEGDME

1141 LDEAGDVIGV LRDQQRYHEDIFGLTLRTQE VTSRIRTQSF SLQERHLRGA VPWAFDPPGP 1201 DTPGP

It is possible to obtain polyclonal antibodies to endothelial NO synthase using the following sequence as an immunogen (antigen) of a whole molecule of endothelial NO synthase:

1 MGNLKSVAQE PGPPCGLGLG LGLGLCGKQG PATPAPEPSR APASLLPPAP EHSPPSSPLT

61 QPPEGPKFPR VKNWEVGSIT YDTLSAQAQQ DGPCTPRRCL GSLVFPRKLQ GRPSPGPPAP

121 EQLLSQARDF INQYYSSIKR SGSQAHEQRL QEVEAEVAAT GTYQLRESEL VFGAKQAWRN

181 APRCVGRIQW GKLQVFDARD CRSAQEMFTYICNHIKYATN RGNLRSAITV FPQRCPGRGD

241 FRIWNSQLVR YAGYRQQDGS VRGDPANVEI TELCIQHGWT PGNGRFDVLP LLLQAPDDPP

301 ELFLLPPELV LEVPLEHPTL EWFAALGLRW YALPAVSNML LEIGGLEFPA APFSGWYMST

361 EIGTRNLCDP HRYNILEDVA VCMDLDTRTT SSLWKDKAAV EINVAVLHSY QLAKVTIVDH

421 HAATASFMKH LENEQKARGG CPADWAWIVP PISGSLTPVF HQEMVNYFLS PAFRYQPDPW

481 KGSAAKGTGI TRKKTFKEVA NAVKISASLM GTVMAKRVKA TILYGSETGR AQS YAQQLGR

541 LFRKAFDPRV LCMDEYDWS LEHETLWLVV TSTFGNGDPP ENGESFAAAL MEMSGPYNSS

601 PRPEQHKSYKIRFNSISCSD PLVSSWRRKR KESSNTDSAG ALGTLRFCVF GLGSRAYPHF

661 CAFARAVDTR LEELGGERLL QLGQGDELCG QEEAFRGWAQ AAFQAACETF CVGEDAKAAA

721 RDIFSPKRSW KRQRYRLSAQ AEGLQLLPGL IHVHRRKMFQ ATIRSVENLQ SSKSTRATIL

781 VRLDTGGQEG LQYQPGDHIG VCPPNRPGLV EALLSRVEDP PAPTEPVAVE QLEKGSPGGP

841 PPGWVRDPRL PPCTLRQALT FFLDITSPPS PQLLRLLSTL AEEPREQQEL EALSQDPRRY

901 EEWKWFRCPT LLEVLEQFPS VALPAPLLLT QLPLLQPRYY SVSSAPSTHP GEIHLTVAVL

961 AYRTQDGLGP LHYGVCSTWL SQLKPGDPVP CFIRGAPSFR LPPDPSLPCILVGPGTGIAP

1021 FRGFWQERLH DIESKGLQPT PMTLVFGCRC SQLDHLYRDE VQNAQQRGVF GRVLTAFSRE

1081 PDNPKTYVQD ILRTELAAEV HRVLCLERGH MFVCGDVTMA TNVLQTVQRI LATEGDMELD

1141 EAGDVIGVLR DQQRYHEDIF GLTLRTQEVT SRIRTQSFSL QERQLRGAVP WAFEPPGSDT 1201NSP

It is possible to obtain polyclonal antibodies to endothelial NO synthase using, as an immunogen (antigen), a synthetic peptide of endothelial NO synthase, selected, for example, from the following amino acid sequences:

1192-1195

Pwaf

1189-1192:

Rgavp

1185-1205 L

RHLRGAVPWAF DPPGPDTPGP

1194-1205:

AF DPPGPDTPGP

1186-1196: HLRGAVPWAF D

1186-1205:

