Liver protection agent containing taurine ursodeoxysodium cholate and preparation method thereof

Abstract

The invention discloses a sodium tauroursodeoxycholate-containing liver protection agent and a preparation method thereof, particularly relates to the technical field of medicines, and relates to a sodium tauroursodeoxycholate-containing liver protection agent and a preparation method thereof. The sodium tauroursodeoxycholate-containing liver protection agent is prepared from sodium tauroursodeoxycholate, a carrier material, a solubilizer, a lubricant and an antioxidant, the sodium tauroursodeoxycholate-containing liver protection agent is prepared from the following raw material components in parts by weight: 5 to 30 parts of sodium tauroursodeoxycholate, 50 to 80 parts of a carrier material, 1 to 10 parts of a solubilizer, 0.1 to 1 part of a lubricant and 0.01 to 0.1 part of an antioxidant, sodium tauroursodeoxycholate is adopted to prepare the liver protection agent, and the sodium tauroursodeoxycholate can prevent the effect of Bax protein, so that the release of cytochrome c and the activation of caspase by mitochondria are prevented, and the stability of a mitochondrial membrane is effectively maintained; meanwhile, bile secretion and gallbladder contraction can be promoted, the pressure in the bile duct is improved, the bile fluidity is improved, the cholestasis phenomenon can be improved, and therefore the application range is wider.

Description

Technical Field

[0001] The present invention relates to the field of medical technology, and more specifically to a liver protecting agent containing sodium taurine ursodeoxycholate and a preparation method thereof. Background Art

[0002] Sodium tauroursodeoxycholate is a conjugated bile acid obtained by chemical synthesis of ursodeoxycholic acid and taurine. It has multiple biological activities such as endoplasmic reticulum stress inhibitor, mitochondrial stabilizer and anti-apoptotic agent. It shows significant therapeutic effects in the treatment of cholestasis, cirrhosis and viral hepatitis. Therefore, it is of great significance to study and develop a highly effective liver protector containing sodium tauroursodeoxycholate.

[0003] The liver protecting agents in the related technology mainly include glycyrrhizic acid, silymarin, alanine, glutathione, curcumin, pyrroloquinoline quinone, inositol and vitamins; among them, glycyrrhizic acid and silymarin, as anti-inflammatory and anti-fibrotic ingredients, can reduce liver inflammation and prevent the progression of fibrosis; alanine and glutathione, as detoxifying ingredients, help the liver eliminate toxic substances and reduce the burden on the liver by combining with toxic substances or participating in detoxification reactions; curcumin protects the liver by promoting fat metabolism in the liver and reducing the accumulation of triglycerides in the liver; pyrroloquinoline quinone can directly act on liver cells, increase the number of fresh mitochondria in liver cells, enhance the liver's metabolic capacity, and help metabolize excess fat, garbage and toxins; inositol can accelerate the metabolism of body fat, regulate the process, emulsify and discharge excess fat in the liver, thereby reducing the risk of fatty liver; vitamin components have reversible reducing properties, participate in redox reactions, can reduce fatty degeneration of liver cells, promote liver cell regeneration and liver glycogen synthesis and detoxification.

[0004] However, there are still some shortcomings in its actual use, such as a single mechanism of action. The mechanism of action of the liver protectors in related technologies is relatively single, mainly focusing on reducing liver inflammation and lowering transaminase levels; low therapeutic effect. The liver protectors in related technologies have a certain effect on liver protection, but for complex or severe liver diseases, their therapeutic effect is relatively low; high risk. Due to the diverse ingredients, the liver protectors in related technologies have complex interactions with other drugs, and their risk level is increased. Summary of the invention

[0005] In order to improve the above problems and reduce the problems of single mechanism of action, low therapeutic effect and high risk, the present invention provides a liver protective agent containing sodium taurine ursodeoxycholate and a preparation method thereof to solve the problems raised in the above background technology.

[0006] To achieve the above object, the present invention provides the following technical solutions:

[0007] A liver protecting agent containing sodium taurine ursodeoxycholate is composed of sodium taurine ursodeoxycholate, a carrier material, a solubilizer, a lubricant and an antioxidant.

[0008] Preferably, the liver protecting agent containing sodium taurine ursodeoxycholate is prepared by the following specific steps:

[0009] A1. Mix sodium taurine ursodeoxycholate, carrier materials, solubilizers and other auxiliary materials in a mixer at a stirring speed of 50-300 r / min to obtain a sodium taurine ursodeoxycholate mixture;

[0010] A2, slowly add the sodium taurine ursodeoxycholate mixture obtained in A1 to 10 times the volume of the binder solution, stirring at a speed of 150-300 r / min for 10-60 min to form a soft material, and pass the wet soft material through a 14-mesh sieve to form wet granules;

[0011] A3, placing the wet granules obtained in A2 into a drying device and drying at a temperature of 50-81°C for 2-6 hours to reduce the moisture content of the wet granules to 3%-5%, thereby obtaining dried granules;

[0012] A4. The dried particles obtained in A3 are fully mixed with a lubricant and an antioxidant in a mixer at a stirring speed of 50-300 r / min, and the obtained mixture is tableted and formed into a preparation to obtain a liver protective agent containing sodium taurine ursodeoxycholate.

[0013] Preferably, the components and weight proportions of the raw materials for preparing the liver protective agent containing sodium taurine ursodeoxycholate are as follows:

[0014] 5-30 parts of sodium tauroursodeoxycholate, 50-80 parts of carrier material, 1-10 parts of solubilizer, 0.1-1 parts of lubricant and 0.01-0.1 parts of antioxidant.

[0015] Preferably, the sodium tauroursodeoxycholate consists of ursodeoxycholic acid, triethylamine, ethyl chloroformate, taurine and sodium carbonate.

