CN112500471B - Method for preparing high-clarity iron protein succinate - Google Patents
Method for preparing high-clarity iron protein succinate Download PDFInfo
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- CN112500471B CN112500471B CN202011524216.XA CN202011524216A CN112500471B CN 112500471 B CN112500471 B CN 112500471B CN 202011524216 A CN202011524216 A CN 202011524216A CN 112500471 B CN112500471 B CN 112500471B
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
- C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
- C07K14/4732—Casein
Abstract
The invention relates to the technical field of medicine production, in particular to a method for preparing high-clarity iron protein succinate. The invention provides a method for preparing high-clarity iron protein succinate, which is characterized in that an adsorbent is added in the preparation stage of iron protein succinate for impurity removal, on one hand, insoluble matters are efficiently removed, and the clarity of an iron protein succinate product is effectively improved; on the other hand, the adsorbent is added in the preparation stage of the iron protein succinate, so that the processes of adsorbing impurities and preparing the iron protein succinate are simultaneously carried out, the time and the operation of removing the impurities after the preparation are finished are saved, the clarity of the iron protein succinate product can be ensured, and the requirements on the product are met.
Description
Technical Field
The invention relates to the technical field of medicine production, in particular to a method for preparing high-clarity iron protein succinate.
Background
Iron succinate (ISP for short) is a polypeptide protein iron-supplementing drug, is a product prepared by complexing casein with ferric trichloride after succinic anhydride acylation, is an organic iron compound, wherein iron in the solution is not free and is in a complex state, the solution is in a precipitation state when the pH value is less than 4, and is changed into a soluble substance again when the pH value is higher (pH 7.5-8.0). Iron proteinsuccinate is suitable for various symptoms, such as recessive or dominant iron deficiency anemia caused by insufficient iron intake or malabsorption, acute or chronic blood loss and infection of patients of various ages, anemia in pregnancy and lactation, etc.
The iron protein succinate material often contains some insolubles after synthesis, resulting in a decrease in its clarity. Insoluble matters are directly introduced from raw materials or introduced during the reaction of the preparation process, such as ferric hydroxide, ferrous succinate or fat impurities. The insoluble substances seriously affect the quality and safety of the raw material medicines, and the original insoluble substances directly cause the oral solution not to be clear.
For the refining of the iron protein succinate, the prior art generally adjusts the pH value for many times, then washes and precipitates, and then filters the crude product after alkali dissolution through a 1.2 micron ceramic membrane or a 0.8 micron filter membrane to improve the clarity, because the iron protein succinate solution has certain viscosity, the resistance is extremely high when the iron protein succinate solution passes through the 1.2 micron ceramic membrane or the 0.8 micron filter membrane, the filtration is difficult to carry out, the production operation consumes long time, the requirement on equipment is high, and the clarity of the filtrate is still worse than that of the original product although being improved to a certain extent.
Therefore, there is a need to develop a method for preparing high-clarity iron protein succinate.
Disclosure of Invention
The present invention is directed to solving, at least to some extent, one of the technical problems in the related art. Therefore, an object of the present invention is to provide a method for preparing high-clarity iron protein succinate, wherein an adsorbent is added in the preparation stage of iron protein succinate to remove impurities, so that insoluble matters are efficiently removed, and the clarity of the iron protein succinate product is effectively improved; on the other hand, the adsorbent is added in the preparation stage of the iron protein succinate, so that the processes of adsorbing impurities and preparing the iron protein succinate are simultaneously carried out, the time and the operation of removing the impurities after the preparation are finished are saved, the clarity of the iron protein succinate product can be ensured, and the requirements on the product are met.
To this end, one aspect of the present invention provides a method for preparing high-clarity iron protein succinate. According to the embodiment of the invention, the method comprises the step of adding an adsorbent to remove impurities in the preparation stage of the iron protein succinate, wherein the adsorbent adsorbs the impurities at the pH value of 7.0-8.0.
