RU2519695C2 - Medication for treating attention deficit disorder and method of treating attention deficit disorder - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: group of inventions relates to medicine, namely to neurology, and deals with treatment of attention deficit disorder. For this purpose introduced is a pharmaceutical composition, containing potentiated form of antibodies to brain-specific protein S-100 and as an additional enhancing component - an activated-potentiated form of antibodies to endothelial NO-synthase.

EFFECT: method provides efficient treatment of attention deficit disorder due to synergic action of active components of the pharmaceutical composition.

9 cl, 4 tbl, 1 dwg, 2 ex

Description

The invention relates to medicine and can be used to treat attention deficit disorder (ADD).

A neurotropic drug based on antiserum to the brain-specific protein S-100 is known in the art (RU 2156621 C1, A61K 39/395, 09/27/2000). However, this drug is not in all cases of treatment of neurological-behavioral disorders, including attention deficit disorder, provides sufficient therapeutic efficacy.

The invention is aimed at improving the effectiveness of the treatment of attention deficit disorder (ADD).

The solution to this problem is provided by the fact that the drug for the treatment of attention deficit disorder, containing the activated-potentiated form of antibodies to the brain-specific protein S-100, according to the invention, is made in the form of a pharmaceutical composition and contains an activated-potentiated form of antibodies to endothelial NO synthase.

In this case, the activated-potentiated form of antibodies to the brain-specific protein S-100 and the activated-potentiated form of antibodies to endothelial NO synthase are used in the form of an activated-potentiated aqueous or aqueous-alcoholic solution, the activity of which is due to the process of multiple sequential dilutions in aqueous or aqueous-alcoholic solvent in combination with external mechanical action - vertical shaking of each dilution.

The pharmaceutical composition may be in solid dosage form and contain an effective amount of a neutral carrier particle saturated with a mixture of aqueous or aqueous-alcoholic solutions of an activated-potentiated form of antibodies to the brain-specific protein S-100 and an activated-potentiated form of antibodies to endothelial NO synthase, and pharmaceutically acceptable additives including lactose, microcrystalline cellulose and magnesium stearate.

Moreover, aqueous or aqueous-alcoholic solutions of activated-potentiated forms of antibodies to the brain-specific protein S-100 and to endothelial NO synthase are obtained by repeated serial dilutions in combination with an external action - vertical shaking of each dilution from matrix solutions of affinity-purified antibodies to the brain-specific protein S- 100 and to endothelial NO synthase with a concentration of 0.5 ÷ 5.0 mg / ml.

Preferably, each of the components of the ultra-low doses of affinity-purified antibodies is used as a mixture of various, mainly hundred, dilutions prepared according to homeopathic technology.

The solution to this problem is also provided by the fact that in the method of treating attention deficit disorder by introducing into the body an activated-potentiated form of antibodies to the brain-specific protein S-100, according to the invention, an additional (simultaneously combined) form of an activated-potentiated form of ultra-low doses of affinity-purified antibodies to endothelial NO synthase.

In this case, the activated-potentiated form of antibodies to the brain-specific protein S-100 and the activated-potentiated form of antibodies to endothelial NO synthase are used in the form of an activated-potentiated aqueous or aqueous-alcoholic solution of each component, the activity of which is due to the process of multiple sequential dilutions in aqueous or aqueous -alcohol solvent in combination with external mechanical action - vertical shaking of each dilution ..

A mixture of various dilutions of antibodies to the brain-specific protein S-100 in combination with a mixture of various dilutions of antibodies to endothelial NO synthase prepared using homeopathic technology is preferably used as a single drug.

In addition, the drug contains active ingredients in a volume ratio of 1: 1, with each component being used as a mixture of three appropriate matrix solutions, diluted, respectively, 100 ¹² , 100 ³⁰ , and 100 ²⁰⁰ times, which is equivalent to hundreds of dilutions of C12, C30, C200 prepared according to homeopathic technology.

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

In the treatment of attention deficit disorder, it is possible to separately, but combined and simultaneously use (administer to the body) the claimed pharmaceutical composition 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 ultrafine doses of affinity-purified antibodies to brain-specific protein S-100 and, accordingly, the activated-potentiated form of ultrafine doses of affinity-purified antibodies to endothelial NO synth aze.

The proposed combination of activated-potentiated forms of antibodies to the brain-specific protein S-100 and to endothelial NO synthase in a pharmaceutical composition (i.e., forms of antibodies to the brain-specific protein S-100 and to endothelial NO synthase prepared according to the homeopathic technology of potentiation by multiple sequential dilutions in combination with external mechanical action - vertical shaking of each dilution (see, for example, V. Schwabe "Homeopathic medicines", M., 1967, p.14-29), which are This activity, due to potentiation technology in pharmacological models and / or clinical methods for treating attention deficit disorder) provides an unexpected synergistic therapeutic effect, confirmed by adequate (valid) experimental models and clinical studies, which consists in increasing the effectiveness of attention deficit disorder (ADD) treatment ) The specified technical result is due to an increase in the neuroprotective activity of antibodies to the S-100 protein, an increase in the vegetative-stabilizing effect, normalization of the vegetative status, the synergistic effect of both components on neuronal plasticity, and, as a result, an increase in the resistance of the brain to toxic effects, which improves integrative activity and restores interhemispheric connections of the brain, helps to eliminate cognitive impairment, stimulates reparative processes and accelerates recovery s central nervous system, improves mental performance, restores learning and memory processes, normalizes somatovegetativnye manifestation, increases cerebral blood flow, and thus enhances the effectiveness of the treatment of attention deficit disorder.

