• 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 invention relates to the production of biologically active mucopolysaccharides by the depolymerization of heparin used in biology and medicine. The invention makes it possible to increase the yield of the target product up to 80% and simplify the process for its preparation. The depolymerization of heparin is carried out in an aqueous medium at a concentration of heparin of 8-12 wt.% And a temperature of 15-20 ° C in the presence in the reaction medium of 0.03-0.07 mol of sodium nitrite. Hydrochloric acid is preliminarily introduced into the reaction mixture to a pH of 2.5-2.95, and at the end of the depolymerization, the pH of the reaction mixture is adjusted to 7 and the desired product is precipitated. 1 tab.
    公开号:SU1531859A3
    申请号:SU823527184
    申请日:1982-12-09
    公开日:1989-12-23
    发明作者:Лормо Жан-Клод；Петиту Морис；Шоай Жан
    申请人:Шоай С.А. (Фирма)；
    IPC主号:
    专利说明:

    The present invention relates to the production of biologically active mucopolysaccharides capable of specifically controlling certain coagulation stages of blood and exhibiting more selective than heparin activity with respect to a more limited number of coagulation factors, for example, activated factor X or blood Xa factor. can be used in biology and medicine.
    The aim of the invention is to increase the yield of biologically active mucopolysaccharides while simplifying the process.
    Example 1. In distilled water, 1500 g of heparin (10% solution) is dissolved at + 20 ° C with a ratio of about 1 YT-J / USF and with a titer of 1BL of 160 ui. Add
    51.8 g of sodium nitrite dissolved in 30 MP of distilled water (0.05 M) and reduce the pH to 2.5 using pure hydrochloric acid.
    Then a reaction occurs, the progress of which is followed up to the determination of the absence of nitrous acid ions. After 40 minutes, at regular intervals, the presence or absence of nitrous acid ions in the reaction medium is determined, for which starch paper is used, and the wire is checked every 5 minutes. After 60 min of reaction, the nitrous acid is completely consumed, and no more N0 ions remain in the reaction mixture. The pH is then adjusted to 7 with pure sodium alkali, and the reaction products are separated by the addition of 31 liters of pure ethanol (2 volumes).
    cl
    with
    00
    ate
    with

    cm
    The precipitate was separated by centrifugation, washed with ethanol and dried under vacuum at 60 ° C. 1200 g of mucopolysaccharides (MIIC) are obtained with the following characteristics: USP19 ui / mg titer
    The titer ARTT1 3 ui / mg
    The titer of Yin and Wessler 202 u / mg Nitrite / nitrate A ppm
    The molecular weight of the obtained product is 2000-8000. The content of chains having affinity for ATIII is 20%. The yield of 80%. The product contains 3% chains of hexasaccharides, 2% of tetrasaccharides, 0% of dicax sychs.
    Example 2. Conducting the process according to the method of example 1, starting from a 10% heparin solution (100 g / l), MIIC is obtained with YW / USP ratios, depending on the concentration of NaNO introduced into the reaction. The results are shown in the table.
    Preferred MIICs correspond to MPS obtained using 0.03-0.07 M NaNo.
    The molecular weight and yield of the resulting product is similar to Example 1.
    Example 3. In 10 ml of distilled water at ambient temperature (15 ° C), 1000 g of injectable heparin with a titer of USP of 170 W / mg and with a titer of YW are dissolved.
    0
    five
    0
    five
    0
    The average molecule weight is less than 6000.
    The percentage of protein with a molecular weight greater than 10,000 is less than 1%.
    PRI me R 4. Use the reaction mixture containing distilled water in 125 ml, 10 g of heparin (8% by weight) and 380 mg (0.055 M); sodium nitrite. The pH is lowered to 2.95 by the addition of pure hydrochloric acid and the mixture is stirred for about 45 minutes.
    A depolymerization product is obtained with a yield of 80% USP titer of 34 ui per mg and YW of 219 units. on mg.
    EXAMPLE 5 The procedure is carried out analogously to Example 4, but 15 g of heparin (12.0% by weight) are used. A de-polymerized mixture is obtained with similar characteristics of the products obtained:
    ShR32 ME / mg.
    YW226 units / mg.
    The yield of 80%.
    The invention makes it possible to obtain a biologist with active mucopolysaccharides with a yield of 80% with a content of reactive chains with 6.4 and 2 sugar units up to 5% (70% by a known method) and chains that have such affinity for ATII1 up to 20% (2% according to the famous cursors). The simpler way compared to the known one is due to the decrease in the number
    160 and / mg. 38 g of nitrite in 35 stages of nitrite are added and the lack of control over
    p (final molar concentration 0.055 M) dissolved in 200 ml of water. The pH value is immediately reduced to 2.5 using hydrochloric acid. The reaction is monitored, as in Example 1, at regular intervals (5-10 minutes). After about 30 minutes, the N0 ions are no longer in the ionic medium and are not detected. Then the pH is adjusted to 7 with 5N sodium hydroxide solution: the reaction products are recovered by adding 21 liters of pure ethanol (2 volumes). The resulting residue is separated by centrifugation, washed with ethanol and dried under vacuum at 60 ° C. Yield of product 80% Received 780 g white powder with the following characteristics:
    Titer SR Titer Yin | Title of ART Sod p.K iHiie nitra H;
    Wesile
    nitrite22
    260
    ten
    ui / mg and / mg ui / mg
    t- 5 m. d.
