• 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:
    Hochaktives Pankreatin gewinnt man durch Autolyse eines mit vorzugsweise Natriumhydrogencarbonat gepufferten wäßrigen isopropanolhaltigen Gewebebreies bis zum positiven Ausfall einer Testfällung mittels wäßrigem Isopropylalkohol und Fällung mit steigender Konzentration an Isopropylalkohol, wobei eine Fasersuspension entsteht, die abgesiebt werden kann und aus der Lösung die unmittelbare Gewinnung von Pankreatin durch weitere Erhöhung der Konzentration an Isopropylalkohol erlaubt. Hohes Schüttgewicht des fertigen, trockenen Präparats erzielt man, indem man das ausgefällte Pankreatin durch Aufrühren mit Isopropylalkohol oder Aceton auf eine Konzentration zwischen 70 und 85 % an Isopropanol bzw. 80 bis 95 % an Aceton bringt, absaugt oder abschleudert und unter Behandlung mittrockener Luft oder Stickstoff trocknet.
    公开号:SU1644712A3
    申请号:SU833682185
    申请日:1983-12-29
    公开日:1991-04-23
    发明作者:Шультце Ханс
    申请人:Нордмарк-Верке Гмбх (Фирма)；
    IPC主号:
    专利说明:

    The invention relates to medicine, in particular to methods for the preparation of drugs.
    The aim of the invention is to increase the yield of the target product with a higher activity.
    Example 1 100 kg of pork pancreas frozen at low temperature, passed through a wolf machine or through a cutting board, are mixed in a 250-liter reactor with a solution of 100 g calcium gluconate in 20 l water together with 200 g silicone anti-foam preparation. Depending on the free trypsin content
    in the glands, up to 1 kg of the prepared pancreatin dissolved in 5 liters of water is added as an aid to the start of the process. This amount of pancreatin is established by 37 ° hydrolysis test. For this purpose, 120 g of starting material is taken from the loaded batch. After adding 15 liters of 84% isopropyl alcohol, knead a solution of 1.3 kg of sodium bicarbonate in 20 liters of water. They are set to stand overnight, with the temperature increasing from about 2 to 12 ° C, the next morning being warmed to 20 ° C and stirring is continued at this temperature.
    sj
    Etank yu
    s
    A notion of the endolysis of an autolysis is recognized by a breakdown for precipitation. For this purpose, during the last autolysis period, first every half hour, then after 15 minutes, 10 g of suspension is taken, stirred for 1 minute with 5.4 ml of 84% isopropyl alcohol using a glass rod the solution is separated from the fibers adhering to the glass rod and kneaded in 20 ml of a 50% magnetically stirred mixer with a magnetic stirrer, 84% aqueous solution of isopropyl alcohol | After a minute, stop the stirrer and leave to precipitate. no pr approximately 3 minutes.
    If the sample is positive, autolysis (the presence of a more or less transparent layer 3 mm high after 1 min or 10 mm after 3 min) is completed.
    As an example, a series of deposition tests are reproduced, which are used as soon as the autolysate temperature reaches 20 ° C. "
    The deposition test data is given in Table. one.
    From this example, it can be seen that the most favorable point in time for termination of autolysis occurs in 3 hours. In order to be able to achieve comparable ratios when using unknown (for example, preserved for a shorter or longer time) preparations of the pork pancreas, ZU0 is being tested for hydrolysis. 120 g are taken from the pasty mass of glands mixed with calcium gluconate, mixed with 1.5 g sodium bicarbonate in 25 ml of water and stirred for 30 minutes at 37 ° C. With the breakdown of this accelerated autolysate, a precipitation test is performed. Free trypsin (in the form of pancreatin) in the following amounts is added to the bulk of the loaded material: less than 2 mm / 3 min - 7. mln. E, up to 12 mm / 1 min - 1 mln. greater free sedimentation rate is not added (1 million units of free trypsin is contained, for example, in 250 g of the pancreas, with 4000 units in I g). In this way, it is possible to standardize for practical production conditions raw materials of different origins.