In this case, the claimed drug, as well as its constituent components, do not have a sedative and muscle relaxant effect, do not cause addiction and addiction.

In addition, the claimed drug expands the arsenal of drugs intended for the treatment and prevention of attention deficit disorder.

The graph shows a decrease in the severity of ADHD symptoms (total score on the ADHDRS-IV-Home Version scale) after 2, 4, 6, 8, 12 weeks of therapy compared to the initial value.

The drug is prepared mainly as follows.

For the preparation of 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. Frimel, M., "Medicine", 1987, S. 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. - N1-2. 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 antigen substances required in accordance with the invention: brain-specific protein S-100 and endothelial NO synthase. As a result of this procedure, monospecific antisera with a high content of antibodies are obtained, which are used to obtain activated-potentiated forms of components. If necessary, the antibodies present in the antiserum are purified, for example, by affinity chromatography, using fractionation by salt precipitation or ion exchange chromatography.

Preferred for the preparation of the claimed pharmaceutical composition is the use of polyclonal antibodies to the brain-specific protein S-100 and to endothelial NO synthase, which are used as a matrix (primary) solution with a concentration of 0.5 ÷ 5.0 mg / ml for the subsequent preparation of 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, respectively, 100 ¹² , 100 ³⁰ , and 100 ²⁰⁰ times, which corresponds to hundreds of dilutions of C12, C30 and C200 prepared according to homeopathic technology. 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 the brain-specific protein S-100 and endothelial NO synthase, which can be obtained by immunization of rabbits as follows.

Example 1

For experimental studies, antibodies were used, prepared by order of a specialized biotechnological 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 DFINQYYSSI KRSGSQAHEE RLQEVEAEVA STGTIHLRES ELVFGAKQAW

181 RNAPRCVGRI QWGKLQVFDA RDCSSAQEMF TYICNHIKYA TNRGNLRSAI TVFPQRAPGR

241 GDFRIWNSQL VRYAGYRQQD GSVRGDPANV EITELCIQHG WTPGNGRFDV LPLLLQAPDE

301 APELFVLPPE LVLEVPLGAP HTGVVRGPGL RWYALPAVSN MLLEIGGLEF SAAPFSGWYM

361 STEIGTRNLC DPHRYNILED VAVCMDLDTR TTSSLWKDKA AVEINLAVLH SFQLAKVTIV

421 DHHAATVSFM KHLDNEQKAR GGCPADWAWI VPPIYGSLPP 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

781 ILVRLDTAGQ EGLQYQPGDH IGISAPNRPG 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 LRDQQRYHED IFGLTLRTQE 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 CRSAQEMFTY ICNHIKYATN 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 AQSYAQQLGR

541 LFRKAFDPRV LCMDEYDVVS LEHETLWLVV TSTFGNGDPP ENGESFAAAL MEMSGPYNSS

601 PRPEQHKSYK IRFNSISCSD 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 LPPDPSLPCI LVGPGTGIAP

1021 FRGFWQERLH DIESKGLQPT PMTLVFGCRC SQLDHLYRDE VQNAQQRGVF GRVLTAFSRE

1081 PDNPKTYVQD ILRTELAAEV HRVLCLERGH MFVCGDVTMA TNVLQTVQRI LATEGDMELD

1141 EAGDVIGVLR DQQRYHEDIF GLTLRTQEVT SRIRTQSFSL QERQLRGAVP WAFEPPGSDT

1201 NSP

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:

Gavp

1185-1205:

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 13000 g 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 (or without adding NaN ₃ at a temperature of -70 ° 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, stirred 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 removal of 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.

To obtain polyclonal antibodies to the brain-specific protein S-100, the brain-specific protein S-100 is used, the physicochemical properties of which are described in the article by M.V. Starostina, S.M. Sviridov, Neurospecific protein S-100, Advances in modern biology, 1977, v.5, p.170-178; the book of MB Stark, Brain-specific proteins / antigens / and neuron functions, M., "Medicine", 1985; p.12-14, isolated from tissue of the brain of a bull by the following method:

- fabric frozen in liquid nitrogen is ground into powder in a special mill;

- the extraction of proteins is carried out in a ratio of 1: 3 (weight / volume) in the extraction buffer during homogenization;

- the homogenate is heated for 10 min at 60 ° C and cooled to 4 ° C in an ice bath;

- thermolabile proteins are removed by centrifugation;

- carry out stepwise fractionation with ammonium sulfate, followed by removal of precipitated impurity proteins;

- the S-100 protein-containing fraction is precipitated with 100% saturated ammonium sulfate when the pH is reduced to 4.0 and collected by centrifugation;

- the precipitate is dissolved in a minimum volume of a buffer containing EDTA and mercaptoethanol, dialyzed against deionized water and freeze-dried;

- fractionation of acidic proteins is continued by chromatography on ion-exchange media — DEAE cellulose DE-52 and then DEAE-Sephadex A-50;

- collected and dialyzed fractions containing S-100 protein are separated by molecular weight by gel filtration on Sephadex G-100;

- purified S-100 protein is dialyzed and freeze-dried.

The molecular weight of the purified brain-specific protein S-100 is 21,000 d.

Due to the high content of aspartic and glutamic acids, the brain-specific protein S-100 is strongly acidic and occupies the extreme anode position during electrophoresis in a discontinuous buffer system in a polyacrylamide gel, which facilitates its identification.

