Application of lanthanum carbonate in treatment of inflammatory bowel disease

Abstract

The invention discloses application of lanthanum carbonate in treatment of inflammatory bowel diseases, lanthanum carbonate achieves the effect of treating inflammatory diseases by depriving cfDNA, eATP and other proinflammatory factors generated at an inflammatory part, and symptoms induced by IBD are effectively relieved. The lanthanum carbonate disclosed by the invention has a strong cfDNA and eATP removal function, has good biocompatibility, has no direct or indirect toxic action on a human body, has no potential toxicity, and can be used for treating inflammatory bowel diseases.

Description

Technical Field

[0001] The present invention relates to the field of biomedical applications of inorganic materials, and particularly to the application of lanthanum carbonate in the treatment of inflammatory bowel disease. Background Art

[0002] Inflammatory bowel disease (IBD) is a non-specific, chronic, recurrent, inflammatory disease of the gastrointestinal tract with unclear etiology, including two types: ulcerative colitis (UC) and Crohn's disease (CD). The interaction between intestinal microorganisms and the mucosal immune system weakens the intestinal barrier, leading to inappropriate immune activation. The pathogenesis of IBD is related to many factors, such as genetics, environment, mucosal immune response disorders, and intestinal mucosal barrier damage. The recognition of damage-associated molecular patterns (DAMPs) released into the external environment after cell injury or death promotes sterile inflammation, in which the released cell-free DNA (cfDNA) binds to TLR9 on immune cells to promote the inflammatory response, and at the same time, the released extracellular ATP (eATP) binds to specific P2 receptors to participate in the inflammatory response process. Therefore, the clearance of cfDNA and eATP can also be used as a potentially effective strategy for the treatment of IBD. In recent years, the adsorption of cfDNA to inhibit inflammation has attracted increasing attention, and a variety of cationic nanomaterials that adsorb cfDNA are being used in the treatment research of various diseases, such as periodontitis, rheumatoid arthritis, inflammatory bowel disease, etc. However, anti-inflammatory materials that can simultaneously clear cfDNA and eATP have not been reported.

[0003] Lanthanum carbonate is a clinical drug mainly used to treat hyperphosphatemia. Lanthanum carbonate is a trivalent insoluble salt of lanthanum, which can combine with phosphates in food to form insoluble lanthanum phosphate complexes to inhibit the absorption of phosphates, thereby reducing the level of serum phosphates in the body. The high affinity of lanthanum carbonate for phosphates reveals its application prospects in adsorbing cfDNA and eATP that also carry phosphate groups. The existing nanoformulations face challenges in ensuring biosafety, which may lead to adverse reactions or increased toxicity. Therefore, there is an urgent need to develop more efficient and safe treatment methods. Generally speaking, after lanthanum carbonate is taken by the human body, due to its low solubility, the ingested lanthanum carbonate is not effectively absorbed by the intestine and most of it will be excreted out of the body with feces and is not easily absorbed into the human body. A method for treating IBD based on lanthanum carbonate nanosheets has not been reported. Summary of the Invention

[0004] To solve the problems such as the poor efficacy of the main drugs for the current clinical treatment of IBD and the difficulty in ensuring the biosafety of traditional nanoformulations, the purpose of the present invention is to construct a nanoformulation that can efficiently clear cfDNA and eATP and has intestinal targeting, and apply it to the treatment of inflammatory bowel disease.

[0005] To solve the technical problems, the present invention adopts the following technical solutions:

[0006] The present invention first provides a coated lanthanum carbonate nanosheet with the functions of clearing cfDNA and eATP, which is characterized in that: the coated lanthanum carbonate nanosheet takes the lanthanum carbonate nanosheet as the core and is coated with an enteric material on the surface. The particle size of the coated lanthanum carbonate nanosheet is 100 - 250 nm, and the thickness is 0.5 - 2 nm.

[0007] Further, the enteric material is polyacrylic resin.

