CN113773381A - Improved production method of human immunoglobulin - Google Patents
Improved production method of human immunoglobulin Download PDFInfo
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- CN113773381A CN113773381A CN202111137087.3A CN202111137087A CN113773381A CN 113773381 A CN113773381 A CN 113773381A CN 202111137087 A CN202111137087 A CN 202111137087A CN 113773381 A CN113773381 A CN 113773381A
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- C07—ORGANIC CHEMISTRY
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- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/06—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies from serum
- C07K16/065—Purification, fragmentation
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Abstract
The invention relates to an improved method for producing human immunoglobulin, dissolving the component II + III precipitate with water at low temperature, adjusting pH value, adding low temperature ethanol again, stirring, standing, adding diatomite, and ultrafiltering to obtain human immunoglobulin supernatant; dissolving the component II + III precipitate with water, sampling in the process of adding low-temperature ethanol, recording the addition amount of the low-temperature ethanol during sampling, filtering the sample, respectively drying the sample precipitate and the sample supernatant at low temperature and weighing, calculating the proportion of the protein of the sample supernatant in the weight of the sample, marking the protein proportion value of the sample supernatant of each sample on a standard relation curve, and comparing a sample line segment obtained by connecting the protein proportion values of any two sample supernatants with a standard line segment obtained by connecting standard points corresponding to the addition amount of the low-temperature ethanol on the standard relation curve. The invention samples and judges in the production process, so that the detection result is synchronous with the production, thereby being beneficial to improving the production efficiency and reducing the production cost.
Description
Technical Field
The invention relates to the technical field of human immunoglobulin production, in particular to an improved production method of human immunoglobulin.
Background
Human immunoglobulins are derived from human plasma, typically by processing fresh plasma or frozen plasma with a shelf life of no more than two years. The human immunoglobulin is mainly used for preventing measles and infectious hepatitis, is combined with antibiotics for use, can improve the curative effect on certain serious bacterial and viral infections, is processed by adopting a low-temperature ethanol protein separation method to prepare a component I, a component II, a component III, a component IV and a component V in sequence, and is derived from the component I and the component II + III, wherein the human immunoglobulin is mainly derived from the precipitation of the component II + III, the component II + III is redissolved, and then the low-temperature ethanol protein separation method is used for separating out the mixed protein precipitate, in order to ensure that the yield of the human immunoglobulin in the component II + III precipitate is as high as possible, the protein content of the separated supernatant is generally required to be detected, but the detection is lagged behind the production, because the protein content of the supernatant can be detected after the production of one batch is completed, the method can not adjust the production process parameters in real time according to the detection result, and can only detect the production process after the production is finished, so that a new method for producing the human immunoglobulin needs to be provided.
Disclosure of Invention
Aiming at the defects in the prior art, the invention aims to provide an improved method for producing human immunoglobulin, which is used for sampling and judging in the production process, so that the detection result is synchronous with the production, the production efficiency is improved, and the production cost is reduced.
The technical purpose of the invention is realized by the following technical scheme:
an improved method for producing human immunoglobulin comprises the following steps:
breaking a bag of raw plasma, conveying the raw plasma to a plasma melting tank, controlling the temperature of the plasma to be 0-4 ℃ after the plasma is melted, performing centrifugal separation and precipitation, and conveying the plasma after the precipitation is removed to a first reaction tank for extraction and separation;
after plasma enters a first reaction tank, stirring is started, buffer solution is dripped to adjust the pH value, low-temperature ethanol is added, the centrifugation is carried out after the ethanol is completely added, a component I precipitate and a component I supernatant are obtained through the centrifugation, the component I precipitate is used for preparing human fibrinogen, the component I supernatant enters a second reaction tank, the buffer solution is dripped to adjust the pH value of the component I supernatant, the low-temperature ethanol is added, then the stirring and the standing are carried out, the filter pressing is carried out, a component II + III precipitate and a component II + III supernatant are obtained after the filter pressing, the weight of the component II + III precipitate is recorded, and the component II + III precipitate is used for preparing human immunoglobulin;
dissolving the component II + III precipitate with water at low temperature, adding low-temperature sodium acetate solution, dropwise adding buffer solution to adjust pH value, adding low-temperature ethanol again, stirring in the process of adding low-temperature ethanol, continuously stirring after completely adding low-temperature ethanol, standing, adding diatomite for ultrafiltration to obtain human immunoglobulin supernatant, wherein in the process of adding low-temperature ethanol, sampling for multiple times, recording the addition amount of low-temperature ethanol during sampling, filtering the sample to obtain sample precipitate and sample supernatant, respectively drying and weighing the sample precipitate and sample supernatant at low temperature, recording the weight of the sample precipitate and sample supernatant protein to obtain the total weight of protein in the sample, calculating the proportion of the sample supernatant protein to the sample weight, namely the proportion of the sample supernatant protein, and marking the proportion value of the sample supernatant protein of each sample on a standard relation curve of the supernatant protein content and the low-temperature ethanol addition amount, comparing a sample line segment obtained by connecting the proportional values of the proteins of the supernatants of any two samples with a standard line segment obtained by connecting standard points corresponding to the addition amount of the low-temperature ethanol on a standard relation curve;
when the sample line segment is basically coincident with the standard line segment, the production is normal;
when the sample line segment is positioned above the standard line segment, the excessive protein separated from the component I supernatant is shown, and the parameters of the component I supernatant separation process need to be adjusted to reduce the protein separated from the component I supernatant;
when the sample line segment is positioned below the standard line segment, the protein separated from the component I supernatant is too little, and the parameters of the component I supernatant separation process need to be adjusted to increase the protein separated from the component I supernatant.
