Method of treating cadmium radiation injury and method for producing preparation for cadmium radiation injury

FIELD: medicine.

SUBSTANCE: group of inventions refers to medicine, namely to radiation biology, and may be used to treat a cadmium radiation injury and to produce a preparation for the cadmium radiation injury. Treating the cadmium radiation injury is ensured by the single subcutaneous administration of a composition consisting of anti-radiation therapeutic globulin and a suspension-forming fraction of bentonite, in a dose of 20-25 mg/kg of body weight that is followed by three more administrations 24, 48, 96 hours later if observing chronic heavy metal administration. The preparation is produced by dissolving the suspension-forming fraction of bentonite in anti-radiation therapeutic globulin in ratio 0.3:99.7 respectively while constantly stirred, and a solid concentration is reduced to 10%; the preparation is sterilised by filtration and then bottled 250-300 cm3 each to be closed tightly and kept at temperature 4-6°C.

EFFECT: method enables a consistent process of the preparation with enhanced therapeutic and decorporating effect ensured by the targeted delivery as a single agent with simplifying the use conditions.

3 cl, 2 tbl

 

The invention relates to radiation biology and toxicology, in particular the production and use of radioprotective and antidote drugs with radiation and chemical damage.

There is a method of treatment of radiation injuries of the body and the method of producing drug for the treatment of radiation injuries by a single subcutaneous injection radioprotective serum during the first 10 days after irradiation (see RF Patent №2169572, IPC AC 35/28, publ. 27.06.2001,).

The disadvantage of this method is the lack of decarburised of action of the drug by the combined action on the body of ionizing radiation and chemical toxicant-cadmium.

The closest in technical essence is a method of treating radiation-cadmium defeat body gamma radiation and cadmium by subcutaneous three times the introduction of radiation treatment-and-prophylactic immunoglobulin at a dose of 50 mg/kg and the introduction in the diet of bentonite based on 2% of its mass (see abstract. Diss. Largartomania "Combined lesions of animals with gamma radiation and cadmium and application of therapies". - Kazan. - 2008. - 23 S.).

The disadvantage of this method is separate (subcutaneous) use of radiation treatment globulin and long-term (over 30 days) oral administration of bentonite as part of the RA the ion. It was found that the method is effective only in animals that were irradiated in the dose LD50(7,0 Gr), and when applying a lethal dose (9,0 G) the desired therapeutic effect is not achieved. Another significant disadvantage of this method is the poor absorption of bentonite through the mucous membrane of the intestine, because the bulk of bentonite clays are of a particle size from 0.1 to 0.01 mm, presents insoluble salts and quartz, which does not participate in the adsorption process of toxicants (radionuclides, heavy metals), transit through the gastrointestinal tract (GIT), creating, thus, the only additional load on the digestive tract, which affects animal health. When this toxicant (cadmium), already that absorb in the blood through the gastrointestinal mucosa, is deposited in critical organs (liver, kidney, bone marrow), and therefore the used adsorbent (bentonite) in oral application, does not reach the target (the target cell), in which the deposited metal, and therefore the effectiveness of therapy in the combined damage to the body with radiation and cadmium does not exceed 60% even when using sub-lethal doses of ionizing radiation (7,0 Gr - LD50) and lethal dose (5 MPC) heavy metal cadmium.

The task of the invention to provide monotherapy by conjugation (SWE is ivania) globulin with microparticles of purified fractions of natural sorbent-bentonite, improving treatment decarbonise activity of the drug in the combined radiation and chemical damage to the body due to targeted delivery of therapeutic agent (globulin) to the affected target cells with simultaneous detoxification and metabolic decorporate heavy metal, a lower dose of bentonite and the burden on the gastrointestinal tract.

The problem is solved in that in the method of treatment of radiation-cadmium lesions involving the introduction into the organism of biological drug, as a specific drug use composition consisting of radiation globulin and suspensionusual fraction of bentonite, which is injected once subcutaneously in doses of 20-25 mg/kg body weight and three times at 24, 48, 96 hours chronic heavy metal.

