Preparation method of ferric carboxymaltose

Abstract

The invention relates to the technical field of medicine preparation, in particular to a preparation method of ferric carboxymaltose. The preparation method comprises the following steps: by taking first maltodextrin and second maltodextrin as raw materials, oxidizing to generate carboxyl maltodextrin; complexing the carboxyl maltodextrin and ferric trichloride to prepare a carboxyl maltodextrin iron complex; and finally, curing and refining the carboxyl maltose iron complex to obtain the carboxyl maltose iron. Wherein the DE value of the first maltodextrin is 10 to 14; the DE value of the second maltodextrin is 16 to 20. According to the invention, two kinds of maltodextrin with specific DE values are used as raw materials, so that the ferric carboxymaltose can keep a relatively small dispersion coefficient, and the molecular weight is accurate and controllable; meanwhile, the source of the raw materials is widened, and the raw materials are not limited to a certain specific DE value any more.

Description

Technical Field

[0001] The present invention relates to the technical field of drug preparation, and in particular to a method for preparing carboxymaltose iron. Background Art

[0002] Iron deficiency anemia is a common nutritional disease, which is caused by the inability of the body's iron storage to meet the needs of normal red blood cell production. At present, about 2 billion people suffer from anemia in the world, and according to clinical statistics, more than 90% of them are iron deficiency anemia.

[0003] Oral or injected iron supplements are the most commonly used to treat iron deficiency anemia. Oral iron supplements are often the first choice for iron deficiency anemia because they are effective, cheap and safe. Oral iron supplements are still the main treatment in China. However, oral iron supplements often have obvious gastrointestinal discomfort symptoms, and some patients interrupt treatment due to intolerance. In addition, they are also affected by food ingredients and iron reserves in the body. Especially in many chronic disease and tumor patients, the inflammatory cell mediators in the body increase. Inflammatory mediators can induce the liver to synthesize iron regulatory proteins, which downregulate the expression of iron transporters on the surface membrane of the gastrointestinal tract and iron storage cells in the body, thereby affecting the absorption and utilization of iron. At this time, oral iron supplements are often ineffective or ineffective. In addition, in gastrointestinal diseases, when iron reserves need to be restored quickly and oral administration is not enough to supplement the body's needs, intravenous iron supplements must be used in cases where oral iron cannot be tolerated or complied with.

[0004] At present, the commonly used intravenous iron preparations for clinical application include iron dextran, complex sodium iron gluconate, iron sucrose, isomaltose iron 1000, Ferumoxytol and carboxymaltose iron. In the iron carboxymaltose injection, the iron is complexed with carbohydrate polymers in a stable trivalent state to release available iron to the body's iron transport and storage proteins (ferritin and transferrin), and is a new type of polysaccharide intravenous iron preparation.

[0005] Ferric carboxymaltose was developed by Weifu Pharmaceuticals and first launched in Germany in 2007. It was launched in the UK in May of the following year under the trade name Ferinject. It is used to treat iron deficiency anemia in which oral iron preparations are ineffective or cannot be used. As of the end of 2014, ferric carboxymaltose injection has been registered in 63 countries around the world, including many European countries, the United States, Australia, Argentina, South Korea, and Singapore, and has been launched in 54 countries, but it has not yet been launched in my country. In the treatment of iron deficiency anemia, ferric carboxymaltose is more effective than iron sucrose, has a more advantageous cost, and is well tolerated. It can rapidly infuse 500 to 1500 mg of Fe within 15 minutes, and the currently approved maximum single dose is 1000 mg of Fe. Ferric carboxymaltose meets the clinical demand for large-dose rapid administration of iron preparations and has become a representative drug for new intravenous iron preparations.

[0006] The synthesis of ferric carboxymaltose is based on maltodextrin as the starting material, which is oxidized to obtain carboxymaltodextrin, and then reacted with a raw material containing trivalent iron ions to generate ferric carboxymaltose.

[0007] In the prior art, related patent applications CN106977621A, CN108129582A, and CN1705682A all involve the synthesis of carboxyl maltose iron, but the description of the refining method of carboxyl maltose iron is quite different, and the final drying of the material generally adopts a vacuum drying method, which is poor in effect and easily leads to a large change in the molecular weight of the material. CN106977621A is complicated in refining: the carboxyl maltose iron aqueous solution obtained by the reaction must be continuously adjusted in the alcohol precipitation process, and is dried after washing with ice ethanol for many times, then re-dissolved in water, and then precipitated with anhydrous ethanol, and the filter cake repeats the process of washing with ice ethanol and adjusting the pH value, and finally vacuum dried. The whole process is complicated and does not meet the requirements of industrialization. CN108129582A and CN1705682A do not involve the refining process.

