A composition for reducing gastroesophageal reflux in an individual, and methods of making and using the same
By combining lactoglucosidin, medium- and long-chain triglycerides, human milk oligosaccharides, and immunoglobulin G, the multiple links in the existing gastroesophageal reflux disease are solved, achieving comprehensive intervention for gastroesophageal reflux, significantly reducing reflux frequency and flow, and enhancing mucosal repair capacity.
Patent Information
- Application Number
- CN202610764186.0
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2026-05-29
- Publication Date
- 2026-07-14
Smart Images
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Abstract
Description
Technical Field
[0001] This invention relates to the field of food technology, and in particular to a composition for reducing gastroesophageal reflux in individuals, its preparation method, and its application. Background Technology
[0002] Gastroesophageal reflux (GER) refers to a series of symptoms caused by the reflux of stomach and duodenal contents into the esophagus. Its incidence rate is as high as 50%–70% in infancy and 10%–30% in adults. The pathophysiological mechanism of GER is complex, involving multiple factors such as transient lower esophageal sphincter relaxation (TLESR), decreased esophageal clearance capacity, delayed gastric emptying, and impaired esophageal mucosal barrier function.
[0003] Currently, commonly used clinical interventions for gastroesophageal reflux disease (GERD) include pharmacological intervention, dietary thickening, combined pharmacological and dietary intervention, and surgical intervention. Medications include proton pump inhibitors (PPIs) and H2 receptor antagonists, which suppress acidity. While these drugs can alleviate GERD symptoms by reducing the acidity of refluxed material, long-term use may lead to adverse reactions such as malabsorption, gut microbiota dysbiosis, and increased risk of osteoporosis. Furthermore, these acid-suppressing drugs are ineffective against non-acidic reflux. Dietary thickening involves adding thickeners such as lactobacillus and rice starch to the diet to physically reduce reflux by increasing the viscosity of gastric contents. Thickened formula foods are currently the standard nutritional intervention for GERD management, but their mechanism of action is singular, relying solely on physical thickening and failing to address fundamental issues such as esophageal mucosal repair, inflammation control, and improved gastric emptying. While combining acid-suppressing drugs with thickened formula foods (i.e., combined pharmacological and dietary intervention) can partially synergistically improve symptoms, it suffers from poor adherence to multiple medication regimens and high costs. In surgical interventions, fundoplication is suitable for severe gastroesophageal reflux, but it is highly invasive, expensive, and carries the risk of postoperative complications.
[0004] Existing thickening-type formula foods only target the single physical barrier mechanism, failing to address multiple aspects simultaneously, such as esophageal mucosal repair, immune inflammation regulation, and improved gastric emptying. Therefore, there is an urgent need to develop an intervention composition that is synergistically effective through multiple mechanisms, safe, efficient, and suitable for long-term use. Summary of the Invention
[0005] To address the aforementioned problems, this invention provides a composition for reducing individual gastroesophageal reflux, its preparation method, and its application. Through the design of the composition, a triple synergistic mechanism of physical barrier, reduction of gastric acid secretion, and enhancement of mucosal repair capacity is employed, which effectively reduces the frequency and amount of individual gastroesophageal reflux.
[0006] To achieve the above-mentioned objectives, the present invention adopts the following technical solution: In a first aspect, the present invention provides a composition for reducing gastroesophageal reflux in individuals, comprising lactoglucosidin, medium- and long-chain triglycerides, human milk oligosaccharides, and immunoglobulin G.
[0007] Compared to existing technologies, the composition provided by this invention for reducing individual gastroesophageal reflux utilizes agglutinin to form a weak gel in the acidic environment of the stomach, increasing the viscosity of gastric contents and physically reducing the frequency and volume of reflux. The formed gel also slows gastric emptying, increasing satiety and reducing reflux triggering from a dynamic perspective. Medium- and long-chain triglycerides (MLCTs) produce medium- and long-chain fatty acids during metabolism, which may indirectly regulate gastric acid secretion by affecting the metabolism or signal transduction of gastric mucosal cells. Furthermore, MLCTs may inhibit the activity of enzymes or gene expression related to gastric acid secretion in gastric parietal cells, reducing gastric acid secretion and decreasing the stimulation of the esophageal mucosa, thereby alleviating reflux symptoms. Human milk oligosaccharides (HMOs) and immunoglobulin G (IgG) can enhance the repair and regeneration of esophageal mucosal cells, helping to restore the integrity of the esophageal mucosa.
