Use of iron oligomannose nanoparticles for the preparation of a gastrointestinal contrast agent

Abstract

The application belongs to the technical field of medicine, and discloses application of oligomannose iron nanoparticles in preparation of gastrointestinal contrast agent, wherein the oligomannose iron nanoparticles are formed by complexing oligomannose and inorganic iron salt, and the weight average molecular weight is 100,000-300,000. The nanoparticles further contain ferroferric oxide to form magnetic oligomannose iron nanoparticles. The oligomannose iron nanoparticles provided by the application remain stable in vitro gastric juice and intestinal juice within 72 hours, have good biocompatibility and safety, are not absorbed by the gastrointestinal tract, and reduce the risk of allergy, peritonitis, renal toxicity and nephrogenic systemic fibrosis of traditional contrast agents. Animal experiments show that the nanoparticles can achieve good contrast development in the gastrointestinal tract, and have excellent imaging effect. The gastrointestinal contrast agent provided by the application has the characteristics of high safety, good stability and clear imaging effect, and can provide a new contrast agent selection for imaging diagnosis of gastrointestinal diseases.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical technology, and in particular relates to the application of oligomannose iron nanoparticles in the preparation of gastrointestinal contrast agents. Background Technology

[0002] Gastrointestinal contrast imaging is one of the important methods for diagnosing gastrointestinal diseases. Currently, the commonly used gastrointestinal contrast agents in clinical practice mainly include barium sulfate, iodine-based contrast agents, and gadolinium-based contrast agents.

[0003] Barium sulfate, as a traditional gastrointestinal contrast agent, has the following drawbacks in clinical application: First, when a patient has gastrointestinal perforation, barium may leak into the abdominal cavity, causing serious infection, namely barium peritonitis; Second, after the examination, patients need to drink plenty of water or use laxatives to promote the excretion of barium, which may aggravate constipation or intestinal obstruction in elderly patients and patients with poor intestinal motility; Third, barium sulfate contrast agent may irritate the gastrointestinal mucosa, leading to mucosal congestion and edema, especially when the patient has pre-existing gastrointestinal diseases.

[0004] While iodine-based contrast agents such as meglumine diatrizoate are suitable for cases where barium sulfate is contraindicated (e.g., perforation), their hyperosmolarity may worsen the condition of patients with electrolyte imbalances or heart failure, and they have poor imaging effects on esophagotracheal fistulas. Furthermore, iodine-based contrast agents may cause contrast-induced nephropathy, especially in patients with renal insufficiency, diabetes, or dehydration; some patients are allergic to iodine or gadolinium, which may lead to rashes, respiratory distress, or even anaphylactic shock.

[0005] Gadolinium-based contrast agents may induce renal systemic fibrosis in patients with renal insufficiency, and gadolinium may accumulate in brain and bone tissues over a long period, posing a risk of metal deposition and impacting patient health. Furthermore, traditional contrast agents generally have limitations due to rapid metabolism and short imaging time, and their use is restricted in special populations such as pregnant women, children, and patients with thyroid disease.

[0006] Therefore, how to develop a safe, stable, and high-quality new gastrointestinal contrast agent is a technical problem that urgently needs to be solved in this field. Summary of the Invention

[0007] To address the aforementioned technical problems, this invention proposes the application of oligomannose iron nanoparticles in the preparation of gastrointestinal contrast agents. These oligomannose iron nanoparticles fully utilize the safety feature of oligomannose not being absorbed by the gastrointestinal tract, using oligomannose to encapsulate an iron core to form nanoscale particles, thus preparing a safe, efficient, homogeneous, stable, and imaging-effective gastrointestinal contrast agent.

[0008] To achieve the above objectives, this invention provides the application of oligomannose iron nanoparticles in the preparation of gastrointestinal contrast agents. The oligomannose iron nanoparticles are formed by complexing oligomannose with inorganic iron salts, and the weight-average molecular weight of the oligomannose iron nanoparticles is 100,000 to 300,000.