[0008] CN 113004429 A reports a relatively detailed ethanol refining process and a fluidized bed drying method, and proposes the control of Mw. The inventors have found that in the complexation reaction system of ferric chloride solution and carboxymaltodextrin solution, the ratio of sodium carbonate to ferric chloride, the concentration of sodium carbonate solution, and the concentration of ferric chloride solution are fixed, and the molecular weight of carboxymaltose iron is only related to the time (or addition speed) of uniformly adding sodium carbonate solution throughout the process, and has nothing to do with the amount of material in the reaction system. By controlling the addition speed of sodium carbonate solution, carboxymaltose iron with a specific molecular weight and molecular weight distribution coefficient can be obtained.

[0009] At present, the quality fluctuation range of maltodextrin raw materials in the industry is large, the molecular weight is unstable, and the molecular weight decreases significantly during the stability placement process, which brings great troubles to the preparation and process amplification of carboxymaltose iron. For example, it will cause large batch fluctuations in the molecular weight distribution of carboxymaltose iron, low molecular weight distribution concentration, and unstable molecular weight. Relevant patent applications CN106977621A, CN108129582A, CN1705682A (original research patents), etc. all involve the synthesis of carboxymaltose iron, but there is no corresponding description of the molecular weight control of carboxymaltose iron.

[0010] In view of this, the present invention is proposed. Summary of the invention

[0011] In order to solve the above problems in the prior art, the present invention provides a method for preparing carboxymaltose iron to obtain carboxymaltose iron with a smaller dispersion coefficient, while making the molecular weight of carboxymaltose iron precisely controllable.

[0012] Based on this, the present invention has the following technical solutions: In a first aspect, the present invention provides a method for preparing carboxymaltose iron, comprising: taking a first maltodextrin and a second maltodextrin as raw materials, oxidizing them to generate carboxymaltodextrin; then complexing the carboxymaltodextrin with ferric chloride to form a carboxymalt iron complex; and finally solidifying and refining the carboxymalt iron complex to obtain the carboxymaltose iron; Wherein, the DE value of the first maltodextrin is 10-14; and the DE value of the second maltodextrin is 16-20.

[0013] The present invention finds that by using the above two specific DE values ​​of maltodextrin as raw materials, the dispersion coefficient of carboxymaltose iron can be kept small, and the molecular weight can be precisely controlled; at the same time, the source of raw materials is also broadened and is no longer limited to a certain specific DE value.

[0014] In a specific implementation process, the DE value of the first maltodextrin can be 10, 11, 12, 13 or 14; the DE value of the second maltodextrin can be 16, 17, 18, 19 or 20.

[0015] In the present invention, the DE value (Dextrose Equivalent) of maltodextrin is an important indicator for measuring the degree of starch hydrolysis, which indicates the percentage of reducing sugar (in terms of glucose) produced during the hydrolysis of starch in the dry matter.

[0016] Preferably, the dispersion coefficient of carboxymaltose iron is adjusted by adjusting the mass ratio of the first maltodextrin and the second maltodextrin.

[0017] Preferably, the mass ratio of the first maltodextrin to the second maltodextrin is (50-60): (40-50).

[0018] The present invention further optimizes the dosage relationship between the first maltodextrin and the second maltodextrin, and finds that at the above dosage ratio, the dispersion coefficient of carboxymaltose iron can be further reduced.

[0019] Preferably, the weight average molecular weight and number average molecular weight of carboxymaltose iron are adjusted by adjusting the mass ratio of the first maltodextrin and the second maltodextrin.

[0020] In the prior art, when preparing carboxymaltose iron, as the process is enlarged, although the various process parameters are fixed, equipment changes, batch changes, etc. will bring about an amplification effect, causing the molecular weight of the product to change. Due to the complexity of the complexation process, the molecular weight cannot be quickly and effectively adjusted when the process parameters are adjusted again. The present invention finds that when two mixed maltodextrins are used as starting materials, the key quality parameters Mw and Mn to be obtained can be adjusted only by adjusting the ratio of the two maltodextrins. For example, when the Mw is low during batch amplification, the Mw of carboxymaltose iron can be increased by increasing the proportion of the first maltodextrin; when the Mw value is high, the Mw of carboxymaltose iron can be reduced by reducing the proportion of the first maltodextrin.

