Composition of the bacterial strain Lactobacillus gasseri SG121 with multiple encapsulation protective layers for maintaining memory and learning ability, and its manufacturing system

Abstract

Composition (10) of the bacterial strain Lactobacillus gasseri SG121 with multiple encapsulation protective layers for maintaining memory and learning ability, comprising the following: a core (20) containing an active ingredient obtained from a Lactobacillus gasseri SG121 culture; a resistant layer (30) arranged on the surface of the core (20); a coating layer (40) arranged on the surface of the resistant layer (30); a nutrient layer (50) arranged on the surface of the coating layer (40); a living core layer (60) arranged on the surface of the nutrient layer (50); a protective layer (70) that is arranged on the surface of the living core layer (60).

Description

TECHNICAL AREA

[0001] The present invention relates to a compositional structure, in particular a composition of the bacterial strain Lactobacillus gasseri SG121 with several encapsulation protective layers for maintaining memory and learning ability, and its manufacturing system. STATE OF THE ART

[0002] Epidemiological studies show a rapid global increase in the number of dementia patients, projected to affect 139 million people by 2050. People with dementia require long-term, continuous care, placing a significant burden on families and society as a whole, and substantially impacting national healthcare spending. Therefore, reducing the risk of dementia has become a critical issue for countries worldwide.

[0003] Research suggests that Alzheimer's disease reduces neurogenesis, and insufficient neurogenesis impairs a person's ability to learn new information while being disrupted by old memories, leading to cognitive decline. Numerous factors influence neurogenesis, including diet, exercise, aging, and stress. Among these, aging is both one of the main risk factors for Alzheimer's disease and closely associated with a decrease in the number of newly formed neurons in the hippocampus of adults.

[0004] Recent research has shown that the composition of the gut microbiota is linked to the regulation of the brain-gut axis. When the gut microbiota becomes unbalanced or the gut is inflamed, hippocampal function is impaired, which can lead to cognitive decline. Given the proven link between the gut microbiota and neurological disorders, current research is focused on developing methods to create a healthy gut microbiota, thereby reducing the risk of Alzheimer's disease and other neurodegenerative disorders. CONTENT OF THE PRESENT INVENTION

[0005] The main objective of the present invention is to provide a composition of the bacterial strain Lactobacillus gasseri SG121 with multiple encapsulation protective layers for maintaining memory and learning ability, as well as a manufacturing system for this composition, wherein active ingredients are encapsulated by a multilayer composite structure to maintain the efficacy of the active ingredients and to improve processing stability and ease of storage.

[0006] To achieve the aforementioned objectives, the present invention discloses a composition of the bacterial strain Lactobacillus gasseri SG121 with multiple encapsulation protective layers for maintaining memory and learning ability, comprising mainly a core and a multilayer encapsulation structure, wherein the core comprises an active ingredient derived from a Lactobacillus gasseri SG121 culture; wherein the multilayer encapsulation structure comprises a resistant layer, a coating layer, a nutrient layer, a living core layer, and a protective layer, which are successively layered from the inside out on the surface of the core. Lactobacillus gasseri SG121 is deposited with the German Collection of Microorganisms and Cell Cultures (DSMZ) under deposit number DSM 35411 and the deposit date of April 16, 2025.

[0007] In one embodiment of the present invention, the thicknesses of the resistant layer, the coating layer, the nutrient layer, the living core layer and the protective layer are essentially the same.

[0008] In another embodiment of the present invention, the core is spherically shaped, wherein the sum of the thicknesses of the resistant layer, the coating layer, the nutrient layer, the living core layer and the protective layer is equal to or less than the diameter of the core.

[0009] In a further embodiment of the present invention, the core is aspherical, wherein the sum of the thicknesses of the resistant layer, the coating layer, the nutrient layer, the living core layer and the protective layer is equal to or less than the length of the longest diameter of the core.

[0010] In one embodiment of the present invention, the composition of the bacterial strain Lactobacillus gasseri SG121 with multiple encapsulation protective layers further comprises a capsule which has a receiving space for receiving a core with a multilayer encapsulation structure.

