Use of vitamin compositions in preparation of medicaments for preventing, treating or delaying alzheimer disease

Abstract

To provide compositions comprising a combination of vitamins for treating Alzheimer disease.SOLUTION: Disclosed is a pharmaceutical composition for preventing, treating or delaying Alzheimer disease that comprises a combination of vitamins, where the combination of vitamins contains ingredients in the following weight ratio, 100 parts of vitamin B1, 100 parts of vitamin B2, 100 parts of vitamin B3, 100 parts of vitamin B5, 100 parts of vitamin B6, 0.1 part of vitamin B7, 0.4 part of vitamin B9, 0.1 part of vitamin B12, and 150 parts of vitamin C.SELECTED DRAWING: None

Description

[Technical field]

[0001] FIELD OF THEINVENTION The present invention relates to a vitamin composition, in particular, a vitamin composition for preventing Alzheimer's disease by promoting energy metabolism. The present invention relates to a composition comprising a vitamin B composition and a vitamin C composition for the treatment of rheumatoid arthritis. The disclosed compositions are suitable for preventing, treating or delaying Alzheimer's disease, the compositions comprising: It can improve learning and memory abilities as well as cognitive impairment. [Background technology]

[0002] BACKGROUND OF THEINVENTION Alzheimer's disease (AD) is a neurodegenerative disorder of the central nervous system that usually affects people over the age of 65. is characterized by progressive cognitive decline and behavioral disturbances; and It is the most common type of senile dementia. Currently, the etiology of Alzheimer's disease is not fully understood. It is not clear whether metabolic disorders are one of the reasons for Alzheimer's disease. Sugar is the body's It is the main source of metabolism, and abnormal glucose metabolism leads to a series of disorders of tissue function. Here, the brain tissue, which uses glucose as its main energy source, will have abnormal Glucose metabolism is significantly affected. Numerous studies have demonstrated that patients with AD have metabolic dysfunction. At the same time, a slowdown in brain metabolism is one of the earliest symptoms of AD, and This suggests that changes occurring earlier than functional impairment can be detected by neuropsychiatric testing. Imaging studies have demonstrated brain atrophy, metabolic disturbances, and other physiological abnormalities in patients with AD. Concomitant metabolic abnormalities were observed and demonstrated to worsen with progression of the disease. Potential mechanisms of glucose metabolism include direct hyperglycemia toxicity, hyperglycemia-induced brain damage, and Insufficient energy supply, insulin resistance, and abnormalities in insulin signal transduction in the It has also been found that this condition may be associated with abnormalities in the insulin-degrading enzyme gene. FDG-PET glucose metabolism imaging has shown that glucose metabolic rate is elevated in the frontal lobe several years before dementia. It was confirmed that a decrease in the cingulate cortex of the parietal and temporal lobes was observed. This suggests that impaired glucose metabolism in the brain is closely related to AD, and that the metabolic disorder It is believed to be one of the causes and development of AD, and therefore improves brain energy metabolism. These results suggest that it may be possible to prevent and reduce the onset of AD by

[0003] Glucose glycolysis and the tricarboxylic acid cycle are the major drivers of glucose production (ATP) in the body. These are the main metabolic pathways. The complete reactions of these two energy metabolic pathways are The activity of these metabolic enzymes requires the participation of coenzymes. Rhodamine dehydrogenase is a multienzyme complex in the mitochondrial matrix. This enzyme is a key player in catalyzing the oxidative decarboxylation of pyruvate to acetyl-CoA. The reaction processes catalyzed by PDH are glycolysis, tricarbamate, and glycerol. It is involved in the phosphate cycle and ATP formation. It is the rate-limiting enzyme in the tricarboxylic acid cycle and catalyzes the oxidative decarboxylation of isocitrate. The H removed during the catalytic reaction is converted to α-ketoglutaric acid. + is NAD + NADH It is the first step in the tricarboxylic acid cycle to produce CO2 and It is an irreversible reaction and is the rate-limiting step in the tricarboxylic acid cycle. α-Ketoglutarate dehydrogenase present in the mitochondrial matrix (α-KGDH) is the rate-limiting enzyme in the tricarboxylic acid cycle. It is a constant It is important to maintain the redox state of the α-ketoglutarate dehydrogenase. Activity changers are closely related to neurodegenerative diseases. Dextrose is the sixth enzyme in the tricarboxylic acid cycle and is involved in the electron transport chain. Succinate dehydrogenase, flavin adenine dinucleotide Cytochromes and 3Fe-S proteins play important roles in sugar metabolism and the oxidative respiratory chain. SDH is an important component of mitochondrial complex II, which plays a key role in the regulation of mitochondrial function. It is present in the inner membrane of the mitochondrion and is a marker for the inner mitochondrial membrane. Its activity is It indicates metabolic status and mitochondrial function. SDHA encodes a flavoprotein and It is a subunit of succinate dehydrogenase, a key enzyme involved in the tricarboxylic acid cycle. As a marker enzyme for mitochondrial function, succinate dehydrogenase is It is one of the enzymes, and its activity is an indicator for evaluating the operation state of the tricarboxylic acid cycle. ATP5B encodes a subunit of ATP synthase. It is involved in hydrogen ion transport in mitochondria. is a type of synthetic enzyme in mitochondria and plays a key role in energy metabolism in living organisms. It is a key enzyme.

[0004] Vitamins are a set of organic compounds essential in human metabolism and are primarily responsible for the normal functioning of the body. They are responsible for maintaining and regulating the metabolic processes required by living organisms. They are generally not produced by the organism itself. Vitamins also play a role in the production of energy. Although they cannot be used to make cells like sugars, proteins and fats, they are essential for the functioning of living organisms. Regulates metabolism and maintains physical health.