[0009] Preferably, the general chemical formula of oligomannose iron nanoparticles is: [FeO] x (OH) y (H2O) z ] n [(C6H 10 O5) m ] k ; Where x, y, and z are all 1 to 3; n is 1000 to 1400, representing the degree of polymerization of the iron core of ferric hydroxide; m is 9 to 30, representing the degree of polymerization of oligomannose; and k is 30 to 50, representing the amount of oligomannose.

[0010] Preferably, oligomannose-iron nanoparticles are prepared by a method comprising the following steps: S1. Oligomannose is prepared by enzymatic method, with an oligomannose having a weight-average molecular weight of 1500~5000; S2. Dissolve oligomannose in water, add sodium bromide as a catalyst and sodium hypochlorite as an oxidant, and react for 2 to 5 hours at pH 6.8~8.0 and 25℃~40℃ to obtain an oxidized solution; S3. Dissolve inorganic iron salts in water to prepare an iron salt solution; S4. The oxidizing solution obtained in step S2 is subjected to a complexation reaction with the iron salt solution obtained in step S3. During the complexation process, an alkaline solution is added dropwise to obtain a complex reaction solution. S5. The complex reaction solution is aged for 2-5 hours at a temperature of 85℃~100℃ and a pH of 6.8~8.0. S6. The aged complex reaction solution is added to anhydrous ethanol to form nanoparticles. After precipitation and filtration, the nanoparticles are washed with anhydrous ethanol and dried to obtain oligomannose iron nanoparticles.

[0011] Preferably, in step S2, oligomannose is dissolved in water to prepare an 8%~15% solution; in step S3, the inorganic iron salt is FeCl3·6H2O, and the mass ratio of FeCl3·6H2O to water is 1:3; in step S4, the complexation reaction specifically involves mixing the oxidized liquid obtained in step S2 with the iron salt solution obtained in step S3 at a volume ratio of 5:2, then adding dropwise to prepare an 8%~15% sodium carbonate solution, and performing the complexation reaction for 3~4 hours at a temperature of 30℃~60℃ and a pH value not exceeding 6.5; in step S6, the drying temperature is 50℃~80℃.

[0012] Preferably, the gastrointestinal contrast agent also includes magnetic oligomannose iron nanoparticles containing iron tetroxide.

[0013] Preferably, the magnetic oligomannose-iron nanoparticles are prepared by a method comprising the following steps: S1. Oligomannose is prepared by enzymatic method, with an oligomannose having a weight-average molecular weight of 1500~5000; S2. Dissolve oligomannose in water to prepare an 8%~15% solution, add sodium bromide catalyst and sodium hypochlorite oxidant, and react for 2~5 hours at pH 6.8~8.0 and 25℃~40℃ to obtain an oxidized solution; S3. Dissolve ferrous sulfate in deionized water, then mix it with ferric chloride. The molar ratio of ferrous ions to ferric ions in the mixed solution is 1.2:2. Under nitrogen protection, a water bath at 50℃~70℃ and a strong magnetic field, add sodium hydroxide solution dropwise until the pH reaches 10~11 and react for 2~5 hours to generate magnetic iron oxide particles. S4. Mix the oxidized liquid obtained in step S2 with the magnetic iron oxide particles obtained in step S3 at a volume ratio of 5:2, add 15%~20% sodium hydroxide solution, and perform a complexation reaction for 2~5 hours under the conditions of temperature 50℃~70℃, magnetic field strength 2T~10T, and pH 10~12 to obtain the complex reaction solution. S5. The complex reaction solution is aged at 90℃~100℃ and pH 7~8 for 2~5 hours; S6. The aged complex reaction solution is added to anhydrous ethanol to form nanoparticles. After precipitation and filtration, the nanoparticles are washed with anhydrous ethanol and dried at 60℃~80℃ to obtain magnetic oligomannose iron nanoparticles.

[0014] Preferably, the gastrointestinal contrast agent is an oral or enema formulation.

[0015] A gastrointestinal contrast agent is also provided, comprising the oligomannose iron nanoparticles or the magnetic oligomannose iron nanoparticles.