[0008] Preferably, the composition comprises the following components in parts by weight: 1 to 10 parts of milk agglutinin, 3 to 20 parts of medium- and long-chain triglycerides, 6 to 25 parts of human milk oligosaccharides, and 0.01 to 0.2 parts of immunoglobulin G.
[0009] Preferably, the human milk oligosaccharide includes 2'-fucosylated lactose (2'-FL) and lactose-N-neotetrasaccharide (LNnT).
[0010] More preferably, the mass ratio of 2'-fucosylated lactose to lactose-N-neotetrasaccharide in the human milk oligosaccharide is (5~15):(1~10).
[0011] More preferably, the composition comprises the following components in parts by weight: 1 to 10 parts of lactose agglutinin, 3 to 20 parts of medium- and long-chain triglycerides, 5 to 15 parts of 2'-fucosylated lactose, 1 to 10 parts of lactose-N-neotetrasaccharide, and 0.01 to 0.2 parts of immunoglobulin G.
[0012] More preferably, the composition comprises the following components in parts by weight: 2 to 5 parts of lactose agglutinin, 4 to 12 parts of medium- and long-chain triglycerides, 6 to 12 parts of 2'-fucosylated lactose, 2 to 8 parts of lactose-N-neotetrasaccharide, and 0.02 to 0.15 parts of immunoglobulin G.
[0013] More preferably, the composition comprises the following components in parts by weight: 2.5 to 4 parts of lactose agglutinin, 5 to 10 parts of medium- and long-chain triglycerides, 7 to 10 parts of 2'-fucosylated lactose, 3 to 6 parts of lactose-N-neotetrasaccharide, and 0.02 to 0.1 parts of immunoglobulin G.
[0014] In a second aspect, the present invention provides a method for preparing the composition for reducing individual gastroesophageal reflux, comprising the following steps: A composition for reducing gastroesophageal reflux is obtained by uniformly mixing lactulin, medium- and long-chain triglycerides, human milk oligosaccharides, and immunoglobulin G.
[0015] Preferably, the human milk oligosaccharide includes 2'-fucosylated lactose and lactose-N-neotetrasaccharide.
[0016] Thirdly, the present invention provides a product comprising the aforementioned composition for reducing individual gastroesophageal reflux.
[0017] Preferably, the product includes foods for special medical purposes.
[0018] The present invention has the following beneficial effects: The composition provided by this invention for reducing individual gastroesophageal reflux disease (GERD) comprises lactoglucosin, medium- and long-chain triglycerides, human milk oligosaccharides, and immunoglobulin G. This invention, through the combination of these four core components, constructs a multi-target synergistic intervention mechanism combining physical protection, secretion regulation, and tissue repair, comprehensively blocking the occurrence and development of GERD. Lactoglucosin constructs a physical barrier, reducing the risk of reflux dynamics at its source; medium- and long-chain triglycerides precisely regulate gastric acid secretion, reducing chemical stimulation; and human milk oligosaccharides combined with immunoglobulin G strengthen the mucosal immune barrier, promoting damage repair. This multi-target synergistic effect, with the combined application of the four main components, simultaneously covers the four core pathological aspects of GERD (abnormal reflux dynamics, excessive gastric acid secretion, weakened mucosal defense, and delayed damage repair), achieving a closed-loop intervention from prevention and relief to repair, significantly improving clinical outcomes. Detailed Implementation
[0019] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to embodiments. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the invention.
[0020] Unless otherwise specified, all materials used in the embodiments of this invention can be obtained through commercial channels or prepared by conventional methods in the art.
[0021] Example 1 This embodiment provides a composition for reducing individual gastroesophageal reflux, comprising the following components in parts by weight: 3 parts of lactoglucosin, 8 parts of medium- and long-chain triglycerides, 7.9 parts of 2'-FL, 4.3 parts of LNnT, and 0.06 parts of IgG.
[0022] The preparation method of the above composition for reducing gastroesophageal reflux in an individual comprises the following steps: Weigh each component according to the designed ratio, and mix the above components evenly in a dry mixer to obtain the composition for reducing gastroesophageal reflux in an individual.
[0023] Example 2 This example provides a composition for reducing gastroesophageal reflux in an individual, comprising the following components in parts by mass: 2 parts of lactoagglutinin, 12 parts of medium-chain triglycerides, 6 parts of 2'-FL, 8 parts of LNnT, and 0.02 parts of IgG.
