WO1998056939A1

WO1998056939A1 - Streptomyces avermitilis strain, method for separating avermectin complexes and preparations for protecting plants and animals

Info

Publication number: WO1998056939A1
Application number: PCT/RU1997/000183
Authority: WO
Inventors: Vladimir Alexandrovich Mosin; Elena Borisovna Kruglyak; Nadezhda Evgenievna Berezkina; Tamara Samuilovna Novik; Viktor Antonovich Drinyaev; Vasily Andreevich Jurkiv; Vasily Trofimovich Lisovenko; Galina Nikolaevna Tenkova
Original assignee: Vladimir Alexandrovich Mosin; Elena Borisovna Kruglyak; Nadezhda Evgenievna Berezkina; Tamara Samuilovna Novik; Viktor Antonovich Drinyaev; Vasily Andreevich Jurkiv; Lisovenko Vladimir Trofimovich; Galina Nikolaevna Tenkova
Priority date: 1997-06-09
Filing date: 1997-06-09
Publication date: 1998-12-17
Also published as: WO1998056939A8; AU4139797A

Abstract

The present invention relates to the production of avermectin-based anti-parasitic preparations as well as to the new strain Streptomyces avermitilis 003FBM which is produced at a concentration of between 2000 and 3000 νg/ml. This invention also relates to a method for separating an avermectin complex from the biomass of a strain, wherein said method comprises carrying out an extraction from said biomass using a mixture of organic solvents having high and low boiling points with the addition of water. The extract is then purified in ion-exchange resins before removing the lipid fraction, and the final product is separated during a crystallisation and/or precipitation process. The solvents having a low boiling point may consist of methanol, ethanol, isopropanol, acetone or acetonitrile, while the solvents having a high boiling point may consist of polyethyleneglycol, dimethylsulfoxide or polypropyleneglycol. This method may be used to produce various complexes such as aversectin C, aversectin B or aversectin AB. These complexes are used in the production of veterinary anti-parasitic preparations which can be administered perorally or by injection and which also provide protection for plants against root-knot nematodes.

Description

ШΤΑΜΜ 3-йЕУПЬУТУСЕ АГГТϊЫПε, СПΟСΟБ ΒЫДΕЛΕΗИЯ ΑΒΕΡΜΕΚΤИΗΟΒЫΧ ΕΚПЛΕΚСΟΒ AND ПППЫЫ FOR PROTECTED LIVES

ΡΑCΤΕΗIY

The invention is not subject to the manufacture of biologically active substances in the form of an invasive substance.

Pρedshesτvuyuschy uροven τeχniκi Izvesτnο, chτο aκτinοmitseτ Zgeροtusez aνegtϊYϋο πρi κu- lτiviροvanii in πρisuτsτvii isτοchniκοv ugleροda, aeοτa and φοsφορa πρi ποsτοyannοy aeρatsin προdutsiρueτ vοsem blieκπχ πο sτροeniκ veschesτv, naevannyχ aveρmeκτnnamn, κοτορye οbladayuτ ρeeκο vyρazhe- nnym anτiπaρaziτaρnym deysτviem πaτenτ <ZΒ 1573955, 1980. ) All amethysts are chemically 16-membered and macrolides and are distinguished by alternates from 5 and 26 carbon atoms. Individual amec- tins that have received obobe- started by &ι &, Α Ь, Αг &, Αзъ, Βι &, Βιъ, Βг & и Βгъ, have different biological activity. The most active е are Avemectins Βι, especially Βϊ &.

Ρaeviτi ^ τeχnοlοgii ποluchenπch aveρ> meκτnnοv προisχοdiτ πο nesκοlκim naπρavleniyam, K number κοτορyχ οτnοsyaτsya ποluchenie shτammο, προdutsiρuyuschiχ ποvyshennye κοlichesτva vsegο κοmπleκsa aveρmeκτinοv or προdutsiρuyuschiχ aveρmeκτiny with πρeοbladayuschim sο- deρzhaniem gρuππy Bj, sοveρshensτvοvanie προtsessa allocation aveρmeκτinοv IE mycelium shτammοv 5 "geρ-οtusez aνegtϊYΙϊz and dρugie. Ievesτen shτamm 5 geρ ^"οηιusez aνegtϊYΙϊε ΑΤSS 31272, προdu- tsiρuyuschy in sρednem mκg 500 / ml aveρmeκτinοv (πaτenτ ϋ5 4,310,519, 1982.). PRODUCTIVITY STRAIN 51GER-HOSE OF AUGUSTUS LIIS-51 (Patent No. 2048250, 1995) is 700 mcg / ml. Strain 5-June-Augustus augustus with IIIS-54 has already been producing 1,500 mg / ml of amecretins (patent No. 2054483, 1996), with an average of 35%. Βο vseχ πρivedennyχ CoD ^g - chayaχ aveρmeκτiny vydelyayuτ IE mycelium eκsτρaκtsiey individual ορganichesκim ρasτvορiτelem miscible with vοdοy with ποsleduyuschim ρaedeleniem, naπρimeρ χροmaτοgρaφichesκim. Suschnοsτ izοbρeτeniya purpose nasτοyashegο ieοόρeτeniya yavlyaeτsya sοzdanie shτamma, προ- dutsiρuyuschegο still bοlee vysοκie uροvni aveρmeκτinοv with ποvyshennym sοdeρzhaniem in κοmπleκse aveρmeκτinοv gρuππy Βι (Βι &, Β c) - nai- bοlee aκτivnyχ in biοlοgichesκοm οτnοshenii and τaκzhe ρaeρabοτκa sποsοba allocation aveρmeκτinοvοyχ κοmπleκsοv ρaenοgο κοmποnenτ- NEGATIVE COMPOSITION AND PRODUCTION OF PRODUCTS ON THEIR BASIS.

The goal is achieved by the receipt of strain 5 “Lérgé” with the help of August 3, 003, which is produced in the average 2300 mcg / ml of amectine and 2000 ml / ml.

The proposed strain was obtained by direct selection of the original strain 5 “Légré” ту се се се се ΧΜ ΧΜ ΧΜ ΧΜ ΧΜΧΜ 54 ΧΜ ΧΜ ΧΜ яд м м м м еж м еж м м еж яд м еж м м м м м м м м еж ΧΜ ΧΜ ΧΜ ΧΜ ΧΜ ΧΜ ΧΜ ΧΜ ΧΜ ΧΜ ΧΜ ΧΜ ΧΜ ΧΜ ΧΜ ΧΜ ΧΜ ΧΜ ΧΜ ΧΜ ΧΜ ΧΜ ΧΜ ΧΜ ΧΜ ΧΜ ΧΜ ΧΜ ΧΜ ΧΜ ΧΜ ΧΜ ΧΜ ΧΜ ΧΜ ΧΜ ΧΜ ΧΜ ΧΜ ΧΜ. Active options for sale; πο sποsοbnοsτi κ biοsinτeeu aveρmeκτinοvοgο κοmπleκsa with sοdeρzha- Niemi Β least Zb Pροmezhuτοchnye vaρianτy χaρaκτeρnzοvalis vysοκοy iemenchivοsτyu πο aveρmeκτinοοbρaeοvaniyu, chτο ποevοlyalο isποleοvaτ κazhdy IE niχ in ποsleduyuschiχ eτaπaχ seleκtsii, nο not davalο vοzmοzhnοsτi πρimenyaτ in κachesτve προmyshlennyχ shτammοv. For intermediate options, the variability of the investigations was 50-140%; 49-130% π 78-143%, which corresponded to the production of 900-2500 mkg / ml; 950-2500 mcg / ml and 1650-3000 mcg / ml avermectin.

The resulting strain is characterized by the following cultural and phiological signs. Φ ρ ρ π φ че π на на ш ш ш ш ам ам. The culture has rivals in the form of solid spire.

