Nanomedicine for treating acute pancreatitis and preparation method thereof

Abstract

The present invention relates to a nano drug for treating acute pancreatitis and a preparation method thereof, including: mixing molybdate, glucose and water to obtain a first formulation; adding the first formulation to a solution of a template at a speed of 0.05mL / s-0.2mL / s in batches to obtain a second formulation; adding ethylene glycol to the second formulation at a speed of 0.01mL / s-0.05mL / s in batches to obtain a third formulation; adjusting the pH of the third formulation to 2-2.5, then adding sulfide to obtain a fourth formulation; subjecting the fourth formulation to a hydrothermal reaction, and separating and obtaining hollow MoS2 nanoparticles; modifying gold nanoparticles on the surface of the hollow MoS2 nanoparticles to obtain Au-MoS2 composite nanomaterials; modifying thioctic acid-polyethylene glycol on the surface of the Au-MoS2 composite nanomaterials to obtain a nano drug for treating acute pancreatitis. The nano drug obtained by this preparation method has excellent therapeutic effect on acute pancreatitis, and has excellent biocompatibility and high safety.

Description

Technical Field

[0001] The present invention relates to the field of medical technology, and in particular to a nano drug for treating acute pancreatitis and a preparation method thereof. Background Art

[0002] Acute pancreatitis (AP) is a sudden inflammation of the pancreas. In my country, AP is a common acute abdominal condition, and its incidence is increasing due to the dietary and lifestyle characteristics of the Chinese population. AP is believed to originate in pancreatic acinar cells, where overactivated intracellular trypsinogen is converted to trypsin, which digests pancreatic tissue, leading to pancreatic edema or necrosis and pancreatitis. Currently, approximately 80% of patients experience mild acute pancreatitis (MAP), which occurs locally in the pancreas and can be quickly resolved with conventional diagnosis and treatment. However, some cases develop severe acute pancreatitis (SAP), which accounts for approximately 15%-20% of acute pancreatitis cases and carries a critical condition and a dismal prognosis. Even with advances in AP diagnostic technology and improved treatment interventions, the incidence of AP continues to rise, with a mortality rate as high as 30%. AP remains a serious health hazard and a significant burden on patients and their families.

[0003] Therefore, in-depth research on pancreatic acinar cell apoptosis and the exploration of new treatment methods are of great significance for alleviating local symptoms of pancreatitis and reducing the incidence of severe illness and mortality. Summary of the Invention

[0004] Based on this, it is necessary to provide a nanomedicine for treating acute pancreatitis and a preparation method thereof to address the above problems. The nanomedicine obtained by the preparation method has excellent therapeutic effect on acute pancreatitis, excellent biocompatibility and high safety.

[0005] The present invention provides a method for preparing a nanomedicine for treating acute pancreatitis, comprising the following steps:

[0006] S1, preparation of hollow MoS2 nanoparticles;

[0007] mixing molybdate, glucose, and water to obtain a first formulation, wherein the mass ratio of the molybdate to the glucose in the first formulation is 1:2-1:3;

[0008] The first formulation was added to the template solution in batches at a rate of 0.05 mL / s-0.2 mL / s to obtain a second formulation, wherein the mass ratio of the template to the glucose in the first formulation was 8:1-9:1;

[0009] Ethylene glycol is added to the second preparation in batches at a rate of 0.01 mL / s-0.05 mL / s to obtain a third preparation, wherein the mass ratio of the ethylene glycol to the template is 8:1-9:1;

[0010] adjusting the pH of the third preparation to 2-2.5, and then adding sulfide to obtain a fourth preparation, wherein the mass ratio of the sulfide to the molybdate in the first preparation is 6:1-7:1;

[0011] The fourth formulation is subjected to a hydrothermal reaction to separate and obtain hollow MoS2 nanoparticles;

[0012] S2, modifying gold nanoparticles on the surface of the hollow MoS2 nanoparticles to obtain Au-MoS2 composite nanomaterials;

[0013] S3. Modifying the surface of the Au-MoS2 composite nanomaterial with lipoic acid-polyethylene glycol to obtain a nanomedicine for treating acute pancreatitis.

[0014] In one embodiment, the templating agent is selected from hexadecyltrimethylammonium bromide;

[0015] And / or, the molybdate is selected from at least one of sodium molybdate and potassium molybdate;

[0016] And / or, the sulfide is selected from thiourea.

[0017] In one embodiment, in the step of subjecting the fourth formulation to a hydrothermal reaction, the reaction temperature is 200° C.-220° C., and the reaction time is 20 h-24 h.

