CN112500471B - A kind of method for preparing high-clarity iron protein succinate - Google Patents

Abstract

The invention relates to the technical field of pharmaceutical production, in particular to a method for preparing high-clarity iron protein succinate. The invention provides a method for preparing high-clarity ferric protein succinate. By adding an adsorbent to remove impurities in the preparation stage of ferric protein succinate, on the one hand, insoluble matter is efficiently removed, and the clarity of ferric protein succinate products is effectively improved; On the other hand, adding an adsorbent in the preparation stage of ferric protein succinate makes the adsorption of impurities and the preparation process of ferric protein succinate to be carried out at the same time, which saves the time and operation of removing impurities after the preparation is completed, and can ensure that ferric protein succinate is The clarity of the product makes it meet the requirements for the product.

Description

A kind of method for preparing high-clarity iron protein succinate

technical field

The present invention relates to the technical field of pharmaceutical production, in particular to a method for preparing high-clarity iron protein succinate.

Background technique

Iron-protein succinylate (ISP) is a polypeptide protein iron supplementation drug, which is a product obtained by complexing casein with ferric chloride after acylation of succinic anhydride. It is an organic iron compound. , the iron in the solution is not free, it is a complex state, the solution is in a precipitation state when the pH value is less than 4, and becomes a soluble substance again when the pH value is higher (pH 7.5 ~ 8.0). Iron protein succinate is indicated for a variety of conditions such as latent or dominant iron deficiency anemia due to insufficient intake or malabsorption of iron, acute or chronic blood loss, and infections in patients of all ages, anemia during pregnancy and lactation Wait.

Ferric protein succinate raw materials often contain some insoluble matter after synthesis, which leads to a decrease in its clarity. Insoluble matter is directly introduced from the raw materials or introduced during the reaction of the preparation process, such as iron hydroxide, ferrous succinate or aliphatic impurities. These insoluble substances will seriously affect the quality and safety of the API, because the original insoluble substances will directly lead to the unclear oral solution.

For the purification of ferric protein succinate, the prior art is generally to adjust the pH for many times and then wash the precipitation, and then filter the crude product after alkali dissolution through a 1.2-micron ceramic membrane or a 0.8-micron filter membrane to improve the clarity. It has a certain viscosity, which causes great resistance when it passes through a 1.2-micron ceramic membrane or a 0.8-micron filter membrane, making filtration difficult, time-consuming production operations, and high equipment requirements. Poor product.

Therefore, there is an urgent need to develop a method for preparing high-clarity iron protein succinate.

SUMMARY OF THE INVENTION

The present invention aims to solve one of the technical problems in the related art at least to a certain extent. For this reason, an object of the present invention is to provide a method for preparing high-clarity iron protein succinate, by adding an adsorbent to remove impurities in the preparation stage of iron protein succinate, on the one hand, insoluble matter is efficiently removed, and the protein succinate is effectively improved. Clarity of ferric acid products; on the other hand, adding an adsorbent in the preparation stage of ferric protein succinate, so that the adsorption of impurities and the preparation process of ferric protein succinate are carried out at the same time, eliminating the time and operation of removing impurities after the preparation is completed, And it can ensure the clarity of iron protein succinate products, so as to meet the requirements of the product.

To this end, one aspect of the present invention provides a method for preparing high-clarity iron protein succinate. According to an embodiment of the present invention, the method includes adding an adsorbent to remove impurities in the preparation stage of iron protein succinate, and the adsorbent adsorbs impurities in the range of pH=7.0-8.0.

The existing method for improving ferric protein succinate is generally to filter the alkali-dissolved ferric protein succinate through a 1.2-micron ceramic membrane or a 0.8-micron filter membrane. Because the ferric protein succinate solution has a certain viscosity, it passes through a 1.2-micron ceramic membrane or a 0.8-micron filter membrane. The resistance of the 0.8 micron filter membrane is extremely large, the filtration is difficult to carry out, and the equipment requirements are also high, and although the clarity of the filtrate has been improved to a certain extent, it is still worse than the original research product. The inventors of the present invention have found that removing impurities by adsorbents in the preparation stage of the ferric protein succinate bulk drug will remove the materials that affect the clarity of the finished product, which can improve the clarity of the finally obtained ferric protein succinate, and to a great extent Ensure the quality of medicines. Especially in the range of pH=7.0～8.0, the impurity is adsorbed, and the obtained clarity is even better than the original one. The clarity of the iron protein succinate obtained by the method provided by the invention is the same as or even better than that of the original research product, and the involved operations are simple and easy to implement, which is convenient for industrial production. In addition, in the method provided by the present invention, by adding an adsorbent in the preparation stage of iron protein succinate, the adsorption of impurities and the preparation process of iron protein succinate are carried out at the same time, and the time and operation of removing impurities after preparation is omitted.

