Preparation method of iron supplement preparation and iron supplement preparation

Abstract

The present invention provides a method for preparing an iron supplement preparation and an iron supplement preparation. The method for preparing the iron supplement preparation of the present invention comprises step (i), preparing a gold nanoparticle solution having a gold nanoparticle concentration of 200 to 1000 μg / mL and an iron solution having an iron concentration of 3 to 50 mg / mL; and step (ii), mixing the gold nanoparticle solution and the iron solution in a volume ratio of 1 to 10:10 to 30. According to the present invention, the side effects of existing oral iron supplement preparations on intestinal flora can be overcome, inflammation can be reduced, and more efficient and safe iron supplementation can be achieved.

Description

Technical Field

[0001] The present invention relates to the field of medicine, and more particularly to a preparation method of an iron supplement preparation and the iron supplement preparation. Background Art

[0002] Iron deficiency anemia, a condition characterized by microcytic hypochromic anemia and other abnormalities caused by iron deficiency, is the most common nutritional disorder worldwide. According to statistics, in 2016, over 1.2 billion people worldwide suffered from iron deficiency anemia, with the incidence rates among preschool children (under 5 years old), women of childbearing age, and pregnant women reaching 41.7%, 32.8%, and 40.1%, respectively. The main causes of iron deficiency anemia include: 1. Insufficient iron intake, which is common in young children, adolescents, and pregnant and lactating women; 2. Excessive iron loss, primarily caused by hemodialysis and chronic gastrointestinal blood loss in patients with end-stage renal disease, and more common in middle-aged and elderly people; and 3. Absorption disorders, which are common in patients with intestinal disorders and those undergoing subtotal gastrectomy.

[0003] Currently, clinical treatments for iron deficiency anemia primarily include oral iron supplements, intravenous iron supplements, and erythropoietin. Intravenous iron supplements, such as iron dextran, sodium ferric gluconate, iron sucrose, and carboxymaltose, offer high bioavailability and minimal gastrointestinal side effects, but their safety remains controversial. The European Medicines Agency's Committee for Medicinal Products for Human Use (CMPH) has concluded that all intravenous iron supplements carry the potential for allergic reactions and carry risks such as iron overload, infection, and venous thrombosis. Erythropoietin has significant limitations in treating iron deficiency anemia, and iron supplementation is still necessary in some cases. Erythropoietin may also increase blood pressure, increase the risk of cardiovascular disease, and promote tumor growth and metastasis. Therefore, both intravenous iron supplements and erythropoietin should be used in settings with emergency medical services to ensure that allergic reactions and other conditions can be managed urgently.

[0004] Oral iron supplements are currently the most widely used method of iron supplementation in clinical practice. The main ingredient of oral iron supplements is ferrous iron, including ferrous sulfate, ferrous fumarate, ferrous gluconate, and ferrous succinate. They offer advantages such as ease of use, immediate effects, low cost, and good patient compliance. However, oral iron supplements have the disadvantages of a high incidence of gastrointestinal adverse reactions and low iron bioavailability. Only 5% to 20% of the iron is absorbed in the duodenum, while the remainder reaches the colon, causing intestinal flora disturbances, systemic inflammation, and intestinal infection. Inflammation can further lead to an increase in the proportion of pathogenic bacteria and elevated hepcidin levels, slowing the treatment of iron deficiency anemia.

[0005] The intestinal flora plays a role in maintaining the host's immune function and stabilizing intestinal function. It is an important biological barrier for the host. Healthy intestinal flora maintains a dynamic balance between the host and the external environment. Oral iron supplements increase the iron content in the intestine in a short period of time, causing the intestinal flora to shift towards pathogenicity. The effects of oral iron supplements on the intestinal flora mainly include: 1) changing the composition of the intestinal flora. Iron-dependent bacteria absorb free iron through iron carriers and can use the iron in hemoglobin and transferrin to promote their own proliferation, among which the increase in pathogenic bacteria is particularly significant; 2) affecting the metabolism of the intestinal flora, leading to an increase in toxic substances produced by intestinal bacterial protein fermentation (such as ammonia, H2S, branched-chain fatty acids, indoles and phenolic compounds, etc.); 3) enhancing the virulence of pathogenic bacteria, accelerating the expression of virulence factors of pathogenic bacteria, increasing the adhesion and colonization of pathogenic bacteria in the intestinal lining, inhibiting the proliferation of probiotics, and increasing the ability to invade intestinal epithelial cells and cross the intestinal barrier, causing inflammation.

[0006] In order to inhibit the excessive proliferation of pathogens caused by oral iron supplementation, the commonly used method in clinical practice is to use antibiotics, such as norfloxacin and levofloxacin. However, the use of antibiotics can have serious side effects on the absorption of iron and intestinal flora. Antibiotics may form insoluble metal chelates with iron supplements, affecting the intestinal absorption of iron. Antibiotics can cause the body to produce antibiotic-type drug antibodies, which react with red blood cells that adsorb drugs, causing red blood cell lysis and hemolysis, further aggravating anemia. Antibiotics (especially broad-spectrum antibiotics) can damage the intestinal mucosa, impair the colonization of normal intestinal flora, and are not conducive to the maintenance of the intestinal homeostasis environment. Antibiotics taken by pregnant and lactating women can also affect the intestinal flora of newborns. Excessive use of antibiotics can cause bacteria to develop drug resistance, reduce the effectiveness of treatment, and lead to increased morbidity and mortality.

[0007] Currently, there is an urgent need for an antibiotic alternative to regulate intestinal flora during oral iron supplementation in clinical practice, achieving more efficient and safe oral iron supplementation. Therefore, it is crucial to develop a new iron supplement formulation to treat iron deficiency anemia.

[0008] It should be noted that the information disclosed in the above background technology section is only used to enhance the understanding of the background of the present invention, and therefore it may contain information that does not constitute the prior art known to those skilled in the art. Summary of the Invention

[0009] In order to solve one or more of the above problems existing in the prior art, the present invention provides a preparation method of an iron supplement preparation and an iron supplement preparation.

[0010] The preparation method of the iron supplement preparation of the present invention comprises: step (i), preparing a gold nanoparticle solution with a gold nanoparticle concentration of 200-1000 μg / mL and an iron solution with an iron concentration of 3-50 mg / mL; and step (ii), mixing the gold nanoparticle solution and the iron solution in a volume ratio of 1-10:10-30.

