Anti-stress feed additive containing gamma-aminobutyric acid as well as preparation method and application of anti-stress feed additive

Abstract

The invention relates to an anti-stress feed additive containing gamma-aminobutyric acid. The anti-stress feed additive is mainly prepared from the following raw materials in percentage by weight: 3-5% of radix astragali crude extract, 15-20% of stearic acid, 20-25% of palmitic acid, 8-10% of glycerol monolaurate, 5-10% of phospholipid and the balance of gamma-aminobutyric acid. According to the anti-stress feed additive, the gamma-aminobutyric acid and the astragalus membranaceus are combined for use, and through the synergistic effect of the astragalus membranaceus and the GABA, after a double-layer coating process, the rumen protection rate and the intestinal absorption rate are improved, the anti-stress capacity of ruminants is enhanced, and animal growth is promoted.

Description

Technical Field

[0001] This invention belongs to the field of feed additive formulation technology, specifically relating to an anti-stress feed additive containing γ-aminobutyric acid, its preparation method, and its application. Background Technology

[0002] Heat stress refers to the abnormal metabolic disorders that occur in livestock under high temperatures, which can lead to reduced feed intake, decreased production performance, and even death in severe cases, resulting in significant economic losses.

[0003] With the intensive development of animal husbandry, heat stress has become increasingly severe in its impact on livestock. For example, heat stress can reduce animal production performance, nutrient digestion and absorption, and the body's immune system. The gastrointestinal tract is one of the primary target organs of heat stress. When cattle are subjected to heat stress, gastrointestinal motility slows down, digestive enzyme activity decreases, and the digestion and absorption of dry matter and nutrients are affected. Heat stress can also induce systemic inflammatory responses in ruminants. To alleviate the adverse effects of high temperature and humidity on beef cattle in summer, some anti-heat stress drugs are receiving increasing attention. However, the use of these drugs can cause certain side effects, such as drug residues and toxic side effects, posing significant risks to human health and public safety. Therefore, finding a green, environmentally friendly, and safe feed additive to alleviate heat stress is particularly important.

[0004] Gamma-aminobutyric acid (GABA) is a non-protein amino acid and a novel functional factor. In animals, it exerts a calming effect on the nervous system and possesses various functions, including anti-stress, anticonvulsant, and increased feed intake. It is converted from glutamate under the catalysis of glutamate decarboxylase and has a wide range of pharmacological effects, such as improving cerebral blood circulation, lowering blood pressure, preventing arteriosclerosis, regulating arrhythmia, and preventing cerebral hypoxia and ischemia. It is an important inhibitory protective substance that plays a crucial regulatory role in the normal physiological functions of animals, perfectly aligning with human needs. Gamma-aminobutyric acid (GABA) is a functional non-protein amino acid feed additive, primarily found in nerve tissue in animals. In livestock production, GABA can improve livestock and poultry production performance, regulate hormone secretion, enhance immunity, and alleviate heat stress. Studies have shown that GABA can increase animal feed intake, providing sufficient nutrients to the body, thereby enhancing immune function. Adding GABA can reduce the adverse effects of heat stress on livestock and poultry.

[0005] Astragalus, a traditional Chinese medicine, possesses multiple benefits, including enhanced immunity, improved gut health, and growth promotion, thanks to its active ingredients (such as polysaccharides and saponins). Adding astragalus to animal feed can significantly improve animal production performance, reduce antibiotic dependence, and provide new ideas for sustainable farming. Studies have shown that astragalus can effectively regulate the animal immune system, improve disease resistance, enhance feed conversion rates, and promote muscle growth. Furthermore, its antioxidant and anti-inflammatory properties help alleviate stress responses and improve overall health. As a natural alternative, the application of astragalus not only meets environmental protection requirements but also reduces farming costs, driving the industry towards a safer and more efficient direction. Astragalus crude extract is a powdered product obtained from dried astragalus root raw materials through washing, drying, pulverizing, water extraction, impurity removal, and spray drying. It is most effective due to its high content of active ingredients, good solubility, and the presence of astragaloside and flavonoids.

