Means for maintaining and restoring cognitive function using corosolic acid and corosolic acid compositions

Abstract

The present invention provides a composition that maintains and restores cognitive function. [Solution] A pharmaceutical and food composition containing corosolic acid with a corosolic acid content of 0.001 to 99.9% is provided for use in preventing, alleviating, and curing dementia and MCI (mild cognitive impairment), delaying the onset of dementia, and for anti-dementia purposes such as restoring and improving cognitive function.

Description

Technical Field

[0001] The technical field of the present invention is [Chemistry][Pharmacy][Medicine][Immunology][Pharmaceutics][Agriculture][Botany][Human Environmental Science][Human Evolution Theory][Internet][Software Development][Digital]. The applied technical field of the present invention is [Memory Forgetting Foreign Substances][Psychiatry][Pharmaceutical and Health Food][Extraction, Isolation and Purification][Mushroom and Plant Culture][Food Manufacturing][Beverage Manufacturing][Nursing and Nursing Dispatch][Facilities for Accepting the Elderly][Facilities for Dementia Care][Physical Therapists][National and Local Administration][Convenience Stores and Retail][Smartphones][Communication Devices][Internet].

Background Art

[0002] The core of the present invention is that an unknown attribute of "usefulness for dementia" has been discovered for the known substance "natural compound colosolic acid", and this fact has been demonstrated by a reasonable method of two clinical trials. It is the discovery of a sub - concept of colosolic acid that has not been described yet. As the super - concept, there are "improvement of insulin resistance", "anti - diabetes", "suppression of blood sugar increase" of colosolic acid, etc. The results of the two clinical trials conducted by the present inventor are that the amyloid - β cascade hypothesis that the cause of dementia is "brain atrophy caused by amyloid - β" has completely collapsed, and major pharmaceutical companies have given up investments of 60 trillion yen and withdrawn. From this fact, experiments were carried out by "inductive method" (inferring the cause from the result) so as not to repeat the same failure. This is also a fact that has not been described yet. Since around 2015 when the fact that the cause of dementia is not amyloid - β became common, the theory that the cause of dementia may be chronic inflammation in the brain caused by insulin resistance that continuously stresses cells has become common. The present inventor has obtained the fact that colosolic acid improves the efficacy of insulin, quickly returns the blood sugar level to the normal value, and reduces the total insulin secretion amount in eight past clinical and non - clinical trials. Therefore, the present inventor conducted the first clinical and non - clinical trial for dementia in August 2019. There is no report on the experiment for dementia with this agent.

[0003] The first clinical trial conducted was the "MMSE" (Mini-Mental State Examination), a globally recognized test for dementia. The initial participants consisted of 20 elderly individuals suspected of having mild cognitive impairment and 20 adults aged 20-60 who were addicted to smartphones. Smartphone addiction was defined as adults who used their smartphones for 12 hours a day and were selected for their information overload and frequent forgetfulness. Participants and their families signed an "informed consent" form, and three tests were conducted: before corosolic acid intake, two weeks after intake, and immediately after intake. The results are shown in the "Figure" at the end of this document. The results of corosolic acid intake were remarkable. It is also believed that interaction with the director created a "connection." The MMSE is a test to determine whether or not someone has dementia, and there are no reports of clinical trials using specific compounds for anti-dementia purposes.

[0004] The inventors believed that physical evidence was also necessary. Therefore, elderly individuals with mild cognitive impairment were asked to participate in three similar "blood sampling tests." The blood sampling tests were conducted using the same method as the OGTT (Oral Glucose Tolerance Test). Participants fasted from 8 p.m. the previous night, and upon arrival at the hospital, they ingested food equivalent to 75 g of sugar water. Blood sampling tests were then conducted 30 minutes and 2 hours after ingestion, for a total of three tests. The clinical trial was conducted at Hi-Precision Diagnose, a top-tier clinical trial facility in Cabanatuan. Blood analysis revealed that corosolic acid intake significantly improved both the insulin resistance indicator "Homa-IR" and the insulin response "II." Insulin resistance decreased, and insulin response improved. This, too, is a world first. [Prior art documents] [Patent Documents]

[0005] [Patent Document 1] Patent application No. 2021-127314 [Patent Document 2] Patent application No. 2022-025144 [Non-patent literature]

[0006] [Non-Patent Document 1] Practical skills taught by dementia treatment physicians and dementia care instructors! Correct understanding of dementia and appropriate ways to communicate and show empathy. General overview of dementia and basic perspectives on dementia care. Authors: Katsunori Yanagi (Kansai Branch of the Dementia Treatment Research Association), Katsunori Yanagi (Hayashiyama Asahi Clinic), Rimiko Ishikawa (Alice Koshien Special Nursing Home for the Elderly) Source: Dementia Care 2018 [Non-Patent Document 2] Dementia Care and Narratives; Focusing on Lifelong Development: A Tentative Study of Fragmentary Narratives as a Connection Between People with Dementia, Their Families, and Ourselves Author: Yumi Rokusha (Unit Day Service Smile Home) Source: Journal of the Japanese Society for Dementia Care, 2023 [Non-Patent Document 3] The Effects of Corosolic Acid on Glucose Metabolism Authors: Michiyo Inozuka (Clinical Research Information Center, Foundation for Advanced Medical Technology), Mitsuo Fukushima (Clinical Research Information Center, Foundation for Advanced Medical Technology), Noriko Tanaka (Clinical Research Information Center, Foundation for Advanced Medical Technology), Futoshi Matsuyama (Youth Techno Corporation), Naoya Ueda (Youth Techno Corporation), Noboru Yonaha (Yonaha Clinic), Masayoshi Murakami (Clinical Research Information Center, Foundation for Advanced Medical Technology), Nobuya Inagaki (Department of Diabetes and Nutrition, Kyoto University), Hiroshi Seino (Department of Diabetes and Nutrition, Kansai Electric Power Hospital) Publication Name: Diabetes (Journal of the Japan Diabetic Society) [Overview of the Initiative] [Problems that the invention aims to solve]

[0007] The "novelty" of this invention lies in the discovery that the safe and reliable compound "corosolic acid" can be used to solve the problem of dementia. The inventiveness of the invention lies in the fact that "corosolic acid" can be used as an ingredient in everyday foods and beverages, helping to realize enjoyable daily "connections with people." Research conducted by the Tokyo Metropolitan Government's care program, the Japanese Society for Dementia Research, Kobe University and Tamba Town's combined program of exercise, diet, games, and connections for dementia, and the Tokyo Metropolitan Institute of Gerontology, among others, has also emphasized the importance of "connections," a concept previously unheard of in relation to dementia. However, this "connection" cannot be realized in the form of medicine tablets or capsules. The novelty of this invention lies in the fact that corosolic acid can be combined with everyday foods, making it possible to provide "conversation," "enjoyment," and "variety" while preventing swallowing difficulties in the elderly, such as in candy, cotton candy, gummies, sweets, bread, jelly, lactic acid bacteria beverages, and carbonated drinks. The discovery of patentability by translating the mental requirement of "connection" into a tangible object is a concrete manifestation of something intangible, much like bright hopes such as music, anime, memories, videos, family, and travel plans. It is essential for dementia care and is an invention that no one has thought of and has not yet been reported.