[0016] Preferably, the general chemical formula of oligomannose iron nanoparticles is: [FeO] x (OH) y (H2O) z ] n [(C6H 10 O5) m ] k ; Where x, y, and z are all 1 to 3; n is 1000 to 1400, representing the degree of polymerization of the iron core of ferric hydroxide; m is 9 to 30, representing the degree of polymerization of oligomannose; and k is 30 to 50, representing the amount of oligomannose.

[0017] Compared with the prior art, the present invention has the following advantages and technical effects: (1) This invention forms nanoparticles by complexing oligomannose with inorganic iron salts. The oligomannose in the oligomannose iron nanoparticles is not absorbed by the gastrointestinal tract, so that the contrast agent remains in the gastrointestinal tract and does not enter the blood circulation. This helps to reduce the impact of the contrast agent on liver and kidney function and the risk of systemic adverse reactions after absorption. At the same time, iron is an essential trace element for the human body, and even if a small amount is absorbed, it will not have an adverse effect on the human body.

[0018] (2) The application of oligomannose iron nanoparticles in contrast agents of the present invention reduces the risk of peritonitis, nephrotoxicity and renal systemic fibrosis in the prior art; at the same time, oligomannose iron nanoparticles can remain stable in gastric and intestinal fluids in vitro for 72 hours, and the contrast agent stays in the gastrointestinal tract for a long time, significantly prolonging the imaging time and meeting the time requirements of gastrointestinal contrast examination.

[0019] (3) The oligomannose in the oligomannose iron nanoparticles of the present invention is a natural polysaccharide with good biocompatibility and does not cause allergic reactions. It avoids the limitations of traditional contrast agents on pregnant women, children, patients with thyroid diseases and patients with renal insufficiency, and has a wider range of applicability. Moreover, it is prepared by enzymatic method, which has the advantages of mild reaction conditions, strong substrate specificity and high purity, which helps to reduce the interference of by-products and impurities on complexation reaction and contrast effect.

[0020] (4) The oligomannose iron nanoparticles provided by the present invention can also be prepared into magnetic oligomannose iron nanoparticles containing iron tetroxide, which is beneficial to expanding the application potential of the contrast agent in more imaging examination scenarios such as magnetic resonance imaging.

[0021] The technical solution of the present invention will be further described in detail below with reference to the accompanying drawings and embodiments. Attached Figure Description

[0022] Figure 1 This is a schematic diagram of the preparation method of oligomannose iron nanoparticles in the embodiment; Figure 2 The 0-hour chromatogram of a 100,000 weight-average molecular weight sample of oligomannose iron; Figure 3 The stability spectrum of 100,000 weight-average molecular weight oligomannose iron in gastrointestinal fluid after 72 hours; Figure 4 The 0-hour chromatogram of a 200,000 weight-average molecular weight sample of oligomannose iron; Figure 5 The stability spectrum of 200,000 weight-average molecular weight oligomannose iron in gastrointestinal fluid after 72 hours; Figure 6 The 0-hour chromatogram of a 300,000 weight-average molecular weight sample of oligomannose iron; Figure 7 The stability spectrum of oligomannose iron with a weight average molecular weight of 300,000 in gastrointestinal fluid after 72 hours; Figure 8 The 0-hour chromatogram of a magnetic oligomannose iron sample with a weight-average molecular weight of 300,000; Figure 9 The stability spectrum of magnetic oligomannose iron with a weight-average molecular weight of 300,000 in gastrointestinal fluid after 72 hours. Figure 10 The image shows the gastric contrast of a mouse sample with a weight-average molecular weight of 100,000 for oligomannose iron. Figure 11 The imaging results of mouse gastroscopy for a 200,000 weight-average molecular weight sample of oligomannose iron. Figure 12 The imaging results of mouse gastroscopy for a 300,000 weight-average molecular weight sample of oligomannose iron. Figure 13 The image shows the gastric contrast of a mouse sample containing 300,000 weight-average molecular weight magnetic oligomannose iron. Figure 14 The figures show the acute toxicity test results of oligomannose iron nanoparticles with weight-average molecular weights of 100,000, 200,000, and 300,000, and magnetic oligomannose iron nanoparticles with a weight-average molecular weight of 300,000. In the figure, 1 is the blank group, 2 is the oligomannose iron sample treatment group with a weight-average molecular weight of 100,000, 3 is the oligomannose iron sample treatment group with a weight-average molecular weight of 200,000, 4 is the oligomannose iron sample treatment group with a weight-average molecular weight of 300,000, and 5 is the magnetic oligomannose iron sample treatment group with a weight-average molecular weight of 300,000. Detailed Implementation

[0023] The technical solution of the present invention will be further described below with reference to the accompanying drawings and embodiments.

