• 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:
    A process for preparing hydroxyethyl starch suitable as a plasma extender by alkaline hydroxyethylation and neutralization wherein the hydroxyethyl starch is extracted with a solvent such as dimethylformamide to remove the salts formed on neutralization.
    公开号:SU797586A3
    申请号:SU782596657
    申请日:1978-04-04
    公开日:1981-01-15
    发明作者:Хольцер Карл
    申请人:Левозан-Гезельшафт Мбх Унд Ко Кг (Фирма)；
    IPC主号:
    专利说明:

    (54) METHOD FOR OBTAINING OXYETHYL-STRAIN
    权利要求:
    Claims (2)
    [1]
    The invention relates to a process for the preparation of oxyethyl starch used as a means for increasing the volume of blood plasma. A known method for the preparation of oxyethyl starch by reacting degraded starch with ethylene oxide in an inert gas atmosphere in an alkaline medium followed by neutralization of the reaction mixture and dialysis l. However, as a result of the neutralization of the strongly alkaline reaction mixture, a relatively large amount of salts are formed (mainly NaCl). target product used in medicine. Dialysis allows you to remove a certain portion of undesirable salt impurities, however, this operation, being rather complicated in terms of instrumentation and requiring an extremely large amount of time, poses the additional danger of microbiological contamination of the target product. The introduction of a preparation based on oxyethyl starch containing such impurities causes an increase in temperature. Thus, there is currently no method for producing oxyethyl starch with the level of purity and microbes required for plasma replacement, which is sufficiently simple for reproduction on an industrial scale. The disadvantage of this method is that the purity of the target product is not high enough. The purpose of the invention is to increase the purity of oxyethyl starch. This goal is achieved by the method of producing oxyethyl starch by reacting destructed starch with ethylene oxide in an inert gas atmosphere in an alkaline medium, followed by neutralization of the reaction mixture, extraction of the target product with dimethylformamide and repeated, preferably 5-6-fold, re-precipitating; 4, acetone. The method is carried out as follows. The starch, degraded by acid hydrolysis, is oxyethylated in an alkaline medium in a stream of nitrogen gas. Then the reaction mass is neutralized with hydrochloric acid, treated with activated charcoal, filtered under pressure and evaporated in vacuo. The resulting thick syrup is dried by drying in vacuum. The dried product is dissolved in dL / 1-methylformamide for extraction, and most of the sodium chloride formed as a result of neuralisation is isolated in an insoluble form. After filtration, a filtrate is obtained, which consists mainly of a solution of α-hydroxyethyl starch extractite. In addition to the insignificant content of residual sodium chloride in this solution, there is ethyl glycol formed as a co-product by ethoxylation. In this case, hydroxyethyl starch is precipitated from the extract with a crude degree of purity, and acetone is used as a precipitant. The reprecipitation is carried out several times, preferably 5-6 times. The pure product does not cause an increase in temperature and contains a small amount of sodium chloride, which is determined potentiometrically. During subsequent processing into a 6% isotonic solution, hydroxyethyl starch, which serves as a means for increasing plasma volume, is weighed and the calculated missing amount of sodium chloride is added. Under practical conditions, the residual content of sodium chloride in the solution of hydroxyethyl starch used to increase the plasma volume, is less than 0; 9% and must be supplemented with Li. The oxystil starch obtained by the proposed method is relatively easy to break down by the amylase inherent in the body and is eliminated from the body within a reasonable period of time. Example. 