Mesalazine enteric-coated sustained-release pellets and preparation method thereof

Abstract

The present invention relates to the technical field of medical, dental or cosmetic preparations, and in particular to a mesalazine enteric-coated sustained-release micro-pill and a preparation method thereof. The mesalazine enteric-coated sustained-release micro-pill comprises the following components: mesalazine, microcrystalline cellulose, a modified guar gum inclusion agent, a binder, and ethyl cellulose. The present invention also provides a preparation method thereof. Compared with the prior art, the enteric-coated sustained-release micro-pill prepared by the present invention has the advantages of intestinal directional release, mildness and no irritation, etc.

Description

Technical Field

[0001] The invention relates to the technical field of medical, dental or cosmetic preparations, and in particular to mesalazine enteric-coated sustained-release micropills and a preparation method thereof. Background Art

[0002] Inflammatory bowel disease (IBD) is a chronic, relapsing intestinal inflammatory disease that is generally divided into two types: ulcerative colitis (UC) and Crohn's disease (CD). UC is a common, nonspecific, chronic inflammatory disease that primarily affects the colon mucosa, manifesting as symptoms such as abdominal pain and diarrhea, and increases the patient's risk of colon cancer. Crohn's disease, also known as segmental enteritis or granulomatous enteritis, can affect any part of the entire digestive tract, but most commonly occurs in the small intestine and terminal ileum. The cause of both UC and CD is currently unclear, and the incidence rate continues to rise.

[0003] At present, the treatment of IBD patients mainly relies on drugs, especially mesalazine. Mesalazine, also known as 5-aminosalicylic acid (5-ASA), is the active ingredient in sulfasalazine (SASP), a traditional drug for the treatment of IBD. Compared with SASP, mesalazine has higher efficacy and fewer adverse reactions, so it has become the first choice for the treatment of mild to moderate ulcerative colitis and an effective choice for the treatment of Crohn's disease. Mesalazine has a significant inhibitory effect on intestinal inflammation, and its mechanism of action is mainly to play an anti-inflammatory role by reducing the production of prostaglandins, leukotrienes and free radicals. It interacts with the mucosa of the intestinal lesions and plays a local role in inhibiting inflammation without affecting the whole body or entering the blood circulation. Mesalazine preparations have become an indispensable drug in the clinical treatment of IBD. It plays an important role in the treatment and management of IBD patients and provides patients with an effective treatment option.

[0004] CN201510945644.2 provides a mesalazine sustained-release pellet and a preparation method thereof and a mesalazine sustained-release capsule, the method comprising: mixing 5-aminosalicylic acid, microcrystalline cellulose and a binder, and obtaining a drug-containing pellet core through an extrusion spheronization process; using a material including ethyl cellulose to coat a sustained-release coating layer on the drug-containing pellet core; using an enteric material and a processing aid to coat an enteric coating layer on the sustained-release coating layer to obtain mesalazine sustained-release pellets; the enteric material is a copolymer of methacrylic acid and ethyl acrylate. The invention combines two drug release mechanisms, pH-dependent and time-dependent, to achieve an ideal drug release curve and improve the accuracy of the drug release position. The mesalazine sustained-release capsule provided by the invention includes the mesalazine sustained-release pellet, which can better release drugs in the gastrointestinal tract and is beneficial to the treatment of ulcerative colitis and Crohn's disease.

[0005] CN201610269892.4 discloses a mesalazine enteric controlled release preparation, which is composed of an inner core, a controlled release coating layer, an adhesive coating layer, and an enteric coating layer from the inside to the outside, wherein the inner core includes mesalazine, hydroxypropyl cellulose, and talcum powder, and the controlled release coating layer is composed of ethyl cellulose and triethyl citrate, and the adhesive coating layer adopts sodium alginate, and the enteric coating layer is composed of methacrylic acid and methyl methacrylate copolymer, triethyl citrate, and talcum powder. The invention also provides a method for preparing the above-mentioned enteric controlled release preparation, which is simple and has controllable parameters. The prepared micropills do not release the drug under gastric acid conditions, and can slowly release the drug for 24 hours under pH7.5 dissolution medium conditions. The preparation has no irritation to gastrointestinal adhesion and can be used for acute treatment of ulcerative colitis (inflammation with ulcers) and maintenance treatment to prevent recurrence.