[0006] Currently, most commercially available γ-aminobutyric acid (GABA) products cannot pass through the rumen. They are degraded by rumen microorganisms and lose their biological activity, with a loss rate exceeding 80%, thus failing to alleviate heat stress. Furthermore, coated GABA products typically use a single coating material (such as hydrogenated oil), resulting in poor sustained-release effects and a release rate of less than 40% in the small intestine.

[0007] Based on this, this application was developed. Summary of the Invention

[0008] The purpose of this invention is to overcome the defects of the prior art and provide an anti-stress feed additive containing γ-aminobutyric acid (GABA). It combines GABA with astragalus, and through the synergistic effect of astragalus and GABA, and after a double-layer coating process, it improves the rumen protection rate and intestinal absorption rate, enhances the anti-stress ability of ruminants, and promotes animal growth.

[0009] The present invention also provides a method for preparing and applying the above-mentioned anti-stress feed additive containing γ-aminobutyric acid.

[0010] To achieve the above objectives, the present invention adopts the following technical solution: This invention provides an anti-stress feed additive containing γ-aminobutyric acid, which is mainly made from the following raw materials in weight percentages: The crude extract of Astragalus membranaceus contains 3-5%, stearic acid 15-20%, palmitic acid 20-25%, monoglyceride of laurate 8-10%, phospholipids 5-10%, and the balance is γ-aminobutyric acid.

[0011] As one specific embodiment, the above-mentioned anti-stress feed additive containing γ-aminobutyric acid is mainly made from the following raw materials in weight percentages: The crude extract of Astragalus membranaceus contains 5%, stearic acid 15%, palmitic acid 20%, monoglyceride of laurate 9%, phospholipids 6%, and γ-aminobutyric acid 45%.

[0012] As one specific embodiment, the above-mentioned anti-stress feed additive containing γ-aminobutyric acid is mainly made from the following raw materials in weight percentages: The extract contains 5% crude Astragalus membranaceus extract, 20% stearic acid, 20% palmitic acid, 8% monolaurate, 5% phospholipids, and 42% γ-aminobutyric acid.

[0013] As one specific embodiment, the above-mentioned anti-stress feed additive containing γ-aminobutyric acid is mainly made from the following raw materials in weight percentages: The crude extract of Astragalus membranaceus contains 4%, stearic acid 18%, palmitic acid 20%, monoglyceride of laurate 10%, phospholipids 5%, and γ-aminobutyric acid 43%.

[0014] The present invention also provides a method for preparing the above-mentioned anti-stress feed additive containing γ-aminobutyric acid, which includes the following steps: (1) Material mixing: γ-aminobutyric acid and crude astragalus extract are put into a dry mixer and mixed evenly. This step aims to preserve the integrity of the natural active ingredients of astragalus and lay the foundation for the subsequent coating process.

[0015] (2) Melt mixing: After the spray can is pre-dried, add stearic acid, palmitic acid, and glyceryl monolaurate, and heat with steam until completely melted. When the temperature inside the can stabilizes at 80-90℃, add the semi-finished product prepared in step (1), maintain a constant temperature of 80-90℃ and continue stirring for 5-10 minutes. This stage achieves the initial dispersion of active ingredients through melt mixing, avoiding high-temperature degradation.

[0016] (3) Double coating: Add phospholipids to the melt obtained in step (2) and continue stirring for 10-20 minutes to form a uniform brown emulsion. The double coating process (stearic acid / monoglyceride + phospholipids) can significantly improve the stability of the active ingredients of Astragalus membranaceus, reduce its release rate in the intestine, and enhance its bioavailability.

[0017] (4) Cold spray granulation: When the molten liquid presents a uniform brown emulsion state, it is cold sprayed through a spray tower. The collected material is then sieved to obtain a 10-40 mesh finished product. This process is completed at low temperature, which effectively avoids the destruction of the active ingredients of Astragalus membranaceus by high temperature. The resulting microcapsule preparation needs to be dried and sealed for storage.