In one embodiment, the method for drawing the standard relation curve of the protein content of the supernatant liquid and the addition amount of the low-temperature ethanol comprises the following steps:
recording the weight of the component II + III precipitate produced each time in a production flow with multiple normal production and qualified product quality, dissolving the component II + III precipitate with water at low temperature, taking a standard sample once every liter of low-temperature ethanol is added, filtering the standard sample to obtain a standard sample precipitate and a standard sample supernatant, respectively drying and weighing the standard sample precipitate and the standard sample supernatant at low temperature, recording the weight of the standard sample precipitate and the standard sample supernatant protein to obtain the total weight of the protein in the standard sample, calculating the proportion of the standard sample supernatant protein to the standard sample weight, namely the standard sample supernatant protein proportion, connecting the standard sample supernatant protein proportion values to obtain multiple standard relation curves.
In one embodiment, the standard relation curve with the closest component II + III precipitate weight is selected according to the weight of the component II + III precipitate prepared in actual production, and the sample line segment obtained after sampling is compared with the standard line segment.
In one embodiment, the weight of the precipitate of components II + III is calculated by: and sampling the precipitates of the components II and III, recording the weight of the sample again after low-temperature evaporation to dryness, and calculating the liquid content of the sample so as to calculate the weight of the precipitates of the components II and III except the liquid.
In one embodiment, in the process of dissolving the component II + III precipitate with water at a low temperature, the temperature is maintained at 0-4 ℃, the stirring time is 2-4 hours, and the temperature of the added sodium acetate solution is controlled at 0-4 ℃; timing is started from the beginning of adding the sodium acetate solution, the time is controlled within 4-5 hours, the stirring time is controlled within 1-2 hours after the adding, the temperature is maintained at 0-4 ℃ when the buffer solution is dripped, the dripping time is controlled within 2-3 hours, and the pH value of the liquid is controlled within 5.15-5.25 after the buffer solution is completely dripped.
In one embodiment, after the component II + III precipitate is dissolved by water at low temperature, adding low-temperature ethanol with the temperature of-15 ℃ and the volume fraction of 95%, timing from the addition of the low-temperature ethanol, controlling the liquid adding time to be 3-5 hours, and after the low-temperature ethanol is completely added, reducing the final concentration of the low-temperature ethanol to-5-6 ℃; after the low-temperature ethanol is completely added, the pH value of the solution is 5.10-5.30.
In one embodiment, the raw material plasma is broken and then conveyed to a plasma melting tank, interlayer circulation is carried out on the plasma by using water at the temperature of 30-35 ℃ for plasma melting, the water circulation is stopped after the plasma is melted, the temperature of the plasma is controlled to be 0-4 ℃, centrifugal separation and precipitation are carried out, and the plasma after the precipitation is removed is conveyed to a first reaction tank for extraction and separation.
