Particle structure of a nutrient composition to reduce colonization by Helicobacter pylori, to reduce inflammation of the gastric mucosa and to promote the repair of the esophageal barrier.

Abstract

Particle structure of a nutrient composition for reducing colonization by Helicobacter pylori, reducing inflammation of the gastric mucosa and promoting the repair of the esophageal barrier, comprising a core layer, a binder layer and an antioxidant layer, wherein the core layer contains a chocolate paprika extract and piperine, the binder layer consists of a honey complex and envelops the core layer so that the structure of the core layer is stabilized, the honey complex is formed by mixing honey and turmeric extract powder and the antioxidant layer contains sea buckthorn powder and envelops the binder layer.

Description

Field of invention

[0001] The present invention relates to a beverage with a particle structure which contains a nutrient composition, in particular a particle structure of a nutrient composition for reducing colonization by Helicobacter pylori, for reducing inflammation of the gastric mucosa and for promoting the repair of the esophageal barrier. State of the art

[0002] Gastritis, or inflammation of the stomach lining, is one of the most common digestive disorders worldwide and can be clinically divided into acute and chronic forms. Symptoms include bloating and stomach pain, heartburn, nausea, and decreased appetite. Chronic gastritis that is not adequately controlled in the long term can not only lead to stomach ulcers but also further increase the risk of stomach cancer. The causes of gastritis are varied, with infection by Helicobacter pylori (H. pylori) being the most well-known and crucial cause.

[0003] Helicobacter pylori is a gram-negative bacterium that can survive in a highly acidic environment. Through the secretion of urease, it breaks down urea into ammonia, thereby neutralizing the acidic environment in the stomach and enabling long-term colonization of the gastric mucosa. This bacterium can release various toxins and enzymes that damage the integrity of the gastric epithelial cells and the esophagus, triggering a persistent immune and inflammatory response. The World Health Organization (WHO) has already classified Helicobacter pylori as a "Group 1 carcinogen," demonstrating that its threat to human health cannot be underestimated.

[0004] Currently, most health products and dietary supplements available on the market focus solely on alleviating gastroesophageal reflux or protecting the gastric mucosa, for example, through the use of calcium carbonate or mucosal protectants to reduce irritation from stomach acid. Products specifically designed to combat Helicobacter pylori colonization, control inflammatory responses, and repair the gastric mucosal barrier—thus offering a comprehensive preventative health effect—are rare.

[0005] The present invention therefore addresses the aforementioned problems and proposes a particle structure of a nutrient composition for reducing colonization by Helicobacter pylori, reducing inflammation of the gastric mucosa and promoting the repair of the esophageal barrier, thereby effectively reducing the occurrence of gastric mucosal inflammation and associated complications and fulfilling the requirements not met by the prior art. Content of the invention

[0006] In light of this, there is an urgent need for a particle structure of a nutrient composition to reduce colonization by Helicobacter pylori, to reduce inflammation of the gastric mucosa and to promote the repair of the esophageal barrier in order to solve the aforementioned problem.

[0007] The present invention provides a particle structure of a nutrient composition for reducing colonization by Helicobacter pylori, reducing inflammation of the gastric mucosa, and promoting the repair of the esophageal barrier. This solves the problem of the difficulty in obtaining sufficient amounts of nutrients from the daily diet to support gastric health, thus effectively reducing the incidence of gastritis and its associated complications.

[0008] To solve the problems of the prior art, the present invention provides the following technical means: a particle structure of a nutrient composition for reducing colonization by Helicobacter pylori, reducing inflammation of the gastric mucosa, and promoting the repair of the esophageal barrier. The particle structure comprises a core layer, a binder layer, and an antioxidant layer, wherein the core layer contains chocolate paprika extract and piperine, the binder layer consists of a honey complex and surrounds the core layer, thus stabilizing its structure, the honey complex is formed by mixing honey and turmeric extract powder, and the antioxidant layer contains sea buckthorn powder and surrounds the binder layer.

[0009] In the particle structure according to the invention of a nutrient composition for reducing colonization by Helicobacter pylori, reducing inflammation of the gastric mucosa and promoting the repair of the esophageal barrier, the diameter of the particle structure is in the range of 1 µm to 10 mm.