[0018] In one embodiment, the specific process of step S2 includes:

[0019] The hollow MoS2 nanoparticles are prepared into a suspension, and the suspension is mixed with a gold precursor solution and an antioxidant and heated to allow gold nanoparticles to grow in situ on the surface of the hollow MoS2 nanoparticles to obtain an Au-MoS2 composite nanomaterial.

[0020] In one embodiment, the gold precursor solution includes chloroauric acid and a surfactant, the gold content in the gold precursor solution is 1.628 mg / mL-2.256 mg / mL, and the molar ratio of the surfactant to the chloroauric acid is 1:10-1:20;

[0021] And / or, the antioxidant is selected from vitamin C, and the molar ratio of the antioxidant to the chloroauric acid is 200:1-100:1;

[0022] And / or, the molar ratio of the hollow MoS2 nanoparticles in the suspension to the gold in the gold precursor solution is 100:1-50:1.

[0023] In one embodiment, in the step of mixing the hollow MoS2 nanoparticle suspension with a gold precursor solution and an antioxidant, the gold precursor solution is added to the hollow MoS2 nanoparticle suspension in batches;

[0024] And / or, in the heating step, the temperature is 25° C.-28° C. and the time is 12 h-18 h.

[0025] In one embodiment, the specific process of step S3 includes:

[0026] A lipoic acid-polyethylene glycol solution is provided, and the lipoic acid-polyethylene glycol solution is mixed with the Au-MoS2 composite nanomaterial, so that the lipoic acid-polyethylene glycol is loaded on the surface of the Au-MoS2 composite nanomaterial to obtain a nanomedicine for treating acute pancreatitis.

[0027] In one embodiment, the mass ratio of the lipoic acid-polyethylene glycol to the Au-MoS2 composite nanomaterial is 2:1-4:1;

[0028] And / or, in the step of mixing the lipoic acid-polyethylene glycol solution with the Au-MoS2 composite nanomaterial, the Au-MoS2 composite nanomaterial is added to the lipoic acid-polyethylene glycol solution in batches.

[0029] A nanomedicine for treating acute pancreatitis obtained by the preparation method as described above, wherein the nanomedicine for treating acute pancreatitis comprises an Au-MoS2 composite nanomaterial and lipoic acid-polyethylene glycol loaded on the surface of the Au-MoS2 composite nanomaterial, wherein the Au-MoS2 composite nanomaterial comprises hollow MoS2 nanoparticles and gold nanoparticles loaded on the surface of the hollow MoS2 nanoparticles.

[0030] In one embodiment, the surface of the nanomedicine for treating acute pancreatitis is further loaded with biological molecules and / or drug molecules for treating acute pancreatitis.

[0031] In the method for preparing a nanomedicine for treating acute pancreatitis of the present invention, a specific order of addition, method of addition, and mass ratio of the materials in step S1 are used to cause the negatively charged molybdate in the fourth configuration to be adsorbed on the surface of spherical micelles of a specific shape and size formed by ethylene glycol and a template agent, and to undergo a reduction reaction with sulfide to generate hollow MoS2 nanoparticles with a high specific surface area. Subsequently, gold nanoparticles are modified on the surface of the hollow MoS2 nanoparticles with a high specific surface area, generating a strong photothermal effect through a resonance effect, significantly improving the therapeutic efficiency when applied to the site of inflammation. Furthermore, the surface of the Au-MoS2 composite nanomaterial is modified with hydrophilic lipoic acid-polyethylene glycol to improve the biocompatibility of the nanomedicine.

[0032] Therefore, the obtained nanomedicine has excellent biocompatibility and high safety, and has excellent therapeutic effect in treating acute pancreatitis. BRIEF DESCRIPTION OF THE DRAWINGS

[0033] Figure 1 This is a scanning electron micrograph of the nanomedicine for treating acute pancreatitis prepared in Example 1;

[0034] Figure 2 are transmission electron micrographs, wherein a is a transmission electron micrograph of the nanomedicine for treating acute pancreatitis prepared in Example 1, and b is a high-resolution transmission electron micrograph of the nanomedicine for treating acute pancreatitis prepared in Example 1;

[0035] Figure 3 X-ray diffraction patterns and Raman spectra of the nanomedicine for treating acute pancreatitis and hollow spherical molybdenum disulfide prepared in Example 1, wherein A and B are the X-ray diffraction patterns of the nanomedicine for treating acute pancreatitis and hollow spherical molybdenum disulfide, respectively, and C and D are the Raman spectra of the nanomedicine for treating acute pancreatitis and hollow spherical molybdenum disulfide, respectively;