In one embodiment, after plasma enters a first reaction tank, stirring is started, the temperature of the plasma is controlled to be 0-1 ℃, a buffer solution with the pH value of 4.0 is dripped to adjust the pH value to be 6.80-7.00, low-temperature ethanol with the temperature of-15 ℃ and the volume fraction of 50% is added until the volume specific concentration of the ethanol is 8%, the flow rate of the added ethanol is 1.0-1.2 liters/minute, the temperature is controlled to be-1-3 ℃ after the ethanol is added, centrifugation is carried out after the ethanol is added, and the component I precipitate and the component I supernatant are obtained.
In one embodiment, the supernatant of the component I is taken and put into a second reaction tank, a buffer solution with the pH value of 4.0 is dripped to adjust the pH value of the supernatant of the component I to be 6.80-6.85, low-temperature ethanol with the temperature of-15 ℃ and the volume fraction of 95% is added until the volume specific concentration of the ethanol is 20%, the flow rate of the added ethanol is 1.0-1.2L/min, the temperature is controlled to be-4 to-6 ℃ after the ethanol is added, the pH value is 6.80-7.00 after the ethanol is added, the mixture is stirred and then kept stand, the mixture is stirred again, and then pressure filtration is carried out, and the precipitate of the component II + III and the supernatant of the component II + III are obtained after the pressure filtration.
In one embodiment, the supernatant of human immunoglobulin is diluted and pasteurized, the inactivated protein solution is sterilized and filtered by a 0.2-micron sterilizing filter element, the protein solution is filled as required, the filled product is transferred to a hatching room at 30-32 ℃ for incubation for 14 days, and the finished product is verified after the incubation.
In one example, 18g of diatomaceous earth per liter of the reaction solution was added to the human immunoglobulin supernatant during the preparation of the supernatant, and the mixture was subjected to pressure filtration.
In conclusion, the invention has the following beneficial effects:
the invention adopts the solution obtained by dissolving the component II + III precipitate to produce the human immunoglobulin, samples for many times in the process of adding the low-temperature ethanol, respectively dries and weighs the sample precipitate and the sample supernatant at low temperature, calculates the proportion of the protein of the sample supernatant in the weight of the sample, marks the protein proportion value of the sample supernatant of each sample on a standard relation curve, compares the sample line segment obtained by connecting the protein proportion values of any two sample supernatants with the standard line segment obtained by connecting the standard points corresponding to the low-temperature ethanol addition amount on the standard relation curve for judgment, and can adjust the process parameters of the subsequent separation of the supernatant of the component I according to the detection and judgment results because the sampling is synchronous with the production in the production process, the production efficiency is improved and the production cost is reduced.
Detailed Description
The present invention will be described in detail with reference to examples.
The invention provides an improved production method of human immunoglobulin, which comprises the following steps:
the method comprises the following steps of (1) breaking a bag of raw plasma, conveying the raw plasma to a plasma melting tank, performing interlayer circulation plasma melting by using water at the temperature of 30-35 ℃, stopping water circulation after the plasma is melted, controlling the temperature of the plasma to be 0-4 ℃, performing centrifugal separation and precipitation, and conveying the plasma after the precipitation is removed to a first reaction tank for extraction and separation;
after plasma enters a first reaction tank, stirring is started, the temperature of the plasma is controlled to be 0-1 ℃, a buffer solution with the pH value of 4.0 is dripped to adjust the pH value to be 6.80-7.00, low-temperature ethanol with the temperature of-15 ℃ and the volume fraction of 50% is added until the volume specific concentration of the ethanol is 8%, the flow rate of the added ethanol is 1.0-1.2L/min, the temperature is controlled to be-1-3 ℃ after the ethanol is added, centrifugation is carried out after the ethanol is added, and the component I precipitate and the component I supernatant are obtained through centrifugation;
taking the supernatant of the component I, adding a buffer solution with the pH value of 4.0 dropwise into a second reaction tank to adjust the pH value of the supernatant of the component I to be 6.80-6.85, adding low-temperature ethanol with the temperature of-15 ℃ and the volume fraction of 95% until the volume specific concentration of the ethanol is 20%, adding the ethanol at the flow rate of 1.0-1.2L/min, controlling the temperature to be-4-6 ℃ after the ethanol is added, keeping the pH value to be 6.80-7.00 after the ethanol is added, stirring, standing, starting stirring, then performing pressure filtration, obtaining a component II + III precipitate and a supernatant of a component II + III after the pressure filtration, recording the weight of the component II + III precipitate, and using the component II + III precipitate for preparing human immunoglobulin;
dissolving the component II + III precipitate with water at low temperature, adding a low-temperature sodium acetate solution, dropwise adding a buffer solution to adjust the pH value, adding low-temperature ethanol again, stirring in the process of adding the low-temperature ethanol, continuously stirring after completely adding the low-temperature ethanol, standing, and then adding diatomite for ultrafiltration to obtain human immunoglobulin supernatant;
wherein, in the process of dissolving the component II + III precipitate with water at low temperature, the temperature is maintained at 0-4 ℃, the stirring time is 2-4 hours, and the temperature of the added sodium acetate solution is controlled at 0-4 ℃; timing when the sodium acetate solution is added from the beginning, controlling the time within 4-5 hours, controlling the stirring time within 1-2 hours after the addition, maintaining the temperature at 0-4 ℃ when the buffer solution is dripped, controlling the dripping time within 2-3 hours, and controlling the pH value of the liquid within 5.15-5.25 after the buffer solution is completely dripped; adding low-temperature ethanol with the volume fraction of 95 percent at the temperature of minus 15 ℃, timing from the addition of the low-temperature ethanol, controlling the liquid adding time to be 3-5 hours, and reducing the temperature to minus 5-minus 6 ℃ after the low-temperature ethanol is completely added, wherein the final concentration of the low-temperature ethanol is 17 percent; after the low-temperature ethanol is completely added, the pH value of the solution is 5.10-5.30.
