A system for producing a Lactobacillus gasseri SG121 strain composition with a multi-layered protective layer to maintain memory and learning abilities

Abstract

A system for producing a Lactobacillus gasseri SG121 strain composition having a multi-layered protective layer for maintaining memory and learning abilities is provided. The device includes a strain culturing section (91) including a culturing unit (911) used to obtain a Lactobacillus gasseri SG121 culture and a control unit (912) connected to the culturing unit by wire or wirelessly and used to control the culture environment of the culturing unit, a core preparation unit (921) used to prepare the Lactobacillus gasseri SG121 culture from the culturing unit into cores, and an encapsulation processing section (92) installed after the strain culturing section, including an encapsulation unit (922) installed after the core preparation unit and used to receive the cores and perform an encapsulation process thereon. The encapsulation processing section further includes a processing unit (923) installed after the encapsulation unit and used to process the cores that have undergone the encapsulation process into a predetermined dosage form. The composition comprises a core and a multilayer encapsulation structure, of which the multilayer encapsulation structure has five types of functional layer structures, which are layered in sequence on the surface of the core, thereby effectively maintaining the active ingredient's activity of reducing the expression of Aβ42 in the intestinal tract or brain and its activity of regulating the composition of the intestinal flora, thereby achieving the effect of preventing or ameliorating Alzheimer's disease.

Description

[Technical Field]

[0001] The present invention relates to the structure of a composition, and more particularly to a system for producing a Lactobacillus gasseri SG121 strain composition with a multi-layered protective layer for maintaining memory and learning abilities. [Background technology]

[0002] According to epidemiological studies, the number of people with dementia worldwide is rapidly increasing, and is expected to reach 139 million by 2050. Because dementia patients require long-term and sustained care, this not only places a heavy burden on families and society as a whole, but also affects national health budget expenditures. Therefore, how to reduce the risk of dementia has become an important issue for countries around the world.

[0003] Research has shown that Alzheimer's disease reduces neurogenesis, and this lack of neurogenesis not only affects an individual's ability to learn new information, but also leads to interference from old memories, resulting in a decline in cognitive ability. Numerous factors affect neurogenesis, including diet, exercise, aging, and stress. Aging is one of the most important risk factors for Alzheimer's disease and is closely related to the decline in the number of newly generated neurons in the parahippocampal gyrus of adults.

[0004] Recent research has shown that the composition of gut bacteria is related to the regulation of the brain-gut axis, and that when the gut microbiota is out of balance or the intestinal tract is in an inflammatory state, the function of the parahippocampus is affected, leading to the development of cognitive impairment. Because there is a link between gut bacteria and neurological disorders, current research is focusing on developing methods to create a healthy gut microbiota environment in order to potentially reduce the risk of Alzheimer's disease and other neurodegenerative diseases. Summary of the Invention [Problem to be solved by the invention]

[0005] The main purpose of the present invention is to provide a manufacturing system for Lactobacillus gasseri SG121 strain composition with a multi-layer encapsulation protective layer for maintaining memory and learning ability, which encapsulates active ingredients through a multi-layer composite structure, thereby maintaining the activity of the active ingredients and improving processing stability and storage convenience. [Means for solving the problem]

[0006] To achieve the above-mentioned objectives, the present invention discloses a Lactobacillus gasseri SG121 strain composition with a multi-layer encapsulation protective layer for maintaining memory and learning ability, which mainly comprises a core and a multi-layer encapsulation structure, of which the core contains an active ingredient derived from Lactobacillus gasseri SG121 culture, and the multi-layer encapsulation structure includes a digestion-resistant layer, a coating layer, a nutrient layer, a core active layer, and a protective layer, which are layered on the surface of the core from the inside to the outside in order.

[0007] Among them, Lactobacillus gasseri SG121 has been deposited at the German Collection of Microorganisms and Cell Cultures (Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH, DSMZ) under the accession number DSM35411, with the date of deposit being April 16, 2025.

[0008] In one embodiment of the present invention, the thicknesses of the digestion-resistant layer, the coating layer, the nutrient layer, the core active layer and the protective layer are approximately the same.