[0036] Figure 4 The photocurrent diagram and impedance diagram of the nanomedicine and hollow spherical molybdenum disulfide for treating acute pancreatitis prepared in Example 1, wherein E and F are the photocurrent diagrams of the nanomedicine and hollow spherical molybdenum disulfide for treating acute pancreatitis, respectively, and G and H are the impedance diagrams of the nanomedicine and hollow spherical molybdenum disulfide for treating acute pancreatitis, respectively;

[0037] Figure 5The BET specific surface area diagram and average pore size diagram of the hollow spherical molybdenum disulfide and gold nanoparticle-hollow spherical molybdenum disulfide composite material obtained in Example 1, wherein J and K are the BET specific surface area diagrams of the gold nanoparticle-hollow spherical molybdenum disulfide composite material and hollow spherical molybdenum disulfide, respectively, and L and M are the average pore size diagrams of the nanoparticle-hollow spherical molybdenum disulfide composite material and hollow spherical molybdenum disulfide, respectively;

[0038] Figure 6 This is a graph showing the hemolysis rate of the nanodrug prepared in Example 1 for treating acute pancreatitis, wherein N, P, Q, R, S, and T represent the hemolysis rate graphs of phosphate buffer, phosphate buffer containing 25 μg / mL nanodrug, phosphate buffer containing 50 μg / mL nanodrug, phosphate buffer containing 75 μg / mL nanodrug, phosphate buffer containing 100 μg / mL nanodrug, and double-distilled water, respectively;

[0039] Figure 7 Graphs of blood biochemical indices at the end of the mouse experiment in Application Example 1, wherein g, h, and i are graphs of the clear amylase index of the blood of mice in the acute pancreatitis group, control group, and experimental group, respectively; j, k, and m are graphs of the clear lipase index of the blood of mice in the acute pancreatitis group, control group, and experimental group, respectively; n, p, and q are graphs of the tumor necrosis factor-α index of the blood of mice in the acute pancreatitis group, control group, and experimental group, respectively; r, s, and t are graphs of the interleukin-6 index of the blood of mice in the acute pancreatitis group, control group, and experimental group, respectively; u, v, and w are graphs of the interleukin-1β index of the blood of mice in the acute pancreatitis group, control group, and experimental group, respectively; and x, y, and z are graphs of the inflammatory cell count of the blood of mice in the acute pancreatitis group, control group, and experimental group, respectively;

[0040] Figure 8The changes in the blood biochemical indicators of mice under different near-infrared light irradiation times in Application Example 1, where g, h, i, j, k, and m are the serum amylase index graphs of the experimental group mice irradiated for 5 min, 10 min, 15 min, 20 min, and 30 min, and the acute pancreatitis group mice, respectively; n, p, q, r, s, and t are the lipase index graphs of the experimental group mice irradiated for 5 min, 10 min, 15 min, 20 min, and 30 min, and the acute pancreatitis group mice, respectively; u, v, w, x, y, and z are the blood biochemical indicators of the experimental group mice irradiated for 5 min, 10 min, 15 min, 20 min, and 30 min, and the acute pancreatitis group mice, respectively. The tumor necrosis factor-α index graph in the blood; A, B, C, D, E, and F are the interleukin-6 index graphs in the blood of the mice in the experimental group at irradiation time of 5 min, 10 min, 15 min, 20 min, and 30 min, and the mice in the acute pancreatitis group, respectively; G, H, J, K, L, and M are the interleukin-1β index graphs in the blood of the mice in the experimental group at irradiation time of 5 min, 10 min, 15 min, 20 min, and 30 min, and the mice in the acute pancreatitis group, respectively; N, P, Q, R, S, and T are the inflammatory cell count graphs in the blood of the mice in the experimental group at irradiation time of 5 min, 10 min, 15 min, 20 min, and 30 min, and the mice in the acute pancreatitis group, respectively;

[0041] Figure 9 Figure 1 shows the pancreatic pathological tissue photographs and pathological score diagrams of each group of mice in Application Example 1. Figures e, f, and g are pancreatic pathological tissue photographs of mice in the acute pancreatitis group, control group, and experimental group, respectively. Figures h, i, j, k, and m are pancreatic pathological tissue photographs of mice in the experimental group after near-infrared light irradiation for 5 min, 10 min, 15 min, 20 min, and 30 min, respectively. Figures n, w, and p are pathological score diagrams of mice in the acute pancreatitis group, control group, and experimental group, respectively. Figures q, r, s, t, and u are pathological score diagrams of mice in the experimental group after near-infrared light irradiation for 5 min, 10 min, 15 min, 20 min, and 30 min, respectively. DETAILED DESCRIPTION

[0042] To facilitate understanding of the present invention, the present invention will be described more fully below with reference to the relevant embodiments. However, the present invention can be implemented in many different forms and is not limited to the embodiments described herein. On the contrary, the purpose of providing these embodiments is to make the understanding of the disclosure of the present invention more thorough and comprehensive.