The existing method for improving the iron protein succinate generally filters the iron protein succinate after alkali dissolution through a 1.2 micron ceramic membrane or a 0.8 micron filter membrane, and because the iron protein succinate solution has certain viscosity, the resistance is extremely high when the iron protein succinate solution passes through the 1.2 micron ceramic membrane or the 0.8 micron filter membrane, the filtration is difficult to carry out, the requirement on equipment is high, and the clarity of the filtrate is improved to a certain extent but is still poorer than that of the original ground product. The inventor of the invention finds that in the preparation stage of the iron protein succinate bulk drug, impurities are removed through the adsorbent, so that materials influencing the clarity of a finished product are removed, the clarity of the finally obtained iron protein succinate can be improved, and the quality of a drug is ensured to the great extent. Particularly, impurities are adsorbed within the pH range of 7.0-8.0, and the obtained clarity is even better than that of the original research. The clarity of the ferric protein succinate obtained by the method is consistent with or even superior to that of the original product, and the related operation is simple and easy, thereby being convenient for industrialized production. In addition, the method provided by the invention has the advantages that the adsorbent is added in the preparation stage of the iron protein succinate, so that the processes of adsorbing impurities and preparing the iron protein succinate are simultaneously carried out, and the time and the operation for removing the impurities after the preparation are finished are saved.
When the adsorbent adsorbs impurities within the range of pH 7.0-8.0, the adsorption efficiency is high, and if the adsorption condition is not within the range, the adsorption of the adsorbent on materials influencing the clarity of a finished product can be influenced, so that the clarity of a finished product of the iron protein succinate is influenced.
According to an embodiment of the present invention, the method for preparing high-clarity iron-protein succinate further has the following additional technical features:
according to an embodiment of the invention, the adsorbent is selected from at least one of polyamide, polyurethane, alumina, polyacrylamide, zeolite molecular sieve.
According to a preferred embodiment of the invention, the adsorbent is selected from the group consisting of polyamide, polyacrylamide, zeolite molecular sieves.
According to an embodiment of the present invention, the preparation stage of the iron protein succinate includes a casein processing stage, an acylation reaction stage, and an iron loading stage.
According to an embodiment of the invention, the adsorbent adsorbs impurities in at least one of the casein treatment stage, acylation reaction stage and iron loading stage.
According to a preferred embodiment of the invention, the adsorbent adsorbs impurities during the casein treatment phase as well as during the acylation reaction phase.
According to another preferred embodiment of the invention, the adsorbent adsorbs impurities during the casein treatment phase as well as during the iron loading phase.
According to another preferred embodiment of the present invention, the adsorbent adsorbs impurities during the acylation reaction stage and the iron loading stage.
According to another preferred embodiment of the present invention, the adsorbent adsorbs impurities in the casein treating stage, the acylation reaction stage and the iron loading stage, respectively.
According to the embodiment of the invention, the addition amount of the adsorbent is 0.5-20 wt% of the content of reaction substrate casein in the casein treatment stage.
According to a preferred embodiment of the invention, the adsorbent is added in an amount of 2-15 wt% of the casein content of the reaction substrate in the casein treatment stage.
According to a further preferred embodiment of the invention, the adsorbent is added in an amount of 4 to 12wt% of the casein content of the reaction substrate in the casein treatment stage.
If the addition amount of the adsorbent is too small, for example, less than 4 wt% of the casein content of the reaction substrate, the adsorbent cannot completely adsorb materials affecting the clarity of the iron protein succinate finished product, the clarity of the finally obtained iron protein succinate product cannot be ensured, and if the addition amount of the adsorbent is too much, the cost is increased.
According to the embodiment of the invention, the concentration of the reaction substrate casein in the casein treatment stage is 10-15 wt%.
When the concentration of casein serving as a reaction substrate in a casein treatment stage is 10-15 wt%, the adsorption effect of the adsorbent can be further improved, and the effect of adsorbing impurities affecting the clarity of a product by the adsorbent can be influenced when the concentration of casein is too high or too low.
According to the embodiment of the invention, the adsorption temperature of the adsorbent for adsorbing the impurities is 20-80 ℃.
According to the preferred embodiment of the invention, the adsorption temperature of the adsorbent for adsorbing the impurities is 30-60 ℃.
According to a further preferred embodiment of the present invention, the adsorption temperature of the adsorbent for adsorbing the impurities is 40 to 50 ℃.
The adsorbent adsorbs impurities within the temperature range of 40-50 ℃, and the adsorption efficiency of the adsorbent can be further improved, so that the clarity of the finally obtained iron protein succinate is improved. If the temperature is lower than 20 ℃ or higher than 80 ℃, the adsorption efficiency of the adsorbent is affected.