[0024] Unless otherwise defined, the technical or scientific terms used in this invention shall have the ordinary meaning as understood by one of ordinary skill in the art to which this invention pertains.

[0025] Based on the embodiments of this invention, all other embodiments obtained by those skilled in the art without inventive effort are within the scope of protection of this invention. Experimental methods in the following embodiments that do not specify specific conditions are generally determined according to national standards. Experimental instruments, equipment, and reagents in the following embodiments that do not specify their sources are all commercially available materials.

[0026] Unless otherwise defined or stated, all technical and scientific terms used in this invention have the same meaning as those skilled in the art. Furthermore, any methods and materials similar to or equivalent to those described herein can be applied to the methods of this invention. It should be noted that, unless otherwise specified, the embodiments and features described in this invention can be combined with each other.

[0027] Example 1 Preparation of oligomannose iron nanoparticles.

[0028] The preparation method flow of this embodiment is as follows: Figure 1 As shown, it includes the following steps: (1) Oligomannose prepared by enzymatic method (purchased from Nanjing Taixin Biotechnology Co., Ltd.) with an average weight-average molecular weight of 1800.

[0029] (2) Weigh 10g of oligomannose and dissolve it in 100mL of water to prepare a 10% solution. Add 0.07g of sodium bromide catalyst and 7.5mL of sodium hypochlorite oxidant (active chlorine concentration of 12%-13%), and place it in a 30℃ water bath for 3h. During this period, the pH value is controlled at 7.5~8.0 to obtain the oxidized solution.

[0030] (3) Dissolve 100g of inorganic iron salt ferric chloride hexahydrate (FeCl3·6H2O) in 300ml of water to prepare an iron salt solution.

[0031] (4) Mix the oxidizing solution from step (2) with the ferric chloride solution (containing 6.56% iron) from step (3) at a volume ratio of 5:2, add sodium carbonate solution (10%) dropwise, and perform a complexation reaction for 3-4 hours under controlled temperature (30℃-60℃) and pH value not exceeding 6.5 to obtain the complex reaction solution.

[0032] (5) The complex reaction solution was aged for 3 hours at a temperature of 90°C and a pH of 7.

[0033] (6) The aged complex reaction solution was added dropwise to anhydrous ethanol, the complex formed nanoparticles and precipitated, filtered, washed with anhydrous ethanol, and the purified nanoparticles were dried in an oven at 60°C to obtain oligomannose iron nanoparticles. The weight-average molecular weight was detected by gel chromatography using a parallax detector.

[0034] The general chemical formula of oligomannose iron nanoparticles is: [FeO x (OH) y (H2O) z ] n [(C6H 10 O5) m ]k .

[0035] Where x, y, and z are all 1 to 3; n is 1000 to 1400, representing the degree of polymerization of the iron core of ferric hydroxide; m is 9 to 30, representing the degree of polymerization of oligomannose; and k is 30 to 50, representing the amount of oligomannose.

[0036] Example 2 Preparation of magnetic oligomannose iron nanoparticles.

[0037] (1) Weigh 10g of oligomannose from Example 1 and dissolve it in 100mL of water to prepare a 10% solution. Add 0.07g of sodium bromide catalyst and 7.5mL of sodium hypochlorite oxidant, and place it in a 30℃ water bath for 3h. During this period, the pH value is controlled at 7.5~8.0 to obtain the oxidized solution.