[0011] According to one embodiment of the present invention, in the above step (i), the concentration of the above gold nanoparticle solution can be 200-800 μg / mL, and the concentration of the above iron solution can be 3-20 mg / mL. In the above step (ii), the above gold nanoparticle solution and the above iron solution can be mixed in a volume ratio of 1-5:10-20.

[0012] According to one embodiment of the present invention, in the above step (i), the reducing agent, the small molecule ligand and the stabilizer can be dissolved in a first solvent under ice bath conditions, mixed for the first time, and chloroauric acid tetrahydrate is added, mixed for the second time, dialyzed with a dialysis bag with a molecular weight cutoff of 5000Da, and filtered with a microporous membrane filter with a pore size of 0.22μm to obtain the above-mentioned gold nanoparticle solution, wherein the above-mentioned first solvent can be any one or more of ultrapure water, methanol, ethanol, ethylene glycol, and n-propanol, the above-mentioned reducing agent can be any one or more of sodium citrate, sodium borohydride, glutathione, hydrazine hydrate, and ascorbic acid, and the above-mentioned small molecule ligand can be 4,6-diamino-2-mercaptopyrimidine, 2,4-diamino-2-mercaptopyrimidine, Any one or more of amino-6-mercaptopyrimidine, 4-mercaptopyridine, 2-mercaptopyridine, 4-mercaptophenylboronic acid, 5-(pyridin-3-yl)-1,3,4-oxadiazole-2-thiol, 5-(pyridin-4-yl)-1,3,4-oxadiazole-2-thiol, quinoline-4-thiol, 3-mercaptoquinoline, 4-aminophenol, 5-aminoindole, tryptophan, 4-aminophenylboronic acid, 6-aminopenicillanic acid, and 7-aminocephalosporanic acid. The stabilizer may be any one or more of Tween 20, Tween 40, Tween 80, polyvinylpyrrolidone with an average molecular weight of 8000, polyvinylpyrrolidone with an average molecular weight of 10000, and polyvinylpyrrolidone with an average molecular weight of 24000.

[0013] According to one embodiment of the present invention, in the above step (i), the above first solvent may be ultrapure water, the above reducing agent may be sodium borohydride and / or glutathione, the above small molecule ligand may be 4,6-diamino-2-mercaptopyrimidine and / or 5-aminoindole, and the above stabilizer may be Tween 80.

[0014] According to one embodiment of the present invention, in the above-mentioned step (i), the addition ratio of the above-mentioned stabilizer can be: 100-500 μL of the above-mentioned stabilizer is added to every 20 mL of the above-mentioned first solvent, and the molar ratio of the above-mentioned chloroauric acid tetrahydrate, the above-mentioned reducing agent and the above-mentioned small molecule ligand can be 1-3:1-5:1-10.

[0015] According to one embodiment of the present invention, in the above step (i), the first mixing may be stirred at a stirring rate of 200-500 rpm for 10-30 minutes, and the second mixing may be stirred at a stirring rate of 800-1200 rpm for 30-60 minutes.

[0016] According to one embodiment of the present invention, in the above step (i), the iron agent solution can be obtained by dissolving the iron agent in the second solvent and filtering it with a microporous membrane filter with a pore size of 0.22 μm, wherein the iron agent can be any one or more of ferrous sulfate, ferrous fumarate, iron dextran, ferrous gluconate, ferrous succinate, and ferrous lactate, and the second solvent can be any one of deionized water, phosphate buffer, and a sodium chloride aqueous solution with a mass fraction of 0.9%.

[0017] According to one embodiment of the present invention, in the above step (i), the iron agent may be ferrous sulfate and / or ferric gluconate, and the above second solvent may be deionized water.

[0018] The present invention also provides an iron supplement preparation, which is prepared by the above-mentioned preparation method of the iron supplement preparation.

[0019] According to one embodiment of the present invention, the iron supplement preparation may be an oral iron supplement preparation.

[0020] The preparation method and iron supplement preparation provided by the present invention can overcome the side effects of existing oral iron supplement preparations on intestinal flora, reduce inflammation, and achieve more efficient and safe iron supplementation. DETAILED DESCRIPTION

[0021] The present invention is described in detail below through specific embodiments so that those skilled in the art can easily implement the present invention according to the contents disclosed in this specification. The embodiments described below are only some embodiments of the present invention, not all. Based on the embodiments described in this specification, all other embodiments obtained by those skilled in the art without paying creative work are within the scope of protection of the present invention. It should be noted that the embodiments in this specification and the features in the embodiments can be combined with each other unless there is a conflict.

[0022] The inventors discovered that using gold nanoparticles in iron supplements instead of conventional antibiotics can effectively regulate intestinal flora, promoting the proliferation of beneficial bacteria, reducing the colonization of harmful bacteria, and lowering the incidence of intestinal infections, thereby minimizing the impact of conventional oral iron supplements on intestinal flora. This led to the completion of the present invention.

[0023] Specifically, the preparation method of the iron supplement preparation of the present invention includes: preparing a gold nanoparticle solution with a gold nanoparticle concentration of 200 to 1000 μg / mL and an iron solution with an iron concentration of 3 to 50 mg / mL, and mixing the gold nanoparticle solution and the iron solution in a volume ratio of 1 to 10:10 to 30.

[0024] The iron supplement preparation prepared by this method can overcome the side effects of existing oral iron supplement preparations on intestinal flora, reduce inflammation, and achieve more efficient and safe iron supplementation.

[0025] Among them, the concentration of the gold nanoparticle solution is preferably 200-800 μg / mL. This is because if the concentration of gold nanoparticles is lower than 200 μg / mL, positive regulation of intestinal flora cannot be achieved. If the concentration of gold nanoparticles exceeds 800 μg / mL, the metabolic time is increased and the burden on the liver and kidneys is increased, so it is not preferred.

[0026] In addition, the concentration of the iron solution is preferably 3 to 20 mg / mL. This is because if the iron concentration is lower than 3 mg / mL, it is not conducive to the recovery of iron deficiency anemia and the iron supplementation effect is poor. If the iron concentration is greater than 20 mg / mL, excessive iron supplementation may lead to serious side effects (intestinal infection, inflammation, etc.), which is not conducive to subsequent treatment and is therefore not preferred.

[0027] Furthermore, oral administration of excessive amounts of gold nanoparticles and a small amount of iron supplements can slow recovery from iron-deficiency anemia and prolong the metabolism of the gold particles. Oral administration of a small amount of gold nanoparticles and a large amount of iron supplements can lead to an excess accumulation of iron supplements in the intestines, causing intestinal flora disturbances and intestinal inflammation. Too few gold nanoparticles cannot positively regulate the intestinal microecology. Only the right oral ratio of gold nanoparticles and iron supplements can achieve efficient iron supplementation while maintaining a stable intestinal microenvironment. The volume ratio of the gold nanoparticle solution to the iron supplement solution should be 1-10:10-30, preferably 1-5:10-20.