The problem is solved and the fact that in the method of producing drug for treating radiation-cadmium lesions involve the dissolution suspensionusual fraction of bentonite in radiation treatment immunoglobulin, taken in the ratio of 0.3:99,7 respectively, with constant stirring and bring a dry matter concentration of 10%, sterilized by filtration, and then poured into bottles with a capacity of 250-300 cm3, sealed and stored at a temperature of 4-6°C. And suspen yearsyou fraction obtained by pre-treatment with hydrochloric acid, followed by removal of the distilled water soluble salt particles and quartz, further otmuchivanie of particle size 0,0006-0,0009 mm and drying.

A fundamental difference between the method of production and application immunotropic-adsorption composition of the drug for treatment of radiation-chemical destruction of animals is that instead of having separate subcutaneous and oral administration of two different drugs (therapeutic globulin and bentonite), use of multifunctional composite monotherapy loaded suspensionusual fraction of bentonite radiation treatment-and-prophylactic globulin, which provides emergency (ekstraimmunnaya) therapy had a combined radiation and chemical exposure of the organism at the expense of extra targeted delivery detoxifying agent - montmorillonite to the affected chemical toxicant (cadmium) target cells - hepatocytes, stem cells from bone marrow (CCM), and lymphocytes - target cells to radiation damage. High detoxifying (antidote, decolorise) effect of application of composite drug containing microparticles of bentonite, is achieved not only due to the physico-chemical binding (adsorption) of cadmium from food in the gastrointestinal tract (which is observed in oral application of bentonite), but part of the microparticles of the bentonite in the compo is icii in complex metabolism of cadmium in the body, in which the zinc ions contained in the composition of the bentonite, are exchanged for ions of cadmium deposited in the hepatocytes of the liver, and zinc ions, in turn, replacing the cadmium in the affected cell, connecting with protein molecules form a zinc-metallothionein (ZnMn), which has a powerful antidote (anticommie) properties, decorporate struck the target cell from the toxicant and eliminating the consequences of cadmium intoxication.

Treatment decarbonise the effect of the proposed composition when combined (radiological and chemical) the defeat of the body is achieved by antiradicalism action of immunoglobulins involved in the neutralization of toxic and neck surgery radicals (H+, OH-H2O2, quinoid and lipid radiotoxins), thereby inhibiting the apoptotic death of immune cells (lymphocytes), changes in the metabolism of heavy metal in the body by effectively linking it and excretion from the body with simultaneous synthesis of zinc-metallothionein (ZnMn)involved in the process of liquidation of consequences of cadmium toxicity. Therefore, when using the composition of the drug is achieved synergies (gain) radioprotective and antidote (anticamera) effect, providing a higher and more rapid (emergency) the cleansing of the body from the toxicant and diindolymethane products of oxidative modification of macromolecules.

The method of producing drug for the treatment of combined radiation and chemical injury, and treatment of combined radiation injuries of the body is as follows.

The first stage is conducted activating mineral sorbent - bentonite by selection of the most active vysokosortnoe fractions, using the principle of selective fractionation of montmorillonite in the clay fraction after the destruction of carbonates, removal of soluble salts and otmuchivanie microparticles (0,0006-0,0009 mm) bentonite (see A.S. USSR №952260, MCL AC 39/00, publ. from 28.08.1982,, bull. No. 31). This bentonite is subjected to special treatment. For the destruction of carbonates clay treated with 1 N. hydrochloric acid, and then 0.1 G. of the Resulting soluble salts and silica is removed by laundering with distilled water. For this the clay with water transfer in vegetation glasses (20×12 cm). On each glass put labels: the first is at a height of 3 cm from the bottom, the second at 7 cm above the third - to 7 cm above the second. Distilled water up to the third label, Usacheva in her bentonite and leave for 12 hours to defend. When the solid part of the clay settles, and over it is a transparent liquid, the latter is removed by siphon and again pour distilled water up to the top of the label. When the suspension remains in vesvese the nom condition, start otmuchivanie of particle size 0,0006-0,0009 mm. To do this, pour into a glass of distilled water to the top of the label, the contents stirred, after 24 hours immersed siphon to a depth of 7 cm and with it, the suspension is poured into a glass receiver. Otmuchivanie continue to enlightenment suspension. In glasses-receivers to each new portion of the suspension add 3-4 drops of concentrated hydrochloric acid for coagulation and sedimentation of the suspension. Fraction washed with distilled water, and then dried in a water bath and used as a sorption component composite globulin-bentonite product.