According to the embodiment of the invention, the adsorption time of the adsorbent for adsorbing the impurities is 0.1-6 h.
According to the preferred embodiment of the invention, the adsorption time of the adsorbent for adsorbing the impurities is 1-5 h.
According to a further preferable embodiment of the invention, the adsorption time of the adsorbent for adsorbing the impurities is 1-3 h.
According to an embodiment of the invention, the method further comprises: and after the adsorbent adsorbs the impurities, removing the adsorbent.
Additional aspects and advantages of the invention will be set forth in part in the description which follows and, in part, will be obvious from the description, or may be learned by practice of the invention.
Detailed Description
The following describes embodiments of the present invention in detail. The following examples are illustrative only and are not to be construed as limiting the invention.
In some specific embodiments of the present invention, the preparation stage of the iron protein succinate provided by the present invention comprises:
1) casein treatment stage:
dispersing casein in purified water, heating and adding a sodium hydroxide solution to keep the pH value of a system to be 8-9, fully dissolving a crude product, then adjusting the pH value of the system back to 7.0-8.0 by using a dilute hydrochloric acid solution, filtering, adding a proper amount of adsorbent (the adding amount of the adsorbent is 0.5-20 wt% of the casein content of a reaction substrate, preferably 2-15 wt%, and further preferably 4-12 wt%) into the obtained filtrate, stirring at a proper temperature (the adsorption temperature is 20-80 ℃, preferably 30-60 ℃, and further preferably 40-50 ℃) for a proper time (0.1-6 hours, preferably 1-5 hours, and further preferably 1-3 hours), and filtering to remove the casein solution, wherein the obtained casein solution is the casein solution with greatly improved clarity;
2) and (3) acylation reaction stage:
heating the purified casein solution to 50-60 ℃, adding succinic anhydride in multiple batches, adding a sodium hydroxide solution to keep the pH of the system at 5-7, reacting for 1-2 hours, cooling to 5-15 ℃, adding a dilute hydrochloric acid solution to keep the pH of the system at 2.0-3.0 to precipitate a solid, adding the solid after centrifugation into a proper amount of purified water, pulping at room temperature for 1-3 hours, and centrifuging to obtain a wet succinylated casein product;
3) and (3) iron loading stage:
dispersing the wet succinyl casein in purified water, heating and adding a sodium hydroxide solution to keep the pH of a system 7-9 to fully dissolve the succinyl casein, filtering to remove a small amount of undissolved hard particles, cooling the filtrate, dropwise adding an aqueous solution of ferric chloride hexahydrate, dropwise adding the sodium hydroxide solution to keep the pH of the system 3-4 when the pH value is reduced to 3-4, reacting for 1-3 hours after dropwise adding is finished, centrifuging, and drying to obtain the ferric succinyl protein with greatly improved clarity, wherein the clarity of the ferric succinyl protein is consistent with that of an original ground product.
In other specific embodiments of the present invention, the preparation stage of the iron protein succinate provided by the present invention comprises:
1) casein treatment stage and acylation reaction stage:
dispersing casein in purified water, heating and adding a sodium hydroxide solution to keep the pH value of the system 8-9 to fully dissolve a crude product, then adding succinic anhydride in multiple batches, simultaneously adding the sodium hydroxide solution to keep the pH value of the system 5-7, reacting for 1-2 hours, cooling to 5-15 ℃, adding a dilute hydrochloric acid solution to keep the pH value of the system 2.0-3.0 to precipitate a solid, and centrifuging to obtain an acylated casein wet product;
2) purification of acylated casein and adsorption with adsorbent:
dispersing the acylated casein in purified water, heating and adding a sodium hydroxide solution to keep the pH value of a system 8-9 to be fully dissolved, adjusting the pH value of the system back to 7.0-8.0 by using a dilute hydrochloric acid solution, filtering, adding a proper amount of adsorbent (the adding amount of the adsorbent is 0.5-20 wt%, preferably 2-15 wt%, and further preferably 4-12 wt% of the casein content of a reaction substrate) into the obtained filtrate, stirring at a proper temperature (the adsorption temperature is 20-80 ℃, preferably 30-60 ℃, further preferably 40-50 ℃) for a proper time (0.1-6 hours, preferably 1-5 hours, and further preferably 1-3 hours), and filtering to remove the adsorbed casein, wherein the obtained acylated casein solution is the acylated casein solution with greatly improved clarity;
3) and (3) iron loading stage:
and (3) dropping the acylated casein solution after cooling, adding an aqueous solution of ferric trichloride hexahydrate dropwise, dropping a sodium hydroxide solution to keep the pH of the system at 3-4 when the pH value is reduced to 3-4, reacting for 1-3 hours after dropping, centrifuging, and drying to obtain the iron protein succinate with greatly improved clarity, wherein the clarity is consistent with that of the originally ground product.