[0018] Preferably, in step (1), γ-aminobutyric acid and crude extract of Astragalus membranaceus are put into a dry mixer and stirred at 50-75 rpm for 2-5 minutes to ensure that the materials are mixed evenly.

[0019] Preferably, the cold spray parameters in step (4) are set as follows: air inlet temperature 5-7℃, high pressure pump pressure 25-30 MPa, blower 40-50 Hz, induced draft fan 20-30 Hz, air supply fan 30-40 Hz, and cold spray gear pump 40-50 Hz.

[0020] In the formulation of the anti-stress feed additive of this invention, the crude extract of Astragalus membranaceus and γ-aminobutyric acid (GABA) work synergistically to enhance rumen passage and exert immunomodulatory functions. Stearic acid and palmitic acid are used as the main encapsulation materials, utilizing their properties of being stable in the acidic environment of the rumen and degrading in the alkaline environment of the intestine to achieve targeted release. The combination of lauric acid monoglyceride and phospholipids as emulsifiers can significantly improve the stability of the emulsion and promote encapsulation efficiency. In this invention, the cold spray process employs low-temperature spray drying technology to avoid the damage of high temperatures to the active ingredients of GABA and Astragalus crude extract, while ensuring the integrity and uniformity of the microcapsule particles; γ-aminobutyric acid is coated through a fluidized bed; and porous microcapsules of γ-aminobutyric acid are formed through a freeze dryer.

[0021] This invention provides an anti-stress feed additive containing γ-aminobutyric acid (GABA) that incorporates an astragalus synergistic system and a double-layer coating structure. Compared with existing technologies, the advantages and beneficial effects of this invention are as follows: This invention employs a low-temperature process to avoid the damage of heat-sensitive components (such as polysaccharides and flavonoids) in the crude extract of Astragalus membranaceus by high temperatures, while also reducing the risk of γ-aminobutyric acid (GABA) degradation, ensuring the bioactivity of the final product. Simultaneously, a dense protective film is formed through a double-layer coating structure of stearic acid / monoglycerate + phospholipids, effectively blocking the oxidation of active ingredients by oxygen, moisture, and light, resulting in good stability and significantly extending the shelf life of the formulation. This invention also optimizes the carrier material; the combination of stearic acid with palmitic acid and lauric acid monoglycerides enhances the fluidity of the melt mixture and slows down the release rate of the active ingredients in the intestine through hydrophobic interactions, achieving a sustained-release effect and extending the duration of action. The addition of phospholipids not only serves as a coating material, but their hydrophilic groups also improve the dispersibility of the active ingredients, further enhancing the bioavailability of GABA and Astragalus membranaceus components. This solution, through low-temperature protection, double-layer coating, and precise temperature control, ensures the stability of active ingredients while achieving functional synergy and sustained-release effects, improving rumen protection and intestinal absorption rates, enhancing the stress resistance of ruminants, and promoting animal growth. It also has process feasibility and environmental friendliness, making it suitable for the development of high-value-added feed additives or functional foods. Attached Figure Description

[0022] Figure 1 The results of rumen-passing tests for different groups of products. Detailed Implementation

[0023] The technical solution of the present invention will be further described in detail below with reference to the embodiments, but the scope of protection of the present invention is not limited thereto.

[0024] In the following examples, all raw materials used are common commercially available products that can be purchased directly, or can be prepared using conventional techniques in the art.

[0025] The crude extract of Astragalus membranaceus is a common commercially available product. It was purchased from Hubei Jiulingcao Biotechnology Co., Ltd. as a type I crude extract of Astragalus membranaceus.

[0026] Room temperature refers to 25±5℃. Example 1

[0027] This invention provides an anti-stress feed additive containing γ-aminobutyric acid, which is mainly made from the following raw materials in weight percentages: The crude extract of Astragalus membranaceus contains 5%, stearic acid 15%, palmitic acid 20%, monoglyceride of laurate 9%, phospholipids 6%, and γ-aminobutyric acid 45%.