HLRGAVPWAF DPPGPDTPGP

Before blood sampling for 1-3 days, 1-3 intravenous injections are performed to increase the level of antibodies. During immunization, small blood samples are taken from rabbits to evaluate the amount of antibody. The maximum level of the immune response to the administration of most soluble antigens is achieved 40-60 days after the first injection. After the end of the first cycle of immunization of rabbits for 30 days, they restore health and re-immunization, including 1-3 intravenous injections. To obtain antisera from immunized rabbits, blood is collected in a 50 ml centrifuge tube. Using a wooden spatula, the formed clots are removed from the walls of the tube and the wand is placed in the clot formed in the center of the tube. Blood is placed in a refrigerator (temperature 4 ° C) at night. The next day, the clot attached to the spatula is removed and the remaining liquid is centrifuged at 13000g for 10 minutes. The supernatant (supernatant) is an antiserum. The resulting antiserum should be yellow. Add to the antiserum 20% (weight concentration) NaN ₃ to a final concentration of 0.02% and store until use in a frozen state at a temperature of -20 ° C. To isolate antibodies to endothelial NO synthase from antiserum, solid phase absorption is performed in the following sequence:

1) 10 ml of rabbit antiserum is diluted 2 times with 0.15 M NaCl, 6.26 g of Na ₂ SO ₄ are added, mixed and incubated for 12-16 hours at 4 ° C;

2) the precipitate formed is removed by centrifugation, dissolved in 10 ml of phosphate buffer and then dialyzed against the same buffer overnight at room temperature;

3) after removing the precipitate by centrifugation, the solution is applied to a column with DEAE-cellulose, balanced with phosphate buffer;

4) the antibody fraction is determined by measuring the optical density of the eluate at 280 nm.

The antibodies are then purified by affinity chromatography by attaching the obtained antibodies to endothelial NO synthase, which is located on an insoluble matrix, followed by elution with concentrated salt solutions.

Thus obtained buffer solution of polyclonal rabbit antibodies to endothelial NO synthase, purified on antigen, with a concentration of 0.5 ÷ 5.0 mg / ml, preferably 2.0 ÷ 3.0 mg / ml, is used as a matrix ( primary) solution for the subsequent preparation of the activated potentiated form.

Polyclonal antibodies to the prostate-specific antigen (PSA) are obtained in a similar manner to the above, using as an immunogen (antigen) for immunization of rabbits an adjuvant and a whole prostate-specific antigen molecule of the following sequence:

1 MWVPVVFLTL SVTWIGAAPL ILSRIVGGWE CEKHSQPWQV LVASRGRAVC GGVLVHPQWV

61 LTAAHCIRNK SVILLGRHSL FHPEDTGQVF QVSHSFPHPL YDMSLLKNRF LRPGDDSSHD

121 LMLLRLSEPA ELTDAVKVMD LPTQEPALGT TCYASGWGSI EPEEFLTPKK LQCVDLHVIS

181 NDVCAQVHPQ KVTKFMLCAG RWTGGKSTCS GDSGGPLVCN

GVLQGITSWG SEPCALPERP

241 SLYTKVVHYR KWIKDTIVAN P

It is possible to obtain polyclonal antibodies to a prostate-specific antigen (PSA) using one polypeptide fragment of a prostate-specific antigen as an immunogen (antigen), selected, for example, from the following amino acid sequences:

193-208:

TKFMLCAG RWTGGKST 211-241:

GDSGGPLVCN GVLQGITSWG SEPCALPERP S 189-200:

PQ KVTKFMLCAG

67-190:

IRNK SVILLGRHSL FHPEDTGQVF QVSHSFPHPL YDMSLLKNRF LRPGDDSSHD LMLLRLSEPA ELTDAVKVMD LPTQEPALGT TCYASGWGSIEPEEFLTPKK LQCVDLHVIS NDVCAQVHPQ

77-99:

RHSL FHPEDTGQVF QVSHSFPHP 101-125:

YDMSLLKNRF LRPGD 122-135:

MLLRLSEPA ELTDA 5-25:

WFLTL SVTWI 107-200:

KNRF LRPGDDSSHD LMLLRLSEPA ELTDAVKVMD LPTQEPALGT TCYASGWGSI EPEEFLTPKK LQCVDLHVIS NDVCAQVHPQ KVTKFMLCAG

25-261:

IVGGWECEKHSQPWQVLVASRGRAVCGGVLVHPQWVLTAAHCIR NKSVILLGRHSLFHPE

DTGQVFQVSHSFPHPLYDMSLLKNRFLRPGDDSSHDLMLLRLSEPA ELTDA VKVMDLPTQ

EPALGTTCYASGWGSIEPEEFLTPKKLQCVDLHVISNDVCAQVHPQ KVTKFMLCAGRWTG

GKSTCSGDSGGPLVCNGVLQGITSWGSEPCALPERPSLYTKVVHYR KWIKDTIVANP

The activated potentiated form of each component is prepared by uniformly decreasing the concentration as a result of successive dilution of 1 part of the matrix solution in 9 parts (for decimal dilution) or in 99 parts (for hundredth dilution) or in 999 parts (for thousandth dilution) of a neutral solvent with multiple vertical shaking ("dynamization") of each dilution obtained and using separate containers for each subsequent dilution to obtain the desired potency - cr dilution characteristics according to the homeopathic method (see, for example, V. Schwabe "Homeopathic medicines". M., 1967, p.14-29).

External processing in the process of reducing the concentration can also be performed by ultrasound, electromagnetic or other physical effects.

For example, for the preparation of the 12th hundredth C12 dilution, one part of the aforementioned matrix solution of antibodies to endothelial NO synthase (or to a prostate-specific antigen) with a concentration of 3.0 mg / ml is diluted in 99 parts of a neutral aqueous or aqueous-alcoholic solvent (mainly 70% ethyl alcohol) and repeatedly (10 or more times) vertically shake - potentiate the obtained 1st hundredth C1 dilution. From the 1st hundredth C1 dilution prepare the 2nd hundredth dilution C2. This operation is repeated 11 times, obtaining the 12th hundredth dilution of C12. Thus, the 12th hundredth dilution of C12 is a solution obtained by diluting successively in different containers 12 times of the first part of the initial matrix solution of antibodies to endothelial NO synthase with a concentration of 3.0 mg / ml in 99 parts of a neutral solvent, those. the solution obtained by diluting the matrix solution in 100 to ¹² times. Similar operations with the appropriate dilution ratio are carried out to obtain dilutions of C 30 and C 200.

When using as a biologically active liquid component a mixture of various homeopathic, mainly hundred, dilutions, active ingredients, each component of the composition (for example, C 12, C 30, C 200) is prepared separately according to the technology described above to the penultimate dilution (respectively, to obtain C 11, C29, C 199) and then, in accordance with the composition of the mixture, make one part of each component in one container and mix with the required amount of solvent (respectively, with 97 parts for hundred-percent dilution). In this case, an activated potentiated form of antibodies to endothelial NO synthase is obtained in an ultra-low dose obtained by diluting the matrix solution 100 ¹² 100 ³⁰ 100 ²⁰⁰ times, equivalent to a mixture of hundred-percent homeopathic dilutions C12, C30, C200.

It is possible to use the active substance in the form of a mixture of other various homeopathic dilutions, for example, decimal and or hundredths (D 20, C 30, C 100 or C12, C30, C50, etc.), the effectiveness of which is determined experimentally.

When potentiating instead of shaking in the process of decreasing the concentration, it is also possible to exert external influence by ultrasound, electromagnetic or other physical effect.

To obtain the claimed pharmaceutical composition, aqueous or aqueous-alcoholic solutions of the active ingredients are mixed, mainly in a ratio of 1: 1 and used in liquid dosage form.

The claimed pharmaceutical composition can be used in solid dosage form, which contains an effective amount of granules of a neutral carrier - lactose, saturated by impregnation of an activated potentiated form of antibodies to endothelial NO synthase with a mixture of aqueous or aqueous-alcohol solutions and an activated potentiated form of antibodies to prostate-specific antigen, and pharmaceutically acceptable additives, including, mainly, lactose, microcrystalline cellulose and magnesium I stearate.

