Gel for in-vivo cultivation of calculus bovis and preparation method thereof

Abstract

The invention discloses gel for in-vivo cultivation of calculus bovis and a preparation method of the gel, and relates to the technical field of in-vivo cultivation of calculus bovis. The gel for in-vivo cultivation of calculus bovis comprises the following components in percentage by mass: 0.1%-5% of a medicine storage, 8%-20% of a polymer gel skeleton, 0.1%-2% of a cross-linking agent, 0.1%-2% of a cross-linking regulator, 50%-65% of a solvent and 10%-40% of a cross-linking agent solution, the drug storage cavern exists in the form of beta-glucuronidase sustained release microspheres. The spongy porous gel prepared by the preparation method disclosed by the invention can be subjected to a cross-linking reaction in the bovine gallbladder by adopting an injection mode to form a spongy bezoar bed, the bezoar bed can slowly release beta-glucuronidase and promote the decomposition of bound bilirubin into free bilirubin, and finally the free bilirubin forms calcium bilirubin which is combined with mucoprotein to form small bezoar particles. And the small particles are enriched by the bezoar bed to form bezoar with high yield and good quality.

Description

Technical Field

[0001] The invention relates to the technical field of in vivo cultivation of bezoar, in particular to a gel for in vivo cultivation of bezoar and a preparation method thereof. Background Art

[0002] Bezoar is a precious Chinese medicinal material with the effects of clearing the heart, cooling the liver, detoxifying, and opening the orifices. It is used to treat a variety of difficult and complicated diseases. However, natural bezoar resources are extremely scarce and it is difficult to meet market demand. Therefore, artificial bezoar technology is gradually developing.

[0003] Patent CN202411057451.9 discloses a thermosensitive gel for bezoar cultivation and its preparation method and application. It uses N-isopropylacrylamide, acrylamide and N,N-methylenebisacrylamide as raw materials to prepare polyacrylamide hydrogel, which is then injected into the gallbladder of a cow for in vivo cultivation of bezoar. The gel prepared by this scheme is thermosensitive and quickly transforms into a viscous state capable of enriching bezoar; however, the gel prepared by this scheme degrades too quickly. When degradation is completed, small bezoar particles have not yet formed, which increases the difficulty of collecting bezoar.

[0004] Therefore, we propose a gel for in vivo cultivation of bezoar and a preparation method thereof to solve the problems mentioned in the background technology. Summary of the Invention

[0005] The purpose of the present invention is to provide a gel for cultivating bezoar in vivo and a preparation method thereof, so as to solve the problems raised in the prior art.

[0006] To achieve the above object, the present invention provides the following technical solution: a gel for in vivo cultivation of bezoar, comprising the following mass components: in mass percentage, 0.1% to 5% drug reservoir, 8% to 20% polymer gel skeleton, 0.1% to 2% cross-linking agent, 0.1% to 2% cross-linking regulator, 50% to 65% solvent, and 10% to 40% cross-linking agent solution; The drug reservoir is in the form of β-glucuronidase sustained-release microspheres.

[0007] A method for preparing a gel for in vivo cultivation of bezoar comprises the following steps: The beta-glucuronidase sustained-release microspheres, a polymer gel skeleton, a crosslinking agent, a crosslinking regulator and a solvent are mixed and stirred evenly to obtain a gel emulsion. The crosslinking agent solution is added to the gel emulsion and stirred evenly to obtain a gel for cultivating bezoar in vivo.

[0008] Furthermore, the gel for in vivo cultivation of bezoar is a sponge-like porous gel, hereinafter referred to as sponge-like gel.

[0009] Furthermore, the preparation method of the cross-linking agent solution is as follows: Mix the crosslinker and the solution in a mass ratio of 1: (9-99), stir evenly, and obtain a crosslinker solution with a mass fraction of 1% to 10%; The solution is ox bile.