[0011] The capsule is either a soft capsule or a hard capsule.

[0012] The capsule comprises two hemispheres, which are connected to each other with their openings facing each other.

[0013] Another embodiment of the present invention discloses a manufacturing system for producing a composition of the bacterial strain Lactobacillus gasseri SG121 mentioned above. In particular, the manufacturing system comprises a bacterial strain culture section and an encapsulation processing section, wherein the bacterial strain culture section and the encapsulation processing section are connected to each other, the bacterial strain culture section being configured to culture the bacterial strain Lactobacillus gasseri SG121 and produce its metabolites; and wherein the encapsulation processing section is positioned downstream of the bacterial strain culture section to receive the metabolites of the bacterial strain Lactobacillus gasseri SG121 and to perform an encapsulation process on them.

[0014] The bacterial strain cultivation section comprises a cultivation unit and a control unit, wherein the cultivation unit is used to cultivate Lactobacillus gasseri SG121; and wherein the control unit is connected to and controls the cultivation unit to regulate the cultivation conditions of the cultivation unit.

[0015] The encapsulation processing section comprises a core production unit and an encapsulation unit, wherein the core production unit is used to produce the Lactobacillus gasseri SG121 culture to the core; wherein the encapsulation unit is arranged downstream of the core production unit to perform an encapsulation processing process on the core.

[0016] Furthermore, the encapsulation processing section also includes a processing unit located behind the encapsulation unit to process the encapsulated core into a predetermined dosage form. BRIEF DESCRIPTION OF THE DRAWING Fig. Figure 1 shows a schematic diagram of a composition of the bacterial strain Lactobacillus gasseri SG121, which is disclosed from a first embodiment of the present invention. Fig. Figure 2 shows a schematic diagram of a composition of the bacterial strain Lactobacillus gasseri SG121, which is disclosed by a second embodiment of the present invention. Fig. Figure 3 shows a schematic diagram of a manufacturing system disclosed by a third embodiment of the present invention. Fig. Figure 4 shows the percentage of spontaneous alternation in the Y-maze behavior test for each group of mice. Fig. Figure 5 shows the results of the analysis of Aß42 expression levels in the hippocampal gyrus of each group of mice. Fig. Figure 6 shows the results of the analysis of Aß42 expression levels in the large intestine of each group of mice. Fig. Figure 7 shows the results of the analysis of Aß42 expression levels in the small intestine of each group of mice. Fig. Figure 8 shows the results of the analysis of the expression levels of the tight junction protein ZO-1 in the small intestine tissue of each group of mice. Fig. Figure 9 shows the LEfSe biomarker heatmap, which analyzes the fecal microbiota of each group of mice. Fig. Figure 10 shows the LEfSe biomarker heatmap, which analyzes the small intestinal microbiota of each group of mice. DETAILED DESCRIPTION

[0017] The present invention discloses a composition of the bacterial strain Lactobacillus gasseri SG121 with multiple encapsulation protective layers for maintaining memory and learning ability, and the manufacturing system for this composition. The bacterial strain Lactobacillus gasseri SG121 composition mainly comprises a core and a multilayer encapsulation structure, wherein the multilayer encapsulation structure comprises five encapsulation layers with different functions that encapsulate the core to protect the active ingredient contained therein and effectively maintain the activity of the active ingredient, thereby enabling the composition to exert its efficacy in improving learning ability and cognitive impairments in an individual.

[0018] The active ingredient is obtained from a Lactobacillus gasseri SG121 culture, and Lactobacillus gasseri SG121 is deposited with the German Collection of Microorganisms and Cell Cultures (DSMZ) under the deposit number DSM 35411 and the deposit date 16 April 2025.