In the second stage, prepare polyfunctional composition based radiation treatment globulin and montmorillonite fraction of bentonite. For compositions take a certain amount (for example, 100 cm3) globulin (PRLG)containing 25-30 mg/ml protein, contribute soluble powder (suspensionusual) fractions of bentonite (SOFB) 29-31 mg on 1 cm3globulin, the mixture was mixed thoroughly, determine its content of biologically active substances (dry matter), which varies 54-61 mg on 1 cm3the concentration of solids in the composition adjusted to 100 mg/ml (10%solution), then it is subjected to conventional sterilization is in Microbiology and immunology methods.

Obtained by the above described method of composite preparation based radiation treatment globulin (PRLG) and montmorillonite fraction of bentonite (AFB) is used as a means for ekstraimmunnaya therapy combined radiation and chemical destruction of the body in lethally irradiated and inoculated in lethal doses of cadmium chloride in laboratory and farm animals.

The method of producing drug for the treatment of combined radiation and chemical injury, and the method of producing drug for the treatment of combined radiation and chemical destruction of animals is illustrated by the following examples.

Example 1. Exploring parenteral use of bentonite. For this purpose from untreated (native) and purified by the above method fractions were prepared 0,1; 0,2; 0,4; 0,8; 1,0; 2,0; 3,0%-nye suspension of bentonite in different liquid media (water, serum, lymph, extracts from organs, globulin). The prepared suspensions were thoroughly mixed in a liquid medium and after 1, 10, 20, 40, 60 min after suspension 1 ml) was subcutaneously injected to white mice. It was found that after the introduction of the suspension of untreated (native) bentonite after 1, 10 min after preparation of the suspension, on the site of injection in animals under the skin is formed of a non-absorbable is Oreshek, consisting of bentonite. This was also observed that the higher the concentration of bentonite in suspension, the large size had formed after injection peas under the skin. After the introduction of the suspensions prepared with 20, 40 and 60 min prior to the introduction, education peas was not observed, since the entire weight of bentonite, which is in the liquid phase, fully precipitated, indicating instability of the suspension and nucleobases and the inability parenteral use of native (untreated) bentonite.

Unlike native suspensions of purified fractions of bentonite, regardless of the length of the suspension and the concentration of particles of bentonite remained stable, remaining in the liquid phase (water, serum globulin) for a long time in suspension and after subcutaneous injection of suspensions at the site of injection education peas were observed, indicating that the absorption of introduced liquid (water, serum globulin with bentonite microparticles) in the blood.

Example 2. Determination of the toxicity of the composition of the drug. To determine reactogenicity and safety of the drug received, the latter in different doses(1,0; 2,0; 3,0; 4,0; 5,0; 6,0; 7,0; 8,0; 9,0; 10,0 mg/kg body weight) orally, intramuscularly, intravenously and intraperitoneally, one-, two - and three times at intervals of 30, 4, 60, 120 min was introduced to white mice, using 6 animals in each version of the experiment, taking into account the presence or absence of adequate or inadequate response to the drug. It is established that the use of the drug in all variants of experience adverse reactions not caused: the animals were active, willingly took food and water to adequately respond to natural stimuli, which testifies to reactogenicity drug and tolerability they used a range of doses, routes and frequency of administration.

Example 3. The study decarbonise activity suspensionusual fraction of bentonite with injecting drug use. For this purpose was previously prepared composite preparation on the basis of serum and suspensionusual fraction of bentonite by suspension of the powder of purified bentonite in serum by dissolving the powder of the adsorbent at the rate of 300 mg per 100 ml of blood serum (0,3%bentonite suspension (3 mg/ml). The experiment was performed in 45 white mice divided into 3 groups of 5 animals each. Animals of all groups orally once was made fun of cadmium chloride at a dose of 1/5 LD50(36 mg/kg 0,72 mg per mouse). After 24 h after priming the animals of the 1st group was subcutaneously injected once a composite product based serum and suspensionusual fraction of bentonite at a dose of 1ml, animals of the 2nd group within 5 days after the seed was received feed containing native (untreated) bentonite 2% of the volume of feed (0.3 g 300 mg of bentonite for 1 day, 1.5 for 5 days). Haunted animals 3rd group no drugs were given and they served as control seed. For metabolic studies of heavy metal (cadmium chloride) in the body (accumulation and excretion) on the background of the application of the tested drugs in 5 days after priming the animals of all groups were killed, they took samples from internal organs (liver, kidney, bone marrow) and determined the content of heavy metal by flame atomic adsorbed spectrophotometer AAS-3.