[0006] Colon targeted drug delivery system (OCDDS) refers to a drug that avoids release in the upper digestive tract after oral administration, and transports the drug to the ileocecal region of the human body before it begins to disintegrate and release the drug, and adheres to the surface of the colon mucosa for a certain period of time, releasing the drug at a certain rate, thereby achieving the purpose of increasing the local concentration and bioeffectiveness of the drug. Currently, most enteric-coated preparations of mesalazine use polymers as carriers, but the mucosal irritation that polymers may cause may have side effects on patients. Summary of the invention

[0007] In view of the above-mentioned defects of the prior art, the technical problem to be solved by the present invention is to provide a mesalazine enteric-coated sustained-release pellet and a preparation method thereof.

[0008] Guar gum is a natural polysaccharide known for its low toxicity, good stability and biodegradability. Guar gum is considered a promising option for colonic drug delivery systems due to its high sensitivity to colonic microorganisms and its ability to achieve sustained drug release. Guar gum is well soluble in water. This hydrophilic polysaccharide has a rod-like structure with mannose forming the backbone and galactose attached as side chains. The mannose units are connected by β-(1-4) glycosidic bonds, while the galactose units are connected in a substitutional mode by (1-6) glycosidic bonds. The hydroxyl groups in the guar gum molecule increase its interactivity when synthesizing derivatives. Its swelling behavior is affected by pH, with the smallest swelling in acidic environments and the largest swelling in alkaline environments. In the large intestine, guar gum also shows microbial enzyme-mediated degradation, which helps to achieve targeted drug release in the colonic area. At the same time, the stability of guar gum in aqueous acidic environments ensures its physical integrity when used as a drug encapsulation wall material. However, the hydration rate of guar gum is too fast at a specific pH and the thickening effect caused by itself will greatly affect its application in practical scenarios, including the failure of drug absorption to be completely absorbed due to sudden release under the pH environment of the colon, and the damage to the integrity of the skeleton caused by its easy decomposition by the flora, etc. Therefore, in the present invention, guar gum is oxidized and then esterified by undecanoyl chloride to obtain modified guar gum, which is then cross-linked with chitosan to obtain a modified guar gum inclusion agent. The water solubility of the modified guar gum is reduced due to esterification and grafting of hydrophobic alkyl chains, thereby reducing the probability of its decomposition by the flora and ensuring its structural integrity in the intestinal environment. The cross-linking of chitosan and modified guar gum can solve the problem of too fast hydration rate of guar gum, thereby preventing its sudden release in the intestine. On the other hand, chitosan and guar gum are biomass materials, and both have certain antibacterial effects. Using them as enteric materials can have a good antibacterial effect and will not cause irritation and side effects to the patient's mucosa.

[0009] To achieve the above object, the present invention provides a mesalazine enteric-coated sustained-release pellet, comprising the following components: mesalazine, microcrystalline cellulose, a modified guar gum inclusion agent, a binder, and ethyl cellulose.

[0010] Furthermore, the adhesive is selected from one of hydroxypropyl methylcellulose, povidone and starch.

[0011] The preparation method of the modified guar gum inclusion agent comprises the following steps:

[0012] X1. Dissolve guar gum in water, then drop an equal volume of sodium periodate solution, stir at room temperature in the dark for 4-8 hours, add ethylene glycol for quenching, and then dialyze, Mw <12000Da, and freeze-dry after the dialysis to obtain oxidized guar gum;

[0013] X2. Dissolve oxidized guar gum in 10 to 20 times the weight of 1-allyl-3-methylimidazolium chloride, add undecanoyl chloride, heat and stir for 4 to 6 hours, then add methanol to dilute, a precipitate appears, let stand and filter, wash the residue with methanol and dry to obtain modified guar gum;

[0014] X3. Dissolve chitosan in acetic acid, add an equal volume of modified guar gum solution, heat and stir for 0.5 to 1 hour, then freeze-dry the mixture to obtain the modified guar gum inclusion compound.