[0008] The preparation method of the coated lanthanum carbonate nanosheet with the functions of clearing cfDNA and eATP in the present invention is obtained by liquid phase exfoliation and single emulsion evaporation method, and includes the following steps:

[0009] (1) Weigh 100 mg of lanthanum acetate powder and disperse it in 10 - 20 mL of an aqueous solution of polyvinylpyrrolidone with a mass concentration of 1 - 3%, to obtain suspension A;

[0010] (2) Dissolve 40 - 60 mg of sodium carbonate in 3 - 7 mL of an aqueous solution of polyvinylpyrrolidone with a mass concentration of 1 - 3% to obtain solution B; under the ice bath condition of -5°C to 0°C, use an ultrasonic cell disruptor to ultrasonically treat suspension A, and while ultrasonicating, drop solution B into suspension A. After the dropping is completed, continue ultrasonicating until it is uniformly dispersed to obtain reaction solution C;

[0011] (3) Centrifuge and wash the obtained reaction solution C to obtain lanthanum carbonate nanosheets;

[0012] (4) Disperse the lanthanum carbonate nanosheets in an ethanol solution of sorbitan sesquioleate with a mass concentration of 3 - 5%, then add a dichloromethane solution of polyacrylic resin with a mass concentration of 2 - 4%, and stir at room temperature for 8 - 12 h; centrifuge and wash the product, and then freeze-dry to obtain the coated lanthanum carbonate nanosheets.

[0013] Further, in step (2), the ultrasonic power of the ultrasonic treatment is 350 W, with an interval of 2.5 s for every 3 s of ultrasonic treatment, and the total ultrasonic time is 20 - 40 min.

[0014] Further, in steps (3) and (4), the rotation speed of the centrifugation is 6000 - 8500 rpm, the centrifugation time is 10 - 20 min, and the washing is carried out with deionized water.

[0015] Further, in step (4), the mass ratio of the lanthanum carbonate nanosheets to the polyacrylic resin is 1:1 - 3.

[0016] The present invention also discloses the application of lanthanum carbonate in the treatment of inflammatory bowel disease, which is characterized in that it is used for preparing a drug for treating inflammatory bowel disease by clearing pro-inflammatory factors cfDNA and eATP in the intestine.

[0017] Further, the lanthanum carbonate is lanthanum carbonate micron particles, lanthanum carbonate nanosheets or the coated lanthanum carbonate nanosheets as described above.

[0018] The drug prepared by using lanthanum carbonate can be used to clear cfDNA and eATP generated by inflammatory diseases, so as to achieve the effect of treating inflammatory bowel disease. The realization mechanism is as follows: during the inflammatory process, damaged cells and tissues release cfDNA as a damage-associated molecular pattern, which activates the immune system and promotes the occurrence of inflammatory reactions. This cfDNA can not only be used as a biomarker of the disease to reflect the disease activity, but also may affect the disease process by regulating the functions of immune cells. At the same time, the release of eATP is often regarded as a signal of cell stress, which can activate a series of immune reactions and promote the exacerbation of inflammation. Both of them jointly participate in the regulation of the inflammatory microenvironment, indicating that they play an important role in the pathogenesis and progression of inflammatory diseases. Lanthanum carbonate has the function of strongly adsorbing cfDNA and eATP, and has no significant toxicity to mammalian cells. Therefore, it can be used to prepare a new type of nanoagent for treating inflammatory bowel disease. However, lanthanum carbonate is not effectively absorbed by the intestine and most of it will be excreted out of the body with feces. The coated lanthanum carbonate nanosheets of the present invention encapsulate the core of lanthanum carbonate nanosheets in a polyacrylic acid resin (Eudragit S100) shell with a negative surface charge, which can protect the lanthanum carbonate nanosheets from the highly acidic environment of the stomach and improve the targeting ability to the positively charged inflammatory sites. Therefore, the coated lanthanum carbonate nanosheets based on the synergy of polyacrylic acid resin and lanthanum carbonate nanosheets of the present invention have better cfDNA and eATP clearance effects than lanthanum carbonate micron particles and lanthanum carbonate nanosheets.