[0010] Furthermore, the polymer gel skeleton is one or a mixture of polyacrylic acid, polyacrylic acid sodium salt, sodium polyacrylate, carbomer, sodium alginate, sodium carboxymethyl cellulose, and cross-linked sodium carboxymethyl cellulose; The cross-linking agent is one or a mixture of aluminum glycinate, aluminum hydroxide, aluminum glycolate, aluminum chloride, aluminum citrate, synthetic aluminum silicate, and calcium chloride; The cross-linking regulator is one or a mixture of tartaric acid, citric acid, phosphoric acid, malic acid, and edetic acid; The solvent is glycerol.

[0011] Furthermore, the β-glucuronidase sustained-release microspheres are prepared by the following process: S1: PLGA (poly(lactic-co-glycolic acid)) was mixed with dichloromethane and vortexed to dissolve to obtain a mixed solution; S2: Add β-glucuronidase to the mixed solution, vortex to disperse evenly, add polyvinyl alcohol, stir, add NaCl, stir to solidify, and obtain β-glucuronidase sustained-release microspheres.

[0012] Furthermore, in S1, the mass ratio of PLGA to dichloromethane was 1:(5~15).

[0013] Furthermore, in S2, the mass ratio of the mixed solution, β-glucuronidase, polyvinyl alcohol and NaCl is 100: (0.01~8): (700~1100): (900~1100).

[0014] Furthermore, in S2, polyvinyl alcohol is added in the form of a solution with a mass fraction of 1% to 4%; In S2, NaCl is added in the form of a solution with a mass fraction of 1% to 10%; The temperature of the NaCl solution is 0°C to 15°C.

[0015] Furthermore, in S2, the process conditions for stirring and solidifying are: temperature 30°C~40°C, time 1h~3h.

[0016] Compared with the prior art, the present invention has the following beneficial effects: 1. The spongy gel prepared by the present invention can undergo a cross-linking reaction in the bovine gallbladder to form a spongy bezoar bed, slowly release β-glucuronidase, promote the decomposition of bound bilirubin into free bilirubin, and finally the free bilirubin forms bilirubin calcium, which combines with mucin to form small bezoar particles. The small particles are enriched in the bezoar bed to form bezoar with high yield and good quality.

[0017] 2. The spongy gel prepared by the present invention has a porous structure and a strong adsorption capacity, which is conducive to the precipitation of bezoar crystals, shortens the formation cycle of bezoar, and is conducive to improving production efficiency.

[0018] 3. The gel emulsion prepared by the present invention has a fast cross-linking speed, good injectability, and can quickly form a gel in the body. The viscoelastic response of the sponge-like gel is characterized by an elastic modulus (G') being greater than the viscous modulus (G"), and it will not be dispersed in the rotating bile, and the bezoar bed can be maintained for a long time. The bezoar bed is implanted by injection without surgery, reducing the risk of disease in cattle, being easy for farmers to operate, and causing little stress on the cattle. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 This is an in vitro release curve of β-glucuronidase in a gel for in vivo cultivation of bezoar according to the present invention; Figure 2 This is a scanning electron micrograph of the sponge gel prepared in Example 1 of the present invention; Figure 3 This is a scanning electron micrograph of the sponge gel prepared in Example 2 of the present invention; Figure 4 This is a scanning electron micrograph of the sponge gel prepared in Example 3 of the present invention; Figure 5 This is a scanning electron micrograph of the sponge gel prepared in Example 4 of the present invention; Figure 6 This is a scanning electron micrograph of the sponge gel prepared in Example 5 of the present invention; Figure 7 This is a scanning electron micrograph of the sponge gel prepared in Example 6 of the present invention; Figure 8 This is a scanning electron micrograph of the sponge gel prepared in Example 7 of the present invention; Figure 9 This is a viscoelasticity curve of the sponge gel prepared in Example 1 of the present invention; Among them, 106022-01 is the viscoelasticity curve of the sponge gel of Example 6; 22012502 is the viscoelasticity curve of the sponge gel of Example 7; The horizontal axis represents the oscillation frequency, and the vertical axis represents the viscoelastic modulus. DETAILED DESCRIPTION

[0020] The following will clearly and completely describe the technical solutions in the embodiments of the present invention in conjunction with the accompanying drawings. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making any creative efforts shall fall within the scope of protection of the present invention.