[0010] In the particle structure according to the invention of a nutrient composition for reducing colonization by Helicobacter pylori, reducing inflammation of the gastric mucosa and promoting the repair of the esophageal barrier, the volume fraction of the core layer is 40% to 50% of the total volume of the particle structure.

[0011] In the particle structure according to the invention of a nutrient composition for reducing colonization by Helicobacter pylori, reducing inflammation of the gastric mucosa and promoting the repair of the esophageal barrier, the volume fraction of the binder layer is 30% to 40% of the total volume of the particle structure.

[0012] In the particle structure according to the invention of a nutrient composition for reducing colonization by Helicobacter pylori, reducing inflammation of the gastric mucosa and promoting the repair of the esophageal barrier, the volume fraction of the antioxidant layer is 10% to 20% of the total volume of the particle structure.

[0013] The particle structure according to the invention of a nutrient composition for reducing colonization by Helicobacter pylori, reducing inflammation of the gastric mucosa and promoting the repair of the esophageal barrier can be mixed into liquid drinks, gel preparations, tablets and other food supplements.

[0014] The technical features of the present invention solve the problem that conventional health products and dietary supplements available on the market focus predominantly only on alleviating gastroesophageal reflux or protecting the gastric mucosa. In contrast, the technical features of the present invention provide a comprehensive nutrient composition in the form of a particle structure, which simultaneously reduces colonization by Helicobacter pylori, reduces inflammation of the gastric mucosa, and promotes the repair of the esophageal barrier. Brief description of the drawings Fig. Figure 1 shows a perspective view of a first embodiment of the particle structure according to the present invention; Fig. Figure 2 shows a diagram of the experimental results, demonstrating the inhibition of the production of the inflammation-associated cytokine IL-1β by the composition of the particle structure of the present invention; Fig. Figure 3 shows a diagram of the experimental results, demonstrating the inhibition of the production of the inflammation-associated cytokine IL-6 by the composition of the particle structure of the present invention; Fig. Figure 4 shows a diagram of the experimental results, demonstrating the inhibition of the production of the inflammation-associated cytokine IL-18 by the composition of the particle structure of the present invention; Fig. Figure 5 shows a diagram of the experimental results, which demonstrates the inhibition of the production of the inflammation-associated cytokine IL-10 by the composition of the particle structure of the present invention; Fig. Figure 6 shows a diagram of the experimental results, which demonstrates the promotion of gastric mucin production by the composition of the particle structure of the present invention; Fig. Figure 7 shows a diagram of the experimental results, which demonstrates the inhibition of the growth of Helicobacter pylori by the composition of the particle structure of the present invention. Detailed description of the exemplary implementations

[0015] Exemplary embodiments of the present invention are explained in more detail below with reference to the accompanying drawings. The exemplary embodiments given below serve only to illustrate the present invention and are not intended to limit the scope of protection of the present invention. All equivalent changes and modifications that can be made by a person skilled in the art in this field according to the description and drawings of the invention fall within the scope of protection of the present invention. The scope of protection of the invention is defined by the accompanying claims.

[0016] As in Fig. Figure 1 shows a first embodiment of the present invention providing a particle structure of a nutrient composition for reducing colonization by Helicobacter pylori, reducing inflammation of the gastric mucosa, and promoting the repair of the esophageal barrier 10. The particle structure 10 comprises a core layer 20, a binder layer 30, and an antioxidant layer 40, wherein the core layer 20 contains a chocolate paprika extract and piperine, the binder layer 30 consists of a honey complex and surrounds the core layer 20, thus stabilizing the structure of the core layer 20, and the antioxidant layer 40 contains sea buckthorn powder and surrounds the binder layer 30.

[0017] According to a preferred embodiment of the present invention, the nutrient composition comprises chocolate paprika extract and piperine in the core layer 20, honey complex in the binder layer 30, and sea buckthorn powder in the antioxidant layer 40.

[0018] According to a preferred embodiment of the present invention, the binder layer 30 consists of a honey complex, wherein the honey complex is formed by mixing honey and turmeric extract powder. With regard to the choice of honey, Leptospermum honey (Manuka) may preferably be selected.