[0019] The beneficial effects of the present invention are reflected in:

[0020] 1. The lanthanum carbonate nanosheets wrapped with polyacrylic acid resin of the present invention have a strong cfDNA and eATP clearance function, and have good dispersibility, stability and high biological safety, and can relieve the symptoms induced by IBD by clearing DAMPs at the inflammatory site.

[0021] 2. Aiming at the problem that the single cationic nanomaterial adsorbing cfDNA adsorbs DAMPs insufficiently, and other DAMPs will still stimulate the signal pathway as products of cell damage to generate inflammation, the present invention prepares lanthanum carbonate nanosheets wrapped with polyacrylic acid resin, so that it adsorbs cfDNA and eATP generated after cell damage, directly blocks its connection with the TLR9 and P2X7 pathways, and thus weakens the ability of this pathway to generate inflammation.

[0022] 3. The lanthanum carbonate nanosheets of the present invention are prepared by simple liquid-phase exfoliation. The synthesis method is simple, the reaction conditions are mild, and the size and shape of the nanomaterials are controllable, which provides the possibility for their application in the biomedical field.

[0023] 4. The surface of the lanthanum carbonate nanosheets of the present invention is coated with an enteric material, which can improve their stability, ensure that they are not affected by the highly acidic environment of the stomach, and is also conducive to improving the targeting ability of the intestinal tract. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Figure 1 Basic characterization of the lanthanum carbonate nanosheets prepared in Example 1: a is a transmission electron micrograph; b is an atomic force micrograph and the corresponding height map.

[0025] Figure 2 Particle size diagrams of the lanthanum carbonate nanosheets and coated lanthanum carbonate nanosheets prepared in Example 1 after incubation under different pH conditions.

[0026] Figure 3 Zeta potential diagrams of the lanthanum carbonate nanosheets and coated lanthanum carbonate nanosheets prepared in Example 1.

[0027] Figure 4 For the lanthanum carbonate nanosheets prepared in Example 1 and La 3+ for ctDNA ( Figure 4 in a) and ATP ( Figure 4 in b) adsorption performance diagrams.

[0028] Figure 5 In vitro hemolysis performance test diagram of the coated lanthanum carbonate nanosheets prepared in Example 1.

[0029] Figure 6 Performance diagrams of the lanthanum carbonate nanosheets and coated lanthanum carbonate nanosheets prepared in Example 1 for clearing CpG-induced macrophage inflammatory factors.

[0030] Figure 7 Performance diagrams of the lanthanum carbonate nanosheets and coated lanthanum carbonate nanosheets prepared in Example 1 for clearing ATP-induced macrophage inflammatory factors.

[0031] Figure 8 Schematic flow diagram of the DSS-induced colitis model constructed in the examples and the treatment time schedule.

[0032] Figure 9 Effect diagrams of the reduction of the disease inflammation index in mice before and after treatment with the nanosheets prepared in Example 1 and the control group.

[0033] Figure 10 Weight monitoring diagrams of mice before and after treatment with the nanosheets prepared in Example 1 and the control group.

[0034] Figure 11 Effect diagram of the recovery of colon length after treatment with the nanosheets prepared in Example 1 and the control group.

[0035] Figure 12 Quantitative analysis chart of inflammatory factors in mouse colon tissues before and after treatment with the lanthanum carbonate nanosheets prepared in Example 1 and the control group. Specific implementation manners

[0036] To make the above objects, features and advantages of the present invention more obvious and understandable, the following describes the specific implementation manners of the present invention in detail with reference to the embodiments. The following content is only an example and explanation of the concept of the present invention. Those skilled in the art of the present technology can make various modifications or supplements to the described specific embodiments or use similar methods to replace them, as long as they do not deviate from the concept of the invention or exceed the scope defined by the claims of the present invention, they should all fall within the protection scope of the present invention.