[0016] Preferably, the preparation method of sodium tauroursodeoxycholate is as follows, comprising the following steps:

[0017] C1. Pour anhydrous acetone into a reaction apparatus and install a condensing device, then slowly add ursodeoxycholic acid into 3 times the volume of acetone, stirring at a speed of 300-500 r / min until the ursodeoxycholic acid is completely dissolved;

[0018] C2, controlling the condensing device to maintain the temperature at (-5)-(-10)°C, adding triethylamine to the dissolved ursodeoxycholic acid obtained in C1, continuing to maintain the above conditions to completely dissolve the triethylamine, then slowly adding ethyl chloroformate dropwise, keeping the reaction system stable, continuing the reaction for 1-3.5 hours, and then filtering the obtained solution to obtain a mixed anhydride solution;

[0019] C3, dissolving taurine in a sodium carbonate solution to obtain a taurine sodium carbonate solution, slowly adding the solution dropwise to the mixed anhydride solution obtained in C2, reacting for 4-9 hours at a temperature of 20-30° C. and a stirring speed of 100-200 r / min, filtering out the precipitate to obtain a filtrate;

[0020] C4, adding dilute hydrochloric acid solution to the filtrate obtained in C3 to adjust the pH of the filtrate to 6.0-7.0, then pouring the solution into an evaporating flask of a rotary evaporator, evaporating to dryness at a speed of 100-300 r / min and a temperature of 50-90° C., and after the solution is evaporated to dryness, continuing to dry at a vacuum degree of 0.001-0.01 mAar and a temperature of 70-90° C. to obtain a crude dried product of tauroursodeoxycholic acid;

[0021] C5, adding the dried crude product obtained in C4 to 10 times the volume of acetone and purified water, stirring at a temperature of 80-100° C. and a rotation speed of 100-300 r / min to completely dissolve it, and then using a cation exchange resin to desalt the solution at a flow rate of 10-40 m / h to obtain desalted sodium tauroursodeoxycholate;

[0022] C6. Add the sodium tauroursodeoxycholate obtained in C5 to a mixed solvent of 10 times the volume of acetone and purified water, stir at a temperature of 80-100°C and a rotation speed of 100-300r / min to completely dissolve it, cool to (-5)-0°C for crystallization, and after the crystallization is completed, filter, rinse and dry again to obtain high-purity sodium tauroursodeoxycholate.

[0023] Preferably, the sodium tauroursodeoxycholate is composed of ursodeoxycholic acid, triethylamine, ethyl chloroformate, taurine and sodium carbonate in a molar ratio of 1:(1-1.3):(1-1.1):(1-1.2):(1.5-3).

[0024] Preferably, the carrier material consists of starch, lactose and microcrystalline cellulose in a weight ratio of (3-4): (2.5-4): (2.5-4.5).

[0025] Preferably, the adhesive consists of ethanol and water in a weight ratio of (1-2):1.

[0026] Preferably, the solubilizer is polyethylene glycol; the lubricant is magnesium stearate; and the antioxidant is vitamin E.

[0027] Technical effects and advantages of the present invention:

[0028] 1. The present invention uses sodium taurine ursodeoxycholate to prepare a liver protective agent, which can prevent the action of Bax protein, thereby preventing the release of cytochrome c and the activation of caspase by mitochondria, effectively maintaining the stability of the mitochondrial membrane; it can also promote bile secretion and gallbladder contraction, increase the pressure in the bile duct, increase bile fluidity, and help improve the phenomenon of cholestasis, so it has a wider range of applications;

[0029] 2. The present invention uses sodium taurine ursodeoxycholate to prepare a liver protective agent, which reduces the burden on the liver by promoting bile secretion and improving bile fluidity, and shows a stronger therapeutic effect in improving liver function, preventing hepatocellular carcinoma, reducing endoplasmic reticulum stress and cell apoptosis.

[0030] 3. The sodium taurine ursodeoxycholate used in the present invention has fewer drug binding sites in its molecular structure and is not easy to react with other drugs, thereby reducing the interaction caused by drug binding and reducing the risk. DETAILED DESCRIPTION

[0031] The present invention is further described in detail below in conjunction with the embodiments of the present invention. The raw materials used in the examples and embodiments of the present invention are all commercially available common materials unless otherwise specified below.

[0032] Preparation Example 1-5

[0033] A sodium taurine ursodeoxycholate, the raw material components and their corresponding weights thereof are shown below, and it is prepared by the following preparation method:

[0034] C1. Pour anhydrous acetone into a reaction apparatus and install a condensing device, then slowly add ursodeoxycholic acid into 3 times the volume of acetone, stirring at a speed of 300 r / min until the ursodeoxycholic acid is completely dissolved;

[0035] C2, control the condensing device to keep the temperature at -5°C, add triethylamine to the dissolved ursodeoxycholic acid obtained in C1, continue to maintain the above conditions to completely dissolve the triethylamine, then slowly drop ethyl chloroformate, keep the reaction system stable, continue the reaction for 1 hour, and then filter the obtained solution to obtain a mixed anhydride solution;

[0036] C3, dissolving taurine in a sodium carbonate solution to obtain a sodium carbonate solution of taurine, slowly adding the solution dropwise to the mixed anhydride solution obtained in C2, reacting for 4 hours at a temperature of 20° C. and a stirring speed of 100 r / min, filtering out the precipitate to obtain a filtrate;

[0037] C4, adding dilute hydrochloric acid solution to the filtrate obtained in C3 to adjust the pH of the filtrate to 6.0, then pouring the solution into an evaporating flask of a rotary evaporator, evaporating to dryness at a speed of 100 r / min and a temperature of 50° C. After the solution is evaporated to dryness, continue drying at a vacuum degree of 0.001 mAar and a temperature of 70° C. to obtain a crude dried product of tauroursodeoxycholic acid;

[0038] C5, adding the dried crude product obtained in C4 to 10 times the volume of acetone and purified water, stirring at a temperature of 80° C. and a speed of 100 r / min to completely dissolve it, and then using a cation exchange resin to desalt the solution at a flow rate of 10 m / h to obtain desalted sodium tauroursodeoxycholate;

[0039] C6. Add the sodium tauroursodeoxycholate obtained in C5 to a mixed solvent of 10 times the volume of acetone and purified water, stir at a temperature of 80°C and a rotation speed of 100 r / min to completely dissolve it, cool to -5°C for crystallization, and after the crystallization is completed, filter, rinse and dry again to obtain high-purity sodium tauroursodeoxycholate.