[0019] The particle structure of a nutrient composition according to the invention for reducing colonization by Helicobacter pylori, reducing inflammation of the gastric mucosa, and promoting the repair of the esophageal barrier 10 is water-soluble and forms a uniformly dispersed solution. The size of the particle structure 10 is designed such that no perceptible particle sensation occurs when a person drinks it, allowing beverages to be produced from it that can be filled into containers and used or sold.

[0020] According to a preferred embodiment of the present invention, the spherical diameter of the particle structure of a nutrient composition for reducing colonization by Helicobacter pylori, reducing inflammation of the gastric mucosa and promoting the repair of the esophageal barrier 10 is in the range of 1 µm to 1 mm.

[0021] According to a preferred embodiment of the present invention, the volume fraction of the core layer 20 is 40% to 50% of the total volume of the particle structure of a nutrient composition for reducing colonization by Helicobacter pylori, reducing inflammation of the gastric mucosa and promoting the repair of the esophageal barrier 10.

[0022] According to a preferred embodiment of the present invention, the volume fraction of the binder layer is 30% to 40% of the total volume of the particle structure of a nutrient composition for reducing colonization by Helicobacter pylori, reducing inflammation of the gastric mucosa and promoting the repair of the esophageal barrier 10.

[0023] According to a preferred embodiment of the present invention, the volume fraction of the antioxidant layer is 40 10% to 20% of the total volume of the particle structure of a nutrient composition for reducing colonization by Helicobacter pylori, reducing inflammation of the gastric mucosa and promoting the repair of the esophageal barrier 10. Example 1: Detection of the inflammation-related cytokines IL-1β, IL-6, IL-10 and IL-18

[0024] In this experiment, peripheral blood mononuclear cells (PBMCs) obtained from ATCC (article number: PCS-800-011) were used. In this embodiment, lipopolysaccharide (LPS) was used to induce an inflammatory cellular response.

[0025] Initially, 24-well culture plates were used, with 1×10 in each well. 6Peripheral blood mononuclear cells and 1 ml of X-VIVO™ 10 culture medium (obtained from Lonza) were introduced and cultured for 24 hours. The X-VIVO™ 10 culture medium contained 10% fetal calf serum, 1% penicillin / streptomycin, and the remainder RPMI-1640 basal medium.

[0026] The cultured peripheral blood mononuclear cells were divided into six groups, namely a blank group, a control group, and experimental groups 1 to 4.

[0027] Blank group and control group: Addition of 500 µl of X-VIVO™ 10 culture medium.

[0028] Experimental group 1: Addition of 500 µl X-VIVO™ 10 culture medium and 2% (v / v) turmeric.

[0029] Experimental group 2: Addition of 500 µl X-VIVO™ 10 culture medium and 2% (v / v) honey.

[0030] Experimental group 3: Addition of 500 µl X-VIVO™ 10 culture medium and 2% (v / v) of a composition of turmeric, honey and sea buckthorn.

[0031] Experimental group 4: Addition of 500 µl X-VIVO™ 10 culture medium and 2% (v / v) of a composition of turmeric, honey, sea buckthorn, piperine and chocolate paprika.

[0032] After a 1-hour cell culture, 100 ng / ml of lipopolysaccharide (LPS) was added to the X-VIVO™ 10 culture medium in the control group and in experimental groups 1 to 4, and then incubated for 16 hours at 37 °C. After 16 hours, the liquid culture media from all groups were collected and centrifuged for 7 minutes at 400 g to obtain a supernatant.

[0033] The concentrations of cytokines (IL-1β, IL-6, IL-10, IL-18) in the supernatant were analyzed using a filter plate (BioLegend, product: LEGENDplex™ Human Inflammation Panel). Data acquisition was performed using a BD Accuri C6 Plus flow cytometer (BD Biosciences). Subsequently, the data were analyzed using the LEGENDplex data analysis software (BioLegend). The experimental results are presented in Fig. 2 to Fig. 5 shown.

