Cholic acid oral composition, method for preparing the same, and use thereof

Abstract

The application belongs to the technical field of pharmaceutical preparations, and particularly relates to a cholic acid oral composition and a preparation method and application thereof. According to weight parts, the cholic acid oral composition comprises the following components in parts by weight: cholic acid 90-110 parts, a polymer carrier 100-300 parts, a stabilizer 60-200 parts, a filling agent 100-200 parts, a disintegrating agent 10-30 parts and a lubricant 1-5 parts; the stabilizer comprises vitamin E polyethylene glycol succinate and sulfobutyl ether-beta-cyclodextrin. The application significantly improves the dissolution effect by adopting polymer solid dispersion, cyclodextrin inclusion and surfactant micelle solubilization, and the dissolution rate can reach more than 85% in 30 minutes.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical preparation technology, specifically relating to an oral composition of bile acids, its preparation method, and its application. Background Technology

[0002] Cholic acid (CA), chemically known as 3α,7α,12α-trihydroxy-5β-cholan-24-acid, has the molecular formula C2. 24 H 40 O5, found in the bile of cattle, sheep, and pigs, is a colorless flaky substance or a white crystalline powder. Bile acids are one of the main primary bile acids in the human body. They are synthesized from cholesterol in the liver, stored in the gallbladder, and released into the intestines after eating to participate in lipid digestion and absorption. In recent years, with the deepening research on bile acid nuclear receptors (such as FXR and TGR5), the pharmacological effects of bile acids and their derivatives in regulating glucose and lipid metabolism, improving insulin resistance, and anti-inflammation have been gradually revealed. Studies have shown that exogenous bile acid supplementation can activate related signaling pathways, regulate the expression of cholesterol 7α-hydroxylase (CYP7A1), and thus promote the conversion of cholesterol into bile acids. It has the potential to reduce serum total cholesterol (TC) and low-density lipoprotein (LDL-C), showing good application prospects in the prevention and treatment of hyperlipidemia and related metabolic diseases.

[0003] However, despite the significant pharmacological activity of bile acids, the development of their oral formulations still faces numerous technical challenges. First, bile acids are poorly soluble drugs with low solubility in water, and their solubility is greatly affected by gastrointestinal pH, resulting in low oral bioavailability and significant individual variability. This makes it difficult to maintain stable and effective blood concentrations, directly impacting the uniformity of their lipid-lowering efficacy. Second, the bile acid molecule contains multiple hydroxyl groups, making it chemically reactive and prone to oxidation, degradation, or crystal transformation under light, high temperature, or high humidity. Existing conventional formulation technologies often fail to effectively suppress the physicochemical instability of bile acids during long-term storage, leading to decreased formulation content, increased impurities, and consequently affecting drug safety and the persistence of efficacy.

[0004] Therefore, there is an urgent need to develop a novel oral composition for bile acids. Through optimization of a specific excipient system, the physicochemical stability of bile acids can be significantly improved while their dissolution behavior can be enhanced, thereby achieving a stable, efficient, and safe lipid-lowering therapeutic effect to meet the needs of long-term clinical use. Summary of the Invention

[0005] To address the shortcomings of existing technologies, this invention provides an oral bile acid composition, its preparation method, and its application.

[0006] To achieve the above-mentioned objectives of this invention, the specific technical solution adopted by this invention is as follows:

[0007] An oral composition of bile acid, comprising, by weight: 90-110 parts of bile acid, 100-300 parts of polymer carrier, 60-200 parts of stabilizer, 100-200 parts of filler, 10-30 parts of disintegrant and 1-5 parts of lubricant; The stabilizers include vitamin E polyethylene glycol succinate and sulfobutyl ether-β-cyclodextrin.

[0008] Preferably, the mass ratio of vitamin E polyethylene glycol succinate to sulfobutyl ether-β-cyclodextrin is 1:5-15 by mass parts.

[0009] Preferably, the polymer carrier is a copolyvinyl acetate and hydroxypropyl methylcellulose acetate succinate in a mass ratio of 1-2:1.

[0010] Preferably, the filler is selected from one or more of microcrystalline cellulose, mannitol and lactose, the disintegrant is selected from at least one of crospovidone, crospovidone sodium carboxymethyl cellulose and sodium carboxymethyl starch, and the lubricant is selected from at least one of sodium stearate fumarate, micronized silica gel and magnesium stearate.