[0040] Table: Components and mol ratios of raw materials extracted in Preparation Examples 1-5

[0041]

[0042]

[0043] Preparation Example 6

[0044] A sodium taurine ursodeoxycholate, which is different from Preparation Example 1 in that the specific preparation steps are as follows:

[0045] C1. Pour anhydrous acetone into a reaction apparatus and install a condensing device, then slowly add ursodeoxycholic acid into 3 times the volume of acetone, stirring at a speed of 300 r / min until the ursodeoxycholic acid is completely dissolved;

[0046] C2, control the condensing device to keep the temperature at -6°C, add triethylamine to the dissolved ursodeoxycholic acid obtained in C1, continue to maintain the above conditions to completely dissolve the triethylamine, then slowly drop ethyl chloroformate, keep the reaction system stable, continue the reaction for 1.5 hours, and then filter the obtained solution to obtain a mixed anhydride solution;

[0047] C3, dissolving taurine in a sodium carbonate solution to obtain a sodium carbonate solution of taurine, slowly adding the solution dropwise to the mixed anhydride solution obtained in C2, reacting for 5 hours at a temperature of 22° C. and a stirring speed of 120 r / min, filtering out the precipitate to obtain a filtrate;

[0048] C4, adding dilute hydrochloric acid solution to the filtrate obtained in C3 to adjust the pH of the filtrate to 6.0, then pouring the solution into an evaporating bottle of a rotary evaporator, evaporating to dryness at a speed of 140 r / min and a temperature of 60° C. After the solution is evaporated to dryness, continue drying at a vacuum degree of 0.002 mAar and a temperature of 74° C. to obtain a crude dried product of tauroursodeoxycholic acid;

[0049] C5, adding 10 times the volume of the crude dried product obtained in C4 to acetone and purified water, stirring at a temperature of 84° C. and a speed of 140 r / min to completely dissolve it, and then using a cation exchange resin at a flow rate of 15 m / h to desalt the solution to obtain desalted sodium tauroursodeoxycholate;

[0050] C6. Add the sodium tauroursodeoxycholate obtained in C5 to a mixed solvent of 10 times the volume of acetone and purified water, stir at a temperature of 84°C and a rotation speed of 140 r / min to completely dissolve it, cool to -4°C for crystallization, and after the crystallization is completed, filter, rinse and dry again to obtain high-purity sodium tauroursodeoxycholate.

[0051] Preparation Example 7

[0052] A sodium taurine ursodeoxycholate, which is different from Preparation Example 1 in that the specific preparation steps are as follows:

[0053] C1. Pour anhydrous acetone into a reaction apparatus and install a condensing device, then slowly add ursodeoxycholic acid into 3 times the volume of acetone, stirring at a speed of 350 r / min until the ursodeoxycholic acid is completely dissolved;

[0054] C2, control the condensing device to keep the temperature at -7°C, add triethylamine to the dissolved ursodeoxycholic acid obtained in C1, continue to maintain the above conditions to completely dissolve the triethylamine, then slowly drop ethyl chloroformate, keep the reaction system stable, continue the reaction for 2 hours, and then filter the obtained solution to obtain a mixed anhydride solution;

[0055] C3, dissolving taurine in a sodium carbonate solution to obtain a sodium carbonate solution of taurine, slowly adding the solution dropwise to the mixed anhydride solution obtained in C2, reacting for 6 hours at a temperature of 24° C. and a stirring speed of 140 r / min, filtering out the precipitate to obtain a filtrate;

[0056] C4, adding dilute hydrochloric acid solution to the filtrate obtained in C3 to adjust the pH of the filtrate to 6.6, then pouring the solution into an evaporating bottle of a rotary evaporator, evaporating to dryness at a speed of 180 r / min and a temperature of 70° C. After the solution is evaporated to dryness, continue drying at a vacuum degree of 0.004 mAar and a temperature of 78° C. to obtain a crude dried product of tauroursodeoxycholic acid;

[0057] C5, adding 10 times the volume of the crude dried product obtained in C4 to acetone and purified water, stirring at a temperature of 88° C. and a speed of 180 r / min to completely dissolve it, and then using a cation exchange resin at a flow rate of 20 m / h to desalt the solution to obtain desalted sodium tauroursodeoxycholate;

[0058] C6. Add the sodium tauroursodeoxycholate obtained in C5 to a mixed solvent of 10 times the volume of acetone and purified water, stir at a temperature of 88°C and a rotation speed of 180r / min to completely dissolve it, cool to -3°C for crystallization, and after the crystallization is completed, filter, rinse and dry again to obtain high-purity sodium tauroursodeoxycholate.

[0059] Preparation Example 8

[0060] A sodium taurine ursodeoxycholate, which is different from Preparation Example 1 in that the specific preparation steps are as follows:

[0061] C1. Pour anhydrous acetone into a reaction apparatus and install a condensing device, then slowly add ursodeoxycholic acid into 3 times the volume of acetone, stirring at a speed of 400 r / min until the ursodeoxycholic acid is completely dissolved;

[0062] C2, control the condensing device to keep the temperature at -8°C, add triethylamine to the dissolved ursodeoxycholic acid obtained in C1, continue to maintain the above conditions to completely dissolve the triethylamine, then slowly drop ethyl chloroformate, keep the reaction system stable, continue the reaction for 2.5 hours, and then filter the obtained solution to obtain a mixed anhydride solution;

[0063] C3, dissolving taurine in a sodium carbonate solution to obtain a sodium carbonate solution of taurine, slowly adding the solution dropwise to the mixed anhydride solution obtained in C2, reacting for 7 hours at a temperature of 26° C. and a stirring speed of 160 r / min, filtering out the precipitate to obtain a filtrate;

[0064] C4, adding dilute hydrochloric acid solution to the filtrate obtained in C3 to adjust the pH of the filtrate to 6.6, then pouring the solution into an evaporating bottle of a rotary evaporator, evaporating to dryness at a speed of 220 r / min and a temperature of 75° C. After the solution is evaporated to dryness, continue drying at a vacuum degree of 0.006 mAar and a temperature of 82° C. to obtain a crude dried product of tauroursodeoxycholic acid;

[0065] C5, adding 10 times the volume of the crude dried product obtained in C4 to acetone and purified water, stirring at a temperature of 92° C. and a speed of 220 r / min to completely dissolve it, and then using a cation exchange resin at a flow rate of 25 m / h to desalinate the solution to obtain desalted sodium tauroursodeoxycholate;

[0066] C6. Add the sodium tauroursodeoxycholate obtained in C5 to a mixed solvent of 10 times the volume of acetone and purified water, stir at a temperature of 92°C and a rotation speed of 220 r / min to completely dissolve it, cool to -2°C for crystallization, and after the crystallization is completed, filter, rinse and dry again to obtain high-purity sodium tauroursodeoxycholate.