To obtain a brain-specific antiserum, a purified S-100 protein (antigen) is prepared in combination with methylated bovine serum albumin as a carrier with Freund's complete adjuvant, which is administered subcutaneously to a laboratory rabbit animal in the amount of 1- to a selected brain-specific protein S-100. 2 ml On the 8th, 15th day, re-immunization is carried out. Blood is taken (for example, from an ear vein) on the 26th and 28th day.

The resulting antiserum has a titer of 1: 500-1: 1000, forms a single precipitation band with extract from nervous tissue, but does not react with extracts of heterologous organs, and forms a single precipitation peak with both pure S-100 protein and nervous tissue extract, which indicates the monospecificity of the obtained antiserum.

The activated-potentiated form of each component is prepared by uniformly decreasing the concentration by sequentially diluting 1 part of the matrix solution in 9 parts (for decimal dilution D) or 99 parts (for hundredth dilution C) or 999 parts (for thousandth dilution M) neutral solvent in combination with repeated (at least 10 times) vertical shaking ("dynamization") of each dilution obtained and the use of separate containers for each subsequent dilution to required potency doctrine - the multiplicity of homeopathic dilution method (see, eg, V. Schwabe "Homeopathic medicines", M., 1967, s.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 above matrix solution of antibodies to the brain-specific protein S-100 (or to NO synthase) with a concentration of 2.5 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 dilution C1, the second hundredth dilution C2 is prepared. 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 the brain-specific protein S-100 with a concentration of 2.5 mg / ml in 99 parts of a neutral solvent , i.e. a solution prepared by diluting the matrix solution in 100 ¹² times. Similar operations with the appropriate dilution ratio are carried out to obtain a dilution of C30 and C200.

When using as a component (for example, an activated-potentiated form of antibodies to the brain-specific protein S-100) mixtures of different, mainly hundred, dilutions, each dilution of the component (for example, C12, C30, C200) is prepared separately according to the technology described above to their penultimate dilution (respectively, to obtain C11, C29, C199) and then add one part of each penultimate dilution obtained in one container and mix with the required amount of solvent (respectively, with 97 parts for hundreds of dilution). In this case, an activated-potentiated form of antibodies to the brain-specific protein S-100 is obtained in an ultra-low dose obtained by super-dilution of the matrix solution, respectively, 100 ¹² , 100 ³⁰ and 100 ²⁰⁰ times, equivalent to a mixture of hundred-percent dilutions of C12, C30 and C200 prepared according to homeopathic technology .

It is possible to use the active substance in the form of a mixture of various different dilutions according to homeopathic technology, for example, decimal and or hundredths (C12, C30, C100; D20, C30, C100 or D10, C30, M100, 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 volume ratio of 1: 1 and used in liquid dosage form.

The claimed pharmaceutical composition can also be used in solid dosage form, which contains an effective amount of particles of a neutral carrier - lactose, saturated by soaking in a mixture of aqueous or aqueous-alcoholic solutions with an activated-potentiated form of antibodies to the brain-specific protein S-100 and an activated-potentized form antibodies to endothelial NO synthase, and pharmaceutically acceptable additives, including mainly lactose, microcrystalline cellulose and magnesium stearate.

To obtain a solid oral form of the claimed medicinal product, a fluidized bed is installed (for example, Huttlin Pilotlab type manufactured by Huttlin GmbH) until the particles of a neutral substance, lactose (milk sugar), with a particle size of 150 ÷ 300, are introduced into the fluidized - boiling layer microns, pre-prepared aqueous or aqueous-alcoholic solution of activated-potentiated forms of antibodies to brain-specific protein C-100 and to endothelial synthase of nitric oxide (NO synthase), mainly in the ratio and 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 estimated amount of 0.17 ÷ 0.34 of the mass of solid oral form) of dried particles saturated with the activated-potentiated form of antibodies is loaded into the mixer and mixed with microcrystalline cellulose introduced in an amount of 3-8 mass. parts of the total mass of the load - from the mass of solid oral form. Then 25 ÷ 45 masses are added to this mixture. 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) and magnesium stearate in an amount of 0.1 ÷ 0.3 mass. 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 of an activated-potentiated form of antibodies to the brain-specific protein S-100 and NO synthase in an ultra-low dose of each component, prepared from a matrix solution diluted in 100 ¹² , respectively, in 100 ³⁰ in ^100,200 , which is equivalent to a mixture of hundred-percent dilutions of C12, C30 and C200 according to homeopathic technology.

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

Example 1

Investigation of the effect of a complex preparation, which includes activated-potentiated forms of polyclonal affinity purified rabbit antibodies to brain-specific protein S-100 (anti-S100) and to endothelial NO synthase (anti-eNOS) in ultra-low doses (SMD) obtained by super-dilution of the original matrix solution (concentration of 2.5 mg / ml) in 100 ¹² , 100 ³⁰ , 100 ²⁰⁰ times, equivalent to a mixture of hundreds of homeopathic dilutions of C12, C30, C200, in a 1: 1 ratio (SMD anti-S100 + anti-eNOS), and also components included in its composition - activated potenti Anna forms polyclonal rabbit antibodies to brain-specific proteins S100, purified on an antigen, in ultralow dose (SMD anti-S100), the obtained sverhrazvedeniem initial matrix solution 100 ^12, 100 ^30, 100 ^{to 200} times equivalent mixture of centesimal homeopathic dilutions C12, C30 , C200 and activated-potentiated form of polyclonal rabbit antibodies to endothelial NO-synthase, purified on an antigen, in ultralow dose (SMD anti-eNOS), obtained sverhrazvedeniem initial matrix solution 100 ^12, 100 ^30, 100 ^{to 200} times equivalent mixture of centesimal homeopathic dilutions of C12, C30, C200 were performed in vitro to bind the standard ligand of [ ³ H] pentazocine to the recombinant human sigma-1 receptor using a radioligand method.