    After determining the most favorable point in time, the autolysis of the loaded batch is completed by pumping 72.5 liters of 84% (regenerated) isopropyl alcohol. Stir for 1/2 hour, forming a clear solution containing insoluble fibers, which are separated by sieving. To do this, the contents of the reactor are lowered into an open boiler of 50 liters with a laid sieve having cells of about 5 mm. The boiler is equipped with a root stirrer. The drain pipe of the boiler, equipped with a sieve, is connected by means of a pump with a 500-liter container of polypropylene. 313 l of 84% isopropyl alcohol is loaded into this container, and a descent solution, passed through a Fiber sieve left in the sieve boiler, is now added with slow stirring for another 10 minutes, with the fibers becoming relatively dry. The weight of the fibers is 7-8 kg.
    Pancreatin is placed in a 500-liter tank as a coarse sediment for 1 hour in a volume of 80 liters (at 20 ° C; at 24 ° C for 1/2 hour. The sediment is drained and siphoned and sent for regeneration to distillation. on the bottom, mix with 63 liters of regenerated 84% isopropyl alcohol and leave overnight for additional precipitation. The next day, repeat the process, mix the bottom precipitate thus obtained with about 45 liters of 84% isopropyl alcohol, t „e. with so much more than necessary l preparation of pancreatin suspension in 84% strength vom isopropyl alcohol. The suspension was filtered on a 40 cm diameter Nooch-filter and sucked to good drying of
    The dense mass pressed on the filter is quickly ground in a cutting machine and spread on a metal sheet. Dried overnight at a heating temperature of up to 55 ° C under a vacuum of approximately 5 mbar
    The output of Pancreatin kg 11.6
    Amylase activity
    P1P E / mg93,6
    Lipase activity
    P1P E / mg90.3
    Protease activity,
    FiP E / Mr:
    5.6 5.6
    activated enterokinase without activating trypsin activity, FiP E / Mr:
     activated with high-kinase4,2
    without activating 4.1
    The activity of chymotrypsin, PR E / mg:
    enterokinase activated 23,3
    without activation 28.3
    Dry matter content
    dogma,% 98,7
    Fat content,% 0.4
    Bulk density, g / ml 0.65 Density, g / ml 0.76
    The number of microorganisms
    on 1 g200
    Larmakopisi C iA 17th edition (USP HUL) is undesirable.
    Examples 2-4. Proceed analogously to example 1, changing the conditions of the process (pH, isopropanol content, autolytic temperature or isopropanol content during interruption or temperature and isopropanol content during precipitation / washing). There is no difference in the yield of pancreatin, if the deposition test varies in each case within the range of 3 to 10 mm / min. | These conditions were tested for each example separately ,,
    The test results are shown in Table. 2 o
    Example 5. The procedure is the same as in Example 1, but without the addition of isopropanol, the end of autolysis is reached in 2.5 hours. Amylase activity is 83% with a load loss of 5% and lipase activity is 80% with a load loss of 15%.
    PRI me R 6. Proceed as in Example 1, adding 5 liters of propanol. At the same time, they reach the end of autolysis in 2.75 hours. Amylase activity is 88% with a load loss of about 5%, and lipase is 88% with a load loss of 10%.