    0
    five
    0
    five
    权利要求:
    Claims (1)
    [1]
    the duration of the depolymerization reaction, the decrease in the volumes of the reaction of the oHHoii medium, due to the increased renapiuia concentration (8-12 wt.% as compared with 3.3 wt.%). Invention Formula
    The method of obtaining biologically active mucopolysaccharides by depolymerization of heparin in an aqueous medium in the presence of a product that forms nitrous acid, followed by precipitation of mucopolysaccharides with alcohol with alcohol, so that it can be used to increase the yield biologically active mucopolysaccharides during the process control, as a product forming nitrous acid. Sodium nitrite is used at a concentration of it and reactionary i; to 0.03–0.07 mol and; icyrrrrrrrrrr () (and; more (:: 1):, вв incorporate into rec- .) 1 laii-j OT M according to design515318596
    The pH is 2.5–2.95 at a concentration of 15–20 ° C, while before precipitating heparin 8.0–12.0 wt.% And the temperature is adjusted to pH 7,
    Concentration I The ratio of titers YW
    NaNGj, Mk credits 1BR MPS
    T
    (140/51) 2.7
    (214/26) B
    (250/19) 13
    (194/12) 16
    (201/9) 22
    (132 / 6,4) 19
    (110/2) 44
    The value of the ratio of titles
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    同族专利:
    公开号 | 公开日
    IT8220662D0|1982-04-09|
    EP0076279A1|1983-04-13|
    IE52878B1|1988-03-30|
    CA1213276A|1986-10-28|
    FR2503714A1|1982-10-15|
    WO1982003627A1|1982-10-28|
    IT1150812B|1986-12-17|
    EP0076279B1|1986-09-17|
    DE3273278D1|1986-10-23|
    FR2503714B1|1986-11-21|
    AU561167B2|1987-04-30|
    AU8279482A|1982-11-04|
    JPS58500485A|1983-03-31|
    US5019649A|1991-05-28|
    IE820878L|1982-10-10|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    IT1083903B|1977-08-09|1985-05-25|Lobo Srl|OLIGO-ETEROPOLISACCARIDI WITH HEPARINOSIMIL ACTIVITIES, PROCEDURE FOR THEIR OBTAINING AND RELATED THERAPEUTIC COMPOSITIONS|
    SE449753B|1978-11-06|1987-05-18|Choay Sa|MUCOPOLYSACCARIDE COMPOSITION WITH REGULATORY EFFECTS ON COAGULATION, MEDICINAL CONTAINING ITS SAME AND PROCEDURE FOR PREPARING THEREOF|
    CA1136620A|1979-01-08|1982-11-30|Ulf P.F. Lindahl|Heparin fragments having selectiveanticoagulation activity|
    FR2461719B2|1979-07-20|1983-01-14|Choay Sa|
    IL61201A|1979-10-05|1984-09-30|Choay Sa|Oligosaccharides having no more than 8 saccharide moieties,their obtention from heparin and pharmaceutical compositions containing them|
    FR2478646B2|1980-03-20|1983-06-24|Choay Sa|
    US4351938A|1980-05-19|1982-09-28|Riker Laboratories, Inc.|Anticoagulant substance|FR2572080B1|1984-10-18|1987-06-26|Dropic|PROCESS FOR THE PREPARATION OF MUCOPOLYSACCHARIDE COMPOSITIONS WITH HIGH ANTITHROMBOTIC ACTIVITY, THE COMPOSITIONS OBTAINED AND THEIR APPLICATION AS MEDICAMENTS|
    CA1260461A|1984-10-18|1989-09-26|Jean-Claude Lormeau|Process for the preparation of mucopolysaccharide compositions having a high antithrombotic activity|
    FR2584606A1|1985-07-12|1987-01-16|Dropic|USE OF POLY- AND OLIGOSACCHARIDES FOR THE PRODUCTION OF ACTIVE MEDICAMENTS IN THE PATHOLOGIES OF CONNECTIVE TISSUE|
    USRE38743E1|1990-06-26|2005-06-14|Aventis Pharma S.A.|Mixtures of particular LMW heparinic polysaccharides for the prophylaxis/treatment of acute thrombotic events|
    FR2663639B1|1990-06-26|1994-03-18|Rhone Poulenc Sante|LOW MOLECULAR WEIGHT POLYSACCHARIDE BLENDS PROCESS FOR PREPARATION AND USE.|
    ES2049561B1|1991-04-27|1994-12-16|Andromaco Lab|PROCEDURE FOR OBTAINING POLYMERS WITH ACTIVITY ON THE HEMATOPOYETIC SYSTEM.|
    FR2704861B1|1993-05-07|1995-07-28|Sanofi Elf|Purified heparin fractions, process for obtaining them and pharmaceutical compositions containing them.|
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    US5646130A|1995-06-30|1997-07-08|Ocean University Of Oingdao|Low molecular weight sulfated polysaccharides and uses thereof|
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    EP1188773A1|2000-08-30|2002-03-20|Nicox S.A.|Nitroderivatives of polysaccharides|
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    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    FR8107283A|FR2503714B1|1981-04-10|1981-04-10|PROCESS FOR OBTAINING BIOLOGICALLY ACTIVE MUCOPOLYSACCHARIDES, OF HIGH PURITY, BY DEPOLYMERIZATION OF HEPARIN|
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