Use of tauroursodeoxycholic acid and controlled release formulations containing tauroursodeoxycholic acid in the preparation of products for improving the growth performance of livestock and poultry

Abstract

The application belongs to the technical field of livestock and poultry feed and feed additive, and particularly relates to application of tauroursodeoxycholic acid and a controlled-release preparation containing tauroursodeoxycholic acid in preparation of a product for improving growth performance of livestock and poultry. The application of tauroursodeoxycholic acid in preparation of the product for improving growth performance of livestock and poultry can inhibit metabolism of epithelial cells through enteric noradrenergic neurons and promote growth of livestock and poultry. It is found through research that addition of the controlled-release tauroursodeoxycholic acid in a daily ration can significantly improve daily weight gain and feed conversion rate of livestock and poultry, and meanwhile, the controlled-release tauroursodeoxycholic acid does not have any toxic side effects on livestock and poultry and can be directly used, thereby providing technical and cost support for preparation of nutrients for improving growth performance of livestock and poultry, and having a good popularization and application prospect.

Description

Technical Field

[0001] This invention belongs to the technical field of livestock and poultry feed and feed additives, specifically relating to the application of tauroursodeoxycholic acid and controlled-release formulations containing tauroursodeoxycholic acid in the preparation of products that improve the growth performance of livestock and poultry. Background Technology

[0002] Feed utilization efficiency is a key economic indicator for measuring livestock and poultry production performance. Historically, livestock and poultry have primarily relied on the small intestine for the digestion and absorption of nutrients. The small intestine, through its well-developed villi and microvilli, abundant digestive enzymes, and specific transport carriers, completes the majority of the digestion and absorption of major nutrients such as starch, protein, and fat. Therefore, existing technical strategies for improving feed utilization efficiency, such as adding exogenous digestive enzymes, optimizing amino acid balance, and improving small intestinal health, are highly focused on regulating small intestinal function. In contrast, the hindgut (including the cecum and colon) has long been considered in traditional nutrition as an organ primarily responsible for the reabsorption of water and electrolytes, as well as the temporary storage of chyme residues. The microbial fermentation processes occurring in the colon, especially the fermentation of dietary fiber and small amounts of protein that are not fully digested and absorbed by the small intestine, are generally considered to contribute very little energy, and the short-chain fatty acids produced only serve as an auxiliary energy source for local intestinal epithelial cells, often overlooked in their contribution to overall energy metabolism and protein utilization. Meanwhile, abnormal fermentation of proteins in the colon can produce potentially harmful substances such as ammonia, phenols, indoles, and amines. These substances not only increase the body's metabolic burden and nitrogen excretion, but may also induce intestinal inflammation, damage the intestinal barrier function, and thus indirectly negatively affect feed utilization efficiency.

[0003] The enteric nervous system (ENS) is a highly complex neural network embedded in the gastrointestinal wall, composed of various neuronal subtypes and neural circuits. The ENS can exert local regulatory functions to a certain extent independently of the central nervous system, while simultaneously cooperating with the central nervous system in regulating the host's energy metabolism. The hindgut (cecum and colon) has a particularly rich number of neurons in the ENS, making it one of the most concentrated areas of intestinal neural network. Structurally, the ENS is mainly divided into the myenteric plexus and the submucosal plexus. The myenteric plexus contains a large number of cholinergic, glutamatergic, and nitric acid-dependent neurons, primarily responsible for regulating colonic motility. Recent studies have gradually revealed that the submucosal plexus also contains various types of neurons and undertakes more refined epithelial regulatory functions. For example, cholinergic and calcium-binding proteolytic neurons in the submucosal plexus can directly sense nutrients (such as glucose and fatty acids) in the intestinal lumen, thereby transmitting chemical signals to epithelial cells and regulating their metabolic activities. Furthermore, neurons expressing the mechanosensory channel proteins Piezo1 and TRPV1 can influence the metabolic state of epithelial cells through an indirect pathway mediated by immune cells, and further intervene in the occurrence and development of local inflammation. Therefore, the enteric nervous system has been considered one of the key links in regulating colonic epithelial cell metabolism.