[0067] Preparation Example 9

[0068] A sodium taurine ursodeoxycholate, which is different from Preparation Example 1 in that the specific preparation steps are as follows:

[0069] C1. Pour anhydrous acetone into a reaction apparatus and install a condensing device, then slowly add ursodeoxycholic acid into 3 times the volume of acetone, stirring at a speed of 450 r / min until the ursodeoxycholic acid is completely dissolved;

[0070] C2, control the condensing device to keep the temperature at -9°C, add triethylamine to the dissolved ursodeoxycholic acid obtained in C1, continue to maintain the above conditions to completely dissolve the triethylamine, then slowly drop ethyl chloroformate, keep the reaction system stable, continue the reaction for 3 hours, and then filter the obtained solution to obtain a mixed anhydride solution;

[0071] C3, dissolving taurine in a sodium carbonate solution to obtain a sodium carbonate solution of taurine, slowly adding the solution dropwise to the mixed anhydride solution obtained in C2, reacting for 8 hours at a temperature of 28° C. and a stirring speed of 180 r / min, filtering out the precipitate to obtain a filtrate;

[0072] C4, adding dilute hydrochloric acid solution to the filtrate obtained in C3 to adjust the pH of the filtrate to 6.8, then pouring the solution into an evaporating bottle of a rotary evaporator, evaporating to dryness at a speed of 260 r / min and a temperature of 80° C. After the solution is evaporated to dryness, continue drying at a vacuum degree of 0.008 mAar and a temperature of 86° C. to obtain a crude dried product of tauroursodeoxycholic acid;

[0073] C5, adding 10 times the volume of the crude dried product obtained in C4 to acetone and purified water, stirring at a temperature of 96° C. and a speed of 260 r / min to completely dissolve it, and then using a cation exchange resin at a flow rate of 30 m / h to desalt the solution to obtain desalted sodium tauroursodeoxycholate;

[0074] C6. Add the sodium tauroursodeoxycholate obtained in C5 to a mixed solvent of 10 times the volume of acetone and purified water, stir at a temperature of 96°C and a rotation speed of 260 r / min to completely dissolve it, cool to -1°C for crystallization, and after the crystallization is completed, filter, rinse and dry again to obtain high-purity sodium tauroursodeoxycholate.

[0075] Preparation Example 10

[0076] A sodium taurine ursodeoxycholate, which is different from Preparation Example 1 in that the specific preparation steps are as follows:

[0077] C1. Pour anhydrous acetone into a reaction apparatus and install a condensing device, then slowly add ursodeoxycholic acid into 3 times the volume of acetone, stirring at a speed of 500 r / min until the ursodeoxycholic acid is completely dissolved;

[0078] C2, control the condensing device to keep the temperature at -10°C, add triethylamine to the dissolved ursodeoxycholic acid obtained in C1, continue to maintain the above conditions to completely dissolve the triethylamine, then slowly drop ethyl chloroformate, keep the reaction system stable, continue the reaction for 3.5 hours, and then filter the obtained solution to obtain a mixed anhydride solution;

[0079] C3, dissolving taurine in a sodium carbonate solution to obtain a sodium carbonate solution of taurine, slowly adding the solution dropwise to the mixed anhydride solution obtained in C2, reacting for 9 hours at a temperature of 30° C. and a stirring speed of 200 r / min, filtering out the precipitate to obtain a filtrate;

[0080] C4, adding dilute hydrochloric acid solution to the filtrate obtained in C3 to adjust the pH of the filtrate to 7.0, then pouring the solution into an evaporating flask of a rotary evaporator, evaporating to dryness at a speed of 300 r / min and a temperature of 90° C. After the solution is evaporated to dryness, continue drying at a vacuum degree of 0.01 mAar and a temperature of 90° C. to obtain a crude dried product of tauroursodeoxycholic acid;

[0081] C5, adding the dried crude product obtained in C4 to 10 times the volume of acetone and purified water, stirring at a temperature of 100° C. and a rotation speed of 300 r / min to completely dissolve it, and then using a cation exchange resin to desalt the solution at a flow rate of 40 m / h to obtain desalted sodium tauroursodeoxycholate;

[0082] C6. Add the sodium tauroursodeoxycholate obtained in C5 to a mixed solvent of 10 times the volume of acetone and purified water, stir at a temperature of 100°C and a rotation speed of 300 r / min to completely dissolve it, cool to 0°C for crystallization, and after the crystallization is completed, filter, rinse and dry again to obtain high-purity sodium tauroursodeoxycholate.

[0083] Preparation Examples 11-15

[0084] A liver protective agent containing sodium taurine ursodeoxycholate, the components of the raw materials and their corresponding weights are shown below, and it is prepared by the following preparation method:

[0085] A1. Mix sodium taurine ursodeoxycholate with carrier materials, solubilizers and other auxiliary materials in a mixer at a stirring speed of 50 r / min to obtain a sodium taurine ursodeoxycholate mixture;

[0086] Wherein sodium tauroursodeoxycholate is prepared by Preparation 1;

[0087] The carrier material is composed of starch, lactose and microcrystalline cellulose in a weight ratio of 4:3:3;

[0088] The solubilizing agent is polyethylene glycol;

[0089] A2, slowly add 10 times volume of the sodium taurine ursodeoxycholate mixture obtained in A1 to the binder solution, stirring at a speed of 150 r / min for 10 min to form a soft material, and pass the wet soft material through a 14-mesh sieve to form wet granules;

[0090] The binder is composed of ethanol and water in a weight ratio of 1:1;

[0091] A3, placing the wet granules obtained in A2 into a drying device and drying at 50°C for 2 hours to reduce the moisture content of the wet granules to 5%, thereby obtaining dried granules;

[0092] A4. The dried granules obtained in A3 are fully mixed with a lubricant and an antioxidant in a mixer at a stirring speed of 50 r / min, and the obtained mixture is tableted and formed into a preparation to obtain a liver protective agent containing sodium taurine ursodeoxycholate.

[0093] Wherein the lubricant is magnesium stearate;

[0094] The antioxidant is vitamin E;

[0095] Table: Components and weights of raw materials extracted in Preparation Examples 11-15 (g)

[0096]

[0097] Preparation Example 16

[0098] A liver protective agent containing sodium taurine ursodeoxycholate, which is different from Preparation Example 11 in that the preparation method is as follows:

[0099] A1. Mix sodium taurine ursodeoxycholate, carrier materials, solubilizers and other auxiliary materials in a mixer at a stirring speed of 100 r / min to obtain a sodium taurine ursodeoxycholate mixture;

[0100] A2, slowly add 10 times volume of the sodium taurine ursodeoxycholate mixture obtained in A1 to the binder solution, stirring at a speed of 180 r / min for 20 min to form a soft material, and pass the wet soft material through a 16-mesh sieve to form wet granules;

[0101] A3, placing the wet granules obtained in A2 into a drying device and drying at 55°C for 3 hours to reduce the moisture content of the wet granules to 5%, thereby obtaining dried granules;

[0102] A4. The dried particles obtained in A3 are fully mixed with a lubricant and an antioxidant in a mixer at a stirring speed of 100 r / min, and the obtained mixture is tableted and formed into a preparation to obtain a liver protective agent containing sodium taurine ursodeoxycholate.

