• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
  • 同族专利
  • 引用文献
  • 法律状态
  • 优先权
    • 专利摘要:
    This disclosure describes a reversible complex of antibiotic AV290 with an alkali metal alkyl sulfate and a process for preparing same. The complex is useful as an animal feed supplement which significantly enhances the growth rate of animals and poultry.
    公开号:SU1047377A3
    申请号:SU742019567
    申请日:1974-04-26
    公开日:1983-10-07
    发明作者:Питер Вэйт Джек
    申请人:Американ Цианамид Компани (Фирма)；
    IPC主号:
    专利说明:

    four
    00
    s3
    The invention relates to a method for producing an antibiotic based feed additive. A 290 and can be used in the microbiological industry to produce feed additives for enhancing the growth of animals, for example, poultry, pigs and ruminants, for example cattle, sheep and goats. A known method for producing an additive to feed based on the antibiotic LU 290, which is formed by enzymatic biosynthesis during cultivation under controlled conditions of the strain of the microorganism Streptomyces candidus NRRZ 3218 and its mutants. The problem of extracting the antibiotic in an economically advantageous way is quite serious. In a known method, adsorption on carbon is used to recover the antibiotic, followed by elution and column chromatography. Such a method cannot be considered too expensive if the antibiotic is necessary for use in medicine. However, if an antibiotic is used as a component for an additive in animal feed, the cost factor becomes a serious problem and therefore it becomes necessary to create an inexpensive method for extracting an antibiotic for this "sharing". Also known is a method for producing an AV antibiotic feed additive 290, including filtering the fermentation medium containing the AV 290 antibiotic, acidifying the resulting fermentation liquid to pH 2.0-2.2, adding the complexing compound and the form of syntan, separating the precipitated compound the complex compound V antibiotic A 290 and the drying egoG2. However, the additive obtained by a known method is not effective enough for korg-shenieyimo animals. The purpose of the invention is to increase the efficiency of the obtained feed additives based on the AV 290 antibiotic. The aim is to achieve that, according to a method that includes filtering the fermentation mixture containing the AV 290 antibiotic, acidifying the resulting fermentation liquid to pH. 2.0-2.2 addition: elimination of the complexing compound, separation of the precipitated AV 290 complex of the antibiotic and drying; sodium alkyl sulfates selected from the group including sodium decyl sulfide, sodium lauryl sulfate and / pasta Empicole 30 are used as complexing compound based on cetyl / lofate sodium liter sodium oleyl sulfate. Alkyl sulfates useful for pred-. The suggested method can be represented by the following general formula; CHf (CH2} f, -0-502-m, where n is an integer from 9 to 17 inclusive; M is a sodium or potassium atom. Typical such alkali metal alkyl sulfates that can be used are, for example, sodium decyl sulfate gendeyl sulfate potassium lofate and sodium heptadecyl sulfate, a mixture of potassium lauryl sulfate and potassium cetyl sulfate, a mixture of sodium tridecyl sulfate, potassium meristil sulfate and sodium pentadecyl sulfate, etc. With and using mixtures of alkali metal alkyl sulfates, the corresponding mixtures of antibiotics with alkyl sulfate complexes are obtained. - removal of the active antibiotic from the enzymatic wort or broth. Moreover, the resulting complex of the antibiotic with alkyl sulfate can be used without separation components of the composition for feed additives, which is of great economic importance. Therefore, in one embodiment, the complex of the antibiotic AV 290 and alkali metal alkyl sulfate is included as a product. The product of the reaction of an antibiotic and an alkali metal alkyl sulfate is considered to be an inverse complex of an antibiotic and alkyl sulfate. Its exact chemical structure has not been established, but - covalent bonds are not; there is and the product is not a physical mixture. This complex, produced by the interaction of an antibiotic and alkali metal alkyl sulfate, does not necessarily combine in any limiting stoichiometric ratio. The chemical bonds are reversible due to the fact that the antibiotic AV 290 can be extracted by the EE complex by any means, for example, by adsorption on a carboxymethyl dextran gel placed in a column, followed by elution with an aqueous acid solution. As a starting material for the proposed method, one can use whole wort obtained after fermentation of S. candidtis NRRZ 3218 or its mutants is completed. Preferably, an enzymatic fluid or enzyme broth is used, which is preliminarily clarified by removing the mycelium and other insoluble substances by filtration. For ease, no filtering can be used. diatom earth or other known means. In any case, the pH of the whole wort or filtered broth is first adjusted to a value in the range of 1.9-22, preferably to about 2.0, with an acid. As soluble acids used for this purpose, for example, hydrochloric acid, sulfuric acid, trifluoroacetic acid and the like can be used, although even ice acetic acid can be used. These pH values are essential, since at pH below 1 g9, the antibiotic AV 290 is decomposed during the drying of the precipitate on the filter even under vacuum. Then, an aqueous solution of an alkali metal alkyl sulfate (or a mixture of alkali metal alkyl sulfate) is added slowly with stirring around the surrounding medium. The whole process of the process is preferably carried out at a temperature of about 15-30 ° C, usually at room temperature. The antibiotic and alkyl sulfate form a complex that is insoluble in water and therefore an IB precipitate falls out. The precipitated complex