    Example 7. Proceed as in Example 1, but 10 L of isopropanol is added. The end of autolysis is reached after 3 hours. Amylase activity is 93% (load loss 5%) and lipase 88% (load loss I%).
    j
    50
    0
    ,
    Q
    ,
    five
    II p and me 8 “If you proceed in the same way as in example 1 and raise the temperature to 25 ° C and then interrupt the reaction, the results achieved will be the same as at the temperature
    Examples 9 - 12 o Autolysis and precipitation of a mixture of enzymes from an aqueous autolysate are carried out as described in Example 1. To determine the effect of isopropyl alcohol concentration on the washing process, isopropyl alcohol of different concentrations is added to the samples of the pancreatin suspension. sediment resulting from siphoning from the outermost liquid layer; 1 liter of sediment corresponds to approximately 200 g of dry pancreatin. 1 liter of isopropyl alcohol is added to each sample. Different concentrations are obtained by diluting absolute isopropyl alcohol. The dense filter cake, obtained as described in Example 1 by double washing and suction with suction, is dried as described in Example 1, after which its activity and bulk density are determined. When using only 65% isopropyl alcohol, a slight decrease in activity is observed. Despite this, the quality of the resulting product is higher than the quality of the well-known products. The bulk density of the product decreases with increasing concentrations of isopropyl alcohol.
    The results are shown in Table. 3
    Data comparing the stability of amylase and lipase in pancreatin prepared according to the known and proposed methods are presented in Table 4.
    Table 4 shows that in Pancreatin, obtained by known methods, the loss during exercise increases significantly with increasing activity. As for pancreatin, produced by the proposed method, despite the significantly high enzyme activity, it differs at the load with the least loss.
    权利要求:
    Claims (1)
    [1]
    Invention Formula
    The method of obtaining pancreatin from the pancreas by conducting autolysis at room temperature,
    mixing with an organic solvent, removing the precipitate by filtration, washing it with an organic solvent and drying, characterized in that, in order to increase the yield of the desired product with higher activity, autolysis is carried out in a reactor at a pH of 6.5-8.5 and temperature (- 2) - (+ 30) C, while simultaneously analyzing a sample taken from the reactor for precipitation in 55-65% aqueous isopropyl alcohol and, as soon as the sample reaches the sedimentation rate of precipitated autoolysis 3-10 mm for 1-3 min, stop autolysis in the reactor by m adding isopropyl alcohol to a final concentration of 30-35%, then after filtration isopropyl alcohol is again added to the resulting solution to a concentration of 55-65% at 20-24 ° C, the resulting precipitate is washed with 75-95%
    isopropyl alcohol, and the drying is carried out in a nitrogen atmosphere at a pressure of 5 mbar.
    iTable1
    Test mm / min
    1030
    1030
    O-2
    O-2
    2015
    2015
    Example
    T 9 T 10 T 11 |
    65
    75
    Bulk weight
    g / 100 ml 5,3 5,6 5,5 5,6
    Table 2
    waiting
    Rinsing + + drying,
    Lh j
    С% С5Н7ОН
    30 30 10 10 15 15
    65 65 55 55 60 60
    Yield (amylase)
    88 85 91 89 94 91
    Table3
    12
    85
    95
    Table4
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    同族专利:
    公开号 | 公开日
    EP0115023A2|1984-08-08|
    UA5996A1|1994-12-29|
    ES8407516A1|1984-09-16|
    HU196435B|1988-11-28|
    DK605583D0|1983-12-29|
    YU252483A|1986-10-31|
    US4623624A|1986-11-18|
    MD411C2|1996-06-30|
    CA1208580A|1986-07-29|
    YU45584B|1992-07-20|
    ES528537A0|1984-09-16|
    EP0115023A3|1986-04-09|
    EP0115023B1|1988-07-27|
    PL245381A1|1984-10-22|
    DD212981A5|1984-08-29|
    PL141118B1|1987-06-30|
    BR8307280A|1984-08-07|
    DK173599B1|2001-04-23|
    DE3377506D1|1988-09-01|
    DK605583A|1984-07-01|
    AR232000A1|1985-04-30|
    引用文献:
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    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    DE19823248588|DE3248588A1|1982-12-30|1982-12-30|Process for obtaining pancreatin with high apparent density|
    DE19823248587|DE3248587A1|1982-12-30|1982-12-30|Process for obtaining pancreatin|
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