• 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 producing an aqueous solution of high heparin content from heparin-containing animal organs comprises forming a heparin-enriched granular raw material from these organs and extracting the raw material at a temperature of 20 DEG to 80 DEG C. with a salt solution having a salt concentration of 1.5 to 12.0% and a pH in the range of 8 to 12.8 or an alkalinity of 0.5 normal to 1.08 normal concentration. The dry substance to liquid ratio should be 1:5.
    公开号:SU1375115A3
    申请号:SU802897802
    申请日:1980-03-20
    公开日:1988-02-15
    发明作者:Такач Иштван；Керей Дьердь；Иллеш Янош；Рудольф Петер；Гере Пал；Цебе Ласло；Несмельи Эржебет
    申请人:Рихтер Гедеон Ведьесети Дьяр Рт (Инопредприятие)；
    IPC主号:
    专利说明:


    s
    The invention relates to medicine, namely to pharmacology, in particular to methods for producing pharmaceutically preparations.
    The purpose of the invention is to realize the yield of the target product.
    The goal is achieved by the fact that heparin-containing raw materials with 90-95% dry matter content are treated with a 1.5-12% solution of salt at pH 8-12.8 with periodic or continuous anti-tect extraction at 20-80 ° WITH.
    The method is carried out as follows.
    Heparin-rich, amorphous, granular, with a stable form, raw material with a large specific surface, containing 90-95% dry matter, in an aqueous medium at a temperature and pH value, optimal for this method of processing raw materials, is subjected to periodic or continuous counter-current extraction with saline . Countercurrent extraction is carried out at 20-80 ° C, electrolyte concentration (salt concentration 1.5-12.0%), and at pH 8-12.8 or in 0.5-1.0 n alkaline solution.
    During the entire extraction process, it is advisable to maintain a constant electrolyte concentration, temperature, and pH. The ratio between the extruding salt solution and the feedstock should be adjusted so that the extraction stretch from the extract contains 150-300 1E / ML heparin. For this, it is advisable to keep the dry matter to liquid ratio about 1: 5. Bases of monovalent or polyvalent metals are used to adjust the pH, it is advisable caustic soda or other alkalis commonly used to extract heparin. As an electrolyte, any salts that are inert with respect to heparin, preferably sodium chloride, are used.
    As a raw material rich in heparin, there is a raw material that contains at least 5-35% (calculated on the dry matter) more heparin,
    than any natural raw material.
    Countercurrent extraction is carried out
    in a batch machine up to complete extraction or
    in a continuous manner, appropriate in an i-shaped extractor.
    Heparin-rich dry concentrate is used as a raw material, which is granular and amorphous and has a high specific surface area.
    The method is explained by the following examples.
    Example 1. Raw materials containing heparin are autolized and extracted in the presence of toluene with electrolyte solutions. 20 kg of this material is intensively mixed in a jacketed reactor together with 100 kg of finely divided pig intestines containing 18% dry matter and 150 l of a 10% ammonium sulfate solution. After, sm-- 0, the mixture is heated to 38 ° C. Then, with stirring, the following was established: R. pK of the mixture 8.8-9.2 by the addition of 40% sodium hydroxide solution. To avoid harmful microbiological processes 5, 3 L of toluene is added to the mixture.
    After the addition of enzymes at C8 for 36 hours, autolysis is carried out, and the mixture is stirred from time to time. Control pH 0 every 6 hours and as needed.
    set to a predetermined amount. the addition of 40% aqueous solution of caustic soda.
    After 36 hours of autolysis, the pH of the medium is set to 7.3-7.7 with 18% hydrochloric acid and the mixture is boiled. After 10 minutes of boiling, the coagulated parts are separated on a sieve filter. The filtrate is separated at 60 C, freeing it from fat. 638 g of a dark brown extraction broth are obtained, in which the concentration of heparin is 18.1 1E / ML, which corresponds to 11.54 M1E of heparin. The yield is only 76%.
    Example 2. 5, O kg of dry concentrate containing heparin is divided into 10 equal parts. These portions, 0.5 kg each, are treated by a method of periodic five-step counter-protracted extraction. The individual steps are carried out as follows. The first portion of the dried concentrate 5 organ and heated to 40 C
    0.25 N sodium hydroxide solution containing 6% sodium chloride is added to 3.2 liters of extraction mixture. After 20 min, the filter extract5
    0
    five
    0
    under a vacuum through a Buchner funnel. The surface of the filter is formed by a metal grid with a hole diameter of 0.6 mm. The first extraction solution collects its volume and measures its heparin activity.