or, in the case of the use of a solid wort, the precipitated complex, together with the fermentation components of the wort, is then removed by filtration or centrifugation and dried. The resulting product can be dried by layering wetted solids in a polar water-miscible precipitant, for example acetone, with following stages of filtration, washing and drying in air, or re-layering wetted solids in water and freeze drying or drying by spraying. After thoroughly drying the products of the proposed method, under temperature conditions that do not decompose the AV 290 antibiotic, usually white to brown powders are obtained in the case of the alkyl sulfate complex. In the case of the alkyl sulfate complex associated with the dried solids of the dried harvested, usually powders or solids from gray to brown. In the dry form, these products are very stable and do not have a significant ability to lose antibiotic activity in a certain period of time. A long shelf life is of practical importance. The advantage of the proposed method is that the amount of alkali metal alkyl sulfate added to the precipitated complex with the antibiotic is not particularly critical and there is no need to use exactly stoichiometric amounts. The amount of alkali metal alkyl sulphate required to precipitate the AV 290 antibiotic from whole harvested wort is 1.5-2. 5 g per gram of substance with the AV 290 antibiotic activity in the wort. Preferably, approximately 2.0 g of alkali metal alkyl sulfate is applied per gram of substance with antibiological activity. The AV 290 content in 1 fir mash can be easily established by microbiological analysis (after a pH of 8.0-9.0 -. The preferred method is a turbidimetric analysis of tetracycline, based on the use of 3taphylococ.cus aureus. A certain amount of alkali metal alkyl sulfate is then preferably diluted, thrown or suspended in a certain amount of water, and an aqueous solution or suspension is added to As described above, only an excess of alkali metal alkyl sulfate remains in the solution after filtration. The amount of alkali metal alkyl sulfate required to precipitate AV 290 antibiotic from the clarified liquid is approximately 1 g per gram of the substance with AV290 activity in the clarified liquid. the high content of alkali metal alkyl sulphate for the necessary precipitation of AV 290 from whole wort or from a clarified liquid leads to the co-precipitation of other proteinaceous material contained in the whole wort. Typically, the minimum amount of alkyl sulfate is an alkaline material necessary to form a complex with an-. Tibiotics in β-clarified liquid, in any fermentation liquid can be easily determined as follows. A sample (usually 50-100 ml) of enzymatic whole wort is collected and clarified by removing the mycelium and other insoluble materials by filtration, preferably by means of a filtering aid. The filtrate is then acidified to a pH of 1.9-2.1 with dilute mineral acid, for example, dilute hydrochloric acid, dilute sulfuric acid, and the like. This solution is then titrated with 9 brine alkaline metal alkyl sulphate solution, which is used until sediment or turbidity occurs in it. Then, the amount of alkali metal alkyl sulfate solution from the titer of the sample taken is counted, and a small excess is also envisaged. The dried alkyl sulphate complex or the dried solid collected wort. Containing the alkyl sulphate complex, either in pure form or in combination with suitable carriers, significantly increases their growth when introduced into animal feed. In addition, there is an improvement in feed efficiency. The advantage of the proposed method is that it significantly increases the growth of crap, for example poultry and pigs, especially piglets separated from the mother, and the digestibility of feed significantly improves. , Compositions for feed additives enter in quantities that provide approximately the following dosages, mg per second per day: Large ruminants 350 Small ruminants 200 Non-ruminant animals 100 Poultry2 The amount of AV 290 antibiotic in milligrams per pound can be easily determined by bioanalysis (after adjusting the pH to 8.0-9.0). Preferred. a turbidimetric method for analyzing tetracycline on streptococcus aureus. From the obtained potential data, it is easy to calculate the amount of feed additive in grams per tonne of feed. For the preparation of feed additives according to the proposed method, with
    The content of the antibiotic AV 290 in the filter and sediment
    Table 1 holding a dried alkylsulf complex or dried solid wort assembly, a wide variety of carriers can be used. As carriers used to formulate feed additives, you can use soy flour, alfalfa flour, cotton, flax flour, corn flour, cane molasses, urea, bone meal, corn stalk flour, and the like. The carrier contributes to the uniform distribution of the complex of the finished feed, in which the additive is blended. Thus, the important function of communicating the proper distribution of the complex throughout the feed is carried out. . PRI me R 1. The precipitation of the AV 290 antibiotic complex with sodium lauryl sulfate is from a clarified liquid. A sample of technical sulphate of the antibiotic LU 290 with a microbiological capacity of 63.8% is used. A portion of AV 290 sulfate was dissolved in water and the pH of the solution was adjusted to 2.0 by the addition of a 15% solution of sulfuric acid. Celite 545 (diatomaceous earth) was added as a filtering aid, and a 2% aqueous solution of sodium lauryl sulfate was added dropwise with stirring. The resulting mixture was incubated for 30 minutes at room temperature and the solids were removed by filtration and dried under vacuum at. The spent filtrate and dry solid mass is subjected to microbiological analysis, the results of which are shown in table 1.