[0043] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art to which this invention pertains. The terms used in this specification of the present invention are for the purpose of describing specific embodiments only and are not intended to limit the present invention. The term "and / or" as used herein includes any and all combinations of one or more of the associated listed items.

[0044] The present invention provides a method for preparing a nanomedicine for treating acute pancreatitis, comprising the following steps:

[0045] S1, preparation of hollow MoS2 nanoparticles;

[0046] mixing molybdate, glucose, and water to obtain a first formulation, wherein the mass ratio of the molybdate to the glucose in the first formulation is 1:2-1:3;

[0047] The first formulation was added to the template solution in batches at a rate of 0.05 mL / s-0.2 mL / s to obtain a second formulation, wherein the mass ratio of the template to the glucose in the first formulation was 8:1-9:1;

[0048] Ethylene glycol is added to the second preparation in batches at a rate of 0.01 mL / s-0.05 mL / s to obtain a third preparation, wherein the mass ratio of the ethylene glycol to the template is 8:1-9:1;

[0049] adjusting the pH of the third preparation to 2-2.5, and then adding sulfide to obtain a fourth preparation, wherein the mass ratio of the sulfide to the molybdate in the first preparation is 6:1-7:1;

[0050] The fourth formulation is subjected to a hydrothermal reaction to separate and obtain hollow MoS2 nanoparticles;

[0051] S2, modifying gold nanoparticles on the surface of the hollow MoS2 nanoparticles to obtain Au-MoS2 composite nanomaterials;

[0052] S3. Modifying the surface of the Au-MoS2 composite nanomaterial with lipoic acid-polyethylene glycol to obtain a nanomedicine for treating acute pancreatitis.

[0053] In step S1, a first formulation containing glucose and molybdate in a specific ratio is added to a second formulation in batches. The viscosity of the second formulation can be adjusted to allow the added ethylene glycol and template to form uniform spherical micelles. Furthermore, by controlling the pH during the hydrothermal reaction, the molybdate is reduced to negatively charged molybdate ions, which are further adsorbed on the surface of the spherical micelles and react with sulfide to form hollow MoS2 nanoparticles.

[0054] Optionally, the method of adding the first configuration and the ethylene glycol in batches is preferably continuous dropwise addition.

[0055] In one embodiment, the template agent is selected from hexadecyltrimethylammonium bromide, and hexadecyltrimethylammonium bromide is dissolved in an organic solvent such as n-butanol to obtain a template agent solution.

[0056] In one embodiment, the molybdate is selected from at least one of sodium molybdate and potassium molybdate.

[0057] In one embodiment, the sulfide is selected from thiourea.

[0058] In order to better generate hollow MoS2 nanoparticles, in one embodiment, in the step of subjecting the fourth formulation to a hydrothermal reaction, the reaction temperature is 200°C-220°C and the reaction time is 20min-24min.

[0059] The specific process of step S2 includes: preparing hollow MoS2 nanoparticles into a suspension, mixing the suspension with a gold precursor solution and an antioxidant and heating it, so that gold nanoparticles grow in situ on the surface of the hollow MoS2 nanoparticles to obtain Au-MoS2 composite nanomaterials.

[0060] During the process of mixing the hollow MoS2 nanoparticle suspension with the gold precursor solution and heating, the gold precursor is reduced to gold nanoparticles and grows in situ on the surface of the hollow MoS2 nanoparticles, and the antioxidant therein can inhibit the oxidation of the gold nanoparticles to obtain Au-MoS2 composite nanomaterials.

[0061] In one embodiment, the gold precursor solution includes chloroauric acid and a surfactant, the gold content in the gold precursor solution is 1.628 mg / mL-2.256 mg / mL, and the molar ratio of the surfactant to the chloroauric acid is 1:10-1:20.

[0062] Optionally, the surfactant is selected from sodium bis(2-ethylhexyl) succinate sulfonate. The surfactant can better stabilize the state of the gold nanoparticles and make the gold nanoparticles more evenly loaded on the surface of the hollow MoS2 nanoparticles.