[0015] Furthermore, the mass ratio of the guar gum to sodium periodate is 1:0.5-1.

[0016] Furthermore, the concentration of the sodium periodate solution is 1-2 wt %.

[0017] Furthermore, the mass ratio of the oxidized guar gum to undecanoyl chloride is 1:5-6.

[0018] Furthermore, the heating temperature in step X2 ranges from 45 to 55°C.

[0019] Furthermore, the mass ratio of chitosan to modified guar gum is 1:1-3.

[0020] Furthermore, the heating temperature in step X3 is in the range of 40 to 50°C.

[0021] Preferably, the preparation method of the modified guar gum inclusion agent comprises the following steps:

[0022] X1. Dissolve guar gum in water, then dropwise add an equal volume of 1-2 wt% sodium periodate solution, the mass ratio of guar gum to sodium periodate being 1:0.5-1, stir in the dark at room temperature for 4-8 h, add ethylene glycol for quenching, and then dialyze, Mw <12000Da, and freeze-dry after the dialysis to obtain oxidized guar gum;

[0023] X2. Dissolve oxidized guar gum in 10 to 20 times the weight of 1-allyl-3-methylimidazole chloride, add undecanoyl chloride, the mass ratio of oxidized guar gum to undecanoyl chloride is 1:5 to 6, heat to 45 to 55° C., stir for 4 to 6 hours, add methanol to dilute, precipitate appears, let stand and filter, wash the residue with methanol and dry to obtain modified guar gum;

[0024] X3. Dissolve chitosan in acetic acid, and then add an equal volume of modified guar gum solution, the mass ratio of chitosan to modified guar gum is 1:1-3. Heat to 40-50°C and stir for 0.5-1h, then freeze-dry the mixture to obtain the modified guar gum inclusion compound.

[0025] A method for preparing mesalazine enteric-coated sustained-release pellets comprises the following steps:

[0026] S1, mixing mesalazine, a binder and microcrystalline cellulose in a mass ratio of 40-50:10-20:20-40, wet granulating, spheronizing, drying and passing through a 0.5-1 mm sieve to obtain a pellet core;

[0027] S2, coating the pellet core with the ethyl cellulose aqueous dispersion in a fluidized bed, and drying the pellets to obtain pellets with a sustained-release layer, wherein the mass of the sustained-release layer is 2 to 10% of the pellet core;

[0028] S3. The micropellets with the sustained-release layer are coated with the modified guar gum inclusion agent aqueous dispersion in a fluidized bed and dried to obtain mesalazine enteric-coated sustained-release micropellets, wherein the mass of the enteric layer is 8-18% of the pellet core.

[0029] Beneficial effects of the present invention:

[0030] 1. The mesalazine enteric-coated sustained-release pellets provided by the present invention include an enteric layer and a sustained-release coating layer, which are wrapped around a pill core containing the drug. The sustained-release coating layer is made of ethyl cellulose, so that the drug is continuously and slowly released, specifically playing a role in controlling the release rate, release time and release site of the drug. The enteric layer does not release in the stomach, but has a role of directional release in the intestinal environment, which is beneficial to the treatment of ulcerative colitis and Crohn's disease.

[0031] 2. The present invention adopts modified guar gum and chitosan cross-linked as the enteric layer as the outermost layer of mesalazine microcapsules, which can not only achieve targeted release in the intestine, but also is mild and non-irritating, and also has a certain inhibitory effect on Escherichia coli. DETAILED DESCRIPTION

[0032] Povidone, model: K30.