Wherein, after the component II + III precipitates are dissolved by water at low temperature, sampling for multiple times in the process of adding low-temperature ethanol, recording the addition amount of the low-temperature ethanol during sampling, filtering the sample to obtain a sample precipitate and a sample supernatant, respectively drying and weighing the sample precipitate and the sample supernatant at low temperature, recording the weight of the sample precipitate and the protein of the sample supernatant to obtain the total weight of the protein in the sample, calculating the proportion of the protein in the sample supernatant to the weight of the sample, namely the protein proportion of the sample supernatant, marking the protein proportion value of the sample supernatant of each sample on a standard relation curve of the protein content of the supernatant and the addition amount of the low-temperature ethanol, and comparing a sample segment obtained by connecting the protein proportion values of any two samples with a standard segment obtained by connecting standard points on the standard relation curve corresponding to the addition amount of the low-temperature ethanol;
when the sample line segment is basically coincident with the standard line segment, the production is normal;
when the sample line segment is positioned above the standard line segment, the situation that the protein is normally separated out in the solution formed by dissolving the component II + III precipitates indicates that the residual protein in the solution is still more, and the situation that the protein separated out from the component I supernatant is too much indicates that the parameters of the component I supernatant separation process need to be adjusted, so that the protein separated out from the component I supernatant is reduced;
when the sample line segment is positioned below the standard line segment, the situation that the protein is precipitated normally in the solution formed by dissolving the component II + III precipitates shows that the residual protein in the solution is less, the situation that the protein precipitated from the component I supernatant is too less, the parameters of the component I supernatant separation process need to be adjusted, and the protein precipitated from the component I supernatant is increased.
It will be appreciated that, during normal production, due to the well-established process, commercial plasma is used, and therefore the weight of the fraction ii + iii precipitate obtained is generally within a defined range, and the human immunoglobulin obtained is within a defined range, which is relevant to the particular production process, and therefore the present invention is a standard curve set formed by continuously accumulating the sampled data of normal production, which is then used in subsequent production.
In the invention, the method for drawing the standard relation curve of the protein content of the supernatant and the addition amount of the low-temperature ethanol comprises the following steps:
recording the weight of the component II + III precipitate produced each time in a production flow with multiple normal production and qualified product quality, dissolving the component II + III precipitate with water at low temperature, taking a standard sample once every liter of low-temperature ethanol is added, filtering the standard sample to obtain a standard sample precipitate and a standard sample supernatant, respectively drying and weighing the standard sample precipitate and the standard sample supernatant at low temperature, recording the weight of the standard sample precipitate and the standard sample supernatant protein to obtain the total weight of the protein in the standard sample, calculating the proportion of the standard sample supernatant protein to the standard sample weight, namely the standard sample supernatant protein proportion, connecting the standard sample supernatant protein proportion values to obtain multiple standard relation curves.
And further, selecting a standard relation curve with the closest component II + III precipitate weight according to the weight of the component II + III precipitate prepared in actual production, and comparing a sample line segment obtained after sampling with a standard line segment.