[0019] The active ingredient is obtained, for example, from bacterial cells derived from a culture of Lactobacillus gasseri SG121, which are then freeze-dried and pulverized. The multilayer encapsulation structure comprises a resistant layer, a coating layer, a nutrient layer, a living core layer, and a protective layer, which are successively layered from the inside out onto the surface of the core. The thicknesses of the resistant layer, the coating layer, the nutrient layer, the living core layer, and the protective layer are essentially the same.

[0020] The core can be manufactured in any shape, for example spherical, square, triangular or elliptical.

[0021] To improve the palatability and transportability of the composition, the composition of the bacterial strain Lactobacillus gasseri SG121 with multiple encapsulation protective layers disclosed in the present invention further comprises a capsule having a receiving chamber for a core with a multilayered structure. Several exemplary embodiments with detailed explanations and accompanying schematic diagrams are presented below to illustrate the technical features and effectiveness of the present invention.

[0022] See Fig. 1, discloses a first embodiment of the present invention a composition 10 of the bacterial strain Lactobacillus gasseri SG121 with several encapsulation protective layers, comprising mainly a core 20, a resistant layer 30, a coating layer 40, a nutrient layer 50, a living core layer 60 and a protective layer 70, wherein the core 20 contains an active ingredient, wherein the active ingredient is produced from Lactobacillus gasseri SG121 bacterial cell powder and its culture.

[0023] The resistant layer 30 is applied to the surface of the core 20 and exhibits resistance to digestive enzymes. This allows the probiotic to withstand destruction by stomach acid and / or bile salts, thus facilitating successful colonization of the intestinal tract. The component of the resistant layer (30) includes, but is not limited to, mannitol and cornstarch.

[0024] The coating layer 40 is applied to the surface of the resistant layer 30 to provide basic protection against external environmental factors and to prevent the probiotics from being damaged by oxygen, light, or other external environmental factors. The components of coating layer 40 include, but are not limited to, arabinogalactan, maltodextrin, corn starch, isomalt, and soy protein.

[0025] The nutrient layer 50 is applied to the surface of the coating layer 40 to supply the probiotics with nutrients and enable them to grow successfully after entering the body. The nutrient layer 50 is made from gelatin, whey protein, fatty acids, liposomes, gum arabic, natural plant gums, or any combination of at least two of the aforementioned materials.

[0026] The live core layer 60 is encapsulated on the surface of the nutrient layer 50, allowing the probiotics to enter a dormant state while retaining their viability and preventing them from dying, thus improving their tolerance and stability. The components of the live core layer 60 include, but are not limited to, hydroxypropyl methylcellulose and locust bean gum.

[0027] The protective layer 70 is encapsulated on the surface of the living core layer 60 to provide enhanced protection against external factors, thereby ensuring better stability and integrity of the probiotics during storage. The components of the protective layer 70 include, but are not limited to, sodium alginate, carrageenan, and potato starch.

[0028] The thicknesses of the resistant layer 30, the coating layer 40, the nutrient layer 50, the living core layer 60 and the protective layer 70 are essentially equal, with the sum of the thicknesses of the above layers being less than or equal to the diameter of the core 20, thus avoiding excessive thickness of the five-layer encapsulation protective structure which could decrease bioavailability or absorption rates.

[0029] The present invention discloses a composite encapsulation structure formed by the layered arrangement of the resistant layer 30, the coating layer 40, the nutrient layer 50, the living core layer 60, and the protective layer 70. The core 20 is encapsulated therein. This protects the Lactobacillus gasseri SG121 bacterial strain from environmental factors and allows for controlled release rates. In this way, the efficacy of the Lactobacillus gasseri SG121 bacterial strain for preventing or alleviating Alzheimer's disease is maintained, while simultaneously enabling stable release in the intestinal tract.

[0030] See Fig. Figure 2 discloses a second embodiment of the present invention, comprising a composition 10' of the bacterial strain Lactobacillus gasseri SG121 with multiple encapsulation protective layers, which has a structure essentially identical to that of the first embodiment, differing only in that it additionally includes a capsule 80'. In particular, the capsule 80' comprises two hemispheres 81', 82', which are connected to each other with their openings facing each other, the capsule having a receiving chamber 83' which is used to receive the core 20' with a multilayer encapsulation structure. The configuration of the aforementioned components not only further improves the protection of the core, but also enhances portability and palatability for consumers, thereby promoting consumer willingness to purchase.