The results are shown in table 1.

Table 1
Organs and tissuesCadmium (mg/kg)
the inoculated CdCl2(control)the inoculated and treated feed with 2% bentonite (a method)the inoculated CdCl2and treated subcutaneously once a suspension of bentonite
Liver0,27±020,23±0,03 0,13±0,01**
Kidney0,35±0,040,30±0,010,15±0,03**
Muscles0,29±0,030,25±0,030,17±0,05**
Bone marrow0,25±0,050,21±0,010,09±0,01***
** P<0,05, *** P<0,001

From the table it is seen that despite feeding the animals of the 2nd group for 5 days a diet containing 2% bentonite was observed a slight decrease in the concentration of toxicant in the organs and tissues of the inoculated animals, which was below 1,17 (liver), 1,16 (kidney, muscle), 1,19 (bone marrow) times compared with controls (P>0,05). In contrast to the known single subcutaneous injection of serum containing 0.3% suspensionusual fraction of bentonite, led to a significant reduction of toxicant (2.08 times in the liver, 2,33 - kidney, 1.70 to muscles and 2.78 times in the bone marrow (P<0,001).

Example 4. Determination of the optimal ratio of components in composite preparation. Before conducting experiments received options composite drug containing various amounts of activated (PTS is placed) fractions of bentonite in radiation globulin: 0,1; 0,3; 0,6; 1,2; 2,4; 2,8; 3,0; 3,2% the total volume of the preparation. The obtained variants of the drug was tested on 40 inoculated cadmium chloride at a dose of 1/5 LD50(31 mg/kg) of white mice, divided into 8 groups of 5 each. Animals of the 1st group at 24 h after seed CdCl2once subcutaneously injected globulin-bentonite composition containing 0.1% of activated bentonite (concentration 1 mg/ml), 2-nd group - 0,3%suspension, 3rd - 0,6%, 4th - 1,2%, 5th - 2,4%, 6th - 2,8%, 7th - 3,0%and 8th - 3,2%suspension of bentonite in globulin. After 5 days after priming and the introduction of composite preparation the animals of all groups were killed and examined on the content in organs and tissues of cadmium. It is established that the lowest concentration of fluorine was detected in the organs and tissues of animals treated with composite preparation with a content of 2.8; 3,0 and 3,2% of activated bentonite, which was in a critical organ (liver) of 0.14±0,03; 0,13±0,01 and 0.13±0.03 mg/g, respectively.

The content of the bentonite in the globulin less than 2.8% (2,4; 1,2; 0.6% and so on) did not provide sufficient decolorise effect, and increased concentrations higher than 3.0% did not lead to the increase of the coefficient of decorporation.

Example 5. Determination of the optimal therapeutic dose of radio-antidote composite drug for parenteral (subcutaneous) administration.

To determine the Opti is the real therapeutic doses of the drug were prepared with different concentrations of the drug content of biologically active substances (BAS), i.e. dry matter content (protein-globulins, bentonite) in it. For this purpose, the preparation was subjected to lyophilization and the precipitate was dissolved in sterile boiled water in concentrations 100,0; 50,0; 25,0; 12,5; 6,25; 3,12; 1,56; 0,78; 0,39; 0,19; 0,95 mg/ml Listed concentrations of the drug subcutaneously once injected irradiated in a lethal dose of 7.7 G) 55 white mice (5 animals for each concentration of the drug) in an amount of 0.2 ml per animal. It is established that after subcutaneous administration of the drug at concentrations 100,0; and 25.0 to 50.0 mg/ml survival of animals was 80% (survived 4 animals 5). With the introduction of animals less concentrated solutions gradual decrease was observed radioprotective activity of the drug with 66,0 to (survived 3 out of 5 animals) 20% (1 animal survived out of 5). Therefore, the optimal therapeutic dose is 20-25 mg/kg Increase in therapeutic doses to 30.0; 100.0 mg/kg does not increase therapeutic effect, less concentrated solutions (12,5; 6,15 mg/kg) do not provide sufficient effect.

Example 6. The choice of the optimal doses of gamma rays and cadmium, causing a lethal effect when combined their action on the body.