[0103] Preparation Example 17

[0104] A liver protective agent containing sodium taurine ursodeoxycholate, which is different from Preparation Example 11 in that the preparation method is as follows:

[0105] A1. Mix sodium taurine ursodeoxycholate with carrier materials, solubilizers and other auxiliary materials in a mixer at a stirring speed of 150 r / min to obtain a sodium taurine ursodeoxycholate mixture;

[0106] A2, slowly add 10 times volume of the sodium taurine ursodeoxycholate mixture obtained in A1 to the binder solution, stirring at a speed of 210 r / min for 30 min to form a soft material, and pass the wet soft material through a 16-mesh sieve to form wet granules;

[0107] A3, placing the wet granules obtained in A2 into a drying device and drying at 60°C for 4 hours to reduce the moisture content of the wet granules to 4%, thereby obtaining dried granules;

[0108] A4. The dried particles obtained in A3 are fully mixed with a lubricant and an antioxidant in a mixer at a stirring speed of 150 r / min, and the obtained mixture is tableted and formed into a preparation to obtain a liver protective agent containing sodium taurine ursodeoxycholate.

[0109] Preparation Example 18

[0110] A liver protective agent containing sodium taurine ursodeoxycholate, which is different from Preparation Example 11 in that the preparation method is as follows:

[0111] A1. Mix sodium taurine ursodeoxycholate, carrier materials, solubilizers and other auxiliary materials in a mixer at a stirring speed of 200 r / min to obtain a sodium taurine ursodeoxycholate mixture;

[0112] A2, slowly add 10 times volume of the sodium taurine ursodeoxycholate mixture obtained in A1 to the binder solution, stirring at 240 r / min for 40 min to form a soft material, and pass the wet soft material through a 14-mesh sieve to form wet granules;

[0113] A3, placing the wet granules obtained in A2 into a drying device and drying at 70°C for 5 hours to reduce the moisture content of the wet granules to 4%, thereby obtaining dried granules;

[0114] A4. The dried particles obtained in A3 are fully mixed with a lubricant and an antioxidant in a mixer at a stirring speed of 200 r / min, and the obtained mixture is tableted and formed into a preparation to obtain a liver protective agent containing sodium taurine ursodeoxycholate.

[0115] Preparation Example 19

[0116] A liver protective agent containing sodium taurine ursodeoxycholate, which is different from Preparation Example 11 in that the preparation method is as follows:

[0117] A1. Mix sodium taurine ursodeoxycholate with auxiliary materials such as carrier materials and solubilizers in a mixer at a stirring speed of 250 r / min to obtain a sodium taurine ursodeoxycholate mixture;

[0118] A2, slowly add 10 times volume of the sodium taurine ursodeoxycholate mixture obtained in A1 to the binder solution, stirring at a speed of 270 r / min for 50 min to form a soft material, and pass the wet soft material through a 14-mesh sieve to form wet granules;

[0119] A3, placing the wet granules obtained in A2 into a drying device and drying at 75°C for 6 hours to reduce the moisture content of the wet granules to 3%, thereby obtaining dried granules;

[0120] A4. The dried particles obtained in A3 are fully mixed with a lubricant and an antioxidant in a mixer at a stirring speed of 250 r / min, and the obtained mixture is tableted and formed into a preparation to obtain a liver protective agent containing sodium taurine ursodeoxycholate.

[0121] Preparation Example 20

[0122] A liver protective agent containing sodium taurine ursodeoxycholate, which is different from Preparation Example 11 in that the preparation method is as follows:

[0123] A1. Mix sodium taurine ursodeoxycholate, carrier materials, solubilizers and other auxiliary materials in a mixer at a stirring speed of 300 r / min to obtain a sodium taurine ursodeoxycholate mixture;

[0124] A2, slowly add the sodium taurine ursodeoxycholate mixture obtained in A1 to 10 times the volume of the binder solution, stirring at a speed of 300 r / min for 60 minutes to form a soft material, and pass the wet soft material through a 14-mesh sieve to form wet granules;

[0125] A3, placing the wet granules obtained in A2 into a drying device and drying at 80°C for 6 hours to reduce the moisture content of the wet granules to 3%, thereby obtaining dried granules;

[0126] A4. The dried particles obtained in A3 are fully mixed with a lubricant and an antioxidant in a mixer at a stirring speed of 300 r / min, and the obtained mixture is tableted and formed into a preparation to obtain a liver protective agent containing sodium taurine ursodeoxycholate.

[0127] Preparation Example 21

[0128] A liver protective agent containing sodium taurine ursodeoxycholate, which is different from Preparation Example 11 in that the carrier material consists of starch, lactose and microcrystalline cellulose in a weight ratio of 3:2.5:4.5.

[0129] Preparation Example 22

[0130] A liver protecting agent containing sodium taurine ursodeoxycholate, which is different from Preparation Example 11 in that the carrier material consists of starch, lactose and microcrystalline cellulose in a weight ratio of 3.5:4:2.5.

[0131] Preparation Example 23

[0132] A liver protective agent containing sodium taurine ursodeoxycholate, which is different from Preparation Example 11 in that the binder consists of ethanol and water in a weight ratio of 2:1;.

[0133] Preparation Examples 24-32

[0134] A liver protective agent containing sodium taurine ursodeoxycholate is different from Preparation Example 11 in that the usage of the liver protective agent containing sodium taurine ursodeoxycholate in its components is different, and the specific corresponding relationship is shown in the following table.

[0135] Table: Comparison of the use of liver protective agents containing sodium taurine ursodeoxycholate in Preparation Examples 24-32

[0136]

[0137] Performance testing

[0138] The liver protective agent containing sodium taurine ursodeoxycholate prepared in each embodiment was selected for testing. The test subjects were 220 healthy mice, 10 mice in each group. The test mice took the liver protective agent containing sodium taurine ursodeoxycholate and maintained normal health.