[0034] As from the Fig. 2 to Fig. As can be seen in Figure 5, the LPS-treated control group induced a significantly increased expression of the pro-inflammatory cytokines IL-1β, IL-6, IL-18, and IL-10 compared to the blank group. If the expression levels of IL-1β, IL-6, IL-18, and IL-10 in the control group are set to 1 (i.e., 100%), the results in Figure 5 show that the LPS-treated control group, compared to the blank group, showed a significantly increased expression of the pro-inflammatory cytokines IL-1β, IL-6, IL-18, and IL-10. Fig. 2 to Fig. The results presented in Figure 5 are as follows: In experimental group 1, which used a liquid culture medium containing only turmeric, the changes in all cytokines were minimal. IL-1β and IL-6 remained above 90% of the LPS-induced levels, while IL-10 and IL-18 were slightly reduced to 74.5 ± 8.96% and 75.1 ± 4.50%, respectively. In experimental group 2, which used a liquid culture medium containing only Leptospermum honey, an improved inhibitory effect was observed, particularly for IL-1β (83.2 ± 9.59%; p < 0.05 vs. LPS). This suggests that, in addition to its antioxidant properties, Leptospermum honey also possesses pronounced anti-inflammatory activity and an intrinsic potential for cytokine regulation. In experimental group 3, which contained a combination of turmeric, honey and sea buckthorn, a stronger and more consistent reduction in cytokines was observed.IL-1β was reduced to 84.7 ± 2.10% (p < 0.01), IL-10 to 69.5 ± 4.26% (p < 0.05), and IL-18 to 74.5 ± 5.03%. However, the reduction of IL-6 remained largely unchanged at 96.5 ± 4.15%, indicating that the combination of turmeric, honey, and sea buckthorn has only a limited effect on this cytokine signaling pathway. Notably, experimental group 4, which contained a combination of turmeric, honey, sea buckthorn, piperine, and chocolate paprika, showed an inhibitory effect on all cytokines examined. Compared to LPS treatment alone, IL-1β was reduced to 72.5 ± 4.58% (p < 0.001), IL-6 to 86.0 ± 5.89% (p < 0.05), IL-10 to 65.7 ± 4.20% (p < 0.05) and IL-18 to 63.8 ± 4.78% (p < 0.05).Experimental group 4 demonstrated that the combination of turmeric, honey, sea buckthorn, piperine, and chocolate paprika exhibited superior inhibitory activity against IL-1β, IL-6, IL-18, and IL-10, thereby enabling a broad reduction of the inflammatory signaling cascade. Furthermore, while turmeric and honey each possess some anti-inflammatory activity, a synergistic effect of the complete formulation is required for maximum inhibition of LPS-induced cytokine production in peripheral blood mononuclear cells (PBMCs), supporting a synergistic and multiple mechanism of action. Example 2: Experiment on the secretion of gastric mucin

[0035] A sufficient amount of gastric mucin can protect the stomach lining. In this experiment, human gastric epithelial cells (hereinafter referred to as gastric epithelial cells) were used, derived from the AGS cell line (ATCC CRL-1739™) from the American Type Culture Collection (ATCC). ® ) were obtained.

[0036] Initially, 96-well culture plates were used, with 1×10 in each well. 4 Gastric epithelial cells and 0.2 ml of RPMI-1640 culture medium were introduced and cultured for 24 hours. The RPMI-1640 culture medium contained 10% fetal calf serum and 1% penicillin / streptomycin.

[0037] The cultured gastric epithelial cells were divided into three groups: a blank group, a control group, and an experimental group.

[0038] Blank group: No treatment was performed. Instead, 200 µl of fresh RPMI-1640 culture medium was added and the cells were then cultured for 48 hours at 37 °C.

[0039] Control group: 10 µg / ml lipopolysaccharide (LPS) was added to 200 µl of fresh RPMI-1640 culture medium, followed by cultivation at 37 °C for 48 hours.

[0040] Experimental group: 10 µg / ml lipopolysaccharide (LPS) and 2% (v / v) of a composition of turmeric, honey, sea buckthorn, piperine and chocolate paprika were added, followed by cultivation at 37°C for 48 hours.

[0041] After 48 hours of cell culture, 100 µl of the culture medium (liquid) was taken from each group and transferred to 1.5 ml microcentrifuge tubes. An ELISA kit (enzyme immunoassay) (Elabscience, Cat. E-EL-H2280) was then used to determine the content of gastric mucin MUC5B.