[0004] Bile acids are metabolic products synthesized from cholesterol in the liver. They have multiple synthetic pathways and derivatives in the body. Primary bile acids are synthesized in the liver and secreted into the intestines, where they are metabolized by intestinal microorganisms into secondary bile acids. These secondary bile acids can then combine with glycine and taurine to form various conjugated bile acids. Previously, bile acids and their salts were mainly used to promote digestion and absorption in livestock and poultry, especially the digestion and absorption of fatty nutrients. Studies have shown that bile acids are also important antibacterial active substances in the body. However, due to the enterohepatic circulation in the livestock and poultry intestines, most bile acids are absorbed in the terminal ileum, with only a small amount reaching the cecum. Furthermore, there is currently no literature reporting which bile acids can regulate colonic metabolism and feed utilization efficiency through enteric nerve regulation. Summary of the Invention

[0005] Addressing at least one deficiency in existing technologies, this invention aims to provide the application of tauroursodeoxycholic acid (TAA) and controlled-release formulations containing TAA in the preparation of products that improve livestock and poultry growth performance. Through research, this invention has found that adding TAA controlled-release formulations to diets can significantly improve daily weight gain and feed conversion ratio in livestock and poultry without any toxic side effects. It can be used directly, providing technical and cost support for the preparation of nutrients that improve livestock and poultry growth performance, and has excellent prospects for widespread application.

[0006] To achieve the above objectives, the present invention adopts the following technical solution: the application of tauroursodeoxycholic acid in the preparation of products that improve the growth performance of livestock and poultry, wherein the tauroursodeoxycholic acid inhibits epithelial cell metabolism through intestinal noradrenergic neurons, thereby promoting the growth of livestock and poultry.

[0007] As one embodiment of the application of tauroursodeoxycholic acid described in this invention in the preparation of products that improve the growth performance of livestock and poultry, the improvement of the growth performance of livestock and poultry includes improving the daily weight gain and feed utilization rate of livestock and poultry.

[0008] As one embodiment of the application of tauroursodeoxycholic acid described in this invention in the preparation of products that improve the growth performance of livestock and poultry, the concentration of tauroursodeoxycholic acid is 10 mg / kg to 100 mg / kg.

[0009] As one embodiment of the application of tauroursodeoxycholic acid described in this invention in the preparation of products that improve the growth performance of livestock and poultry, the products that improve the growth performance of livestock and poultry include feed additives, pharmaceuticals, food or health products.

[0010] The present invention also claims protection for the use of a controlled-release formulation containing tauroursodeoxycholic acid in products for improving the growth performance of livestock and poultry, wherein the controlled-release formulation containing tauroursodeoxycholic acid inhibits epithelial cell metabolism through intestinal noradrenergic neurons, thereby promoting the growth of livestock and poultry.

[0011] As one embodiment of the application of the controlled-release formulation containing tauroursodeoxycholic acid described in this invention in the preparation of products that improve the growth performance of livestock and poultry, the improvement of the growth performance of livestock and poultry includes improving the daily weight gain and feed utilization rate of livestock and poultry.

[0012] As one embodiment of the application of the controlled-release formulation containing tauroursodeoxycholic acid described in this invention in the preparation of products that improve the growth performance of livestock and poultry, the controlled-release formulation containing tauroursodeoxycholic acid is a hindgut-targeted controlled-release formulation.

[0013] As one embodiment of the application of the controlled-release formulation containing tauroursodeoxycholic acid described in this invention in the preparation of products that improve the growth performance of livestock and poultry, the hindgut-targeted controlled-release formulation includes controlled-release tablets, controlled-release pills, and controlled-release capsules.