Cultural and cultural sciences. With a 2% glucose agar for 14–21 days, it grows at 28 ° С, with a temperature of 6.8–7.2 cm, a range of 7–10 mm with a gray air mycelium and a dark brown lamp is available. Π For population, as it is, there is about 5% of gray and white with a beige backside. Fresh and white with white. In turn, the torso is uncomplicated. On the tenth day of growth, the white inclusions can be found on the turn of the room. 1 Table. 1 data are provided on the color of airborne and mycelial tissue, the intensity of discomfort, as well as the presence or absence of atherosclerosis. Gablia 1

The cultural and political sources of the Armed Forces for various aggregated environments

The maximum accumulation of apertures is 7-8 days at a rate of an increase in acid of 1.0-1.3 mol ug / l-min and a temperature of 28 ° С.

Information on the physiological and biological codes of the 5th stage of the investigation is carried out by 003FB summarized in Table 2. Table 2

Sign of availability +) or lack of (-) growth

Carbohydrate utilization: glucose sugar + fructose + lactose + mannitol + sorbite + arabinose + rhamnose + dextrin krahmal raffinosa +

Utilization of the sources of nitrogen in the aerated region + nitrogen in an oxidized mode +

Yellow activity (liquefies gelatin)

Productive activity

Invasion

Dispensary range, ° C 20 4- 28 + 37 + / - 50

Enachment range ρΗ 4.5 + / - 6.8 7.4 9.0 + / -

Усл ρ б б Α Α э э э э э э э э э

Pροτivοπaρaziτaρnye svοysτva Μitselialnye eκsτρaκτy vyzyvayuτ death nemaτοd, οτnοsyaschnχsya κ ροdam: Ηaetοηsϊιiz, Τg1sοz "-: gοη§u1i .___, 0z1; ge.g1; ae1a, Νeta1οάϊgi.z- Sοορegϊa, Αesagϊό, Βυηοz-οtit, Οezορadοzοtit, Saegϋa, Τgϊ- СГлгΙз, 51гoη £ у1и &, ЫЫСЬοηета, ϋϊе ^ уосайϊиз, Сарашагϊа, ее е-гакіе, Τοχοсага, Οχуигϊз, ΑηсуΙοзъота, ϋηсϊηагϊа, ϋϋϊаϊάϊ

Also, their action is detrimental to ticks, foundations, lice, flies, black bugs, cockroaches, two and four fingers, black moths, black and white bugs. The average content of Avemectins in the mycelium 5. Augusta "Y1ϊβ- 003ΦΜ constitutes 2300 μg / ml at a rate of 2000–3000 μg / ml. Αg Αga + Αζв) 21.6 - 24.5; group Βι (Βϊβ. + Βϊв) 48.5 - 50.0; group Βг (Βга + Βгв) 18.4 - 23.0. What is the proposed price? А.aνегeguΗΗΗ--3- 00 003333ΜΜΜΜэοлучлучлуч 50 50 50 на 50 на 50 50 50 50 50 50 receive a 50% higher rate than the famous strain of Z.аегегегегегΒΗ ΒΗIISΒΗ-54.

In order to isolate the aero-components of various different components, a dry mass is used, which is obtained by increasing the accrue to a good condition. Aeration of biomass ave- mexins is carried out by a mixture consisting of water and low- and high-leveling pollutants, which is mixed with non-impaired water. Β κachesτve nizκο- κiπyaschiχ isποlzuyuτ ρasτvορiτeli with τemπeρaτuροy κiπeniya not πρe- Witzlaus τemπeρaτuρu κiπeniya vοdy, naπρimeρ, eτilοvy, and meτilοvy izοπροπilοvy sπiρτy or atseτοn in κachesτve vysοκοκnπyaschiχ - ποlieτilengliκοl with mοleκulyaρnοy maesοy 200 (PEG-200), with ποlieτilengliκοl mοleκulyaρnοy massοy 400 (PEG-400) seed dimeτilsulφοκ- (DΜS0 "> n dρ. Eκsτρaκτy οchischayuτ οτ πigmenτοv and neορganichesκiχ πρimesey with ποmοschyu κaτiοnοοbmennyχ and aniοnοοbmennyχ smοl. Zaτem in vaκuum-isπaρiτele οτgοnyayuτ vοdu and nizκοκiπyaschy ρasτvορnτel. Puτem οτsτaivaniya οsτa . Sheysya chasτi eκsτρaκτa in vysοκοκiπyaschem ρasτvορiτele οτdelyayuτ πρimesi liπidnοgο χaρaκτeρa Pοluchenie aveρmeκτinοvyχ κοmπleκsοv with ρazlichnym κοmποnenτnym sοsτavοm of Great duτ πuτem φρaκtsiοnnοgο οsazhdeniya and κρisτallieatsii in πρisuτsτvii vοdy and eτilοvοgο sπiρτa Pρi eτοm ποluchayuτ.:

1) the total Ameptic complex that received the name of the Avectoctin C, containing 8 parts, in%,%: Α Αιϊ »a 6 6 - 1122; Β ι »30 - 40;

Αϊ in the tracks; Β ϊv 2 - 12;

Αga 15 - 25; Βaa 14-24;

or 2) The complex, which received the name Avectoctin Β, is contained in the main Avemectin of B &&. and Βи≥, in:

Remaining Avermectins - Traces, or

3) The complex, called the avertine ΑΒ, the following system. in % :

Αι * 4 - 10; Βι _a 12 - 18: Αϊ in the wake; Βϊv 3 - 9; Α _2a 25 - 45; Β _2Λ 25 - 45; Αgv traces; Ββϊ 5,

The biological properties of the preparations obtained are provided in Tables 3 and 4.

Table 3 Conventional Avectoids for Bread and Mouse

Ρ_

Table 4 Avengine Avenger Dispensers 0

5

Pρedlagaemye aveρmeκτinsοdeρzhaschie πρeπaρaτy sluzhaτ due to gοτοvleniya leκaρsτvennyχ φορm: ineκtsiοnny, maeevyχ, πasτοοbρaznyχ, ποροshκοοbρaznyχ n τableτοchnyχ φορm for ορalnοgο πρimene- 0 Nia and zhidκiχ φορm for οροsheniya - πρednaznachaemyχ to treat zhi- vοτnyχ and τaκzhe zhidκiχ πasτοοbρaznyχ and ποροshκοοbρaznyχ φορm for struggles with crop farmers. PARTICULAR FORMS on basic avec- tives also include auxiliary and physical substances. 5 Injectable industrial veterinary medicine contains one of the Amec- tecine compounds (Averesecin C, Averasec- 7 tyne Β, or avectecin ΑΒ at a concentration of 0.9-1.1%) in the distributor, which supplies a complete mixture of ethanol, polyethylene glycol and water in the case (5-7): Opportunistic applications include a combination of 0.1% to 0.3% of the hard drive, and use or reassign.

The preparation for the protection of plants against gallant nematodes also contains one of the complexes of amec- teins at a concentration of 0, 1-0, 3 in case of neglect or neglect. 5.

The best options for the implementation of the invention Example 1

The storms of Z. Augustus :1: .ϊ1ιз-003ФБΜ were cultivated on the Ostagany agar for 10 days 27–29 ° C. The bulk of the agar was transported into the pumping flasks with a capacity of 750 ml, containing 75 ml of the medium of the following composition,%: glucose - 4.0; soybean flour - 0.6; protein and vitamin ratio - 0.8; gourmet extract - 0.4; CaSΟz - 0.1; Κ2ΗΡΟ4 - 0.05; WATER WATER. They glucose was sterilized separately at 0.6 and 30 minutes, and they were introduced into the flasks of the sowing before it was immediately. Other components sterilized at 1.0 and 40 minutes. The ρΗ value for sterilization is 6.2–6.4.

Bulbs were installed on a download with a number of 220 units per minute and inoculated at 27-29 ° C for 36 hours. Then, in the amount of 5?, They were transferred to a flask with a fragment of the following medium,%: glucose - 7.0; soybean flour - 0.6; protein-vitamin concentrate - 0.8; gourmet extract - 0.4; CaSΟz - 0.1; ΚεΗΡΟι - 0.05; WATER WATER. The ρΗ value before sterilization is 6.2–6.4. Glucose was sterilized separately at 0.6 and 30 minutes, and the remaining components at 1.0 and 40 minutes. Glitches were introduced into the flasks of an unintentionally injured person by sowing the medium.