Sigma-1 receptor is an intracellular receptor localized in the cells of the central nervous system, the cells of most peripheral tissues and immunocompetent cells. Receptors demonstrate a unique ability to translocate, which is caused by many psychotropic drugs. The dynamics of sigma-1 receptors is directly related to the various effects carried out by the drugs when they act on sigma-1 receptors. These effects include regulation of activity channels, ecocytosis, signaling, plasma membrane remodeling (raft formation), and lipid transport / metabolism. All this can contribute to the development of plasticity of neurons in the brain. There is evidence that sigma-1 receptors have a modulating effect on all major neurotransmitter systems: noradrenergic, serotonergic, dopaminergic, cholinergic systems and NMDA-regulated glutamate effects. Sigma-1 receptor plays an important role in the pathophysiology of neurodegenerative diseases, mental and affective disorders, stroke, and is involved in learning and memory. In this regard, the ability of drugs to influence the effectiveness of the interaction of ligands with the sigma-1 receptor indicates the presence of neuroprotective, anti-ischemic, anxiolytic, antidepressant, anti-asthenic components in the spectrum of their pharmacological activity, which allows us to consider these drugs as effective drugs, including including, for the treatment of cerebrovascular disease.

Potentiated distilled water (a mixture of homeopathic dilutions C12 + C30 + C200) was used as a control.

In the experiment (for measuring total binding), 20 μl of the complex preparation of SMD anti-S100 + anti-eNOS or 10 μl of SMD AT to S100 or 10 μl of SMD AT to NOS was added to the incubation medium. Thus, the amount of SMD anti-S100 + anti-eNOS introduced into the experimental well when testing the complex preparation was identical to the number of SMD AT to S100 and SMD AT to NOS tested as single drugs, which allows a comparison of the effectiveness of the complex preparation with its individual components included in its composition. Potentiated distilled water was introduced into the incubation medium in a volume of 20 μl and 10 μl.

Then 160 μl (~ 200 μg protein) of the homogenate of the cell membranes of the Jurkat line (human leukemic T-lymphocyte line), and lastly 20 μl of the tritium-labeled [ ³ H] pentazocine radioligand (15 nM), were added.

To measure nonspecific binding, instead of preparations or potentized water, 20 μl of unlabeled ligand, haloperidol (10 μM), was added to the incubation medium.

Radioactivity was measured on a scintillation counter (Topcount, Packard) using a scintillation mixture (Microscint 0, Packard) after incubation for 120 minutes at 22 ° C in 50 mM Tris-HCl buffer (pH = 7.4) and filtering on glass fiber filters (GF / B, Packard). Specific binding (in experiment or control) was calculated as the difference between total (in experiment or control) and non-specific binding.

The results are presented as percent inhibition of specific binding in the control (distilled water was used as a control) (Table 1).

Table 1. The effect of drugs and potentiated water on the binding of a standard radioligand [ ³ H] pentazocine to a recombinant human sigma 1 receptor Experimental group The amount introduced into the experimental well % of specific radioligand binding in the control % inhibition of radioligand binding in the control 1st dimension 2nd dimension Average value SMD anti-S100 + anti-eNOS 20 μl 48,4 35.5 42.0 58.0 SMD anti-S100 10 μl 67.3 63.1 65,2 34.8 SMD anti-eNOS 10 μl 147.5 161.1 154.3 -54.3 Potentized water 20 μl 98.1 75.8 86.9 13.1 Potentized water 10 μl 140.1 106,2 123,2 -23.2 Note: % specific binding in the control = (specific binding in the experiment / specific binding in the control) * 100%; % inhibition of specific binding in the control = 100% - (specific binding in the experiment / specific binding in the control) * 100%).

Results reflecting inhibitions above 50% represent significant effects of the test compounds; inhibition from 25% to 50%, indicate effects from mild to moderate; inhibitions of less than 25% are considered minor effects of the test compound and are within the background level.

Thus, under the conditions of this experimental model, it was shown that: the complex preparation of SMD anti-S100 + anti-eNOS is more effective than its individual components (SMD anti-S100 and SMD anti-eNOS), inhibits the binding of the standard radioligand [ ³ H] pentazocine with recombinant human sigma 1 receptor; SMD anti-S100, introduced into the experimental well in a volume of 10 μl, inhibits the binding of the standard radioligand [ ³ H] pentazocine to the recombinant human sigma-1 receptor, but the severity of the effect is less than that of the complex drug SMD anti-S100 + anti-eNOS; SMD anti-eNOS introduced into the experimental well in a volume of 10 μl did not affect the binding of the standard radioligand [ ³ H] pentazocine to the recombinant human sigma-1 receptor; potentiated water introduced into the experimental well in a volume of 10 μl or 20 μl did not affect the binding of the standard radioligand [ ³ H] pentazocine to the recombinant human sigma-1 receptor.