[0033] Ethyl cellulose, model: surelease, Colorcon, USA.

[0034] Copolymer of methacrylic acid and ethyl acrylate, Eudragit-L100, Rohm, Germany.

[0035] Escherichia coli, CGMCC1.12883, was purchased from China General Microbiological Culture Collection and Management Center.

[0036] Comparative Example 1

[0037] A method for preparing mesalazine enteric-coated sustained-release pellets comprises the following steps:

[0038] S1, mixing mesalazine, povidone and microcrystalline cellulose in a mass ratio of 40:15:25, wet granulating, spheronizing, drying and passing through a 1 mm sieve to obtain pellet cores;

[0039] S2, coating the pellet core with 60 wt % ethyl cellulose aqueous dispersion in a fluidized bed, and drying to obtain pellets with a sustained-release layer, wherein the mass of the sustained-release layer is 3.5% of the pellet core;

[0040] S3. In a fluidized bed, the micropellets with a sustained-release layer are coated with an enteric layer using a 15 wt % aqueous dispersion of a copolymer of methacrylic acid and ethyl acrylate, and then dried to obtain mesalazine enteric-coated sustained-release micropellets, wherein the mass of the enteric layer is 10% of the pellet core.

[0041] Example 1

[0042] A method for preparing mesalazine enteric-coated sustained-release pellets comprises the following steps:

[0043] S1, mixing mesalazine, povidone and microcrystalline cellulose in a mass ratio of 40:15:25, wet granulating, spheronizing, drying and passing through a 1 mm sieve to obtain pellet cores;

[0044] S2, coating the pellet core with 60 wt % ethyl cellulose aqueous dispersion in a fluidized bed, and drying to obtain pellets with a sustained-release layer, wherein the mass of the sustained-release layer is 3.5% of the pellet core;

[0045] S3. In a fluidized bed, 15 wt% of the modified guar gum inclusion agent aqueous dispersion is used to coat the micropellets with a sustained-release layer with an enteric layer, and the mixture is dried to obtain mesalazine enteric-coated sustained-release micropellets, wherein the mass of the enteric layer is 10% of the pellet core.

[0046] The preparation method of the modified guar gum inclusion agent comprises the following steps:

[0047] X1. Dissolve guar gum in water, then dropwise add an equal volume of 1.5 wt% sodium periodate solution, the mass ratio of guar gum to sodium periodate being 1:0.65, stir in dark at room temperature for 6 h, add ethylene glycol for quenching, and then dialyze, Mw < 12000Da, and freeze-dry after the dialysis to obtain oxidized guar gum;

[0048] X2. Dissolve oxidized guar gum in 15 times the weight of 1-allyl-3-methylimidazolium chloride, add undecanoyl chloride, the mass ratio of oxidized guar gum to undecanoyl chloride is 1:5.5, heat to 50° C. and stir for 5 hours, then add methanol to dilute, a precipitate appears, let stand and filter, wash the residue with methanol and dry to obtain modified guar gum;

[0049] X3. Dissolve chitosan in acetic acid, and then add an equal volume of modified guar gum solution, the mass ratio of chitosan to modified guar gum is 1:3. Heat to 40°C and stir for 0.5h, then freeze-dry the mixture to obtain the modified guar gum inclusion compound.

[0050] Example 2

[0051] A method for preparing mesalazine enteric-coated sustained-release pellets comprises the following steps:

[0052] S1, mixing mesalazine, povidone and microcrystalline cellulose in a mass ratio of 40:15:25, wet granulating, spheronizing, drying and passing through a 1 mm sieve to obtain pellet cores;

[0053] S2, coating the pellet core with 60 wt % ethyl cellulose aqueous dispersion in a fluidized bed, and drying to obtain pellets with a sustained-release layer, wherein the mass of the sustained-release layer is 3.5% of the pellet core;

[0054] S3. In a fluidized bed, 15 wt% of the modified guar gum inclusion agent aqueous dispersion is used to coat the micropellets with a sustained-release layer with an enteric layer, and the mixture is dried to obtain mesalazine enteric-coated sustained-release micropellets, wherein the mass of the enteric layer is 10% of the pellet core.