[0011] More preferably, the filler is microcrystalline cellulose, the disintegrant is crospovidone, and the lubricant is sodium stearate fumarate.

[0012] Preferably, the cholic acid is micronized cholic acid with a particle size distribution D90 ≤ 50 μm.

[0013] This invention uses copovidone (PVP VA64) and hydroxypropyl methylcellulose acetate succinate (HPMCAS) as a carrier. PVP VA64 has excellent hydrophilicity and film-forming properties; the carbonyl group on its pyrrolidone ring can form hydrogen bonds with the hydroxyl groups in bile acid molecules, inhibiting drug molecule migration and improving wettability. HPMCAS, as a pH-dependent polymer, ionizes in the intestinal pH environment, not only playing a role in enteric-coated localized release, but its succinyl and acetyl structures can also effectively inhibit the recrystallization of amorphous bile acids through steric hindrance. At a specific ratio, the two can form a stable amorphous glassy solid dispersion, preventing drug precipitation during storage.

[0014] This invention employs vitamin E polyethylene glycol succinate (TPGS) and sulfobutyl ether-β-cyclodextrin (SBE-β-CD) as stabilizers. SBE-β-CD possesses a hydrophobic lumen and a hydrophilic outer wall, which can encapsulate the hydrophobic steroidal skeleton of bile acids within the lumen through host-guest inclusion, significantly improving apparent solubility. Its anionic properties also contribute to maintaining solution stability. TPGS, as a nonionic surfactant, can form micelles in gastrointestinal fluids, solubilizing free bile acid molecules. Simultaneously, TPGS acts as an inhibitor of the P-gp efflux pump, reducing the efflux of bile acids from intestinal epithelial cells and promoting passive diffusion absorption. SBE-β-CD provides molecular-level isolation in the solid state, while TPGS provides micellar solubilization in the dissolution medium; the two have a synergistic effect.

[0015] The present invention also relates to a method for preparing the above-mentioned oral bile acid composition, comprising the following steps: (1) Add the polymer carrier and vitamin E polyethylene glycol succinate to anhydrous ethanol and stir until clear to obtain mixture 1; (2) Dissolve sulfobutyl ether-β-cyclodextrin in water, mix well, then add to mixture 1 and stir to obtain mixture 2; (3) Add cholic acid to mixture 2, adjust pH, stir, filter, spray dry, and granulate to obtain drug-containing solid dispersion particles; (4) Mix the drug-containing solid dispersion particles with fillers and disintegrants, then add lubricant, stir, compress into tablets, and the product is obtained.

[0016] Preferably, the amount of anhydrous ethanol used in step (1) is 8-12 times the total mass of the polymer carrier and vitamin E polyethylene glycol succinate; the amount of water used in step (2) is 2-3 times the mass of sulfobutyl ether-β-cyclodextrin; the stirring speed is 200-400 rpm; and the stirring time is 3-10 min.

[0017] Preferably, the reagent used to adjust the pH in step (3) is ammonia or triethylamine, and the pH is adjusted to 7-8.5. The stirring conditions are: stirring at 200-400 rpm for 25-35 minutes.

[0018] Preferably, the filtration in step (3) is performed using a 0.4-0.5μm filter membrane, and the conditions for spray drying are: inlet air temperature of 80℃-120℃, outlet air temperature of 45℃-60℃, and atomization pressure of 0.3-0.6MPa.

[0019] Preferably, before step (1), the polymer carrier is further subjected to a pre-drying treatment at a temperature of 30°C-50°C, and the moisture content after drying is ≤2%.

[0020] Compared with the prior art, the present invention has the following beneficial effects: (1) The present invention significantly improves the dissolution effect by using polymer solid dispersion, cyclodextrin inclusion and surfactant micelle solubilization, and the dissolution rate can reach more than 85% in 30 minutes.

[0021] (2) Through the crystallization inhibition effect of HPMCAS and the inclusion protection effect of SBE-β-CD, recrystallization and degradation of bile acids during storage are effectively prevented. Accelerated stability test (40℃ / 75% RH, 3 months) shows that the content of the composition of the present invention remains above 98% and there is no significant increase in impurities. Detailed Implementation

[0022] The present invention will be further described in detail below with reference to specific embodiments. The following embodiments are not intended to limit the present invention, but only to illustrate the present invention. Unless otherwise specified, the experimental methods used in the following embodiments are generally performed under conventional conditions. Unless otherwise specified, the materials and reagents used in the following embodiments are commercially available.