[0037] Example 1

[0038] The lanthanum carbonate nanosheets were prepared by the following method in this example:

[0039] (1) Weigh 100 mg of lanthanum acetate powder and disperse it in 15 mL of an aqueous solution of polyvinylpyrrolidone with a mass concentration of 2%, to obtain suspension A, and place it in a 50 mL centrifuge tube;

[0040] (2) Dissolve 50 mg of sodium carbonate in 5 mL of an aqueous solution of polyvinylpyrrolidone with a mass concentration of 2% to obtain solution B; under the ice bath condition of 0 °C, place the centrifuge tube under the ultrasonic probe of an ultrasonic cell disruptor, and slowly drip solution B while ultrasonicating. The dripping time is about 5 minutes. After the dripping is completed, continue ultrasonicating. The total ultrasonic time is 30 minutes. The ultrasonic power of the ultrasonic treatment is 350 W, and there is an interval of 2.5 s every 3 s of ultrasonicating. After the ultrasonicating is completed, obtain reaction solution C.

[0041] (3) Centrifuge the obtained reaction solution C at a speed of 6000 rpm for 5 minutes and wash it three times with deionized water to remove PVP, to obtain pure lanthanum carbonate nanosheets, which are freeze-dried for standby as a control (denoted as LCNs) or proceed to step (4).

[0042] (4) Disperse 20 mg of the lanthanum carbonate nanosheets in step (3) in 10 mL of an ethanol solution of sorbitan sesquioleate with a mass concentration of 4%, then add a dichloromethane solution of polyacrylic acid resin (Eudragit S100) with a mass concentration of 3%, and stir at room temperature for 12 h; centrifuge the product at a speed of 6000 rpm for 15 minutes and wash it three times with deionized water, and then freeze-dry it to obtain coated lanthanum carbonate nanosheets (denoted as LCN@S100), where the mass ratio of lanthanum carbonate nanosheets to polyacrylic acid resin is 1:2.

[0043] The obtained LCNs and LCN@S100 nanosheets in this example were characterized for their morphology and properties as follows:

[0044] I. Morphology characterization

[0045] Figure 1 This is the basic characterization of the LCNs prepared in this example. Figure 1 In the transmission electron microscopy image of a, it can be seen that the nanosheets are flaky and have a diameter of 100 - 250 nm; Figure 1 The atomic force microscopy image of b shows that the thickness of the nanosheets is about 0.5 - 2 nm.

[0046] Figure 2 This is the particle size diagram of the LCNs and LCN@S100 nanosheets prepared in Example 1 after incubation under different pH conditions. The LCNs and LCN@S100 nanosheets were placed in simulated gastrointestinal buffer solutions (buffers with pH values of 1.2 and 7.4) and incubated at room temperature for 2 h to examine their stability in the gastrointestinal tract. Under the condition of pH 7.4, the particle size of LCNs is 100 - 250 nm, which is consistent with the transmission electron microscopy results. After coating with Eudragit S100, the size of the product significantly increases from 114 nm to 151 nm, indicating the successful construction of LCN@S100 nanosheets. Under the condition of pH 1.2, the particle size of LCNs significantly decreases, showing its degradation in an acidic environment compared with that at pH 7.4. And LCN@S100 aggregates at pH 1.2, and the size significantly increases. However, after incubating LCN@S100 in an environment of pH 1.2 for 2 h and then adjusting the buffer solution to pH 7.4 (i.e., pH = 7.4 after pH = 1.2 treated in the figure), the aggregation tendency of LCN@S100 is reversed, indicating that LCN@S100 has the ability to resist acidolysis and is not affected by the highly acidic environment of the stomach.

[0047] Figure 3 This is the Zeta potential diagram of the LCNs and LCN@S100 nanosheets prepared in Example 1. It can be seen from the figure that the Zeta potential value of LCNs is +2 mV. After being modified with Eudragit S100, the Zeta potential value decreases to -22 mV, indicating that Eudragit S100 has successfully coated the lanthanum carbonate nanosheets. After freeze-drying storage for 7 days and 14 days, the Zeta potential spectrum of LCN@S100 changes little, indicating its long-term stability.