[0031] See Fig. 3, discloses a third embodiment of the present invention a manufacturing system 90 for producing a composition of the bacterial strain Lactobacillus gasseri SG121 with several encapsulation protective layers, wherein the manufacturing system comprises a bacterial strain cultivation section 91 and an encapsulation processing section 92, wherein the bacterial strain cultivation section 91 and the encapsulation processing section 92 are connected to each other, wherein the bacterial strain cultivation section 91 comprises: a cultivation unit 911, which is used to cultivate Lactobacillus gasseri SG121 under predetermined conditions in order to produce a Lactobacillus gasseri SG121 culture; and wherein the control unit 92 is connected wired or wirelessly to the cultivation unit 911 in order to regulate the cultivation environment of the cultivation unit, such as temperature and humidity; wherein the encapsulation processing section 92 is arranged downstream of the bacterial strain cultivation section 91 and comprises: a core manufacturing unit 921, which is used to produce the Lactobacillus gasseri SG121 culture coming from the cultivation unit 911 into a core; an encapsulation unit 922, which is arranged downstream of the core manufacturing unit 921 and can perform multiple encapsulation processes to receive the core and to perform an encapsulation processing process on it, such that the surface of the core has a multilayer encapsulation structure; a processing unit 923, which is arranged downstream of the encapsulation unit 922, to process the core with the multilayer encapsulation structure into pellets, capsules or other dosage forms.

[0032] By configuring the above-mentioned components, the manufacturing system 90 disclosed by the present invention is able to produce a composition of the bacterial strain Lactobacillus gasseri SG121 with multiple encapsulation protective layers through a standardized process, thereby achieving advantages such as quality control, ensuring the viability of the bacterial strain and increasing economic efficiency.

[0033] The effectiveness of the active ingredient disclosed by the present invention will now be illustrated by means of animal experiments and their results.

[0034] The active ingredient used in the following animal experiments is produced in the following steps: a single colony of Lactobacillus gasseri SG121 is subjected to liquid culture to obtain a bacterial suspension; bacterial cells (precipitate) are obtained by centrifugation of the suspension; subsequent processing, including freeze-drying and grinding, yields Lactobacillus gasseri SG121 powder.

[0035] The disease model used in the following animal experiments is APP. NL-C-F Transgenic mice, transgenic mice with Alzheimer's disease, abbreviated as AD mice (Alzheimer's disease). These mice exhibit characteristic features of the onset of Alzheimer's disease, including Aβ accumulation in the brain, astrocyte activation, glial cell proliferation, inflammatory response, memory deficits, and behavioral disturbances, thus simulating the pathological state of Alzheimer's disease.

[0036] The normal mice used in the following animal experiments are C57BL / 6 mice. The animal experiments are conducted under the following conditions for group assignment and treatment administration, with a duration of 8 weeks. Group 1: C57BL / 6 mice, normal diet; Group 2: AD mice, normal diet; Group 3: AD mice, normal diet, supplemented daily with 10 9 CFU Lactobacillus gasseri SG121 powder.

[0037] After the trial period, the following analyses will be carried out: (1) Behavioral tests on the memory of animals

[0038] Mice from each group are subjected to the Y-maze test for 8 minutes. During the test, the number of entries into each arm and the exploration paths are recorded for each group. The percentage of spontaneous alternation is calculated using the following formula, where "alternation" refers to successive entry into three different arms of the Y-maze. The results are presented in Fig. 4 shown. Percentage of spontaneous alternation = [Number of alternations / (Total number of entries − 2)] × 100%

[0039] The results from Fig. Figure 3 shows that the mice in group 2 exhibit significantly less exploration of new spaces compared to group 1, indicating a markedly impaired spatial short-term memory performance in AD mice. Conversely, the mice in group 3 show significantly more exploration of new spaces than group 2, thus approaching the level of group 1.