[0023] Bile acid, purchased from Zhejiang Aoxing Pharmaceutical Co., Ltd., pharmaceutical grade, content ≥98.5%, controlled by air jet milling with D90≤50μm; copovidone (PVP VA64), purchased from BASF (China) Co., Ltd., Kollidon® VA 64 Fine; hydroxypropyl methylcellulose acetate succinate (HPMCAS), purchased from Shin-Etsu Chemical Co., Ltd., AQOAT® AS-HF, pharmaceutical grade; vitamin E polyethylene glycol succinate (TPGS), purchased from Rovo Pharmaceuticals Technology (Shanghai) Co., Ltd.; sulfobutyl ether-β-cyclodextrin (SBE-β-CD), product number ajce44244, purchased from Anjiekai Biopharmaceutical Technology Co., Ltd.; microcrystalline cellulose (MCCPH102), pharmaceutical grade, purchased from Huzhou Linghu Xinwang Chemical Co., Ltd.; crospovidone (PVPP), model SH-SL; sodium stearate fumarate, model SH-PLA, all purchased from Anhui Shanhe Pharmaceutical Excipients Co., Ltd.

[0024] Example 1 An oral composition for bile acids, comprising, by weight, the following raw materials: 100 parts bile acids, 80 parts copovidone (PVP VA64), 60 parts hydroxypropyl methylcellulose acetate succinate (HPMCAS), 10 parts vitamin E polyethylene glycol succinate (TPGS), 150 parts sulfobutyl ether-β-cyclodextrin (SBE-β-CD), 120 parts microcrystalline cellulose (MCC PH102), 15 parts crospovidone (PVPP), and 2 parts sodium stearate fumarate.

[0025] The preparation method of the above-mentioned oral bile acid composition is as follows: (1) Place PVP VA64 and HPMCAS in a vacuum drying oven and dry at 45°C for 4 hours; place TPGS in a vacuum drying oven at 30°C for 2 hours (to prevent melting). The moisture content of the above raw materials after drying is ≤2%.

[0026] (2) Add the dried PVP VA64, HPMCAS and TPGS to anhydrous ethanol in sequence (the amount of anhydrous ethanol is 10 times the total mass of PVP VA64, HPMCAS and TPGS), stir at 300 rpm until clear, and obtain mixture 1.

[0027] (3) Dissolve SBE-β-CD in purified water (the amount of water is twice the mass of SBE-β-CD), mix well, and slowly add it to mixture 1. Stir at 300 rpm for 5 min to obtain mixture 2.

[0028] (4) Add cholic acid to mixture 2, add ammonia water to adjust the pH to 7.5, continue stirring at 300 rpm for 30 min until the solution is clear, filter through a 0.45 μm filter membrane, spray dry (inlet air temperature 100℃, outlet air temperature 52℃, atomization pressure 0.45 MPa, feed rate 12 mL / min), collect the powder and granulate it through a 40 mesh sieve to obtain drug-containing solid dispersion particles.

[0029] (5) Mix the drug-containing solid dispersion particles with MCC PH102 and PVPP in a three-dimensional mixer at 20 rpm for 10 min, then add sodium stearate fumarate and continue mixing for 3 min, then compress into tablets to obtain the final product.

[0030] Example 2 An oral composition for bile acids, comprising, by weight, the following raw materials: 90 parts bile acids, 100 parts copovidone (PVP VA64), 50 parts hydroxypropyl methylcellulose acetate succinate (HPMCAS), 8 parts vitamin E polyethylene glycol succinate (TPGS), 120 parts sulfobutyl ether-β-cyclodextrin (SBE-β-CD), 100 parts microcrystalline cellulose (MCC PH102), 10 parts crospovidone (PVPP), and 1 part sodium stearate fumarate.

[0031] The preparation method of the above-mentioned oral bile acid composition is as follows: (1) Place PVP VA64 and HPMCAS in a vacuum drying oven and dry at 45°C for 4 hours; place TPGS in a vacuum drying oven at 30°C for 2 hours (to prevent melting). The moisture content of the above raw materials after drying is ≤2%.