Example 2

To study the properties of the claimed drug for the treatment of patients with attention deficit hyperactivity disorder (ADHD) of the active drug group, 300 mg tablets were used, impregnated with a pharmaceutical composition containing water-alcohol solutions (6 mg / tablet) of activated-potentiated affinity polyclonal forms antigen-purified rabbit antibodies to brain-specific protein S-100 (anti-S100) and to endothelial NO synthase (anti-eNOS) in ultra-low doses (SMD) obtained by super-dilution of the original matrix solution (with a concentration of 2.5 mg / ml) 100 ¹² , 100 ³⁰ , 100 ²⁰⁰ times, equivalent to a mixture of hundred-percent homeopathic dilutions C12, C30, C200 (SMD anti-S100 + anti-eNOS). For patients of the comparison group, 300 mg tablets were used, impregnated with an aqueous-alcoholic solution (3 mg / tablet) of an activated-potentiated form of polyclonal rabbit antibodies to brain-specific protein S-100, purified on antigen, in an ultra-low dose (SMD anti-S100) obtained by over-dilution of the initial matrix solution 100 ¹² , 100 ³⁰ , 100 ⁵⁰ times, equivalent to a mixture of hundred-percent homeopathic dilutions of C12, C30, c50. For patients of the control group (placebo), 300 mg tablets were used containing auxiliary substances (lactose monohydrate - 267 mg, microcrystalline cellulose - 30 mg, magnesium stearate - 3 mg).

The effectiveness of the active drug SMD anti-S100 + anti-eNOS in the treatment of patients with attention deficit hyperactivity disorder (ADHD) was evaluated in a comparative double-blind, placebo-controlled study involving 146 children aged 6 to 12 years (mean age 9.3 ± 0.24 years), which were randomized into three groups depending on the prescribed therapy. For 12 weeks, patients of the active drug group No. 1 (n = 46) received a composition of SMD anti-S100 + anti-eNOS 2 tablets 2 times a day; participants in comparison group No. 2 (n = 50) received 2-daily 2-day SMD anti-S100; patients of the control group No. 3 (n = 50) received placebo 2 tablets 2 times a day. All patients included in the study had clinically pronounced manifestations of ADHD, which was confirmed by high scores on the ADHDRS-IV-Home Version rating scale for symptoms of ADHD: 33.8 ± 0.92 in group No. 1; 32.5 ± 1.14 in group No. 2 and 33.6 ± 0.91 in group No. 3. Most children were characterized by moderate severity of ADHD according to the CGI-ADHD-Severity questionnaire. The total score on this scale was 4.0 ± 0.02 points in group No. 1, 4.0 ± 0.03 points in group No. 2, 4.0 ± 0.00 points in group No. 3. Thus, initially the patients of the three groups had comparable indicators of the severity of ADHD. According to the results of neurological, clinical, laboratory and instrumental examination at the time of inclusion in the study, patients did not register any pathological abnormalities. During the treatment, patients paid the doctor 6 visits for 12 weeks, during which the researcher recorded the dynamics of the severity of the clinical manifestations of ADHD (total score according to the ADHDRS-IV-Home Version scale) and the severity of the disease (according to the CGI-ADHD-Severity scale), supervised the prescribed and concomitant therapy, evaluated the safety of the treatment.

Analysis of the effectiveness of 12-week therapy in three groups showed a decrease of more than 25% of the initial total score on the ADHDRS-IV-Home Version scale in 75% (n = 36) of children who took the composition of SMD anti-S100 + anti-eNOS; 66% (n = 33) of patients taking anti-S100 SMD and 56% (n = 28) of placebo-treated children. Differences in effectiveness between the groups, established during a more detailed assessment, taking into account a three-level gradation of improvement (lowering the total score on the ADHDRS-IV scale by <25%; 25-49.9% or ≥50% of the initial value) are presented in Table 2. Significant improvement with a decrease in the total score by 50 or more percent of the initial value was observed in 52% of children of group No. 1 taking SMD anti-S100 + anti-eNOS, and in 34% of children of group No. 2 taking SMD anti-S100 (versus 8% group 3 patients taking a placebo).

The dynamics of the reduction in the severity of ADHD symptoms during the treatment period (the total score on the ADHDRS-IV-Home Version scale at each of the six visits) is presented in the graph and table 3. A significant decrease (p <0.001) in the clinical manifestations of ADHD compared to the initial state occurred after 2 weeks of therapy in all three observation groups. The positive dynamics was more significant in patients No. 1 and No. 2 groups, because they revealed significant differences in the total score of the ADHDRS-IV-Home Version, not only when compared with the screening visit, but also when compared with the placebo group No. 3. In the following weeks of therapy, the effectiveness of treatment with the SMD composition anti-S100 + anti-eNOS and the monocomponent drug SMD anti-S100 increased, most significantly in the active drug group (p <0.05). The total decrease in the total score according to the ADHDRS-IV-Home Version scale in children of group No. 1 SMD anti-S100 + anti-eNOS was 16.5 points, in patients of group No. 2 SMD anti-S100 - 12.4 points (versus 6.3 points in the placebo group No. 3). As a result of the 12-week treatment, the severity of the clinical manifestations of ADHD in children treated with the anti-S100 + anti-eNOS SMD composition decreased by almost half (-48.8%), and in patients treated with the anti-S100 SMD more than a third (-38.2%), compared with the initial state.