[0008] "Contribution to Industry and New Technology 1" of this invention refers to solving the global challenge of dementia prevention. Despite being a natural compound, it has undergone teratogenicity testing, toxicity testing, and accelerated growth testing at the compound level, as well as chromosomal aberration testing using mammalian cultured cells with an extract containing corosolic acid, which is commercially versatile. Its efficacy and safety have been confirmed through eight clinical trials to date, and including the conclusions of the Cabinet Office Food Safety Commission, there is no doubt that it will form the basis of a wide range of dementia countermeasures industries. Writing a month's worth of "daily snacks" for the elderly on a calendar and discussing it is sure to be a topic of conversation.

[0009] The "Contribution to Industry and New Technology 2" of this invention is that it can create a broad range of new industries for addressing dementia, a global social problem. These fields include [memory loss clinics], [psychiatry], [pharmaceuticals and health foods], [extraction, isolation, and purification], [mushroom and plant cultivation], [food manufacturing], [beverage manufacturing], [nursing care and caregiver dispatch], [elderly care facilities], [dementia care facilities], [physical therapists], [national and local government], and [convenience stores and retail], and export to overseas markets is also possible. The manufacturing technology is reliable and allows for low-cost mass production. By establishing this structure, it becomes possible to create new industries in a wide range of fields. At the same time, in order to achieve this, corosolic acid, the subject of this invention, should be granted a substance patent not only for its use in dementia-related applications, but also as an insulin linker in antibody-drug conjugates (ADCs), leveraging its physical properties and safety. This is because it is a discovery that has not yet been reported anywhere as a linker for insulin, a hormone protein that reaches all cells.

[0010] The "essential points" of this invention can be summarized as follows: 1. Subject matter of the invention: Corosolic acid. A pale white corosolic acid extract with a wide range of applications. 2. Embodiment of the invention: Oral daily foods and medicines for anti-dementia. Data will be collected and used to create "connections". 3. Purpose and Use: Prevention and mitigation of dementia and MCI (mild cognitive impairment). 4. Basis for the invention: Analysis results of MMSE scores and blood sampling tests from two dementia clinical trials. 5. Novelty of the evidence: The intake has been increased ninefold, from the conventional 1 mg of corosolic acid per day to 9 mg per day, which is a safety-assured dosage. (KGK / USA has confirmed the safety of 10 mg / day in clinical trials.) 6. Novelty of the invention: The world's first safe anti-dementia compound, and the digitization of personal information of individuals with dementia and MCI (mild cognitive impairment) to utilize for mental "connections." 7. Inventiveness of the invention: Simultaneous improvement of emotions and memory, and realization of the site of action and "connection". 8. Industrial applicability: It will be a boon to all sectors, including pharmaceuticals, food, nursing care, clothing, and elderly care facilities. 9. Definition of the present invention: The following three points. 1) The world's first favorable result against dementia, 2) The world's first identification of a compound effective against dementia, and the world's first elucidation of the specific mechanism of action in the onset of dementia. 10. Epoch-making nature of the invention: Regarding dementia as a problem of mental and physical functions and presenting a solution thereto.

[0011] What is meant by the "points of the present invention" shown in chronological order is 1) There was a significant difference in two clinical trials for dementia. 2) The test reagent was colostrinate. 3) The subjects of the trial were 30 elderly people and 20 adults. 4) The target subjects were those with MCI (mild cognitive impairment) and smartphone addiction-related amnesia syndrome. 5) The intake amount of the reagent was 9 mg / day (within the range with safety assurance, but nine times the conventional amount). 6) The tests were MMSE and OGTT blood sampling tests for analysis. 7) The residential areas of the subjects of the trial were two districts in Tarlac, Nueva Ecija, Philippines. 8) The blood sampling analysis facility was Hi-Precision Diagnose, and the analysis items were blood glucose level, Homa-IR (insulin resistance), I.I. (insulin response index), γ-GTP (liver load), etc. 9) The leader of this research was the former deputy director of the Takeda Pharmaceutical Industries Research Institute. 10) The site of action was the frontal temporal lobe. 11) There are two causes of dementia: "emotional anxiety and dissatisfaction" (mental) and chronic inflammation of the "frontal temporal lobe". 12) Chronic inflammation leads to metabolic and blood flow insufficiency. 13) Chronic inflammation causes an overrun of the immune system. 14) Immunity refers to macrophages. 15) The battle between chronic inflammation and immunity leaves remnants and causes a decrease in blood flow. 16) Colostrinate reaches each part of the brain as a linker of insulin. 17) Insulin passes through the blood-brain barrier (from research on Hurler's disease). 18) Colostrinate enhances the efficacy of insulin (superordinate concept). 19) Colostolic acid improved the metabolism and blood flow of the frontal lobe that controls emotions, memory, and learning. 20) As a result, cognitive function was restored (sub - concept). 21) At the same time, the importance of "connection" was proven. 22) The directors of MMSE and blood sampling tests are warm - hearted and trustworthy people among local residents. 23) Colostolic acid is a fat - soluble compound. 24) Tannins can be eluted with hot water. 25) Remove water - soluble compounds and apply pressure to efficiently extract colostolic acid with ethanol - hot water. 26) Colostolic acid can be made into a pale - white extract. 27) It can be a raw material for all general foods such as indigestible dextrin, oils and fats, lactic acid bacteria beverages, and confectionery. 28) Then it can also be applied to "daily snacks" and "side dishes", which leads to conversation. 29) There is no report yet that anything other than colostolic acid can solve "connection" both physically and mentally. 30) It is the world's first oral anti - dementia drug and a general food raw material. 31) Colostolic acid can be mass - produced at low cost by plant cultivation. 32) It is possible to create a new industry that spans from smartphone digital to mushroom factories, confectionery and noodle manufacturers. 33) It will also make a great contribution to the world where dementia is progressing.