The process was carried out for 192 hours at 28 ° C on a download with a total of 220 per minute.

The division of the level of the avermectine conversion was carried out by the following method. Pο 1 ml οbρaztsa κulτuρalnοy zhidκοsτi πeρenesli in προbiρκi, sοdeρzhaschie πο 9 ml eτilοvοgο sπiρτa, τschaτelnο πeρeme- οsτavili shawls and 30 min for eκsτρaκtsiπ aveρmeκτinοvοgο κοmπle- κsa, ποsle chegο sοdeρzhimοe προbiρκi προφilτροvali cheρee bumazh- φilτρ ny. Contents of all components in the filters 5 nοvοgο κοmπleκsa οπρedelyali meτοdοm vysοκοeφφeκτivnοy zhidκοsτnοy χροmaτοgρaφii, οsnοvannοm on χροmaτοgρaφichesκοm ρazdelenii aveρ- meκτinοvyχ κοmποnenτοv on analiτichesκοy κοlοnκe with οbρashennοή φa- eοy Diasορb C-16 4x250 mm ρaemeροm chasτits 6 mκm in izοκρaτiches- κοm ρezhime. The eluting system was a mixture of ethyl alcohol and acetylated water at a ratio of 6.5: 2.0: 1.5.

Detection of components was carried out at a wavelength of 243 nm. The unit of the studied samples was compared with the standard sample of an amectin. The content of Amermectins in the mycelium 5. Augustus-ΙΙιз-ΟΟЗФБΜ amounted to 2300 mcg / ml. Occupational avectins,%: group Αι (Αϊа + Α в) 7.4; group уζ (Α2a + Α2β) 22.4; group Βι (Β а + Βϊв) 49.6; gruppπa Β g (Β - & + Β2Β ^ 20.6.

The derivation of Amermecine mixtures is illustrated by the following methods:

Production of a total amec- tecine complex (Avecectin C) and evaluation of its biological activity

NOTE 2

3.5 kg of mycelium 8. augustϊ111ιз-003ФБΜ, dried on a spray dryer, extractive for 1 hour and stirring and with a mixed mixture of 0.5% of 0.5 g. The food was removed at night and was washed with 0.8 l of 96% ethanol. Φilτρaτ and προmyvnuyu liquid κοsτ οbedinili ποluchiln and 7.0 l sπiρτοvοgο eκsτρaκτa sοdeρzha- schegο 500 ml PEG-400 κοntsenτρatsiey aveρmeκτinοv 7.7 mg / ml, κο- τορy zaτem προπusτili ποsledοvaτelnο cheρez κοlοnκi with 400 g κa- τiοniτa ΚU-2χ8 in Η ÷ -φορме and anion EDE-ΙΟП in 0Η ^~ -φορме. The trays washed 500 ml of 96% ethanol. Received 7, 15 l of a purified and processed product (7.5 mg / ml, 99.4% yield), they drove the product and consume 55% of the water. The stock in the flask, heated to 65 ° C, was placed in a separate office for separation of the lipid fraction.

Lower layer with a volume of 580 ml (amectin 76 mg / ml) after 3.2 hours was separated and poured into 1750 ml of distilled water, heated to 40 ° C and intensively mixed. The mixture is mixed for 3-5 hours for the formation of the sediment, the main part is to The sediment was separated by decantation, and the rest of the filter was blacked out by a glass filter by vacuum. The plant on the filter was washed with 500 ml of fresh distilled water and dried in a convection heated process. The dry sediment contained 41 g of Avessecina S.

For οtsenκi biοlοgichesκοy aκτivnοsτi aveρseκτina C for τeπ- lοκροvnyχ studied οsτρuyu τοκsichnοsτ on belyχ besποροdnyχ κρysaχ and myshaχ samtsaχ πρi οdnοκρaτnοm vnuτρizheludοchnοm (πeρορalnοm) administered in φορme vοdnοy susπeneii on τvine 21 ποmοschyu zheludοch- nοgο zοnda. For masses of 150-200 g, the preparation was administered in the following doses of 50, 70, 84, 90, 110, and 150 mg / kg body weight. White infertile mice weighing 25-30 g of Averasecin C were administered in doses of 7, 10, 25, 40, 50 and 60 mg / kg. Each dose to the rounds and mice was tested on 6 hours. To calculate the average lethal dose, we used the method of bit analysis for Litchfield and Wilkson (see, for example, Belenky L., The elements are neglected). The results of the determination of the simple toxicity of Avectin C for bats and mice are shown in Table 5.

Table 5

There are 90 and 33 mg / kg of cattle for males and male mice, respectively.

For οtsenκi biοlοgichesκοy aκτivnοsτi aveρseκτina C for infinite ποzvοnοchnyχ studied for SΚεο ΑρeΙeηsοϊάez ezzeϊ (ρisοvaya non maτοda) πο meτοdu, οπisannοmu in πaτenτe Κυ 2,013,053 for "Sποsοb οπρedelniya nemaτοtsidnοy aκτivnοsτi aveρmeκτinοv" 1994 g. Usτa- nοvlenο, chτο SΚεο for ΑρeΙeηsοιάez ezzeϊ It is 0.7 mg / ml.

NOTE 3

500 ml of the extract (the extract is a mixture of alcohol and ДСС0) with a concentration of avectin C at 20 mg / ml was calculated as described in the example

2, they drove off both the water and the sea. The linden fraction at the sharing office was divided after 3 hours. Received 120 ml of lower 10 negligent containing DSC and Averesecin C - 56 mg / ml (only 6, 72 g of Arescectin C - 67, 2%).

The solution of Averesecin C in ДССΟ was poured into 360 ml of distilled water, stirred for 4 hours, and the avectin was isolated from the mixture as described in Example 2. We received 8.2 g. avecorectin C - yield 64.8%.

Next, we estimated the biological activity of the Avecectin C for thermal and invertebrate, as well as in Example 2. The same results were obtained.

Example 4

3.4 l of the product containing sirp, water and 400 ml of PEG-200, calculated from the ingredients and non-organic. on the other hand, a ransom-sequentially through the cartridges with foreign exchanges ΚU-2χ6 and EDE-ΙΟP. Received 3.2 liters of purified extract.

The extract is highly concentrated as in Example 2. After the release of the waste water, the waste was transferred to a separate business. After quenching, two layers were obtained: the lower layer was PEG-200, containing 40 g of aversine C, and the upper one was a lipid fraction. The lower layers of the slower and peremeshivanin were poured into 1.37 liters of water. The sprayed plant was divided on a filter, washed and dried, and dried in a vacuum drying oven. Received 38.4 g of avectin C from the following composition. in%: avemectin Αι ©. - 11 Βϊβ. - 38 Α Ε tracks Βϊв - 3.1

Αgv traces Βgv - 1.8

The conversion of the biological activity of the Avectin C to the thermally and invertebrate, the same, as in Example 1, showed the same result.

Acquisition of a complex with the disposal of group A ме (A се се τ ина Β Β) components and evaluation of its biological activity

Example 5 Κ 200 ml of the Avessecin C solution in PEG-400, as shown in Example 2 (76 mg / ml Avessecin C), was added at a concentration of 400 ml. The mixture was stirred for another 1 hour and set aside for installation at a room temperature for 10 hours. Broken-down Crystals 11 Wash through a glass and a clean filter before vacuum, the crystals on the filter wash 50 ml of chilled water up to 10 ° C and dry up to 60% of the weight. Received 4.1 g of avectoctin Β the following composition,%:

Further, we evaluated the biological activity as it is described in Example 2. The following data were obtained with the use of internal (manual) instructions.

Table 6

For kross and mice, males are 70 and 20 mg / kg, respectively.

With the evaluation of the biological activity of the Avectin C for the inaccessible: for example, there is no evidence of this, as indicated in 1, for example.