Reception of the composition of SMD anti-S100 + anti-eNOS or SMD anti-S100 had an effect on both clusters of ADHD symptoms, which was confirmed by the dynamics of estimates in two sections of the scale with the ADHDRS-IV-Home Version (Table 3). Moreover, treatment with the anti-S100 + anti-eNOS SMD composition significantly exceeded the effectiveness of the anti-S100 SMD treatment with the degree of effect on the severity of manifestations and attention deficit hyperactivity / impulsivity.

The positive therapeutic effect of the active drug SMD anti-S100 + anti-eNOS and the drug comparison SMD anti-S100 was also demonstrated by evaluating the results of treatment of patients on the scale for assessing the severity of ADHD (CGI-ADHR-Severity) (Table 4). In almost a quarter of patients with SMD anti-S100 + anti-eNOS, the severity of the disease decreased from moderate to mild and even minimal, which was confirmed by a 15% decrease in the average CGI-ADHR-Severity score after 3 months of therapy (from 4.0 ± 0.02 to 3.4 ± 0.06; p <0.001). The effect of monotherapy with SMD anti-S100 was slightly less and amounted to -10% on the CGI-ADHR-Severity scale for 3 months (versus -5% in the placebo group).

The safety analysis included data from all patients participating in the study. Throughout the observation period, tolerance of both the active anti-S100 + anti-eNOS SMD preparation and the anti-S100 SMD comparison drug was good, comparable to placebo. Adverse events were recorded in one patient of the SMD anti-S100 group (headaches that were transient during the fourth week of the study) and in one patient in the placebo group (convergence during the second month of observation). The listed adverse events were not associated with the therapy. In addition, during the treatment there were isolated cases of acute respiratory diseases, also not related to the therapy. All patients of the study groups completed the treatment within the time period established by the study protocol; there were no prematurely retired patients. The absence of pathological changes according to the physical examination of patients and during repeated analyzes of laboratory parameters confirmed the safety of the studied therapy.

According to the results of the physical examination (heart rate, SBP, DBP, body temperature), patients did not register any pathological changes during treatment. Differences in the analyzed indicators for visits and in the compared groups did not reach statistical significance and did not go beyond physiologically acceptable deviations. High levels of adherence to therapy additionally testified both to the effectiveness and safety of the studied drugs. By the end of the 3rd month, adherence to treatment was 99.8 ± 1.15% and 98.8 ± 2.25% in groups No. 1 of SMD anti-S100 + anti-eNOS and No. 2 of SMD anti-S100, respectively (versus 74 , 6 ± 2.54% in the placebo group No. 3).

Thus, the study demonstrated the efficacy and safety of the anti-S100 + anti-eNOS SMD composition and the anti-S100 single-component SMD preparation in the treatment of children with ADHD. The most pronounced therapeutic effect as a result of a 12-week course was observed in the complex drug (SMD anti-S100 + anti-eNOS), which was manifested by the positive dynamics of clinical symptoms in the majority (75%) of children. The composition of SMD anti-S100 + anti-eNOS had a corrective effect on both clusters of ADHD symptoms, resulting in a significant reduction in attention disorders and manifestations of hyperactivity in patients with ADHD.

Table 2. The dynamics of the total score on the scale of ADHDRS-IV-Home Version by the end of 12 weeks of therapy Patient groups The proportion of patients with a decrease in the total score on the scale ADHDRS-IV-Home Version less than 25.0% of the original 25.0-49.9% of the original 50.0% or more of the original SMD anti-S100 + anti-eNOS, n = 48 12 (25%) 11 (23%) 25 (52%) ^## SMD anti-S100, n = 50 17 (34%) 16 (32%) 17 (34%) ^## Placebo, n = 50 22 (44%) 24 (48%) 4 (8%) Significance of differences compared with the placebo group: ^## p <0.01.

Table 3. The dynamics of the severity of the clinical manifestations of ADHD according to the ADHDRS-IV-Home Version scale Treatment stage SMD anti-S100 + anti-eNOS, n = 48 SMD anti-S100, n = 50 Placebo, n = 50 Value (M ± SE) Δ from the original Value (M ± SE) Δ from the original Value (M ± SE) Δ from the original Total score Screening 33.8 ± 0.96 32.5 ± 1.14 33.6 ± 0.91 2 weeks 24.1 ± 0.97 *** ^# -28.7% 25.1 ± 1.03 *** ^# -22.8% 28.8 ± 1.26 *** -14.3% 4 weeks 22.6 ± 0.98 *** ^## -33.1% 22.7 ± 1.23 *** ^## -30.2% 29.9 ± 1.06 *** -11.0% 6 weeks 19.4 ± 0.95 *** ^## -42.6% 20.8 ± 1.06 *** ^## -36.0% 29.0 ± 1.25 *** -13.7% 8 weeks 18.9 ± 0.94 *** ^### -44.1% 20.9 ± 1.30 *** ^### -35.7% 27.6 ± 1.35 *** -17.9% 12 weeks 17.3 ± 0.96 *** ^{### &} -48.8% 20.1 ± 1.21 *** ^### -38.2% 27.3 ± 1.48 *** -18.8% Attention Disorders Screening 18.4 ± 0.55 17.4 ± 0.57 18.4 ± 0.43 2 weeks 12.8 ± 0.57 *** ^# -30.4% 13.7 ± 0.68 *** ^# -21.3% 16.1 ± 0.66 *** -12.5% 4 weeks 11.6 ± 0.56 *** ^### -37.0% 12.9 ± 0.79 *** ^### -25.9% 16.4 ± 0.57 *** -10.9% 6 weeks 10.7 ± 0.54 *** ^### -41.8% 11.9 ± 0.64 *** ^### -31.6% 16.0 ± 0.70 *** -13.0% 8 weeks 10.3 ± 0.53 *** ^### -44.0% 11.5 ± 0.70 *** ^### -33.9% 15.1 ± 0.76 *** -17.9% 12 weeks 9.7 ± 0.55 *** ^{## &} -47.3% 11.4 ± 0.68 *** ^## -34.5% 14.9 ± 0.78 *** -19.0% Hyperactivity / impulsivity