[0005] Many vitamins are known to be involved in metabolic processes and they It is an essential component of the body's biochemical reactions. Vitamin B promotes metabolism in the body and They are essential substances for converting sugars, fats, proteins, etc. into heat. Most of them are coenzymes. Once a vitamin B deficiency occurs in the body, If this occurs, cell function will immediately decline and metabolic disorders will occur. Some of the members of the thymus group are known for their positive effects on the nervous system and psychological state. It is even called the psychotropic vitamin because of its high content of vitamin B1, B2, B3, B5, B6, B7 and B12. Vitamin B members, including those involved in glycolysis and the tricarboxylic acid cycle during glucose metabolism, Once these vitamins are deficient, this metabolic pathway is inhibited, This causes a series of diseases associated with metabolic disorders. Research has shown that vitamins B1, B2, B3, B5, It also indicates that B6, B7 and B12 are directly involved in energy metabolism processes. They are known to reduce the production of amyloid (Aβ), promote the metabolism of homocysteine ​​(Hcy), and inhibit tumor growth. May also play a role in the pathogenesis of AD, such as by reducing tumor necrosis factor (TNF-α) levels and supporting the synthesis of neurotransmitters. Therefore, these B vitamins are involved in the energy metabolism in the brain. By modulating the levels of This could be one of the potential treatment methods.

[0006] In addition to the B vitamins, supplementation with some fat-soluble vitamins such as vitamins D, E, and K may be beneficial. It can reduce the risk of atherosclerotic syndrome, lower fasting blood sugar levels, and improve insulin resistance. Clinical studies have shown that it induces insulin secretion and increases glucose metabolism in the brain. In addition, they reduce Aβ and TNF-α levels in the brains of animals with AD. and improved cognitive function in AD patients. It has been shown that it can simultaneously exert its effects on both glucose metabolism and neuronal function, and It also suggests that there may be some relationship between them. Taking these vitamins can regulate energy metabolism in the brains of AD patients and improve AD It is possible to improve the symptoms of. Trace elements are one of the essential components in the body. In addition, some trace elements have been reported to be involved in energy metabolism and the progression of AD. Clinical studies have shown that AD patients have significantly lower and more severe magnesium levels in the brain. Animal studies suggest that higher magnesium intake may reduce the risk of AD. showed that after 10 min of hypoxia in rats, ATP levels in the CA1 region were normalized. The ATP levels in brain slices treated with magnesium ions were only 16% of those in normal controls. The decrease in ATP levels in the CA1 region due to hypoxia was confirmed by Magnetoscopy. Therefore, the results suggest that the brain’s magnesium levels improved significantly. Regulation of calcium levels may prevent a depletion of the energy metabolite ATP in the brain, This improves neuronal function in the brain.

[0007] Through previous basic research, it has been demonstrated that vitamins are beneficial for maintaining health and preventing disease. In clinical applications, it has been gradually confirmed that Various vitamins are also used as dietary supplements to promote health and prevent disease. For neurological disorders, vitamins such as B1, B3, B6, B9, B12, C and E may be used. The authors report that the effects of high homocysteine ​​on neurodevelopment and homocysteine ​​metabolism (high homocysteine ​​is one of the risk factors for AD) It can promote the synthesis of neurotransmitters, and can improve the neurological disorders caused by pernicious anemia. They can prevent damage and improve neurological disorders in order to maintain the health of nervous tissue. Of particular importance are the following clinical applications: It has a significant therapeutic effect on peripheral neuritis disease and reducing oxidative stress (a potential cause of AD) is doing.

[0008] From the perspective of energy metabolism, vitamins B1, B2, B3, B5, B7, B6, B9, and B12 are It is involved in the biooxidation and physiological metabolism of carbohydrates, fats, and proteins in the body. In clinical applications, these vitamins promote metabolism and formation of energy. Min has been shown to treat the symptoms and causes of metabolic-related diseases, such as improving blood sugar regulation and promoting fat metabolism. With this in mind, vitamin drugs have a significantly higher clinical benefit. and for preventing and treating energy metabolism disorders, regulating the nervous system and delaying the onset of AD. It can be seen that the FDA is playing a significant role even in the development of new drugs. The combined results suggest that vitamin drugs may have potential value in energy metabolism and the treatment of AD. There is no doubt that vitamin A plays a role in the regulation of energy metabolism in the brain. Research into this has societal and clinical implications for preventing and reducing the incidence of AD.

[0009] Recently, a Phase 3 clinical study (NCT00235716) has shown that vitamin E has the potential to reduce cardiovascular disease by 2050-2060 after long-term supplementation (6-48 months). showed that it can effectively improve cognitive function in patients with mild cognitive impairment (MCI). Another Phase II clinical study (NCT01320527) also tested a multivitamin (containing B9, B12, E, and other nutrients) ) has also been shown to be beneficial for cognition and emotional regulation in MCI patients, which may explain the cognitive impairment. These results suggest that vitamin therapy may have a therapeutic effect on AD in the early stages of the disease. is.

[0010] In summary, basic and clinical research has demonstrated that: (1) B vitamins (B1, B2, B3, B5, B6, B7, and B12) (2) fat-soluble vitamins (D, E, K) and (3) trace elements (magnesium, iodine, etc.) All of these drugs have effects that regulate metabolism and contribute to the protection of neuronal function, as well as early bilirubin. However, to date, In fact, no vitamin drugs are used clinically to treat AD.