[0028] Furthermore, the inventors of the present invention further discovered for the first time that if the gold nanoparticles are gold nanoparticles modified with specific small molecules, and are used in combination with iron agents to make iron supplements, then it can not only effectively regulate the intestinal flora, promote the proliferation of beneficial bacteria, reduce the colonization of harmful bacteria, reduce the occurrence of intestinal infections, and reduce the impact of traditional oral iron supplements on the intestinal flora, but also further promote the improvement of the absorption rate of iron and accelerate the recovery of iron deficiency anemia.

[0029] Specifically, the gold nanoparticle solution of the present invention can be prepared by the following method: dissolving a reducing agent, a small molecule ligand and a stabilizer in a first solvent, gently stirring for a period of time (hereinafter also referred to as the first mixing), then adding tetrahydrated chloroauric acid, vigorously stirring for a period of time (hereinafter also referred to as the second mixing), collecting the solution, dialyzing with a dialysis bag with a molecular weight cutoff of 5000Da, and finally filtering with a microporous membrane filter with a pore size of 0.22μm to obtain a gold nanoparticle solution.

[0030] The first solvent may be any one or more of ultrapure water, methanol, ethanol, ethylene glycol, and n-propanol. Ultrapure water is preferably used as the first solvent because the gold particles subsequently prepared require dialysis and oral administration. Ultrapure water facilitates thorough dialysis, removes unreacted ligands, and is more suitable for oral administration.

[0031] In addition, the reducing agent can be any one or more of sodium citrate, sodium borohydride, glutathione, hydrazine hydrate, and ascorbic acid. Preferably, the reducing agent is sodium borohydride and / or glutathione, because sodium borohydride and glutathione have stronger reducing properties, which is conducive to the preparation of smaller gold nanoparticles (5-30 nm).

[0032] In addition, the small molecule ligand can be any one or more of 4,6-diamino-2-mercaptopyrimidine (DAPT), 2,4-diamino-6-mercaptopyrimidine (LDAPT), 4-mercaptopyridine (4-P), 2-mercaptopyridine (2-P), 4-mercaptophenylboronic acid (4-MBA), 5-(pyridin-3-yl)-1,3,4-oxadiazole-2-thiol (5-3-PO), 5-(pyridin-4-yl)-1,3,4-oxadiazole-2-thiol (5-4-PO), quinoline-4-thiol (Q4T), 3-mercaptoquinoline (3-Q), 4-aminophenol (4-AP), 5-aminoindole (5-AI), tryptophan (W), 4-aminophenylboronic acid (4-ABA), 6-aminopenicillanic acid (6-APA), and 7-aminocephalosporanic acid (7-ACA). The preferred small molecule ligands are 4,6-diamino-2-mercaptopyrimidine (DAPT) and / or 5-aminoindole (5-AI). This is because DAPT and 5-AI modified gold nanoparticles are positively charged, which is beneficial to the positive regulation of intestinal flora and the reduction of intestinal inflammation.

[0033] Alternatively, the stabilizer may be any one or more of Tween 20, Tween 40, Tween 80, polyvinyl pyrrolidone (average mw = 8000), polyvinyl pyrrolidone (average mw = 10000), and polyvinyl pyrrolidone (average mw = 24000). Tween 80 is preferred as the stabilizer due to its good biosafety, low hemolysis rate, and ability to maintain stable dispersion of gold nanoparticles for a longer period of time.

[0034] Furthermore, when preparing the gold nanoparticle solution, the stabilizer can be added in a ratio of 100 to 500 μL per 20 mL of the first solvent. However, if more than 200 μL of stabilizer is added per 20 mL of the first solvent, the emulsification effect is too strong, foaming increases, and dialysis is not conducive. If the stabilizer is added in an amount less than 100 μL, the stabilization effect is not significant and particle agglomeration is likely to occur. Therefore, it is preferred to add 100 to 200 μL of stabilizer per 20 mL of the first solvent.

[0035] In addition, the molar ratio of chloroauric acid tetrahydrate, the reducing agent, and the small molecule ligand added to the first solvent can be 1-3:1-5:1-10.

[0036] In addition, when preparing the gold nanoparticle solution, the first mixing can be stirred at a stirring rate of 200 to 500 rpm for 10 to 30 minutes. Considering that if the stirring time of the first mixing is less than 15 minutes, it may cause uneven mixing of the solute and insufficient dissolution, if the stirring time is greater than 25 minutes, the presence of the stabilizer may cause the stabilizer to produce a large amount of foam. Moreover, if the stirring rate of the first mixing is lower than 300 rpm, the solute dissolves slowly, and if it is greater than 400 rpm, a large amount of foam is likely to occur. Therefore, it is preferred that the first mixing be stirred at a stirring rate of 300 to 400 rpm for 15 to 25 minutes.

[0037] When preparing a gold nanoparticle solution, the second mixing step can be performed at a stirring rate of 800-1200 rpm for 30-60 minutes. However, if the stirring time for the second mixing step is less than 30 minutes and the stirring rate is less than 1000 rpm, the gold nanoparticles will be unevenly dispersed and easily agglomerated. If the stirring time is greater than 40 minutes and the stirring rate is greater than 1200 rpm, energy consumption will increase and the growth of the gold nanoparticles will be detrimental. Therefore, the second mixing step is preferably performed at a stirring rate of 1000-1200 rpm for 30-40 minutes.

[0038] The iron solution of the present invention can be prepared by the following method: dissolving the iron in the second solvent, and filtering with a microporous membrane filter with a pore size of 0.22 μm to obtain the iron solution.

[0039] Wherein, iron preparation can be any one or more of ferrous sulfate, ferrous fumarate, dextran iron, ferrous gluconate, ferrous succinate, ferrous lactate. Considering that ferrous sulfate is typical inorganic acid ferrous salt, ferrous gluconate is typical organic acid ferrous salt, and ferrous sulfate has a wider scope of application, is the primary choice of oral iron supplementation clinically, and iron content is high; and the iron content of ferrous gluconate is relatively low, is easily absorbed, and has less stimulation to the gastrointestinal tract. Therefore, preferably iron preparation is ferrous sulfate and / or ferrous gluconate.