[0021] In the following specific embodiments, PLGA, CAS No. 34346-01-5, Product No. P879466-5g, from Macklin; Sodium polyacrylate, CAS number 9003-04-7, product number S818399-2.5kg, from Macklin; Polyacrylic acid, CAS No. 9003-01-4, Product No. P815683-500g, from Macklin; β-glucuronidase, CAS number 9001-45-0, purity 1000u / mg, product number TX21552-100KU, from Shanghai Yingxin Laboratory; Sodium alginate, CAS number 9005-38-3, product number S100126-2.5kg, from aladdin; Carbomer, CAS No. 54182-57-9, product No. S31102-250g, was obtained from Shanghai Yuanye Biotechnology; Sodium carboxymethyl cellulose, CAS number 9004-32-4, viscosity: 10000 mPa·s, from Anhui Shanhe; Cross-linked sodium carboxymethyl cellulose, CAS No. 74811-65-7, model SD-711, from FMC; Example 1: A method for preparing a gel for in vivo cultivation of bezoar, comprising the following steps: (1) Preparation of β-glucuronidase sustained-release microspheres: S1: 10 g of PLGA was mixed with 100 g of dichloromethane and vortexed to dissolve to obtain a mixed solution; S2: 0.01 g of β-glucuronidase was added to the mixed solution and vortexed to disperse it evenly, 800 g of a 2% polyvinyl alcohol solution was added and stirred, and 1000 g of a 5% NaCl solution at 0°C was added and stirred to obtain β-glucuronidase sustained-release microspheres; the stirring and curing process conditions were: temperature 40°C, time 3 h; (2) Preparation of calcium chloride solution: Calcium chloride and ox bile were mixed in a mass ratio of 1:19 and stirred evenly to obtain a 5% calcium chloride solution; (3) Preparation of sponge gel: 2 g of β-glucuronidase sustained-release microspheres, 15 g of sodium polyacrylate, 1 g of aluminum glycolate, 1 g of tartaric acid and 80 g of glycerol were mixed and stirred evenly to obtain a gel emulsion. 40 g of a 5% by mass calcium chloride solution was added to the gel emulsion and stirred evenly to obtain a sponge gel.

[0022] Example 2: A method for preparing a gel for in vivo cultivation of bezoar, comprising the following steps: (1) Preparation of β-glucuronidase sustained-release microspheres: S1: 10 g of PLGA was mixed with 100 g of dichloromethane and vortexed to dissolve to obtain a mixed solution; S2: 0.01 g of β-glucuronidase was added to the mixed solution and vortexed to disperse it evenly, 800 g of a 2% polyvinyl alcohol solution was added and stirred, and 1000 g of a 5% NaCl solution at 0°C was added and stirred to obtain β-glucuronidase sustained-release microspheres; the stirring and curing process conditions were: temperature 40°C, time 3 h; (2) Preparation of calcium chloride solution: Calcium chloride and ox bile were mixed in a mass ratio of 1:19 and stirred evenly to obtain a 5% calcium chloride solution; (3) Preparation of sponge gel: 1 g of β-glucuronidase sustained-release microspheres, 10 g of polyacrylic acid, 5 g of sodium carboxymethyl cellulose, 0.5 g of aluminum hydroxide, 0.5 g of edetic acid and 80 g of glycerol were mixed and stirred uniformly to obtain a gel emulsion. 40 g of a 5% by mass calcium chloride solution was added to the gel emulsion and stirred uniformly to obtain a sponge gel.