When the adsorbent adsorbs impurities in the range of pH=7.0-8.0, the adsorption efficiency is high. If the adsorption conditions are not in this range, the adsorbent will affect the adsorption of materials that affect the clarity of the finished product, thereby affecting the iron protein succinate. The clarity of the finished product.

According to an embodiment of the present invention, the method for preparing high-clarity iron protein succinate also has the following additional technical features:

According to an embodiment of the present invention, the adsorbent is selected from at least one of polyamide, polyurethane, alumina, polyacrylamide, and zeolite molecular sieve.

According to a preferred embodiment of the present invention, the adsorbent is selected from polyamide, polyacrylamide, and zeolite molecular sieve.

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 present invention, the adsorbent adsorbs impurities in at least one of the casein processing stage, the acylation reaction stage and the iron loading stage.

According to a preferred embodiment of the present invention, the adsorbent adsorbs impurities in the casein processing stage and the acylation reaction stage.

According to another preferred embodiment of the present invention, the adsorbent adsorbs impurities in the casein processing stage and the iron loading stage.

According to another preferred embodiment of the present invention, the adsorbent adsorbs impurities in the acylation reaction stage and the iron loading stage.

According to another preferred embodiment of the present invention, the adsorbent adsorbs impurities respectively in the casein processing stage, the acylation reaction stage and the iron loading stage.

According to an embodiment of the present invention, the addition amount of the adsorbent is 0.5-20 wt % of the casein content of the reaction substrate in the casein processing stage.

According to a preferred embodiment of the present invention, the added amount of the adsorbent is 2-15 wt % of the casein content of the reaction substrate in the casein processing stage.

According to a further preferred embodiment of the present invention, the addition amount of the adsorbent is 4-12 wt % of the casein content of the reaction substrate in the casein processing stage.

The added amount of the adsorbent is too small, for example, lower than 4wt% of the casein content of the reaction substrate, so that the adsorbent cannot completely adsorb the materials that affect the clarity of the finished iron protein succinate, and the final obtained iron protein succinate cannot be guaranteed. Product clarity, if too much adsorbent adds to the cost.

According to an embodiment of the present invention, the concentration of the reaction substrate casein in the casein processing stage is 10-15 wt %.

When the concentration of the reaction substrate casein in the casein treatment stage is 10-15 wt%, the adsorption effect of the adsorbent can be further improved. If the concentration of casein is too high or too low, it will affect the adsorption of the adsorbent and affect the clarity of the product. effect of impurities.

According to an embodiment of the present invention, when the adsorbent adsorbs impurities, the adsorption temperature is 20-80°C.

According to a preferred embodiment of the present invention, when the adsorbent adsorbs impurities, the adsorption temperature is 30-60°C.

According to a further preferred embodiment of the present invention, when the adsorbent adsorbs impurities, the adsorption temperature is 40-50°C.

The adsorbent adsorbs impurities in the temperature range of 40-50° C., which can further improve the adsorption efficiency of the adsorbent, thereby improving the clarity of the finally obtained iron protein succinate. If the temperature is lower than 20°C or higher than 80°C, the adsorption efficiency of the adsorbent will be affected.

According to the embodiment of the present invention, when the adsorbent adsorbs impurities, the adsorption time is 0.1-6 h.

According to a preferred embodiment of the present invention, when the adsorbent adsorbs impurities, the adsorption time is 1-5 hours.

According to a further preferred embodiment of the present invention, when the adsorbent adsorbs impurities, the adsorption time is 1-3 hours.

According to an embodiment of the present invention, the method further includes: removing the adsorbent after the adsorption of the impurities by the adsorbent is completed.

Additional aspects and advantages of the present invention will be set forth, in part, from the following description, and in part will be apparent from the following description, or may be learned by practice of the invention.

Detailed ways

Embodiments of the present invention are described in detail below. The embodiments described below are exemplary, only for explaining the present invention, and should not be construed as limiting the present invention.