The following describes embodiments of the present invention in detail. The following examples are illustrative only and are not to be construed as limiting the invention. The examples, where specific techniques or conditions are not indicated, are to be construed according to the techniques or conditions described in the literature in the art or according to the product specifications. The reagents or instruments used are not indicated by the manufacturer, and are all conventional products commercially available.
The original research used in the following examples is the marketed drug "phenanthroline".
Example 1:
dispersing 37.5g of casein in 250g of purified water, heating to 60 ℃, dropwise adding 8.5g of 4N sodium hydroxide solution to keep the pH of the system at 8.5 so as to fully dissolve the casein, then adjusting the pH of the system to 7.0 by using dilute hydrochloric acid solution, filtering, then adding 1.5g of polyacrylamide into the obtained filtrate, stirring at 44 ℃ for 1 hour, filtering to remove the polyacrylamide, adding 5.5g of succinic anhydride into the obtained filtrate in multiple batches, simultaneously dropwise adding 30.0g of 4N sodium hydroxide solution to keep the pH of the system at 6, after dropwise adding, carrying out heat preservation reaction for 1.5 hours, then cooling to 10 ℃, then dropwise adding 35.5g of 4N hydrochloric acid solution to keep the pH of the system at 2.5 so as to precipitate solids, after centrifugation, adding an appropriate amount of 250g of purified water into the obtained solids, pulping at room temperature for 2 hours, and then centrifuging to obtain 240g of a succinylated casein wet product.
Dispersing 240g of the wet succinylated casein in 500g of purified water, heating to 60 ℃, dropwise adding 41.5g of a 4N sodium hydroxide solution to maintain the pH of the system to be 8 so as to fully dissolve the succinylated casein, filtering to remove a small amount of undissolved hard particles, cooling the filtrate to 8 ℃, dropwise adding 310.17g of an aqueous solution of ferric trichloride hexahydrate (10.17g of ferric trichloride hexahydrate is dissolved in 300g of purified water), dropwise adding 20.0g of a 1N sodium hydroxide solution to maintain the pH of the system to be 3.5 when the pH value is reduced to 3.5, reacting for 2 hours after the dropwise addition is finished, centrifuging, drying to obtain 34.3g of a protein iron succinate solid, wherein the mass yield is as follows: 91.5 percent.
And (3) clarity detection result: and (4) passing.
Remarking: the clarity detection method is carried out according to the general rule of clarity inspection method in pharmacopoeia.
Example 2
Dispersing 1.50kg of casein in 10.00kg of purified water, heating to 60 ℃, dropwise adding 0.34kg of 4N sodium hydroxide solution to keep the pH value of the system at 8.5 so as to fully dissolve the casein, then adjusting the pH value of the system to 8.0 by using dilute hydrochloric acid solution, filtering, then adding 0.12kg of polyacrylamide into the obtained filtrate, stirring at 50 ℃ for 2.5h, filtering to remove the polyacrylamide, adding 0.22kg of succinic anhydride into the obtained filtrate in batches, dropwise adding 1.16kg of 4N sodium hydroxide solution to keep the pH value of the system at 6, after dropwise adding, carrying out heat preservation reaction for 1.5 h, then cooling to 10 ℃, then dropwise adding 1.36kg of 4N hydrochloric acid solution to keep the pH value of the system at 2.5 so as to precipitate solids, centrifuging, then adding a proper amount of the obtained solids into 16.00kg of purified water, pulping at room temperature for 2h, and centrifuging to obtain a 4.48kg of succinylated casein wet product.