[0014] The controlled-release pellets described in this invention can be prepared into controlled-release microgranules using polypropylene resin as a coating.

[0015] As one embodiment of the application of the controlled-release formulation containing tauroursodeoxycholic acid described in this invention in the preparation of products that improve the growth performance of livestock and poultry, the hindgut-targeted controlled-release formulation has an effective pH value of 6.5 or higher.

[0016] As one embodiment of the application of the controlled-release formulation containing tauroursodeoxycholic acid described in this invention in the preparation of products that improve the growth performance of livestock and poultry, the amount of tauroursodeoxycholic acid added in the controlled-release formulation containing tauroursodeoxycholic acid is 10~100ppm.

[0017] As a preferred embodiment of the application of the controlled-release formulation containing tauroursodeoxycholic acid described in this invention in the preparation of products that improve the growth performance of livestock and poultry, the amount of tauroursodeoxycholic acid added in the controlled-release formulation is 10~80 ppm.

[0018] As one embodiment of the application of the controlled-release formulation containing tauroursodeoxycholic acid described in this invention in the preparation of products that improve the growth performance of livestock and poultry, the products that improve the growth performance of livestock and poultry include feed additives, pharmaceuticals, food or health products.

[0019] Compared with the prior art, the present invention has the following beneficial effects: (1) In this invention, explants were used to screen for the optimal types and combinations of bile acids that can enhance noradrenergic neurons. A controlled-release coating technique was employed to achieve precise release of bile acids in the cecum and colon, thereby improving the growth performance and feed utilization efficiency of livestock and poultry. Bile acids are endogenous bioactive substances in the intestines of livestock and poultry. This invention achieves its goals of antibacterial action, antibiotic substitution, cost reduction, and efficiency improvement simply by altering the location of bile acids in the intestines, thus offering better safety and timeliness.

[0020] (2) Through research, this invention has found that adding controlled-release tauroursodeoxycholic acid to the diet can significantly improve the daily weight gain and feed conversion rate of livestock and poultry, while having no toxic side effects on livestock and poultry. It can be used directly, providing technical and cost support for the preparation of nutrients that improve the growth performance of livestock and poultry, and has a good prospect for promotion and application. Attached Figure Description

[0021] Figure 1This diagram illustrates the regulation of epithelial cell metabolism by tauroursodeoxycholic acid (TADO) through intestinal norepinephrine neurons in an embodiment of the present invention. Figure A shows a schematic diagram of colonic explants co-treated with TUDCA and norepinephrine; Figures B, C, and D show data on oxygen consumption, ammonia production, and ATP content of the colonic explants after co-treatment with TUDCA and norepinephrine, respectively; Figure E shows a schematic diagram of colonic explants co-treated with TUDCA and an adrenergic blocker; Figures F, G, and H show data on oxygen consumption, ammonia production, and ATP content of the colonic explants after co-treatment with TUDCA and an adrenergic blocker, respectively. Figure I shows a schematic diagram of mouse experiments involving colonic perfusion of TUDCA and intraperitoneal injection of an adrenergic blocker; Figures J, K, and L show data on cumulative food intake, body weight gain, and blood ammonia content in mice, respectively. NS indicates no statistical significance; * indicates p-value ≤ 0.05, the difference is statistically significant; ** indicates p-value ≤ 0.01, the difference is highly statistically significant; *** indicates p-value ≤ 0.001, the difference is extremely statistically significant.

[0022] Figure 2 This is a diagram illustrating the in vitro release pattern of controlled-release tauroursodeoxycholic acid microspheres in an embodiment of the present invention. Detailed Implementation

[0023] The technical solutions of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of the present invention.

[0024] Unless otherwise specified, the experimental methods used in the examples and comparative examples are conventional methods, and the materials and reagents used are commercially available unless otherwise specified.