[0032] (2) Add the dried PVP VA64, HPMCAS and TPGS to anhydrous ethanol in sequence (the amount of anhydrous ethanol is 9 times the total mass of PVP VA64, HPMCAS and TPGS), stir at 300 rpm until clear, and obtain mixture 1.

[0033] (3) Dissolve SBE-β-CD in purified water (the amount of water is twice the mass of SBE-β-CD), mix well, and slowly add it to mixture 1. Stir and mix at 200 rpm for 10 min to obtain mixture 2.

[0034] (4) Add cholic acid to mixture 2, add ammonia water to adjust the pH to 7.8, continue stirring at 200 rpm for 35 min until the solution is clear, filter through a 0.45 μm filter membrane, spray dry (inlet air temperature 100℃, outlet air temperature 52℃, atomization pressure 0.45 MPa, feed rate 12 mL / min), collect the powder and granulate it through a 40 mesh sieve to obtain drug-containing solid dispersion particles.

[0035] (5) Mix the drug-containing solid dispersion particles with MCC PH102 and PVPP in a three-dimensional mixer at 20 rpm for 10 min, then add sodium stearate fumarate and continue mixing for 3 min, then compress into tablets to obtain the final product.

[0036] Example 3 An oral composition of bile acid, comprising, by weight, the following raw materials: 110 parts bile acid, 120 parts copovidone (PVP VA64), 70 parts hydroxypropyl methylcellulose acetate succinate (HPMCAS), 15 parts vitamin E polyethylene glycol succinate (TPGS), 140 parts sulfobutyl ether-β-cyclodextrin (SBE-β-CD), 150 parts microcrystalline cellulose (MCC PH102), 20 parts crospovidone (PVPP), and 4 parts sodium stearate fumarate.

[0037] The preparation method of the above-mentioned oral bile acid composition is as follows: (1) Place PVP VA64 and HPMCAS in a vacuum drying oven and dry at 45°C for 4 hours; place TPGS in a vacuum drying oven at 30°C for 2 hours (to prevent melting). The moisture content of the above raw materials after drying is ≤2%.

[0038] (2) Add the dried PVP VA64, HPMCAS and TPGS to anhydrous ethanol in sequence (the amount of anhydrous ethanol is 10 times the total mass of PVP VA64, HPMCAS and TPGS), stir at 300 rpm until clear, and obtain mixture 1.

[0039] (3) Dissolve SBE-β-CD in purified water (the amount of water is 3 times the mass of SBE-β-CD), mix well, and slowly add it to mixture 1. Stir at 300 rpm for 5 min to obtain mixture 2.

[0040] (4) Add cholic acid to mixture 2, add ammonia water to adjust the pH to 7.5, continue stirring at 300 rpm for 30 min until the solution is clear, filter through a 0.45 μm filter membrane, spray dry (inlet air temperature 100℃, outlet air temperature 52℃, atomization pressure 0.45 MPa, feed rate 12 mL / min), collect the powder and granulate it through a 40 mesh sieve to obtain drug-containing solid dispersion particles.

[0041] (5) Mix the drug-containing solid dispersion particles with MCC PH102 and PVPP in a three-dimensional mixer at 20 rpm for 10 min, then add sodium stearate fumarate and continue mixing for 3 min, then compress into tablets to obtain the final product.

[0042] Comparative Example 1 The only difference between this comparative example and Example 1 is that copovidone (PVP VA64) was replaced with an equal amount of polyethylene glycol 6000.

[0043] Comparative Example 2 The only difference between this comparative example and Example 1 is that it does not contain copovidone (PVP VA64) and its amount is added to hydroxypropyl methylcellulose acetate succinate (HPMCAS).

[0044] The preparation method is as follows: (1) Dry HPMCAS in a vacuum drying oven at 45°C for 4 hours; dry TPGS in a vacuum oven at 30°C for 2 hours (to prevent melting). The moisture content of the above raw materials after drying is ≤2%.

[0045] (2) Add the dried HPMCAS and TPGS to anhydrous ethanol in sequence (the amount of anhydrous ethanol is 10 times the total mass of HPMCAS and TPGS), stir at 300 rpm until clear, and obtain mixture 1.

[0046] The remaining steps are the same as in Example 1.

[0047] Comparative Example 3 The only difference between this comparative example and Example 1 is that it does not contain hydroxypropyl methylcellulose acetate succinate (HPMCAS) and its amount is added to the supercopovidone (PVP VA64).