[0139] Then take 5g twice a day with 50ml of water, and then test the liver function indicators on the day of taking and after taking for 30 consecutive days. The specific test steps are as follows:

[0140] Serum liver function index pathological factor inhibition rate ΔK%:

[0141] First, samples were taken from healthy mice before the test, on the day of taking the drug, and after taking the drug for 30 consecutive days. The difference between the liver function indexes before the test, on the day of taking the drug, and after taking the drug for 30 consecutive days was obtained based on the liver function indexes in the test serum, so as to characterize the improvement effect of the liver protection agent containing sodium taurine ursodeoxycholate on liver ecology. The liver function indexes tested above only take the two typical liver function indexes of alanine aminotransferase and total bilirubin as examples. The test results and evaluation criteria are as follows:

[0142] Θ: 40 < ΔK value (considered as significant inhibition);

[0143] Ο: 10<ΔK value<40 (considered as small inhibitory effect);

[0144] X: ΔK value < 10 (considered to have substantially no inhibitory effect).

[0145] It should be specifically noted that the above-mentioned mice were mainly healthy mice, and the data of the mice that produced abnormal data after taking the medicine for 30 consecutive days were discarded.

[0146] Examples 1-5

[0147] A liver protecting agent containing sodium taurine ursodeoxycholate, and the corresponding relationship of the preparation method used is shown in the following table.

[0148] Table: Comparison of the use of liver protective agents containing sodium taurine ursodeoxycholate in Examples 1-5

[0149] Group Liver Protector Containing Taurine Ursodeoxycholate Sodium Example 1 Prepared from Preparation Example 11 Example 2 Prepared from Preparation Example 12 Example 3 Prepared from Preparation Example 13 Example 4 Prepared from Preparation Example 14 Example 5 Prepared from Preparation Example 15

[0150] The liver protecting agents containing sodium taurine ursodeoxycholate in the above Examples 1-5 were extracted, and their serum liver function index pathological factor inhibition rate ΔK% was tested according to the above measurement steps and measurement standards. The test results were averaged and recorded in the following table.

[0151] Table: Performance test results of serum liver function index pathological factor inhibition rate ΔK% of Example 1-5

[0152]

[0153]

[0154] As can be seen from the above table, the liver protective agents containing sodium taurine ursodeoxycholate prepared in Examples 1-5 all have a good effect of improving liver ecology, and can achieve the purpose of beneficial liver cells occupying a dominant position in liver ecology by lowering cholesterol levels, improving bile acid metabolism and promoting liver cell regeneration;

[0155] The inhibition rate of alanine aminotransferase ΔK% on the day of taking the drug was 24.6%-26.1%, and the inhibition rate of total bilirubin was 24.1%-28.5%, which was considered to have an inhibitory effect;

[0156] After continuous use for 30 days, the inhibition rate of alanine aminotransferase ΔK% was 42.2%-50.5%, and the inhibition rate of total bilirubin was 50.1%-59.4%, which was considered to have a significant inhibitory effect;

[0157] It can be seen that when the dosage of sodium taurine ursodeoxycholate liver protector is certain, the improvement effect on liver ecology can be increased by adjusting the proportion of each component. Combined with the data in the above table, it is not difficult to see that the increase of sodium taurine ursodeoxycholate can enhance the inhibitory effect on pathological factors of liver function indicators, and it will tend to saturation after reaching a certain amount, while the remaining components have less effect on performance.

[0158] Embodiment 6-10

[0159] A liver protective agent containing sodium taurine ursodeoxycholate is different from Example 1 in that the use conditions of the liver protective agent containing sodium taurine ursodeoxycholate are different, and the specific corresponding relationship is shown in the following table.

[0160] Table: Comparison table of the use of liver protective agents containing sodium taurine ursodeoxycholate in Examples 6-10

[0161]

[0162]

[0163] The liver protecting agents containing sodium taurine ursodeoxycholate in the above Examples 6-10 were extracted, and their serum liver function index pathological factor inhibition rate ΔK% was tested according to the above measurement steps and measurement standards. The test results were averaged and recorded in the following table.

[0164] Table: Performance test results of Example 1, 6-10 serum liver function index pathological factor inhibition rate ΔK%

[0165]

[0166] As can be seen from the above table, the liver protective agents containing sodium taurine ursodeoxycholate prepared in Examples 6-10 all have a good effect of improving liver ecology, and can achieve the purpose of beneficial liver cells occupying a dominant position in liver ecology by lowering cholesterol levels, improving bile acid metabolism and promoting liver cell regeneration;

[0167] The inhibition rate of alanine aminotransferase ΔK% on the day of taking the drug was 24.6%-25.1%, and the inhibition rate of total bilirubin was 24.1%-26.3%, which was considered to have an inhibitory effect;

[0168] After continuous use for 30 days, the inhibition rate of alanine aminotransferase ΔK% was 42.2%-46.2%, and the inhibition rate of total bilirubin was 50.1%-57.0%, which was considered to have a significant inhibitory effect;

[0169] It can be seen that when the dosage of the liver protective agent containing sodium taurine ursodeoxycholate is certain, the improvement effect on liver ecology can be increased by adjusting the parameters of the preparation process. It is not difficult to see from the data in the above table that increasing the mixing speed and time in the preparation process of the liver protective agent containing sodium taurine ursodeoxycholate, reducing the water content of the wet granules obtained in the wet granulation process, and increasing the mesh number of the sieve in the wet granulation process can slightly improve the inhibitory effect of the liver protective agent containing sodium taurine ursodeoxycholate on the pathological factors of liver function indicators. The reason for this is that increasing the mixing speed and time can make the drug components more fully mixed, reduce the phenomenon of excessive or low local concentration, thereby improving the stability and consistency of the drug; reducing the water content of the wet granules makes the release of the drug in the liver more stable and lasting, thereby improving its inhibitory effect on the pathological factors of liver function indicators; increasing the mesh number of the sieve makes it easier for the drug to enter the liver cells and interact with the pathological factors, thereby improving its inhibitory effect on the pathological factors of liver function indicators. See Examples 1, 6-10 for details.

[0170] Examples 11-13

[0171] A liver protective agent containing sodium taurine ursodeoxycholate is different from Example 1 in that the use conditions of the liver protective agent containing sodium taurine ursodeoxycholate are different, and the specific corresponding relationship is shown in the following table.

[0172] Table: Comparison table of the use of liver protective agents containing sodium taurine ursodeoxycholate in Examples 11-13

[0173] Group Liver Protector Containing Taurine Ursodeoxycholate Sodium Embodiment 11 Prepared from Preparation Example 21 Example 12 Prepared from Preparation Example 22 Example 13 Prepared from Preparation Example 23

[0174] The liver protecting agents containing sodium taurine ursodeoxycholate in the above Examples 11-13 were extracted, and their serum liver function index pathological factor inhibition rate ΔK% was tested according to the above measurement steps and measurement standards. The test results were averaged and recorded in the following table.