[0028] This embodiment provides a method for preparing the above-mentioned anti-stress feed additive containing γ-aminobutyric acid, which includes the following steps: (1) Material mixing: γ-aminobutyric acid and crude extract of Astragalus membranaceus are put into a dry mixer and stirred at 50 rpm for 3 minutes at room temperature to ensure that the materials are mixed evenly; (2) Melting and mixing: Ensure the inside of the spray tank is dry, add stearic acid, palmitic acid and lauric acid monoglyceride, and heat with steam until completely melted; when the temperature inside the tank is stable at 80℃, turn on the stirring function, stir for 10 minutes, add the mixture of GABA and crude extract of Astragalus membranaceus prepared in step (1), continue to maintain the stirring function, maintain a constant temperature of 80℃ and continue stirring for 10 minutes; (3) Double coating: Add phospholipids to the melt obtained in step (2) and continue stirring at 80°C for 15 minutes to form a uniform brown emulsion; (4) Cold spray granulation: When the molten liquid presents a uniform brown emulsion state, set the cold spray parameters as follows: inlet air temperature 5℃, high-pressure pump pressure 25 MPa, blower 45 Hz, induced draft fan 25 Hz, blower 35 Hz, and cold spray gear pump 45 Hz; perform cold spraying through the spray tower, collect the material and sieve it to obtain a 10-40 mesh finished product. The microcapsule formulation is completed and stored in a dry place. Example 2

[0029] This invention provides an anti-stress feed additive containing γ-aminobutyric acid, which is mainly made from the following raw materials in weight percentages: The extract contains 5% crude Astragalus membranaceus extract, 20% stearic acid, 20% palmitic acid, 8% monolaurate, 5% phospholipids, and 42% γ-aminobutyric acid.

[0030] This embodiment provides a method for preparing the above-mentioned anti-stress feed additive containing γ-aminobutyric acid, which includes the following steps: (1) Material mixing: γ-aminobutyric acid and crude extract of Astragalus membranaceus are put into a dry mixer and stirred at 70 rpm for 4 minutes at room temperature to ensure that the materials are mixed evenly; (2) Melting and mixing: Ensure the inside of the spray tank is dry, add stearic acid, palmitic acid and lauric acid monoglyceride, and heat with steam until completely melted; when the temperature inside the tank is stable at 90℃, turn on the stirring function, stir for 10 minutes, add the mixture of GABA and crude extract of Astragalus membranaceus prepared in step (1), continue to maintain the stirring function, maintain a constant temperature of 90℃ and continue stirring for 6 minutes; (3) Double coating: Add phospholipids to the melt obtained in step (2) and continue stirring at 90°C for 12 minutes to form a uniform brown emulsion; (4) Cold spray granulation: When the molten liquid presents a uniform brown emulsion state, set the cold spray parameters as follows: inlet air temperature 7℃, high-pressure pump pressure 28 MPa, blower 45 Hz, induced draft fan 25 Hz, blower 35 Hz, and cold spray gear pump 45 Hz; perform cold spraying through the spray tower, collect the material, and sieve it to obtain a 10-40 mesh finished product. The microcapsule formulation is completed and stored in a dry place. Example 3

[0031] This invention provides an anti-stress feed additive containing γ-aminobutyric acid, which is mainly made from the following raw materials in weight percentages: The crude extract of Astragalus membranaceus contains 4%, stearic acid 18%, palmitic acid 20%, monoglyceride of laurate 10%, phospholipids 5%, and γ-aminobutyric acid 43%.

[0032] The preparation method of the above-mentioned anti-stress feed additive containing γ-aminobutyric acid is as described in Example 1. Comparative Example

[0033] This invention provides an anti-stress feed additive containing γ-aminobutyric acid, which is mainly made from the following raw materials in weight percentages: 54% γ-aminobutyric acid, 9% light calcium carbonate, 8% microcrystalline cellulose, 15% bentonite, and 14% water.

