Aisuanling 9001: A Leap Forward in Intestinal Bacteriostatic Efficacy

Since the ban on antibiotic growth promoters in animal feed, controlling intestinal bacterial growth to prevent diarrhea has remained a key challenge and focal issue in the industry. Benzoic acid, with its broad-spectrum antibacterial activity, stable efficacy, and favorable impact on beneficial bacteria—exhibiting a clear “punish the bad, promote the good” profile—is widely used in animal husbandry. However, due to benzoic acid’s unique physiological properties, the critical factor for practical application is enhancing the retention of molecular‑form benzoic acid in the gut. Big‑data analyses reveal that most domestic and international companies add 3–5 kg/t of pure benzoic acid to feed, achieving both anti‑diarrheal and growth‑promoting effects. The latest meta‑analysis indicates that the optimal supplementation level of pure benzoic acid for promoting healthy piglet production is 6.0 kg/t. Consequently, higher dosages of pure benzoic acid have become the primary strategy for improving the retention of molecular‑form benzoic acid in the intestine and thereby eliciting pronounced antibacterial activity. So how can we achieve a leap in the antibacterial effect of intestinal benzoic acid derivatives? Recently, Researcher Hu Youjun, Chief Scientist at the nuacid Center, argued that conventional approaches to developing alternatives to antibiotics are unlikely to yield breakthroughs. He proposed that it is essential to empower and liberate thinking—achieving a leap in R&D mindset. Fundamentally, such a leap corresponds to an energy transition of electrons within the particles (atoms, ions, or molecules) that constitute matter, which aligns closely with the microscopic mechanisms underlying the antibacterial action of Lewis acids as described by Lewis acid–base theory. By applying Lewis acid–base theory and molecular docking techniques for optimized controlled release, and employing strategies such as “synergy,” “guardian,” and “permeabilization” to upgrade intestinal acid-controlled release, the approach has undergone rigorous in vitro and in vivo scientific evaluation as well as large-scale field trials, thereby truly realizing this transformative leap. The following outlines several key perspectives and recent research findings from the NIC, the nuacid Innovation Center:

As research and applications of pure benzoic acid deepen across industries, the potential risks associated with its high-dose use are gradually coming to light and are also manifesting in production processes:

1.1 Research indicates that only benzoic acid in its molecular form exhibits antibacterial activity. However, since pure benzoic acid has a pKa of 4.2, it dissociates in the stomach, releasing hydrogen ions and failing to reach the intestine to exert its antibacterial effect. Even if some undissociated benzoic acid does reach the intestine, the high intestinal pH rapidly ionizes it, rendering it inactive. Consequently, in industrial production, it is typically added at a high dose of at least 5 kg.

1.2 Due to the physicochemical and metabolic properties of benzoic acid itself, when pure benzoic acid is consumed by animals, it is rapidly absorbed into the bloodstream, leading to an increase in blood glucose levels. This interacts synergistically with monosaccharides and disaccharides in the feed, inducing a feeling of satiety and reducing feed intake; moreover, the higher the level of addition in the feed, the more pronounced this feed-intake inhibitory effect becomes.

1.3 May lead to glycine deficiency because, after ingestion by pigs, benzoic acid combines with glycine in the liver and, under the action of benzoyl‑CoA, forms hippuric acid, which is excreted in the urine (in poultry, metabolism results in excretion as allantoic acid). Therefore, when pure benzoic acid is used extensively—particularly in low‑protein, low‑soybean meal diets—excessive supplementation can cause endogenous glycine deficiency.

1.4 High-dose benzoic acid supplementation can induce damage to animal organs such as the liver, kidneys, and spleen. For example, Fujitani et al. (1993) found that high doses of sodium benzoate cause liver injury, characterized pathologically by necrotic foci around portal veins and hyaline cytoplasmic enlargement in hepatocytes, resembling swelling and necrosis. Sinha et al. (2010) reported that excessive intake of sodium benzoate disrupts hepatic lipid metabolism, leading to fatty liver and activating hepatoma cells, thereby inducing hepatoma. Oyewole et al. (2012) demonstrated that sodium benzoate damages the liver and kidneys of mice, resulting in elevated activities of the serum aminotransferases ALT and AST.

3.1 Improved controlled-release performance: With upgraded packaging materials and a refined controlled-release process, the formulation incorporates fumaric acid, ensuring safe passage through the stomach. After reaching the duodenum, the sustained-release matrix gradually disintegrates to release the active ingredient, which is then steadily delivered to different regions of the intestine over 6–12 hours.

3.2 Higher molecular retention rate: An optimized permeabilizing agent facilitates the accelerated uptake of more molecular benzoic acid into pathogenic bacterial cells through effective permeabilization, thereby preventing the high intestinal pH from ionizing the released benzoic acid molecules.

3.3 Improved antibacterial performance: The permeabilization effect enhances both the penetration ability and quantity of molecular benzoic acid, resulting in a more pronounced antibacterial effect. Test results from NIC Microbiology Laboratory and third-party testing organizations show that Aisuanling 9001 inhibits Salmonella at 1000 ppm and achieves complete inhibition at 1500 ppm; it inhibits Escherichia coli and Staphylococcus aureus at 1500 ppm and achieves complete inhibition at 1800 ppm, demonstrating significantly superior efficacy compared to similar products on the market.

How effective is Aisuanling 9001 in practical applications? Joint experiments conducted by the Acid Innovation Center with several leading academic institutions—including the Institute of Animal Nutrition at Sichuan Agricultural University, the Subtropical Ecology Institute of the Chinese Academy of Sciences, and Jiangxi Agricultural University—have demonstrated that:

4.1 Degree of dissociation of Aisuanling 9001 in aqueous solution: After dissolving in water, the pH of Aisuanling 9001 gradually decreases over time. The results show that after 4 hours, the pH of the aqueous solution has decreased by only 0.27, indicating that Aisuanling 9001 exhibits a low degree of dissociation and can remain in molecular form for an extended period, thereby conferring long-lasting antibacterial activity.

4.2 Artificial gastric simulation of the controlled-release performance of Aisuanling 9001: In artificial gastric fluid, after 1 hour, Aisuanling 9001 exhibited a retention rate as high as 74.7%, and after 2 hours, it still maintained a retention rate of 69.3%. In contrast, the retention rate of benzoic acid raw powder was only 21.6% after 1 hour and extremely low after 2 hours.

4.3 In vitro simulated intestinal release of Aisuanling 9001: In artificial intestinal fluid, benzoic acid in its original powder form was completely released by 1 hour. By 4 hours, the retention rate of Aisuanling 9001 had decreased gradually from 70.1% at 1 hour to 49.1%; by 5 hours, it further declined to 32.5%, and by 6 hours, it reached 10.5%, demonstrating sustained antibacterial activity in the distal intestine.

4.4 Application trial of Aisuanling 9001 in animal production: Results from trials conducted at the nuacid Innovation Center’s animal testing facility and on weaned piglets at a breeding company in Guangdong Province demonstrate that adding just 1 kg of Aisuanling 9001 per ton of feed significantly reduces diarrhea and improves intestinal health, with efficacy superior to that achieved by adding 3 kg of pure benzoic acid.

Summary

 

Written by: Emperor Cheng

Review: Hu Youjun