In some specific embodiments of the present invention, the preparation stage of ferric protein succinate provided by the present invention includes:

1) Process casein stage:

Disperse the casein in purified water, keep the pH of the system at 8-9 by heating up and adding sodium hydroxide solution to fully dissolve the crude product, then adjust the pH of the system to 7.0-8.0 by dilute hydrochloric acid solution and filter, and then add an appropriate amount to the obtained filtrate. The adsorbent (the amount of adsorbent added is 0.5-20wt% of the casein content of the reaction substrate, preferably 2-15wt%, more preferably 4-12wt%) at a suitable temperature (the adsorption temperature is 20-80 ℃, preferably 30-60 ℃ , more preferably at 40-50°C), stir for a suitable long time (0.1-6h, preferably 1-5h, more preferably 1-3h), then filter and remove, and the obtained casein solution is the casein solution with greatly improved clarity;

2) Acylation reaction stage:

After the above-mentioned purified casein solution is heated to 50-60° C., succinic anhydride is added in multiple batches and sodium hydroxide solution is added to maintain the pH of the system at 5-7, and the temperature is lowered to 5-15° C. after 1-2 hours of reaction. Add dilute hydrochloric acid solution to keep the pH of the system at 2.0 to 3.0 to separate out solids. After centrifugation, the obtained solids are added to an appropriate amount of purified water for beating at room temperature for 1 to 3 hours and centrifuged to obtain succinyl casein wet products;

3) Iron-carrying stage:

Disperse the succinyl casein wet product in purified water, and fully dissolve the succinyl casein by raising the temperature and adding sodium hydroxide solution to keep the pH of the system at 7-9. Then filter to remove a small amount of undissolved hard particles. Add the aqueous solution of ferric trichloride hexahydrate, when the pH value drops to 3-4, dropwise add sodium hydroxide solution to keep the pH of the system at 3-4, react for 1-3 hours after the dropwise addition, centrifuge, and dry to obtain a very clear solution. Greatly improved iron protein succinate with the same clarity as the original product.

In other specific embodiments of the present invention, the preparation stage of ferric protein succinate provided by the present invention includes:

1) Process casein stage and acylation reaction stage:

The casein is dispersed in purified water, the crude product is fully dissolved by heating up and adding sodium hydroxide solution to keep the pH of the system at 8-9, then adding succinic anhydride in batches, and adding sodium hydroxide solution to keep the pH of the system at 5-7, reaction 1 After ~2 hours, the temperature is lowered to 5 ~ 15 ℃, and a dilute hydrochloric acid solution is added to keep the pH of the system at 2.0 ~ 3.0 to separate out solids, and centrifugation to obtain acylated casein wet product;

2) Purification of acylated casein and adsorbent adsorption:

Disperse the above acylated casein in purified water, keep the pH of the system at 8-9 by heating up and add sodium hydroxide solution to make it fully dissolved, then adjust the pH of the system to 7.0-8.0 by dilute hydrochloric acid solution, filter, and then add in the obtained filtrate. Add an appropriate amount of adsorbent (the amount of adsorbent added is 0.5-20wt% of the casein content of the reaction substrate, preferably 2-15wt%, more preferably 4-12wt%) at a suitable temperature (the adsorption temperature is 20-80 ℃, preferably 30- 60°C, more preferably 40-50°C), stir for an appropriate time (0.1-6h, preferably 1-5h, more preferably 1-3h), then filter and remove, and the obtained acylated casein solution has greatly improved clarity. Acylated casein solution;

3) Iron-carrying stage:

After cooling the above-mentioned acylated casein solution, add dropwise an aqueous solution of ferric chloride hexahydrate, when the pH value drops to 3～4, dropwise add sodium hydroxide solution to keep the pH of the system at 3～4, and react 1～3 after the dropwise addition hours, centrifugation and drying to obtain iron protein succinate with greatly improved clarity, the clarity of which is consistent with the original product.

Embodiments of the present invention are described in detail below. The embodiments described below are exemplary, only for explaining the present invention, and should not be construed as limiting the present invention. If no specific technique or condition is indicated in the examples, the technique or condition described in the literature in the field or the product specification is used. The reagents or instruments used without the manufacturer's indication are conventional products that can be obtained from the market.

The original research used in the following examples is a commercially available drug "Fipril".