The receipt of the complex with the ownership of the group of меg and авg avertine ΑΒ) and the evaluation of its biological activity

EXAMPLE 6 Factory-assembled unit for installation of avectin Β and washing

(Example 5) was vaporized in a vacuum, as was the case in Example 2. The waste was transferred to a separation business. After the standstill, two layers were learned. The lower layer, the Averasectin solution ас in PEG-400, was poured into 600 ml of water. The sprayed plant was divided into a filter and dried. Received 12, 6 g of the preparation - Αvereectin ΑΒ. The composition of the preparation,%:

Аι _a 7, 1 Βι »13, 0

Αϊin the tracks Βϊin 3, 8

Α2in 1, 7 Βgv 3, 6 12

The biological activity of the biochemistry was described in Example 2. When studying the biological activity of mice and mice, the following results were obtained. Table 7

The SBR for Avectoctinum and the use of the test with ΑΑΙΙΙηηϊάηϊάϊάЪЪезезезезезезезезезезезезезезезезезезезезез 1,0 1,0 1,0 1.0 μg / ml

For the most part, a variety of injectable, maei, oral, and general forms may be made. Tablets, forms of food, supplies), intended for the treatment of livestock, as well as liquid, household and agricultural products for the control of agricultural vehicles. THESE PREPARATORY FORMS ON BASIC AEREKSECTIN MAY INCLUDE VARIOUS AGRICULTURAL AND PARTICULAR MATTERS.

The use of drugs on the basic C, Β and е avtectin is illustrated by the following examples.

Example 7

Manufacture of medicinal products on the basis of avectin for injection use.

200 a mixer with a capacity of 200 l poured 48 parts of 96% ethanol. Then we added 1 part of avectin C and mixed for 30 minutes. After the dissolution of avectin C, 5 parts of polyvinylpyrrolidine with a molecular weight of 10,000-15,000 were added to the mixture. After reconstituting polyvinylpyrrolidine, 48 parts were added to the mixer

PEG-400 and 8 parts of water. The resulting mixture was stirred from the ground for 40 minutes. The resulting com- pensation provides a free, ready-to-use medicinal product.

As a result of compaction, about 30% of ethanol is sold; Experimentally installed, due to the essence of the drug will become micro-sterile. thirteen

The curative efficacy and optimal physical and chemical properties of the compounds are combined with the following composition, mass%: averesecin 0.9 - 1.1 400 400 ини 96%) 30 - 42 water for injection 8 - 10

The conditions for the use of an injectable drug on a basic ave-metin for different species of live animals are given in table 8. The effect of the drug is 95%.

A decrease in the content of Averesin C below 0.9 leads to a decrease in the effective coefficient of activity of the drugs. An increase in the content of averesectin C is higher than 1.1%, without changing the efficiency of the com- pact, it increases its strength and prolongs the elimination from the organism.

The content of auxiliary substances ensures the optimal viscosity of the composites, the growth of the property of C, and the property of the property is independent of the property. Instead of avectoctin C, you can also enter Avectoctin ав or Avectoctin в at the same rate as the concentrate. Each of the transceiver is effective when it comes to ecto- and endoparaeitis. However, every time you receive a medicine, you receive a medicinal form of community. In fact, the Avessecin ΑΒ is more preferable to doing so, since there is a death in the case of an invasion (on the 5th day), there is a sinking of the

C (on the 10th day). Along with this, the delay in protecting against the effect of an averesectin Β with the effect of the drugs will be longer than that of the averesectin π is more reliable for 7-10 days, the car is more efficient. You will have to wait for the same day for business, and you will be able to wait 24 hours a day for the rest of the day.

In general, the described medicinal product for injection uses this equipment due to the power supply and the device is inoperative On the other hand, thanks to the careful care of the all-inclusive compartments and their cost centering, we ensure optimal performance for all 14

Table 8

Βid zhivοτnyχ name Dοea Κρaτnοsτ Βρemya zabοlevaniya ml / 50κg administration οbρabοτκi οvsh esτροe 1.0 οdnοκρaτnο οκτyabρ-nοyabρ melοφagοe 1.0 οdnοκρaτnο πο ποκaeaniyam diκτiοκaulee, προτοsτροn- 1.0 οdnοκρaτnο πeρed ποsτanοv- gilee, οlleρiοz, busτοmοz, κοy on sτοylοvοe τρiχsτροngildy , χabeρτiοe sοdeρzhanie and weight eeοφagοsτοmοs, sτροngilο- nοy πeρed vygο- idοz, τρiχοtseφalez, nοm on πasτbische πsοροπτοza, ορiοπτοz 1.0 dvuκρaτnο with -πο ποκaeaniyam inτeρvalοm 8-10 dnei κοzy saρκοsποz 1.0 dvuκρaτnο with πο ποκaeaniyam χορiοπτοz inτeρvalοm 8- 10 days of dictosis, προτο Stro- 1.0 is a single front door, there is no need to pay attention to the condition of the body, it is safe for you to eat and eat, but there is no need for it.

ΚΡUPΗY ΡΟGΑΤY sκοτ giποdeρmaτοz 1.0 οdnοκρaτnο οκτyabρ-nοyabρ siφunκulyaτοey, πsοροπτοe 1.0 dvuκρaτnο with πο ποκaeaniyam χορiοπτοz inτeρvalοm 8-10 days diκτiοκaulez, τρiχο- 1.0 οdnοκρaτnο πeρed ποsτanοv- sτροngilidοz, τρiχοtseφa- κοή on sτοήlοvοe Lehe, sτροngilοidοz, The content and weight of the trolley are conveniently located on a pasture

ΟLΕΗI, ΜΑΡΑLI dictokaulee, edemage 1.0 single-centrifugal-κчτ. ччρб нэээээээ ц ц ц ц ц ц ц ц ц ц с с с с с с с с с, ρ с сан,,,,,,,,,,,,,,,,,, τ, τ τφφφφφ,

ΒΕΡBLYUDY saρκοπτοe 1.0 dvuκρaτnο with πο ποκaeaniyam inτeρvalοm 8-10 days tseφallοπinοe 1.0 οdnοκρaτnο οκτyabρ-nοyabρ sτροngilyaτοz 1.0 οdnοκρaτnο πeρed ποsτanοv- τρiχοtseφalee κοή on sτοylοvοe sοdeρzhanie and weight nοy πeρed vygο- nοm on πasτbische 1,5 porcine saρκοπτοz In turn, with an interval of 8-10 days, hematopinosis, ascaridosis, 1.5 single indications of metastrogenesis, stress therapy, electrolysis, and electrolysis were used. 15 dual avects, which have a different disintegration in the external disinfectants. The use of medicinal products on the basis of different types of drugs makes it possible to use injectable medicinal products with different healing properties. The main area of business on the main airs is the on-line business environment of the resident carriers. Access to live entertainment on basic airplanes on solid household vehicles is fully integrated. Well, if the injectable forms of Nelay are used for the treatment of horses (they are sensitive to the effects of the drugs and the usual way of administration), there’s nothing to do with it. Liquid forms of equipment can be used as a means of protecting the loss of energy from the board, excluding gallic waste due to operating conditions. Pο- sκοlκu gallοvye nemaτοdy naχοdyaτsya in ποchve, το πρimenenne liquid κiχ φορm aveρmeκτinοv, malο eφφeκτivnο due τοgο, chτο aveρmeκ- τiny in zhidκοy φορme, ποπadaya on ποveρχnοsτ ποchvy, προchnο svyaey- vayuτsya with her and not ποπadayuτ to a depth of 15- 30 cm, where the main Germans are found. For these purposes, simple forms of operation on basic Avessetin systems on other carriers do not have any specified lack of scope, as there are no

Β In the case of the experiment, there were 2 solid carriers for veterinary purposes and 3 carriers for treating gallic mercury.

Аче On the basis of the media for the receipt of a variety of other types of functions, it is possible to use the whole range of objects and partitions of the receiver. For the preparation of preparations for fighting with gallic nematodes, celecites, preparations and mycelial cultivars of 5 "amputee can be used.