[0009] In another embodiment of the present invention, the core is spherical, and the sum of the thicknesses of the indigestible layer, the coating layer, the nutrient layer, the core active layer and the protective layer is equal to or less than the diameter of the core.

[0010] In the following embodiment of the present invention, the core is non-spherical, and the sum of the thicknesses of the indigestible layer, coating layer, nutrient layer, core active layer and protective layer is less than the longest diameter of the core.

[0011] In one embodiment of the present invention, the Lactobacillus gasseri SG121 strain composition having a multi-layer encapsulation structure further comprises a capsule having a receiving space for receiving and providing the core having the multi-layer encapsulation structure.

[0012] The capsules are either soft capsules or hard capsules.

[0013] The capsule is made up of two half shells joined together with their openings facing each other.

[0014] Another embodiment of the present invention provides a production system for preparing the above-mentioned Lactobacillus gasseri SG121 strain composition. Specifically, the production system includes a strain culturing unit and an encapsulation processing unit, which are connected to each other. The strain processing unit is for cultivating Lactobacillus gasseri SG121 to produce Lactobacillus gasseri SG121 strain metabolites, and the encapsulation processing unit is located after the strain processing unit and receives the Lactobacillus gasseri SG121 strain metabolites for encapsulation.

[0015] The strain culture section includes a culture unit and a control unit. The culture unit is for cultivating Lactobacillus gasseri SG121, and the control unit is for controlling the culture conditions of the culture unit and is connected to the culture unit to perform the control.

[0016] The encapsulation processing section includes a core preparation unit and an encapsulation unit. The core preparation unit is used to prepare Lactobacillus gasseri SG121 culture into cores, and the encapsulation unit is installed after the core preparation unit to perform the encapsulation processing process on the cores.

[0017] The encapsulation processing section further includes a processing unit, which is installed after the encapsulation unit and is used to process the cores that have been encapsulated into a predetermined dosage form. [Brief explanation of the drawings]

[0018] [Figure 1] 1 is a schematic diagram of the Lactobacillus gasseri SG121 strain composition disclosed in the first embodiment of the present invention. [Figure 2] 1 is a schematic diagram of the Lactobacillus gasseri SG121 strain composition disclosed in the second embodiment of the present invention. [Figure 3] FIG. 10 is a conceptual diagram of a manufacturing system disclosed in a third embodiment of the present invention. [Figure 4] 1 shows the spontaneous alternation rate in the Y-maze behavior test for each group of mice. [Figure 5] This shows the results of an analysis of Aβ42 expression levels in the parahippocampal gyrus in each group of mice. [Figure 6] This shows the results of analyzing the Aβ42 expression levels in the colon of each group of mice. [Figure 7] This shows the results of analyzing the Aβ42 expression levels in the small intestine of each mouse group. [Figure 8] This shows the results of analyzing the expression level of the tight junction protein ZO-1 in the small intestinal tissue of each mouse group. [Figure 9] LEfSe biomarker heat maps of fecal flora analyzed for each group of mice. [Figure 10] LEfSe biomarker heat maps analyzing the small intestinal flora of each mouse group. DETAILED DESCRIPTION OF THE INVENTION

[0019] The present invention discloses a system for producing a Lactobacillus gasseri SG121 strain composition with a multi-layer encapsulation protective layer for maintaining memory and learning ability, wherein the Lactobacillus gasseri SG121 strain composition mainly comprises a core and a multi-layer encapsulation structure, wherein the multi-layer encapsulation structure is composed of five encapsulation layers with different functions, which are used to encapsulate the core within, thereby protecting the active ingredients in the core and effectively maintaining the activity of the active ingredients, enabling the composition to achieve the effect of improving learning ability and cognitive impairment in an individual's body.

[0020] The active ingredient is derived from Lactobacillus gasseri SG121 culture, which has been deposited at the German Collection of Microorganisms and Cell Cultures (Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH, DSMZ) under the accession number DSM35411, with the date of deposit being April 16, 2025.

[0021] For example, the active ingredient is obtained by extracting Lactobacillus gasseri SG121 from a bacterial liquid obtained by culturing the bacteria, and then freeze-drying and pulverizing the bacteria.