Dispersing 4.48kg of the wet succinylated casein in 10.00kg of purified water, heating to 60 ℃, dropwise adding 0.79kg of 4N sodium hydroxide solution to keep the pH value of the system to be 8 so as to fully dissolve the succinylated casein, filtering to remove a small amount of undissolved hard particles, cooling the filtrate to 9 ℃, dropwise adding 12.338kg of an aqueous solution of ferric chloride hexahydrate (obtained by dissolving 0.338kg of ferric chloride hexahydrate in 12.00kg of purified water), dropwise adding 0.62kg of 1N sodium hydroxide solution to keep the pH value of the system to be 3.5 when the pH value is reduced to 3-4, reacting for 2 hours after the dropwise adding is finished, centrifuging, and drying to obtain 1.43kg of protein ferrous succinate solid, wherein the mass yield is as follows: 95.0 percent.
And (3) clarity detection result: and (4) passing.
Example 3
Dispersing 1.50kg of casein in 10.00kg of purified water, heating to 60 ℃, dropwise adding 0.34kg of 4N sodium hydroxide solution to keep the pH of the system at 8.5 to fully dissolve the casein, then adjusting the pH of the system to 7.5 by using dilute hydrochloric acid solution, filtering, then adding 0.12kg of polyamide into the obtained filtrate, stirring at 40 ℃ for 3.0h, filtering to remove the polyamide, adding 0.22kg of succinic anhydride into the obtained filtrate in batches, dropwise adding 1.16kg of 4N sodium hydroxide solution to keep the pH of the system at 6, keeping the temperature after the dropwise adding reaction for 1.5 h, cooling to 10 ℃, then dropwise adding 1.36kg of 4N hydrochloric acid solution to keep the pH of the system at 2.5 to precipitate solids, centrifuging, adding an appropriate amount of 16.00kg of purified water into the obtained solids, pulping at room temperature for 2h, and centrifuging to obtain a 4.60kg of succinylcasein wet product.
Dispersing 4.60kg of the wet succinylated casein in 10.00kg of purified water, heating to 60 ℃, dropwise adding 0.79kg of 4N sodium hydroxide solution to keep the pH of the system equal to 8 so as to fully dissolve the succinylated casein, filtering to remove a small amount of undissolved hard particles, cooling the filtrate to 9 ℃, dropwise adding 12.338kg of an aqueous solution of ferric chloride hexahydrate (0.338kg of ferric chloride hexahydrate is dissolved in 12.00kg of purified water), dropwise adding 0.62kg of 1N sodium hydroxide solution to keep the pH of the system equal to 3.5 when the pH value is reduced to 3.5, reacting for 2 hours after the dropwise adding is finished, centrifuging, and drying to obtain 1.45kg of protein ferrous succinate solid, wherein the mass yield is as follows: 96.6 percent.
And (3) clarity detection result: and (4) passing.
Example 4
Dispersing 1.50kg of casein in 10.00kg of purified water, heating to 60 ℃, dropwise adding 0.34kg of 4N sodium hydroxide solution to keep the system pH at 8.5 so as to fully dissolve the casein, adding 0.22kg of succinic anhydride in batches, dropwise adding 1.16kg of 4N sodium hydroxide solution to keep the system pH at 6, reacting for 1.5 hours after dropwise adding, cooling to 10 ℃, dropwise adding 1.36kg of 4N hydrochloric acid solution to keep the system pH at 2.5 so as to precipitate solid, adding an appropriate amount of 16.00kg of purified water after centrifugation, pulping for 2 hours at room temperature, and centrifuging to obtain 4.48kg of succinylated casein wet product.
Dispersing 4.48kg of the wet succinylated casein in 10.00kg of purified water, heating to 60 ℃, dropwise adding 0.79kg of 4N sodium hydroxide solution to keep the pH value of the system at 8 so as to fully dissolve the succinylated casein, then adjusting the pH value of the system to 7.7 by using dilute hydrochloric acid solution, filtering, then adding 0.06kg of polyacrylamide into the obtained filtrate, stirring at 50 ℃ for 2.5h, filtering to remove the polyacrylamide, cooling the filtrate to 9 ℃, then dropwise adding 12.338kg of an aqueous solution of ferric chloride hexahydrate (obtained by dissolving 0.338kg of ferric chloride hexahydrate in 12.00kg of purified water), dropwise adding 0.62kg of 1N sodium hydroxide solution when the pH value is reduced to 3.5 so as to keep the pH value of the system at 3.5, reacting for 2 hours after dropwise adding, centrifuging, drying to obtain 1.39kg of a protein ferrous succinate solid, wherein the mass yield is as follows: 92.3 percent.