[0040] In addition, the second solvent can be any one of deionized water, phosphate buffered saline (PBS), and a 0.9% sodium chloride aqueous solution. The second solvent is preferably deionized water, which can avoid interference from other ions.

[0041] It should be noted that in the present invention, the gold nanoparticle solution and the iron solution are preferably each filtered through a microporous membrane filter with a pore size of 0.22 μm before being mixed to form the iron supplement. This is because a 0.22 μm microporous membrane filter can achieve the 99.99% sterilization requirement specified in the Pharmacopoeia. A pore size larger than 0.22 μm risks incomplete microbial filtration, making it unsuitable for oral administration. A pore size too small increases the filtration resistance. Therefore, using a microporous membrane filter with a pore size of 0.22 μm fully meets the sterility and oral requirements.

[0042] In addition, the prepared gold nanoparticle solution is preferably stored at low temperatures, specifically at 4°C, until ready for use. This is because the concentration of gold nanoparticles in the solution is relatively high at this temperature. Storing it at low temperatures prevents the gold nanoparticles from aggregating and settling, making the gold nanoparticle solution more stable. When the gold nanoparticle solution is mixed with the iron solution, the concentration of the gold nanoparticles decreases, so the prepared iron supplement does not need to be stored at low temperatures.

[0043] The technical scheme and technical effects of the present invention are described in more detail below through Examples 1 to 8.

[0044] It should be noted that the SD rat iron deficiency anemia model used in the present invention is established by feeding female SD rats with an iron deficiency model feed for 30-40 days to induce anemia. The modeling period is preferably 35 days, and the rats are preferably 21-day-old weaned female SD rats. Furthermore, when the SD rat iron deficiency anemia model is treated by gavage, the gavage period is 7 to 21 days, preferably 7 to 14 days.

[0045] Example 1

[0046] 0.06 mmol sodium borohydride, 0.06 mmol DAPT, and 100 μL Tween 80 were dissolved in 20 mL ultrapure water and added to a 50 mL round-bottom flask. The mixture was placed in an ice bath and stirred at 300 rpm for 15 min. 0.06 mmol chloroauric acid tetrahydrate was then added and stirred at 1000 rpm for 30 min. The solution was collected and dialyzed using a dialysis bag with a molecular weight cutoff of 5000 Da. Finally, it was filtered through a microporous membrane filter with a pore size of 0.22 μm. The collected DAPT-modified gold nanoparticle (DAPT-Au NPs) solution was stored at 4°C until use. The particle size and concentration of the small molecule ligand-modified gold nanoparticles prepared in Example 1 were characterized using a nanoparticle size analyzer and an inductively coupled plasma mass spectrometer, respectively. The results showed that the hydrated particle size of the prepared DAPT-Au NPs was 15 ± 1.2 nm, and the concentration of the DAPT-Au NPs solution was 650 μg / mL.

[0047] 5 mg of ferrous sulfate was dissolved in 1 mL of deionized water and filtered through a 0.22 μm pore size microporous membrane filter to obtain an iron supplement solution. The DAPT-Au NPs solution and the ferrous sulfate solution were mixed at a volume ratio of 1:10 to obtain the iron supplement preparation of Example 1 of the present invention.

[0048] Take 1.1 mL of the iron supplement preparation of Example 1 (it should be noted that 1.1 mL here refers to the amount obtained by mixing 100 μL of DAPT-Au NPs solution and 1 mL of ferrous sulfate solution. For the sake of convenience, it is collectively referred to as "1.1 mL", but in actual operation, the mixing of the two solutions will cause some deviation in the volume of the mixed solution. The following Examples 2 to 8 are the same as this situation and will not be repeated hereafter) and 35-day-old weaned SD female rats with iron deficiency anemia were treated by gavage for 7 days and set as a combined treatment group. In addition, normal rats, iron deficiency anemia rats, iron deficiency anemia rats orally administered with 100 μL of DAPT-Au NPs solution alone, and iron deficiency anemia rats orally administered with 1 mL of ferrous sulfate solution alone were set as control groups. After the treatment, blood and fresh feces were collected for the detection of blood routine, inflammatory factors and intestinal flora, respectively.

[0049] The collected whole blood, serum obtained by centrifugation, and fresh feces were characterized using animal blood routine tester, ELISA kit, and 16S rRNA sequencing, respectively. The normal range of red blood cell count was 6.36-9.42×10 12 / L, the normal range of hemoglobin is 110-143g / L, and the following test results are obtained.

[0050] Table 1: Animal experiment results of Example 1

[0051]

[0052] As can be seen from Table 1, compared with single treatment, the iron supplement preparation of Example 1 significantly increased the content of RBC and HGB in the blood, effectively promoting the recovery of iron deficiency anemia; at the same time, the iron supplement preparation of Example 1 reduced the content of the pro-inflammatory factor TNF-α in the serum, increased the content of the anti-inflammatory factor IL-10, and effectively reduced the occurrence of inflammation; secondly, the iron supplement preparation of Example 1 reduced the abundance of opportunistic pathogens Escherichia-Shigella and Enterococcus, promoted the colonization of Butyricicoccus and Lactobacillus, was beneficial to maintaining the intestinal microecology, reduced bacterial competition for iron, and promoted the host's absorption of iron.

[0053] Example 2

[0054] 0.18 mmol sodium borohydride, 0.06 mmol DAPT, and 200 μL Tween 80 were dissolved in 20 mL ultrapure water and added to a 50 mL round-bottom flask. The mixture was placed in an ice bath and stirred at 400 rpm for 20 min. 0.12 mmol chloroauric acid tetrahydrate was then added and stirred at 1200 rpm for 30 min. The solution was collected and dialyzed using a dialysis bag with a molecular weight cutoff of 5000 Da. Finally, the solution was filtered through a microporous membrane filter with a pore size of 0.22 μm. The collected DAPT-modified gold nanoparticle (DAPT-Au NPs) solution was stored at 4°C until use. The particle size and concentration of the small molecule ligand-modified gold nanoparticles prepared in Example 2 were characterized using a nanoparticle size analyzer and an inductively coupled plasma mass spectrometer, respectively. The results showed that the hydrated particle size of the prepared DAPT-Au NPs was 10 ± 2.3 nm, and the concentration of the collected solution was 700 μg / mL.

[0055] Dissolve 10 mg of ferrous sulfate in 1 mL of deionized water and filter through a 0.22 μm pore size microporous membrane filter to obtain an iron supplement solution. Mix the DAPT-Au NPs solution with the ferrous sulfate solution in a volume ratio of 1:20 to obtain the iron supplement preparation of Example 2 of the present invention.