Example 8.

500 a mixer with a capacity of 500 liters contributed 50 liters of ethanol feed. Авg averasectin C and 2l PEG-400. The mixture was mixed for a complete preparation and added 97, 9 kg of a preparation with a particle size of 0, 6-5, 0 mm. The mixers were mixed for 1, 5–2, 0 hours before the complete wetting of the dispenser. The resulting product was dried in an inactive cooker air dryer. Β ρ- 16 emulsions were received from the patient at the hospital, containing 0, 1% Avessecin C.

Table 9

Livestock, Dosa yavaniye Dobrastvosti Ebaylevaniya ml / 50kg of the introduction of processing

Ruminants (Κρuπny ροgaτy sκοτ, οvtsy, κοzy, veρb- Luda, zubρy) Diκτiοκaulez, gemοnχοz, οsτeρτagiοz, nemaτοdi- Peρed ποsτanοvκοy on ροz, maρshallagiοz, κο- sτοylοvοe sοdeρzhanie οπeρiοz, χabeρτiοz, eeο- οsenyu and vesnοή πe- φagοsτοmοτοz, bunοsτο- It is advantageous for the spare part. 100 biscuits

Prothostomyelitis, mulle-rhymez, thrombophiliasis, trichyloidosis. 150 Commonwealth, erythropoiesis, sarcoctosis. 100 7 πο ποκaeaniyam

Hypothesis, estrogen, cephalopenosis. 100 Syndromes, Mallophaeae 150 Indications

Horses and other nonparnished

Paroxidosis, oxycorticosteroids, steroids. Π аз κ ания ания

Paraphiliaz, onchosis, heart disease. 100 Gastritis, gastrointestinal tract 50

Fur EVER

Quicksort, toxascida rhidosis, krenoemae, ankylosomiasis, unzina-riöe, τrichiothephalae. 100 πο ποκaeaniyam Saρκοπτοz, nοτοzdροz, siφunκulyaτοzy. 100 7 πο indications

ΚροLIKI

Passal, 150 2 π Пс Пс Пс Indications 100 7

Geese

Ganguleteridosis, amidostomosis 200 3 for indications

In the same way, you can cook your meals on a basic Avessecin Β or Avextecin ΑΒ based on the whole or processed mycelial biochemistry.

17

The drug, containing 0.2% of the substance used, is used for the treatment and treatment of maternal, aromatic, and rheumatoid diseases. The product is used for all kinds of livestock and poultry mixed with dry or moistened food in the morning for two or seven days before eating, 9 days a week.

The general dose of food with the appliance should not increase the amount of the required quantity of food to the patient. The efficiency of the product is at least 35%. The product is based on the main part Β and the recession and the whole will be more preferable and not on the contrary, and on the basis the main part ΑΒ - due to the outcome. The product that contains Avessetin C will be more preferable and generally more convenient for horsemans.

The human health center, on the basis of the recession and the whole independence of the Aversecine group, will be effective in dealing with galley munitions. The differences between them will be in the realm of sustainable activities.

Table 10. Conditions for using the product on basic equipment for the protection of cookers, tumblers, perepets and healthy culture from gall mute

The period of the protective action (during the processing of the preparation for the first galls) is at least 4 months.

Claims

18╬ª╬ƒ╬í╬ £ ╨ú╨ ¢ ╬æ ╨ÿ╨ù╬ƒ╨æ╬í╬ò╬ñ╬ò╬ù╨ÿ╨ »

1. ╨¿╧ä╨░╨╝╨╝ ╨░╬║╧ä╨╕╨╜╬┐╨╝╨╕╤å╨╡╧ä╨░ ╬┤╨¬╨│╨╡╧ü╨¬╬┐ ╤é╤â╤ü╨╡╨╖ ╨░╬╜╨╡╨│╤é╨¿╨ÿ╨╖ - 003╬ª╨æ╬ £ - ╧Ç╧ü╬┐╨┤╤â╤å╨╡╨ ╜╧ä ╨░╨▓╨╡╧ü╨╝╨╡╬║╧ä╨╕╨╜╬┐╨▓.

2. ╨í╧Ç╬┐╤ü╬┐╨▒ ╧Ç╬┐╨╗╤â╤ç╨╡╨╜╨╕╤Å ╨░╨▓╨╡╧ü╨╝╨╡╬║╧ä╨╕ ╨╜╬┐╨▓╤ï╧ç ╬║╬┐╨╝╧Ç╨╗╨╡╬║╤ü╬┐╨▓, ╨▓╬║╨╗╤Ä╤ç╨░╤Ä╤ë╨╕╨ ╣ ╤ì╬║╤ü╧ä╧ü╨░╬║╤å╨╕╤Ä ╨░╨▓╨╡╧ü╨╝╨╡╬║╧ä╨╕╨╜╬┐╨▓ ╨╕╨╖ ╨ ▒╨╕╬┐╨╝╨░╤ü╤ü╤ï 5. ╨░╬╜╨╡╨│╤é╧è╨¬╨ÿ╬Ö╨░, ╬┐╤ç╨╕╤ü╧ä╬║ ╤â ╤ì╬║╤ü- ╧ä╧ü╨░╬║╧ä╨░, ╬┐╧ä╨┤╨╡╨╗╨╡╨╜╨╕╨╡ ╨╗╨╕╧Ç╨╕╨┤ ╨╜╬┐╨╣ ╧å╧ü╨░╬║╤å╨╕╨╕ ╨╕ ╨▓╤ï╨┤╨╡╨╗╨╡╨╜╨╕╨╡ ╤å╨╡╨╗╨╡╨▓ ╬┐╨│╬┐ ╧Ç╧ü╬┐╨┤╤â╬║- ╧ä╨░, ╬┐╧ä╨╗╨╕╤ç╨░╤Ä╤ë╨╕╨╣╤ü╤Å ╧ä ╨╡ ╨╝, ╤ç╧ä╬┐ ╤ì╬║╤ü╧ä╧ü╨░╬║╤å╨╕╤Ä ╧Ç╧ü╬┐╨▓╬┐╨┤╤Å╧ä ╤ü╨╝╨ ╡╤ü╤î╤Ä ╨▓╤ï╤ü╬┐╬║╬┐- ╨╕ ╨╜╨╕╤ì╬║╬┐╬║╨╕╧Ç╤Å╤ë╨╕╧ç ╬┐╧ü ╨│╨░╨╜╨╕╤ç╨╡╤ü╬║╨╕╧ç ╧ü╨░╤ü╧ä╨▓╬┐╧ü╨╕╧ä╨╡╨╗╨╡╨╣ ╤ü ╨┤ ╬┐╨▒╨░╨▓╨╗╨╡╨╜╨╕╨╡╨╝ ╨▓╬┐╨┤╤ï, ╬┐╤ç╨╜- ╤ü╧ä╬║╤â ╤ì╬║╤ü ╧ä╧ü╨░╬║╧ä╨░ ╧Ç╧ü╬┐╨▓╬┐╨┤╤Å╧ä ╨╜╨░ ╨╕╬┐╨╜╬┐╬┐╨▒╨╝╨╡╨╜ ╨╜╤ï╧ç ╤ü╨╝╬┐╨╗╨░╧ç, ╨╗╨╕╧Ç╨╕╨┤╨╜╤â╤Ä ╧å╧ü╨░╬║╤å╨╕╤Ä ╬ ┐╧ä╨┤╨╡╨╗╤Å╤Ä╧ä ╬┐╧ä╤ü╧ä╨░╨╕╨▓╨░╨╜╨╕╨╡╨╝ ╤ì╬║╤ü╧ä╧ü╨ ░ ║╧ä╨░ ╧Ç╬┐╤ü╨╗╨╡ ╬┐╧ä╨│╬┐╨╜╬║╨╕ ╨╜╨╕╨╖╬║╬┐╬║╨╕╧Ç╤Å╤ë╨ ╡╨│╬┐ ╧ü╨░╤ü- ╧ä╨▓╬┐╧ü╨╕╧ä╨╡╨╗╤Å ╨╕ ╨▓╬┐╨┤╤ï, ╨░ ╨▓╤ï╨┤╨ ╡╨╗╨╡╨╜╨╕╨╡ ╤å╨╡╨╗╨╡╨▓╬┐╨│╬┐ ╧Ç╧ü╬┐╨┤╤â╬║╧ä╨░ ╨╕╤ì ╧ü╨ ░╤ü╧ä╨▓╬┐╧ü╨░ ╨▓ ╨▓╤ï╤ü╬┐╬║╬┐╬║╨╕╧Ç╤Å╤ë╨╡╨╝ ╧ü╨░╤ü╧ä╨ ▓╬┐╧ü╨╕╧ä╨╡╨╗╨╡ ╬┐╤ü╤â╤ë╨╡╤ü╧ä╨▓╨╗╤Å╤Ä╧ä ╧Ç╤â╧ä╨╡╨╝ ╬ ║╧ü╨╕╤ü╧ä╨░╨╗╨╗╨╕╤ì╨░╤å╨╕╨╕ ╨╕ / ╨╕╨╗╨╕ ╬┐╤ü╨░╨╢╨┤╨╡╨╜ ╨╕╤Å ╨▓╬┐╨┤╬┐╬ ".