[0023] Example 3: A method for preparing a gel for in vivo cultivation of bezoar, comprising the following steps: (1) Preparation of β-glucuronidase sustained-release microspheres: S1: 10 g of PLGA was mixed with 100 g of dichloromethane and vortexed to dissolve to obtain a mixed solution; S2: 0.01 g of β-glucuronidase was added to the mixed solution and vortexed to disperse it evenly, 800 g of a 2% polyvinyl alcohol solution was added and stirred, and 1000 g of a 5% NaCl solution at 0°C was added and stirred to obtain β-glucuronidase sustained-release microspheres; the stirring and curing process conditions were: temperature 40°C, time 3 h; (2) Preparation of calcium chloride solution: Calcium chloride and ox bile were mixed in a mass ratio of 1:19 and stirred evenly to obtain a 5% calcium chloride solution; (3) Preparation of sponge gel: Mix 5 g of β-glucuronidase sustained-release microspheres, 15 g of sodium polyacrylate, 5 g of sodium alginate, 1.5 g of aluminum glycolate, 0.5 g of aluminum hydroxide, 1.5 g of tartaric acid, 0.5 g of citric acid and 80 g of glycerol, stir evenly to obtain a gel emulsion, add 40 g of 5% by mass calcium chloride solution to the gel emulsion, stir evenly to obtain a sponge gel.

[0024] Example 4: A method for preparing a gel for in vivo cultivation of bezoar, comprising the following steps: (1) Preparation of β-glucuronidase sustained-release microspheres: S1: 10 g of PLGA was mixed with 100 g of dichloromethane and vortexed to dissolve to obtain a mixed solution; S2: 0.01 g of β-glucuronidase was added to the mixed solution and vortexed to disperse it evenly, 800 g of a 2% polyvinyl alcohol solution was added and stirred, and 1000 g of a 5% NaCl solution at 0°C was added and stirred to obtain β-glucuronidase sustained-release microspheres; the stirring and curing process conditions were: temperature 40°C, time 3 h; (2) Preparation of calcium chloride solution: Calcium chloride and ox bile were mixed in a mass ratio of 1:19 and stirred evenly to obtain a 5% calcium chloride solution; (3) Preparation of sponge gel: 0.5 g of β-glucuronidase sustained-release microspheres, 10 g of polyacrylic acid, 1 g of cross-linked sodium carboxymethyl cellulose, 10.5 g of aluminum glycinate, 0.5 g of citric acid and 80 g of glycerol were mixed and stirred uniformly to obtain a gel emulsion. 40 g of a 5% by mass calcium chloride solution was added to the gel emulsion and stirred uniformly to obtain a sponge gel.

[0025] Example 5: A method for preparing a gel for in vivo cultivation of bezoar, comprising the following steps: (1) Preparation of β-glucuronidase sustained-release microspheres: S1: 10 g of PLGA was mixed with 100 g of dichloromethane and vortexed to dissolve to obtain a mixed solution; S2: 0.01 g of β-glucuronidase was added to the mixed solution and vortexed to disperse it evenly, 800 g of a 2% polyvinyl alcohol solution was added and stirred, and 1000 g of a 5% NaCl solution at 0°C was added and stirred to obtain β-glucuronidase sustained-release microspheres; the stirring and curing process conditions were: temperature 40°C, time 3 h; (2) Preparation of calcium chloride solution: Calcium chloride and ox bile were mixed in a mass ratio of 1:19 and stirred evenly to obtain a 5% calcium chloride solution; (3) Preparation of sponge gel: 3 g of β-glucuronidase sustained-release microspheres, 10 g of sodium polyacrylate, 5 g of sodium alginate, 5 g of carbomer, 1 g of aluminum citrate, 1 g of citric acid and 80 g of glycerol were mixed and stirred evenly to obtain a gel emulsion. 40 g of a 5% by mass calcium chloride solution was added to the gel emulsion and stirred evenly to obtain a sponge gel.