[0056] 1.05 mL of the iron supplement preparation of Example 2 was taken for 14 days of gavage treatment of the iron deficiency anemia model of 35-day-old weaned SD female rats. Normal rats, iron deficiency anemia rats, iron deficiency anemia rats orally administered with 50 μL of DAPT-Au NPs solution alone, and iron deficiency anemia rats orally administered with 1 mL of ferrous sulfate solution alone were set as control groups. After the treatment, blood and fresh feces were collected for the detection of blood routine, inflammatory factors and intestinal flora, respectively.

[0057] The collected whole blood, serum obtained by centrifugation, and fresh feces were characterized using animal blood routine tester, ELISA kit, and 16S rRNA sequencing, respectively. The normal range of red blood cell count was 6.36-9.42×10 12 / L, the normal range of hemoglobin is 110-143g / L, and the following test results are obtained.

[0058] Table 2: Animal experiment results of Example 2

[0059]

[0060] As can be seen from Table 2, compared with single treatment, the iron supplement preparation of Example 2 significantly increased the content of RBC and HGB in the blood, effectively promoting the recovery of iron deficiency anemia; at the same time, the iron supplement preparation of Example 2 reduced the content of pro-inflammatory factor TNF-α in serum, increased the content of anti-inflammatory factor IL-10, and effectively reduced the occurrence of inflammation; secondly, the iron supplement preparation of Example 2 reduced the abundance of opportunistic pathogens Escherichia-Shigella and Enterococcus, promoted the colonization of Butyricicoccus and Lactobacillus, was beneficial to maintaining intestinal microecology, reduced bacterial competition for iron, and promoted the host's absorption of iron.

[0061] Example 3

[0062] 0.06 mmol sodium borohydride, 0.06 mmol DAPT, and 100 μL Tween 80 were dissolved in 20 mL ultrapure water and added to a 50 mL round-bottom flask. The mixture was placed in an ice bath and stirred at 300 rpm for 15 min. 0.12 mmol chloroauric acid tetrahydrate was then added and stirred at 1000 rpm for 30 min. The solution was collected and dialyzed using a dialysis bag with a molecular weight cutoff of 5000 Da. Finally, the solution was filtered through a microporous membrane filter with a pore size of 0.22 μm. The collected DAPT-modified gold nanoparticle (DAPT-Au NPs) solution was stored at 4°C until use. The particle size and concentration of the small molecule ligand-modified gold nanoparticles prepared in Example 3 were characterized using a nanoparticle size analyzer and an inductively coupled plasma mass spectrometer, respectively. The results showed that the hydrated particle size of the prepared DAPT-Au NPs was 19 ± 1.8 nm, and the concentration of the collected solution was 600 μg / mL.

[0063] 5 mg of ferric gluconate was dissolved in 1 mL of deionized water and filtered through a 0.22 μm pore size microporous membrane filter to obtain an iron supplement solution. The DAPT-Au NPs solution was mixed with the ferrous sulfate solution in a volume ratio of 2:10 to obtain the iron supplement preparation of Example 3 of the present invention.

[0064] 1.2 mL of the iron supplement preparation of Example 3 was taken for 7 days of gavage treatment of the iron deficiency anemia model of 35-day-old weaned SD female rats, and normal rats, iron deficiency anemia rats, iron deficiency anemia rats orally administered with 200 μL of DAPT-Au NPs solution alone, and iron deficiency anemia rats orally administered with 1 mL of ferric gluconate solution alone were set as control groups. After the treatment, blood and fresh feces were collected for the detection of blood routine, inflammatory factors and intestinal flora, respectively.

[0065] The collected whole blood, serum obtained by centrifugation, and fresh feces were characterized using an animal blood routine tester, ELISA kit, and 16S rRNA sequencing, respectively. The normal range of red blood cell count was 6.36-9.42×10 12 / L, the normal range of hemoglobin is 110-143g / L, and the following test results are obtained.

[0066] Table 3: Animal experiment results of Example 3

[0067]

[0068] As can be seen from Table 3, compared with single treatment, the iron supplement preparation of Example 3 increased the content of RBC and HGB in the blood, effectively promoting the recovery of iron deficiency anemia; at the same time, the iron supplement preparation of Example 3 reduced the content of pro-inflammatory factor TNF-α in serum, increased the content of anti-inflammatory factor IL-10, and effectively reduced the occurrence of inflammation; secondly, the iron supplement preparation of Example 3 reduced the abundance of opportunistic pathogens Escherichia-Shigella and Enterococcus, promoted the colonization of Butyricicoccus and Lactobacillus, which is beneficial to maintaining intestinal microecology, reducing bacterial competition for iron, and promoting the host's absorption of iron.

[0069] Example 4

[0070] 0.18 mmol sodium borohydride, 0.06 mmol DAPT, and 100 μL Tween 80 were dissolved in 20 mL ultrapure water and added to a 50 mL round-bottom flask. The mixture was placed in an ice bath and stirred at 400 rpm for 25 min. 0.12 mmol chloroauric acid tetrahydrate was then added and stirred at 1200 rpm for 40 min. The solution was collected and dialyzed using a dialysis bag with a molecular weight cutoff of 5000 Da. Finally, it was filtered through a microporous membrane filter with a pore size of 0.22 μm. The collected DAPT-modified gold nanoparticle (DAPT-Au NPs) solution was stored at 4°C until use. The particle size and concentration of the small molecule ligand-modified gold nanoparticles prepared in Example 4 were characterized using a nanoparticle size analyzer and an inductively coupled plasma mass spectrometer, respectively. The results showed that the hydrated particle size of the prepared DAPT-Au NPs was 8±0.9 nm, and the concentration of the collected solution was 500 μg / mL.

[0071] Dissolve 10 mg of ferric gluconate in 1 mL of deionized water and filter through a 0.22 μm pore size microporous membrane filter to obtain an iron supplement solution. Mix the DAPT-Au NPs solution with the ferric gluconate solution in a volume ratio of 2:15 to obtain the iron supplement preparation of Example 4 of the present invention.

[0072] 1.7 mL of the iron supplement preparation of Example 4 was taken for 14 days of gavage treatment of the iron deficiency anemia model of 35-day-old weaned SD female rats, and normal rats, iron deficiency anemia rats, iron deficiency anemia rats orally administered with 200 μL of DAPT-Au NPs solution alone, and iron deficiency anemia rats orally administered with 1.5 mL of ferric gluconate solution alone were set as control groups. After the treatment, blood and fresh feces were collected for the detection of blood routine, inflammatory factors and intestinal flora, respectively.