Before examining the clinical effectiveness of composite drug when combined radiation and chemical damage to the body, with the purpose of modeling this type of lesion, the need is to choose the optimal dose damaging agents, since this defeat is the summation of the effects of the individual components, which when isolated action does not have a lethal effect.

For this purpose, experiments were performed on 50 white mice, divided into 5 groups of 10 each. Animals of the 1st group were subjected to a seed within 5 days of cadmium chloride (CdCl2dose of 1/5 LD50and was irradiated with γ-rays at a dose LD50(6,0 G); 2nd group - once CdCl2(1/4 LD50)+γ-rays (6,0 G); 3rd group - CdCl2(5-fold 1/5 LD50)+γ-rays of 7.0 G (LD50); 4th group - CdCl2(1-fold LD50)+γ-rays of 6.0 G (LD50); 5-th group - CdCl2(once LD50)+γ-rays (7,0 Gr - LD50).

For zatravlenny and irradiated animals were monitored for 30 days by registering dead and surviving animals in the respective groups.

It is established that the mortality in the 1st group was 80%, in the 2nd, 3rd, 4th and 5th groups - 100%. Therefore, if the combined damage to the body even non-lethal doses of the individual components (CdCl2- 1/4 LD50, γ-rays - LD50), causing separately only 30%and 50%lethal effect, the combined effect of them showed 100%lethal effect, suggesting a synergistic action of damaging agents when a combination of the effect on the body. So the dose CdCl 2and γ-rays were used for the modelling of radiation-chemical destruction when assessing the clinical effectiveness of composite preparation.

Example 7. Assessment of clinical effectiveness composition of the drug when combined radiation and chemical damage to the body. To evaluate therapeutic efficiency of composite preparation on the basis of radiation globulin and activated (purified, fractionated) bentonite (PRLG-B)experiments were performed on 15 sheep breed "Preco", 18 months of age with an average live weight of 38±3 kg the Animals were divided into 3 groups of 5 animals each. The animals of the 1st group received cadmium chloride single dose of 1/4 LD50(45 mg/kg) followed by irradiation at a dose of 4.2 G (LD50for sheep); a sheep of the 2nd group asked to cadmium chloride at a dose of 1/4 LD50, were irradiated at a dose of 4.2 G and subjected to treatment by a known method by a single subcutaneous injection radiation treatment globulin (PLG) at a dose of 50 mg/kg and oral in diet composition were fed for 30 days untreated (native) bentonite 2% of the volume of feed; animals of the 3rd group was subcutaneously injected once compositional drug PRLG-B at a dose of 25 mg/kg body weight.

The animals were clinical observation, recording of dead and surviving animals within 30 when t after combined radiation and chemical effects on animals. Criteria for clinical effectiveness of the tested drugs were the survival of the affected two environmental agents (CdCl2+γ-rays) animals, the severity of clinical manifestations of radiation sickness and cadmium intoxication, and the degree of decorporation (excretion) of cadmium from the body, inhibition of the synthesis radiomodifying oxidative macromolecules (MDA) and hemotoxins effect hit by two environmental agents of animals. The results of the experiments are presented in table 2.

Table 2
The group of animalsThe concentration of MDA, µm/gDeath of lymphocytes, %Concentrations of CdCl2in a critical organ, mg/kgThe survival of animals, %
1-I (control of radiation-chemical destruction-CdCl2+γ-rays)to 8.57±0,29of 89.7±2,50,31±0,50
2-I control well-known treatment method5,98±0,71*57,9±3,1**0,22±0,0333,3
3-I control the proposed method of treatment1,29±0,15***21,5±1,7***0,11±0,01**80,0***
MDA - malondialdehyde, * - P<0,05, *** P<0,001; control of radiation-chemical destruction (CdCl2- 1/4 LD50+γ-rays - LD50); the known control method of treatment (CdCl2- 1/4 LD50+γ-rays - LD50+PRLG - 50 mg/kg+oral dose of bentonite in feed at the rate of 2% of the amount within 30 days; the control of the proposed method (CdCl2- 1/4 LD50+γ-rays - LD50+1 - fold subcutaneous administration PRLG-B at a dose of 25 mg/kg of dry matter).