[0040] These results show that the Lactobacillus gasseri SG121 powder disclosed in the present invention can effectively improve the spatial memory performance of AD mice and thus exhibits efficacy in alleviating the memory loss associated with Alzheimer's disease. (II) Immunohistochemical analysis

[0041] After completion of the animal experiments, the mice in each group are euthanized. Tissue samples are taken from the brain, small intestine, and large intestine of each group, embedded in paraffin, sectioned, and then stained. An analysis is performed to evaluate the Aβ amyloid accumulation in each tissue and the expression levels of the tight junction protein ZO-1 in the small intestine. The results are presented in Fig. 5 to 8 are shown.

[0042] It's out Fig. 5 shows that the Aß42 expression levels in the hippocampal gyrus of mice in group 2 are significantly higher than those of mice in group 1, while the Aß42 expression levels in the brain of mice in group 3 are significantly reduced compared to mice in group 2.

[0043] It's out Fig. 6 and Fig. It is evident from Figure 7 that the Aβ42 expression levels in the small intestine and large intestine of mice in group 2 are significantly higher than those of mice in group 1, while the Aβ42 expression levels in the small intestine and large intestine of mice in group 3 are significantly lower than those of mice in group 2 and even lower than those of mice in group 1. It is from Fig. 8 shows that the expression levels of the tight junction protein ZO-1 in the small intestine of mice in group 2 are lower than those of the other two groups, while the expression levels of the tight junction protein ZO-1 in the small intestine of mice in group 3 are significantly increased.

[0044] The results from Fig. Figures 5 to 8 show that the Lactobacillus gasseri SG121 powder disclosed in the present invention effectively reduces Aβ accumulation in the brain and intestine of AD mice. It also maintains the integrity of the intestinal barrier and prevents endotoxins or inflammatory factors produced by harmful bacteria in the intestine from entering the bloodstream. This mechanism results in a reduction of damage to brain neurons, an improvement in memory and cognitive functions, and a reduction in inflammation in intestinal or nerve cells. (3) Analysis of the intestinal microbiota of mice

[0045] Feces and small intestinal contents are collected from each group of mice. After DNA extraction, PCR amplification and sequencing are performed to analyze the microbiota; the results are presented in Fig. 9 and Fig. 10 are shown.

[0046] It's out Fig. Figure 9 shows that the relative abundance of Lactobacillus, Kineothrix, and its representative species Kineothrix alysoides in the fecal samples of mice in group 2 is significantly lower compared to group 1. Conversely, the relative abundance of Ligilactobacillus and Prevotella oralis is significantly higher in group 2 than in group 1. In contrast, mice in group 3, which are administered Lactobacillus gasseri SG 121 powder, show a significantly increased relative abundance of Lactobacillus and Kineothrix alysoides in their fecal samples, while the relative abundance of Ligilactobacillus and Prevotella oralis is significantly reduced.

[0047] Furthermore, as in Fig. Figure 10 shows that the relative abundance of the family Clostridiaceae, the genus Clostridium and its representative species Clostridium polynesiense in the small intestine microbiota of mice in group 2 is significantly higher than in group 1. In the small intestine of mice in group 3, however, the relative abundance of the family Clostridiaceae, the genus Clostridium and its representative species Clostridium polynesiense is significantly lower than in group 2.

[0048] The results in Fig. 9 and Fig. Figure 10 shows that the Lactobacillus gasseri SG121 powder disclosed by the present invention can effectively regulate the composition of the intestinal microbiota of Alzheimer's patients. This, in turn, enables participation in regulatory processes of the central nervous system via the gut-brain axis mechanism, thereby achieving the effectiveness of maintaining brain health and preventing or alleviating Alzheimer's disease.