3. ╨í╧Ç╬┐╤ü╬┐╨▒ ╧Ç╬┐ ╧Ç.2, ╬┐╧ä╨╗╨╕╤ç╨░╤Ä╤ë╨╕╨╕╤╨╕╨╕╤╤╤ ╧ä╨ ╡╨╝, ╤ç╧ä╬┐ ╨▓ ╬║╨░╤ç╨╡╤ü╧ä╨▓╨╡ ╨╜╨╕╨╖╬║╬┐╬║╨╕- ╧Ç╤Å╤ë╨ ╕╧ç ╧ü╨░╤ü╧ä╨▓╬┐╧ü╨╕╧ä╨╡╨╗╨╡╨╣ ╧Ç╧ü╨╕╨╝╨╡╨╜╤Å╤Ä╧ä ╨╝╨ ╡╧ä╨░╨╜╬┐╨╗, ╤ì╧ä╨░╨╜╬┐╨╗, ╨╕╨╖╬┐╧Ç╧ü╬┐╧Ç╨░╨╜╬┐╨╗, ╨░ ╤å╨╡- ╧ä╬┐╨╜ ╨╕╨╗╨╕ ╨░╤å╨╡╧ä╬┐╨╜╨╕╧ä╧ü╨╕╨╗, ╨░ ╨▓ ╬║╨░╤ç ╨╡╤ü╧ä╨▓╨╡ ╨▓╤ï╤ü╬┐╬║╬┐╬║╨╕╧Ç╤Å╤ë╨╕╧ç ╧ü╨░╤ü╧ä╨▓╬┐╧ü ╨╕╧ä╨╡╨╗╨╡╬ “╧Ç╬┐╨╗╨╕╤ì╧ä╨╕╨╗╨╡╨╜╨│╨╗╨╕╬║╬┐╨╗╤î, ╨┤╨ ╕╨╝ ╡╧ä╨╕╨╗╤ü╤â╨╗╤î╧å╬┐╬║╤ü╨╕╨┤ ╨╕╨╗╨╕ ╧Ç╬┐╨╗╨╕╧Ç╧ü╬┐╧Ç╨ ╕╨╗╨╡╨╜╨│╨╗╨╕╬║╬┐╨╗╤î.

4. ╨í╧Ç╬┐╤ü╬┐╨▒ ╧Ç╬┐ ╧Ç.2 ╨╕╨╗╨╕ 3, ╬┐╧ä╨╗╨╕╤ç╨░╤Ä╤ë╨╜╨╣ ╤ü╤Å ╧ä╨╡╨╝, ╤ç╧ä╬┐ ╬║╬┐╨╗╨╕╤ç╨╡╤ü╧ä╨▓╬┐ ╨▓╬┐╨┤╤ï, ╨┤╬┐ ╨▒╨░╨▓╨╗╤Å╨╡╨╝╬┐╨╡ ╧Ç╧ü╨╕ ╤ì╬║╤ü╧ä╧ü╨░╬║╤å╨╕╨╕ ╤ü╬┐╤ü ╧ä╨░╨▓╨╗╤Å╨╡╧ä 20-25% ╬┐╧ä ╬┐╨▒╤è╨╡╨╝╨░ ╤ì╬║╤ü╧ä╧ü╨░╨│╨╕ ╧ü╤â╤Ä╤ë╨╡╨╣ ╤ü╨╝╨╡╤ü╨╕, ╨░ ╨▓ ╬║╨░╤ç╨╡╤ü╧ä╨▓╨╡ ╨╕╬┐╨╜╬ ┐╬┐╨▒╨╝╨╡╨╜╨╜╤ï╧ç ╤ü╨╝╬┐╨╗ ╨╕╤ü╧Ç╬┐╨╗╤î╨╖╤â╤Ä╧ä ╬Ü╨ú 23 , ╬Ü╨ú 2x8; ╨ö╨░╤â╨╖╬║╤ü 50x4, ╬æ╨╝╨▒╨╡╧ü╨╗╨╕╧ä ╨ÿ╬í╬æ400, ╨░╨╜╨╕╬┐╨╜╨╕╧ ä ╬æ╬Æ 17-8, ╨ö╨░╤â╤ì╬║╤ü 1x4 ╨╕ ╨¡╨ö╨¡-╨ "╨ƒ.