And (3) clarity detection result: and (5) passing the test result.
Example 5
Dispersing 1.50kg of casein in 10.00kg of purified water, heating to 60 ℃, dropwise adding 0.34kg of 4N sodium hydroxide solution to keep the system pH value at 8.5 so as to fully dissolve the casein, adding 0.22kg of succinic anhydride in batches, dropwise adding 1.16kg of 4N sodium hydroxide solution to keep the system pH value at 6, reacting at the same time for 1.5 hours after dropwise adding, cooling to 10 ℃, dropwise adding 1.36kg of 4N hydrochloric acid solution to keep the system pH value at 2.5 so as to precipitate solid, adding the obtained solid into a proper amount of 16.00kg of purified water after centrifugation, pulping at room temperature for 2 hours, and centrifuging to obtain 4.60kg of succinylated casein wet product.
Dispersing 4.60kg of the wet succinylated casein in 10.00kg of purified water, heating to 60 ℃, dropwise adding 0.79kg of 4N sodium hydroxide solution to keep the pH value of the system at 8 to fully dissolve the succinylated casein, then adjusting the pH value of the system to 8.0 by using dilute hydrochloric acid solution, filtering, then adding 0.12kg of polyacrylamide into the obtained filtrate, stirring at 40 ℃ for 3.0h, filtering to remove the polyacrylamide, cooling the filtrate to 9 ℃, then dropwise adding 12.338kg of an aqueous solution of ferric chloride hexahydrate (obtained by dissolving 0.338kg of ferric chloride hexahydrate in 12.00kg of purified water), when the pH value is reduced to 3.5, simultaneously dropwise adding 0.62kg of 1N sodium hydroxide solution to keep the pH value of the system at 3.5, reacting for 2 hours after dropwise adding, centrifuging, drying to obtain 1.40kg of a protein ferrous succinate solid, wherein the mass yield is as follows: 93.3 percent.
And (3) clarity detection result: and (4) passing.
Example 6
Dispersing 1.00kg of casein in 6.67kg of purified water, heating to 60 ℃, dropwise adding 0.23kg of 4N sodium hydroxide solution to keep the pH of the system equal to 8.5 to fully dissolve the casein, then adjusting the pH of the system back to 7.2 by using dilute hydrochloric acid solution, filtering, then adding 0.12kg of zeolite molecular sieve into the obtained filtrate, stirring for 2 hours at 45 ℃, filtering to remove the zeolite molecular sieve, adding 0.15kg of succinic anhydride into the obtained filtrate in multiple batches, simultaneously dropwise adding 0.80kg of 4N sodium hydroxide solution to keep the pH of the system equal to 6, after dropwise adding, carrying out heat preservation reaction for 1.5 hours, cooling to 8 ℃, then dropwise adding 0.94kg of 4N hydrochloric acid solution to keep the pH of the system equal to 2.5 to precipitate solids, centrifuging, then adding a proper amount of the obtained solids into 8.00kg of purified water, pulping at room temperature for 2 hours, and centrifuging to obtain 2.26kg of succinylated casein wet product.
Dispersing 2.26kg of the wet succinylated casein in 6.67kg of purified water, heating to 60 ℃, dropwise adding 0.57kg of 4N sodium hydroxide solution to keep the pH of the system equal to 8 so as to fully dissolve the succinylated casein, filtering to remove a small amount of undissolved hard particles, cooling the filtrate to 9 ℃, dropwise adding 8.24kg of an aqueous solution of ferric trichloride hexahydrate (0.24kg of ferric trichloride hexahydrate is dissolved in 8.00kg of purified water), dropwise adding 0.48kg of 1N sodium hydroxide solution to keep the pH of the system equal to 3.5 when the pH value is reduced to 3.5, reacting for 2 hours after dropwise adding, centrifuging, drying to obtain 0.93kg of protein ferrous succinate solid, wherein the mass yield is as follows: 93.0 percent.