Continuation of table 3. Hyperactivity / impulsivity Screening 15.4 ± 0.61 15.1 ± 0.77 15.2 ± 0.62 2 weeks 11.3 ± 0.63 *** -26.6% 11.4 ± 0.61 *** -24.5% 12.7 ± 0.74 *** -16.4% 4 weeks 11.0 ± 0.62 *** ^### -28.6% 9.8 ± 0.64 *** ^### -35.1% 13.5 ± 0.67 ** -11.2% 6 weeks 8.7 ± 0.59 *** ^## -43.5% 8.9 ± 0.64 *** ^### -41.1% 12.9 ± 0.73 ** -15.1% 8 weeks 8.6 ± 0.60 *** ^## -44.2% 9.5 ± 0.76 *** ^## -37.1% 12.5 ± 0.81 *** -17.8% 12 weeks 7.6 ± 0.57 *** ^{### &} -50.6% 8.7 ± 0.70 *** ^### -42.4% 12.5 ± 0.82 *** -17.8% Note. Significance of differences compared with the initial indicator: * p <0.05, ** p <0.01, *** p <0.001. Significance of differences compared with the placebo group: ^# p <0.05, ^## p <0.01, ^### p <0.001. Significance of differences compared with the anti-S100 SMD group: ^& p <0.05.

Table 4 CGI-ADHD-Severity ADHD Severity Dynamics Indicator SMD anti-S100 + anti-eNOS, n = 48 SMD anti-S100, n = 50 Placebo, n = 50 Screening 4 weeks 12 weeks Screening 4 weeks 12 weeks Screening 4 weeks 12 weeks Severity of ADHD M ± SE 4.0 ± 0.02 3.6 ± 0.02 ** 3.4 ± 0.06 *** 4.0 ± 0.03 3.8 ± 0.06 ** 3.6 ± 0.08 *** 4.0 ± 0.01 3.9 ± 0.05 3.8 ± 0.06 *** Δ from ref -10% -fifteen% -5% -10% -2.5% -5% Significance of differences compared with the initial indicator: ** p <0.01, *** p <0.001.

During the study, the following methods were used and the following state parameters were determined:

Diagnostic and Statistical Handbook of Mental Disorders (DSM-IV) (to be completed by the researcher) A 1. six (or more) of the following symptoms of inattention were observed for at least 6 months and are so pronounced that they indicate insufficient adaptation and discrepancy with normal age characteristics: Inattention (circle the correct statement) (a) often unable to maintain attention to detail; due to negligence, frivolity, makes mistakes in school assignments, in the work performed and other activities; (b) it is usually difficult to maintain attention when completing tasks or during games; (c) often it seems that the child is not listening to the speech addressed to him; (d) often it is not able to adhere to the proposed instructions and cope to the end with the implementation of lessons, homework or duties at the workplace (which is in no way connected with negative or protest behavior, inability to understand the task); (e) often has difficulty organizing independent tasks and other activities; (e) usually avoids engaging in assignments that require continued retention of mental stress (e.g., school assignments, homework); (g) often loses things needed at school and at home (for example, toys, school supplies, pencils, books, work tools); (h) easily distracted by extraneous stimuli; (i) often shows forgetfulness in everyday situations. 2. six (or more) of the following symptoms of hyperactivity / impulsivity were observed for at least 6 months with a degree of intensity that is unacceptable and does not correspond to the level of development: Hyperactivity (circle the correct statement) (a) restless movements in the hands and feet are often observed; fidgets a chair; (b) often leaves his place in the classroom and in other situations where it is required to remain in his place; (c) often exhibits aimless motor activity: runs, spins, tries to climb somewhere, and in situations where this is unacceptable;

(d) usually can’t play quietly or calmly or do anything at leisure; (e) is often in motion or acts as if "with a motor" (e) often speaks too much Impulsivity (circle the correct statement) (g) often begins to answer without hearing the question to the end; (h) it is usually difficult to wait for their turn in various situations; (i) often interferes with others, pestering others (for example, intervenes in conversations or games) B. Some symptoms of impulsiveness, hyperactivity, and inattention begin to cause concern for those around the age of a child under seven years of age. C. Problems caused by the above symptoms occur in two or more types of environments (for example, at school and at home). D. There is convincing evidence of clinically significant impairment in social contact or schooling. E. Symptoms occur not only as a manifestation of pervasive developmental disorder (PDD), schizophrenia, or other psychotic disorders and cannot be clearly explained by other mental disorders (e.g., mood disorder, anxiety disorder, dissociative disorder, or personality disorder). Type Based Code Conditions
Diagnosis Criterion A1 is met Criterion A2 is fulfilled 314.01 Attention Deficit Hyperactivity Disorder

ДА

YES

YES 314.00 Attention Deficit Hyperactivity Disorder, with a dominance of inattention

YES

NO 314.01 Attention Deficit Hyperactivity Disorder with Hyperactivity / Impulsivity Dominance