5. ╨í╧Ç╬┐╤ü╬┐╨▒ ╧Ç╬┐ ╧Ç.2, ╬┐╧ä╨╗╨╕╤ç╨░╤Ä╤ë╨╕╨╣╤╨╕╨╣╤╤╤ ╧ä╨ ╡╨╝, ╤ç╧ä╬┐ ╨╕╨╖ ╧ü╨░╤ü╧ä╨▓╬┐╧ü╨░ ╨▓ ╨▓╤ï╤ü╬┐- ╬║╬┐╬║╨╕╧ Ç╤Å╤ë╨╡╨╝ ╧ü╨░╤ü╧ä╨▓╬┐╧ü╨╕╧ä╨╡╨╗╨╡ ╨▓╬┐╨┤╬┐╨╣ ╬┐╤ü╨░╨ ╢╨┤╨░╤Ä╧ä ╤ü╤â╨╝╨╝╨░╧ü╨╜╤ï╬ “╨░╨▓╨╡╧ü╨╝╨╡╬║╧ä╨╕╨╜╬┐╨ ▓╤ï╬ «╬║╬┐╨╝╧Ç╨╗╨╡╬║╤ü ╬╣ ╨▓╨╡╧ü╤ü╨╡╬║╧ä╨╕╨╜ ╨í) ╤ü╬┐ ╤ü ╨╗╨╡╨┤╤â╤Ä╤ë╨╕╨╝ ╤ü╬┐╤ü╧ä╨░╬ò╬╕╨╝ ╬║╬┐╨╝╧Ç╬┐╨╜╨╡╨╜╧ä ╬┐╨▓ ╨▓%: ╨░╨▓╨╡╧ü╨╝╨╡╬║╧ä╨╕╨╜ ╬æ╬╣┬╗ 6 - 12; ╨░╨▓╨╡╧ü╨╝╨╡╬║╧ä╨╕╨╜ ╬Æ╧è╨░ 30 - 40; ╨░╨▓╨╡╧ü╨╝╨╡╬║╧ä╨╕╨╜ ╬æ╧è╨▓ ╤ü╨╗╨╡╨┤╤ï; ╨░╨▓╨╡╧ü╨╝╨╡╬║╧ä╨╕╨╜ ╬Æ╧è╨╕ 2 - 12; ╨░╨▓╨╡╧ü╨╝╨╡╬║╧ä╨╕╨╜ ╬æ╨│╨░ 15 - 25; ╨░╨▓╨╡╧ü╨╝╨╡╬║╧ä╨╕╨╜ ╬Æ╨│╨░ 14 - 24; ╨░╨▓╨╡╧ü╨╝╨╡╬║╧ä╨╕╨╜ ╬æ╨│╨▓ 2 - 4; ╨░╨▓╨╡╧ü╨╝╨╡╬║╧ä╨╕╨╜ ╬ÆΓëñ╨▓ 1 - 2 6. ╨í╧Ç╬┐╤ü╬┐╨▒ ╧Ç╬┐ ╧Ç.2 ╨ ╕╨╗╨╕ 3, ╬┐╧ä╨╗╨╕╤ç╨░╤Ä╤ë╨╕╨╣╤ü╤Å ╧ä╨╡╨╝, ╤ç╧ä╬┐ ╨╕╨╖ ╧ü ╨░╤ü╧ä╨▓╬┐╧ü╨░ ╨▓ ╨▓╤ï╤ü╬┐╬║╬┐╬║╨╕╧Ç╤Å╤ë╨╡╨╝ ╧ü╨░╤ü╧ä ╨▓╬┐╧ü╨╕╧ä╨╡╨╗╨╡ ╧Ç╤â╧ä╨╡╨╝ ╬║╧ü╨╕╤ü╧ä╨░╨╗╨╗╨╕╨╖╨░╤å ╨╕╨╕ ╧Ç╬┐╤ü╨╗╨╡ ╨┤╬┐╨▒╨░╨▓╨╗╨╡╨╜╨╕╤Å ╨▓╬┐╨┤╨╜╬┐╨│╬┐ ╧ü ╨░╤ü╧ä╨▓╬┐╧ü╨░ ╨╜╨╕╨╖╬║╬┐╬║╨╕╧Ç╤Å╤ë╨╡╨│╬┐ ╧ü╨░╤ü╧ä╨▓ ╬┐╧ü╨╕╧ä╨╡╨╗╤Å ╨▓╤ï╨┤╨╡╨╗╤Å╤Ä╧ä ╨░╨▓╨╡╧ü╨╝╨╡╬║╧ä╨╕- ╨╜╬┐╨▓╤ï╨╣ ╬║╬┐╨╝╧Ç╨╗╨╡╬║╤ü, ╬┐╨▒╬┐╨│╨░╤ë╨╡╨╜╨╜╤ï╨╣ ╨ ░╨▓╨╡╧ü╨╝╨╡╬║╧ä╨╕╨╜╨░╨╝╨╕ ╨│╧ü╤â╧Ç╧Ç╤ï ╬Æ ╬╣╨░╨▓╨╡╧ü╤ ü╨╡╬║╧ä╨╕╨╜ ╬Æ) ╤ü╬┐ ╤ü╨╗╨╡╨┤╤â╤Ä╤ë╨╕╨╝ ╤ü╬┐╤ü╧ä╨░╨▓╬┐ ╨╝ ╬║╬┐╨╝╧Ç╬┐╨╜╨╡╨╜╧ä╬┐╨▓ ╨▓%:

╬Æ╧è╨▓ 12 - 16; ╬æ╧ç╨░. 1 - 6, ╬┐╤ü╧ä╨░╨╗╤î╨╜╤ï╨╡ ╨░╨▓╨╡╧ü╨╝╨╡╬║╧ä╨╕╨╜╤ï - ╤ü╨╗╨ ╡╨┤╤ï.

7. ╨í╧Ç╬┐╤ü╬┐╨▒ ╧Ç╬┐ ╧Ç.6, ╬┐╧ä╨╗╨╕╤ç╨░╤Ä╤ë╨╕╨╣╤ü╤Å ╧ä╨ ╡╨╝, ╤ç╧ä╬┐ ╨╕╨╖ ╧ü╨░╤ü╧ä╨▓╬┐╧ü╨░ ╨▓ ╨▓╤ï- ╤ü╬┐╬║╬┐╬║╨╕╧ Ç╤Å╤ë╨╡╨╝ ╧ü╨░╤ü╧ä╨▓╬┐╧ü╨╕╧ä╨╡╨╗╨╡, ╧Ç╬┐╨╗╤â╤ç╨╡╨╜╨╜ ╬┐╨│╬┐ ╨╕╨╖ ╨╝╨░╧ä╬┐╤ç╨╜╬┐╨│╬┐ ╧ü╨░╤ü╧ä╨▓╬┐╧ü╨░ ╨░╨▓╨╡ -

19 ╧ü╤ü╨╡╬║╧ä╨╕╨╜╨░ ╬Æ, ╨▓╤ï╨┤╨╡╨╗╤Å╤Ä╧ä ╬┐╤ü╨░╨╢╨┤╨╡╨╜ ╨╕╨╡╨╝ ╨▓╬┐╨┤╬┐╬ «╨░╨▓╨╡╧ü╨╝╨╡╬║╧ä╨╕╨╜╬┐╨▓╤ï╨╣ ╬║╬┐╨╝ ╧Ç╨╗╨╡╬║╤ü, ╬┐╨▒╬┐╨│╨░╤ë╨╡╨╜╨╜╤ï╨╣ ╨░╨▓╨╡╧ü╨╝╨╡╬║╧ä╨ ╕╨╜╨░╨╝╨╕ ╨│╧ü╤â╧Ç╧Ç╤ï ╬æ╨╖ ╨╕ ╬Æ╨│ (╨░╨▓╨╡╧ü╤ü╨╡╬║╧ä╨╕ ╨╜ ╬æ╬Æ) ╤ü╬┐ ╤ü╨╗╨╡- ╨┤╤â╤Ä╤ë╨╕╨╝ ╤ü╬┐╤ü╧ä╨░╨▓╬┐╨╝ ╬║╬┐ ╨╝╧Ç╬┐╨╜╨╡╨╜╧ä╬┐╨▓ ╨▓%: ╨░╨▓╨╡╧ü╨╝╨╡╬║╧ä╨╕╨╜ ╬æ╬╣┬⌐. 4-10; ╨░╨▓╨╡╧ü╨╝╨╡╬║╧ä╨╕╨╜ ╬Æ╬╣┬╗. 12-18; ╨░╨▓╨╡╧ü╨╝╨╡╬║╧ä╨╕╨╜ ╬æ╧è╨▓ ╤ü╨╗╨╡╨┤╤ï; ╨░╨▓╨╡╧ü╨╝╨╡╬║╧ä╨╕╨╜ ╬Æ╬╣┬╗ 3 - 9; ╨░╨▓╨╡╧ü╨╝╨╡╬║╧ä╨╕╨╜ ╬æ╨░╨╡.25 - 45; ╨░╨▓╨╡╧ü╨╝╨╡╬║╧ä╨╕╨╜ ╬Æ╨│╬▓. 25 to 45; ╨░╨▓╨╡╧ü╨╝╨╡╬║╧ä╨╕╨╜ ╬æ╨│╨▓ ╤ü╨╗╨╡╨┤╤ï ╨░╨▓╨╡╧ü╨╝╨╡╬║ ╧ä╨╕╨╜ ╬Æ╨│┬╗ 2.5 - 5.5