Example 1:

Disperse 37.5g of casein in 250g of purified water, warm up to 60°C, add 8.5g of 4N sodium hydroxide solution dropwise to keep the pH of the system at 8.5 to fully dissolve the casein, and then adjust the pH of the system to 7.0 by dilute hydrochloric acid solution and filter, Then, 1.5 g of polyacrylamide was added to the obtained filtrate, stirred at 44° C. for 1 hour, and then filtered to remove the polyacrylamide. In the obtained filtrate, 5.5 g of succinic anhydride was added in batches and 30.0 g of 4N sodium hydroxide solution was added dropwise to maintain the The pH of the system is 6. After the dropwise addition, the temperature is lowered to 10° C. after the reaction is incubated for 1.5 hours. Then, 35.5g of 4N hydrochloric acid solution is added dropwise to keep the pH of the system at 2.5. The solid is precipitated. Centrifuged after 1 hour to obtain 240 g of succinyl casein wet product.

Disperse 240 g of the above succinyl casein wet product in 500 g of purified water, and then add 41.5 g of 4N sodium hydroxide solution dropwise to 60 °C to keep the pH of the system at 8 to fully dissolve the succinyl casein, and then filter to remove a small amount of undissolved Hard particles, then the filtrate is cooled to 8 ° C, then the aqueous solution of 310.17g ferric chloride hexahydrate (10.17g ferric chloride hexahydrate is dissolved in 300g purified water) is added dropwise, and when the pH value drops to 3.5, dropwise simultaneously Add 20.0 g of 1N sodium hydroxide solution to keep the pH of the system at 3.5, react for 2 hours after the dropwise addition, centrifuge, and dry to obtain 34.3 g of iron protein succinate solid, mass yield: 91.5%.

Clarity test result: qualified.

Remarks: The testing method for clarity is tested in accordance with the "General Rules for Checking Clarity" in the Pharmacopoeia.

Example 2

Disperse 1.50kg of casein in 10.00kg of purified water, add 0.34kg of 4N sodium hydroxide solution dropwise to 60°C to keep the pH of the system at 8.5 to fully dissolve the casein, then adjust the pH of the system to 8.0 by dilute hydrochloric acid solution and filter Then, 0.12kg polyacrylamide was added to the obtained filtrate, stirred at 50°C for 2.5 hours, and then filtered to remove the polyacrylamide. In the obtained filtrate, 0.22kg of succinic anhydride was added in batches and 1.16kg of 4N sodium hydroxide solution was added dropwise to keep the The pH of the system is 6. After the dropwise addition, the temperature is lowered to 10° C. after the reaction is incubated for 1.5 hours, and then 1.36kg of 4N hydrochloric acid solution is added dropwise to keep the pH of the system at 2.5. The solid is precipitated. After 2 hours, it was centrifuged to obtain 4.48 kg of succinyl casein wet product.

Disperse 4.48 kg of the above succinyl casein wet product in 10.00 kg of purified water, and then add 0.79 kg of 4N sodium hydroxide solution dropwise to 60 °C to keep the pH of the system at 8 to fully dissolve the succinyl casein. Dissolved hard particles, then the filtrate is cooled to 9 ℃, then the aqueous solution of 12.338kg ferric chloride hexahydrate (0.338kg ferric chloride hexahydrate is dissolved in 12.00kg purified water) is added dropwise, when the pH value is reduced to 3 At ~4 o'clock, 0.62kg of 1N sodium hydroxide solution was added dropwise to maintain pH=3.5 of the system, and the reaction was performed for 2 hours after the dropwise addition, centrifugation, and drying to obtain 1.43kg of iron protein succinate solid, mass yield: 95.0%.

Clarity test result: qualified.

Example 3

Disperse 1.50kg of casein in 10.00kg of purified water, add 0.34kg of 4N sodium hydroxide solution dropwise to 60°C to keep the pH of the system at 8.5 to fully dissolve the casein, then adjust the pH of the system to 7.5 by dilute hydrochloric acid solution and filter Then, 0.12kg of polyamide was added to the obtained filtrate, stirred at 40°C for 3.0 hours, and then filtered and removed. In the obtained filtrate, 0.22kg of succinic anhydride was added in batches and 1.16kg of 4N sodium hydroxide solution was added dropwise to maintain the pH of the system at 6. After the dropwise addition, the temperature was lowered to 10° C. after the incubation reaction for 1.5 hours, and then 1.36kg of 4N hydrochloric acid solution was added dropwise to keep the pH of the system at pH=2.5 to separate out solids. , to obtain 4.60kg of succinyl casein wet product.