[0055] The preparation method of the modified guar gum inclusion agent comprises the following steps:

[0056] X1. Dissolve guar gum in water, then dropwise add an equal volume of 1.5 wt% sodium periodate solution, the mass ratio of guar gum to sodium periodate being 1:0.65, stir in dark at room temperature for 6 h, add ethylene glycol for quenching, and then dialyze, Mw < 12000Da, and freeze-dry after the dialysis to obtain oxidized guar gum;

[0057] X2. Dissolve oxidized guar gum in 15 times the weight of 1-allyl-3-methylimidazolium chloride, then add undecanoyl chloride, the mass ratio of oxidized guar gum to undecanoyl chloride is 1:5.5, heat to 50°C and stir for 5 hours, then add methanol to dilute, a precipitate appears, let it stand and filter, wash the residue with methanol and dry.

[0058] Example 3

[0059] A method for preparing mesalazine enteric-coated sustained-release pellets comprises the following steps:

[0060] S1, mixing mesalazine, povidone and microcrystalline cellulose in a mass ratio of 40:15:25, wet granulating, spheronizing, drying and passing through a 1 mm sieve to obtain pellet cores;

[0061] S2, coating the pellet core with 60 wt % ethyl cellulose aqueous dispersion in a fluidized bed, and drying to obtain pellets with a sustained-release layer, wherein the mass of the sustained-release layer is 3.5% of the pellet core;

[0062] S3. In a fluidized bed, 15 wt% of the modified guar gum inclusion agent aqueous dispersion is used to coat the micropellets with a sustained-release layer with an enteric layer, and the mixture is dried to obtain mesalazine enteric-coated sustained-release micropellets, wherein the mass of the enteric layer is 10% of the pellet core.

[0063] The preparation method of the modified guar gum inclusion agent comprises the following steps:

[0064] X1. Dissolve guar gum in water, then dropwise add an equal volume of 1.5 wt% sodium periodate solution, the mass ratio of guar gum to sodium periodate being 1:0.65, stir in dark at room temperature for 6 h, add ethylene glycol for quenching, and then dialyze, Mw < 12000Da, and freeze-dry after the dialysis to obtain oxidized guar gum;

[0065] X2. Dissolve chitosan in acetic acid, and then add an equal volume of oxidized guar gum solution, the mass ratio of chitosan to oxidized guar gum being 1:3. Heat to 40°C and stir for 0.5h, then freeze-dry the mixture to obtain a modified guar gum inclusion compound.

[0066] Example 4

[0067] A method for preparing mesalazine enteric-coated sustained-release pellets comprises the following steps:

[0068] S1, mixing mesalazine, povidone and microcrystalline cellulose in a mass ratio of 40:15:25, wet granulating, spheronizing, drying and passing through a 1 mm sieve to obtain pellet cores;

[0069] S2, coating the pellet core with 60 wt % ethyl cellulose aqueous dispersion in a fluidized bed, and drying to obtain pellets with a sustained-release layer, wherein the mass of the sustained-release layer is 3.5% of the pellet core;

[0070] S3. In a fluidized bed, 15 wt% of the modified guar gum inclusion agent aqueous dispersion is used to coat the micropellets with a sustained-release layer with an enteric layer, and the mixture is dried to obtain mesalazine enteric-coated sustained-release micropellets, wherein the mass of the enteric layer is 10% of the pellet core.