    PRI mme R 2. Deposition of the AV 290 antibiotic complex with sodium lauryl sulfate from whole harvested wort. Collect specimens from agitated flasks for S.candidus fermentation.
    85.8 95.0 92.7 - 60 5 and increase their strength by adding technical AV 290 sulfate. In the experiments, the results of which are summarized in Table 2, 100 ml of wort are used, and the pH of the wort is adjusted to 2.0 with 15% aqueous sulfuric acid.
    Then, 3.0 g of Dicalite 478 (diatomaceous earth) and a 2% aqueous solution of sodium lauryl sulfate are added dropwise with stirring. The mixture was incubated for 3 hours at room temperature, the precipitate was removed.
    The activity of the filtrate and sediment Number of experience
    1300 1300
    5130 5130
    0.78 0.78
    Primerz, The effect of pH on precipitation of the complex from the whole collected wort.
    Samples of whole harvested wort after fermentation were adjusted to an activity of 4.930 J- / ml with the addition of technical AV 290 sulfate and brought to the samples with the addition of 15% aqueous sulfuric acid, as shown in / table.3. Then added dropwise at
    the pH of the wort for fermentation
    Amount of active substance,%:
    Waste filtrate
    Filtration and dried under vacuum at 40 ° C. Spent filters and dry osal1 and subjected to microbiological analysis, the results of which are given in
    tab- 2,
    Table
    FROM 975 975
    1400 1400 FROM
    5230 5230. 4960
    4960
    2.02 3.08 4.10
    1.15 1.53 1.61
    With stirring, 3.0 g of Dicalite 478, after which a 2% aqueous solution of sodium lauryl sulphate is added to the solution to a ratio of) SO NajAV 290 of 1.62, the mixture is kept
    45. for 3 h at room temperature and dried under vacuum at 40c. Waste filtrates and: dry precipitates on the filter are subjected to microbiological analysis, the results of which are shown in Table 3,
    Table 3
    2.4
    2.2
    2.0
    1.8
    10.1
    6.9
    6.1
    6.4 IL; :::: L: ::: L: I :::: LI :: L: :: L; I :: Z ::: I:
    . In dry filter cake 55.3
    ; Total AV 290 content,% 62.6. EXAMPLE 4. Drying of the AV 290 antibiotic from a whole harvested wort using sodium lauryl sulfate. 30 l of the wort sample obtained from the semi-production fermenter with the content found microbiologically and comprising 3-, 740 y / MP (Processed as follows. The pH of the wort was adjusted to 2.0 by adding 219 ml of concentrated sulfuric acid, and then As a filter aid, 1 kg Dee: Kalita 478 is added. To the stirred wort, a solution of 240 mg of sodium lauryl sulfate is slowly added in 3 liters. The treated wort is then kept for one hour at room temperature and the solid particles are removed on filter press. The wet filter cake was dried under vacuum at which 1.978 g of dry product was obtained, microbial analysis of which showed 4.72%. This corresponds to the extraction of the AV 290 antibiotic from the wort into a dry precipitate on the filter comprising 83 , 2%. Example 5. Deposition of AV 290 antibiotic from whole wort collected using sodium decyl sulfate. 400 ml of sample from a shaken flask (with an activity of 4.590 U / ml under acidification to pH 2, O-addition of 3.0 m. concentrated sulfuric acid / and then 5 g of Dicalite j478 are added. as a filtering aid. To the stirred wort, 9.68 g of Empicol 0137 sodium decyl sulfate solution with an activity of 30.5%, supplied by Albright and Wilson Chemicals Ltd, diluted with WATER up to 50 ml, are slowly added. The treated wort is then kept under stirring for one hour at room temperature and the undissolved substances are removed on a vacuum filter. The filter cake is dried under vacuum at and 20.2 g of dry product are obtained (microbiological analysis showed 9.14%). This constitutes 100.5% recovery of the AV 290 antibiotic from the wort. EXAMPLE 6, AV 290 Antibiotic Deposition from Whole, Collected