Disperse 4.60 kg of the above succinyl casein wet product in 10.00 kg of purified water, and then add 0.79 kg of 4N sodium hydroxide solution dropwise to 60 °C to keep the pH of the system at 8 to fully dissolve the succinyl casein. Dissolved hard particles, then the filtrate is cooled to 9 ℃, then the aqueous solution of 12.338kg ferric chloride hexahydrate (0.338kg ferric chloride hexahydrate is dissolved in 12.00kg purified water) is added dropwise, when the pH value is reduced to 3.5 At the same time, 0.62kg of 1N sodium hydroxide solution was added dropwise to keep the pH of the system at 3.5. After the dropwise addition, the reaction was performed for 2 hours, centrifuged, and dried to obtain 1.45kg of iron protein succinate solid, mass yield: 96.6%.

Clarity test result: qualified.

Example 4

Disperse 1.50kg of casein in 10.00kg of purified water, add 0.34kg of 4N sodium hydroxide solution dropwise after warming to 60°C to keep the pH of the system at 8.5 to fully dissolve the casein, and add 0.22kg of succinic anhydride in batches while adding dropwise The 4N sodium hydroxide solution of 1.16kg maintains the pH of the system at pH=6. After the dropwise addition, the temperature is lowered to 10° C. after the insulation reaction is performed for 1.5 hours. An appropriate amount of 16.00 kg of purified water was added to make pulp at room temperature for 2 hours, and then centrifuged to obtain 4.48 kg of succinyl casein wet product.

Disperse 4.48 kg of the above succinyl casein wet product in 10.00 kg of purified water, and then add 0.79 kg of 4N sodium hydroxide solution dropwise to 60°C to keep the pH of the system at 8 to fully dissolve the succinyl casein, and then pass the diluted hydrochloric acid solution. Adjust the pH of the system to 7.7 and filter, then add 0.06kg of polyacrylamide to the obtained filtrate, stir at 50°C for 2.5h, filter to remove the polyacrylamide, then cool the filtrate to 9°C, and then dropwise add 12.338kg of trichlorohexahydrate The aqueous solution of iron (0.338kg ferric trichloride hexahydrate is dissolved in 12.00kg purified water and gained), when the pH value drops to 3.5, the 1N sodium hydroxide solution of 0.62kg is added dropwise to keep the system pH=3.5, after the dropping is completed The reaction was carried out for 2 hours, centrifuged, and dried to obtain 1.39 kg of iron protein succinate solid, and the mass yield: 92.3%.

Clarity test result: qualified.

Example 5

Disperse 1.50kg of casein in 10.00kg of purified water, add 0.34kg of 4N sodium hydroxide solution dropwise after warming to 60°C to keep the pH of the system at 8.5 to fully dissolve the casein, and add 0.22kg of succinic anhydride in batches while adding dropwise The 4N sodium hydroxide solution of 1.16kg maintains the pH of the system at pH=6. After the dropwise addition, the temperature is lowered to 10° C. after the insulation reaction is performed for 1.5 hours. An appropriate amount of 16.00 kg of purified water was added to make pulp at room temperature for 2 hours, and then centrifuged to obtain 4.60 kg of succinyl casein wet product.

Disperse 4.60kg of the above succinyl casein wet product in 10.00kg purified water, add 0.79kg of 4N sodium hydroxide solution dropwise to 60°C to keep the pH of the system at 8 to fully dissolve the succinyl casein, and then pass the diluted hydrochloric acid solution. The pH of the system was adjusted to 8.0, and then filtered. Then, 0.12 kg of polyacrylamide was added to the obtained filtrate, stirred at 40 °C for 3.0 h, and then filtered to remove the polyacrylamide. The aqueous solution of iron (0.338kg ferric trichloride hexahydrate is dissolved in 12.00kg purified water and gained), when the pH value drops to 3.5, the 1N sodium hydroxide solution of 0.62kg is added dropwise to keep the system pH=3.5, after the dropping is completed The reaction was carried out for 2 hours, centrifuged, and dried to obtain 1.40 kg of iron protein succinate solid, mass yield: 93.3%.