[0012] Feature and Requirement of the Invention Part 1: "Novelty" means Novelty Part 1: The fact that dementia was alleviated. One of the causes of dementia is the chronic inflammation of the frontal - temporal lobe that controls emotions, memory, and learning, and colostolic acid adjusted the rampage of macrophages, improved metabolism, and led to the recovery of brain function. The said invention is supported by the clear results of MMSE scores and blood sampling tests (Homa - IR and I.I.) before colostolic acid intake, 2 weeks later, and 1 month later. Novelty #2: Corosolic acid acted as a linker (bridge) to insulin. Corosolic acid bound to insulin and crossed the blood-brain barrier in the cerebral blood vessels, improving the metabolism of brain cells and increasing blood flow, thereby improving the function of the frontal lobe and hippocampus. This is thought to be one of the reasons why dementia symptoms were alleviated after taking corosolic acid for two weeks or one month. Novelty #3: The discovery that corosolic acid acts as a linker (bridge) for insulin. Corosolic acid has both binding affinity to insulin. Corosolic acid is a type of pentacyclic triterpene and has a carboxyl group. The carboxyl group, a functional group, is most likely to bind to amino acids as a linker. On the other hand, insulin is a protein in which two amino acids are intertwined in a chain, and the carboxyl group is the most likely linker to which it binds. In other words, corosolic acid bound as a linker to insulin and, like insulin which all cells need, crossed the blood-brain barrier and was delivered to brain cells. As a result, cognitive function was restored.

[0013] Features and Requirements of an Invention, Part 2: "Inventive Step" Innovative aspect #1: It can be used as an oral daily food or medicine for dementia prevention and treatment. By discovering an oral dementia alleviating and curative material through two clinical trials and applying it to commercialize it in daily foods (e.g., sweets) and beverages, it not only alleviates dementia but also fosters enjoyable conversations among elderly people and their caregivers. Inventive step #2: The discovery that corosolic acid has immune-modulating properties. Descriptions of traditional medicines in Southeast Asian countries (Philippines, Thailand, Taiwan, etc.) and in Indian Ayurveda also mention the immune-modulating functions of medicinal plants containing corosolic acid. According to research from Standard University, dementia is caused by chronic inflammation in the frontal lobe, and this chronic inflammation is attributed to an overrun of the immune substance macrophages. Frontal lobe cells develop inflammation due to stress from excessive longevity beyond evolutionary limits and the constant over-insulin stress caused by a rich lifestyle. The immune system perceives these as "foreign substances," similar to bacteria and cancer cells, and deploys a large number of macrophages to engulf them. As a result, remnants (sometimes blood clots) remain, leading to decreased metabolism and poor blood flow. This is considered one of the causes of dementia.

[0014] The Tokyo Metropolitan Government has been implementing a dementia care program since 2018. It started around the same time that the amyloid-beta cascade hypothesis for dementia collapsed and no method for restoring cognitive function was found. As a result, it was confirmed that "connection," and the resolution of mental issues such as anxiety, frustration, hearing loss, depression, and sulking, as well as verbal communication, are crucial for alleviating dementia. The only substance that can specifically achieve this through food and snacks is "corosolic acid." Features and Requirements of the Invention 3: "Industrial Applicability" means, New technology: Capable of mass production. Although corosolic acid is a natural compound, it can be isolated and purified. At the compound level, teratogenicity tests, accelerated growth tests, and eight clinical and non-clinical trials were conducted, similar to those for synthetic compounds, confirming efficacy and safety. This paved the way for "low-cost, mass production through plant cultivation." As a result, a new, vast industry with a broad base is being created.

[0015] Points of inventiveness: A discovery not yet reported 1 1) It utilizes the immunomodulatory capabilities of corosolic acid. We discovered that corosolic acid, a naturally occurring compound, possesses unique immune-modulating and anti-inflammatory capabilities. We found that these capabilities alleviate metabolic dysfunction in the frontotemporal lobe caused by chronic inflammation resulting from macrophage overrun in the frontotemporal lobe, which is a contributing factor to dementia, and thus lead to cognitive function recovery.

[0016] Points of inventiveness: Two previously unreported discoveries 2) Focusing on "emotions," another important factor in dementia. Dementia is not limited to dysfunction of bodily organs; emotional states such as "connections with others" and "anxiety, loneliness, and sulking" are involved in inflammation not only in the brain but also in the body. Clinical trials have shown that corosolic acid extends the lifespan of the frontal lobe, which controls emotions, alleviates chronic inflammation caused by lifestyle-related diseases, suppresses insulin resistance stress caused by chronic hyperglycemia, improves brain metabolism, and even improves emotional states.

[0017] Points of inventiveness: 3 previously unreported discoveries 3) The active ingredients were tested at the compound level, not just as extracts. Development of oral dementia drugs and health foods: Corosolic acid has long been distributed as an extract tablet for diabetes and as a health food that suppresses blood sugar spikes. This can be considered a kind of long-term safety test result. Points of inventiveness: 4 previously unreported discoveries 4) The inventor developed know-how for inexpensive, mass production of corosolic acid simultaneously with clinical trials. From the start of his research on corosolic acid, the inventor predicted an annual demand of 8 to 20 tons and dispatched several researchers to the Department of Herbal Medicine at a national university's Faculty of Pharmaceutical Sciences in Japan to study mass production. As a result, he observed banaba (crape myrtle), which is rich in corosolic acid, for 365 days, collected small amounts from a single leaf over 24 hours, analyzed and compared them, and systematized the study of content and movement based on type, season, and time. As a result, he discovered banabacalus, which contains 5 to 1000 times more corosolic acid than normal, and established a path to mass production of corosolic acid.

[0018] Points of inventiveness: 5 previously unreported discoveries 5) The development of "crystals" as a measure of corosolic acid. Corosolic acid is said to have the molecular formula C30H48O4 and a molecular weight of 472.70, but this is merely a calculation. The crystallization of corosolic acid is an embodiment of natural laws. At the same time, it is also a creation of biological phenomena and cosmic laws that are not found in synthetic compounds. On the other hand, the immunomodulatory effect of corosolic acid in this invention against chronic inflammation cannot be achieved with synthetic drugs. Many plant-derived antimicrobial compounds "promote the production of immunity" when bacteria or viruses invade the human body, as well as when cancer cells or chronic inflammation occur. In such cases, the immune system often overreacts, creating blood clots and disrupting metabolism. However, corosolic acid has the ability to suppress this immune overreaction, thus calming chronic inflammation and restoring blood flow—in other words, it possesses immune-modulating capabilities. This ability is found in only a limited number of naturally occurring compounds. It is also found in giloy, a representative Ayurvedic herb, and has been calculated by AI at numerous Indian universities and proven in clinical trials. It is also listed in the relevant links of the WHO and NIH.

[0019] Points of inventiveness: 6 previously unreported discoveries 6) The intake of corosolic acid was increased from the conventional 1 mg per day to 9 mg per day, which ensures safety. Plants that originally contain corosolic acid include banaba, guava, persimmon, loquat, and shiso, some of which have been eaten as vegetables and fruits. Therefore, overall they are safe and there have been no reports of side effects. However, isolating and purifying the compound for use is a different matter, and caution must be exercised regarding safety. United States (clinical trial site) In Canada, a clinical trial was conducted to confirm the safety of ingesting 56 mg of banaba extract containing 18% corosolic acid (10 mg of corosolic acid intake), and in Japan, the Cabinet Office Food Safety Commission has also stated that 9 mg per day is safe. Therefore, the inventor conducted a clinical trial for dementia with a daily intake of 9 mg and obtained the results.