[0063] In one embodiment, the antioxidant is selected from vitamin C, and the molar ratio of the antioxidant to the chloroauric acid is 200:1-100:1.

[0064] In order to better generate Au-MoS2 composite nanomaterials, in one embodiment, the molar ratio of the hollow MoS2 nanoparticles in the suspension to the gold in the gold precursor solution is 100:1-50:1.

[0065] In the step of mixing and heating the suspension with a gold precursor solution and an antioxidant, the gold precursor solution can be added to the suspension in batches or all at once. Preferably, the gold precursor solution is added to the suspension in batches, wherein the batch addition is preferably continuous dropwise addition, so that the gold nanoparticles can be grown in situ and loaded on the surface of the hollow MoS2 nanoparticles for a better effect.

[0066] In order to better grow gold nanoparticles on the surface of hollow MoS2 nanoparticles, in one embodiment, in the heating step, the temperature is 25°C-28°C and the time is 12h-18h.

[0067] The specific process of step S3 includes: providing a thioctic acid-polyethylene glycol solution, mixing the thioctic acid-polyethylene glycol solution with the Au-MoS2 composite nanomaterial, and loading the thioctic acid-polyethylene glycol on the surface of the Au-MoS2 composite nanomaterial to obtain a nanomedicine for treating acute pancreatitis.

[0068] Lipoic acid-polyethylene glycol has excellent hydrophilicity and biocompatibility, and can make the obtained nanomedicine for treating acute pancreatitis have excellent biocompatibility and safety.

[0069] The present invention does not limit the source of lipoic acid-polyethylene glycol. Commercially available lipoic acid-polyethylene glycol can be directly purchased, or it can be synthesized from mPEG-NH2 (methoxypolyethylene glycol amine) and lipoic acid. In one embodiment, the synthesis steps of lipoic acid-polyethylene glycol are specifically as follows: mPEG-NH2, lipoic acid, and a solvent are mixed, dried, dissolved, and the filtrate is adjusted to pH 8, then extracted with dichloromethane, and the lower layer of liquid is rotary evaporated to dryness to obtain lipoic acid-polyethylene glycol, and the lipoic acid-polyethylene glycol is dissolved in deionized water to obtain a lipoic acid-polyethylene glycol solution.

[0070] In one embodiment, the mass ratio of the lipoic acid-polyethylene glycol to the Au-MoS2 composite nanomaterial is 2:1-4:1.

[0071] In the step of mixing the thioctic acid-polyethylene glycol solution with the Au-MoS2 composite nanomaterial, the Au-MoS2 composite nanomaterial can be added to the thioctic acid-polyethylene glycol solution in batches or all at once. Preferably, the Au-MoS2 composite nanomaterial is added to the thioctic acid-polyethylene glycol solution in batches, wherein the batch addition method is preferably to continuously dropwise add the suspension of the Au-MoS2 composite nanomaterial to the thioctic acid-polyethylene glycol solution, so that the effect of thioctic acid-polyethylene glycol modification on the surface of the Au-MoS2 composite nanomaterial is better.

[0072] The present invention also provides a nanomedicine for treating acute pancreatitis obtained by the preparation method as described above, wherein the nanomedicine for treating acute pancreatitis comprises an Au-MoS2 composite nanomaterial and lipoic acid-polyethylene glycol loaded on the surface of the Au-MoS2 composite nanomaterial, wherein the Au-MoS2 composite nanomaterial comprises hollow MoS2 nanoparticles and gold nanoparticles loaded on the surface of the hollow MoS2 nanoparticles.

[0073] Gold nanoparticles are modified on the surface of hollow MoS2 nanoparticles with a high specific surface area, which can produce a strong photothermal effect through the resonance effect, and can significantly improve the treatment efficiency when acting on the inflammatory site. At the same time, the surface of the Au-MoS2 composite nanomaterial is modified with hydrophilic lipoic acid-polyethylene glycol, which can improve the biocompatibility of nanomedicines.

[0074] Therefore, the obtained nanomedicine has excellent biocompatibility and high safety, and has excellent therapeutic effect in treating acute pancreatitis.

[0075] In order to better enable the nanomedicine to have an excellent therapeutic effect, in one embodiment, the surface of the nanomedicine for treating acute pancreatitis is also loaded with biological molecules and / or drug molecules for treating acute pancreatitis.

[0076] Hereinafter, the nanomedicine for treating acute pancreatitis and the preparation method thereof will be further described through the following specific examples.