[0011] Currently, drugs used to treat AD are primarily acetylcholinesterase inhibitors. These drugs alter the levels of neurotransmitters in the brain. These drugs slow the decline of cognitive function by slowing the progression of symptoms for 6-12 months. It was known that it could only delay the

[0012] The present invention provides a multivitamin drug that contains some or all of the above elements, and In this study, the authors improved AD by regulating and slowing down energy metabolism in the brain. The purpose of the present invention is to prevent and treat the diseases caused by the following causes: The present invention aims to improve neurological and cognitive functions by improving the energy metabolism in the brain, Its mechanism of action is different from that of conventional neurotransmitter improving drugs and has obvious advantages. Conventional drugs can only treat symptoms, not diseases. At the same time, the present invention The disclosed drug is relatively safe and it regulates energy metabolism in the brain. It has no obvious side effects on the body and can be considered a gentle treatment method. Therefore, the energy metabolism drug of the present invention provides an innovative drug for the treatment of AD, and can reduce the severity of AD. It may play an important role in treatment.

[0013] Alzheimer's disease is a global disease that poses an enormous economic burden to families and society in the 21st century. According to reports, in 2016, the number of Alzheimer's patients in the United States was The economic loss caused by AD is estimated at $236 billion. The drugs used in this study are mainly acetylcholinesterase inhibitors and NMDA receptor antagonists. These drugs affect cognitive function by altering the levels of neurotransmitters in the brain. Although these drugs inhibit the decline of the immune system, the deterioration of symptoms can only be delayed by 6-12 months. It was known that these drugs could not completely halt the progression of AD. This is the biggest problem in AD treatment. The energy metabolism drugs included in the present invention are It is a new AD treatment drug. In animal experiments, we have shown that the drug effectively improves the cognition level of animals. The effect of the drug is to improve the efficacy and its mechanism is completely different from the current drugs on the market. After the drug was approved, It is expected that this will cover a large number of AD patients and the market potential will be vast. can be. Summary of the Invention

[0014] A. DISCLOSURE OF THEINVENTION The present invention relates to a method for treating Alzheimer's disease by promoting energy metabolism. The present invention relates to a certain vitamin composition, in particular a multivitamin B and C composition. Prevent, treat or delay Zheimer's disease and improve learning and memory abilities and cognitive impairment The vitamins referred to in this invention are suitable for improving the For example, vitamin B1 means thiamine as well as its analogs or derivatives; Vitamin B2 refers to riboflavin and its analogs or derivatives; Vitamin B3 refers to nicotinamide adenine diphosphate phosphate phosphate phosphate Vitamin B5 refers to pantothenic acid and its analogs or derivatives; Vitamin B6 means pyridoxine and its analogs or derivatives. Vitamin B7 means biotin and its analogs or derivatives; Vitamin B9 means , folic acid and its analogs or derivatives; Vitamin B12 means cyanocobalamin and Vitamin C means ascorbic acid and its analogs or derivatives; or derivatives thereof. In one preferred embodiment, the vitamin B composition and The composition, which contains vitamin C, contains vitamin B1 (thiamine), vitamin B2 (riboflavin), bottle), Vitamin B3 (nicotinic acid), Vitamin B5 (pantothenic acid), Vitamin B6, In a further preferred embodiment, the composition comprises vitamin B7 (biotin) and vitamin C. In the present invention, the composition containing a vitamin B composition and a vitamin C composition is Vitamin B2 (riboflavin), Vitamin B3 (nicotinic acid), Vitamin B5 (pantothenate) Vitamin B6, Vitamin B7 (Biotin), Vitamin B9 (Folic Acid), Vitamin C, Tartar In another further preferred embodiment, the composition comprises choline hydrogen carbonate and inositol. The composition, which includes a vitamin B composition and a vitamin C composition, contains vitamin B1 (thiamine ), Vitamin B2 (riboflavin), Vitamin B3 (nicotinic acid), Vitamin B5 (pantothenic acid) Vitamin B6, Vitamin B12, Vitamin B7 (biotin), Vitamin B9 (folic acid), A composition comprising: min C, choline bitartrate, inositol, and p-aminobenzoic acid.

[0015] In another aspect, the present invention provides a combination of an effective amount of a vitamin B composition and a vitamin C composition. and a pharma- ceutically acceptable carrier. The composition contains effective amounts of vitamin B1 (thiamine), vitamin B2 (riboflavin), vitamin B3 (vitamin B4), and vitamin B5 (vitamin B6). Vitamin B3 (nicotinic acid), Vitamin B5 (pantothenic acid), Vitamin B6, Vitamin B7, In a further preferred embodiment, the composition comprises: The composition contains effective amounts of vitamin B1 (thiamine), vitamin B2 (riboflavin), vitamin Vitamin B3 (nicotinic acid), Vitamin B5 (pantothenic acid), Vitamin B6, Vitamin B9 (folic acid), Vitamin B7 (biotin), Vitamin C, Choline Bitartrate, Inositol, and Pharmacological In another further preferred embodiment, the composition comprises an effective amount of Vitamin B1 (thiamine), Vitamin B2 (riboflavin), Vitamin B3 (nicotinic acid), Vitamin B5 (pantothenic acid), Vitamin B6, Vitamin B12, Vitamin B9 (folic acid), Vitamin B7 (biotin), Vitamin C, Choline Bitartrate, Inositol, p-Aminobenzoic Acid, and a pharma- ceutically acceptable carrier.