[0038] (2) Weigh 36g of ferrous sulfate (FeSO4·7H2O) solid and dissolve it in 60ml of deionized water. Mix it with 180ml of ferric chloride solution (containing 6.56% iron), wherein the molar ratio of ferrous (Fe2+) to ferric (Fe3+) is 1.2:2. Place the above solution in a three-necked flask under nitrogen protection and react it in a water bath at 60℃. At the same time, under the action of a strong magnetic field (2T~10T), add sodium hydroxide solution (20%) dropwise and stir vigorously to adjust the pH of the reaction solution to about 11. React for 3 hours. Wash the generated magnetic iron(III) oxide three times with deionized water and ethanol to obtain magnetic iron(III) oxide particles.

[0039] (3) Mix the oxidizing liquid from step (1) with the magnetic iron oxide particles from step (2) in a volume ratio of 5:2, add sodium hydroxide solution (20%), and under the conditions of controlling the temperature at 100℃ and the pH value at around 11, perform the complexation reaction for 3~4 hours to obtain the complex reaction solution.

[0040] (4) The complex reaction solution was aged for 3 hours at a temperature of 90°C and a pH of 7.

[0041] (5) The aged complex reaction solution was added dropwise to anhydrous ethanol, the complex formed nanoparticles and precipitated, filtered, washed with anhydrous ethanol, and the purified nanoparticles were dried in an oven at 60°C to obtain magnetic oligomannose iron nanoparticles. The weight-average molecular weight was detected by gel chromatography using a parallax detector.

[0042] Example 3 Stability of iron oligomannan nanoparticles with different weight-average molecular weights and magnetic iron oligomannan nanoparticles in gastrointestinal fluids.

[0043] Oligomannose iron nanoparticles with weight-average molecular weights of 100,000, 200,000, and 300,000 prepared by the method in Example 1, and magnetic oligomannose iron nanoparticles with a weight-average molecular weight of 300,000 prepared by the method in Example 2 were placed in in vitro gastric and intestinal fluids (artificial stomach and intestinal fluids were purchased from Beijing Cooler Technology Co., Ltd.). At 0 hours and 72 hours, their weight-average molecular weights and their distribution were detected by gel chromatography using a parallax detector.

[0044] The test results showed that the oligomannose iron nanoparticle sample with a weight-average molecular weight of 100,000 had the following 0-hour detection spectrum: Figure 2 As shown, the detection chromatogram after 72 hours in gastrointestinal fluid is as follows. Figure 3 As shown, there was no significant change within 72 hours; the 0-hour detection spectrum of the oligomannose iron nanoparticle sample with a weight-average molecular weight of 200,000 is as follows. Figure 4 As shown, the detection chromatogram after 72 hours in gastrointestinal fluid is as follows. Figure 5 As shown, there was no significant change within 72 hours; the 0-hour detection spectrum of the oligomannose iron nanoparticle sample with a weight-average molecular weight of 300,000 is as follows. Figure 6 As shown, the detection chromatogram after 72 hours in gastrointestinal fluid is as follows. Figure 7 As shown, there was no significant change within 72 hours; the magnetic oligomannose-iron nanoparticle sample with a weight-average molecular weight of 300,000 showed the following 0-hour detection spectrum: Figure 8 As shown, the detection chromatogram after 72 hours in gastrointestinal fluid is as follows. Figure 9 As shown, there were no significant changes within 72 hours.

[0045] The above results indicate that the oligomannose iron nanoparticles prepared in this invention have good stability in simulated gastrointestinal fluid and remain stable for 72 hours, which can meet the time requirements for gastrointestinal imaging examinations.

[0046] Example 4 An imaging experiment of mouse gastroscopy using iron oligomannosyl nanoparticles with different weight-average molecular weights and magnetic iron oligomannosyl nanoparticles.

[0047] Oligomannose iron nanoparticles with weight-average molecular weights of 100,000, 200,000, and 300,000 prepared by the method in Example 1, and magnetic oligomannose iron nanoparticles with a weight-average molecular weight of 300,000 prepared by the method in Example 2 were dissolved in water and prepared into a solution with an Fe concentration of 300 mg / mL. The solutions were administered to mice by gavage, and X-ray imaging was performed on the mice's stomachs.