    Continued tab
    rI
    - I
    92.883.3 64.2
    71,6
    98.990.2 74.3 78.0 wort using a mixture of sodium cetyl sulfate and sodium oleyl sulfate. 400 ml of a sample of whole wort from a stirred flask (with an activity of 4.590 y / vin} is acidified to a pH of 2.0 by adding 3.0 ml of concentrated sulfuric acid, and then 5 g of Dicalite 478 is added as a filter aid. 13.51 g of Empicol® SIS 30 (30% active pasta containing a mixture of sodium cetyl sulfate and sodium olensulfate, produced by Albright and Wilmon Chemicals Ltd.) were slowly added to the wort, dispersed in water to a total dispersion of 50 ml. , kept under stirring The mixture is dried under vacuum at 50 ° C to obtain 24.0 g of a dry product from microbial-4). KIM analysis of 8.08%. This represents a 10.6% recovery of the antibiotic AV 290IZ wort to dry filter cake. Example 7: Effect of AV 290 Antibiotic Complex with Sodium Lauryl Sulfate on Growth Enhancement. Scheme of experiments. The growth gain estimate is based on average results obtained using four two-week trials. In each experiment, for each treatment, three brooders were used for 1L chicks for each experiment. Komlpeks AV 290 with lauryl sulfate is subjected.} "Tests with concentration O, 0005, 0.0010, 0.0020 and 0.0040% by weight of the feed. Diet. As the main feed for these experiments, ration No. 453 dp of broilers was used (Table 4 |. Experimental feed was prepared by mixing an appropriate amount of the test material with the main diet in a Hobbert mixer. All feed was provided ad libitum. Simultaneous broiler chickens (Hubbird breed mixed and Airborne Acre) are placed in electrically heated brooders in a room with air conditioning (24 seconds for two weeks. Each cage contains 5 clamps of different sexes. The following data is recorded: initial weight, average weight of chickens In addition to assimilation of trace elements, Manganese Iron Zinc Copper Iodine Cobalt Calcium Vitamin mixture per 1 ton of feed D-Methionine Thiamine Vitamin A (ZOOOO u / gI Vitamin D, 200000 u / g) Vitamin E (50 units / g. Riboflavin Nicotinamide Calcium Pantothenate Vitamin K (menadian; Parvo 10%, folic acid Choline chloride (50%) Profums (0.5 mm Hz / g) Corn oil Crushed corn 11104737712 after 2 weeks and consumption of AV 290 with lauryl sulfate. Medium, 2 weeks . the results obtained after 2 weeks, x test dosages at table 5, where weight increase and improvement are shown in parentheses, as compared with the control of the form, caused by the 5% complex. Components I Content,% Crushed yellow maize 53.45 Soyeva flour (49% soybean oil / 28.0 Fish meal (60% fish oil / 5.0 Flour from corn gluten (60% / 5.0 Dehydrated flour from alfalfa (17%) 2.0 Stabilized fat4.0 Dicalcium phosphate. Chopped limestone k .0.5 Sodium chloride .0.3 Trace element 0.05 Vitamin mixture .0.5 in all four experiments / bring Table 4 of the weight of the carrier 12.50 6.00 5.00 0.65 0.35 0.25 30-18.35 453.6 113.6 100.0 5.0 45.4 4.0 25.0 8 , 0, 1.0 13.0 908.0 227.0 50.0 582.4
    Control
    AV complex, 290-lauryl, based on A 290 i
    Example One-day clings (Ross-f strain give the same feed, containing doses of AV 290 25 antibiotic in the form of a synthane or ethyl sulfate complex for 56 days: j 1 group A received the antibiotic AV 290 in the form of sodium lauryl sulfate complex; It B received ZO antibiotic AV 290 in the form of Synthetic control and experimental feed add means to prevent coccidiosis: to the initial and growth parts - a child preparation. Table 5
    1.46
    191.38
    group III - control. Each group had 51 pegs and 51 chickens, which were kept in designated grounds. All chicks tg1m E1 aged 29 days were vaccinated against Newcastle disease. Feed for chickens of different ages has characteristics given in para. 6.