[0016] In yet another aspect, the present invention provides a method for treating a chronic bronchitis comprising administering to a patient a therapeutically effective amount of a vitamin B composition and a vitamin C composition. Combinations and effective amounts of drugs (including combinations) for preventing, treating, or delaying Alzheimer's disease In one preferred embodiment, the composition comprises an effective amount of Vitamin B1 (thiamine), Vitamin B2 (riboflavin), Vitamin B3 (nicotinic acid), Vitamin B5 (pantothenic acid), Vitamin B6, Vitamin B7 (biotin), Vitamin C, and The present invention includes an effective amount of a drug or drugs for preventing, treating or delaying Alzheimer's disease. In one further preferred embodiment, the composition comprises an effective amount of vitamin B1 (thiamine). , Vitamin B2 (riboflavin), Vitamin B3 (nicotinic acid), Vitamin B5 (pantothenic acid) ), Vitamin B6, Vitamin B9 (Folic Acid), Vitamin B7 (Biotin), Vitamin C, Tartaric Acid Water Choline, inositol, and an effective amount of choline to prevent, treat, or delay Alzheimer's disease In another further preferred embodiment, the composition comprises a drug or drugs for: Effective amounts of Vitamin B1 (thiamine), Vitamin B2 (riboflavin), Vitamin B3 (nicotine Vitamin B5 (pantothenic acid), vitamin B6, vitamin B12, folic acid, biotin, vitamin MinC, choline bitartrate, inositol, p-aminobenzoic acid, and effective amounts of Alzheimer's The present invention includes a drug or drugs for preventing, treating or delaying myeloma.

[0017] In still yet another aspect, the present invention provides a method for treating a chronic bronchitis, comprising administering to a patient a composition comprising an effective amount of a vitamin B composition and a vitamin C composition. and an effective amount of another vitamin compound. In an embodiment, the composition comprises an effective amount of vitamin B1 (thiamine), vitamin B2 (riboflavin), bottle), Vitamin B3 (nicotinic acid), Vitamin B5 (pantothenic acid), Vitamin B6, A more preferred embodiment of the present invention includes vitamin B7 (biotin), vitamin C, and effective amounts of other vitamin compounds. In a preferred embodiment, the composition comprises an effective amount of vitamin B1 (thiamine), vitamin B2 (riboflavin), vitamin B3 (nicotinic acid), vitamin B5 (pantothenic acid), vitamin Vitamin B6, Vitamin B9 (Folic Acid), Vitamin B7 (Biotin), Vitamin C, Choline Bitartrate, In another further preferred embodiment, the composition further comprises a vitamin C supplement, a vitamin B12 supplement, a vitamin B2 supplement, and an effective amount of another vitamin compound. The composition contains effective amounts of vitamin B1 (thiamine), vitamin B2 (riboflavin), Vitamin B3 (nicotinic acid), Vitamin B5 (pantothenic acid), Vitamin B6, Vitamin B12, Vitamin B9 (folic acid), Vitamin B7 (biotin), Vitamin C, choline bitartrate, wild boar Other vitamin compounds. These include vitamin A, vitamin D, vitamin E, vitamin K compounds, and the like.

[0018] In still yet another aspect, the present invention provides a method for treating a chronic bronchitis, comprising administering to a patient a composition comprising an effective amount of a vitamin B composition and a vitamin C composition. and an effective amount of trace element(s). In an embodiment, the composition comprises an effective amount of vitamin B1 (thiamine), vitamin B2 (riboflavin), bottle), Vitamin B3 (nicotinic acid), Vitamin B5 (pantothenic acid), Vitamin B6, A more preferred embodiment of the present invention includes vitamin B7 (biotin), vitamin C, and effective amounts of other vitamin compounds. In a preferred embodiment, the composition comprises an effective amount of vitamin B1 (thiamine), vitamin B2 (riboflavin), vitamin B3 (nicotinic acid), vitamin B5 (pantothenic acid), vitamin Vitamin B6, Vitamin B9 (Folic Acid), Vitamin B7 (Biotin), Vitamin C, Choline Bitartrate, In another further preferred embodiment, the composition further comprises a vitamin C supplement, a vitamin B12 supplement, a vitamin B2 supplement, and an effective amount of another vitamin compound. The composition contains effective amounts of vitamin B1 (thiamine), vitamin B2 (riboflavin), Vitamin B3 (nicotinic acid), Vitamin B5 (pantothenic acid), Vitamin B6, Vitamin B12, Vitamin B9 (folic acid), Vitamin B7 (biotin), Vitamin C, choline bitartrate, wild boar It contains vitamin C, niacin, p-aminobenzoic acid, and effective amounts of other vitamin compounds. Trace elements include iron, These include magnesium, zinc, etc.

[0019] The dosage form of the composition containing the vitamin B composition and vitamin C composition of the present invention is not limited to the following. No, but can be a chewable tablet; disintegrants, lubricants, binders, antioxidants, complexing agents, and Various conventional adjuvants are required to prepare various dosage forms, such as other pharmaceutical carriers. The compound is prepared by conventional preparation methods into dispersible tablets, granules, capsules, oral liquids, and other dosage forms. The compositions of the present invention can be used to prepare any of the commonly used oral dosage forms, such as It can also be added to things.