[0034] This comparative example provides a method for preparing the above-mentioned anti-stress feed additive containing γ-aminobutyric acid, which includes the following steps: (1) Material mixing: Add γ-aminobutyric acid, light calcium carbonate, microcrystalline cellulose, bentonite and water into a dry mixer and stir at 50 rpm for 3 minutes at room temperature to ensure that the materials are mixed evenly; (2) Extrusion granulation: The material that was mixed evenly in step (1) was put into a rotary extrusion granulator and extruded at 100 rpm. The granulated material was then put into a centrifugal spheroidizer and extruded at 300 rpm for 2 minutes to make the material into uniform round particles. (3) Drying and coating: The fluidized bed temperature is 80℃ for drying, and then coating is carried out. The coating liquid is hydrogenated palm oil (the amount added is about 25% of the material mass); the melting temperature of the coating liquid is 90℃.

[0035] 1. Results of the application effect test.

[0036] During the experiment, the rearing temperature was maintained between 25 and 35°C. Thirty healthy Simmental crossbred cattle with an average weight of (380±20) kg and appropriate age were selected and randomly divided into three groups, with five replicates per group and two cattle per replicate. The control group was fed a basal diet (without GABA), experimental group 1 was fed an anti-stress feed additive product (Example 1), and experimental group 2 was fed a comparative anti-stress feed additive product. TMR was mixed into the feed and administered. The pre-trial period was 7 days, and the formal trial period was 30 days.

[0037] Control group: basal diet Experimental group: basal diet + 1 kg / t rumen-protected GABA.

[0038] On the start and end days of the experiment, the fasting weight of the cattle was measured using a weighbridge and recorded as the initial weight and final weight. The daily feed intake and remaining feed amount of the herd were also recorded, and growth performance indicators were calculated. The results are shown in Table 1 below.

[0039] Table 1 Results of feeding trials on different groups of beef cattle

[0040] The suitable temperature range for beef cattle growth is typically 10-20℃. When the ambient temperature exceeds 25℃, heat stress may begin to occur in beef cattle. Therefore, the breeding conditions for this experiment were selected as "breeding temperature between 25-35℃ during the experimental period." The experimental results in Table 1 demonstrate that adding the anti-stress feed additive containing γ-aminobutyric acid of this invention to the diet significantly improved the average daily weight gain and average daily feed intake of beef cattle under high temperature (25-35℃) conditions, while significantly reducing the feed conversion ratio and improving feed utilization. Furthermore, the application effect was significantly better than the control group.

[0041] 2. Results of stability test.

[0042] Samples of the anti-stress feed additives from Example 1 and the comparative example were taken and packaged in simulated small packages (using the same material as the actual production large packages), with each sample weighing 100g. Six bags were packaged for each batch of samples. The samples were placed in a constant temperature and humidity chamber at 40±2℃ and 75±5% relative humidity. Samples were tested at 0 (starting point), 1, 2, 3, and 6 months of storage, with the first test date being the determining factor. Samples after each test were discarded and not placed back in the constant temperature and humidity chamber. The results are shown in Table 2 below.

[0043] Table 2. Stability test results for different groups

[0044] The experimental results in Table 2 show that after 6 months of accelerated testing, the γ-aminobutyric acid content in the sample of Example 1 was stable and in good condition, indicating good product stability; the content in the comparative sample was slightly reduced and the sample was slightly clumped.

[0045] 3. Results of rumen-passing test.

[0046] Preparation of simulated rumen buffer: Take 1.74g of sodium dihydrogen phosphate, 2.7g of disodium hydrogen phosphate and 1.7g of sodium chloride, add water to dissolve to make 400mL, and adjust the pH to 6.6 using hydrochloric acid or sodium hydroxide.

[0047] Take 50 ml sterile centrifuge tubes and add 15 mL of sterile rumen-simulated buffer, 5 mL of filtered fresh rumen fluid, and 1 g of the corresponding sample: Group 1 received the anti-stress feed additive from Example 1, and Group 2 received the comparative anti-stress feed additive. Purge the centrifuge tubes with nitrogen for 30 seconds to expel air, quickly tighten the caps, and place the tubes in a 39°C constant temperature water bath shaker at 100 r / min. Remove the centrifuge tubes at 2 h, 4 h, 8 h, and 12 h (do not return the removed tubes), and cool them in an ice bath for 10 minutes to terminate the microbial reaction. Centrifuge the cooled samples at 8000 r / min and 4°C for 15 minutes, collect the supernatant, and determine the γ-aminobutyric acid (GABA) content by high-performance liquid chromatography (the content measured at 0 h is considered 100%). Results are shown below. Figure 1 .