243 g of starch obtained from waxy corn, partially degraded by acid hydrolysis, having a viscosity index of 2.35c (c 6, water, 37 ° C) is dissolved by passing a stream of nitrogen gas at room temperature and stirring in solution 240 g of sodium hydroxide sodium in 6 liters of water. In a water-cooled yellow alkaline solution of degraded starch, with additional nitrogen flow, 317 g of ethylene oxide are introduced within 2-3 hours. After many hours of standing in an atmosphere of nitrogen, neutralization with a dilute hydrochloric acid solution (obtained by dissolving 480 ml of 37% concentrated hydrochloric acid, d 1.1 in 3 l of water) is carried out while cooling with water (pH about 6). After treatment, 15 g of activated carbon (Norit, SX plus) is filtered under pressure, and the filtrate is evaporated in vacuo at 60 For drying, heated for 15-20 hours under the vacuum created by an oil pump. The product obtained after drying is stirred while rotating in 900 ml of dimethylformamide at 80 ° C until a homogeneous, turbid solution is obtained. After cooling to room temperature, filter; the remaining sodium chloride on the filter is washed with dimethylformamide and the filtrate is admixed to about 10 liters of acetone. The precipitated hydroxyethyl starch as a yellow granular product (crude in purity) is sucked off, washed with acetone and dried under vacuum until a glassy bubble mass is obtained. The yield is 352 g. It is then dissolved in 2 l of water under mild heating, filtered with 22 g of activated carbon, the filtrate is evaporated in vacuo to a volume of 90 ml and mixed with 9 l of acetone. The precipitated resinous mass is twice mixed with fresh acetone and dried under vacuum at. Yield 272 g. For further purification, the yields after five similar operations with a total weight of about 1350 g are dissolved with stirring in 9.5 l of water and, after being mixed with 64 g of activated carbon, filtered under pressure. Filt-. The mixture is mixed with the same amount of activated carbon and re-filtered under pressure. It is then evaporated in vacuo at a volume up to about 4 liters and mixed into 20 liters of acetone. The white resinous mass is mixed three times with fresh acetone and then dried under vacuum at. The yield is 1173 g of a solid in the form of a white foamy mass, having a viscosity index of f 2.95 cp (water, 37 ° C); degree of substitution 0.71; sodium chloride content 5.2%; a test for the ability to cause a rise in temperature gives negative results. The proposed method allows to obtain hydroxyethyl starch with a low content of salt impurities (NaCI), not exceeding 5.2%, and not causing an increase in temperature when used for therapeutic purposes. Claim 1. Method for producing oxyethyl starch by reacting degraded starch with ethylene oxide in an inert gas atmosphere in an alkaline medium followed by neutralization of the reaction mixture, characterized in that, in order to increase the purity of the target product, hydroxyethyl starch is extracted
    5 7975866
    from the reaction mixture dimet silt forms-Sources of information,
    house followed by multiple re-taken into account during the examination
    precipitation with acetone. Husemann E., Resz R. Uber
    [2]
    2. The method according to p. 1, distinguish-naturliche und synthetische amylose,
    u and with the fact that they carry out V, Uber Ohuthy I atulosen. - g.
    5-6 times re-precipitation of the target. Pollm. Science, 1956, 19, 389 (of prod- uct acetone. Totype).
    类似技术:
    公开号 | 公开日 | 专利标题
    SU797586A3|1981-01-15|Method of preparing oxyethylstarch
    SU1658820A3|1991-06-23|Method for preparing mucopolysaccharides
    JPH09324001A|1997-12-16|Purification method for sodium hyaluronate
    JP3856337B2|2006-12-13|Recovery of natamycin
    EP0867453A2|1998-09-30|A method of purifying sodium hyaluronate
    HU202282B|1991-02-28|Process for separating 2-keto-l-gulonic acid from fermentation juice
    RU2369611C2|2009-10-10|Treatment of m-|glycine
    JP2006291028A|2006-10-26|Low-molecular heparin or salt thereof, and manufacturing method thereof
    CA2779168A1|2011-05-12|Process for preparing a mixed salt of glucosamine sulfate and an alkali metal chloride
    JPH0791302B2|1995-10-04|Method for producing ellagic acid
    JP2000034302A|2000-02-02|Manufacture of polyguluronic acid
    US4350791A|1982-09-21|Vinylpyrrolidone polymers, their preparation, their use in the preparation of plasma substitutes, and the substitutes thus obtained
    JP4186294B2|2008-11-26|Method for producing polyguluronic acid