[0020] The weight ratio of each component of the composition containing the vitamin B composition and the vitamin C composition in the present invention is as follows: There are multiple options, all of which can promote energy metabolism and may be effective in treating Alzheimer's disease. In certain embodiments, it may be used to prevent, treat, or delay The following ingredients are mixed in the following ratios by weight: 30-300 parts vitamin B1, 30-300 parts vitamin B2, 30-300 parts vitamin Vitamin B3, 30-300 parts Vitamin B5, 30-300 parts Vitamin B6, 0.01-1 part Vitamin B7 (Bio 0.01-2 parts vitamin B9 (folic acid), 0.01-1 part vitamin B12, and 50-500 parts vitamin In one preferred embodiment, the vitamin B composition may comprise, based on vitamin C, the following components: The weight ratio is: 100 parts of vitamin B1, 100 parts of vitamin B2, 100 parts of vitamin B3, 100 parts of vitamin B Vitamin B5, 100 parts Vitamin B6, 0.1 parts Biotin, 0.4 parts Folic Acid, 0.1 parts Vitamin B12, and 150 parts vitamin C. In one preferred embodiment, the vitamin B composition The product contains the following ingredients in the following weight ratio: 10 parts vitamin B1, 15 parts vitamin B2, 25 parts vitamin B3, Based on 110 parts Vitamin B5, 10 parts Vitamin B6, 0.1 parts Biotin, and 150 parts Vitamin C In one more preferred embodiment, the vitamin B composition comprises the following ingredients by weight: Ratio: 10 parts vitamin B1, 15 parts vitamin B2, 25 parts vitamin B3, 110 parts vitamin B5, 10 0.1 part Vitamin B6, 0.1 part Biotin, 0.4 part Folic Acid, 250 parts Choline Bitartrate, 250 parts Iodine In one more preferred embodiment, the composition comprises 100 parts by weight of vitamin C, 150 parts by weight of inositol, and 150 parts by weight of vitamin C. The vitamin B composition contains the following ingredients in a weight ratio: 10 parts vitamin B1, 15 parts vitamin B2, 25 parts vitamin B3, 110 parts vitamin B5, 10 parts vitamin B6, 0.1 parts biotin, 0.4 parts leaves Based on 100 parts choline bitartrate, 250 parts choline bitartrate, 0.025 parts vitamin B12, and 150 parts vitamin C. In another more preferred embodiment, the vitamin B composition comprises the following ingredients in weight ratios: : 10 parts Vitamin Bl, 15 parts Vitamin B2, 25 parts Vitamin B3, 110 parts Vitamin B5, 10 parts of Vitamin B6, 0.1 parts Biotin, 0.4 parts Folic Acid, 250 parts Choline Bitartrate, 250 parts Inositol Based on 0.025 parts of vitamin B12, 50 parts of p-aminobenzoic acid, and 150 parts of vitamin C This includes:

[0021] (B. Definition) Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by a person skilled in the art to which this invention pertains. All patents, applications, issued applications and other publications referenced herein are hereby incorporated by reference in their entirety. , all of which are incorporated by reference in their entireties. In the patents, applications, issued applications and other publications incorporated herein by reference. If there is any contradiction or ambiguity with the definitions specified in this section, the definitions specified in this section shall prevail. , which take precedence over the definitions incorporated herein by reference.

[0022] As used herein, the singular forms "a," "an," and "the" are used where the context clearly indicates. Unless otherwise specified, "at least one" or "one or more."

[0023] The term "parts", when referring specifically to a quantity, refers to that quantity with a positive or negative deviation within 10%. do.

[0024] As used herein, the terms "comprise", "comprising" and " ", "includes", "including", "contains" ", "containing" and any variations thereof extend to a non-exclusive inclusion. It is intended that the term "contains" refers to an element or list of elements. A process, method, or product that includes or contains something - The bi-process or composition does not include only those elements, but explicitly lists A process, method, product-by-product, or other such item that is not listed The composition may include other elements not inherent to the composition.

[0025] As used herein, the term "vitamin B composition" refers to any type of vitamin B composition. Vitamin B or their corresponding analogs or derivatives, e.g., vitamin B1 (thiamine), Vitamin B2 (riboflavin), Vitamin B3 (nicotinic acid), Vitamin B5 (pantothenic acid) , vitamin B6, etc.

[0026] As used herein, the terms "analogs" and "analog logues) have roughly the same structure and the same biological activity, but at different levels of activity. As used herein, the term refers to any two or more molecules or fragments that may have the following structure: When referring to a compound, the term "derivative" refers to a compound in which a hydrogen atom or a group of an atom is replaced by another atom or Refers to more complex compounds derived from the substitution of atoms with groups. [Brief description of the drawings]

[0027] BRIEF DESCRIPTION OF THE DRAWINGS [Figure 1] Latency to platform during acquisition trials (D1-D5) for each group of animals. [Diagram 2] The residence time of each group animal in the target quadrant (1 being the target quadrant). [Diagram 3] The swimming distance of each group animal in the target quadrant (1 being the target quadrant). [Figure 4] Activity of energy metabolism-related enzymes in the cerebral cortex. [Diagram 5] Gene expression of energy metabolism-related enzymes in the cerebral cortex. EXAMPLES

[0028] (Detailed Description) Example 1: Therapeutic effect of multivitamins on ICV-STZ-induced AD rats 1. Research Objective The aim of this study was to evaluate the relationship between Alzheimer's disease and energy metabolism in the brain. Furthermore, the vitamin compounds regulate the energy metabolism in the brain. To evaluate whether these findings could play a role in the prevention and treatment of Alzheimer's disease It was to do so.

[0029] 2. Experimental Materials 2.1 Reagents Streptozotocin, containing the following ingredients in the following weight ratios: 100 parts vitamin B1, 100 parts vitamin B2 Vitamin B2, 100 parts Vitamin B3, 100 parts Vitamin B5, 100 parts Vitamin B6, 0.1 parts Vitamin B7 , 0.4 parts Vitamin B9, 0.1 parts Vitamin B12, 150 parts Vitamin C, liquid magnesium, Vitamin B12 tablets (ZENSUN) containing vitamins (D, E, K). Chloral hydrate. Solar ba IO Mitochondrial Enzyme Activity Kit (PDH Product No.: MS2103, α-KGDH Product No.: MS2100; ICDHm: MS2104, SDH: MS2102), Takara SYBR II, total RNA isolation kit (TIANGEN) , RT-PCR kit (Toyobo), and primers (synthesized by Biotechnology).