[0025] The component information used in the examples is shown below: CA (cholic acid), TCA (taurocholic acid), TCDCA (taurine chenodeoxycholic acid), GCDCA (glycine chenodeoxycholic acid), DCA (deoxycholic acid), UDCA (ursodeoxycholic acid), GDCA (glycine deoxycholic acid), TUDCA (taurine ursodeoxycholic acid), and GUDCA (glycine ursodeoxycholic acid) are all commercially available.

[0026] Example 1: Effects of different types of primary and secondary bile acids on the activity of intestinal noradrenergic neurons 1. Colon explant culture C57BL / 6J mice of uniform littermate weight were used in the experiment. After euthanasia by cervical dislocation, the mice were disinfected by immersion in 75% alcohol. The intact colonic tissue (from cecum to rectum) was then dissected longitudinally. The dissected colonic tissue was repeatedly washed 2-3 times in sterile PBS (containing 100 μg / mL penicillin and streptomycin) to remove any remaining contents. Finally, the colonic tissue was transversely cut into 1 cm long segments and incubated in Krebs-Hensleit's solution (containing 200 μg / mL penicillin and streptomycin) at 37°C and 5% CO2 for 2 hours.

[0027] 2. Detection of norepinephrine (NE) content Colonic explant mucosa was collected as a sample and analyzed using a norepinephrine ELISA kit (Elabscience). The test results are shown in Table 1.

[0028] Table 1. Effects of different types of primary and secondary bile acids on NE content in colonic mucosa.

[0029] The test results are shown in Table 1. Different types of tauroursodeoxycholic acid were used to test colon explants. Among them, colon explants treated with TUDCA (tauroursodeoxycholic acid) significantly increased the content of NE in the mucosa.

[0030] Example 2: TUDCA's effect on the regulation of colonic epithelial cell metabolism through intestinal norepinephrine neurons 1. Colon explant culture C57BL / 6J mice of uniform littermate weight were used in the experiment. After euthanasia by cervical dislocation, the mice were disinfected by immersion in 75% alcohol. The intact colonic tissue (from cecum to rectum) was then dissected longitudinally. The dissected colonic tissue was repeatedly washed 2-3 times in sterile PBS (containing 100 μg / mL penicillin and streptomycin) to remove any remaining contents. Finally, the colonic tissue was transversely cut into 1 cm long segments and incubated in Krebs-Hensleit's solution (containing 200 μg / mL penicillin and streptomycin) at 37°C and 5% CO2 for 2 hours.

[0031] 2. Effects of adrenergic receptor blockade on growth performance in TUDCA-infused mice To investigate whether TUDCA regulates colonic metabolism through intestinal noradrenergic neurons, 32 eight-week-old C57BL / 6J mice of uniform weight were selected and randomly divided into four groups as follows: Control group: Colonic instillation with normal saline + intraperitoneal injection of normal saline; Treatment group 1: Intracolonic instillation of 10 mg / kg mouse body weight of TUDCA solution + intraperitoneal injection of physiological saline; Treatment group 2: Colonic instillation of normal saline solution + intraperitoneal injection of 5 mg / kg of adrenergic receptor blocker Labetalol HCl; Treatment group 3: 10 mg / kg mouse body weight of TUDCA solution was instilled into the colon and 5 mg / kg of Labetalol HCl, an adrenergic receptor blocker, was injected intraperitoneally. The pH of the reagents in each group was adjusted to 7.0. Mice were allowed free access to food and water, 12-hour circulating light, environmental humidity of 70%±10%, and constant temperature of 23℃±1℃ for 12 days.