[0048] II. Test on the scavenging ability of cfDNA and ATP

[0049] Serum cfDNA levels are closely related to the expression levels of TLR9, TNF-α, iNOS, and F4 / 80 in the colon. Higher serum cfDNA levels are jointly associated with the severity of IBD and the expression of TLR9 in the colon, indicating that cfDNA-TLR9 signaling is a target for IBD treatment. To verify the cfDNA clearance ability of LCNs, in this example, calf thymus DNA (ctDNA) was used as a model, and LCNs and La 3+ were used as a comparison. The specific characterization method was as follows: LCNs or lanthanum acetate was added to the ctDNA solution, and the mass ratio of the material (quantified by La 3+ ) to ctDNA was 20:1 to 1:4. Then, the binding ability of the nanoreagent to ctDNA was evaluated using the Quant-iT TM PicoGreen TM dsDNA kit. The results are as Figure 4 shown in a. When the mass ratio of the LCNs material to DNA was 10:1, the cfDNA clearance ability was the best.

[0050] To evaluate the ATP clearance ability of LCNs, the specific steps were as follows: LCNs or lanthanum acetate was added to the ATP solution, and the mass ratio of the material (quantified by La 3+ ) to ctDNA was 20:1 to 1:4; subsequently, the mixture was centrifuged, and the ATP level in the supernatant was detected using a luciferase / luciferin ATP detection kit, and the chemiluminescence value was recorded using an Infinite 200Pro device. The ATP clearance ability at different mass ratios was calculated, and the optimal mass ratio for ATP clearance was screened. The results are as Figure 4 shown in b. When the mass ratio of LCNs to DNA was 20:1, the ATP clearance ability was the best. Such a high clearance efficiency should be attributed to the strong electrostatic attraction between La 3+ in LCNs and DNA and ATP phosphates.

[0051] III. In vivo biosafety test of materials

[0052] Figure 5In vitro hemolysis performance test chart of LCN@S100 prepared in this example. The characterization method is as follows: Dilute LCN@S100 in the whole system dispersion to 12.5 μg / mL, 25 μg / mL, 50 μg / mL, 75 μg / mL, 100 μg / mL, and 200 μg / mL. Add 0.2 mL of LCN@S100 aqueous solutions with different concentration gradients to 0.2 mL of treated blood (add 0.5 mL of fresh blood to 4.5 mL of physiological saline and centrifuge and wash 5 - 8 times, centrifuge speed 3000 rpm, centrifuge time 10 min. After the blood supernatant is clear and transparent, discard the supernatant and make up to 5 mL with physiological saline) and 0.6 mL of physiological saline, and incubate at 37 °C for 4 h. Set positive control (replace the LCN@S100 solution with water) and negative control (replace the LCN@S100 solution with physiological saline). Then centrifuge at 3000 rpm for 10 min, aspirate the supernatant, measure the absorbance at OD541 nm, and calculate the hemolysis rate. It can be seen from the figure that the hemolysis rates of LCN@S100 at different concentrations are all lower than 5%, indicating good biocompatibility of the material.

[0053] At the same time, through the in vitro hemolysis performance test, it can be known that the hemolysis rate of La 3+ (tested with lanthanum acetate) is very high and the biocompatibility is poor.

[0054] IV. In vitro anti-inflammatory ability for the constructed macrophage inflammation model

[0055] Figures 6-7 Interpreted the in vitro anti-inflammatory ability of lanthanum carbonate nanosheets in the constructed macrophage inflammation model. Since macrophages are important participants in the immune pathogenesis, the present invention speculates that cfDNA-mediated TLR9 activation is the key to M1 macrophage polarization, because macrophage polarization leads to the release of pro-inflammatory cytokines in cells. First, use CpG1826 as an in vitro substitute for cfDNA to induce macrophages to produce inflammation, and then add LCN@S100, La 3+ (lanthanum acetate), LCNs or S100 materials into the cell culture dish and co-incubate with the stimulated macrophages for 12 h, and then detect the levels of inflammatory factors in the supernatant of the culture medium.