[0049] The present invention discloses a composition of the bacterial strain Lactobacillus gasseri SG121 with multiple encapsulation protective layers for maintaining memory and learning ability, and its manufacturing system. The composition comprises a core and a multilayer encapsulation structure, wherein the multilayer encapsulation structure comprises five functional layered structures that are sequentially stacked on the core surface to effectively maintain the efficacy of the active ingredient in reducing Aβ42 expression in the intestine or brain and regulating the composition of the intestinal microbiota, thereby achieving the effect of preventing or alleviating Alzheimer's disease.

Claims

[1] Composition (10) of the bacterial strain Lactobacillus gasseri SG121 with multiple encapsulation protective layers for maintaining memory and learning ability, comprising the following: a core (20) containing an active ingredient obtained from a Lactobacillus gasseri SG121 culture; a resistant layer (30) arranged on the surface of the core (20); a coating layer (40) arranged on the surface of the resistant layer (30); a nutrient layer (50) arranged on the surface of the coating layer (40); a living core layer (60) arranged on the surface of the nutrient layer (50); a protective layer (70) that is arranged on the surface of the living core layer (60). [2] Composition (10) of the bacterial strain Lactobacillus gasseri SG121 with several encapsulation protective layers for maintaining memory and learning ability according to claim 1, wherein the thicknesses of the resistant layer (30), the coating layer (40), the nutrient layer (50), the living core layer (60) and the protective layer (70) are substantially the same. [3] Composition (10) of the bacterial strain Lactobacillus gasseri SG121 with several encapsulation protective layers for maintaining memory and learning ability according to claim 1, wherein the core (20) is spherically shaped. [4] Composition (10) of the bacterial strain Lactobacillus gasseri SG121 with several encapsulation protective layers for maintaining memory and learning ability according to claim 3, wherein the sum of the thicknesses of the resistant layer (30), the coating layer (40), the nutrient layer (50), the living core layer (60) and the protective layer (70) is equal to or less than the diameter of the core (20). [5] Composition (10) of the bacterial strain Lactobacillus gasseri SG121 with several encapsulation protective layers for maintaining memory and learning ability according to claim 1, wherein the core (20) is aspherical. [6] Composition of the bacterial strain Lactobacillus gasseri SG121 with several encapsulation protective layers for maintaining memory and learning ability according to claim 5, wherein the sum of the thicknesses of the resistant layer (30), the coating layer (40), the nutrient layer (50), the living core layer (60) and the protective layer (70) is equal to or less than the length of the longest diameter of the core (20). [7] Composition (10') of the bacterial strain Lactobacillus gasseri SG121 with multiple encapsulation protective layers for maintaining memory and learning ability according to claim 1, further comprising a capsule (80') having a receiving space (83') for receiving a core (20') with a multilayer encapsulation structure. [8] Composition (10') of the bacterial strain Lactobacillus gasseri SG121 with several encapsulation protective layers for maintaining memory and learning ability according to claim 7, wherein the capsule (80') comprises two half-shells (81'), (82') which are connected to each other with their openings facing each other. [9] Manufacturing system (90) for producing a composition of the bacterial strain Lactobacillus gasseri SG121 with multiple encapsulation protective layers for maintaining memory and learning ability according to claim 1, comprising the following: a bacterial strain cultivation section (91) comprising: a cultivation unit (911) used to cultivate Lactobacillus gasseri SG121 to obtain a Lactobacillus gasseri SG121 culture, a control unit (912) connected wired or wirelessly to the cultivation unit (911) to regulate the cultivation environment of the cultivation unit (911); an encapsulation processing section (92) located downstream of the bacterial strain cultivation section (91) and comprising: a core production unit (921) used to produce the Lactobacillus gasseri SG121 culture from the cultivation unit (911) into a core; an encapsulation unit (922) located downstream of the core production unit (921) to receive the core and perform an encapsulation processing process on it. [10] Manufacturing system (90) according to claim 9, wherein the encapsulation processing section (92) further comprises a processing unit (923) arranged downstream of the encapsulation unit (922) to process the encapsulated core into a predetermined dosage form.

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