[0175] Table: Performance test results of serum liver function index pathological factor inhibition rate ΔK% in Examples 1, 11-13

[0176]

[0177] As can be seen from the above table, the liver protective agents containing sodium taurine ursodeoxycholate prepared in Examples 11-13 all have a good effect of improving liver ecology, and can achieve the purpose of beneficial liver cells occupying a dominant position in liver ecology by lowering cholesterol levels, improving bile acid metabolism and promoting liver cell regeneration;

[0178] The inhibition rate of alanine aminotransferase ΔK% on the day of taking the drug was 24.6%-24.9%, and the inhibition rate of total bilirubin was 23.9%-24.2%, which was considered to have an inhibitory effect;

[0179] After continuous use for 30 days, the inhibition rate of alanine aminotransferase ΔK% was 42.1%-42.3%, and the inhibition rate of total bilirubin was 50.1%-50.4%, which was considered to have a significant inhibitory effect;

[0180] It can be seen that when the dosage of the liver protector containing sodium taurine ursodeoxycholate is certain, the improvement effect on the liver ecology can be changed by adjusting the proportion of the components. Combined with the data in the above table, it is not difficult to see that changing the proportion of the binder component and the proportion of the carrier material component in the preparation process of the liver protector containing sodium taurine ursodeoxycholate has little effect on the inhibitory effect of the liver protector containing sodium taurine ursodeoxycholate on the pathological factors of liver function indicators. The reason for this is that these changes mainly affect the physical properties and stability of the preparation, but have limited effect on the main active ingredients and pharmacological effects of the drug. For details, see Examples 1, 11-13.

[0181] Examples 14-17

[0182] A liver protective agent containing sodium taurine ursodeoxycholate is different from Example 1 in that the use conditions of the liver protective agent containing sodium taurine ursodeoxycholate are different, and the specific corresponding relationship is shown in the following table.

[0183] Table: Comparison table of the use of liver protective agents containing sodium taurine ursodeoxycholate in Examples 14-17

[0184] Group Liver Protector Containing Taurine Ursodeoxycholate Sodium Embodiment 14 Prepared from Preparation Example 24 Embodiment 15 Prepared from Preparation Example 25 Example 16 Prepared from Preparation Example 26 Embodiment 17 Prepared from Preparation Example 27

[0185] The liver protecting agents containing sodium taurine ursodeoxycholate in the above Examples 14-17 were extracted, and their serum liver function index pathological factor inhibition rate ΔK% was tested according to the above measurement steps and measurement standards. The test results were averaged and recorded in the following table.

[0186] Table: Performance test results of serum liver function index pathological factor inhibition rate ΔK% in Examples 1, 14-17

[0187]

[0188] As can be seen from the above table, the liver protective agents containing sodium taurine ursodeoxycholate prepared in Examples 11-13 all have a good effect of improving liver ecology, and can achieve the purpose of beneficial liver cells occupying a dominant position in liver ecology by lowering cholesterol levels, improving bile acid metabolism and promoting liver cell regeneration;

[0189] The inhibition rate of alanine aminotransferase ΔK% on the day of taking the drug was 24.6%-29.4%, and the inhibition rate of total bilirubin was 24.1%-27.9%, which was considered to have an inhibitory effect;

[0190] After continuous use for 30 days, the inhibition rate of alanine aminotransferase ΔK% was 42.2%-45.3%, and the inhibition rate of total bilirubin was 50.1%-54.4%, which was considered to have a significant inhibitory effect;

[0191] It can be seen that when the dosage of the liver protective agent containing sodium taurine ursodeoxycholate is certain, the improvement effect on liver ecology can be improved by adjusting the proportion of components. Combined with the data in the above table, it is not difficult to see that increasing the sodium carbonate content, taurine and ethyl chloroformate content in the preparation process of sodium taurine ursodeoxycholate can enhance the inhibitory effect on the pathological factors of liver function indicators, and it will tend to saturation after reaching a certain amount, while the remaining components have less effect on the performance. See Examples 1, 14-17 for details.

[0192] Examples 18-22

[0193] A liver protective agent containing sodium taurine ursodeoxycholate is different from Example 1 in that the use conditions of the liver protective agent containing sodium taurine ursodeoxycholate are different, and the specific corresponding relationship is shown in the following table.

[0194] Table: Comparison table of the use of liver protective agents containing sodium taurine ursodeoxycholate in Examples 18-22

[0195] Group Liver Protector Containing Taurine Ursodeoxycholate Sodium Embodiment 18 Prepared from Preparation Example 28 Embodiment 19 Prepared from Preparation Example 29 Embodiment 20 Prepared from Preparation Example 30 Embodiment 21 Prepared from Preparation Example 31 Embodiment 22 Prepared from Preparation Example 32

[0196] The liver protecting agents containing sodium taurine ursodeoxycholate in the above Examples 18-22 were extracted, and their serum liver function index pathological factor inhibition rate ΔK% was tested according to the above measurement steps and measurement standards. The test results were averaged and recorded in the following table.

[0197] Table: Performance test results of Example 1, 18-22 serum liver function index pathological factor inhibition rate ΔK%

[0198]

[0199]

[0200] As can be seen from the above table, the liver protective agents containing sodium taurine ursodeoxycholate prepared in Examples 18-22 all have a good effect of improving liver ecology, and can achieve the purpose of beneficial liver cells occupying a dominant position in liver ecology by lowering cholesterol levels, improving bile acid metabolism and promoting liver cell regeneration;

[0201] The inhibition rate of alanine aminotransferase ΔK% on the day of taking the drug was 24.6%-27.4%, and the inhibition rate of total bilirubin was 24.1%-30.9%, which was considered to have an inhibitory effect;

[0202] After continuous use for 30 days, the inhibition rate of alanine aminotransferase ΔK% was 42.2%-46.5%, and the inhibition rate of total bilirubin was 50.1%-56.5%, which was considered to have a significant inhibitory effect;