[0032] 3. Indicator Testing: Ammonia levels in colon explant culture medium and mouse serum were detected using a megazyme ammonia kit. Oxygen consumption of colon explants: Dissolved oxygen concentrations were measured at 0, 5, 15, 25, 35, 45, 55, and 60 minutes after administration of 0 and 50 μM TUDCA or other combinations of treatments using a Micro 4 dissolved oxygen meter (PreSens Precision Sensing GmbH, Regensburg, Germany). ATP content detection in colon explants: After explant culture, the explants were weighed and homogenized with pre-cooled HClO4 at a ratio of 1:4. The homogenate was then centrifuged at 3500 r / min for 10 minutes, and the supernatant was collected. Subsequently, an equal volume of 1 mL MMK2HPO4 was added, mixed, and centrifuged again. The supernatant was then filtered (filter diameter: 0.22 μm). Finally, the samples were analyzed using a high-performance liquid chromatography (HPLC) instrument (Model 1260, Agilent Technologies, USA), with K3PO4 at pH 6.5 as the mobile phase.

[0033] Test results are as follows Figure 1 As shown, adding norepinephrine (NE) to colonic explants reproduced the phenotype of TUDCA inhibiting epithelial cell metabolism (decreased oxygen consumption, ammonia levels, and ATP). Adding adrenergic receptors to colonic explants to block norepinephrine signaling reversed the metabolic-inhibiting phenotype of TUDCA. Furthermore, in vivo mouse experiments showed that blocking adrenergic receptor signaling eliminated the growth-promoting effect of TUDCA and the reduction in blood ammonia levels, further demonstrating that TUDCA promotes mouse growth by inhibiting epithelial cell metabolism through intestinal norepinephrine neurons.

[0034] Example 3: Preparation and release verification of controlled-release tauroursodeoxycholic acid microspheres 1. Preparation of tauroursodeoxycholic acid microspheres, the specific method is as follows: (1) Weigh 250 g of TUDCA tauroursodeoxycholic acid powder, 700 g of excipients (corn starch) and 50 g of binder (maltodextrin) and mix them evenly to prepare a powder for later use. (2) Granulation was performed using centrifugal granulation. Specifically, 600 g of the prepared powder was weighed and put into a centrifugal granulator. The parameters were set as follows: rotation speed 300 rpm, spray rate 30 mL / min, and air inlet rate 30 m / s. After the master pellets were formed, powder was continuously added in small amounts to maintain the streamlined rotation of the microspheres until most of the microspheres had a mesh size of approximately 20-40 mesh. The resulting wet microspheres were then placed in a 50℃ oven and dried for 12 hours. After passing through a 16-60 mesh sieve, phosphoric acid liquid was sprayed onto the microspheres to adjust the pH to 6.8 for later use.

[0035] (3) Preparation of coating material: Specifically, domestic enteric-coated acrylic resin No. III was used. 300 mL of water was taken and 25 g of the matching premix (purchased from Lianyungang Hengyang Pharmaceutical Co., Ltd., Intech® L30D-65 polyacrylic acid resin latex (enteric-coated type), the main components of which are hydroxypropyl methylcellulose, polyethylene glycol, talc and polysorbate-80) was stirred. 250 g of enteric-coated latex (the main components of which are methacrylic acid and acrylate copolymers) was slowly added to the water and stirred for 30 min. After filtration, it was used for subsequent coating. (4) The microcapsules were coated using a centrifugal granulation and coating machine. The coating solution was transported by a constant flow peristaltic pump. After coating, the microcapsules were dried at the set material temperature for 5 minutes before being removed. The coating parameters were: top spray coating, constant flow pump flow rate 0.8-1.2 mL / min, material temperature 32-37℃, air volume 30 m / s, spray pressure 1.0-1.5 bar, inlet temperature 40-45℃, and the final weight gain of the coated microcapsules was 20%.