[0021] Preferably, when the mass ratio of the first maltodextrin to the second maltodextrin is (50-60): (40-50), the weight average molecular weight of the carboxymaltose iron is 150,000-180,000, and the number average molecular weight is 110,000-130,000; when the mass ratio of the first maltodextrin to the second maltodextrin is (45-50): (50-55), the weight average molecular weight of the carboxymaltose iron is 130,000-150,000, and the number average molecular weight is 90,000-110,000.

[0022] Preferably, the preparation method of the carboxymaltose iron comprises: S1: mixing the first maltodextrin, the second maltodextrin, a catalyst, water and sodium hypochlorite, adjusting the pH value to 10.5-11.5 for reaction, and obtaining a carboxymaltodextrin solution after the reaction is completed; S2: mixing the carboxymaltodextrin solution with ferric chloride hexahydrate, and slowly adding a sodium carbonate aqueous solution dropwise thereto until the pH value of the reaction solution reaches 4-5, thereby obtaining a carboxymalt iron complex; S3: sequentially subjecting the carboxyl malt iron complex to alkaline curing, acid curing and high temperature curing to obtain a carboxyl malt iron curing liquid; S4: cooling the carboxyl maltose iron solidified liquid and filtering it, and performing alcohol precipitation, eluting and drying the filtrate to obtain the carboxyl maltose iron.

[0023] In S2 of the present invention, when adding an aqueous sodium carbonate solution to a mixed solution of a carboxymaltodextrin solution and ferric chloride hexahydrate, adding the solution too quickly may cause the carboxymaltose iron to agglomerate, so the adding speed should not be too fast.

[0024] Preferably, the catalyst in S1 is a mixture of sodium bromide and TEMPO; based on the total mass of the first maltodextrin and the second maltodextrin, the amount of the catalyst is 1.5-3.0wt%; more preferably, the mass ratio of sodium bromide to TEMPO is 1:(0.01-0.13).

[0025] Preferably, in S3, the alkaline curing comprises: adjusting the pH value of the carboxyl malt iron complex to 10.5-11.5, and curing at 40-60° C. to obtain a first mixed solution; The acid curing comprises: adjusting the pH value of the first mixed solution to 4.5-5.5, and curing at 40-60° C. to obtain a second mixed solution; The high temperature solidification comprises: solidifying the second mixed solution at 80-100° C. to obtain a carboxyl malt iron solidified liquid.

[0026] Preferably, in S1, the mass ratio of the mixture of the first maltodextrin and the second maltodextrin to the sodium hypochlorite is (5-10):1.

[0027] Preferably, in S2, the concentration of the sodium carbonate aqueous solution is 20-30 wt %.

[0028] As a preferred embodiment of the present invention, the preparation method of carboxymaltose iron comprises: S1: mixing the first maltodextrin, the second maltodextrin, sodium bromide, TEMPO, water and sodium hypochlorite, adjusting the pH value to 10.5-11.5 for reaction, and obtaining a carboxymaltodextrin solution after the reaction; the mass ratio of the mixture of the first maltodextrin and the second maltodextrin to the sodium hypochlorite is (5-10):1; the mass ratio of the sodium bromide to TEMPO is 1:(0.01-0.13); S2: mixing the carboxymaltodextrin solution with ferric chloride hexahydrate, and slowly adding 20-30 wt % of a sodium carbonate aqueous solution until the pH value of the reaction solution is 4-5, to obtain a carboxymalt iron complex; S3: adjusting the pH value of the carboxyl malt iron complex to 10.5-11.5, and curing at 40-60° C. to obtain a first mixed solution; then adjusting the pH value of the first mixed solution to 4.5-5.5, and curing at 40-60° C. to obtain a second mixed solution; finally, curing the second mixed solution at 80-100° C. to obtain a carboxyl malt iron solidified solution; S4: cooling the carboxyl maltose iron solidified liquid and filtering it, and performing alcohol precipitation, eluting and drying the filtrate to obtain the carboxyl maltose iron.

[0029] The preparation method of ferric carboxymaltose provided by the present invention can maintain a small dispersion coefficient of ferric carboxymaltose and accurately control the molecular weight by using maltodextrins with two specific DE values ​​as raw materials; at the same time, it also broadens the source of raw materials and is no longer limited to a certain specific DE value. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] In order to more clearly illustrate the technical solutions in the present invention or the prior art, the following briefly introduces the drawings required for use in the embodiments or the description of the prior art. Obviously, the drawings described below are some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0031] Figure 1 It is a molecular weight distribution diagram of carboxymaltose iron in Example 1 provided by the present invention.