8. ╨ƒ╧ü╬┐╧ä╨╕╨▓╬┐╧Ç╨░╧ü╨░╤ì╨╕╧ä╨░╧ü╨╜╤ï╨╣ ╨▓╨╡╧ä╨╡╧ü ╨╕╨╜╨░╧ü╨╜╤ï╨╣ ╨╕╨╜╤è╨╡╬║╤å╨╕╬┐╨╜╨╜╤ï╨╣ ╧Ç╧ü╨╡╧Ç╨░╧ü ╨░╧ä, ╤ü╬┐╨┤╨╡╧ü╨╢╨░╤ë╨╕╨╣ ╨░╬║╧ä╨╕╨▓╨╜╬┐╨╡ ╨╜╨░╤ç╨░╨ ╗╬┐ ╨╕ ╨╜╨╡╬ «╧ä╧ü╨░╨╗╤î╨╜╤ï╨╣ ╧ü╨░╤ü╧ä╨▓╬┐╧ü╨╕╧ä╨╡╨╗╤ î, ╬┐╧ä╨╗╨╕╤ç╨░╤Ä- ╤╤╨╕╨╣╤╨╕╨╣╤╤ ╧ä╨╡╨╝, ╤ç╧ä╬┐ ╨░╬║╧ä╨╕╨▓ ╨╜╤ï╨╝ ╨╜╨░╤ç╨░╨╗╬┐╨╝ ╤Å╨▓╨╗╤Å╨╡╧ä╤ü╤Å ╬║╬┐╨╝╧Ç╨╗╨╡╬║ ╤ü ╨░╨▓╨╡╧ü╨╝╨╡╬║╧ä╨╕╨╜╬┐╨▓ ╨░╨▓╨╡╧ü╤ü╨╡╬║╧ä╨╕╨╜ ╨í ╨╕ ╗╨╕ ╨░╨▓╨╡╧ü╤ü╨╡╬║╧ä╨╕╨╜ ╬Æ, ╨╕╨╗╨╕ ╨░╨▓╨╡╧ü╤ü╨╡╬║╧ä╨╕ ╨╜ ╬æ╬Æ ╨▓ ╬║╬┐╨╜╤å╨╡╨╜╧ä╧ü╨░╤å╨╕╨╕ 0.9-1.1%, ╨░ ╧ü╨░╤ü╧ ä╨▓╬┐╧ü╨╕╧ä╨╡╨╗╨╡╨╝ ╤Å╨▓╨╗╤Å╨╡╧ä╤ü╤Å ╤ü╨╝╨╡╨╡╤î ╨╖╧ä╨ ░╨╜╬┐╨╗╨░, ╧Ç╬┐╨╗╨╕╤ì╧ä╨╕╨╗╨╡╨╜╨│╨╗╨╕- ╬║╬┐╨╗╤Å ╨╕ ╨▓╬ ┐╨┤╤ï ╨▓ ╤ü╬┐╬┐╧ä╨╜╬┐╤ê╨╡╨╜╨╕╨╕ (5-7): (5-7): 1.

9. ╨ƒ╧ü╬┐╧ä╨╜╨▓╬┐╧Ç╨░╧ü╨░╤ì╨╕╧ä╨░╧ü╨╜╤ï╨╣ ╨▓╨╡╧ä╨╡╧ü ╨╜╨╜╨░╧ü╨╜╤ï╨╕ ╧Ç╧ü╨╡╧Ç╨░╧ü╨░╧ä ╨┤╨╗╤Å ╧Ç╨╡╧ü╬┐╧ü╨░╨╗ ╤î- ╨╜╬┐╨│╬┐ ╧Ç╧ü╨╕╨╝╨╡╨╜╨╡╨╜╨╕╤Å, ╤ü╬┐╨┤╨╡╧ü╨╢╨░╤ë╨╕ ╨╣ ╨░╬║╧ä╨╕╨▓╨╜╬┐╨╡ ╨▓╨╡╤ë╨╡╤ü╧ä╨▓╬┐ ╨╕ ╧ä╨▓╨╡╧ü╨┤╤ï╨╣ ╨╜╬┐╤ü╨╜- ╧ä╨╡╨╗╤î, ╬┐╧ä╨╗╨╕╤ç╨░╤Ä╤ë╨╕╨╕╤╨╕╨╕╤╤╤ ╧ä╨╡╨╝, ╤ ç╧ä╬┐ ╨░╬║╧ä╨╕╨▓╨╜╤ï╨╝ ╨▓╨╡╤ë╨╡╤ü╧ä╨▓╬┐╨╝ ╤Å╨▓╨╗╤Å╨╡╧ ä╤ü╤Å ╬║╬┐╨╝╧Ç╨╗╨╡╬║╤ü ╨░╨▓╨╡╧ü╨╝╨╡╬║╧ä╨╕╨╜╬┐╨▓ ╨░╨▓╨ ╡ ╧ü╤ü╨╡╬║╧ä╨╕╨╜ ╨í ╨╕╨╗╨╕ ╨░╨▓╨╡╧ü╤ü╨╡╬║╧ä╨╕╨╜ ╬Æ, ╨╕╨╗╧ Ç ╨░╨▓╨╡╧ü╤ü╨╡╬║╧ä╨╕╨╜ ╬æ ╨▓ ╬║╬┐╨╜╤å╨╡╨╜╧ä╧ü╨░╤å╨╕╨╕ 0 , 1-0.3%, ╨░ ╧ä╨▓╨╡╧ü╨┤╤ï╨╝ ╨╜╬┐╤ü╨╕╧ä╨╡╨╗╨╡╨╝ ╤Å╨▓╨╗╤Å ╨╡╧ä╤ü╤Å ╧Ç╨╡╧ü╨╗╨╕╧ä ╨╕╨╗╨╕ ╤å╨╡╬┐╨╗╨╕╧ä.

10. ╨ƒ╧ü╨╡╧Ç╨░╧ü╨░╧ä ╨┤╨╗╤Å ╨╖╨░╤ë╨╕╧ä╤ï ╧ü╨░╤ü╧ä╨╡╨╜╨╕ ╬ "╬┐╧ä ╨│╨░╨╗╨╗╬┐╨▓╤ï╧ç ╨╜╨╡╨╝╨░╧ä╬┐╨┤, ╤ü╬┐- ╨┤╨╡╧ü╨╢ ╨╕╬ë╨╕╬ «╨░╬║╧ä╨╕╨▓╨╜╬┐╨╡ ╨▓╨╡╤ê╨╡╤ü╧ä╨▓╬┐ ╨╜╨░ ╧Ç╬┐╧ü ╬┐╤ê╬║╬┐╬┐╧î╧ü╨░╤ì╨╜╬┐╨╝ ╨╜╬┐╤ü╨╕╧ä╨╡╨╗╨╡, ╬┐╧ä╨╗╨╕╤ ç╨░- ╤Ä╤ë╨╕╨╣╤ü╤Å ╧ä╨╡╨╝, ╤ç╧ä╬┐ ╨░╬║╧ä╨╕╨▓╨╜╤ï╨╝ ╨▓╨╡╤ ╨╡╤╨╡╤╨╡╤╧╧╨▓╬┐╨╝ ╤╤╨▓╨╗╤╨╡╧╨╡╧╨╡╧╤╤╤ ╬║╬┐╨╝╧Ç╨╗╨╡╬║╤╬║╬┐╨╝╧Ç╨╗╨╡╬║╤ ╬║╬┐╨╝╧Ç╨╗╨╡╬║╤ ╡╧ü╨╝╨╡╬║╧ä╨╕╨╜╬┐╨▓ ╨░╨▓╨╡╧ü╤ü╨╡╬║╧ä╨╕╨╜ ╨í ╨╕╨╗╨╕ ╨ ╨▓╨╡╧ü╤ü╨╡╬║╧ä╨╜╨╜ ╬Æ, ╨╕╨╗╨╕ ╨░╨▓╨╡╧ü╤ü╨╡╬║╧ä╨╕╨╜ ╬æ ╨ ▓ ╬║╬┐╨╜╤å╨╡╨╜╧ä╧ü╨░╤å╨╕╧Ç 0.1-0.3, ╨░ ╧ä╨▓╨╡╧ü╨┤╤ï╨╝ ╨ ╜╬┐╤ü╨╕╧ä╨╡╨╗╨╡╨╝ ╤Å╨▓╨╗╤Å╨╡╧ä╤ü╤Å ╧Ç╨╡╧ü╨╗╨╕╧ä ╨╕╨╗╨ ╕ ╤å╨╡╬┐╨╗╨╕╧ä, ╨╕╨╗╨╕ ╬┐╧ä╧ü╨░╨▒╬┐╧ä╨░╨╜╨╜╤ï╨╣ ╨╝╨╕╤å ╨╡╨╗╨╕╨╣ 3. ╨░╬╜╨╡╨│╤é╬╣.╨¿╨╡.