[0026] Example 6: A method for preparing a gel for in vivo cultivation of bezoar, comprising the following steps: (1) Preparation of β-glucuronidase sustained-release microspheres: S1: 10 g of PLGA was mixed with 100 g of dichloromethane and vortexed to dissolve to obtain a mixed solution; S2: 0.01 g of β-glucuronidase was added to the mixed solution and vortexed to disperse it evenly, 800 g of a 2% polyvinyl alcohol solution was added and stirred, and 1000 g of a 5% NaCl solution at 0°C was added and stirred to obtain β-glucuronidase sustained-release microspheres; the stirring and curing process conditions were: temperature 40°C, time 3 h; (2) Preparation of calcium chloride solution: Calcium chloride and ox bile were mixed in a mass ratio of 1:19 and stirred evenly to obtain a 5% calcium chloride solution; (3) Preparation of sponge gel: Mix 4 g of β-glucuronidase sustained-release microspheres, 8 g of polyacrylic acid, 8 g of sodium alginate, 4 g of cross-linked sodium carboxymethyl cellulose, 1 g of aluminum glycolate, 1 g of calcium chloride, 1 g of citric acid, 1 g of tartaric acid and 100 g of glycerol, stir evenly to obtain a gel emulsion, add 50 g of 5% by mass calcium chloride solution to the gel emulsion, stir evenly to obtain a sponge gel.

[0027] Example 7: A method for preparing a gel for in vivo cultivation of bezoar, comprising the following steps: (1) Preparation of β-glucuronidase sustained-release microspheres: S1: 10 g of PLGA was mixed with 100 g of dichloromethane and vortexed to dissolve to obtain a mixed solution; S2: 0.01 g of β-glucuronidase was added to the mixed solution and vortexed to disperse it evenly, 800 g of a 2% polyvinyl alcohol solution was added and stirred, and 1000 g of a 5% NaCl solution at 0°C was added and stirred to obtain β-glucuronidase sustained-release microspheres; the stirring and curing process conditions were: temperature 40°C, time 3 h; (2) Preparation of calcium chloride solution: Calcium chloride and ox bile were mixed in a mass ratio of 1:19 and stirred evenly to obtain a 5% calcium chloride solution; (3) Preparation of sponge gel: 5 g of β-glucuronidase sustained-release microspheres, 10 g of sodium polyacrylate, 8 g of sodium alginate, 2 g of cross-linked sodium carboxymethyl cellulose, 1.5 g of aluminum chloride, 2 g of citric acid and 100 g of glycerol were mixed and stirred evenly to obtain a gel emulsion. 50 g of a 5% by mass calcium chloride solution was added to the gel emulsion and stirred evenly to obtain a sponge gel.

[0028] Example 8: Using Example 1 as a comparison, the mass ratio of each component in the β-glucuronidase sustained-release microspheres, the process parameters during preparation, and the mass fraction of the calcium chloride solution were adjusted, while the other conditions remained unchanged. The specific process is as follows: (1) Preparation of β-glucuronidase sustained-release microspheres: S1: 5 g of PLGA was mixed with 75 g of dichloromethane and vortexed to dissolve to obtain a mixed solution. S2: 5.2 g of β-glucuronidase was added to the mixed solution and vortexed to disperse it evenly. 650 g of a 4% polyvinyl alcohol solution was added and stirred. 700 g of a 5% NaCl solution at 10°C was added and stirred to obtain β-glucuronidase sustained-release microspheres. The stirring and curing process conditions were: temperature 35°C, time 2 h. (2) Preparation of calcium chloride solution: Calcium chloride and ox bile were mixed in a mass ratio of 1:9 and stirred evenly to obtain a 10% calcium chloride solution; (3) Preparation of sponge gel: 2 g of β-glucuronidase sustained-release microspheres, 15 g of sodium polyacrylate, 1 g of aluminum glycolate, 1 g of tartaric acid and 80 g of glycerol were mixed and stirred evenly to obtain a gel emulsion. 40 g of a 10% calcium chloride solution was added to the gel emulsion and stirred evenly to obtain a sponge gel.