[0073] The collected whole blood, serum obtained by centrifugation, and fresh feces were characterized using an animal blood routine tester, ELISA kit, and 16S rRNA sequencing, respectively. The normal range of red blood cell count was 6.36-9.42×10 12 / L, the normal range of hemoglobin is 110-143g / L, and the following test results are obtained.

[0074] Table 4: Animal experiment results of Example 4

[0075]

[0076] As can be seen from Table 4, compared with single treatment, the iron supplement preparation of Example 4 increased the content of RBC and HGB in the blood, effectively promoting the recovery of iron deficiency anemia; at the same time, the iron supplement preparation of Example 4 reduced the content of pro-inflammatory factor TNF-α in serum, increased the content of anti-inflammatory factor IL-10, and effectively reduced the occurrence of inflammation; secondly, the iron supplement preparation of Example 4 reduced the abundance of opportunistic pathogens Escherichia-Shigella and Enterococcus, promoted the colonization of Butyricicoccus and Lactobacillus, which is beneficial to maintaining the intestinal microecology, reducing bacterial competition for iron, and promoting the host's absorption of iron.

[0077] Example 5

[0078] 0.06mmoL sodium borohydride, 0.06mmol 5-AI and 100μL Tween 80 were dissolved in 20mL ultrapure water and added to a 50mL round-bottom flask, placed in an ice bath, and stirred at 300rpm for 15min. Then 0.06mmol tetrahydrated chloroauric acid was added and stirred at 1000rpm for 30min. The solution was collected and dialyzed with a dialysis bag with a molecular weight cutoff of 5000Da. Finally, it was filtered with a microporous membrane filter with a pore size of 0.22μm. The collected 5-AI modified gold nanoparticles (5-AI-Au NPs) solution was stored at 4°C for later use. The particle size and concentration of the small molecule ligand modified gold nanoparticles prepared in Example 5 were characterized by a nanoparticle size analyzer and an inductively coupled plasma mass spectrometer, respectively. The results showed that the hydrated particle size of the prepared 5-AI-Au NPs was 25±1.2nm, and the concentration of the collected solution was 400μg / mL.

[0079] 5 mg of ferrous sulfate was dissolved in 1 mL of deionized water and filtered through a 0.22 μm pore size microporous membrane filter to obtain an iron supplement solution. The 5-AI-Au NPs solution and the ferrous sulfate solution were mixed in a volume ratio of 1:10 to obtain the iron supplement preparation of Example 5 of the present invention.

[0080] 1.1 mL of the iron supplement preparation of Example 5 was taken for 7 days of gavage treatment of the iron deficiency anemia model of 35-day-old weaned SD female rats, and normal rats, iron deficiency anemia rats, iron deficiency anemia rats orally administered with 100 μL of 5-AI-Au NPs solution alone, and iron deficiency anemia rats orally administered with 1 mL of ferrous sulfate solution alone were set as control groups. After the treatment, blood and fresh feces were collected for the detection of blood routine, inflammatory factors and intestinal flora, respectively.

[0081] The collected whole blood, serum obtained by centrifugation, and fresh feces were characterized using an animal blood routine tester, ELISA kit, and 16S rRNA sequencing, respectively. The normal range of red blood cell count was 6.36-9.42×10 12 / L, the normal range of hemoglobin is 110-143g / L, and the following test results are obtained.

[0082] Table 5: Animal experiment results of Example 5

[0083]

[0084] As can be seen from Table 5, compared with single treatment, the iron supplement preparation of Example 5 significantly increased the content of RBC and HGB in the blood, effectively promoting the recovery of iron deficiency anemia; at the same time, the iron supplement preparation of Example 5 reduced the content of pro-inflammatory factor TNF-α in serum, increased the content of anti-inflammatory factor IL-10, and effectively reduced the occurrence of inflammation; secondly, the iron supplement preparation of Example 5 reduced the abundance of opportunistic pathogens Escherichia-Shigella and Enterococcus, promoted the colonization of Butyricicoccus and Lactobacillus, was beneficial to maintaining the intestinal microecology, reduced bacterial competition for iron, and promoted the host's absorption of iron.

[0085] Example 6

[0086] 0.18mmoL glutathione, 0.06mmol 5-AI and 200μL Tween 80 were dissolved in 20mL ultrapure water and added to a 50mL round-bottom flask, placed in an ice bath, stirred at 400rpm for 20min, then 0.12mmol tetrahydrate chloroauric acid was added and stirred at 1200rpm for 30min. The solution was collected and dialyzed with a dialysis bag with a molecular weight cutoff of 5000Da. Finally, it was filtered with a microporous membrane filter with a pore size of 0.22μm. The collected 5-AI modified gold nanoparticles (5-AI-Au NPs) solution was stored at 4°C for later use. The particle size and concentration of the small molecule ligand-modified gold nanoparticles prepared in Example 6 were characterized using a nanoparticle size analyzer and an inductively coupled plasma mass spectrometer, respectively. The results showed that the hydrated particle size of the prepared 5-AI-Au NPs was 12±0.8nm and the concentration of the collected solution was 750μg / mL.

[0087] Dissolve 10 mg of ferrous sulfate in 1 mL of deionized water and filter through a 0.22 μm pore size microporous membrane filter to obtain an iron supplement solution. Mix the 5-AI-Au NPs solution with the ferrous sulfate solution in a volume ratio of 1:20 to obtain the iron supplement preparation of Example 6 of the present invention.

[0088] 1.05 mL of the iron supplement preparation of Example 6 was taken for 14 days of gavage treatment of the iron deficiency anemia model of 35-day-old weaned SD female rats, and normal rats, iron deficiency anemia rats, iron deficiency anemia rats orally administered with 50 μL of 5-AI-Au NPs solution alone, and iron deficiency anemia rats orally administered with 1 mL of ferrous sulfate solution alone were set as control groups. After the treatment, blood and fresh feces were collected for the detection of blood routine, inflammatory factors and intestinal flora, respectively.

[0089] The collected whole blood, serum obtained by centrifugation, and fresh feces were characterized using an animal blood routine tester, ELISA kit, and 16S rRNA sequencing, respectively. The normal range of red blood cell count was 6.36-9.42×10 12 / L, the normal range of hemoglobin is 110-143g / L, and the following test results are obtained.