[0032] Figure 2 It is a molecular weight distribution diagram of carboxymaltose iron in Example 2 provided by the present invention. DETAILED DESCRIPTION

[0033] In order to make the purpose, technical solution and advantages of the present invention clearer, the technical solution of the present invention will be described clearly and completely below. Obviously, the described embodiments are part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0034] Unless otherwise specified, the various raw materials used in the examples and comparative examples are commercially available conventional raw materials, and the technical means used are conventional means well known to those skilled in the art.

[0035] Example 1

[0036] The present embodiment provides a carboxymaltose iron, and the preparation method thereof comprises the following steps: S1: Dissolve 600 g of maltodextrin with a DE value of 12, 600 g of maltodextrin with a DE value of 19, 20 g of sodium bromide and 2.5 g of TEMPO in 2 L of water. After the solution is clear, add 20% sodium hydroxide aqueous solution dropwise to adjust the pH to 11, slowly add 2 L of sodium hypochlorite aqueous solution (8wt%), and stir at room temperature for 2 h to obtain a carboxymaltodextrin solution.

[0037] S2: In a 50 L reactor, 2000 g of ferric chloride hexahydrate was dissolved in 2 L of water to obtain a ferric chloride hexahydrate solution, the carboxymaltodextrin solution was slowly added to the ferric chloride hexahydrate solution, and a 20% aqueous sodium carbonate solution was slowly added dropwise to the system for about 6 hours until the pH was adjusted to 4.5; a carboxymalt iron complex was obtained; S3: adjusting the pH value of the carboxyl malt iron complex to 11 with a 20% sodium hydroxide solution, and stirring at 50°C for 0.5 h for solidification to obtain a first mixed solution; then adjusting the pH value of the first mixed solution to 5 with 2.4 M hydrochloric acid, and stirring at 50°C for 0.5 h for solidification to obtain a second mixed solution; finally, heating the second mixed solution to 90°C for reaction for 1 h for solidification to obtain a carboxyl malt iron solidified solution; S4: The carboxyl malt iron solidified liquid is cooled to room temperature and filtered with a PP sterile filter membrane. The 14 L filtrate is added with 28 L ethanol and stirred at room temperature for crystallization for 1 h. Filter the alcohol precipitation system and rinse with ethanol. Filter and dry the filter cake. Dissolve the filter cake in 5 L purified water and heat to 50 °C to dissolve. Add 10 L ethanol for alcohol precipitation and stir for 1 hour. Filter, rinse the filter cake with 4 L ethanol and dry it and slurry it with 10 L ethanol. Filter and dry to obtain 1.37 kg of product.

[0038] The molecular weight distribution diagram is shown in Figure 1 .

[0039] Example 2

[0040] This embodiment provides carboxymaltose iron, and the preparation method thereof is different from that of Example 1 only in that the mass ratio of maltodextrin with a DE value of 12 and maltodextrin with a DE value of 19 is adjusted to 75:25. 1.32 kg of the product is obtained.

[0041] The molecular weight distribution diagram is shown in Figure 2 .

[0042] Example 3

[0043] This embodiment provides a carboxymaltose iron, and the difference between the preparation method thereof and that of Example 1 is that the mass ratio of maltodextrin with a DE value of 12 and maltodextrin with a DE value of 19 is adjusted to 60:40; specifically: S1: Dissolve 72 g of maltodextrin with a DE value of 12, 48 g of maltodextrin with a DE value of 19, 2 g of sodium bromide and 0.25 g of TEMPO in 0.2 L of water. After the solution is clear, add 20% sodium hydroxide aqueous solution dropwise to adjust the pH to 11, slowly add 0.2 L of sodium hypochlorite aqueous solution (8wt%), and stir at room temperature for 2 h to obtain a carboxymaltodextrin solution.