[0048] Depend on Figure 1The experimental results show that both samples had a 100% rumen-passing rate at 0 hours, indicating that none of the samples were initially degraded by the rumen. As time progressed, both curves showed a downward trend, indicating that the rumen-passing rate of both samples decreased over time, meaning the samples were gradually degraded in the rumen. At all time points, the rumen-passing rate of Example 1 was higher than that of the comparative example. This indicates that Example 1 has a better resistance to rumen degradation than the comparative example. Therefore, the experimental results show that Example 1 can maintain a higher rumen-passing rate for a longer period in the rumen, meaning that more active ingredients can pass through the rumen and be absorbed and utilized in the intestines. This demonstrates that the anti-stress feed additive product of the present invention has a good rumen protection effect.

Claims

1. A stress-resistant feed additive containing γ-aminobutyric acid, characterized in that, It is mainly made of the following raw materials in percentage by weight: Radix Astragali crude extract 3~5%, stearic acid 15~20%, palmitic acid 20~25%, lauric acid monoglyceride 8~10%, phospholipid 5~10%, and the rest is γ-aminobutyric acid.

2. The anti-stress feed additive containing γ-aminobutyric acid according to claim 1, characterized in that, It is mainly made of the following raw materials in percentage by weight: Radix Astragali crude extract 5%, stearic acid 15%, palmitic acid 20%, lauric acid monoglyceride 9%, phospholipid 6%, and γ-aminobutyric acid 45%.

3. The anti-stress feed additive containing γ-aminobutyric acid according to claim 1, characterized by, It is mainly made of the following raw materials in percentage by weight: Radix Astragali crude extract 5%, stearic acid 20%, palmitic acid 20%, lauric acid monoglyceride 8%, phospholipid 5%, and γ-aminobutyric acid 42%.

4. The anti-stress feed additive containing γ-aminobutyric acid according to claim 1, characterized by, It is mainly made of the following raw materials in percentage by weight: Radix Astragali crude extract 4%, stearic acid 18%, palmitic acid 20%, lauric acid monoglyceride 10%, phospholipid 5%, and γ-aminobutyric acid 43%.

5. A method for the preparation of a stress-resistant feed additive containing γ-aminobutyric acid according to any one of claims 1 to 4, characterized in that, It comprises the following steps: (1) mixing of materials: uniformly mix γ-aminobutyric acid and Radix Astragali crude extract; (2) melt mixing: after pre-drying the spray tank, add stearic acid, palmitic acid, and lauric acid monoglyceride, and heat to complete melting by steam; when the temperature in the tank is stabilized at 80-90℃, put in the semi-finished product prepared in step (1), maintain constant temperature at 80-90℃ and continue stirring for 5-10 minutes; (3) double-layer coating: add phospholipid to the melt liquid obtained in step (2), continue stirring, and form a uniform brown emulsion; (4) cold spraying granulation: collect the material after sieving to obtain 10-40 mesh finished product through cold spraying by spray tower.

6. The method for preparing the anti-stress feed additive containing γ-aminobutyric acid as described in claim 5, characterized in that, In step (1), put γ-aminobutyric acid and Radix Astragali crude extract into a dry mixing machine, stir at a speed of 50-75 rpm for 2-5 minutes to ensure uniform mixing of the materials.

7. The method for preparing the anti-stress feed additive containing γ-aminobutyric acid as described in claim 5, characterized in that, In step (4), set the cold spraying parameters as follows: inlet air temperature 5-7℃, high-pressure pump pressure 25-30 MPa, air blower 40-50 Hz, air induction fan 20-30 Hz, air supply fan 30-40 Hz, and cold spraying gear pump 40-50 Hz.

Images