[0030] 2.2 Experimental equipment and devices 1. Animal Behavior Testing Apparatus: Morris Water Maze for Rats 2. Video recording and analysis software for animal behavior 3. Digital brain stereoscope for rats and mice 4. Stereotaxic Infusion Pump for Rat / Mouse Brain 5. Rat / Mouse Skull Drilling 6. Automated tissue homogenizer: Shanghai Jinxin Industrial Development Co., Ltd. JXFSTPRP-24 7. Ultrasonic Cell Disintegrator: Ningbo Xinqi Biological Technology Co., Ltd. JY92-IIDN 8. Thermostatic water bath: Shanghai Pingxuan Scientific Instruments Co., Ltd. DK-8D 9. Benchtop Centrifuge: Thermo Scientific FRESCO 17 10. Microplate Reader for Enzyme-Linked Immunosorbent Assay: Molecular Dev ice SpectraMax M2 11. PCR equipment: BIORAD CFX-Coupled TM Instant System Thermal Cycler Block 5020

[0031] 2.2 Experimental animals Male Wistar rats (250-320g)

[0032] 3. Experimental design and methods 3.1 Preparation of a model of AD in rats using intracerebroventricular injection of streptozotocin (intracerebral (Induced glucose metabolic disorders) This model is characterized by oxidative stress, activated inflammatory responses, abnormalities in the cholinergic pathway, and tau expression. Sporadic AD (SAD) (Icv-ST), such as hyperphosphorylation and Aβ aggregation, learning and memory dysfunction, Z model), atherosclerosis induced by injection of streptozotocin (STZ) through the lateral ventricle Impaired brain glucose / energy metabolism, successfully mimicking various pathological symptoms of SAD This was an AD animal model. The model required a short time and within 2-3 weeks, A There were some cognitive impairments and pathological features of D. It is important to establish an AD model. It is a relatively fast and easy method to identify the triplet of APPIPS1 / tauP301L with AD model. This overcomes the time and cost issues of heavy transgenic mice. Therefore, this project is While establishing the v-STZ model, we aim to breed the triple transgenic animal model and The effects of vitamins on energy metabolism, prevention and treatment of AD through treatment and detection methods The aim is to repeatedly demonstrate the effectiveness of vitamins through different models. It is expected that...

[0033] The Icv-STZ model was constructed as follows:

[0034] Wistar rats (250-320 g) were anesthetized and placed in a digital brain stereoscope. The head was depilated and the skin disinfected. A midline incision was made at the top of the head, exposing the front bones. Traces 0.9 mm behind the anterior apex, 1.5 mm to the left and right of the midline, and 3.6 mm perpendicular to the surface Injection was performed using a syringe. 5 μL of STZ (3 mg / kg) was slowly injected into the left and right ventricles. The injection time was 8 minutes, and the needle was left in place for 2 minutes before being slowly withdrawn. The procedure is performed under sterile conditions. The skin incision is disinfected with penicillin. The wound is sutured. The group received an injection of an equal volume of normal saline.

[0035] 3.2 Grouping and dosing of Icv-STZ model rats After constructing the Icv-STZ model, the rats were kept for one week and then treated with drugs for two months. The experimental animals were divided into four groups: normal control group, model group, treatment group, and positive drug group. The animals were divided into groups of 20, with each group having 20 animals. The specific groups are shown in the table below.

[0036] Table 1. Icv-STZ model rat groups (n=20 / group) [Table 1]

[0037] 3.3 Validation of the Icv-STZ animal model To confirm the stability and reliability of the Icv-STZ rat model, a formal drug administration experiment was conducted simultaneously. The other two groups were set up as normal control group (Icv-saline) and model group (Icv-STZ injection). Each group had 20 animals. Behavioral tests were performed one and two months after modeling was completed. I did.

[0038] I. Conversion of Multivitamin BC Tablets to Mouse Dose = (÷ 60 kg x 12.3 Mouse Factor x 5 Dose ) II. Conversion of Multivitamin BC Tablets to Rat Dose = (÷ 60 kg x 6.2 rat factor x 5 doses) ) III. Rat converted to mouse dose = 1.98 x Mouse converted to rat dose = 0.5 x IV. Conversion of animal subcutaneous dose to intragastric dose = 3 x

[0039] Table 2. Composition and dosage of multivitamin BC tablets [Table 2]

[0040] 3.4 Preparation of reagents a) 0.5% CMC-Na solution: Weigh out 2.0 g of CMC-Na powder and slowly add 300 ml of ultrapure water. The mixture was stirred magnetically until it was completely dissolved and a constant volume of 400 ml was reached. , thereby preparing a 0.5% clear solution, which was stored at 4° C. for future use. Multivitamin BC Tablet Dosage: Dose for mice: 1 multivitamin BC tablet ÷ 60 kg × 12.3 mouse factor × 5 dose = 1.025 tablets / kg Dose for rats: 1 multivitamin BC tablet ÷ 60 kg × 6.2 rat factor × 5 times dose = 0.516 tablets / kg

[0041] b) Preparation of Multivitamin BC Tablet Suspension: Crush the appropriate multivitamin BC tablet. Then, 0.5% CMC-Na was added thereto, and the mixture was subjected to vibration to make it uniform, whereby A stable suspension was formed. 1.025 tablets / kg per mouse and 0.516 tablets / kg per rat. / kg of drug was dosed once in the morning and once in the evening. Doses of positive control drug-donepezil hydrochloride: Dose for mice: Clinical dose (5 mg / day) ÷ 60 kg × 12.3 mouse factor = 1.025 mg / kg Rat dose: Clinical dose (5 mg / day) ÷ 60 kg × 6.2 rat factor = 0.516 mg / kg

[0042] c) Donepezil Hydrochloride Solution: Weigh out the appropriate amount of donepezil hydrochloride powder and add 0.5% C-Na is added and the mixture is subjected to vibration to homogenize, thereby forming a stable suspension. Donepezil hydrochloride was administered as follows: 1.025 mg / kg (mice) and 0.516 mg / kg (rats). Animals were administered donepezil hydrochloride twice daily in the morning. solution in the afternoon and equal volumes of 0.5% CMC-Na and multivitamin BC solution in the afternoon.