It can be understood that when the product is determined to be abnormal after the production is finished, the production is also normal, and a sample curve graph formed in the production is also used as a standard relation curve for subsequent production.
And further, diluting and pasteurizing the supernatant of the human immunoglobulin, sterilizing and filtering the inactivated protein liquid by using a 0.2-micrometer sterilizing filter element, filling according to requirements, transferring the filled product to a hatching room at 30-32 ℃, incubating for 14 days, and performing finished product verification after incubation.
Further, in the process of preparing the supernatant of human immunoglobulin, 18g of diatomaceous earth was added per liter of the reaction solution to carry out filter pressing.
The above description is only a preferred embodiment of the present invention, and the protection scope of the present invention is not limited to the above embodiments, and all technical solutions belonging to the idea of the present invention belong to the protection scope of the present invention. It should be noted that modifications and embellishments within the scope of the invention may occur to those skilled in the art without departing from the principle of the invention, and are considered to be within the scope of the invention.
Claims (10)
1. An improved production method of human immunoglobulin is characterized in that raw material plasma is conveyed to a plasma melting tank after being broken, the temperature of the plasma is controlled to be 0-4 ℃ after the plasma is melted, centrifugal separation and precipitation are carried out, and the plasma after the precipitation is removed is conveyed to a first reaction tank for extraction and separation;
after plasma enters a first reaction tank, stirring is started, buffer solution is dripped to adjust the pH value, low-temperature ethanol is added, the centrifugation is carried out after the ethanol is completely added, a component I precipitate and a component I supernatant are obtained through the centrifugation, the component I precipitate is used for preparing human fibrinogen, the component I supernatant enters a second reaction tank, the buffer solution is dripped to adjust the pH value of the component I supernatant, the low-temperature ethanol is added, then the stirring and the standing are carried out, the filter pressing is carried out, a component II + III precipitate and a component II + III supernatant are obtained after the filter pressing, the weight of the component II + III precipitate is recorded, and the component II + III precipitate is used for preparing human immunoglobulin;
dissolving the component II + III precipitate with water at low temperature, adding low-temperature sodium acetate solution, dropwise adding buffer solution to adjust pH value, adding low-temperature ethanol again, stirring in the process of adding low-temperature ethanol, continuously stirring after completely adding low-temperature ethanol, standing, adding diatomite for ultrafiltration to obtain human immunoglobulin supernatant, wherein in the process of adding low-temperature ethanol, sampling for multiple times, recording the addition amount of low-temperature ethanol during sampling, filtering the sample to obtain sample precipitate and sample supernatant, respectively drying and weighing the sample precipitate and sample supernatant at low temperature, recording the weight of the sample precipitate and sample supernatant protein to obtain the total weight of protein in the sample, calculating the proportion of the sample supernatant protein to the sample weight, namely the proportion of the sample supernatant protein, and marking the proportion value of the sample supernatant protein of each sample on a standard relation curve of the supernatant protein content and the low-temperature ethanol addition amount, comparing a sample line segment obtained by connecting the proportional values of the proteins of the supernatants of any two samples with a standard line segment obtained by connecting standard points corresponding to the addition amount of the low-temperature ethanol on a standard relation curve;
when the sample line segment is basically coincident with the standard line segment, the production is normal;
when the sample line segment is positioned above the standard line segment, the excessive protein separated from the component I supernatant is shown, and the parameters of the component I supernatant separation process need to be adjusted to reduce the protein separated from the component I supernatant;
when the sample line segment is positioned below the standard line segment, the protein separated from the component I supernatant is too little, and the parameters of the component I supernatant separation process need to be adjusted to increase the protein separated from the component I supernatant.
2. The method for producing human immunoglobulin of claim 1 wherein the standard curve of the supernatant protein content versus the amount of cold ethanol added is plotted by:
recording the weight of the component II + III precipitate produced each time in a production flow with multiple normal production and qualified product quality, dissolving the component II + III precipitate with water at low temperature, taking a standard sample once every liter of low-temperature ethanol is added, filtering the standard sample to obtain a standard sample precipitate and a standard sample supernatant, respectively drying and weighing the standard sample precipitate and the standard sample supernatant at low temperature, recording the weight of the standard sample precipitate and the standard sample supernatant protein to obtain the total weight of the protein in the standard sample, calculating the proportion of the standard sample supernatant protein to the standard sample weight, namely the standard sample supernatant protein proportion, connecting the standard sample supernatant protein proportion values to obtain multiple standard relation curves.