[0048] The preparation method is as follows: (1) Place PVP VA64 in a vacuum drying oven and dry at 45°C for 4 hours; place TPGS in a vacuum drying oven at 30°C for 2 hours (to prevent melting). The moisture content of the above raw materials after drying is ≤2%.

[0049] (2) Add the dried PVP VA64 and TPGS to anhydrous ethanol in sequence (the amount of anhydrous ethanol is 10 times the total mass of PVP VA64 and TPGS), stir at 300 rpm until clear, and obtain mixture 1.

[0050] The remaining steps are the same as in Example 1.

[0051] Comparative Example 4 The only difference between this comparative example and Example 1 is that vitamin E polyethylene glycol succinate (TPGS) is not added, and the amount of microcrystalline cellulose is increased accordingly to maintain the same total weight.

[0052] The preparation method is as follows: (1) Place PVP VA64 and HPMCAS in a vacuum drying oven and dry at 45°C for 4 hours. The moisture content after drying is ≤2%.

[0053] (2) Add the dried PVP VA64 and HPMCAS to anhydrous ethanol in sequence (the amount of anhydrous ethanol is 10 times the total mass of PVP VA64 and HPMCAS), stir at 300 rpm until clear, and obtain mixture 1.

[0054] The remaining steps are the same as in Example 1.

[0055] Comparative Example 5 The only difference between this comparative example and Example 1 is that sulfobutyl ether-β-cyclodextrin (SBE-β-CD) is not added, and the amount of microcrystalline cellulose is increased accordingly to maintain the same total weight.

[0056] The preparation method is as follows: (1) Place PVP VA64 and HPMCAS in a vacuum drying oven and dry at 45°C for 4 hours; place TPGS in a vacuum drying oven at 30°C for 2 hours (to prevent melting); the moisture content after drying is ≤2%.

[0057] (2) Add the dried PVP VA64, HPMCAS and TPGS to anhydrous ethanol in sequence (the amount of anhydrous ethanol is 10 times the total mass of PVP VA64, HPMCAS and TPGS), stir at 300 rpm until clear, and obtain mixture 1.

[0058] (3) Add cholic acid to mixture 1, add ammonia water to adjust the pH to 7.5, continue stirring at 300 rpm for 30 min until the solution is clear, filter through a 0.45 μm filter membrane, spray dry (inlet air temperature 100℃, outlet air temperature 52℃, atomization pressure 0.45 MPa, feed rate 12 mL / min), collect the powder and granulate it through a 40 mesh sieve to obtain drug-containing solid dispersion particles.

[0059] (4) Mix the drug-containing solid dispersion particles with MCC PH102 and PVPP in a three-dimensional mixer at 20 rpm for 10 min, then add sodium stearate fumarate and continue mixing for 3 min, then compress into tablets to obtain the final product.

[0060] Comparative Example 6 The only difference between this comparative example and Example 1 is the ratio of TPGS to SBE-β-CD.

[0061] By weight, the raw materials are: 100 parts of cholic acid, 80 parts of copovidone (PVP VA64), 60 parts of hydroxypropyl methylcellulose acetate succinate (HPMCAS), 3 parts of vitamin E polyethylene glycol succinate (TPGS), 157 parts of sulfobutyl ether-β-cyclodextrin (SBE-β-CD), 120 parts of microcrystalline cellulose (MCC PH102), 15 parts of crospovidone (PVPP), and 2 parts of sodium stearate fumarate.

[0062] The preparation method is the same as in Example 1.

[0063] Comparative Example 7 An oral composition of bile acids, with the same formulation as in Example 1.

[0064] The only difference between the preparation method and Example 1 is that the addition of ammonia to adjust the pH value in step (4) is replaced by NaOH aqueous solution to adjust the pH value.

[0065] Effect test Test Example 1: Dissolution Test The Chinese Pharmacopoeia paddle method was used, with 900 mL of pH 6.8 phosphate buffer solution as the medium, a rotation speed of 50 rpm, and a temperature of 37℃. Bile acid concentrations were measured at 5, 15, 30, and 60 minutes. The results are shown in Table 1.

[0066] Table 1 Dissolution test results

[0067] Examples 1-3 all showed a dissolution rate of over 90% within 30 minutes, which was significantly better than Comparative Examples 1-7.