[0042] It is particularly important to note that the results presented in the following figures are given as relative values. The standard deviation was calculated using the STDEV function in Excel. A one-sided Student's t-test was also performed in Excel to determine whether there were statistically significant differences. In the figures, the symbol "*" indicates a p-value < 0.05, the symbol "**" a p-value < 0.01, and the symbol "***" a p-value < 0.001. The more "*" symbols are displayed, the more significant the statistical difference. Compared to the LPS treatment, the symbol "###" indicates that p < 0.001.

[0043] The purpose of this experiment was to confirm whether the composition of the experimental group was capable of normalizing the disturbance in gastric mucin secretion caused by lipopolysaccharide-induced inflammation in gastric epithelial cells. The results are presented in Fig. Figure 6 illustrates this. When the gastric mucin content measured in the blank group is set to 100 (i.e., 100%), the control group, in which an inflammatory response of gastric cells was induced using LPS, showed an abnormally increased secretion of gastric mucin MUC5B by 22.6%. This represents a protective response of the stomach and indicates impaired gastric function. Compared to the LPS control group, the experimental group showed a significant reduction in MUC5B secretion of 21.2%, thus restoring the value almost to normal levels. This suggests that the experimental group helps to reduce abnormal mucus secretion under inflammatory conditions, maintain normal gastric function, and decrease the risk of gastric disease.The results further confirm that the combination of turmeric, honey, sea buckthorn, piperine, and chocolate paprika not only inhibits lipopolysaccharide-induced excessive mucin production but can also maintain gastric mucosal homeostasis. Statistically, the p-value of the experimental group compared to the control group is < 0.001, indicating a highly significant difference. Example 3: Growth experiment of Helicobacter pylori

[0044] Helicobacter pylori is a gram-negative, spiral-shaped bacterium closely associated with diseases such as gastritis, peptic ulcers, and stomach cancer. The present experiment serves to evaluate the inhibitory effect of the particle structure according to the invention on Helicobacter pylori using the disc diffusion method.

[0045] To further confirm the influence of the particle structure according to the invention on Helicobacter pylori, a BD culture medium was used in the activation step, which was produced from BHI culture medium with the addition of 5% sheep blood.

[0046] First, an activation step for Helicobacter pylori was performed. The Helicobacter pylori strain (ATCC 43504) obtained from the Food Industry Research and Development Institute (FIRDI) was used. Cultivation was carried out at 37 °C for 72 hours to complete activation, using an inoculation ratio of 10% Helicobacter pylori bacterial suspension to 90% of the aforementioned BD culture medium.

[0047] Subsequently, an evaluation of the influence of the particle structure according to the invention on the growth of Helicobacter pylori was carried out. The culture medium used in the evaluation step was BD Trypticase Soy Agar II, which was also prepared from culture medium with the addition of 5% sheep blood.

[0048] In the experimental group, 100 µl of the previously activated Helicobacter pylori culture was applied to the BD culture medium. Subsequently, a portion of the culture medium was removed, creating an agar borehole with a diameter of 5 mm. Then, 20 µl of supernatant of the particle structure according to the invention was introduced into the agar borehole and cultured at 37 °C for 72 hours, after which the appearance of an inhibition zone was observed.

[0049] In the Blank group, the activated Helicobacter pylori culture was also applied to the BD culture medium. Subsequently, a portion of the culture medium was removed to create an agar borehole. Cultivation then took place at 37 °C for 72 hours to observe the appearance of an inhibition zone.

[0050] With reference to Fig. Figure 7 shows that the experimental group exhibited a clearly identifiable inhibition zone, while no inhibition zone was observed in the blank group. An actual measurement revealed that the area of ​​the inhibition zone in the experimental group was 754.8 mm². 2 The area covered by the Helicobacter pylori culture was 2165 mm². 2The inhibition rate was approximately 34.9%. This demonstrated that the test group exhibited good inhibitory activity against Helicobacter pylori. It is evident from this that the particle structure according to the invention can effectively inhibit the growth of Helicobacter pylori and thus contributes to supporting gastric health.