[0020] Points of inventiveness: 7 previously unreported discoveries 7) Water-soluble tannins are extracted from plant raw materials containing corosolic acid using hot water or steam, and this process is repeated to remove bitterness, astringency, and other off-flavors. Finally, a pale white, highly concentrated corosolic acid extract containing 0.1-80% corosolic acid is obtained using an ethanol-hot water solvent in a pressure vessel, etc. This, along with the indigestible dextrin mixed powder produced using the extracted raw materials, is inexpensive, suitable for everyday use, easy for various manufacturers to handle, and versatile for use in general food products such as oils and fats, wheat flour, rice flour, seasonings, alcoholic beverages, confectionery, tofu, health foods, noodles, beverages, yogurt, gummies, and candies.

[0021] Points of inventiveness: 8 previously unreported discoveries 8) Another key point of this invention is its focus on solving the mental problems associated with dementia. This can be digitized and used as digital information (DX) to facilitate "connections" in anti-dementia efforts. At the same time, it may open up the possibility of discovering solutions to dementia from family DNA. The frontal lobe is the area that controls emotions, and if chronic inflammation develops there, the battle with the immune system results in debris (such as blood clots) that obstructs blood flow. The solution to this is corosolic acid (a tiny molecule with 1.36 trillion times 1 trillion molecules in just 1 milligram) which activates cells as an insulin linker. In short, corosolic acid can soothe mood and create opportunities for "connection," and it is corosolic acid used as a mixed ingredient with indigestible dextrin and DHA. If this connection is digitized and saved as individual data, and personality is analyzed with AI, it will be possible to use information such as preferred snacks, topics of conversation, hobbies, interests, anxieties, and personality as positive "connections" on tablets, PCs, and smartphones, and to assist in caregiving.

[0022] Corosolic acid is, as explained above: Basic explanation of corosolic acid, part 1: From a pharmacological and pharmacognostic perspective, corosolic acid is a type of triterpenoid. In animal and cell studies of diabetic models, it is known to induce the glucose transporter GLUT4, which is involved in the uptake of sugar into tissues, to the cell membrane. It has also been reported to promote glucose uptake by promoting the phosphorylation of insulin receptors. (Higher-level concept) Corosolic acid is a five-ring compound. A type of species. The structure is It is similar to oleanolic acid, trimentic acid, and maslinic acid. The only difference from ursolic acid is that it has a 2-α-hydroxy bond. It is a lipid-soluble compound with the chemical formula C30H48O4 and a molecular weight of 472.710.

[0023] Corosolic acid is, part 2: Basic explanation of corosolic acid, part 2: Corosolic acid is a naturally occurring compound. Corosolic acid and its related compounds, as well as the representative medicinal herb banaba, are plants belonging to the Lythraceae family, and their Japanese name is Oobana Sarusuberi. They are widely distributed from Southeast Asia and southern China to northern Australia. The components in banaba leaves have been shown to lower blood sugar levels, and it is attracting attention as a supplement for diabetes. In addition, it is well known that the leaves of loquat, guava, persimmon, mulberry, and quince also contain large amounts of corosolic acid and its related terpenes. Alleviation and treatment of dementia. The problem that this invention aims to solve is to provide a product for people with dementia, MCI (mild cognitive impairment), and smartphone addiction syndrome who often experience "forgetfulness" that: 1) restores cognitive function safely and reliably; 3) can be taken orally anytime; 4) is inexpensive and convenient; 5) is a health food, confectionery, bread, or noodle product; and 6) promotes conversation and a cheerful mood.

[0024] Clearly present affordable dementia prevention methods and solutions. Dementia and MCI (mild cognitive impairment) affect approximately 10 million people in Japan, and over 20 million including their families, making it one of the biggest health and social problems alongside cancer. Currently, the only medications available for dementia are intravenous drugs that "may delay the onset of dementia."

[0025] This treatment costs patients 10,000 to 100,000 yen per month, and including government subsidies, each treatment costs a hefty 116,000 yen. If 10 million people were to receive this treatment, the total cost would exceed 10 trillion yen. Furthermore, this prescription requires a specialist's license, meaning it cannot be administered just anywhere. The intravenous infusion takes over an hour and a half, and memory clinics, psychiatric hospitals, and other memory clinics quickly become full, creating a problem where they cannot accept other patients. At the same time, elderly people living alone or in rural areas face the problem of transportation costs and taxi arrangements. Solutions to the mental and physical challenges of dementia. Mentally, for the elderly and those with MCI (mild cognitive impairment), the feeling of "connection" ("I am connected to you") is crucial. Not letting them feel lonely and listening to their anxieties and frustrations creates that "connection," and the drugs, health foods, and general foods containing corosolic acid of this invention create opportunities for that. It is safe, inexpensive, and can be consumed anytime, anywhere in sweets, drinks, or jellies, eliminating concerns about accidental ingestion or swallowing difficulties, thus enabling dementia prevention.

[0026] An unprecedented solution to alleviate the burden of dementia care. Another solution is the digitalization and mechanization of dementia care. As mentioned, both "mind and body" care are important in elderly care and dementia care. However, each person is different, and the response must be tailored to the individual and their personality. This is where the digitalization and robotization of care comes in. If "monitoring," "checking," and "conversation" can be done remotely, it may be possible to rationalize care, and the data collection for the "connection" that is the foundation of this begins with "conversation" with general foods, snacks, and lactic acid bacteria beverages containing corosolic acid, as described in this invention.

[0027] The following is an example of changes in MMSE scores before, 2 weeks after, and 1 month after corosolic acid intake in a clinical trial participant aged 70 or older. Before and after corosolic acid intake in elderly individuals aged 70 and over MMSE test score results after 2 weeks to 1 month of corosolic acid intake. JPEG2026119548000002.jpg255162 The following are the MMSE scores of young and adult participants who developed smartphone addiction and began experiencing memory loss, before, 2 weeks after, and 1 month after taking corosolic acid. Before and after corosolic acid intake in adults aged 20-60 MMSE test results after two weeks of corosolic acid intake The following is an example of blood analysis results from an OGTT (Oral Glucose Tolerance Test) performed before, 2 weeks after, and 1 month after corosolic acid intake in a clinical trial participant aged 70 or older with MCI (Mild Cognitive Impairment). Corosolic acid intake and improvement of insulin resistance and dementia Experimental data proving the correlation The following is an overview of the dementia clinical trial in question. JPEG2026119548000004.jpg255167JPEG2026119548000005.jpg141170

[0028] Overview of the MMSE trial: We used a precisely measured ethanol hot water extract, with each tablet containing 1 milligram of corosolic acid.