[0068] Test Example 2 Accelerated Stability Test The tablets prepared in Examples 1-3 and Comparative Examples 1-7 were subjected to accelerated testing at 40℃ / 75%RH for 3 months, and the changes in content, dissolution rate, and impurity growth rate were measured. The results are shown in Table 2.

[0069] Table 2 Stability Test Results

[0070] In Examples 1-3, the content and dissolution rate remained stable under accelerated conditions, with minimal increase in impurities. In contrast, Comparative Examples 1-3 (with modified polymer carriers) showed a significant decrease in dissolution rate and a substantial increase in impurities, demonstrating that the polymer carrier combination (PVP VA64 and HPMCAS) of this invention, combined with the stabilizer, effectively inhibits the degradation and crystal transformation of bile acids.

[0071] The above detailed description is a specific description of one of the feasible embodiments of the present invention. This embodiment is not intended to limit the patent scope of the present invention. All equivalent implementations or modifications that do not depart from the present invention should be included within the scope of the technical solution of the present invention.

Claims

1. An oral composition for bile acids, characterized in that, By weight, it includes: 90-110 parts of cholic acid, 100-300 parts of polymer carrier, 60-200 parts of stabilizer, 100-200 parts of filler, 10-30 parts of disintegrant and 1-5 parts of lubricant; The stabilizers include vitamin E polyethylene glycol succinate and sulfobutyl ether-β-cyclodextrin.

2. The oral bile acid composition according to claim 1, characterized in that, The mass ratio of the vitamin E polyethylene glycol succinate to sulfobutyl ether-β-cyclodextrin is 1:5-15, based on parts by mass.

3. The oral bile acid composition according to claim 1, characterized in that, The polymer carrier is a copolyvinyl ketone and hydroxypropyl methylcellulose acetate succinate in a mass ratio of 1-2:

1.

4. The oral bile acid composition according to claim 1, characterized in that, The filler is selected from one or more of microcrystalline cellulose, mannitol and lactose, the disintegrant is selected from at least one of crospovidone, crospovidone sodium carboxymethyl cellulose and sodium carboxymethyl starch, and the lubricant is selected from at least one of sodium stearate fumarate, micronized silica gel and magnesium stearate.

5. The oral bile acid composition according to claim 4, characterized in that, The filler is microcrystalline cellulose, the disintegrant is crospovidone, and the lubricant is sodium stearate fumarate.

6. A method for preparing the oral bile acid composition according to any one of claims 1-5, characterized in that, Includes the following steps: (1) Add the polymer carrier and vitamin E polyethylene glycol succinate to anhydrous ethanol and stir until clear to obtain mixture 1; (2) Dissolve sulfobutyl ether-β-cyclodextrin in water, mix well, then add to mixture 1 and stir to obtain mixture 2; (3) Add cholic acid to mixture 2, adjust pH, stir, filter, spray dry, and granulate to obtain drug-containing solid dispersion particles; (4) Mix the drug-containing solid dispersion particles with fillers and disintegrants, then add lubricant, stir, compress into tablets, and the product is obtained.

7. The preparation method according to claim 6, characterized in that, The amount of anhydrous ethanol used in step (1) is 8-12 times the total mass of the polymer carrier and vitamin E polyethylene glycol succinate; the amount of water used in step (2) is 2-3 times the mass of sulfobutyl ether-β-cyclodextrin; the stirring speed is 200-400 rpm; and the stirring time is 3-10 min.

8. The preparation method according to claim 6, characterized in that, In step (3), the pH adjustment reagent is ammonia or triethylamine, and the pH is adjusted to 7-8.

5. The stirring conditions are: stirring at 200-400 rpm for 25-35 min. The filtration is carried out using a 0.4-0.5 μm filter membrane. The spray drying conditions are: inlet air temperature of 80℃-120℃, outlet air temperature of 45℃-60℃, and atomization pressure of 0.3-0.6 MPa.

9. The preparation method according to claim 6, characterized in that, Before step (1), there is also a step of pre-drying the polymer carrier and vitamin E polyethylene glycol succinate at a drying temperature of 30℃-50℃, and the moisture content after drying is ≤2%.

10. The use of an oral bile acid composition according to any one of claims 1-5 or an oral bile acid composition prepared by any one of claims 6-9 in the preparation of lipid-lowering drugs.

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