[0029] Example 9: Using Example 1 as a comparison, the mass ratio of each component in the β-glucuronidase sustained-release microspheres, the process parameters during preparation, and the mass fraction of the calcium chloride solution were adjusted, while the other conditions remained unchanged. The specific process is as follows: (1) Preparation of β-glucuronidase sustained-release microspheres: S1: 10 g of PLGA was mixed with 50 g of dichloromethane and vortexed to dissolve to obtain a mixed solution. S2: 2.8 g of β-glucuronidase was added to the mixed solution and vortexed to disperse it evenly. 660 g of a 1% polyvinyl alcohol solution was added and stirred. 540 g of a 10% NaCl solution at 15°C was added and stirred to obtain β-glucuronidase sustained-release microspheres. The stirring and curing process conditions were: temperature 30°C, time 1 hour. (2) Preparation of calcium chloride solution: Calcium chloride and ox bile were mixed in a mass ratio of 1:99 and stirred evenly to obtain a 1% calcium chloride solution; (3) Preparation of sponge gel: 2 g of β-glucuronidase sustained-release microspheres, 15 g of sodium polyacrylate, 1 g of aluminum glycolate, 1 g of tartaric acid and 80 g of glycerol were mixed and stirred evenly to obtain a gel emulsion. 40 g of a 1% calcium chloride solution was added to the gel emulsion and stirred evenly to obtain a sponge gel.

[0030] Comparative Example 1: Using Example 1 as a comparison, β-glucuronidase sustained-release microspheres were not prepared, and β-glucuronidase was directly blended with sodium polyacrylate, aluminum glycolate, tartaric acid and glycerol, while other conditions remained unchanged.

[0031] Comparative Example 2: Using Example 1 as a comparison, calcium chloride solution was not prepared, and calcium chloride was directly blended with β-glucuronidase sustained-release microspheres, sodium polyacrylate, aluminum glycolate, tartaric acid and glycerol, while other conditions remained unchanged.

[0032] experiment: In vitro release experiment: 10 g of each sponge gel obtained in the example and comparative example was added to 250 mL of fresh ox bile solution, and the mixture was placed in a 37°C constant temperature water bath shaker at a shaking speed of 50 r / min. The in vitro release was measured, and samples were taken daily. After 15 days of release, the release curve of β-glucuronidase in the sponge gel was obtained using the MicroBCA method on a microplate reader. Sponge gel surface morphology: Take 10 g of the sponge gel obtained in the example and the comparative example respectively, observe the surface morphology using a scanning electron microscope and record the results; Cross-linking time and gel morphology: Take 10 g of the gel emulsion obtained in the example and comparative example respectively, use a 1 mm needle and a 10 ml syringe to inject the gel emulsion into a rotating 5% calcium chloride bile solution, and observe and record the cross-linking time and state; Rheological properties of sponge gel: The sponge gel obtained in Example 6 and Example 7 was measured using a ThermoScientific rheometer (model: HAAKEMARS40), with a flat rotor, rotor model P35 / Ti-02190347, a detection gap of 1 mm, a detection temperature of 32°C, an Osc oscillation frequency sweep mode, and a controlled shear stress (CS) mode. The shear stress τ = 200 Pa, the oscillation frequency variable range f = 100 Hz to 0.1 Hz, and 8 data points were collected within each order of magnitude of the variable. The measurement program was started, the sample was evenly coated on the rheometer measuring table, the rotor was lowered, the edge was scraped, and the viscoelasticity curve was obtained by detection. like Figure 9As shown in the figure, the viscoelastic response is that the elastic modulus (G') is greater than the viscous modulus (G"), which mainly shows elastic properties and will not be dispersed in the rotating bile.

[0033] The following table shows the test results of sponge gel properties;

[0034] Based on the data in the above table, we can draw the following conclusions: The gels obtained in Examples 1 to 9 all have a sponge porous structure and have a strong adsorption capacity, which is conducive to enriching small bezoar particles; The in vitro release rate of β-glucuronidase in the spongy gel obtained in Examples 3, 6, and 7 is relatively slow, which is more conducive to the production of bezoar particles when cultivating bezoar in vivo; In Examples 6 and 7, the viscoelastic response of the sponge gel is shown as the elastic modulus (G') being greater than the viscous modulus (G"), mainly exhibiting elastic properties; Comparative Example 1: β-glucuronidase is directly blended with sodium polyacrylate, aluminum glycolate, tartaric acid and glycerol. The in vitro release rate of β-glucuronidase is fast, which is not conducive to the production of bezoar granules. Comparative Example 2: Calcium chloride was directly blended with β-glucuronidase sustained-release microspheres, sodium polyacrylate, aluminum glycolate, tartaric acid, and glycerol. The in vitro release rate of β-glucuronidase was faster, and the resulting product was flocculent particles with poor gelation. In summary, the gel emulsions obtained in Examples 3, 6 and 7 have a short crosslinking time and will not be dispersed in the rotating bile. They have good injectability and can quickly gel in vivo, and can more effectively enrich the bezoar particles.