[0029] JPEG2026119548000006.jpg971701) Exam Period: June 15, 2019 (Sat) - October 5, 2019 (Sat) 2) Test location: San Pascual district, Talavera town, Nueva Ecija province, Republic of the Philippines 3) Implementation period and test subject: Corosolic acid administration period: 2 weeks (14 days). Tablets containing banaba ethanol hot water extract and 1 milligram of corosolic acid, taken 1 tablet at a time, 3 times a day. 4) Manufacturer: Kowa Co., Ltd., 99-5 Chigusa-cho, Hanamigawa-ku, Chiba City 5) Tablets: Total weight of one tablet is 250 milligrams (3 tablets equal 0.75 grams) 6) Contents: Banaba tablets: Lagerstroemia speciosa ethanol hot water extract 40% (corosolic acid 1 mg), lactose 25%, dextrin 28%, cellulose 5%, ester 2%. Calories 0, Protein 0, Carbohydrates 0, Ash 0, Fat 0, Other chemical components 0, Corosolic acid 1.0 mg (See image below / This was given in 3 tablets x 14 days = 42 tablets) 7) Dosage: Take 3 tablets at a time, before or after each meal (morning, noon, and evening), approximately 3 times a day. Take with water. (Regarding the safety of corosolic acid intake, a safety study of 20 milligrams per day has been conducted in human clinical trials in Canada.) Approved as a "Food for Specified Health Uses" (FOSHU) in Japan and South Korea. 9 mg per day, within the range where safety has been confirmed in Japan and the US. 8) Confirmation of safety and side effects: Participants were checked for health effects twice during the clinical trial, and no one reported any abnormalities, malaise, or changes in their physical condition. 9) Person in Charge of Implementation: Futoshi Matsuyama, 117-7 Amada (Kitamoto 1-ku), Fukuchiyama City, Kyoto Prefecture 10) Interviewer and Director: Ellynor C. Dumont. Address: 662 San Pascual, Talavera, Nueva, Ecija, Philippines. This project involves utilizing the contact capabilities of corosolic acid to create a generative AI (e.g., ChatGPT). Corosolic acid can generate conversations that foster "connection." This conversation is captured on a smartphone and analyzed by a generative AI to create a "personal map of dementia and MCI (mild cognitive impairment)." The AI ​​then develops software and hardware to suggest to caregivers things that make the individual with dementia enjoyable, things that soothe their mood, favorite snacks, hobbies, changes in mood over time, physical condition, illnesses, family, and other concerns and ways to alleviate them. [Means for solving the problem]

[0030] This invention is the discovery of a material for solving dementia. It is a medical device containing corosolic acid with a corosolic acid content of 0.001-99.9%, used for the prevention, alleviation, and treatment of dementia and MCI (mild cognitive impairment), as well as to delay the onset of dementia, and for the recovery and improvement of cognitive function, etc. Compositions for pharmaceuticals and food products.

[0031] Furthermore, there is the discovery of natural compounds with immunomodulatory functions. Using corosolic acid and extracts containing it, active pharmaceutical ingredients and pharmaceutical compositions are developed to alleviate and cure anti-dementia problems at each stage of dementia progression.

[0032] Furthermore, this involves the discovery of a composition that improves or enhances the metabolism of the frontotemporal lobe. This composition, containing corosolic acid at a concentration of 0.001-99.9%, is used for the prevention, alleviation, and treatment of dementia and MCI, as well as to delay the onset of dementia, and for the recovery and improvement of cognitive function, while simultaneously improving the metabolism and blood flow of the frontotemporal lobe, which controls emotions in individuals with dementia, and is also used as a raw material for extracted health foods containing this composition.

[0033] Furthermore, this involves the discovery of a composition that can be used in general foods for anti-dementia purposes. This composition is a pale white, highly concentrated corosolic acid extract containing 0.1-80% corosolic acid, and is used for anti-dementia purposes such as preventing, alleviating, and curing dementia and MCI (mild cognitive impairment), delaying the onset of dementia, and restoring and improving cognitive function. It also includes a non-digestible dextrin mixed powder manufactured using the extracted raw material containing this extract, as well as compositions for general foods such as oils and fats, wheat flour, rice flour, seasonings, alcoholic beverages, confectionery, tofu, health foods, noodles, beverages, yogurt, gummies, and candies.

[0034] Furthermore, this involves the discovery of the functional group of corosolic acid and semi-synthetic materials. These include active pharmaceutical ingredients and pharmaceuticals created by cleaving corosolic acid and synthesizing the resulting portion, for use in the prevention, alleviation, and treatment of dementia and MCI (mild cognitive impairment), as well as for delaying the onset of dementia, and for restoring and improving cognitive function, and for anti-dementia purposes, as well as active pharmaceutical ingredients and pharmaceuticals and compositions for use as general food ingredients, in which corosolic acid is modified with sugar chains, etc.

[0035] Furthermore, this involves the discovery of a composition for data collection for anti-dementia purposes using generated AI. This composition uses corosolic acid as a raw material for general food products, which serves as the starting point for a "conversation tool" and "personal map" that digitizes conversations with each individual with dementia or MCI (mild cognitive impairment), converts that conversation into personal data, develops software to install on smartphones and tablets, and digitizes topics of "connection" and care for the individual's mental well-being.

[0036] Furthermore, this involves the discovery of the application of corosolic acid to antibody-drug conjugates (ADCs). This includes active pharmaceutical ingredients and compositions for use in pharmaceuticals and general food ingredients that contain 0.001-99.9% corosolic acid, which crosses the blood-brain barrier as an insulin linker and improves metabolism and blood flow in the frontotemporal lobe and hippocampus. Furthermore, this involves the discovery of raw materials for the rational production of anti-dementia substances. It involves utilizing the properties of plants containing corosolic acid, such as banaba, loquat, persimmon, and mulberry, to alleviate and treat dementia and MCI (mild cognitive impairment). Specifically, it involves using callus cultured from plants during the autumn foliage season, before leaf fall, and expanding it using mushroom (ascomycetes and basidiomycetes) cultivation methods. The resulting extract contains 0.001-99.9% corosolic acid, which is isolated and purified. This is used in active pharmaceutical ingredients, pharmaceuticals, and general food ingredients.

[0037] Furthermore, it involves discovering a dosage that provides a safe and reliable effect for anti-dementia purposes. This involves isolating and purifying the natural compound corosolic acid, and using it as a raw material, pharmaceutical, or health food for the prevention, alleviation, and treatment of dementia and MCI (mild cognitive impairment), as well as delaying the onset of dementia, and for restoring and improving cognitive function. The dosage is 1 mg to 180 mg per day.