And (3) clarity detection result: and (4) passing.
Example 7
Dispersing 1.00kg of casein in 6.67kg of purified water, heating to 60 ℃, dropwise adding 0.23kg of 4N sodium hydroxide solution to keep the pH of the system equal to 8.5 to fully dissolve the casein, then adjusting the pH of the system to 7.2 by using dilute hydrochloric acid solution, filtering, then adding 0.12kg of polyacrylamide into the obtained filtrate, stirring at 45 ℃ for 2h, filtering, removing, adding 0.15kg of succinic anhydride into the obtained filtrate in multiple batches, simultaneously dropwise adding 0.80kg of 4N sodium hydroxide solution to keep the pH of the system equal to 6, after dropwise adding, carrying out heat preservation reaction for 1.5 h, cooling to 8 ℃, then dropwise adding 0.94kg of 4N hydrochloric acid solution to keep the pH of the system equal to 2.5 to precipitate solids, after centrifugation, adding an appropriate amount of 8.00kg of purified water into the obtained solids, pulping at room temperature for 2h, and then centrifuging to obtain 2.26kg of a succinylated casein wet product.
Dispersing 2.26kg of the wet succinylated casein in 6.67kg of purified water, heating to 60 ℃, dropwise adding 0.57kg of 4N sodium hydroxide solution to keep the pH value of the system equal to 8 so as to fully dissolve the succinylated casein, then adjusting the pH value of the system back to 7.6 by using dilute hydrochloric acid solution, filtering, then adding 0.08kg of polyacrylamide into the obtained filtrate, stirring at 50 ℃ for 2 hours, filtering to remove the polyacrylamide, then cooling the filtrate to 7 ℃, dropwise adding 8.24kg of an aqueous solution of ferric trichloride hexahydrate (obtained by dissolving 0.24kg of ferric trichloride hexahydrate in 8.00kg of purified water), dropwise adding 0.48kg of 1N sodium hydroxide solution when the pH value is reduced to 3-4 so as to keep the pH value of the system equal to 3.5, reacting for 2 hours after dropwise adding, centrifuging, drying to obtain 0.85kg of protein ferric succinate solid, wherein the mass yield is as follows: 85.0 percent.
And (3) clarity detection result: and (4) passing.
EXAMPLE 8 Effect of pH on the decontamination of Polyacrylamide
When the pH of the system was adjusted back by using the dilute hydrochloric acid solution, different pH gradients, specifically 6.7, 7.0, 7.5, 8.0, and 8.3, were set, and the clarity of the obtained iron protein succinate is as shown in table 1 below:
TABLE 1
| Sample numbering | pH | Clarity of the product |
| 1 | 6.7 | Slightly worse than the original one |
| 2 | 7.0 | Is superior to the original research |
| 3 | 7.5 | Consistent with the original research |
| 4 | 8.0 | Consistent with the original research |
| 5 | 8.3 | Slightly worse than the original grinding |
The results show that when the adsorbent adsorbs impurities at a pH of 7.0-8.0, the clarity of the obtained iron protein succinate is consistent with that of the original grinding, and that at a pH of 7.0, the clarity is even better than that of the original grinding.
EXAMPLE 9 Effect of temperature on the decontamination Effect of Polyacrylamide
Iron protein succinate was prepared by the same method as in example 1, except that different adsorbents were provided to adsorb impurities at temperature gradients of 35 ℃, 40 ℃, 45 ℃ and 50 ℃, respectively, and the clarity of the obtained iron protein succinate was as follows in table 2:
TABLE 2
| Finished product number | Clarity of the product | Temperature of |
| 1 | Slightly worse than the original one | 35℃ |
| 2 | In accordance with the original research | 40℃ |
| 3 | Is superior to the original product | 45℃ |
| 3 | In accordance with the original research | 50℃ |
The results show that when the adsorbent adsorbs impurities within the temperature range of 40-50 ℃, the clarity of the obtained iron protein succinate is consistent with that of the original research, and at 45 ℃, the clarity is even superior to that of the original research.