[0035] It will be apparent to those skilled in the art that the present invention is not limited to the details of the exemplary embodiments described above and that the invention can be embodied in other specific forms without departing from the spirit or essential characteristics of the invention. Therefore, the embodiments should be considered in all respects as illustrative and non-restrictive, and the scope of the invention is defined by the appended claims, not the foregoing description, and all variations within the meaning and range of equivalents of the claims are intended to be included therein. Any reference sign in a claim should not be construed as limiting the claim to which it relates.

Claims

1. A gel for cultivating bezoar in vivo, characterized in that: The invention comprises the following mass components: by mass percentage, 0.1% to 5% drug reservoir, 8% to 20% polymer gel skeleton, 0.1% to 2% cross-linking agent, 0.1% to 2% cross-linking regulator, 50% to 65% solvent, and 10% to 40% cross-linking agent solution; The drug reservoir is in the form of β-glucuronidase sustained-release microspheres; The polymer gel skeleton is one or a mixture of polyacrylic acid, polyacrylic acid sodium salt, sodium polyacrylate, carbomer, sodium alginate, sodium carboxymethyl cellulose, and cross-linked sodium carboxymethyl cellulose; The cross-linking agent is one or a mixture of aluminum glycinate, aluminum hydroxide, aluminum glycolate, aluminum chloride, aluminum citrate, synthetic aluminum silicate, and calcium chloride; The cross-linking regulator is one or a mixture of tartaric acid, citric acid, phosphoric acid, malic acid, and edetic acid; The solvent is glycerol; The cross-linking agent solution is prepared by mixing the cross-linking agent and ox bile in a mass ratio of 1: (9-99).

2. A method for preparing a gel for in vivo cultivation of bezoar, characterized in that: The following steps are involved: The beta-glucuronidase sustained-release microspheres, a polymer gel skeleton, a crosslinking agent, a crosslinking regulator and a solvent are mixed and stirred evenly to obtain a gel emulsion. The crosslinking agent solution is added to the gel emulsion and stirred evenly to obtain a gel for cultivating bezoar in vivo.

3. The method for preparing a gel for in vivo cultivation of bezoar according to claim 2, wherein: The β-glucuronidase sustained-release microspheres are prepared by the following process: S1: PLGA was mixed with dichloromethane and vortexed to dissolve to obtain a mixed solution; S2: Add β-glucuronidase to the mixed solution, vortex to disperse evenly, add polyvinyl alcohol, stir, add NaCl, stir to solidify, and obtain β-glucuronidase sustained-release microspheres.

4. The method for preparing a gel for in vivo cultivation of bezoar according to claim 3, wherein: In S1, the mass ratio of PLGA to dichloromethane was 1:(5-15).

5. The method for preparing a gel for in vivo cultivation of bezoar according to claim 3, wherein: In S2, the mass ratio of the mixed solution, β-glucuronidase, polyvinyl alcohol and NaCl is 100: (0.01~8): (700~1100): (900~1100).

6. The method for preparing a gel for in vivo cultivation of bezoar according to claim 2, wherein: The preparation method of the cross-linking agent solution is as follows: The cross-linking agent and ox bile are mixed in a mass ratio of 1: (9-99), stirred evenly, and a cross-linking agent solution with a mass fraction of 1%-10% is obtained.

7. The method for preparing a gel for in vivo cultivation of bezoar according to claim 3, wherein: In S2, polyvinyl alcohol is added in the form of a solution with a mass fraction of 1% to 4%; In S2, NaCl is added in the form of a solution with a mass fraction of 1% to 10%.

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