[0038] Furthermore, the discovery of effective combinations with other materials for anti-dementia treatment is noteworthy. The most effective materials are *Tricholoma rhodopolium* and ginkgo biloba, which have immune-modulating functions and improve blood flow. In addition, intravenous drugs that reduce amyloid-beta production and eliminate existing amyloid-beta are used to make anti-dementia therapy more effective. A corosolic acid active pharmaceutical ingredient that can be used in combination to obtain the desired effect, as well as a composition containing corosolic acid for use in pharmaceuticals, general foods, and health food ingredients.

[0039] Furthermore, it is the invention of "Personal Map," AI-powered personal information software for people with dementia. It collects data through conversations based on the "connection" between the hearts of elderly people with dementia and their caregivers, including their favorite foods, toys, care, tools, online images, music, exercises, etc. The AI ​​analyzes this data and guides the user to create a personal information file called "Personal Map," which serves as a trigger or entry point for automating care for the elderly, those with MCI (mild cognitive impairment), and people with dementia using robots and digital tools. This is a composition of foods, beverages, digital tools, etc.

[0040] Furthermore, this invention relates to a DX network for people with dementia, caregivers, facilities, and local governments. It is a business model that utilizes AI generation and digital tools to alleviate dementia care by leveraging the contact capabilities of corosolic acid. To realize this, a computer AI analyzes conversations of the elderly and others from everyday conversations as voice data, aiming to rationalize care, such as by developing care robots. Claim 12 is a composition for an IoT information tool and a business model that utilizes the contact capabilities of corosolic acid as an information entry point. [Effects of the Invention]

[0041] 1) Anti-dementia everyday foods: Manufacturing and selling general foods containing corosolic acid. In particular, using a broader concept (the theory that insulin resistance is the cause of dementia, and the extraction, isolation, and purification technologies of corosolic acid described in past patent applications related to corosolic acid, such as those in prior patent documents 6, 8, and 9), we will create a variety of inexpensive, child-sized candies in the style of a traditional Japanese candy store, focusing on sweets. It would be interesting to create candies that incorporate airplanes and cars for men, and dolls and play sets for women. Anti-dementia health foods: Traditional tablets and capsules are still necessary. However, we also manufacture and sell products that don't feel like medicine, such as bite-sized jellies, Yakult-sized lactic acid bacteria drinks, and cup puddings. The key points of development are that the products are "fun," "conversational," and "light and not burdensome." Therefore, design is also important; we must create products that elderly people will want to look at.

[0042] 2) Active pharmaceutical ingredients and drugs for anti-dementia: The basic approach is licensing to pharmaceutical companies. However, leveraging the know-how and network cultivated in reagent manufacturing, we also undertake contract manufacturing of active pharmaceutical ingredients. Our knowledge of the "polarity" of corosolic acid enables us to achieve low-cost, high-volume production using large columns.

[0043] 3) Anti-Dementia DX: The purpose of data collection is "connection." Data will be collected by incorporating the knowledge and opinions of caregivers, physical therapists, care managers, doctors, and nurses. The criteria for data collection will be "individually input" data into the caregiver's smartphone or tablet regarding when elderly people, people with dementia, and people with MCI (mild cognitive impairment) "showed happy expressions," "showed unpleasant expressions," "gave cheerful replies," "showed depressed expressions," "positive things," "silence," "anger," "dissatisfaction," "positive," "negative," "past," "present," "future," "family," "money," and "illness." If a large amount of data is collected, it will be used to develop "remote daily care tablets" and robots.

[0044] 4) Anti-dementia Digital IoT: Utilizing the data from this invention, we will connect it to a comprehensive anti-dementia network industry for society as a whole. With the government at the forefront, Japan, the world's most aging society, will realize the world's leading happiest society for the elderly through an IoT network. Information sharing among individuals, caregivers, facilities, physical therapists, doctors, clinics, hospitals, care managers, and government agencies will lead to efficient anti-dementia projects.

[0045] The concretization of new anti-dementia materials and methods is beginning. Despite the collapse of the amyloid-beta cascade hypothesis and the setbacks in the development of new amyloid-beta dementia drugs, no effective anti-dementia drugs have emerged. However, this invention... Corosolic acid was developed using an inductive method (determining the cause from the result). In other words, corosolic acid intake resulted in a significant improvement in dementia. This result is a "fact" and cannot be denied. Photographs showing each person's facial expressions from before the start, 2 weeks after, and 1 month after the end of the program, as well as MMSE scores and OGTT blood analysis data, have all been analyzed and stored, leaving no room for doubt about the effectiveness of corosolic acid. A consistent cause and theoretical mechanism of action of dementia has been elucidated. Previous overarching concepts only indicated that the cause of dementia was cellular stress due to insulin resistance and the development of chronic inflammation. However, it has been shown that a "sense of connection"—the feeling that "you and I are connected"—is important in dementia, and that mental aspects such as "sulking, anxiety, dissatisfaction, hearing loss, depression, and loneliness" are significantly involved. At the same time, a paper from Standard University confirmed that in the brain, the toxicity of amyloid-beta is primarily caused not by the dissolution of the cerebral cortex and brain atrophy, but by "chronic inflammation of the frontal lobe, which is responsible for emotions, learning, and memory." This does not contradict the higher-level concept of this invention, but rather proves consistency. A consistent mechanism of action that will convince experts worldwide. To explain the consistency between higher-level and lower-level concepts, 1) Corosolic acid is a naturally occurring compound that exerts an immune-regulating function in living organisms. 2) Corosolic acid is a low-molecular-weight molecule with 1.36 million times 1 trillion molecules in 1 milligram. A tiny amount is sufficient to spread throughout the body. 3) The carboxyl group of corosolic acid binds to the amino protein of insulin. 4) Corosolic acid has affinity for insulin as a linker and promotes its binding to the receptor. 5) Corosolic acid improves the effectiveness of insulin. 6) Longevity and fast-digesting foods that are rich in nutrients can lead to chronically high blood sugar and insulin resistance. 7) Insulin resistance is an "insulin overflow" caused by chronically high blood sugar levels. 8) Insulin resistance means that insulin is not working well. Because it is not working well, more insulin is produced. 9) Insulin overflow continues to stress cells. 10) Cells and organs that are subjected to continuous stress develop inflammation. 11) Inflammation spreads and becomes chronic inflammation. The same is true for the development of cancer cells. 12) When chronic inflammation occurs, the immune system's defense forces are deployed. These include killer T cells and macrophages. 13) The battle leaves behind wreckage. Blood clots. These obstruct blood flow and lead to metabolic failure. 14) Dementia has two aspects: "emotional instability" plus "memory impairment." 15) The part of the brain that controls both emotions and memories is the "frontal lobe." 16) Chronic inflammation was found in the frontal lobe of dementia patients, and the cause was found to be immune macrophages. 17) An excess of macrophages was interfering with the metabolism of the frontal lobe. 18) To solve this, we must improve the metabolism of the frontal lobe. In other words, we need to restore blood flow. 19) However, the brain has a blood-brain barrier that only allows small molecules (molecular weight 400) to pass through. 20) However, insulin is an exception. Insulin can cross the blood-brain barrier. 21) Corosolic acid traveled on insulin, crossed the blood-brain barrier, and reached the frontotemporal lobe. 22) Chronic inflammation in the frontal lobe, which controls emotions and memory, was alleviated, blood flow improved, and cognitive function recovered. 23) This indirectly proved that dementia cannot be solved with synthetic drugs. It is the immune system's ability to regulate it. 24) Corosolic acid can be industrialized. More than 100 million people are waiting for corosolic acid. [Brief explanation of the drawing]