[0022] The multi-layer encapsulation structure includes a digestion-resistant layer, a coating layer, a nutrient layer, a core active layer, and a protective layer, which are layered on the surface of the core from the inside to the outside in that order, and the thicknesses of the digestion-resistant layer, coating layer, nutrient layer, core active layer, and protective layer are approximately the same.

[0023] The core can be prepared in any shape, such as a sphere, square, triangle, or ellipse.

[0024] In addition, in order to improve the palatability and portability of the composition, the Lactobacillus gasseri SG121 strain composition with a multi-layer encapsulation structure disclosed in the present invention further includes a capsule having a storage space for accommodating the core with a multi-layer structure.

[0025] In the following, in order to explain the technical features and effects of the present invention, examples will be described in detail with reference to the drawings. [Example]

[0026] See Figure 1. The first embodiment of the present invention discloses a Lactobacillus gasseri SG121 strain composition 10 with a multi-layer encapsulating protective layer, which mainly includes a core 20, an indigestible layer 30, a coating layer 40, a nutrient layer 50, a core active layer 60, and a protective layer 70.

[0027] Among them, core 20 contains an active ingredient, which is prepared from Lactobacillus gasseri SG121 cell powder and its culture.

[0028] The digestion-resistant layer 30 is provided by coating the surface of the core 20 and has digestive enzyme resistance properties, allowing the probiotics to smoothly reach and settle in the intestinal tract without being destroyed by stomach acid and / or bile acid. Ingredients of the digestion-resistant layer 30 include, but are not limited to, mannitol and corn starch.

[0029] The coating layer 40 covers the surface of the indigestible layer 30 and provides basic protection against external environmental factors, preventing the probiotics from being destroyed by oxygen, light, or other external environmental factors. Components of the coating layer 40 include, but are not limited to, arabinogalactan, maltodextrin, xanthan gum, isomaltulose, and soy protein.

[0030] The nutrient layer 50 covers the surface of the coating layer 40 and provides nutrients to the probiotics so that they can grow normally after entering the individual. The nutrient layer 50 is made of gelatin, whey protein, fatty acids, liposomes, gum arabic, natural vegetable gum, or at least two of the above-mentioned materials.

[0031] The core active layer 60 is provided to cover the surface of the nutrient layer 50, and is intended to improve the durability and stability of the probiotics by allowing them to enter a dormant state while maintaining their activity without dying. Ingredients of the core active layer 60 include, but are not limited to, hypromellose and locust bean gum.

[0032] The protective layer 70 is provided on the surface of the core active layer 60 to provide protection against external factors and further enhance the stability and reliability of the probiotics during storage. Ingredients of the protective layer 70 include, but are not limited to, sodium alginate, carrageenan, and potato starch.

[0033] The thicknesses of the indigestible layer 30, coating layer 40, nutrient layer 50, core active layer 60 and protective layer 70 are approximately the same, and the sum of the thicknesses of the above layers is less than the diameter of the core 20, thereby preventing the five-layer encapsulating and protective structure from being too thick, which would reduce bioavailability and absorption rate.

[0034] With the above-mentioned component configuration, the digestion-resistant layer 30, coating layer 40, nutrient layer 50, core active layer 60 and protective layer 70 disclosed in the present invention are stacked to form a composite encapsulation structure, and by encapsulating the core 20 inside, the Lactobacillus gasseri SG121 strain composition can be prevented from being destroyed by environmental factors and the release rate can be controlled, thereby achieving the effect of maintaining the activity of the Lactobacillus gasseri SG121 strain composition used to prevent or ameliorate Alzheimer's disease and stably releasing it in the intestinal tract. [Example]

[0035] See FIG. 2. The structure of the Lactobacillus gasseri SG121 strain composition 10' with a multilayer encapsulation protective layer disclosed in the second embodiment of the present invention is generally the same as that disclosed in the first embodiment, except that it further includes a capsule 80'. Specifically, capsule 80' is composed of two half shells 81' and 82' joined together with their openings facing each other, and has a receiving space 83' for receiving and accommodating core 20' with a multilayer encapsulation structure. The above-mentioned component configuration not only further strengthens protection for the core, but also improves consumer portability and preference, thereby increasing consumer purchasing interest. [Example]

[0036] As shown in Figure 3, the third embodiment of the present invention discloses a manufacturing system 90 for preparing a Lactobacillus gasseri SG121 strain composition having the above-mentioned multi-layer encapsulation protective layer, which includes a strain culture section 91 and an encapsulation processing section 92, and the strain culture section 91 and the encapsulation processing section 92 are connected to each other.