[0036] 2. Verification of in vitro release of tauroursodeoxycholic acid-coated microspheres, the specific method is as follows: (1) Preparation of each dissolution medium: Prepared according to Part IV of the 2020 edition of the Pharmacopoeia of the People's Republic of China: Artificial gastric fluid (1.17 mL concentrated hydrochloric acid diluted with water to 1000 mL); Artificial small intestinal fluid: Solution a: 0.2 mol / L potassium dihydrogen phosphate (27.22 g potassium dihydrogen phosphate diluted with water to 1000 mL); Solution b: 0.2 mol / L sodium hydroxide (8 g sodium hydroxide diluted with water to 1 L); Then, add 9 mL of solution b to 250 mL of solution a and dilute to 1000 mL to obtain an artificial small intestinal buffer solution with pH=5.5; Artificial hind intestinal fluid: 6.8 g potassium dihydrogen phosphate plus 152 mL of 0.1 mol / L sodium hydroxide solution. Dilute with water to 1000 mL to obtain the final solution.

[0037] (2) Establishment of standard curve: 0.03 g of microspheres were weighed, ground, and placed in a 2 mL centrifuge tube. The mixture was then serially diluted twofold using various dissolution media to prepare standard solutions with concentrations of 0.05859375, 0.1171875, 0.234375, 0.46875, 0.9375, 1.875, 3.75, 7.5, 15, and 30 mg / mL. OD was then measured using an ELISA reader. 600 To find the linear range of absorbance values, plot the standard concentration (c, mg / mL) on the x-axis and the absorbance values ​​(Y, OD) on the y-axis. 600 Using y as the ordinate, establish the equations for the standard curves of each solute.

[0038] (3) Referring to the dissolution determination method in the 2020 edition of the Chinese Pharmacopoeia, 0.03 g of microparticles were weighed into a 2 mL centrifuge tube (n≥3). First, 1 mL of artificial gastric fluid with pH=2 was added to the centrifuge tube. The centrifuge tube was then horizontally inverted and incubated on a 37℃ constant temperature shaker. Every 30 min, 20 μL of solution was taken and artificial gastric fluid of the same temperature and volume was added. After incubation for 1 h, the centrifuge tube was inverted and all the artificial gastric fluid in the centrifuge tube was aspirated. Then, 1 mL of artificial small intestinal fluid with pH=5.5 was added, and the above operation was repeated. Finally, after aspirating the artificial small intestinal fluid, artificial hind intestinal fluid was added, and the above operation was repeated. Finally, the liquid taken each time was diluted 10 times with the same dissolution medium and placed in an ELISA reader to detect OD. 600 The release concentration is obtained by substituting the values ​​into the standard curve.

[0039] 3. Test Results The results are as follows Figure 2 As shown, Figure 2 This describes the in vitro release pattern of TUDCA microparticles.

[0040] The experimental results showed that the in vitro release pattern of TUDCA microparticles was determined by using artificial gastric fluid (SGF) at pH=2, artificial small intestinal fluid (SIF) at pH=5.5, and artificial large intestinal fluid (LIF) at pH=6.5. TUDCA microparticles were not released in artificial gastric fluid and artificial small intestinal fluid, but were completely released in artificial large intestinal fluid within 1 hour.

[0041] Example 4: Effects of adding controlled-release tauroursodeoxycholic acid microcapsules to the diet on the growth performance of broilers To investigate the effects of different doses of TUDCA controlled-release microcapsules on broiler growth, 120 21-day-old yellow-feathered broilers were selected and randomly divided into four groups according to their body weight, as follows: Control group: blank controlled-release microgranules; Experimental group 1: Controlled-release microspheres containing 40 ppm TUDCA; Experimental group 2: Controlled-release microspheres containing 80 ppm TUDCA; Experimental group 3: 80 ppm TUDCA powder; The preparation methods of the controlled-release microspheres in the control group, experimental group 1, and experimental group 2 are as described in Example 3.

[0042] All groups were allowed free access to feed and water during the experiment, with 24-hour light, a constant temperature of 26℃±1℃, and an ambient humidity of 60%±10%, for 21 days. Feed intake was recorded every 3 days during the experiment, and the weight of the broilers was weighed at the end of the experiment. Finally, the average daily feed intake, average daily weight gain, and feed conversion ratio were calculated.