[0024] The preparation method of the above composition for reducing gastroesophageal reflux in an individual is the same as that in Example 1 and will not be elaborated here.
[0025] Example 3 This example provides a composition for reducing gastroesophageal reflux in an individual, comprising the following components in parts by mass: 5 parts of lactoagglutinin, 4 parts of medium-chain triglycerides, 12 parts of 2'-FL, 2 parts of LNnT, and 0.15 parts of IgG.
[0026] The preparation method of the above composition for reducing gastroesophageal reflux in an individual is the same as that in Example 1 and will not be elaborated here.
[0027] Animal experiment verification 1. Experimental animals and grouping Healthy adult SD rats were selected for the experiment, provided by Spf (Suzhou) Biotechnology Co., Ltd. (China), with the certificate number SCXK (Su) 2022-0006, and the body weight was 200 g to 300 g. The rats were required to be adaptively raised in a constant temperature (22°C to 25°C) and constant humidity (50% to 60%) environment for 1 week, with free access to food and water to ensure good physical condition. A relaxant (such as a vasodilator like nitroglycerin or a specific neurotransmitter regulator) was locally injected near the lower esophageal sphincter, and the sphincter relaxation was observed. When the LES pressure dropped to ≤5 mmHg, it indicated that the sphincter had been fully relaxed and reached the required relaxation state for the experiment.
[0028] Fasting was maintained for 24 hours preoperatively, but water intake was permitted to minimize interference from stomach contents. Rats were anesthetized using isoflurane inhalation anesthesia or intraperitoneal injection of sodium pentobarbital (dosage adjusted according to rat weight). The rats were then fixed in a supine position on the operating table, with their limbs secured with clips to maintain a clear airway. The skin and subcutaneous tissue were incised along the midline of the xiphoid process in the upper abdomen, allowing entry into the abdominal cavity layer by layer. The incision length was approximately 1-2 cm, exposing the stomach. The hepatogastric ligament was severed, and the esophagus was freed, taking care to preserve the vagus nerve. A 1-1.5 cm incision was made along the long axis at the esophagogastric junction and at the free edge of the duodenum 1 cm from the pylorus for a lateral esophagoduodenal anastomosis, sutured using 3 / 0 suture needles, preserving the entire stomach. Before closing the abdomen, 10-20 mL of 0.9% sodium chloride injection solution was poured into the abdominal cavity to flush it, and then the abdominal wall was sutured layer by layer.
[0029] Rats that successfully developed the model were randomly divided into 17 groups, with 12 rats in each group, as shown in Table 1. Rats in each group were administered the medication by gavage once daily for 14 consecutive days. The concentration of the composition in treatment groups G2-G17 was 10 mg / kg, and the specific volume administered each time was 2.5 mL. Esophageal pH was monitored for 24 hours after the last gavage, and the number of reflux events was recorded. After 24 hours of monitoring, the rats were anesthetized and sacrificed, and esophageal tissue was collected for mucosal damage index scoring and to detect the levels of inflammatory factors IL-6 and TNF-α. Gastric fluid was collected for 4 hours using the pyloric ligation method to measure gastric acid secretion.
[0030] Table 1 Experimental group design
[0031] 2. Experimental Results (1) Comparison of esophageal mucosal injury index After the esophagus was cut open, the morphology, length, and extent of the mucosal damage were assessed immediately. The scoring criteria are shown in Table 2, and the scoring results are shown in Table 3. A higher score indicates a more severe injury.
[0032] Table 2. Scoring criteria for esophageal mucosal injury index
[0033] Table 3. Esophageal Mucosal Injury Index Scoring Results
[0034] As can be seen from the table above, the esophageal mucosal injury index scores of groups G15 to G17 were significantly lower than those of the model group, and significantly lower than those of the single group (G2 to G5), the double group (G6 to G11), and the triple group (G12 to G14) (p < 0.05).
[0035] (2) Comparison of inflammatory factor levels The levels of IL-6 and TNF-α in esophageal tissue are shown in Table 4.
[0036]
[0037] Table 4. Levels of inflammatory factors in esophageal tissue As can be seen from the table above, the levels of IL-6 and TNF-α in the esophageal tissue of the G15 group were reduced by 70.4% and 74.4% respectively compared with the model group, which was significantly better than other groups (p<0.05).
[0038] (3) Comparison of the overall improvement rate of gastroesophageal reflux Based on the number of reflux events, the overall improvement rate of gastroesophageal reflux in each group compared to the model group was calculated, and the results are shown in Table 5. Overall improvement rate = (1 - number of reflux events in the treatment group / number of reflux events in the model group) × 100%.