[0037] The strain culturing section 91 includes a culturing unit 911 capable of culturing Lactobacillus gasseri SG121 under predetermined conditions to produce a Lactobacillus gasseri SG121 culture, and a control unit 912 connected to the culturing unit 911 by wire or wirelessly and used to control the culturing environment of the culturing unit, such as the temperature and humidity.

[0038] The encapsulation processing unit 92 is installed after the strain cultivation unit 91 and includes a core preparation unit 921 used to prepare the Lactobacillus gasseri SG121 culture coming from the cultivation unit 911 into cores; an encapsulation unit 922 installed after the core preparation unit 921, capable of performing multiple encapsulation processes, and used to receive cores and perform encapsulation processing processes on them to give them a multi-layer encapsulation structure on their surface; and a processing unit 923 installed after the encapsulation unit 922 and used to process the cores having a multi-layer encapsulation structure into tablets, capsules or other dosage forms.

[0039] By configuring the above-mentioned components, the manufacturing system 90 disclosed in the present invention can prepare Lactobacillus gasseri SG121 strain compositions with a multi-layer encapsulating protective layer in a standardized flow, thereby achieving effects such as quality control, ensuring the activity of the strain, and improving economy.

[0040] The effects of the active ingredients disclosed in this invention are explained below through animal experiments and their results.

[0041] The active ingredient used in the animal experiments below was prepared in the following steps: First, a single colony of Lactobacillus gasseri SG121 was cultured in liquid to obtain a bacterial solution, which was then centrifuged to separate the bacterial cells (precipitate). After that, post-treatment processes such as freeze-drying and pulverization were carried out to obtain Lactobacillus gasseri SG121 powder.

[0042] The diseased animal model used in the animal experiments described below is the APPNL-GF knock-in mouse, which is an Alzheimer's disease transgenic mouse, abbreviated as AD (Alzheimer's disease) mouse. It exhibits symptoms such as Aβ accumulation in the brain, astrocyte activation, glial cell proliferation, inflammatory response, memory impairment, and behavioral disorder, and can be used to reproduce the onset of Alzheimer's disease.

[0043] The normal mice used in the following animal experiments were C57BL / 6 mice.

[0044] In this animal experiment, animals were divided into groups based on the following conditions, and different treatment conditions were applied. The test period was 8 weeks in total.

[0045] Group 1: C57BL / 6 mice, normal chow diet.

[0046] Group 2: AD mice, normal chow.

[0047] Group 3: AD mice were given 109 CFU of Lactobacillus gasseri SG121 powder daily.

[0048] After the test was completed, the following tests and analyses were carried out.

[0049] (1) Animal memory behavior test Each group of mice underwent a Y-maze test for 8 minutes. The number of times each group of mice entered each branch arm and the path they explored were recorded during the test, and the spontaneous alternation rate for each group of mice was calculated using the following formula: Here, "alternation" refers to consecutive entry into three different branches in the Y-maze. The test results are shown in Figure 4. Spontaneous alternation behavior rate = [number of alternations / (total number of entries - 2)] x 100%

[0050] The results in Figure 3 show that the number of times the mice in Group 2 explored the new space was significantly less than that of Group 1, indicating a clear decline in the short-term spatial memory ability of the AD mice. Meanwhile, the number of times the mice in Group 3 explored the new space was significantly more than that of Group 2 and was similar to that of Group 1. These results demonstrate that the Lactobacillus gasseri SG121 powder disclosed in the present invention can indeed improve the spatial memory ability of AD mice and effectively alleviate memory decline caused by Alzheimer's disease.