[0077] Example 1

[0078] S1, preparation of hollow MoS2 nanoparticles;

[0079] Dissolve 0.206 g of anhydrous sodium molybdate and 0.6 g of glucose in a 500 mL beaker containing 300 mL of deionized water to obtain a first formulation;

[0080] Dissolve 5.4460 g of hexadecyltrimethylammonium bromide in a 1000 mL beaker containing 100 mL of n-butanol to obtain a template solution. Add the first preparation to the template solution in batches at a rate of 0.1 mL / s and stir for 2 h to obtain a second preparation.

[0081] 50 mL of ethylene glycol was added to the second preparation in batches at a rate of 0.02 mL / s and stirred for 10 min to obtain a third preparation;

[0082] Hydrochloric acid was added dropwise to adjust the pH of the third preparation to 2, and after stirring for 1 hour, 1.142 g of thiourea was added and stirred for 3 hours to obtain a fourth preparation;

[0083] The fourth preparation was transferred to a high-pressure reactor and placed in a vacuum drying oven for hydrothermal reaction at 220°C. After the reaction for 20 hours, the liquid in the reactor was filtered and dried. The precipitate was then collected by centrifugation at a centrifugal speed of 9000 r / min for 3 minutes. The precipitate was washed five times by centrifugation with deionized water and anhydrous ethanol to obtain a black precipitate. Finally, the black precipitate was placed in a vacuum drying oven and dried at 60°C to obtain a specific surface area of ​​47.725 m 2 / g hollow MoS2 nanoparticles;

[0084] S2, 80mg hollow MoS2 nanoparticles were dissolved in a mixed solution of 36mL ethanol and 12mL deionized water to obtain a hollow MoS2 nanoparticle suspension, chloroauric acid and 0.08g sodium bis(2-ethylhexyl) succinate sulfonate were dissolved in a 50mL beaker containing 12mL deionized water to obtain a gold precursor solution, the hollow MoS2 nanoparticle suspension was continuously dropped into the gold precursor solution, and 0.4g vitamin C was added after stirring for 10min, and then stirred for 12h and transferred to a high-pressure reactor, placed in a vacuum drying oven and heated at 26°C for 12h, and the obtained mixed solution was centrifuged at a centrifugal speed of 9500r / min for 3min to collect the precipitate, and then centrifuged and washed 5 times with deionized water and anhydrous ethanol, and the black precipitate was placed in a vacuum drying oven, and the sample was dried at a temperature of 60°C to obtain Au-MoS2 composite nanomaterials;

[0085] S3. Dissolve 500 mg of mPEG-NH2 with a molecular weight of 5k, 45 mg of thioctic acid and 10 mg of dicyclohexylcarbodiimide in a mixed solution of 2 ml of dichloromethane and 6 μL of triethylamine, stir under magnetic stirring for 24 h, and then evaporate to complete dryness. Add 100 mL of deionized water to dissolve, filter, and adjust the pH of the filtrate to 8 with sodium bicarbonate. Extract with dichloromethane three times, remove the lower layer of liquid, and evaporate to complete dryness. Then add 2 mL of deionized water to dissolve, and lyophilize to obtain thioctic acid-polyethylene glycol.

[0086] 100 mg of thioctic acid-polyethylene glycol was dissolved in a 25 mL flask filled with 2 mL of deionized water to obtain a thioctic acid-polyethylene glycol solution. 50 mg of Au-MoS2 composite nanomaterial was dissolved in a 25 mL flask filled with 3 mL of ethanol to obtain a composite nanomaterial suspension. The composite nanomaterial suspension was continuously dropped into the thioctic acid-polyethylene glycol solution. After magnetic stirring for 12 h, the precipitate was collected by centrifugation at a centrifugal speed of 9500 r / min for 3 min. The precipitate was then washed five times by centrifugation with deionized water and anhydrous ethanol. The black precipitate was dried at room temperature to obtain a specific surface area of ​​15.63 m 2 / g of nanomedicine for the treatment of acute pancreatitis.

[0087] Figure 1This is a scanning electron microscope image of the nanomedicine for treating acute pancreatitis prepared in this example. Figure 2 This is a projection electron microscope image. Figure 3 X-ray diffraction pattern and Raman spectrum of the nanomedicine and hollow spherical molybdenum disulfide for treating acute pancreatitis prepared in Example 1, Figure 4 The photocurrent graph and impedance graph of the nanomedicine and hollow spherical molybdenum disulfide for treating acute pancreatitis prepared in Example 1 are shown. Figure 5 These are the BET specific surface area diagrams and average pore size diagrams of the hollow spherical molybdenum disulfide and gold nanoparticle-hollow spherical molybdenum disulfide composite materials obtained in Example 1.