[0056] In intestinal inflammation, eATP significantly enhances the inflammatory response through the P2X7-NLRP3 inflammasome pathway. First, pretreatment is carried out with LPS, which induces the release of cytokines (such as IL-1β, TNF-α, etc.) by activating TLR4, and these factors provide the necessary initial signals for the assembly and activation of the NLRP3 inflammasome. Subsequently, the material is co-incubated with macrophages for 2 h, and then the cells are stimulated with 5 μM ATP for inflammasome activation. As a danger signal, ATP can activate the NLRP3 inflammasome through P2X7, enabling pro-inflammatory cytokines (such as IL-1β and IL-18) to be cleaved and matured, and finally released extracellularly, triggering an inflammatory response. In addition, extracellular ATP can also activate the NF-κB pathway through the P2Y receptor, promoting the release of TNF-α and further amplifying the inflammatory response.

[0057] Through the significant comparison of the final data, it was found that LCN@S100 had a good inhibitory effect on the M1 macrophage polarization marker TNF-α in both models.

[0058] V. Therapeutic performance of colitis

[0059] Figures 8-11 To evaluate the therapeutic performance of LCN@S100 nanosheets on colitis. Figure 8 To construct a schematic diagram of the DSS-induced colitis model and treatment process. To evaluate the therapeutic effects of the LCNs and LCN@S100 prepared in this example on DSS-induced colitis, the following design was carried out: 64 5-week-old female c57 mice were prepared, with 8 mice in each cage and raised in groups, and they were acclimatized to the environment for one week before being included in the study; the healthy mice were randomly divided into 8 groups (n = 8): ① normal control group PBS + water; ② PBS + 2.5% DSS; ③ 5-ASA (i.e., the penta-aminosalicylic acid group, the dosage is 30 mg / kg) + 2.5% DSS; ④ treatment group LCNs (the dosage in terms of lanthanum is 30 mg / kg) + 2.5% DSS; ⑤ S100 (the dosage is 30 mg / kg) + 2.5% DSS; ⑥ LCN@S100 (the dosage in terms of lanthanum is 15 mg / kg) + 2.5% DSS; ⑦ LCN@S100 (the dosage in terms of lanthanum is 30 mg / kg) + 2.5% DSS; ⑧ LCN@S100 (the dosage in terms of lanthanum is 60 mg / kg) + 2.5% DSS. The treatment methods for each group are as follows:

[0060] The first day of oral administration of DSS was designated as day 0, and on day 6, the DSS-containing drinking water was replaced with ordinary drinking water. Intragastric administration was carried out on days 6, 8, 10, and 12. During the 0-14-day experiment period, the body weight, visible fecal consistency, and fecal bleeding were evaluated every day. On day 14, the mice in each group were dissected and their blood and colon tissues were separated, and the colon length was photographed and recorded.

[0061] Figure 9 The reduction effect diagram of the disease inflammation index of the nanosheets prepared in Example 1 and the control group in mice before and after treatment. To verify the therapeutic effect of the nanosheets prepared in this example on DSS-induced colitis, the changes in the disease inflammation index from 0 to 14 days were observed and recorded. It can be seen from the figure that the therapeutic effect of LCN@S100 is excellent, and the disease inflammation index of the mice returns to the normal level after treatment.

[0062] Figure 10 The weight monitoring diagram of the lanthanum carbonate nanosheets prepared in Example 1 and the control group in mice before and after treatment. It can be seen that the weight of the mice in the DSS group continued to decline from 0 to 6 days. However, after treatment with LCN@S100, the weight loss trend was alleviated, and the weight after treatment could recover to the normal level, and the therapeutic effect of 60 mg / kg LCN@S100 was better than that of 5-aminosalicylic acid. By Figure 11 Looking at the colon pictures, it can be seen that DSS caused a significant shortening of the colon of the mice, and the colon length of the mice in the treatment group was alleviated to varying degrees. After treatment with LCN@S100, the colon length basically returned to the normal level.