[0039] Table 5 Results of the overall improvement rate of gastroesophageal reflux
[0040] As can be seen from the table above, the overall improvement rate of gastroesophageal reflux with single-component (G2~G5) is only 8%~15%, the overall improvement rate of gastroesophageal reflux with two-component (G6~G11) is 30%~43%, and the overall improvement rate of gastroesophageal reflux with three-component (G12~G14) is 50%~60%; while the overall improvement rate of gastroesophageal reflux with the four-component combination (G15~G17) of this invention is over 83%, which is significantly better than the other groups (p<0.05).
[0041] (4) Comparison of gastric acid secretion and improvement rate The results of gastric acid secretion are shown in Table 6.
[0042] Table 6. Esophageal Mucosal Injury Index Scoring Results
[0043] As can be seen from the table above, compared with the model group, the gastric acid secretion of the G15~G17 groups of the present invention was significantly reduced, which was significantly better than other groups (p<0.05). Among them, the gastric acid secretion in the esophageal tissue of the G15 group reached the lowest level (102.5μmol / 4h).
[0044] In summary, the composition provided by this invention for reducing individual gastroesophageal reflux disease (GERD) exhibits a super-additive synergistic effect among its four components: lactoglucan, medium- and long-chain triglycerides, human milk oligosaccharides, and immunoglobulin G. The four core indicators comprehensively demonstrate from three dimensions—function, structure, and molecular mechanism—that this invention achieves comprehensive intervention in GERD through a triple synergistic mechanism of physical barrier action, reduction of gastric acid secretion, and enhancement of mucosal repair capacity. Its effect is significantly superior to any single component, two-component, or three-component combination.
[0045] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions or improvements made within the spirit and principles of the present invention should be included within the protection scope of the present invention.
Claims
1. A composition for reducing individual gastroesophageal reflux, characterized in that: It includes lactohemagglutinin, medium- and long-chain triglycerides, human milk oligosaccharides, and immunoglobulin G.
2. The composition for reducing individual gastroesophageal reflux as described in claim 1, characterized in that: The composition comprises the following components in parts by weight: 1 to 10 parts of milk agglutinin, 3 to 20 parts of medium- and long-chain triglycerides, 6 to 25 parts of human milk oligosaccharides, and 0.01 to 0.2 parts of immunoglobulin G.
3. The composition for reducing individual gastroesophageal reflux as described in claim 1, characterized in that: The human milk oligosaccharides include 2'-fucosylated lactose and lactose-N-neotetrasaccharide.
4. The composition for reducing individual gastroesophageal reflux as described in claim 3, characterized in that: The mass ratio of 2'-fucosylated lactose to lactose-N-neotetrasaccharide in the human milk oligosaccharide is (5~15):(1~10).
5. The composition for reducing individual gastroesophageal reflux as described in claim 4, characterized in that: The composition comprises the following components in parts by weight: 2 to 5 parts of lactose agglutinin, 4 to 12 parts of medium- and long-chain triglycerides, 6 to 12 parts of 2'-fucosylated lactose, 2 to 8 parts of lactose-N-neotetrasaccharide, and 0.02 to 0.15 parts of immunoglobulin G.
6. The composition for reducing individual gastroesophageal reflux as described in claim 5, characterized in that: The composition comprises the following components in parts by weight: 2.5 to 4 parts of lactose agglutinin, 5 to 10 parts of medium- and long-chain triglycerides, 7 to 10 parts of 2'-fucosylated lactose, 3 to 6 parts of lactose-N-neotetrasaccharide, and 0.02 to 0.1 parts of immunoglobulin G.
7. A method for preparing the composition for reducing individual gastroesophageal reflux according to any one of claims 1 to 6, characterized in that: Includes the following steps: A composition for reducing gastroesophageal reflux is obtained by uniformly mixing lactulin, medium- and long-chain triglycerides, human milk oligosaccharides, and immunoglobulin G.
8. The method for preparing the composition for reducing individual gastroesophageal reflux as described in claim 7, characterized in that: The human milk oligosaccharides include 2'-fucosylated lactose and lactose-N-neotetrasaccharide.
9. A product, characterized in that: Includes the composition for reducing individual gastroesophageal reflux as described in any one of claims 1 to 6.
10. The product as described in claim 9, characterized in that: The products include foods formulated for special medical purposes.