[0088] As can be seen from the above figure, the hollow MoS2 nanoparticles prepared in this embodiment have a high specific surface area, which makes it easy to combine with gold nanoparticles, so that the surface of the obtained nanomedicine for treating acute pancreatitis is evenly loaded with gold nanoparticles, thereby improving the treatment efficiency of acute pancreatitis.

[0089] Application Example 1

[0090] The nanomedicine for treating acute pancreatitis obtained in Example 1 is used to treat acute pancreatitis. The specific process is as follows:

[0091] Male Sprague-Dawley rats weighing 240 ± 10 g and aged 3-4 months were obtained from the Animal Experimental Center. All rats were randomly divided into three groups: acute pancreatitis group, control group, and experimental group. All rats were fed an adaptive diet for one week before the start of the experiment. After confirming that all rats were anesthetized and maintained normal respiration and heart rate with no significant abnormalities in vital signs, 20% arginine was administered intraperitoneally at a dose of 12.5 mL / 500 g twice, with a 1-hour interval between each injection.

[0092] 24 hours after the completion of the acute pancreatitis model, the experimental group was intraperitoneally injected with 1 mL of nanodrug solution for the treatment of acute pancreatitis, and the control group also used the same volume of nanodrug for the treatment of acute pancreatitis. 24 hours after the injection of the nanodrug solution for the treatment of acute pancreatitis, the rats in the experimental group were excited with near-infrared light with a wavelength of 808 nm, and irradiated for 15 minutes each time, twice a day. 24 hours after the completion of irradiation, all rats were killed and blood and tissue specimens were collected for examination. The collected blood specimens were tested for biochemical indicators. The collected pancreatic tissue samples were fixed with 4% paraformaldehyde for 1 hour and then embedded in paraffin. Next, the samples were cut into sagittal sections with a thickness of 4 μm and stained with hematoxylin-eosin. Finally, the obtained pathological sections were scored and photographed for observation.

[0093] Groups: acute pancreatitis group; control group; experimental group.

[0094] Acute pancreatitis group: all mice suffered from acute pancreatitis;

[0095] Control group: mice with acute pancreatitis were treated with nanomedicine for the treatment of acute pancreatitis;

[0096] Experimental group: Mice with acute pancreatitis were treated with a combination of nanomedicine for the treatment of acute pancreatitis and near-infrared light.

[0097] Figure 6 The hemolysis rate graph of the nanomedicine for treating acute pancreatitis prepared in Example 1 shows that compared with the blank control, the hemolysis rate of the nanomedicine is below 5%, proving that the nanomedicine for treating acute pancreatitis has low toxicity, high safety, and can be used on the human body.

[0098] Figure 7 This is a graph of biochemical indicators in the blood of mice at the end of the experiment. It can be seen that the indicators of the mice in the experimental group dropped to the lowest.

[0099] Using near-infrared light as the external excitation light source, and using 808nm and 660nm near-infrared light sources respectively, it was found that under the same experimental conditions, 808nm light was better than 660nm light in improving inflammation of pancreatic tissue. Figure 8 These are the biochemical indicators of mouse blood under different irradiation times of 808nm near-infrared light. It can be seen that 15 minutes of irradiation has the best effect. At this time, the serum amylase, lipase, TNF-α, IL-6, IL-β and inflammatory cell count levels of the experimental group mice dropped to the lowest.

[0100] Figure 9 Photos of pancreatic pathological tissues and pathological scoring charts were taken for each group. It can be seen that the number of inflammatory cells such as neutrophils, lymphocytes and monocytes in the experimental group was significantly reduced compared with that in the control group, indicating that the inflammation in the experimental group was significantly suppressed.

[0101] The technical features of the above-mentioned embodiments can be combined arbitrarily. In order to make the description concise, not all possible combinations of the technical features in the above-mentioned embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0102] The above-described embodiments merely illustrate several implementations of the present invention, and while their descriptions are relatively specific and detailed, they should not be construed as limiting the scope of the patent. It should be noted that a person skilled in the art would be able to make numerous variations and improvements without departing from the spirit of the present invention, all of which fall within the scope of protection of the present invention. Therefore, the scope of protection of the patent for this invention shall be determined by the appended claims.