[0048] Experimental results showed that oligomannose-iron nanoparticles with a weight-average molecular weight of 100,000 had a significant effect on gastric imaging in mice. Figure 10 As shown; the imaging results of oligomannose-iron nanoparticles with a weight-average molecular weight of 200,000 on the mouse stomach are as follows. Figure 11 As shown; the imaging results of oligomannose-iron nanoparticles with a weight-average molecular weight of 300,000 on the mouse stomach are as follows. Figure 12 As shown, the imaging results of magnetic oligomannose-iron nanoparticles with a weight-average molecular weight of 300,000 on the mouse stomach are as follows. Figure 13 As shown in the figure. The above results indicate that both oligomannose iron nanoparticles and magnetic oligomannose iron nanoparticles can achieve contrast imaging in the mouse stomach with good imaging effects, and can be used as gastrointestinal contrast agents.

[0049] Example 5 Acute and long-term toxicity experiments of iron oligomannan nanoparticles with different weight-average molecular weights and magnetic iron oligomannan nanoparticles.

[0050] Oligomannose iron nanoparticles with weight-average molecular weights of 100,000, 200,000, and 300,000, respectively, prepared by the method in Example 1, and magnetic oligomannose iron nanoparticles with a weight-average molecular weight of 300,000, prepared by the method in Example 2, were dissolved in water to prepare a solution with an Fe concentration of 300 mg / mL. Mice were administered the maximum dose via gavage (maximum dose gavage administered to mice, with blood samples taken at different time points after gavage for testing; mice in the control group were not gavage administered, and all mice were fed a normal diet). Acute toxicity was observed after one week of feeding. Results are as follows: Figure 14 As shown, the Fe content in the blood of mice after the acute toxicity test was the same as that in the control group, and no mice died.

[0051] Oligomannose iron nanoparticles with weight-average molecular weights of 100,000, 200,000, and 300,000 prepared by the method in Example 1, and magnetic oligomannose iron nanoparticles with a weight-average molecular weight of 300,000 prepared by the method in Example 2 were dissolved in water to prepare a solution with an Fe concentration of 2 mg / ml. These solutions were used as drinking water for mice, while mice in the control group received normal drinking water. All mice were fed a normal diet. Blood samples were collected after two months of feeding (as shown in Table 1).

[0052] Table 1 Blood Test Results

[0053] Experimental results showed that the Fe content in the blood of mice prepared by the method in Example 1 (with weight average molecular weights of 100,000, 200,000, and 300,000, respectively) and the magnetic oligomannose iron nanoparticles prepared by the method in Example 2 (with a weight average molecular weight of 300,000) were consistent with those in the control group after long-term toxicity testing, and no mice died.

[0054] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and not to limit them. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications or equivalent substitutions can still be made to the technical solutions of the present invention, and these modifications or equivalent substitutions cannot cause the modified technical solutions to deviate from the spirit and scope of the technical solutions of the present invention.

Claims

1. The application of oligomannose-iron nanoparticles in the preparation of gastrointestinal contrast agents, characterized in that, The oligomannose iron nanoparticles are formed by complexing oligomannose with inorganic iron salts, and the weight-average molecular weight of the oligomannose iron nanoparticles is 100,000 to 300,000.

2. The application of the oligomannose iron nanoparticles according to claim 1 in the preparation of gastrointestinal contrast agents, characterized in that, The general chemical formula of the oligomannose iron nanoparticles is: [FeO] x (OH) y (H2O) z ] n [(C6H 10 O5) m ] k ; Where x, y, and z are all 1 to 3; n is 1000 to 1400, representing the degree of polymerization of the iron core of ferric hydroxide; m is 9 to 30, representing the degree of polymerization of oligomannose; and k is 30 to 50, representing the amount of oligomannose.