[0046] [Figure 1] Corosolic acid molecular formula and 3D image [Figure 2] Line graph of MMSE experimental scores for 70-year-olds in the Philippines [Figure 3] Line graph showing the results of corosolic acid intake improving insulin response and saving total insulin secretion. [Figure 4] Statistical table showing that corosolic acid intake restored memory function in both the elderly and adults. [Figure 5] Line graph showing MMSE scores before, 2 weeks after, and 1 month after MMSE corosolic acid intake in individuals aged 30-50. [Figure 6] Photo 1 of evidence showing MMSE administered to a clinical trial participant aged 70 or older. [Figure 7] Bruised apples taste sweet, and corosolic acid is a compound with the same properties. [Figure 8] Professor Kaihei Oshio of Tokyo University of Agriculture studied corosolic acid in banaba leaves for 24 hours. [Figure 9] Corosolic acid reagent standard extracted from banaba by HPLC (white, purity 96% or higher) [Figure 10] Takeshi Fujita, former Deputy Director of Takeda Pharmaceutical Company Research Institute and early research leader of corosolic acid. [Figure 11] Three-dimensional image and chemical formula of corosolic acid [Figure 12] Adult female clinical trial participant who has started experiencing memory loss due to smartphone addiction [Figure 13] A 20-year-old young participant in a clinical trial, suffering from smartphone addiction and memory loss. [Figure 14] One of the elderly clinical trial participants and the MMSES test [Figure 15] One of the elderly clinical trial participants and the MMSES test [Figure 16] A group of elderly clinical trial participants, including an 88-year-old named Lacruz. [Figure 17] Hi-PrecisionDiagnose reception counter [Figure 18] Hi-Precision Diagnosis in Cabanatuan City, Nueva Ecija Province, Philippines [Figure 19] Clinical trial participants waiting their turn at the OGTT facility, Hi-Precision Diagnose. [Figure 20] After one month of taking corosolic acid, the participants' appetites and smiles returned. [Figure 21] Everyone is looking at their smartphones, even on the train. [Figure 22] Elderly people are also addicted to smartphones. [Figure 23]Professor Steve Cole of the University of California emphasizes the importance of "connections" for healthy longevity. [Figure 24] The history of evolution explains the importance of "connections." [Figure 25] Based on data from 300,000 long-lived individuals, "connections" are the most important factor. [Figure 26] "Connecting" and "You and I are connected": Key points for alleviating dementia symptoms [Figure 27] Digitalization of nursing care [Figure 28] Strawberry Daifuku (corosolic acid can be added to the mochi) Strawberry Rice Cake [Figure 29] Yamamoto Kampo Banaba Tea Teabags [Figure 30] Yakult's Bansourei Tea (bottled tea, contains corosolic acid) [Figure 31] Bread containing corosolic acid [Figure 32] Corosolic acid tablets (health food) [Figure 33] Sushi (It is possible to add a pale white extract of corosolic acid) [Figure 34] American Banaba Extract Health Supplement (Contains Corosolic Acid) [Figure 35] Yakult [Figure 36] Cup Jelly (MiniCap Jelly) [Figure 37] Ramune candy (MeltPop Candy) [Figure 38] Conceptual diagram of the frontal lobe's position [Figure 39] Image of the frontal lobe [Figure 40] Cerebral scan (taken from above) [Figure 41] The role of the brain's functions: the frontal lobe controls emotions and memory. [Figure 42] Linkers are considered a "bridge" that connects antibodies and drugs, and are attracting attention for "targeted cancer therapy." [Figure 43]Corosolic acid is likely an insulin linker. [Figure 44] Conceptual diagram of an antibody-drug conjugate (ADC). [Figure 45] 3D stereoscopic image of corosolic acid (docking simulation possible) [Figure 46] 3D image of corosolic acid [Figure 47] Standard University [Figure 48] Standard University published CT scans of the frontal lobe in healthy individuals (showing active blood flow). [Figure 49] Standard University published CT scans of the frontal lobe of dementia patients (showing low blood flow). [Figure 50] Chronic inflammation of the frontal lobe (macrophage overrun hypothesis) published by Standard University [Figure 51] Constant stress on cells causes inflammation. [Figure 52] Doctors say dementia is chronic inflammation of the brain. [Figure 53] Recanemab, an intravenous drug believed to reduce amyloid-beta and delay dementia. [Figure 54] A female doctor says it's difficult to tell if recanemab is working. [Figure 55] A doctor at a memory clinic says he can no longer accept the use of recanemab infusions for dementia. [Figure 56] One example of the difficulty in administering recanemab: it cannot be administered intravenously by anyone other than a specialist. [Figure 57] For conversations with people with dementia and the elderly, information is collected through conversations using a headset and then used to generate AI. [Figure 58] For elderly people living alone, tablets can be used for conversation and health checks. [Figure 59] Gathering information through smartphone conversations [Figure 60] The increase in centenarians in Japan and the average life expectancy of men and women [Figure 61] Using AI devices in elderly care [Figure 62] Mizuho researcher Katsuhiko Fujimori explains the socialization of family functions that "connect" people. [Figure 63] DX tool tablet devices [Figure 64] IoT for sharing information on anti-dementia while strictly managing personal information [Figure 65] An IoT image illustrating the sharing of dementia information obtained using corosolic acid within society. [Figure 66] Photos of banaba leaves and flowers (Philippines), which were the raw materials for the initial extraction of corosolic acid. [Modes for carrying out the invention]