Claims

1. A method for preparing a nanomedicine for treating acute pancreatitis, characterized in that: The steps include: S1, preparation of hollow MoS2 nanoparticles; mixing molybdate, glucose, and water to obtain a first formulation, wherein the mass ratio of the molybdate to the glucose in the first formulation is 1:2-1:3; The first formulation was added to the template solution in batches at a rate of 0.05 mL / s-0.2 mL / s to obtain a second formulation, wherein the mass ratio of the template to the glucose in the first formulation was 8:1-9:1; Ethylene glycol is added to the second preparation in batches at a rate of 0.01 mL / s-0.05 mL / s to obtain a third preparation, wherein the mass ratio of the ethylene glycol to the template is 8:1-9:1; adjusting the pH of the third preparation to 2-2.5, and then adding sulfide to obtain a fourth preparation, wherein the mass ratio of the sulfide to the molybdate in the first preparation is 6:1-7:1; The fourth formulation is subjected to a hydrothermal reaction to separate and obtain hollow MoS2 nanoparticles; S2, modifying gold nanoparticles on the surface of the hollow MoS2 nanoparticles to obtain Au-MoS2 composite nanomaterials; S3. Modifying the surface of the Au-MoS2 composite nanomaterial with lipoic acid-polyethylene glycol to obtain a nanomedicine for treating acute pancreatitis.

2. The method for preparing a nanomedicine for treating acute pancreatitis according to claim 1, wherein: The template agent is selected from hexadecyltrimethylammonium bromide; And / or, the molybdate is selected from at least one of sodium molybdate and potassium molybdate; And / or, the sulfide is selected from thiourea.

3. The method for preparing a nanomedicine for treating acute pancreatitis according to claim 1, wherein: In the step of subjecting the fourth preparation to a hydrothermal reaction, the reaction temperature is 200° C.-220° C., and the reaction time is 20 h-24 h.

4. The method for preparing a nanomedicine for treating acute pancreatitis according to claim 1, wherein: The specific process of step S2 includes: The hollow MoS2 nanoparticles are prepared into a suspension, and the suspension is mixed with a gold precursor solution and an antioxidant and heated to allow gold nanoparticles to grow in situ on the surface of the hollow MoS2 nanoparticles to obtain an Au-MoS2 composite nanomaterial.

5. The method for preparing a nanomedicine for treating acute pancreatitis according to claim 4, wherein: The gold precursor solution includes chloroauric acid and a surfactant, the gold content in the gold precursor solution is 1.628 mg / mL-2.256 mg / mL, and the molar ratio of the surfactant to the chloroauric acid is 1:10-1:20; And / or, the antioxidant is selected from vitamin C, and the molar ratio of the antioxidant to the chloroauric acid is 200:1-100:1; And / or, the molar ratio of the hollow MoS2 nanoparticles in the suspension to the gold in the gold precursor solution is 100:1-50:

1.

6. The method for preparing a nanomedicine for treating acute pancreatitis according to claim 4, characterized in that: In the step of mixing the hollow MoS2 nanoparticle suspension with a gold precursor solution and an antioxidant, the gold precursor solution is added to the hollow MoS2 nanoparticle suspension in batches; And / or, in the heating step, the temperature is 25° C.-28° C. and the time is 12 h-18 h.

7. The method for preparing a nanomedicine for treating acute pancreatitis according to claim 1, wherein: The specific process of step S3 includes: A lipoic acid-polyethylene glycol solution is provided, and the lipoic acid-polyethylene glycol solution is mixed with the Au-MoS2 composite nanomaterial, so that the lipoic acid-polyethylene glycol is loaded on the surface of the Au-MoS2 composite nanomaterial to obtain a nanomedicine for treating acute pancreatitis.

8. The method for preparing the nanomedicine for treating acute pancreatitis according to claim 7, characterized in that: The mass ratio of the lipoic acid-polyethylene glycol to the Au-MoS2 composite nanomaterial is 2:1-4:1; And / or, in the step of mixing the lipoic acid-polyethylene glycol solution with the Au-MoS2 composite nanomaterial, the Au-MoS2 composite nanomaterial is added to the lipoic acid-polyethylene glycol solution in batches.

9. A nanomedicine for treating acute pancreatitis obtained by the preparation method according to any one of claims 1 to 8, characterized in that: The nanomedicine for treating acute pancreatitis includes an Au-MoS2 composite nanomaterial and lipoic acid-polyethylene glycol loaded on the surface of the Au-MoS2 composite nanomaterial, wherein the Au-MoS2 composite nanomaterial includes hollow MoS2 nanoparticles and gold nanoparticles loaded on the surface of the hollow MoS2 nanoparticles.

10. The nanomedicine for treating acute pancreatitis according to claim 9, characterized in that: The surface of the nano drug for treating acute pancreatitis is also loaded with drug molecules for treating acute pancreatitis.

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