This table shows that the use of the known method of treatment of combined radiation and chemical destruction (γ-rays±CdCl2) did not provide reliable protection of the body from radiation and toxic factors - survival rate was 33.3%. Radiation death of animals on the background of heavy metal intoxication occurred in catastrophic destruction of the immune cells (lymphocytes) in the peripheral blood and a significant increase in the concentration radiomodifying oxidative macromolecules, causing apoptotic cell death of target radiation (lymphocytes). Oral paragraph shall enter into the body of the mineral adsorbent - native (untreated) bentonite did not provide reliable decorporation chemical toxicant content of cadmium in the critical organ is the liver was high enough, yielding to the control of only 1.4 times (P>0,05).

In contrast to the known, the use of the proposed tools provided effective treatment of radiation-chemical destruction, greatly increasing the survival of irradiated and inoculated CdCl2animals, which was 80% against 33.3% in known. Effective radiation protection and antidote when applying the proposed method realized by neutralizing toxic radicals - MDA (4,63 times, P<0,001), blocking and neck surgery apoptotic cell death of target lesions - lymphocytes (2.69 times less in comparison with the known) and the effective elimination of toxin from the body depo - liver (2 times more than in the known method, P<0,001).

Thus, the resulting composite product has a bifunctional (radioprotective and antidote) property, providing a reliable treatment of the combined radiation-chemical destruction of the body and excretion of the toxicant (cadmium) from the body, i.e. combining in a single drug treatment and decarbonise property, while reducing therapeutic dose of radiation globulin 2 the Aza (vs. 50 mg/kg of the known 25 mg/kg of the offer) and 30 times faster time removing heavy metals from the body, as well as reducing the consumption of bentonite 20 times in comparison with the known.

1. A method of treating radiation-cadmium lesions involving the introduction into the organism of biological drug, characterized in that as a specific drug use composition consisting of radiation treatment globulin and suspensionusual fraction of bentonite, which is injected once subcutaneously in doses of 20-25 mg/kg body weight and three times at 24, 48 and 96 h in chronic heavy metal.

2. The method of producing drug for treating radiation-cadmium lesions involving the dissolution suspensionusual fraction of bentonite in radiation treatment immunoglobulin in the ratio of 0.3:99,7 respectively, with constant stirring and adjusting the concentration of dry matter of the mixture to 10%, sterilized by filtration, and then poured into bottles with a capacity of 250-300 cm3, sealed and stored at a temperature of 4-6°C.

3. The method according to claim 2, characterized in that suspensionusual fraction obtained by pre-treatment with hydrochloric acid bentonite with the subsequent removal of distilled water soluble salt particles and quartz, further otmuchivanie of particle size 0,0006-0,0009 mm and drying.



 

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SUBSTANCE: invention refers to pharmaceutical industry, namely a method for preparing an antioxidant homogenous sterile holothurian solution. The method for preparing the antioxidant homogenous sterile holothurian solution consisting in the fact that raw residual tissue is washed, ground, placed in containers and exposed to heat in a steam steriliser at pressure by formula min./degree wherein n is optimal tissue degradation time 55 to 65 min.

EFFECT: method provides preparing the homogenous sterile solution showing high pharmacological value.

6 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmaceutical and cosmetic industry and concerns preparing shelf fungus extract. A method for preparing shelf fungus extract involving extraction of ground shelf fungus in sodium or potassium hydroxide under certain conditions; the prepared extract is filtered.

EFFECT: shelf fungus extract prepared by the method described above shows high antioxidant activity and prolonged shelf life.

1 tbl, 2 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to combinations of peptides in each case with the same sequence length (SEQL) which can be prepared in a stable reproducible quality and quantity of a mixture (A) containing a number of x amino acid with protected acid groups or a number of z peptides with the acid groups protected by the protective groups and the activated amino groups, with the amino acids in the mixture (A) found in a specific molar ratio, and a mixture (B), containing a number of y amino acids with the amino groups protected by the protective groups, with a molar ratio of the amino acids of the mixture (B) being the same as the molar ratio of the amino acids of the mixture (A), and the number x=y, and x is a figure from 11 to 18.

EFFECT: new combinations of the peptides are presented.