[0090] Table 6: Animal experiment results of Example 6

[0091]

[0092] As can be seen from Table 6, compared with single treatment, the iron supplement preparation of Example 6 significantly increased the content of RBC and HGB in the blood, effectively promoting the recovery of iron deficiency anemia; at the same time, the iron supplement preparation of Example 6 reduced the content of pro-inflammatory factor TNF-α in serum, increased the content of anti-inflammatory factor IL-10, and effectively reduced the occurrence of inflammation; secondly, the iron supplement preparation of Example 6 reduced the abundance of opportunistic pathogens Escherichia-Shigella and Enterococcus, promoted the colonization of Butyricicoccus and Lactobacillus, which is beneficial to maintaining intestinal microecology, reducing bacterial competition for iron, and promoting the host's absorption of iron.

[0093] Example 7

[0094] 0.06mmoL sodium borohydride, 0.06mmol 5-AI and 100μL Tween 80 were dissolved in 20mL ultrapure water and added to a 50mL round-bottom flask, placed in an ice bath, and stirred at 300rpm for 15min. Then 0.12mmol tetrahydrated chloroauric acid was added and stirred at 1000rpm for 30min. The solution was collected and dialyzed with a dialysis bag with a molecular weight cutoff of 5000Da. Finally, it was filtered with a microporous membrane filter with a pore size of 0.22μm. The collected 5-AI modified gold nanoparticles (5-AI-Au NPs) solution was stored at 4°C for later use. The particle size and concentration of the small molecule ligand modified gold nanoparticles prepared in Example 7 were characterized using a nanoparticle size analyzer and an inductively coupled plasma mass spectrometer, respectively. The results showed that the hydrated particle size of the prepared 5-AI-Au NPs was 25±2.4nm, and the concentration of the collected solution was 700μg / mL.

[0095] 5 mg of ferric gluconate was dissolved in 1 mL of deionized water and filtered through a 0.22 μm pore size microporous membrane filter to obtain an iron supplement solution. The 5-AI-Au NPs solution and the ferric gluconate solution were mixed in a volume ratio of 2:10 to obtain the iron supplement preparation of Example 7 of the present invention.

[0096] 1.2 mL of the iron supplement preparation of Example 7 was taken for 7 days of gavage treatment of the iron deficiency anemia model of 35-day-old weaned SD female rats, and normal rats, iron deficiency anemia rats, iron deficiency anemia rats orally administered with 200 μL of 5-AI-Au NPs solution alone, and iron deficiency anemia rats orally administered with 1 mL of ferric gluconate solution alone were set as control groups. After the treatment, blood and fresh feces were collected for the detection of blood routine, inflammatory factors and intestinal flora, respectively.

[0097] The collected whole blood, serum obtained by centrifugation, and fresh feces were characterized using an animal blood routine tester, ELISA kit, and 16S rRNA sequencing, respectively, and the following test results were obtained.

[0098] Table 7: Animal experiment results of Example 7

[0099]

[0100] As can be seen from Table 7, compared with single treatment, the iron supplement preparation of Example 7 increased the content of RBC and HGB in the blood, effectively promoting the recovery of iron deficiency anemia; at the same time, the iron supplement preparation of Example 7 reduced the content of pro-inflammatory factor TNF-α in serum, increased the content of anti-inflammatory factor IL-10, and effectively reduced the occurrence of inflammation; secondly, the iron supplement preparation of Example 7 reduced the abundance of opportunistic pathogens Escherichia-Shigella and Enterococcus, promoted the colonization of Butyricicoccus and Lactobacillus, which is beneficial to maintaining intestinal microecology, reducing bacterial competition for iron, and promoting the host's absorption of iron.

[0101] Example 8

[0102] 0.18mmoL glutathione, 0.06mmol 5-AI and 100μL Tween 80 were dissolved in 20mL ultrapure water and added to a 50mL round-bottom flask, placed in an ice bath, stirred at 400rpm for 25min, then 0.12mmol tetrahydrate chloroauric acid was added and stirred at 1200rpm for 40min. The solution was collected and dialyzed with a dialysis bag with a molecular weight cutoff of 5000Da. Finally, it was filtered with a microporous membrane filter with a pore size of 0.22μm. The collected 5-AI modified gold nanoparticles (5-AI-Au NPs) solution was stored at 4°C for later use. The particle size and concentration of the small molecule ligand-modified gold nanoparticles prepared in Example 8 were characterized by a nanoparticle size analyzer and an inductively coupled plasma mass spectrometer, respectively. The hydrated particle size of the prepared 5-AI-Au NPs was 5±1.2nm, and the concentration of the collected solution was 500μg / mL.

[0103] 10 mg of ferric gluconate was dissolved in 1 mL of deionized water and filtered through a 0.22 μm pore size microporous membrane filter to obtain an iron supplement solution. The 5-AI-Au NPs solution and the ferric gluconate solution were mixed in a volume ratio of 2:15 to obtain the iron supplement preparation of Example 8 of the present invention.

[0104] 1.7 mL of the iron supplement preparation of Example 8 was taken for 14 days of gavage treatment of the iron deficiency anemia model of 35-day-old weaned SD female rats, and normal rats, iron deficiency anemia rats, iron deficiency anemia rats orally administered with 200 μL of 5-AI-Au NPs solution alone, and iron deficiency anemia rats orally administered with 1.5 mL of ferrous sulfate solution alone were set as control groups. After the treatment, blood and fresh feces were collected for the detection of blood routine, inflammatory factors and intestinal flora, respectively.

[0105] The collected whole blood, serum obtained by centrifugation, and fresh feces were characterized using an animal blood routine tester, ELISA kit, and 16S rRNA sequencing, respectively. The normal range of red blood cell count was 6.36-9.42×10 12 / L, the normal range of hemoglobin is 110-143g / L, and the following test results are obtained.

[0106] Table 8: Animal experiment results of Example 8

[0107]

[0108] As can be seen from Table 8, compared with single treatment, the iron supplement preparation of Example 8 increased the content of RBC and HGB in the blood, effectively promoting the recovery of iron deficiency anemia; at the same time, the iron supplement preparation of Example 8 reduced the content of pro-inflammatory factor TNF-α in serum, increased the content of anti-inflammatory factor IL-10, and effectively reduced the occurrence of inflammation; secondly, the iron supplement preparation of Example 8 reduced the abundance of opportunistic pathogens Escherichia-Shigella and Enterococcus, promoted the colonization of Butyricicoccus and Lactobacillus, which is beneficial to maintaining the intestinal microecology, reducing bacterial competition for iron, and promoting the host's absorption of iron.