[0051] (2) Immunostaining analysis After the animal study, each group of mice was sacrificed, and tissues from the cerebrum, small intestine, and colon were collected. The sections were embedded in paraffin and stained to analyze the amyloid-β accumulation status in the tissues and the expression level of the tight junction protein ZO-1 in the small intestine. The results are shown in Figures 5 to 8.

[0052] The results in Figure 5 show that the Aβ42 expression level in the parahippocampal gyrus of the brains of Group 2 mice was significantly higher than that of Group 1 mice, while the Aβ42 expression level in the brains of Group 3 mice was significantly lower than that of Group 2 mice.

[0053] The results in Figures 6 and 7 show that the expression levels of Aβ42 in the small intestine and colon of Group 2 mice were significantly higher than those of Group 1 mice, while the expression levels of Aβ42 in the small intestine and colon of Group 3 mice were significantly lower than those of Group 2 mice, and even lower than those of Group 1. The results in Figure 8 show that the expression level of the tight junction protein ZO-1 in the small intestine of Group 2 mice was lower than those of the other two groups, while the expression level of the tight junction protein ZO-1 in the small intestine of Group 3 mice was significantly elevated.

[0054] The results in Figures 5 to 8 show that the Lactobacillus gasseri SG121 powder disclosed in the present invention can indeed reduce the accumulation of amyloid beta in the brain and intestines of AD mice, and maintain the integrity of the intestinal barrier, preventing endotoxins and inflammatory cytokines produced by harmful bacteria in the intestinal tract from entering the bloodstream, thereby reducing brain nerve damage, improving memory and cognitive ability, and reducing inflammation in the intestinal tract or neurons.

[0055] (3) Mouse intestinal microbiota analysis Feces and small intestinal contents were collected from each group of mice, and DNA was extracted and subjected to polymerase chain reaction (PCR) and sequencing to analyze the bacterial flora. The results are shown in Figures 9 and 10.

[0056] 9, it can be seen that the relative abundance of Lactobacillus, Kineothrix genus, and its representative species Kineothrix alysoides in the fecal samples of Group 2 mice was significantly lower than that of Group 1, and the relative abundance of Ligilactobacillus genus and Prevotella oralis was significantly higher than that of Group 1. On the other hand, it can be seen that the relative abundance of Lactobacillus genus and Kineothrix alysoides in the fecal samples of Group 3 mice administered with the Lactobacillus gasseri SG121 powder disclosed in the present invention was significantly increased, and the relative abundance of Ligilactobacillus genus and Prevotella oralis was significantly decreased.

[0057] Furthermore, the results in Figure 10 show that the relative abundance of the Clostridiaceae family, Clostridium genus, and its representative species, Clostridium polynesiense, in the small intestinal flora of Group 2 mice was significantly higher than that of Group 1, while the relative abundance of the Clostridiaceae family, Clostridium genus, and its representative species, Clostridium polynesiense, in the small intestine of Group 3 mice was significantly lower than that of Group 2.

[0058] The results in Figures 9 and 10 show that the Lactobacillus gasseri SG121 powder disclosed in the present invention can effectively adjust the composition of the intestinal microbiota in patients with Alzheimer's disease, thereby participating in the related regulatory process of the central nervous system through the brain-gut axis mechanism, thereby maintaining brain health and achieving the effects of preventing or ameliorating Alzheimer's disease.

Claims

1. A strain culture section including a culture unit used to culture Lactobacillus gasseri SG121 to obtain a Lactobacillus gasseri SG121 culture, and a control unit connected to the culture unit by wire or wirelessly and used to control the culture environment of the culture unit; A manufacturing system for preparing a Lactobacillus gasseri SG121 strain composition having a multilayer encapsulation protective layer for maintaining memory and learning capabilities, comprising: an encapsulation processing unit installed after the strain cultivation unit, which includes a core preparation unit used to prepare the Lactobacillus gasseri SG121 culture coming from the cultivation unit into cores; and an encapsulation unit installed after the core preparation unit and used to receive the cores and perform an encapsulation processing step on them.

2. The manufacturing system according to claim 1, wherein the encapsulation processing section further includes a processing unit, which is installed after the encapsulation unit and is used to process the cores that have undergone the encapsulation process into a predetermined dosage form.

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