13 cl, 2 dwg, 1 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention provides RANK-L targeted amino acid sequences, as well as to a compound or a construct, and particularly, proteins and polypeptides which comprise or substantially consist of one or more of these amino acid sequences. The invention also discloses nucleic acids encoding such amino acid sequences and polypeptides; methods for preparing such amino acid sequences and polypeptides; host cells expressing or able for expressing such amino acid sequences or polypeptides. There are also disclosed compositions and particularly, pharmaceutical compositions for preventing and/or treating bone diseases and disorders, which include such amino acid sequences, polypeptides, nucleic acids and/or host cells. What is shown is a possibility to use the amino acid sequences or polypeptides, nucleic acids, host cells and/or compositions for the preventive, therapeutic or diagnostic purposes.

EFFECT: polyvalent construct of the invention has a half-life in human serum from 12 hours to 19 days.

32 cl, 30 dwg, 24 tbl, 17 ex

FIELD: chemistry.

SUBSTANCE: invention discloses artificial peptide mini-antigens (PMA) which can be used to induce controlled protective humoral IgG-mediated immune response against allergen. The mini-antigen includes: hydrophobic peptides from different proteins and any pathogens which are linked with pockets of the most common MHC (major histocompatibility complex) molecules class II and to which, in the human population, there are memory T cells (memory T cell T epitopes (MTC)), and hydrophilic peptides from different proteins which are on the surface of wild type allergen, which are conjugated onto the support of the cladding of the polymer particle and are accessible for antibodies. (The structure of the mini-antigen is shown on fig 14 in the description). The mini-antigens are characterised by the capacity to replace B epitopes with peptides of another allergen while preserving the nucleus of the MTC T epitopes, which enables to use the peptide mini-antigens to make anti-allergy vaccines against different types of allergies. The presence of memory T cells helps to considerably speed up immune response triggering. The introduction of peptides of only basic allergen proteins into the structure ensures anti-allergy protection with minimal load on the immune system.

EFFECT: absence of binding of IgE with peptides makes vaccination safe and fast.

14 dwg, 2 tbl, 3 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, in particular to neuroophthalmology, and may be used for treating the visual pathway disorders in the patients with multiple sclerosis. For this purpose, the preparation cortexin is introduced retrobulbar or parabulbar. Then 30 minutes after the introduction of cortexin, upper cervical and stellate ganglia of the sympathetic nervous system are percutaneously exposed to a rotating electric pulse field. This field is generated in a space between the left and right ganglia using two multiple electrodes. The electrodes consist of a number of partial galvanic isolated conductive elements functioning as cathodes and two anodes which are placed in a projection of the ganglia. While forming the electric current pulses, the partial elements of the multiple electrodes are switched; the exposure is paused. Thereafter, a zone of ganglia activity block is switched. It is followed by electrical stimulation of the visual pathway via an electrode applied on the eyelids. For this purpose, the rotating electric pulse field is generated in the space between this electrode which is as the anode, and the partial elements of the multiple electrodes.

EFFECT: method provides relieved demyeliniation, neurodegenerative processes within the visual pathway, improved visual function, including visual acuity and functional characteristics.

5 ex

FIELD: chemistry.

SUBSTANCE: invention discloses an antibody or a functional fragment thereof, which specifically identifies a polypeptide coded by a gene in the human body, and inhibits formation of osteoclasts and, optionally, osteoclastic bone resorption. The antibody or functional fragment thereof can be obtained particularly by hybridoma technology using hybridoma #32A1(FERM BP-10999) and #41B1 (FERM BP-11000) disclosed in the invention. Described is a pharmaceutical composition based on the antibody or functional fragment thereof for treating and/or preventing bone pathobolism in a patient, as well as methods of treating and preventing anomalous metabolism of bone tissue using antibodies or functional fragments thereof.

EFFECT: use of the invention enables specific identification gene-expressed human Siglec-15 using the disclosed antibody and inhibit formation of osteoclasts.

39 cl, 80 dwg, 9 tbl, 38 ex

FIELD: medicine.

SUBSTANCE: invention relates to field of veterinary. Method includes application of anti-protozoa medication and immunomodulator. As anti-protozoa medication applied is Neosidin M in a single injection intramuscularly in dose 2.0 mg/kg of animal body weight (in terms of active substance). As immunomodulator applied is Ribotan in a single injection subcutaneously in dose 1 ml per an animal.

EFFECT: method is highly efficient in treatment and prevention of reindeer babesiosis, ensures reduction of parasites in blood of animals and protection against spontaneous babesiosis for a long term.