    The wet residue of the organ remaining on the wire sieve is again mixed with a 0.25 N solution of sodium hydroxide heated to 40 ° C and containing 6% sodium chloride, while again the extraction mixture is set to 3.2 liters. The second extraction is already extracted once organ weights are carried out in the same way. The filtrate formed during the second extraction of the first portion of the organ concentrate is mixed with the second portion of the dried concentrate. Again set the volume of the extraction mixture, 3.2 l,
    The subsequent stages, respectively, are carried out in a similar way. In the final result, periodic countercurrent extraction is carried out in 5 stages. The extraction volume is always 3.2 liters, the temperature is 40 seconds.
    From 5 kg of starting material containing 90.4% of dry matter, a five-step, periodic extraction gives 2.599 M1E of heparin.
    Example 3. Heparin-containing dry concentrate is extracted. 40 kg of raw material is well mixed with 400 liters of water. The pH is adjusted to 2.7 with hydrochloric acid and the mixture is heated to 38 ° C. Pepsin is added in an amount corresponding to 10 kg of the mucous membrane of the porcine stomach, then the pH is adjusted to 2.7 s With constant stirring, the temperature is maintained for 20 hours 37-39 ° C. After a 20-hour proteolysis, the pH is adjusted to 8.0 with a 40% sodium hydroxide solution and 20 L of the activated pancreas mixture is added to the mixture at 37 C. The second proteolysis lasts 10 hours. Every 2 hours, the pH is monitored and, if necessary, it is again adjusted to 8.0 with a solution of caustic nat.
    about 5 0
    five
    about
    Q with
    five
    ra. The temperature is maintained at 37 ° C. After the second proteolysis, the mixture is boiled and then filtered through a sieve filter. 417 l of brown filtrate are obtained, the concentration of heparin in which is 32.0 1 E / ml, i.e. total heparin is 13.32 M1E.
    Example 4. Heparin-rich dry concentrate is extracted in a continuous counter-current manner in an i-shaped extractor. The dried starting material is continuously fed to the apparatus using a screw feeder. From the spray head, located above the dosing unit, add a double volume of 0.55 N solution of caustic soda heated to 70 C and containing 6% of common salt. The residence time of the material in the screw stop is 10 minutes.
    A 0.1 N solution of caustic soda containing 6% of common salt is fed in a countercurrent to the swollen material, which is located in a separate I-shaped extractor.
    During continuous countercurrent extraction, a constant temperature of 50 ° C is maintained, with the aim of improving mass transfer, a vibrator located at the bottom of the i-shaped extruder is turned on. The concentration of heparin is determined in samples taken every 0.5 hour. The heparin contained in the extract is also precipitated continuously, and the resulting precipitate is separated on a drum-type filter.
    H
    The equipment used has a productivity of 10 kg of dry concentrate / h, the residence time is 35 minutes. In a 10-hour operation, 210 L of extract is obtained, the average activity of which for heparin is 252 1E / ML. The yield is 52.9 M1E, based on 100 kg of starting material containing 90.4% dry matter.
    权利要求:
    Claims (1)
    [1]
    METHOD FOR PRODUCING HEPARIN 'by extraction of heparin-containing raw materials under alkaline conditions when heated, characterized in that, in order to increase the yield of the target product, heparin-containing raw materials with 90-95% dry matter content are treated with a 1.5-12% sodium chloride solution at a pH of 8-12.8 with periodic or continuous countercurrent extraction at 20-80 ° C.