[0051] In summary, the technical features of the present invention provide a comprehensive nutrient composition that simultaneously reduces colonization by Helicobacter pylori, reduces inflammation of the gastric mucosa, and promotes the repair of the esophageal barrier, wherein a particle structure of the nutrient composition 10 is provided. The particle structure 10 is an edible colloid. The diameter of the particle structure 10 ranges from 1 µm to 10 mm. The volume fraction of the core layer 20 is 40% to 50% of the total volume of the particle structure. The volume fraction of the binder layer 30 is 30% to 40% of the total volume of the particle structure. The volume fraction of the antioxidant layer 40 is 10% to 20% of the total volume of the particle structure. Furthermore, the particle structure 10 is water-soluble and forms a uniformly dispersed solution.The particle structure 10 is designed to be so fine that it does not create a perceptible particle sensation when consumed by a person, making it suitable for the production of beverages that can be packaged and used or sold. Furthermore, particle structure 10 can also be incorporated into liquid beverages, gel preparations, tablets, and other dietary supplements.

[0052] The present invention thus provides a particle structure of a nutrient composition for reducing colonization by Helicobacter pylori, reducing inflammation of the gastric mucosa, and promoting the repair of the esophageal barrier 10. The particle structure 10 comprises a core layer 20, a binder layer 30, and an antioxidant layer 40, wherein the core layer 20 contains a chocolate paprika extract and piperine, the binder layer 30 consists of a honey complex and surrounds the core layer 20, thus stabilizing the structure of the core layer 20, the honey complex is formed by mixing honey and turmeric extract powder, and the antioxidant layer 40 contains sea buckthorn powder and surrounds the binder layer 30.The chocolate paprika extract and piperine of core layer 20, the honey complex of fixing layer 30, and the sea buckthorn powder of antioxidant layer 40 combine to form a nutrient composition that provides optimal stomach-soothing benefits. Furthermore, the particle structure 10 is water-soluble and forms a uniformly dispersed solution. The size of the particle structure 10 is designed so that no perceptible particle sensation is felt when consumed, allowing it to be used in beverages that can be packaged and sold. Reference symbol list 10 Particle structure of a nutrient composition to reduce colonization by Helicobacter pylori, to reduce inflammation of the gastric mucosa and to promote the repair of the esophageal barrier 20 core layer 30 Bonding layer 40 Antioxidant layer

Claims

[1] Particle structure of a nutrient composition for reducing colonization by Helicobacter pylori, reducing inflammation of the gastric mucosa and promoting the repair of the esophageal barrier, comprising a core layer, a binder layer and an antioxidant layer, wherein the core layer contains a chocolate paprika extract and piperine, the binder layer consists of a honey complex and envelops the core layer so that the structure of the core layer is stabilized, the honey complex is formed by mixing honey and turmeric extract powder and the antioxidant layer contains sea buckthorn powder and envelops the binder layer. [2] Particle structure of a nutrient composition for reducing colonization by Helicobacter pylori, reducing inflammation of the gastric mucosa and promoting the repair of the esophageal barrier according to claim 1, wherein the diameter of the particle structure is in the range of 1 µm to 10 mm. [3] Particle structure of a nutrient composition for reducing colonization by Helicobacter pylori, reducing inflammation of the gastric mucosa and promoting the repair of the esophageal barrier according to claim 1, wherein the volume fraction of the core layer is 40% to 50% of the total volume of the particle structure. [4] Particle structure of a nutrient composition for reducing colonization by Helicobacter pylori, reducing inflammation of the gastric mucosa and promoting the repair of the esophageal barrier according to claim 1, wherein the volume fraction of the binder layer is 30% to 40% of the total volume of the particle structure. [5] Particle structure of a nutrient composition for reducing colonization by Helicobacter pylori, reducing inflammation of the gastric mucosa and promoting the repair of the esophageal barrier according to claim 1, wherein the volume fraction of the antioxidant layer is 10% to 20% of the total volume of the particle structure. [6] Particle structure of a nutrient composition for reducing colonization by Helicobacter pylori, reducing inflammation of the gastric mucosa and promoting the repair of the esophageal barrier according to claim 1, wherein it can be mixed into liquid drinks, gel preparations as well as tablets and other food supplements.

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