[0044] S2: In a reaction bottle, 200 g of ferric chloride hexahydrate was dissolved in 0.2 L of water to obtain a ferric chloride hexahydrate solution, the carboxymaltodextrin solution was slowly added to the ferric chloride hexahydrate solution, and a 20% aqueous sodium carbonate solution was slowly added dropwise to the system for about 6 hours until the pH was adjusted to 4.5; a carboxymalt iron complex was obtained; S3: adjusting the pH value of the carboxyl malt iron complex to 11 with a 20% sodium hydroxide solution, and stirring at 50°C for 0.5 h for solidification to obtain a first mixed solution; then adjusting the pH value of the first mixed solution to 5 with 2.4 M hydrochloric acid, and stirring at 50°C for 0.5 h for solidification to obtain a second mixed solution; finally, heating the second mixed solution to 100°C and reacting for 1 h for solidification to obtain a carboxyl malt iron solidified solution; S4: Cool the carboxyl malt iron solidified liquid to room temperature and filter it with a PP sterile filter membrane. Add 3 L of ethanol to the obtained 1.5 L filtrate and stir at room temperature for crystallization for 1 h. Filter the alcohol precipitation system and rinse with ethanol. Filter and dry the filter cake. Dissolve the filter cake in 0.5 L of purified water and heat to 50 °C to dissolve. Add 1 L of ethanol for alcohol precipitation and stir for 1 hour. Filter and dry to obtain 122 g of the product.

[0045] Example 4

[0046] This embodiment provides a carboxymaltose iron, and the difference between the preparation method thereof and that of Example 1 is that the mass ratio of maltodextrin with a DE value of 12 and maltodextrin with a DE value of 19 is adjusted to 45:55; specifically: S1: Dissolve 27 g of maltodextrin with a DE value of 12, 33 g of maltodextrin with a DE value of 19, 1 g of sodium bromide and 0.13 g of TEMPO in 0.1 L of water. After the solution is clear, add 20% sodium hydroxide aqueous solution dropwise to adjust the pH to 11, slowly add 0.1 L of sodium hypochlorite aqueous solution (8wt%), and stir at room temperature for 2 h to obtain a carboxymaltodextrin solution.

[0047] S2: In a reaction bottle, 100 g of ferric chloride hexahydrate was dissolved in 0.1 L of water to obtain a ferric chloride hexahydrate solution, the carboxymaltodextrin solution was slowly added to the ferric chloride hexahydrate solution, and a 20% aqueous sodium carbonate solution was slowly added dropwise to the system for about 6 hours until the pH was adjusted to 4.5; a carboxymalt iron complex was obtained; S3: adjusting the pH value of the carboxyl malt iron complex to 11 with a 20% sodium hydroxide solution, and stirring at 50°C for 0.5 h for solidification to obtain a first mixed solution; then adjusting the pH value of the first mixed solution to 5 with 2.4 M hydrochloric acid, and stirring at 50°C for 0.5 h for solidification to obtain a second mixed solution; finally, heating the second mixed solution to 90°C for reaction for 1 h for solidification to obtain a carboxyl malt iron solidified solution; S4: Cool the carboxyl malt iron solidified liquid to room temperature and filter it with a PP sterile filter membrane. Add 1.8 L of ethanol to the obtained 0.9 L filtrate and stir at room temperature for crystallization for 1 h. Filter the alcohol precipitation system and rinse with ethanol. Filter and dry the filter cake. Dissolve the filter cake in 0.25 L of purified water and heat to 50 °C to dissolve. Add 0.5 L of ethanol for alcohol precipitation and stir for 1 hour. Filter and slurry the filter cake with 0.25 L of ethanol. Filter and dry to obtain 56 g of product.

[0048] Example 5

[0049] The present embodiment provides a carboxymaltose iron, and the preparation method thereof is different from that of Example 1 only in that maltodextrin with a DE value of 12 is replaced by an equal amount of maltodextrin with a DE value of 14, and maltodextrin with a DE value of 19 is replaced by an equal amount of maltodextrin with a DE value of 20.

[0050] Example 6

[0051] The present embodiment provides carboxymaltose iron, and the preparation method thereof is different from that of Example 1 only in that maltodextrin with a DE value of 12 is replaced by an equal amount of maltodextrin with a DE value of 10, and maltodextrin with a DE value of 19 is replaced by an equal amount of maltodextrin with a DE value of 16.

[0052] Comparative Example 1

[0053] This embodiment provides a carboxymaltose iron, and the preparation method thereof is different from that of Example 1 only in that maltodextrin with a DE value of 12 is replaced by an equal amount of maltodextrin with a DE value of 19.

[0054] Comparative Example 2

[0055] This embodiment provides carboxymaltose iron, and its preparation method is different from that of Example 1 only in that maltodextrin with a DE value of 19 is replaced by maltodextrin with a DE value of 12.