Clarity test result: qualified.

Example 6

Disperse 1.00kg of casein in 6.67kg of purified water, add 0.23kg of 4N sodium hydroxide solution dropwise to 60°C to keep the pH of the system at 8.5 to fully dissolve the casein, then adjust the pH of the system to 7.2 by dilute hydrochloric acid solution and filter Then, 0.12kg of zeolite molecular sieve was added to the obtained filtrate, stirred at 45°C for 2 hours, and then filtered and removed. In the obtained filtrate, 0.15kg of succinic anhydride was added in batches and 0.80kg of 4N sodium hydroxide solution was added dropwise to maintain the pH of the system at 6. After the completion of the dropwise addition, the temperature was lowered to 8° C. for 1.5 hours, and then the 4N hydrochloric acid solution of 0.94kg was added dropwise to keep the pH of the system at pH=2.5. The solid was precipitated. 2.26 kg of succinyl casein wet product were obtained.

Take 2.26 kg of the above succinyl casein wet product and disperse it in 6.67 kg of purified water. After the temperature is raised to 60 °C, 0.57 kg of 4N sodium hydroxide solution is added dropwise to keep the pH of the system at 8 to fully dissolve the succinyl casein. Dissolved hard particles, then the filtrate is cooled to 9 ℃, then the aqueous solution of 8.24kg ferric chloride hexahydrate (0.24kg ferric chloride hexahydrate is dissolved in 8.00kg purified water) is added dropwise, when the pH value is reduced to 3.5 At the same time, 0.48kg of 1N sodium hydroxide solution was added dropwise to keep the pH of the system at 3.5. After the dropwise addition, the reaction was performed for 2 hours, centrifuged, and dried to obtain 0.93kg of iron protein succinate solid, mass yield: 93.0%.

Clarity test result: qualified.

Example 7

Disperse 1.00kg of casein in 6.67kg of purified water, add 0.23kg of 4N sodium hydroxide solution dropwise to 60°C to keep the pH of the system at 8.5 to fully dissolve the casein, then adjust the pH of the system to 7.2 by dilute hydrochloric acid solution and filter Then, 0.12kg polyacrylamide was added to the obtained filtrate, stirred at 45°C for 2 hours, and then removed by filtration. In the obtained filtrate, 0.15kg of succinic anhydride was added in batches and 0.80kg of 4N sodium hydroxide solution was added dropwise to maintain the pH of the system at 6. After the dropwise addition was completed, the temperature was lowered to 8° C. for 1.5 hours, and the 4N hydrochloric acid solution was added dropwise to keep the pH of the system at pH=2.5. After centrifugation, the obtained solid was added to an appropriate amount of 8.00kg of purified water and then centrifuged at room temperature for 2 hours , to obtain 2.26kg of succinyl casein wet product.

Disperse 2.26 kg of the above succinyl casein wet product in 6.67 kg of purified water, and then add 0.57 kg of 4N sodium hydroxide solution dropwise to 60°C to keep the pH of the system at 8 to fully dissolve the succinyl casein, and then pass the diluted hydrochloric acid solution. The pH of the system was adjusted to 7.6, and then filtered. Then, 0.08 kg of polyacrylamide was added to the obtained filtrate, stirred at 50 °C for 2 hours, and then filtered to remove the polyacrylamide. Then the filtrate was cooled to 7 °C, and 8.24 kg of ferric trichloride hexahydrate was added dropwise. The aqueous solution (0.24kg ferric chloride hexahydrate is dissolved in 8.00kg purified water), when the pH value drops to 3～4, the 1N sodium hydroxide solution of 0.48kg is added dropwise to keep the system pH=3.5, after the dropping is completed The reaction was carried out for 2 hours, centrifuged, and dried to obtain 0.85 kg of iron protein succinate solid, and the mass yield: 85.0%.

Clarity test result: qualified.

Example 8 The effect of pH on the removal of impurities from polyacrylamide

Using the same method as in Example 1 to prepare ferric protein succinate, when adjusting the pH of the system by dilute hydrochloric acid solution, set different pH gradients, specifically 6.7, 7.0, 7.5, 8.0, 8.3, the obtained ferric protein succinate was clarified. The degrees are as follows in Table 1:

Table 1

Sample serial number pH Clarity 1 6.7 Slightly worse than the original research 2 7.0 better than 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 research

The above results show that when the adsorbent adsorbs impurities in the range of pH=7.0-8.0, the clarity of the obtained iron protein succinate is consistent with the original research, and when pH=7.0, the clarity is even better than the original research.