3. The application according to claim 1, characterized in that, The oligomannose-iron nanoparticles are prepared by a method comprising the following steps: S1. Oligomannose is prepared by enzymatic method, with an oligomannose having a weight-average molecular weight of 1500~5000; S2. Dissolve oligomannose in water, add sodium bromide as a catalyst and sodium hypochlorite as an oxidant, and react for 2 to 5 hours at pH 6.8~8.0 and 25℃~40℃ to obtain an oxidized solution; S3. Dissolve inorganic iron salts in water to prepare an iron salt solution; S4. The oxidizing solution obtained in step S2 is subjected to a complexation reaction with the iron salt solution obtained in step S3. During the complexation process, an alkaline solution is added dropwise to obtain a complex reaction solution. S5. The complex reaction solution is aged for 2-5 hours at a temperature of 85℃~100℃ and a pH of 6.8~8.

0. S6. The aged complex reaction solution is added to anhydrous ethanol to form nanoparticles. After precipitation and filtration, the nanoparticles are washed with anhydrous ethanol and dried to obtain oligomannose iron nanoparticles.

4. The application according to claim 3, characterized in that, In step S2, the oligomannose is dissolved in water to prepare an 8%~15% solution; in step S3, the inorganic iron salt is FeCl3·6H2O, the mass ratio of FeCl3·6H2O to water is 1:3, and the iron content is 4%~8%; in step S4, the complexation reaction specifically involves mixing the oxidized liquid obtained in step S2 with the iron salt solution obtained in step S3 at a volume ratio of 5:2, then adding dropwise to prepare an 8%~15% sodium carbonate solution, and performing the complexation reaction for 3~4 hours at a temperature of 30℃~60℃ and a pH value not exceeding 6.5; in step S6, the drying temperature is 50℃~80℃.

5. The application according to claim 1, characterized in that, The gastrointestinal contrast agent also includes magnetic oligomannose iron nanoparticles containing iron tetroxide.

6. The application according to claim 5, characterized in that, The magnetic oligomannose-iron nanoparticles are prepared by a method comprising the following steps: S1. Oligomannose is prepared by enzymatic method, with an oligomannose having a weight-average molecular weight of 1500~5000; S2. Dissolve oligomannose in water to prepare an 8%~15% solution, add sodium bromide catalyst and sodium hypochlorite oxidant, and react for 2~5 hours at pH 6.8~8.0 and 25℃~40℃ to obtain an oxidized solution; S3. Dissolve ferrous sulfate in deionized water, then mix it with ferric chloride. The molar ratio of ferrous ions to ferric ions in the mixed solution is 1.2:

2. Under nitrogen protection, a water bath at 50℃~70℃ and a strong magnetic field, add sodium hydroxide solution dropwise until the pH reaches 10~11 and react for 2~5 hours to generate magnetic iron oxide particles. S4. Mix the oxidizing solution obtained in step S2 with the magnetic iron oxide particles obtained in step S3 at a volume ratio of 5:2, add 15%~20% sodium hydroxide solution, and perform a complexation reaction for 2~5 hours under the conditions of temperature 50℃~70℃, magnetic field strength 2T~10T, and pH 10~12 to obtain the complex reaction solution. S5. The complex reaction solution is aged at 90℃~100℃ and pH 7~8 for 2~5 hours; S6. The aged complex reaction solution is added to anhydrous ethanol to form nanoparticles. After precipitation and filtration, the nanoparticles are washed with anhydrous ethanol and dried at 60℃~80℃ to obtain magnetic oligomannose iron nanoparticles.

7. The application according to claim 1, characterized in that, The gastrointestinal contrast agent is an oral or enema preparation.

8. A gastrointestinal contrast agent, characterized in that, The gastrointestinal contrast agent comprises the oligomannose iron nanoparticles of claim 1 or the magnetic oligomannose iron nanoparticles of claim 5.

9. The gastrointestinal contrast agent according to claim 8, characterized in that, The general chemical formula of the oligomannose iron nanoparticles is: [FeO] x (OH) y (H2O) z ] n [(C6H 10 O5) m ] k ; Where x, y, and z are all 1 to 3; n is 1000 to 1400, representing the degree of polymerization of the iron core of ferric hydroxide; m is 9 to 30, representing the degree of polymerization of oligomannose; and k is 30 to 50, representing the amount of oligomannose.

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