To obtain a solid oral form of the claimed medicinal product, a fluidized bed is installed (for example, of the “Htittlin Pilotlab” type manufactured by Huttlin GmbH) irrigation until saturation of the granules of a neutral substance — lactose (milk sugar) with a particle size of 150–300 μm, a pre-prepared aqueous or aqueous-alcoholic solution of activated potentiated forms of antibodies to prostate-specific antigen and to endothelial synthase of nitric oxide (NO synthase), mainly in the ratio SRI 1 kg of antibody solution to 5 or 10 kg of lactose (1: 5-1: 10) with simultaneous drying in a heated air stream supplied under the grate at a temperature of not higher than 40 ° C. The calculated amount of 0.17 ÷ 0.34 of the mass of solid oral form) of dried granules saturated with the activated potentiated form of antibodies is loaded into a mixer and mixed with microcrystalline cellulose introduced in an amount of 3-8 wt. parts of the total mass of the load - from the mass of solid oral form. Then 25 ÷ 45 wt. parts of the total mass of the load of "unsaturated" pure lactose (to reduce the cost and some simplification and acceleration of the process without reducing the effectiveness of the therapeutic effect), magnesium stearate in an amount of 0.1 ÷ 0.3 wt. parts of the total mass of the load and microcrystalline cellulose in an amount of 3 ÷ 8 wt. parts of the total mass of the load. The resulting tablet mass is uniformly mixed and tabletted by direct dry pressing (for example, in a Korsch tablet press - XL 400) with the formation of round tablets weighing 150 ÷ 500 mg. After tabletting, 300 mg tablets are obtained, impregnated with an aqueous-alcoholic solution (3.0-6.0 mg / tablet) with an activated β-potentiated form of antibodies to the prostate-specific antigen and to NO synthase in an ultra-low dose of each component prepared from the matrix solution, diluted in 100 ¹² , in 100 ³⁰ in 100 ²⁰⁰ , which is equivalent to a mixture of hundreds of homeopathic dilutions C12, C30 and C200.

Preferably, the claimed pharmaceutical composition is recommended to take 1-2 tablets 2-4 times a day.

Claims (9)

1. A drug for the treatment of erectile dysfunction, containing an activated potentiated form of antibodies to endothelial NO synthase, characterized in that it is made in the form of a pharmaceutical composition and includes, as an additional component, an activated potentiated form of antibodies to a prostate-specific antigen. 2. The drug according to claim 1, characterized in that the activated potentiated form of antibodies to endothelial NO synthase and the activated potentiated form of antibodies to prostate-specific antigen are used in the form of an activated potentiated aqueous or aqueous-alcohol solution obtained in the process of sequential multiple dilution of the matrix solution corresponding antibodies in an aqueous or aqueous-alcoholic solvent and intermediate external mechanical action - vertical shaking. 3. The drug according to claim 1 or 2, characterized in that the pharmaceutical composition is in solid dosage form and contains an effective amount of granules of a neutral carrier saturated with a mixture of an activated potentiated form of antibodies to endothelial NO synthase and an activated potentiated form of antibodies to prostate-specific antigen, and pharmaceutically acceptable additives. 4. The drug according to claim 1 or 2, characterized in that aqueous or aqueous-alcoholic solutions of activated potentiated forms of antibodies to endothelial NO synthase and to prostate-specific antigen are obtained by repeated serial dilution and intermediate external exposure from matrix solutions of affinity-purified antibodies to endothelial NO synthase and prostate-specific antigen with a concentration of 0.5 ÷ 5.0 mg / ml 5. The drug according to claim 1 or 2, characterized in that each of the components of the affinity purified antibodies is used as a mixture of various, mainly hundred, homeopathic dilutions. 6. The drug according to claim 3, characterized in that the pharmaceutically acceptable additives include lactose, microcrystalline cellulose and magnesium stearate. 7. A method of treating erectile dysfunction of various origins by introducing into the body an activated potentiated form of antibodies to endothelial NO synthase, characterized in that an activated potentiated form of affinity-purified antibodies to prostate-specific antigen is additionally simultaneously combined. 8. The method according to claim 7, characterized in that the activated potentiated form of antibodies to endothelial NO synthase and the activated potentiated form of antibodies to prostatispecific antigen are used in the form of an activated potentiated aqueous or aqueous-alcoholic solution of each component obtained in the process of serial multiple dilutions in aqueous or aqueous-alcoholic solvent and intermediate external mechanical stress - vertical shaking. 9. The treatment method according to claim 7, characterized in that they use a mixture of various homeopathic dilutions of antibodies to endothelial NO synthase prepared in the form of a single drug - a single dosage form in combination with a mixture of various homeopathic dilutions of antibodies to a prostate-specific antigen.