[0047] The basic form for implementing the invention is the efficient extraction, isolation, purification, and mass production of corosolic acid using plant culture, which is the higher-level concept. The form for implementing the lower-level concept of anti-dementia will be collaboration among new main players. There are two ways to industrialize this invention: 1) applying it to health foods and general foods, and 2) collaborating with bio-venture companies aiming to develop it into pharmaceuticals. To implement the invention of corosolic acid as described in 1), collaboration with a major trading company possessing comprehensive capabilities will be crucial. The first step is to connect with a trading company or a company with comparable comprehensive capabilities and international reach in areas such as raw material import, processing, procurement, sales, and contracts. 2) Patent applications are not made public for 1.5 to 2 years. This is to protect the invention from companies and individuals who might copy it or steal its innovativeness and step-by-step capabilities. However, dementia countermeasures are an urgent matter. Pharmaceutical approval is said to take about 10 years, and considering the current circumstances, a confidentiality agreement must be signed and basic research data collection must begin immediately. In that sense, it is important that corosolic acid is granted patentability similar to that of a substance patent. [Industrial applicability]

[0048] As for its potential industrial applications, corosolic acid for dementia will create new industries worldwide. Its range of applications will extend to pharmaceuticals, food, medical care, retail, beverages, home appliances, telecommunications, elderly care, and software development. The reasons for this are 1) there is no effective drug for dementia, and 2) intravenous drugs are not widely available. 3) It is difficult to introduce, dementia and MCI (mild cognitive impairment) affect 20 million people in Japan alone, involving their families, 4) there are no safety concerns with the corosolic acid of the invention, 5) teratogenicity tests and accelerated aging tests have been conducted at the compound level.

Claims

1. Claim 1 of the present invention is the discovery of a material for solving dementia. A pharmaceutical and food composition containing corosolic acid with a content of 0.001 to 99.9%, to be used for the prevention, alleviation, and cure of dementia and MCI (mild cognitive impairment), to delay the onset of dementia, and for anti-dementia purposes such as the recovery and improvement of cognitive function.

2. Claim 2 of the present invention is the discovery of a natural compound having an immunomodulatory function. A drug substance and pharmaceutical composition using corosolic acid and extracts containing the same to solve the anti-dementia problem of alleviation and cure at each stage of dementia progression.

3. Claim 3 of the present invention is the discovery of a composition that improves or enhances the metabolism of the frontotemporal lobe. A composition containing corosolic acid with a corosolic acid content of 0.001 to 99.9%, which can be used for the prevention, alleviation, and treatment of dementia and MCI, as well as to delay the onset of dementia, and for the recovery and improvement of cognitive function, and at the same time improves the metabolism and blood flow of the frontotemporal lobe, which controls the emotions of people with dementia, and a raw material composition for a health food extracted therefrom.

4. Claim 4 of the present invention is the discovery of a composition that can be used in general foods for anti-dementia purposes. A pale white, highly concentrated corosolic acid extract containing 0.1-80% corosolic acid, and a composition for general foods such as oils and fats, wheat flour, rice flour, seasonings, alcoholic beverages, confectionery, tofu, health foods, noodles, beverages, yogurt, gummies, and candies, which can be used for the prevention, alleviation, and treatment of dementia and MCI (mild cognitive impairment), as well as to delay the onset of dementia, and for the recovery and improvement of cognitive function.

5. Claim 5 of the present invention is the discovery of a functional group of corosolic acid and a semi-synthetic material. A drug substance and pharmaceutical product prepared by cleaving corosolic acid and synthesizing the resulting portion for use in the prevention, alleviation, and treatment of dementia and MCI (mild cognitive impairment), as well as for delaying the onset of dementia, and for restoring and improving cognitive function, and for anti-dementia purposes, as well as a drug substance and pharmaceutical product and a composition for use as a general food ingredient, in which corosolic acid is modified with sugar chains, etc.

6. Claim 6 of the present invention is the discovery of a composition for data collection for anti-dementia using generated AI. A general food ingredient composition using corosolic acid that serves as the starting point for a "conversation tool" and "personal map" that digitizes conversations with each individual with dementia or MCI (mild cognitive impairment), digitizes personal data, develops software to install on smartphones and tablets, and digitizes topics of "connection" and care for the individual's mental well-being.

7. Claim 7 of the present invention is the discovery of the application of corosolic acid to antibody-drug conjugates (ADCs). A drug substance and composition for use as a pharmaceutical and general food ingredient containing 0.001 to 99.9% corosolic acid, which crosses the blood-brain barrier as an insulin linker and improves metabolism and blood flow in the frontotemporal lobe and hippocampus.

8. Claim 8 of the present invention is the discovery of a raw material for rationally producing an anti-dementia substance. A raw material for pharmaceuticals and general food ingredients containing 0.001 to 99.9% corosolic acid, which is obtained by utilizing the properties of plants containing corosolic acid, such as banaba, loquat, persimmon, and mulberry, used to alleviate and treat dementia and MCI (mild cognitive impairment), and by utilizing callus obtained by cell culture of plants, particularly during the autumn foliage season and before leaf fall, and increasing its volume using a mushroom (ascomycete and basidiomycete) cultivation method, and extracting, isolating, and purifying the extract thereof.

9. Claim 9 of the present invention is the discovery of a formulation that provides a safe and reliable effect for anti-dementia purposes. A natural compound to be used for anti-dementia purposes, such as for the prevention, alleviation, and treatment of dementia and MCI (mild cognitive impairment), as well as for delaying the onset of dementia, and for the recovery and improvement of cognitive function. A drug, pharmaceutical, or health food containing isolated and purified corosolic acid, administered daily at doses of 1 mg to 180 mg to treat dementia and MCI (mild cognitive impairment).

10. Claim 10 of the present invention is the discovery of effective combinations with other materials for anti-dementia purposes. The most effective materials are *Tricholoma rhodopolium* and *Ginkgo biloba*, which have immune-modulating functions and improve blood flow. In addition, the present invention relates to corosolic acid active pharmaceutical ingredients and pharmaceuticals, as well as compositions containing corosolic acid for use in general foods and health food ingredients, which can be used in combination with other materials such as intravenous drugs that reduce the production of amyloid-beta and eliminate amyloid-beta that has been produced, in order to obtain more effective anti-dementia therapy.

11. Claim 11 of the present invention relates to the invention of an AI personal information software for dementia patients called "Personal Map". The invention relates to a composition of food, beverages, digital tools, etc., which collects data through conversations based on the "connection" between the minds of elderly people with dementia and their caregivers, such as their favorite foods, toys, care, tools, internet images, music, exercises, etc., and an AI analyzes this data to guide users to a personal information file called "Personal Map," which serves as a trigger or entry point for automating care by robots or by digital tools for the elderly, MCI (mild cognitive impairment), and people with dementia.

12. Claim 12 of the present invention is a DX network invention for people with dementia, caregivers, facilities, local governments, etc. It is a business model that utilizes generation AI and digital tools to alleviate dementia care by leveraging the contact power of corosolic acid. To realize this, a computer AI analyzes conversations of the elderly and others from everyday conversations as voice data, and aims to rationalize care, such as by developing care robots. Claim 12 is a composition for an IoT information tool and a business model that uses the contact capabilities of corosolic acid as an information entry point.

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