    MXPA96004372A|1997-06-01|Procedure for the recovery of natamic
    CN110283869A|2019-09-27|The preparation method of 7-amino-cephalosporanic acid
    CN109265460A|2019-01-25|A kind of purification process of folic acid
    CN108383745B|2021-12-28|Preparation method of aceclofenac
    US4010167A|1977-03-01|Method for the recovery of zearalenone
    CN109851568B|2020-07-28|Method for purifying prothioconazole
    JP2012121963A|2012-06-28|Method for producing polyguluronic acid, method for producing polymannuronic acid, polyguluronic acid, and polymannuronic acid
    EP0434145B1|1998-08-12|Acrylamide copolymers containing |acrylamide benzene dicarboxylic units
    US3196146A|1965-07-20|Production and recovery of benzyl dextran
    CN105884866B|2021-04-20|Chemical synthesis method of glatiramer
    SU1723122A1|1992-03-30|Method of hyaluronidase preparation
    CA3142882A1|2020-12-10|Improved method of synthesis and purification of citrulline
    同族专利:
    公开号 | 公开日
    SE7803892L|1978-10-09|
    FR2386558B1|1980-08-08|
    IL54388A|1981-07-31|
    DK158791C|1990-12-03|
    NL7803334A|1978-10-10|
    CS193499B2|1979-10-31|
    IL54388D0|1978-06-15|
    YU40514B|1986-02-28|
    NL188753B|1992-04-16|
    FR2386558A1|1978-11-03|
    HU176274B|1981-01-28|
    CA1092603A|1980-12-30|
    DK155178A|1978-10-09|
    CH632281A5|1982-09-30|
    DD135352A5|1979-05-02|
    YU82378A|1984-02-29|
    IT7821997D0|1978-04-05|
    IT1094297B|1985-07-26|
    SE430068B|1983-10-17|
    FI781058A|1978-10-09|
    JPS5460385A|1979-05-15|
    DE2814032A1|1978-10-19|
    JPS6334161B2|1988-07-08|
    DK158791B|1990-07-16|
    AT348548B|1979-02-26|
    ATA248977A|1978-07-15|
    NL188753C|1992-09-16|
    SI7810823A8|1994-12-31|
    FI63762B|1983-04-29|
    FI63762C|1983-08-10|
    US4167622A|1979-09-11|
    DE2814032C2|1989-12-14|
    GB1551807A|1979-08-30|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    FR88043E|1964-07-20|1966-06-17|Staley Mfg Co A E|Preparation of amylose ethers by catalytic etherification of an aqueous solution of amylose|
    US3414530A|1965-12-23|1968-12-03|Agriculture Usa|Graft polymers of polyalkylene oxides on starch and dextrin|
    US3523938A|1967-12-13|1970-08-11|American Hospital Supply Corp|Starch plasma expanders and process of preparation|
    JPS538750B2|1971-08-18|1978-03-31|
    US3937821A|1971-08-21|1976-02-10|Kyorin Seiyaku Kabushiki Kaisha|Plasma substitute including artificial starch and method for the preparation thereof|
    JPS495193A|1972-05-02|1974-01-17|
    DE2260785A1|1972-12-12|1974-06-20|Morishita Pharma|Prepn of hydroxyethyl starches - using organic base catalyst useful as blood serum extenders|
    JPS5222872B2|1974-11-25|1977-06-20|US4431800A|1982-03-30|1984-02-14|General Foods Corporation|Process for hydroxypropylating starch|
    DE3428201A1|1984-07-31|1986-02-06|Laevosan-Gesellschaft mbH & Co. KG, Linz|PERITONEAL DIALYSIS SOLUTIONS|
    SE462100B|1985-08-08|1990-05-07|Perstorp Ab|COMPOSITION AND ITS USE IN A TWO OR MULTIPLE SYSTEM|
    DE19975071I2|1989-06-16|2000-02-03|Fresenius Ag|Hydroxyethyl starch as a plasma expander Process for their production and use as a colloidal plasma substitute|
    GB9121559D0|1991-10-10|1991-11-27|Dowty Defence & Air Syst|Pumps|
    US6051700A|1999-02-11|2000-04-18|Grain Processing Corporation|Process and method for hydroxyalkylation of starch and hydroxyalkyl starch prepared accordingly|
    US6746836B1|2000-12-08|2004-06-08|Abe Widra|Alpha-keratose as a blood plasma expander and use thereof|
    AU2008342260B2|2007-12-27|2013-10-17|Baxter Healthcare S.A.|Chemically modified Factor IX|
    CN102617743B|2012-03-31|2015-02-18|李育强|Preparation method for hydroxyethyl starch|
    CN103588888A|2013-11-17|2014-02-19|石家庄四药有限公司|Preparation method of hydroxyethyl starch with low-medium molecular weight|
    DE202016102800U1|2016-05-25|2016-09-02|Joint-Stock Company "MEDPOLYMER"|Plasma replacement solution|
    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    AT248977A|AT348548B|1977-04-08|1977-04-08|METHOD FOR THE PRODUCTION OF HYDROXYAETHYL STARCH SUITABLE FOR AS BLOOD PLASMA EXPANDERS|LV920680A| LV5529A3|1977-04-08|1992-12-30|Sediment for obtaining starch oxyethyl derivative|
    MD940057A| MD22B1|1977-04-08|1994-02-09|Process for obtaining oxyethyl starch|
    [返回顶部]