3. The method of claim 2, wherein the standard relationship curve having the closest weight of the precipitates of fractions II + III is selected based on the weight of the precipitates of fractions II + III actually produced, and the line segment of the sample obtained after sampling is compared with the standard line segment.
4. An improved method for the production of human immunoglobulins as claimed in any one of claims 1 to 3 in which the weight of the fraction II + III precipitate is calculated by: and sampling the precipitates of the components II and III, recording the weight of the sample again after low-temperature evaporation to dryness, and calculating the liquid content of the sample so as to calculate the weight of the precipitates of the components II and III except the liquid.
5. The improved process for producing human immunoglobulin according to claim 1, wherein the temperature of the precipitate of the fractions II + III is maintained at 0 to 4 ℃ during the low temperature dissolution with water, the stirring time is 2 to 4 hours, and the temperature of the solution of sodium acetate is controlled at 0 to 4 ℃; timing is started from the beginning of adding the sodium acetate solution, the time is controlled within 4-5 hours, the stirring time is controlled within 1-2 hours after the adding, the temperature is maintained at 0-4 ℃ when the buffer solution is dripped, the dripping time is controlled within 2-3 hours, and the pH value of the liquid is controlled within 5.15-5.25 after the buffer solution is completely dripped.
6. The improved process of claim 5, wherein the precipitate of fraction II + III is dissolved in water at low temperature, then low temperature ethanol with a volume fraction of 95% at-15 ℃ is added, the timing is started from the addition of the low temperature ethanol, the time for adding the solution is controlled to be 3-5 hours, after the low temperature ethanol is completely added, the final concentration of the low temperature ethanol is 17%, and the temperature is reduced to-5 to-6 ℃; after the low-temperature ethanol is completely added, the pH value of the solution is 5.10-5.30.
7. The improved human immunoglobulin production method of claim 1, wherein the raw plasma is broken and then transferred to a plasma melting tank, the plasma is melted by water at 30-35 ℃ in a sandwich circulation manner, the water circulation is stopped after the plasma is melted, the temperature of the plasma is controlled between 0-4 ℃, the plasma is centrifugally separated and precipitated, and the plasma after the precipitation is removed is transferred to the first reaction tank for extraction and separation.
8. The improved human immunoglobulin production method of claim 7, wherein after the plasma enters the first reaction tank, stirring is started, the temperature of the plasma is controlled to be between 0 and 1 ℃, a buffer solution with pH of 4.0 is dripped to adjust the pH value to be between 6.80 and 7.00, low-temperature ethanol with the temperature of-15 ℃ and the volume fraction of 50 percent is added until the volume specific concentration of the ethanol is 8 percent, the flow rate of the added ethanol is 1.0 to 1.2 liters/minute, the temperature is controlled to be between-1 and-3 ℃ after the ethanol is added, centrifugation is carried out after the ethanol is added, and the component I precipitate and the component I supernatant are obtained.
9. The improved human immunoglobulin production method of claim 8, wherein the supernatant of component I is taken out and put into a second reaction tank, a buffer solution with pH of 4.0 is dripped to adjust the pH of the supernatant of component I to be 6.80 to 6.85, low-temperature ethanol with-15 ℃ and volume fraction of 95% is added until the volume ratio concentration of the ethanol is 20%, the flow rate of the added ethanol is 1.0 to 1.2 liters/minute, the temperature is controlled to be-4 to-6 ℃ after the ethanol is added, the pH is 6.80 to 7.00 after the ethanol is added, the mixture is stirred and kept stand, the stirring is started again, then the pressure filtration is carried out, and the component ii + iii precipitate and the supernatant of component ii + iii are obtained after the pressure filtration.
10. The improved method for producing human immunoglobulin of claim 1, wherein the supernatant of human immunoglobulin is diluted and pasteurized, the inactivated protein solution is sterilized and filtered by a 0.2 μm sterilizing filter, filled as required, the filled product is transferred to a incubation room at 30-32 ℃ for incubation for 14 days, and the finished product is tested after incubation.
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Cited By (1)
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| CN116731162A (en) * | 2023-06-09 | 2023-09-12 | 广东丹霞生物制药有限公司 | Human immunoglobulin production process |
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| CN116731162B (en) * | 2023-06-09 | 2024-03-19 | 广东丹霞生物制药有限公司 | Human immunoglobulin production process |
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Application publication date: 20211210 |