NO

YES

ADHDRS-IV-Home Version (DuPaul G., et al. 1998) (filled out by the researcher according to the legal representatives / parents) Note: Circle the answer that best reflects the child’s behavior since the last visit. Behavior description Never / Rarely Periodically Often Often one. He was unable to keep his attention to detail; due to negligence, frivolity made mistakes in school assignments 0 one 2 3 2. Restless movements in cysts and feet were observed; fidget on a chair 0 one 2 3 3. I hardly kept my attention when doing tasks or during games 0 one 2 3 four. Leaving his place in the classroom and in other situations where it is required to remain in his place 0 one 2 3 5. It seemed that the child was not listening to the speech addressed to him 0 one 2 3 6. He showed aimless motor activity: he ran, spun, tried to climb somewhere, and in such situations when it is unacceptable 0 one 2 3 7. I was not able to adhere to the proposed instructions and cope to the end with the implementation of lessons, homework or duties at the workplace (not associated with negative or protest behavior, inability to understand the task) 0 one 2 3 8. I couldn’t play quietly or calmly or do anything at my leisure 0 one 2 3 9. I experienced difficulties in organizing independent fulfillment of tasks and other activities 0 one 2 3 10. Was in motion or acts as if “with a motor” 0 one 2 3 eleven. Avoid involvement in tasks that require a long-term preservation of mental stress (for example, school tasks, homework) 0 one 2 3 12. Talked too much 0 one 2 3 13. Lost things needed at school and at home (e.g. toys, school supplies, pencils, books) 0 one 2 3 fourteen. He began to answer without listening to the question until the end 0 one 2 3 fifteen. Easily distracted by extraneous stimuli 0 one 2 3 16. Hardly waiting in line 0 one 2 3 17. Forgetful in everyday situations 0 one 2 3 eighteen. Interfered with others, molested others (for example, interferes in conversations or games) 0 one 2 3 Total score

Inattention (the sum of all odd points)

Hyperactivity / Impulsivity (the sum of all even points)

CGI-ADHD-Severity (Guy W., et al. 1976) (filled out by the researcher) Note: Circle the score for the severity of ADHD. Score Description Severity of ADHD one A child is adequate in any environment Normal, healthy No external structure required No different from other children 2 Minor difficulties in any one environment Minimum disease severity If an external structure is required, then only a little Border degradation 3 Some degradation in any one environment Mild disease severity four Some degradation in at least two types of environment Moderate severity of disease Significant difficulties at school and / or control of their behavior 5 Deterioration in all types of environments Severe disease severity Significant stress for others Disrupted social connections 6 Significant degradation constantly in all types of environments Seriously ill Insolvency in study / social environment Daily surveillance is required throughout the day or most of it. 7 The most severe form of the disease One of the hardest patients Complete failure even with constant supervision

Claims (10)

1. A drug for the treatment of attention deficit hyperactivity disorder, containing an activated-potentiated form of antibodies to the brain-specific protein S-100, characterized in that it is made in the form of a pharmaceutical composition and contains an activated-potentiated form of antibodies to endothelial NO as an additional reinforcing component synthase. 2. The drug according to claim 1, characterized in that the activated-potentiated form of antibodies to the brain-specific protein S-100 and the activated-potentiated form of antibodies to endothelial NO synthase are used in the form of an activated-potentiated aqueous or aqueous-alcoholic solution, the activity of which due to the process of successive multiple dilutions in an aqueous or hydroalcoholic solvent in combination with an external mechanical action - shaking of each dilution. 3. The drug according to claim 1 or 2, characterized in that the pharmaceutical composition is made in solid dosage form and contains an effective amount of granules of a neutral carrier saturated with a mixture of aqueous or aqueous-alcoholic solutions of an activated-potentiated form of antibodies to the brain-specific protein S-100 and an activated-potentiated form of antibodies to endothelial NO synthase; and pharmaceutically acceptable additives. 4. The drug according to claim 1 or 2, characterized in that the aqueous or aqueous-alcoholic solutions of the activated-potentiated forms of antibodies to the brain-specific protein S-100 and to endothelial NO synthase are obtained by repeated serial dilution in combination with external exposure - shaking each dilution from matrix solutions of affinity-purified antibodies to brain-specific protein S-100 and to NO synthase 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 based on activated-potentiated forms of antibodies is used as a mixture of various, mainly hundred, dilutions according to homeopathic technology. 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 attention deficit hyperactivity disorder by introducing into the body an activated-potentiated form of antibodies to the brain-specific protein S-100, characterized in that an activated-potentiated form of antibodies to endothelial NO synthase is additionally simultaneously administered. 8. The method according to claim 7, characterized in that the activated-potentiated form of antibodies to the brain-specific protein S-100 and the activated-potentiated form of antibodies to endothelial NO synthase are used in the form of an activated-potentiated aqueous or aqueous-alcoholic solution of each component, activity which is due to the process of multiple dilutions in an aqueous or hydroalcoholic solvent in combination with an external mechanical action - shaking of each dilution. 8. The treatment method according to claim 7, characterized in that a mixture of different dilutions of antibodies to the brain-specific protein S-100 in combination with a mixture of different dilutions of antibodies to endothelial NO synthase prepared according to homeopathic prepared in the form of a single drug is used technologies. 9. A pharmaceutical composition for treating attention deficit hyperactivity disorder comprising an activated-potentiated form of antibodies to the brain-specific protein S-100 and an activated-potentiated form of antibodies to endothelial NO synthase.