[0109] In summary, the present invention aims to overcome the side effects of existing oral iron supplements on intestinal flora, reduce inflammation, and improve iron absorption. For the first time, it combines the high antibacterial effect of gold nanoparticles with the advantages of oral iron supplements, such as good patient compliance, to achieve more efficient and safe oral iron supplementation, providing a new approach for treating patients with iron deficiency anemia. The present invention focuses on mixing metal nanoparticles with iron supplements to prepare an iron supplement. The small-molecule-modified gold nanoparticles can significantly reduce the side effects of a simple oral iron supplement while improving the efficiency of iron supplementation.

[0110] The technical solution according to the present invention mainly has the following technical effects:

[0111] (1) The present invention combines gold nanoparticles modified with small molecule ligands with iron agents to obtain an iron supplement preparation, which can promote the absorption of iron and accelerate the recovery of iron deficiency anemia.

[0112] (2) The present invention combines gold nanoparticles modified with small molecule ligands with iron agents to obtain an iron supplement preparation, which can effectively regulate intestinal flora, promote the proliferation of beneficial bacteria, reduce the colonization of harmful bacteria, and reduce the occurrence of intestinal infections.

[0113] (3) The present invention combines gold nanoparticles modified with small molecule ligands with iron agents to obtain an iron supplement preparation, which can effectively reduce intestinal inflammation and promote the absorption of iron by the duodenum.

[0114] (4) The present invention is the first to combine functional metal nanoparticles with iron agents to obtain an iron supplement preparation, which is used to treat iron deficiency anemia, providing a new approach for the treatment of iron deficiency anemia and a new idea for the treatment of deficiencies of other metal elements.

[0115] The above embodiments, particularly any "preferred" embodiments, are possible examples of implementations and are presented merely for a clear understanding of the principles of the present invention. Many changes and modifications may be made to the above embodiments without departing substantially from the spirit and principles of the technology described herein. All modifications are intended to be included within the scope of this disclosure.

[0116] All documents mentioned in this specification are incorporated herein by reference, as if each document were incorporated herein by reference in its entirety.

[0117] In addition, it should be understood that after reading the above description of the present invention, those skilled in the art may make various changes or modifications to the present invention, and these equivalent forms also fall within the scope of protection of the present invention.

Claims

1. A method for preparing an iron supplement preparation, characterized in that: The preparation method of the iron supplement preparation comprises: Step (i), preparing a gold nanoparticle solution having a gold nanoparticle concentration of 200 to 1000 μg / mL and an iron solution having an iron concentration of 3 to 50 mg / mL; and Step (ii) mixing the gold nanoparticle solution and the iron solution in a volume ratio of 1-10:10-30.

2. The method for preparing the iron supplement preparation according to claim 1, wherein In the step (i), the concentration of the gold nanoparticle solution is 200-800 μg / mL, and the concentration of the iron solution is 3-20 mg / mL. In the step (ii), the gold nanoparticle solution and the iron solution are mixed in a volume ratio of 1-5:10-20.

3. The method for preparing the iron supplement preparation according to claim 1, wherein: In the step (i), the reducing agent, the small molecule ligand and the stabilizer are dissolved in a first solvent under ice bath conditions, mixed for the first time, chloroauric acid tetrahydrate is added, mixed for the second time, dialyzed with a dialysis bag with a molecular weight cutoff of 5000 Da, and filtered with a microporous membrane filter with a pore size of 0.22 μm to obtain the gold nanoparticle solution. Wherein, the first solvent is any one or more of ultrapure water, methanol, ethanol, ethylene glycol, and n-propanol, The reducing agent is any one or more of sodium citrate, sodium borohydride, glutathione, hydrazine hydrate, and ascorbic acid. The small molecule ligand is any one or more of 4,6-diamino-2-mercaptopyrimidine, 2,4-diamino-6-mercaptopyrimidine, 4-mercaptopyridine, 2-mercaptopyridine, 4-mercaptophenylboronic acid, 5-(pyridin-3-yl)-1,3,4-oxadiazole-2-thiol, 5-(pyridin-4-yl)-1,3,4-oxadiazole-2-thiol, quinoline-4-thiol, 3-mercaptoquinoline, 4-aminophenol, 5-aminoindole, tryptophan, 4-aminophenylboronic acid, 6-aminopenicillanic acid, and 7-aminocephalosporanic acid. The stabilizer is any one or more of Tween 20, Tween 40, Tween 80, polyvinyl pyrrolidone with an average molecular weight of 8,000, polyvinyl pyrrolidone with an average molecular weight of 10,000, and polyvinyl pyrrolidone with an average molecular weight of 24,000.

4. The method for preparing the iron supplement preparation according to claim 3, wherein: In the step (i), the first solvent is ultrapure water, The reducing agent is sodium borohydride and / or glutathione, The small molecule ligand is 4,6-diamino-2-mercaptopyrimidine and / or 5-aminoindole, The stabilizer is Tween 80.

5. The method for preparing the iron supplement preparation according to claim 3, wherein: In said step (i), The addition ratio of the stabilizer is: add 100 to 500 μL of the stabilizer to every 20 mL of the first solvent, The molar ratio of the tetrahydrated chloroauric acid, the reducing agent and the small molecule ligand is 1-3:1-5:1-10.

6. The method for preparing the iron supplement preparation according to claim 3, wherein: In the step (i), the first mixing is carried out at a stirring rate of 200 to 500 rpm for 10 to 30 minutes, and the second mixing is carried out at a stirring rate of 800 to 1200 rpm for 30 to 60 minutes.

7. The method for preparing the iron supplement preparation according to claim 1, wherein: In the step (i), the iron solution is obtained by dissolving the iron agent in the second solvent and filtering the solution through a microporous membrane filter with a pore size of 0.22 μm. Wherein, the iron agent is any one or more of ferrous sulfate, ferrous fumarate, iron dextran, ferrous gluconate, ferrous succinate, and ferrous lactate. The second solvent is any one of deionized water, phosphate buffer, and a sodium chloride aqueous solution with a mass fraction of 0.9%.

8. The method for preparing the iron supplement preparation according to claim 7, wherein: In the step (i), the iron agent is ferrous sulfate and / or ferric gluconate, and the second solvent is deionized water.

9. An iron supplement preparation, characterized in that: The iron supplement preparation is prepared by the preparation method of the iron supplement preparation according to any one of claims 1 to 8.

10. The iron supplement preparation according to claim 9, characterized in that The iron supplement preparation is an oral iron supplement preparation.

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