Embodiment 9 The influence of temperature on the effect of removing impurities from polyacrylamide

Utilize the same method as in Example 1 to prepare ferric protein succinate, the difference only lies in setting the temperature gradient when different adsorbents adsorb impurities, the temperature is 35 ℃, 40 ℃, 45 ℃, 50 ℃ respectively, the obtained protein amber The clarity of ferric acid is as follows in Table 2:

Table 2

Finished product number Clarity temperature 1 Slightly worse than the original research 35℃ 2 Consistent with the original research 40℃ 3 better than the original product 45℃ 3 Consistent with the original research 50℃

The above results show that when the adsorbent adsorbs impurities in the temperature range of 40-50 °C, the clarity of the obtained iron protein succinate is consistent with the original research, and at 45 °C, the clarity is even better than the original research.

Example 10 The effect of adsorbent dosage on the effect of removing impurities from polyacrylamide

Utilize the same method as in Example 1 to prepare iron protein succinate, set different gradients of the amount of adsorbent, and the amount of adsorbent is 12%, 8%, 4%, 0 of the reaction substrate casein, and the obtained iron protein succinate has Clarity is as follows in Table 3:

table 3

The results in Table 3 show that when the added 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 the original one.

Example 11 Influence of adsorption time on the effect of removing impurities from polyacrylamide

Utilize the same method as in Example 6 to prepare ferric protein succinate, set different adsorption times, respectively 0.5h, 1h, 3h, the clarity of the obtained ferric protein succinate is as follows Table 4:

Table 4

Finished product number time Clarity 1 0.5h Slightly worse than the original research 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 1 h to 3 h, the clarity of the obtained iron protein succinate is consistent with the original one. Below 1h, the clarity of the obtained iron protein succinate does not meet the standard.

In the description of this specification, description with reference to the terms "one embodiment," "some embodiments," "example," "specific example," or "some examples", etc., mean specific features described in connection with the embodiment or example , structure, material or feature is included in at least one embodiment or example of the present invention. In this specification, schematic representations of the above terms are not necessarily directed 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, those skilled in the art may combine and combine the different embodiments or examples described in this specification, as well as the features of the different embodiments or examples, without conflicting each other.

Although the embodiments of the present invention have been shown and described above, it should be understood that the above-mentioned embodiments are exemplary and should not be construed as limiting the present invention. Embodiments are subject to variations, modifications, substitutions and variations.

Claims (9)

1. a method for preparing high-clarity iron protein succinate, is characterized in that, described method comprises adding adsorbent to remove impurities in the preparation stage of iron protein succinate, and described adsorbent is to pH=7.0～8.0 scope. impurities are adsorbed, The preparation stage of the iron protein succinate includes a casein treatment stage, an acylation reaction stage and an iron loading stage, and the casein treatment stage is adsorbed by an adsorbent, or, The preparation stage of the iron protein succinate includes a casein treatment stage and an acylation reaction stage, a purification acylated casein and an adsorbent adsorption stage, and an iron loading stage, and is utilized in the purified acylated casein and the adsorbent adsorption stage. adsorbent adsorption, The addition amount of the adsorbent is 4-12wt% of the casein content of the reaction substrate in the casein processing 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 the reaction substrate casein in the casein processing stage is 10-15 wt%. 3 . The method according to claim 1 , wherein, when the adsorbent adsorbs impurities, the adsorption temperature is 20-80° C. 4 . The method according to claim 1, characterized in that, when the adsorbent adsorbs impurities, the adsorption temperature is 30-60°C. 5 . The method according to claim 1 , wherein, when the adsorbent adsorbs impurities, the adsorption temperature is 40-50° C. 6 . 6 . The method according to claim 1 , wherein, when the adsorbent adsorbs impurities, the adsorption time is 0.1 to 6 h. 7 . 7. The method according to claim 1, characterized in that, when the adsorbent adsorbs impurities, the adsorption time is 1-5h. 8 . The method according to claim 1 , wherein, when the adsorbent adsorbs impurities, the adsorption time is 1 to 3 hours. 9 . 9 . The method according to claim 1 , further comprising: removing the adsorbent after the adsorbent completes the adsorption of impurities. 10 .