    oo m SL
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    同族专利:
    公开号 | 公开日
    SE451297B|1987-09-28|
    AU5663680A|1980-09-25|
    JPS55164201A|1980-12-20|
    AU533021B2|1983-10-27|
    DK119480A|1980-09-22|
    BE882369A|1980-09-22|
    AT365927B|1982-02-25|
    FR2451743B1|1983-05-27|
    GB2045271A|1980-10-29|
    DE3011062A1|1980-10-02|
    US4315923A|1982-02-16|
    IN153527B|1984-07-21|
    ES490537A0|1981-02-16|
    NL8001693A|1980-09-23|
    SE453725B|1988-02-29|
    YU76580A|1983-10-31|
    FR2451743A1|1980-10-17|
    PL222794A1|1981-01-02|
    CA1137081A|1982-12-07|
    ES8102581A1|1981-02-16|
    IT8067444D0|1980-03-21|
    ATA144280A|1981-07-15|
    DE3010972A1|1980-10-02|
    DK166504B|1993-06-01|
    FR2451744B1|1983-07-29|
    HU177887B|1982-01-28|
    DD149467A5|1981-07-15|
    DK166504C|1993-10-18|
    PL134709B1|1985-09-30|
    ES490538A0|1981-02-16|
    NZ193215A|1984-11-09|
    CS248011B2|1987-01-15|
    BE882370A|1980-09-22|
    GR67681B|1981-09-04|
    IT8067438D0|1980-03-21|
    SE8002126L|1980-09-22|
    DD149532A5|1981-07-15|
    FR2451744A1|1980-10-17|
    AU529809B2|1983-06-23|
    BR8001711A|1980-11-18|
    DK166393B|1993-05-10|
    PL222906A1|1981-01-02|
    DE3010972C2|1989-08-31|
    GB2045272A|1980-10-29|
    IT1133068B|1986-07-09|
    AR222215A1|1981-04-30|
    SE8002125L|1980-09-22|
    JPH039121B2|1991-02-07|
    CA1152894A|1983-08-30|
    ATA134880A|1982-01-15|
    JPS55164202A|1980-12-20|
    DK119780A|1980-09-22|
    NZ193188A|1984-11-09|
    IT1133074B|1986-07-09|
    ZA801480B|1981-03-25|
    NL8001695A|1980-09-23|
    CS248012B2|1987-01-15|
    DK166393C|1993-09-27|
    AT368004B|1982-08-25|
    GB2045271B|1983-04-20|
    BR8001717A|1980-11-18|
    YU76980A|1984-02-29|
    ES8102580A1|1981-02-16|
    GB2045272B|1983-03-30|
    SU1366042A3|1988-01-07|
    AR219226A1|1980-07-31|
    JPH0232282B2|1990-07-19|
    PL128250B1|1984-01-31|
    AU5663780A|1980-09-25|
    GR67682B|1981-09-04|
    ZA801564B|1981-03-25|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    US2410084A|1943-12-09|1946-10-29|Upjohn Co|Recovery of heparin|
    US2587924A|1948-05-27|1952-03-04|Univ Alberta|Methods of producing heparin|
    US2571679A|1948-07-08|1951-10-16|Carlo Erba S A|Process for preparing purified heparin|
    DE950594C|1953-07-01|1956-10-11|Upjohn Co|Method for obtaining heparin|
    GB872214A|1957-09-23|1961-07-05|Upjohn Co|Extraction process for the recovery of heparin|
    US2989438A|1958-12-29|1961-06-20|Roussel Uclaf|Process of purifying heparin, and product produced therefrom|
    GB1221784A|1967-04-07|1971-02-10|John Ernest Scott|Precipitation of heparin from aqueous solution|
    US3451996A|1968-02-12|1969-06-24|Thompson Farms Co|Method for the preparation of heparin|
    IT1019525B|1972-03-21|1977-11-30|Ferdinando D|APPARATUS AND PRODUCT METHOD TO FORM STABLE COMPLEXES OF POLY NIONS|
    US4192916A|1975-10-31|1980-03-11|A. H. Robins Company, Incorporated|Process for producing defatted heparin tissue for heparin production|
    US4188467A|1975-10-31|1980-02-12|A. H. Robins Company, Incorporated|Process for tempering tissue for heparin production|
    DE2646677C2|1975-10-31|1985-11-07|A. H. Robins Co. Inc., Richmond, Va.|Method for annealing frozen heparinized animal tissue|
    DE2646678C2|1975-10-31|1985-11-28|A. H. Robins Co. Inc., Richmond, Va.|Process for the production of a defatted heparin tissue|
    DE2660052A1|1976-11-12|1979-01-25|Schering Ag|Pure anticoagulant heparin prodn. - using salt lakes obtd. from mucus-free animal intestines by sprinkling with salt|
    DE2652272C2|1976-11-12|1979-02-15|Schering Ag, 1000 Berlin Und 4619 Bergkamen|Process for the production of heparin|
    US4175182A|1978-07-03|1979-11-20|Research Corporation|Separation of high-activity heparin by affinity chromatography on supported protamine|US4692435A|1978-11-06|1987-09-08|Choay, S.A.|Mucopolysaccharide composition having a regulatory action on coagulation, medicament containing same and process of preparation|
    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|
    US4826600A|1987-06-24|1989-05-02|Amoco Corporation|Process for treatment of wastewater|
    US6232093B1|1997-07-16|2001-05-15|Akzo Nobel N.V.|Process for the production of heparin|
    CA2489662C|2002-06-19|2011-04-12|Can Technologies, Inc.|Animal feed composition comprising mucosa byproduct|
    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    HU79RI705A|HU177887B|1979-03-21|1979-03-21|Process for preparing a raw material containing heparin|LTRP751A| LT2280B|1979-03-21|1993-07-01|THE GEPARINO RECEIVING BUDGET|
    LV931176A| LV5403A3|1979-03-21|1993-10-27|Heparin retention|
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