[0071] The preparation method of the modified guar gum inclusion agent comprises the following steps:

[0072] X1. Dissolve guar gum in water, then dropwise add an equal volume of 1.5 wt% sodium periodate solution, the mass ratio of guar gum to sodium periodate being 1:0.65, stir in dark at room temperature for 6 h, add ethylene glycol for quenching, and then dialyze, Mw < 12000Da, and freeze-dry after the dialysis to obtain oxidized guar gum;

[0073] X2. Dissolve oxidized guar gum in 15 times the weight of 1-allyl-3-methylimidazole chloride, add acetyl chloride, the mass ratio of oxidized guar gum to acetyl chloride is 1:5.5, heat to 50° C. and stir for 5 hours, then add methanol to dilute, a precipitate appears, let stand and filter, wash the residue with methanol and dry to obtain modified guar gum;

[0074] X3. Dissolve chitosan in acetic acid, and then add an equal volume of modified guar gum solution, the mass ratio of chitosan to modified guar gum is 1:3. Heat to 40°C and stir for 0.5h, then freeze-dry the mixture to obtain the modified guar gum inclusion compound.

[0075] Test Example 1

[0076] The release of mesalazine enteric-coated sustained-release pellets prepared in the control example and the example in pH = 1.2 hydrochloric acid solution, pH = 6.8 phosphate buffer, pH = 7.2 phosphate buffer, and pH = 7.5 phosphate buffer was determined by the first method of the Chinese Pharmacopoeia dissolution assay. The specific data are shown in Table 1.

[0077] Table 1 Release test of mesalazine enteric-coated sustained-release pellets in vitro in simulated gastric and intestinal environments

[0078]

[0079] From the simulated drug release in vitro, it can be seen that the mesalazine enteric-coated sustained-release pellets prepared by the present invention can basically not release the drug in the simulated stomach environment, and start to slowly release the drug in the intestinal environment, so as to achieve targeted drug delivery to the intestinal environment. The mesalazine enteric-coated sustained-release pellets provided by the present invention include an enteric layer and a sustained-release coating layer, which are wrapped on the pill core, and the sustained-release coating layer is made of ethyl cellulose, so that the drug is continuously and slowly released, specifically playing a role in controlling the release rate, release time and release site of the drug. The enteric layer plays a role of not releasing in the stomach and directional release in the intestinal environment, which is beneficial to the treatment of ulcerative colitis and Crohn's disease. Compared with the conventional enteric material in Control Example 1, the modified guar gum used as the enteric material in the embodiment achieves a better sustained-release effect. This may be because the swelling behavior of guar gum is affected by the pH value, with the smallest swelling degree in an acidic environment and the largest swelling degree in an alkaline environment. The modified guar gum inclusion agent after modification and cross-linking avoids the defect of too fast hydration rate, and together with the sustained-release layer, achieves a longer release time, thereby prolonging the efficacy.

[0080] Test Example 2

[0081] The enteric layer and modified guar gum inclusion agent prepared by the control example and the embodiment were subjected to in vitro antibacterial test, and the antibacterial activity was evaluated by the inhibition zone using Escherichia coli. A small disc of modified guar gum inclusion agent (diameter 5 mm) was placed on an agar plate. The plate was incubated at 37°C for 24 hours, and the diameter of the inhibition zone was measured. Each group was performed three times, the average value was taken, and the standard antibiotic ciprofloxacin was used as a positive control.

[0082] Table 2 In vitro antibacterial test of enteric layer

[0083] Experimental protocol Diameter of inhibition zone / mm Positive Control 11.1 Comparative Example 1 / Example 1 8.5 Example 2 5.3 Example 3 6.9 Example 4 7.4