[0056] Test example

[0057] The present invention detects the molecular weight and dispersion coefficient of the carboxyl maltose iron obtained in the above-mentioned embodiments and comparative examples, and the results are shown in Table 1: Table 1

[0058] The molecular weight properties of carboxymaltose iron for iron supplementation are usually characterized by: weight average molecular weight (Mw): 110,000-230,000, number average molecular weight (Mn): ≥60,000, and molecular weight distribution coefficient (Mw / Mn) ≤1.9.

[0059] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit it. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or make equivalent replacements for some of the technical features therein. However, these modifications or replacements do not deviate the essence of the corresponding technical solutions from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A method for preparing carboxymaltose iron, characterized in that, include: The first maltodextrin and the second maltodextrin are used as raw materials, and oxidized to generate carboxymaltodextrin; then the carboxymaltodextrin is complexed with ferric chloride to obtain a carboxymalt iron complex; finally, the carboxymalt iron complex is solidified and refined to obtain the carboxymaltose iron; Wherein, the DE value of the first maltodextrin is 10-14; and the DE value of the second maltodextrin is 16-20.

2. The method for preparing carboxyl maltose iron according to claim 1, wherein The dispersion coefficient of carboxymaltose iron is adjusted by adjusting the mass ratio of the first maltodextrin and the second maltodextrin.

3. The preparation method of carboxyl maltose iron according to claim 2, characterized in that, The mass ratio of the first maltodextrin to the second maltodextrin is (50-60): (40-50).

4. The method for preparing carboxyl maltose iron according to claim 1, wherein The weight average molecular weight and number average molecular weight of ferric carboxymaltose are adjusted by adjusting the mass ratio of the first maltodextrin and the second maltodextrin.

5. The method for preparing carboxyl maltose iron according to claim 4, wherein When the mass ratio of the first maltodextrin to the second maltodextrin is (50-60): (40-50), the weight average molecular weight of the carboxymaltose iron is 150,000-180,000, and the number average molecular weight is 110,000-130,000; When the mass ratio of the first maltodextrin to the second maltodextrin is (45-50): (50-55), the weight average molecular weight of the carboxymaltose iron is 130,000-150,000, and the number average molecular weight is 90,000-110,000.

6. The method for preparing carboxyl maltose iron according to any one of claims 1 to 5, characterized in that include: S1: mixing the first maltodextrin, the second maltodextrin, a catalyst, water and sodium hypochlorite, adjusting the pH value to 10.5-11.5 for reaction, and obtaining a carboxymaltodextrin solution after the reaction is completed; S2: mixing the carboxymaltodextrin solution with ferric chloride hexahydrate, and slowly adding a sodium carbonate aqueous solution thereto until the pH value of the reaction solution reaches 4-5, thereby obtaining a carboxymalt iron complex; S3: sequentially subjecting the carboxyl malt iron complex to alkaline curing, acid curing and high temperature curing to obtain a carboxyl malt iron curing liquid; S4: cooling the carboxyl maltose iron solidified liquid and filtering it, and performing alcohol precipitation, eluting and drying the filtrate to obtain the carboxyl maltose iron.

7. The method for preparing carboxymaltose iron according to claim 6, characterized in that, The catalyst in S1 is a mixture of sodium bromide and TEMPO; based on the total mass of the first maltodextrin and the second maltodextrin, the amount of the catalyst is 1.5-3.0wt%; Preferably, the mass ratio of sodium bromide to TEMPO is 1:(0.01-0.13).

8. The method for preparing carboxyl maltose iron according to claim 6 or 7, characterized in that, In S3, the alkaline curing includes: adjusting the pH value of the carboxyl malt iron complex to 10.5-11.5, and curing at 40-60° C. to obtain a first mixed solution; The acid curing comprises: adjusting the pH value of the first mixed solution to 4.5-5.5, and curing at 40-60° C. to obtain a second mixed solution; The high temperature solidification comprises: solidifying the second mixed solution at 80-100° C. to obtain a carboxyl malt iron solidified liquid.

9. The method for preparing carboxyl maltose iron according to any one of claims 6 to 8, characterized in that In S1, the mass ratio of the mixture of the first maltodextrin and the second maltodextrin to the sodium hypochlorite is (5-10):

1.

10. The method for preparing carboxyl maltose iron according to any one of claims 6 to 9, characterized in that In S2, the concentration of the sodium carbonate aqueous solution is 20-30wt%.

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