    Table 6
    Table 7 din, and to the end part - pano. Coxin. The results of the experiments are presented in table.7.
    B0,005 17512,287
      17502,286
    B0,0015 17652.273
    The results of the experiments show that the lauryl sulfate complex; the AV 290 complex, both AV 290 forms with all the tested-expressed more than the comparable dosages improve the dose rate of the synthane weight gain and reduce the amount of core-AV 290 as for the increase required by the weight gain . live weight, so in relation to However, the effect on birds, consumption v-efficiency feed.
    Continued table. 7,
    权利要求:
    Claims (1)
    [1]
    METHOD FOR PRODUCING FODDER ADDITIVE ON THE BASIS OF ANTIBIOTIC AV290, including filtering a fermentation medium containing an antibiotic
    AV 290, acidification of the resulting fermentation liquid to. pH 2.0-2.2, by adding a complexing compound, separating the precipitated antibiotic complex compound
    AX / 290 and drying, so that with the aim of increasing the efficiency of the feed additive, sodium alkyl sulfates selected from the group consisting of sodium decyl sulfate, sodium lauryl sulfate and paste are used as complexing compounds Empikol SNS 30 based on sodium cetyl sulfate and sodium oleyl sulfate.
    1,047,377 '
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    同族专利:
    公开号 | 公开日
    SE434645B|1984-08-06|
    HK57078A|1978-10-06|
    DD112898A5|1975-05-12|
    US3856937A|1974-12-24|
    PL90477B1|1977-01-31|
    DE2419801A1|1974-11-14|
    BE814267A|1974-10-28|
    GB1441703A|1976-07-07|
    IE39967B1|1979-02-14|
    FR2227277B1|1977-10-14|
    HU168350B|1976-04-28|
    CA1017274A|1977-09-13|
    SU674653A3|1979-07-15|
    AU6714674A|1975-10-02|
    IT1047135B|1980-09-10|
    ATA347574A|1976-05-15|
    NL167594B|1981-08-17|
    PH12144A|1978-11-07|
    DK142672B|1980-12-15|
    ZA741801B|1975-03-26|
    YU39110B|1984-06-30|
    AR201139A1|1975-02-14|
    AT334528B|1976-01-25|
    JPS5013594A|1975-02-13|
    PL91872B1|1977-03-31|
    IE39967L|1974-10-27|
    NL167594C|1982-01-18|
    DE2419801C2|1983-12-29|
    NL7405514A|1974-10-29|
    ES425744A1|1976-07-01|
    IL44445D0|1974-06-30|
    HU169960B|1977-03-28|
    YU108274A|1982-05-31|
    JPS5421438B2|1979-07-30|
    DK142672C|1981-08-03|
    CH594735A5|1978-01-31|
    CS194206B2|1979-11-30|
    DD114342A5|1975-08-05|
    FR2227277A1|1974-11-22|
    IL44445A|1976-12-31|
    MY8000181A|1980-12-31|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    US3338786A|1966-07-29|1967-08-29|American Cyanamid Co|Antibiotic av290 and production thereof|
    ZA716946B|1970-11-03|1972-06-28|American Cyanamid Co|Antibiotic av290-syntan complexes|US3950515A|1973-04-27|1976-04-13|American Cyanamid Company|Animal feeds containing antibiotic AV290|
    NZ189369A|1978-02-02|1982-05-25|American Cyanamid Co|Animal feed supplement containing antibiotic trans-bm123 gamma or salts alkylated derivatives or certain complexes thereof|
    US4259320A|1979-03-02|1981-03-31|American Cyanamid Company|Concurrent use of avoparcin with growth-promoting implants in cattle|
    JPS5832554Y2|1979-03-09|1983-07-19|
    JPS5623969A|1979-08-01|1981-03-06|Shiyoubouchiyou Chiyoukan|Cooling and respirating apparatus of fireeproof garment|
    US4485102A|1982-08-16|1984-11-27|American Cyanamid Company|High potency, mycelial-free avoparcin alkyl sulfate complex, and method for the preparation thereof|
    GB2169200B|1985-01-08|1989-02-15|American Cyanamid Co|Animal feed block compositions|
    US6362009B1|1997-11-21|2002-03-26|Merck & Co., Inc.|Solid phase synthesis of heterocycles|
    DE102006028817A1|2006-06-21|2007-12-27|Evonik Degussa Gmbh|Processing of Reaction Solutions from Whole Cell Biotransformations|
    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    US00355240A|US3856937A|1973-04-27|1973-04-27|Process for isolation of antibiotic av290|
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