[0084] Colorectal cancer (CRC) is the third most common and second most deadly cancer. In recent years, the role of intestinal microbiota in the occurrence and development of colorectal cancer has received more attention. According to sequencing studies of CRC patients and functional studies of cell culture and animal models, some bacterial species, such as Fusobacterium nucleatum, Escherichia coli, Bacteroides fragilis, Enterococcus faecalis and Salmonella, are associated with CRC. These bacteria can cause host DNA damage through genotoxic substances, including colicin secreted by pks+ Escherichia coli, Bacillus fragilis toxin (BFT) produced by Bacteroides fragilis, and typhoid toxin TT produced by Salmonella. These bacteria can also indirectly promote CRC by affecting host signaling pathways (such as E-cadherin / β-catenin, TLR4 / MYD88 / NF-κB and SMO / RAS / p38 MAPK). It can be seen from the antibacterial test that the modified guar gum inclusion agent prepared in the embodiment has a certain inhibitory effect on Escherichia coli, which has a certain probability of reducing the risk of colon cancer in IBD patients. Guar gum and chitosan, as natural antibacterial substances, show good antibacterial effects at this time. Compared with Examples 2-3, Example 1 has a more obvious antibacterial effect because it contains both guar gum and chitosan. Compared with Example 1, Example 4 uses undecanoyl chloride for esterification to obtain modified guar gum, which is then cross-linked with chitosan to obtain a modified guar gum inclusion agent. The water solubility of the modified guar gum is reduced due to esterification and grafting of hydrophobic alkyl chains, thereby reducing the adhesion of Escherichia coli. On the other hand, esterification can also reduce the probability of the inclusion agent being decomposed by the flora to a certain extent, thereby better ensuring its structural integrity in the intestinal environment.

[0085] The preferred specific embodiments of the present invention are described in detail above. It should be understood that a person skilled in the art can make many modifications and changes based on the concept of the present invention without creative work. Therefore, any technical solution that can be obtained by a person skilled in the art through logical analysis, reasoning or limited experiments based on the concept of the present invention on the basis of the prior art should be within the scope of protection determined by the claims.

Claims

1. A mesalazine enteric-coated sustained-release pellet, characterized in that: The invention comprises the following components: mesalazine, microcrystalline cellulose, modified guar gum encapsulating agent, binder, and ethyl cellulose; The preparation method of the modified guar gum inclusion agent comprises the following steps: X1. Dissolve guar gum in water, then dropwise add an equal volume of 1-2 wt% sodium periodate solution, the mass ratio of guar gum to sodium periodate being 1:0.5-1, stir in the dark at room temperature for 4-8 h, add ethylene glycol for quenching, and then dialyze, Mw <12000Da, and freeze-dry after the dialysis to obtain oxidized guar gum; X2. Dissolve oxidized guar gum in 10 to 20 times the weight of 1-allyl-3-methylimidazole chloride, add undecanoyl chloride, the mass ratio of oxidized guar gum to undecanoyl chloride is 1:5 to 6, heat to 45 to 55° C., stir for 4 to 6 hours, add methanol to dilute, precipitate appears, let stand and filter, wash the residue with methanol and dry to obtain modified guar gum; X3. Dissolve chitosan in acetic acid, and then add an equal volume of modified guar gum solution, the mass ratio of chitosan to modified guar gum is 1:1-3. Heat to 40-50°C and stir for 0.5-1h, then freeze-dry the mixture to obtain the modified guar gum inclusion compound.

2. The mesalazine enteric-coated sustained-release pellets according to claim 1, characterized in that: The binder is selected from one of hypromellose, povidone and starch.

3. A method for preparing mesalazine enteric-coated sustained-release pellets according to any one of claims 1 or 2, characterized in that: The steps include: S1, mixing mesalazine, a binder and microcrystalline cellulose in a mass ratio of 40-50:10-20:20-40, wet granulating, spheronizing, drying and passing through a 0.5-1 mm sieve to obtain a pellet core; S2, coating the pellet core with the ethyl cellulose aqueous dispersion in a fluidized bed, and drying the pellets to obtain pellets with a sustained-release layer, wherein the mass of the sustained-release layer is 2 to 10% of the pellet core; S3. The micropellets with the sustained-release layer are coated with the modified guar gum inclusion agent aqueous dispersion in a fluidized bed and dried to obtain mesalazine enteric-coated sustained-release micropellets, wherein the mass of the enteric layer is 8-18% of the pellet core.

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