2 tbl, 2 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine and veterinary science, namely a method for preparing a biologically active peptide complex of Gadidae fam. liver. The method involves grinding a raw material, extracting in mixed oil and water in proportions of raw material: extractant 1:5-1:30 at room temperature for 2-4 hours with agitation. Further, the end product is purified by treating in an organic solvent in relation of 1:0.5-2 followed by separation and drying of an aqueous residue. The raw material is presented by cod liver either fresh, frozen or dry, while the organic solvent is specified in a number of diethyl ester, ethyl acetate, butanol, chloroform.

EFFECT: invention provides preparing the peptide complex of cod liver possessing the balanced amino acid composition, the high content of peptides and high antioxidant activity.

3 cl, 4 ex

FIELD: medicine.

SUBSTANCE: there are presented hyaluronidase protein of molecular weight approximately 44±1 kDa containing an amino acid sequence at least by 90% identical to an amino acid sequence containing SEQ ID NO: I, SEQ ID NO: 2 and SEQ ID NO: 4 presented in the description, as well as DNA coding it. What is described is a pharmaceutical medical composition for increasing tissue penetration and decreasing connective tissue viscosity containing an effective amount of recovered said hyaluronidase and a pharmaceutically acceptable excipient, a carrier, a solvent and an additive agent. The following methods are presented: 1) prevented or minimised cicatrisation involving the local introduction of said pharmaceutical composition; 2) reduced wrinkle formation by decreasing connective tissue viscosity involving the local introduction of said pharmaceutical composition; 3) relieved discomfort and pain caused by rheumatic arthritis, systemic sclerosis, peritendinitis or tendovaginitis involving the introduction of said pharmaceutical composition into a patient; 4) improved agent penetration into tissue involving the introduction of the agent together with the pharmaceutical composition into an individual.

EFFECT: invention provides extending the range of pharmaceutical preparations.

14 cl, 23 tbl, 15 dwg, 12 ex

FIELD: chemistry.

SUBSTANCE: invention relates to humanised anti-beta 7 antibodies; a composition containing said antibody; a method of inhibiting interaction of human integrin beta 7 subunits with a second integrin subunit using said antibody; as well as a version of use of the listed antibodies.

EFFECT: invention can be used to treat chronic inflammatory diseases such as asthma, Crohn's disease, ulcerative colitis, diabetes, complications during organ transplantation and diseases associated with allotransplantation.

47 cl, 22 dwg, 10 tbl, 3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to medicine, namely to chemical-pharmaceutical industry and can be applied for industrial manufacturing injection preparation of alpha-fetoprotein (AFP). AFP is obtained from placental and(or) abortion human blood, by separation of ballast proteins from blood by centrifugation, filtration, carrying out chromatographic purifications, stabilisation by dextran, characterised by the fact that before centrifugation auxiliary substances - sodium chloride, triton X-100, chloroform and aprotinin are added.

EFFECT: reduction of number of technological operations with simultaneous reduction of production process duration and increase of output of product obtained during one technological cycle with preservation of purity of obtained alpha fetoprotein and its effectiveness as medication, fixation of optimal modes of cooling, freezing, sublimation and desorption of AFP preparation, reduction of energy consumption, improvement of stability of obtained preparation in storage.

7 cl, 1 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely paediatrics and may be used for treating rumination syndrome in infants. For this purpose, the state of the infant's vegetative nervous system is assessed by cardiointervalography. It is followed by electrophoresis on the area of the cervical sympathetic ganglia by Steam 1 galvaniser apparatus at current density 0.01-0.03 mA/cm2. The electrophoresis procedure is performed in the infant lying on his/her back with a head lifted at 45°-60° in a fixed position from 13 to 14 o'clock 1 hour prior to the feeding. The length of the procedure is 8 minutes; the therapeutic course makes 8 daily sessions. If observing sympathicotonia, a cathode is placed on the both side surfaces of the infant's neck, an anode is placed on the posterior surface of the neck. In this case, 5% sodium bromide is introduced from the cathode. If observing vagotonia, the anode is placed on the both side surfaces of the infant's neck, and the cathode - on the posterior surface of the neck. In this case, 5% calcium chloride is introduced from the anode.

EFFECT: method provides the higher clinical effectiveness, reduced length of treatment, and faster rumination syndrome relief, reduction of complications, improved protective and adaptive body responses by correcting imbalances in the state of the vegetative nervous system depending on the characteristics of the patient's vegetative status.

3 tbl

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