[0043] The test results are shown in Table 2.

[0044] Table 2 Effects of each group on broiler growth performance

[0045] Note: Different shoulder marks in the same row (a, b) indicate significant differences (P<0.05).

[0046] The experimental data in Table 2 show that the combination of 40 and 80 ppm tauroursodeoxycholic acid can significantly increase the average daily weight gain of yellow-feathered broilers and significantly reduce the feed conversion ratio, but has no effect on the average daily feed intake. The 80 ppm addition level is the most effective.

[0047] Compared with other experimental groups, in experimental group three, where 80 ppm of TUDCA powder was directly added to the diet, the average daily weight gain of yellow-feathered broilers was not significantly different from that of the control group, and the average daily feed intake and feed conversion ratio were also close to those of the control group.

[0048] The above embodiments are merely illustrative of the principles and effects of the present invention and are not intended to limit the invention. Any person skilled in the art can modify or alter the above embodiments without departing from the spirit and scope of the present invention. Therefore, all equivalent modifications or alterations made by those skilled in the art without departing from the spirit and technical concept disclosed in the present invention should still be covered by the claims of the present invention.

Claims

1. The application of tauroursodeoxycholic acid in the preparation of products that improve the growth performance of livestock and poultry, characterized in that, Tauroursodeoxycholic acid inhibits epithelial cell metabolism and promotes livestock and poultry growth through intestinal noradrenergic neurons.

2. The application of tauroursodeoxycholic acid as described in claim 1 in the preparation of products that improve the growth performance of livestock and poultry, characterized in that, Improving livestock and poultry growth performance includes increasing daily weight gain and feed utilization.

3. The application of tauroursodeoxycholic acid as described in claim 1 in the preparation of products that improve the growth performance of livestock and poultry, characterized in that, The concentration of tauroursodeoxycholic acid is 10 mg / kg to 100 mg / kg.

4. The application of tauroursodeoxycholic acid as described in claim 1 in the preparation of products that improve the growth performance of livestock and poultry, characterized in that, The products that improve the growth performance of livestock and poultry include feed additives, pharmaceuticals, food, or health products.

5. The application of a controlled-release formulation containing tauroursodeoxycholic acid in products for improving the growth performance of livestock and poultry, characterized in that, The controlled-release formulation containing tauroursodeoxycholic acid inhibits epithelial cell metabolism and promotes livestock and poultry growth by intestinal noradrenergic neurons.

6. The application of the controlled-release formulation containing tauroursodeoxycholic acid as described in claim 5 in the preparation of products that improve the growth performance of livestock and poultry, characterized in that, Improving livestock and poultry growth performance includes increasing daily weight gain and feed utilization.

7. The application of the controlled-release formulation containing tauroursodeoxycholic acid as described in claim 5 in the preparation of products that improve the growth performance of livestock and poultry, characterized in that, The controlled-release formulation containing tauroursodeoxycholic acid is a hindgut-targeted controlled-release formulation.

8. The application of the controlled-release formulation containing tauroursodeoxycholic acid as described in claim 7 in the preparation of products that improve the growth performance of livestock and poultry, characterized in that, The hindgut-targeted controlled-release formulations include controlled-release tablets, controlled-release pills, and controlled-release capsules; The hindgut-targeted controlled-release formulation has an effective pH value of 6.5 or higher.

9. The application of the controlled-release formulation containing tauroursodeoxycholic acid as described in claim 5 in the preparation of products that improve the growth performance of livestock and poultry, characterized in that, The controlled-release formulation containing tauroursodeoxycholic acid contains 10-100 ppm of tauroursodeoxycholic acid.

10. The application of the controlled-release formulation containing tauroursodeoxycholic acid as described in claim 5 in the preparation of products that improve the growth performance of livestock and poultry, characterized in that, The products that improve the growth performance of livestock and poultry include feed additives, pharmaceuticals, food, or health products.

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