[0063] Figure 12 The quantitative analysis diagram of inflammatory factors (TNF-α, IL-6, IL-1β and IL-18) in the colon tissues of the lanthanum carbonate nanosheets prepared in Example 1 and the control group in mice before and after treatment. It can be seen that the levels of these factors in the DSS group increased significantly, while the LCN@S100 (60 mg / kg) treatment group showed a significant inhibitory effect on the production of these inflammatory factors. Compared with the clinical drug 5-aminosalicylic acid (5-ASA), the improvement effect of the LCN@S100 group in terms of inflammatory factor levels was more significant.

[0064] In summary, the above results indicate that the nanosheets obtained in this example can achieve a therapeutic effect on inflammatory bowel disease.

[0065] The above are only the preferred embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent replacements, and improvements made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. A coated lanthanum carbonate nanosheet with the function of clearing cfDNA and eATP, characterized in that: The coated lanthanum carbonate nanosheets have lanthanum carbonate nanosheets as the core and are coated with enteric materials on the surface.

2. The coated lanthanum carbonate nanosheets with the function of clearing cfDNA and eATP according to claim 1, wherein: The enteric material is polyacrylic resin.

3. A method for preparing the coated lanthanum carbonate nanosheets having the function of clearing cfDNA and eATP as described in claim 1 or 2, characterized in that, It is prepared by liquid-phase exfoliation and single-emulsion evaporation method, and includes the following steps: (1) Weigh 100 mg of lanthanum acetate powder and disperse it in 10 - 20 mL of an aqueous solution of polyvinylpyrrolidone with a mass concentration of 1 - 3% to obtain suspension A; (2) Dissolve 40 - 60 mg of sodium carbonate in 3 - 7 mL of an aqueous solution of polyvinylpyrrolidone with a mass concentration of 1 - 3% to obtain solution B; Under an ice bath condition of -5°C to 0°C, use an ultrasonic cell disruptor to ultrasonically treat suspension A, and while ultrasonicating, drop solution B into suspension A. After the dropping is completed, continue ultrasonicating until it is uniformly dispersed to obtain reaction solution C; (3) Centrifuge and wash the obtained reaction solution C to obtain two-dimensional lanthanum carbonate nanosheets; (4) Disperse the lanthanum carbonate nanosheets in an ethanol solution of sorbitan sesquioleate with a mass concentration of 3 - 5%, then add a dichloromethane solution of polyacrylic resin with a mass concentration of 2 - 4%, and stir at room temperature for 8 - 12 h; Centrifuge and wash the product, and then freeze-dry to obtain coated lanthanum carbonate nanosheets.

4. The preparation method according to claim 3, characterized in that: In step (2), the ultrasonic power of the ultrasonic treatment is 350 W, with an interval of 2.5 s every 3 s of ultrasonic treatment, and the total ultrasonic time is 20 - 40 min.

5. The preparation method according to claim 3, wherein: In steps (3) and (4), the rotation speed of the centrifugation is 6000 - 8500 rpm, the centrifugation time is 10 - 20 min, and the washing is carried out with deionized water.

6. The preparation method according to claim 3, characterized in that: In step (4), the mass ratio of the lanthanum carbonate nanosheets to the polyacrylic resin is 1:1 - 3.

7. Use of lanthanum carbonate in the treatment of inflammatory bowel disease, characterized in that: It is used for preparing a drug for treating inflammatory bowel disease by clearing pro-inflammatory factors cfDNA and eATP in the intestine.

8. The application according to claim 7, characterized in that: The lanthanum carbonate is lanthanum carbonate micro-particles, lanthanum carbonate nanosheets or coated lanthanum carbonate nanosheets.

9. The application according to claim 8, characterized in that: The coated lanthanum carbonate nanosheets are the coated lanthanum carbonate nanosheets with the function of clearing cfDNA and eATP as described in claim 1 or 2.

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