[0203] It can be seen that when the dosage of sodium taurine ursodeoxycholate liver protector is certain, the improvement effect on liver ecology can be increased by adjusting the parameters of the preparation process. Combined with the data in the above table, it is not difficult to see that increasing the mixing and stirring speed and stirring time in the preparation process of sodium taurine ursodeoxycholate, reducing the condensation temperature in the preparation process of mixed anhydride, increasing the condensation reaction temperature, increasing the acid adjustment pH, the vacuum degree in the vacuum drying process, and the flow rate in the desalting and concentration process can improve the inhibitory effect of the sodium taurine ursodeoxycholate liver protector on the pathological factors of liver function indicators. The reason for this is that increasing the mixing and stirring speed and stirring time are helpful for the raw materials in the reaction system. More complete mixing and dispersion make the reaction more uniform and thorough; lowering the condensation temperature helps reduce the formation of by-products and improve the purity and yield of the target product; increasing the reaction temperature can accelerate the reaction rate and make the reaction more complete; appropriately increasing the pH value makes it easier for drug molecules to bind or react with pathological factors in the liver, thereby improving their efficacy; increasing the vacuum degree can accelerate the evaporation and removal of water, making the product drier and more stable; increasing the flow rate of the desalination and concentration process helps remove impurities and salts in the product and improve the purity and quality of the product, see Examples 1, 18-22 for details.

[0204] This specific embodiment is only an explanation of the present invention, not a limitation of the present invention. After reading this specification, those skilled in the art can make non-creative modifications to this embodiment as needed, but as long as it is within the scope of the claims of the present invention, it is protected by the patent law.

Claims

1. A liver protecting agent containing sodium taurine ursodeoxycholate, It is characterized in that The invention consists of sodium taurine ursodeoxycholate, a carrier material, a solubilizer, a lubricant and an antioxidant.

2. A liver protecting agent containing sodium taurine ursodeoxycholate according to claim 1, Features: The specific preparation steps are as follows: A1. Mix sodium taurine ursodeoxycholate, carrier materials, solubilizers and other auxiliary materials in a mixer at a stirring speed of 50-300 r / min to obtain a sodium taurine ursodeoxycholate mixture; A2, slowly add the sodium taurine ursodeoxycholate mixture obtained in A1 to 10 times the volume of the binder solution, stirring at a speed of 150-300 r / min for 10-60 min to form a soft material, and pass the wet soft material through a 14-mesh sieve to form wet granules; A3, placing the wet granules obtained in A2 into a drying device and drying at a temperature of 50-81°C for 2-6 hours to reduce the moisture content of the wet granules to 3%-5%, thereby obtaining dried granules; A4. The dried particles obtained in A3 are fully mixed with a lubricant and an antioxidant in a mixer at a stirring speed of 50-300 r / min, and the obtained mixture is tableted and formed into a preparation to obtain a liver protective agent containing sodium taurine ursodeoxycholate.

3. A liver protecting agent containing sodium taurine ursodeoxycholate according to claim 1, Features: The raw material components and weight proportions of the liver protective agent containing sodium taurine ursodeoxycholate are as follows: 5-30 parts of sodium tauroursodeoxycholate, 50-80 parts of carrier material, 1-10 parts of solubilizer, 0.1-1 parts of lubricant and 0.01-0.1 parts of antioxidant.

4. A liver protecting agent containing sodium taurine ursodeoxycholate according to claim 1, Features: The sodium tauroursodeoxycholate is composed of ursodeoxycholic acid, triethylamine, ethyl chloroformate, taurine and sodium carbonate.

5. A liver protecting agent containing sodium taurine ursodeoxycholate according to claim 4, Features: The preparation method of sodium tauroursodeoxycholate is as follows, comprising the following steps: C1. Pour anhydrous acetone into a reaction apparatus and install a condensing device, then slowly add ursodeoxycholic acid into 3 times the volume of acetone, stirring at a speed of 300-500 r / min until the ursodeoxycholic acid is completely dissolved; C2, controlling the condensing device to maintain the temperature at (-5)-(-10)°C, adding triethylamine to the dissolved ursodeoxycholic acid obtained in C1, continuing to maintain the above conditions to completely dissolve the triethylamine, then slowly adding ethyl chloroformate dropwise, keeping the reaction system stable, continuing the reaction for 1-3.5 hours, and then filtering the obtained solution to obtain a mixed anhydride solution; C3, dissolving taurine in a sodium carbonate solution to obtain a taurine sodium carbonate solution, slowly adding the solution dropwise to the mixed anhydride solution obtained in C2, reacting for 4-9 hours at a temperature of 20-30° C. and a stirring speed of 100-200 r / min, filtering out the precipitate to obtain a filtrate; C4, adding dilute hydrochloric acid solution to the filtrate obtained in C3 to adjust the pH of the filtrate to 6.0-7.0, then pouring the solution into an evaporating flask of a rotary evaporator, evaporating to dryness at a speed of 100-300 r / min and a temperature of 50-90° C., and after the solution is evaporated to dryness, continuing to dry at a vacuum degree of 0.001-0.01 mAar and a temperature of 70-90° C. to obtain a crude dried product of tauroursodeoxycholic acid; C5, adding the dried crude product obtained in C4 to 10 times the volume of acetone and purified water, stirring at a temperature of 80-100° C. and a rotation speed of 100-300 r / min to completely dissolve it, and then using a cation exchange resin to desalt the solution at a flow rate of 10-40 m / h to obtain desalted sodium tauroursodeoxycholate; C6. Add the sodium tauroursodeoxycholate obtained in C5 to a mixed solvent of 10 times the volume of acetone and purified water, stir at a temperature of 80-100°C and a rotation speed of 100-300r / min to completely dissolve it, cool to (-5)-0°C for crystallization, and after the crystallization is completed, filter, rinse and dry again to obtain high-purity sodium tauroursodeoxycholate.

6. A liver protecting agent containing sodium taurine ursodeoxycholate according to claim 4, Features: The sodium tauroursodeoxycholate is composed of ursodeoxycholic acid, triethylamine, ethyl chloroformate, taurine and sodium carbonate in a molar ratio of 1:(1-1.3):(1-1.1):(1-1.2):(1.5-3).

7. A liver protecting agent containing sodium taurine ursodeoxycholate according to claim 1, Features: The carrier material is composed of starch, lactose and microcrystalline cellulose in a weight ratio of (3-4): (2.5-4): (2.5-4.5).

8. A liver protecting agent containing sodium taurine ursodeoxycholate according to claim 1, Features: The adhesive is composed of ethanol and water in a weight ratio of (1-2):

1.

9. A liver protecting agent containing sodium taurine ursodeoxycholate according to claim 1, Features: The solubilizer is polyethylene glycol; the lubricant is magnesium stearate; and the antioxidant is vitamin E.

Images