EXAMPLE 10 Effect of the amount of adsorbent used on the removal of impurities from Polyacrylamide
Iron protein succinate was prepared by the same method as in example 1, with different adsorbent dosage gradients set, with adsorbent dosages of 12%, 8%, 4%, 0% of reaction substrate casein, and the clarity of the obtained iron protein succinate is shown in table 3 below:
TABLE 3
The results in Table 3 show that when the addition amount of the adsorbent is 4-12 wt% of the casein content of the reaction substrate, the clarity of the obtained iron protein succinate is consistent with that of the original research.
EXAMPLE 11 Effect of adsorption time on the decontamination of Polyacrylamide
The ferric protein succinate prepared by the same method as in example 6, with different adsorption times set at 0.5h, 1h and 3h, respectively, had the clarity as shown in table 4 below:
TABLE 4
| Finished product numbering | Time | Clarity of the product |
| 1 | 0.5h | Slightly worse than the original one |
| 2 | 1h | Consistent with the original research |
| 3 | 3h | Consistent with the original research |
The results in table 4 show that when the adsorbent adsorbs impurities for 1h to 3h, the clarity of the obtained iron protein succinate is consistent with that of the original research. And if the time is less than 1h, the clarity of the obtained iron protein succinate can not reach the standard.
In the description herein, references to the description of the term "one embodiment," "some embodiments," "an example," "a specific example," or "some examples," etc., mean that a particular feature, structure, material, or characteristic described in connection with the embodiment or example is included in at least one embodiment or example of the invention. In this specification, the schematic representations of the terms used above are not necessarily intended to refer to the same embodiment or example. Furthermore, the particular features, structures, materials, or characteristics described may be combined in any suitable manner in any one or more embodiments or examples. Furthermore, various embodiments or examples and features of different embodiments or examples described in this specification can be combined and combined by one skilled in the art without contradiction.
Although embodiments of the present invention have been shown and described above, it will be understood that the above embodiments are exemplary and not to be construed as limiting the present invention, and that changes, modifications, substitutions and alterations can be made to the above embodiments by those of ordinary skill in the art within the scope of the present invention.
Claims (9)
1. A method for preparing high-clarity iron protein succinate is characterized by comprising the steps of adding an adsorbent to remove impurities in the preparation stage of iron protein succinate, adsorbing the impurities by the adsorbent within the pH range of = 7.0-8.0,
the preparation stage of the iron protein succinate comprises a casein processing stage, an acylation reaction stage and an iron loading stage, and the casein processing stage utilizes an adsorbent to adsorb,
alternatively, the first and second electrodes may be,
the preparation stage of the iron protein succinate comprises a casein processing stage, an acylation reaction stage, a purified acylated casein and adsorbent adsorption stage and an iron loading stage, wherein the purified acylated casein and the adsorbent adsorption stage are adsorbed by an adsorbent,
the addition amount of the adsorbent is 4-12 wt% of the casein content of the reaction substrate in the casein treatment stage,
the adsorbent is selected from at least one of polyamide, polyacrylamide and zeolite molecular sieve.
2. The method according to claim 1, wherein the concentration of reaction substrate casein in the casein treatment stage is 10-15 wt%.
3. The method according to claim 1, wherein the adsorbent adsorbs the impurities at an adsorption temperature of 20 to 80 ℃.
4. The method according to claim 1, wherein the adsorbent adsorbs the impurities at an adsorption temperature of 30 to 60 ℃.
5. The method according to claim 1, wherein the adsorbent adsorbs the impurities at an adsorption temperature of 40 to 50 ℃.
6. The method according to claim 1, wherein the adsorbent adsorbs the impurities for 0.1-6 h.
7. The method according to claim 1, wherein the adsorbent adsorbs the impurities for 1-5 h.
8. The method according to claim 1, wherein the adsorbent adsorbs the impurities for 1-3 h.
9. The method of claim 1, further comprising: and after the adsorbent adsorbs the impurities, removing the adsorbent.
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| FR2810667B1 (en) * | 2000-06-23 | 2004-09-03 | Warner Lambert Co | PROCESS FOR ISOLATING AND PURIFYING PROTEIN, AND PROTEIN OBTAINED |
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| CN108794616A (en) * | 2018-07-03 | 2018-11-13 | 湖北华世通生物医药科技有限公司 | Iron protein succinylate crude product refining method |
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