[0043] 3.5 Dosage Method The intragastric dose volumes for mice and rats were 20 mL / kg and 10 mL / kg, respectively. The control and model groups received the corresponding 0.5% CMC-Na vitamin BC tablet adjuvant solution by weight. The dose was administered.

[0044] 3.6 Behavioral testing Morris Water Maze The Morris water maze was used as a behavioral test to study spatial learning and memory. Rodents in the water environment had a strong escape motivation and attempted to escape from the water environment. The learning process to escape reflects the animal's learning ability. A safe place (platform) is spatially located in the water, and the swimmer is not intentionally allowed to swim toward the platform. This could reflect the animal's spatial association memory ability. The Morris water maze facility consists of an automatic image acquisition and software analysis system. It consists of a pool and a platform with adjustable height and movable position.

[0045] The water maze experiment had two parts.

[0046] 1) Acquisition phase The pool is divided into four quadrants, and the platform is 1 cm above the liquid level. The animals were placed in the water against the wall of the pool and in one quadrant. The position of the animal was randomly selected in different orientations at one of four starting positions. The time it takes to find and climb onto the platform (escape latency) was recorded to test the learning ability of the animals. If the animal does not find the platform after 60 seconds, it must be guided to the platform. The specimen was then placed on the platform for 2 seconds, after which it was removed, dried under far infrared light, and placed in a cool, dark place until the next experimental period. Each animal was then placed back in its cage. Each animal was then monitored 4 times daily for 5 days (or longer depending on the model's learning status). The models were trained in a short time and a mean latency of less than 20 seconds was considered successful.

[0047] 2) Exploration training After the acquisition phase, 1.5 hours and 1 day, exploration training was performed. Before the experiment, the platform was removed and the mouse was placed The rat was then placed in the water on the opposite side of the original quadrant and a 60-second recording session was started. Detection metrics were: 1) the time when the animal first crossed the platform; 2) the time when the animal entered the target quadrant (where the platform was originally located); The time spent in the target quadrant was included in the time spent in the target quadrant, and 3) how often the animal entered the target quadrant. It was.

[0048] 3.7 Assay of mitochondrial enzyme activity 1) Brain tissue sampling Brain tissue from AD rats deeply anesthetized with 10% chloral hydrate was rapidly extracted after decapitation. The cerebral cortex was placed in a clean, pre-chilled 2 mL centrifuge tube. The samples were then rapidly weighed and placed in liquid nitrogen for rapid freezing, after which they were uniformly collected and sorted. The cells were then placed in a freezer and stored at -80°C.

[0049] 2) Extraction of mitochondrial enzymes In the experiment, we used a Solarbio mitochondrial enzyme activity detection kit. The cortex was weighed, and 1 mL of Reagent 1 and 10 μL of Reagent 3 were added to the cortex. The pellet was crushed in an ice bath. The precipitate was removed by centrifugation at 4°C. The supernatant was The precipitate was transferred to a centrifuge tube and centrifuged at 4°C to remove the supernatant. Add 2 μL of reagent 3 and ultrasonically destroy the mixture, then use it in the enzyme activity detection assay. did.

[0050] 3.8 Detection of mRNA related to energy metabolism 1) Brain tissue sampling Brain tissue from AD rats deeply anesthetized with 10% chloral hydrate was rapidly extracted after decapitation. The cerebral cortex was placed in a clean, pre-chilled 2 mL centrifuge tube. The samples were then rapidly weighed and placed in liquid nitrogen for rapid freezing, after which they were uniformly collected and sorted. The cells were then placed in a freezer and stored at -80°C.

[0051] 2) mRNA Expression In the experiment, the TIANGEN total RNA extraction kit was used. Approximately 0.1 g of cerebral cortex was weighed and 1 m Lysate RZ of L was added to the cortex and the sample was then homogenized. After 5 min. Add 200 μL of chloroform to the precipitate, shake vigorously for 15 seconds, and then leave at room temperature for 3 minutes. The mixture was centrifuged at 37°C. The aqueous phase was transferred to a new tube, and 0.5 volumes of absolute alcohol were added to the tube. The mixture was transferred to a CR3 tube and centrifuged at 4°C to remove the liquid waste. Protein removal solution was added and the liquid waste was removed by centrifugation. The tubes were rinsed twice with 30-100 μl of RNase-free water and centrifuged to remove the liquid waste. After adding deionized distilled water, the mixture was stored at room temperature for 2 minutes and centrifuged at 4°C. was detected by real-time PCR after reverse transcription with a Toyobo RT-PCR kit.

[0052] 4 Results During the acquisition phase of the Morris water maze (D1-D5), we evaluated the ability of animals to find the hidden platform. The time it took to reach the platform was used as an index of spatial memory detection. The shorter the latency to reach the platform, the better the memory. As seen, the latency to the platform for each group of animals decreased significantly with increasing training time. It was suggested that learning and memory skills improve with repeated training. The learning and memory abilities of D5 model animals were significantly worse than those of normal controls. The learning and memory abilities of the model animals were improved by treatment with an energy metabolism drug (multivitamin BC). After the treatment, the memory and learning abilities of the animals with dementia were significantly improved. This shows that significant improvements have been made.

[0053] In exploration training, the animal was placed in the water from the opposite quadrant of the original platform. The time and distance spent in the target quadrant (the quadrant where the hidden platform was originally located) were recorded as The better the animal's memory ability, the more time it took to complete the target quadrant. The time to swim was longer and the swimming distance was longer. The results are shown in Figures 2 and 3. Quadrant-Quadrant 1 (the original hidden platform quadrant) time and distance swam were significantly higher than the other groups. The results also showed that their memory levels were the best. The time and swimming distance in the target quadrant of the BC group animals were higher than those of the model group. Furthermore, two months of vitamin BC treatment could effectively improve the memory performance of animals with dementia. He suggested that...

[0054] The results of the mitochondrial enzyme activity detection assay are shown in Figure 4. Multivitamin BC , a key enzyme in the tricarboxylic acid cycle in the cerebral cortex (pyruvate dehydrogenase PDH, α-ketoglutarate dehydrogenase, and mitochondrial isocitrate dehydrogenase It significantly improved the activities of interleukin-3 (ICDHm), succinate dehydrogenase (SDH), and succinate dehydrogenase (SDH). , thus improving mitochondrial metabolic activity.

[0055] As shown in Figure 5, the results of the energy metabolism-related mRNA assay showed that the cerebral The expression of SDHA and ATP5B genes in the cortex was lower than that in the normal group. Multivitamin BC and combination treatment increased the expression of SDHA and ATP5B, and Improved chondrial metabolism and improved cognitive function.

[0056] 5 Conclusion The learning and memory abilities of ICV-STZ model rats were significantly reduced in the Morris water maze test. The learning and memory abilities of rats were significantly improved after 2 months of multivitamin BC treatment. The activity of key enzymes involved in the tricarboxylic acid cycle was enhanced, and the energy The expression levels of mRNA related to glucose metabolism were improved in the cerebral cortex. However, it has a certain therapeutic effect in treating cognitive impairment in AD and is a new drug for AD patients. This indicates that the Board is expected to provide

[0057] In order to more clearly explain and understand the present invention, we will now describe the invention in detail with reference to examples. Those skilled in the art will appreciate that modifications and variations of the present invention may be made without departing from the scope and spirit of the present invention. It is clear that modifications and variations will be apparent. The present application provides the following aspects of the invention. (Aspect 1) For the preparation of a medicament for preventing, treating or delaying Alzheimer's disease, Use of Min's composition. (Aspect 2) The vitamin composition comprises a vitamin B composition or an analog or derivative thereof. 2. The use according to embodiment 1. (Aspect 3) 1. The vitamin composition comprises vitamin C or an analog or derivative thereof. Use as described. (Aspect 4) The vitamin composition comprises a vitamin B composition or an analog or derivative thereof and a vitamin 2. The use according to embodiment 1, comprising Amin C or an analogue or derivative thereof. (Aspect 5) 3. The use according to any one of the preceding claims, wherein the vitamin composition further comprises choline bitartrate. (Aspect 6) The pharmaceutical composition comprises an effective amount of a vitamin B composition, a vitamin C composition, and a pharma- ceutical acceptable salt thereof. 3. The use according to embodiment 1 or 2, comprising a carrier. (Aspect 7) The pharmaceutical composition comprises an effective amount of a vitamin B composition, a vitamin C composition, and a composition for preventing Alzheimer's disease. 3. The method of claim 1 or 2, further comprising administering to said patient an effective amount of a drug or drugs for preventing, treating or delaying said use. (Aspect 8) The pharmaceutical composition comprises an effective amount of a vitamin B composition, a vitamin C composition and an effective amount of another vitamin 3. The use according to embodiment 1 or 2, comprising (Aspect 9) The pharmaceutical composition comprises an effective amount of a vitamin B composition, a vitamin C composition and an effective amount of trace elements (compounds). The use according to embodiment 1 or 2, comprising: (Aspect 10) The medicinal product contains the following ingredients: 100 parts of vitamin B1, 100 parts of vitamin B2, 100 parts of vitamin Vitamin B3, 100 parts Vitamin B5, 100 parts Vitamin B6, 0.1 parts Vitamin B7, 0.4 parts Vitamin B9 0.1 parts vitamin B12, and 150 parts vitamin C based on a weight ratio of 1:1. For.

Claims

1. A pharmaceutical composition for preventing, treating or delaying Alzheimer's disease, comprising: Combinations of The vitamin combination is as follows: 100 parts vitamin B1, 100 parts vitamin B2, 10 0 parts Vitamin B3, 100 parts Vitamin B5, 100 parts Vitamin B6, 0.1 parts Vitamin B7, 0.4 parts 0.1 parts of vitamin B9, 0.1 parts of vitamin B12, and 150 parts of vitamin C based on a weight ratio of The pharmaceutical composition.

2. 10. The pharmaceutical composition of claim 1, further comprising choline bitartrate.

3. The pharmaceutical composition contains a drug (or drugs) for preventing, treating or delaying Alzheimer's disease.

2. The pharmaceutical composition of claim 1, further comprising one or more

4. 10. The pharmaceutical composition of claim 1, further comprising other vitamins.

5. The other vitamin is (i) one or more fat-soluble vitamins, (ii) vitamin A, or (iii) one 5. The pharmaceutical composition according to claim 4, comprising both the fat-soluble vitamins and vitamin A.

6. The one or more fat-soluble vitamins are selected from the group consisting of vitamin D, vitamin E, and vitamin K. The pharmaceutical composition of claim 5, wherein the compound is selected from the group consisting of

7. 10. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition further comprises a trace element(s).

8. The trace element(s) is selected from the group consisting of magnesium, iron and zinc. The pharmaceutical composition according to claim 7.

9. The vitamin B1 is thiamine, the vitamin B2 is riboflavin, and the vitamin Vitamin B3 is nicotinic acid, the vitamin B5 is pantothenic acid, and the vitamin B7 is biotin, the vitamin B9 is folic acid, and the vitamin B12 is cyanocobalamin.

2. The pharmaceutical composition according to claim 1, wherein the vitamin C is ascorbic acid and the vitamin C is baramin. thing.

10. 10. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition is in an oral dosage form.

11. The oral dosage form is a chewable tablet, a dispersible tablet, a granule, a capsule, or an oral liquid. Item 11. The pharmaceutical composition according to item 10.

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