Application of magnesium nervonate compound preparation in protection of brain nervous system

Abstract

The invention discloses application of a magnesium nervonate compound preparation to protection of a brain nervous system. According to the preparation, magnesium L-threonate (MgT) and nervonic acid (NA) are taken as core raw materials, and are compounded with PQQ, NMN, SOD, dihydroquercetin, nicotinamide (NAM), gamma aminobutyric acid (GABA) and other components. The innovation of the invention is combined application of NA and MgT, and the combined product is called as magnesium nervonate. MgT and NA can mutually enhance the effect of protecting neural media in the brain.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicine applications, and particularly to the application of magnesium nervonic acid complex preparations in protecting the brain nervous system. Background Art

[0002] There is a wide variety of common nerve and brain health supplements, but two stand out. One is magnesium-L-threonate, and the other is nervonic acid.

[0003] 1. Magnesium-L-threonate (MgT): In caring for physical health, especially nervous system and brain health, the importance of magnesium cannot be overemphasized. Magnesium is an essential trace element indispensable in hundreds of enzymatic biochemical reactions in the body. It plays a key role especially in memory formation and has a crucial sedative effect on the nervous system. Magnesium also has excellent antioxidant and anti-inflammatory properties, which are very beneficial to the nervous system, especially the brain and the whole body. Unfortunately, even in many Western countries and regions, it is estimated that two out of every three people do not meet the recommended daily magnesium intake standard. Many common chronic diseases are related to magnesium deficiency, including diabetes mellitus, osteoporosis, chronic airway problems in the bronchus, heart disease, dementia, migraine, depression, and anxiety. Therefore, there are an endless stream of magnesium supplements, making people dazzled. However, it is not easy to find a suitable and preferred product for oneself. Magnesium must be combined with another substance (such as citrate or chloride) to form a stable magnesium salt structure. The choice of different compound compositions often affects the absorption and distribution of magnesium in the body. What makes magnesium-L-threonate different is not only that the body can fully absorb it through the gastrointestinal system, but also that it has the unique ability to enter the brain from the blood. This remarkable feature makes it very different from traditional magnesium supplements, because the impact of traditional magnesium supplements on the magnesium level around nerve cells in the nervous system, especially in the brain, is almost negligible.

[0004] 2. Nervonic acid (cis-15-Tetracosenoic acid, NA): Nervonic acid is a core natural component of the nervous system, especially brain nerve cells and nerve tissues. It is known as the protector of the human brain and is another important brain health supplement. Given that nervonic acid is a core component of brain nerve cells and nerve tissues, there are approximately two situations for supplementing nervonic acid. One is nerve damage, and the other is natural aging.

[0005] Human aging often begins with brain aging, and brain aging is often caused by a lack of white matter. Nervonic acid is a long-chain unsaturated fatty acid that is enriched in sphingomyelin and was first discovered in the nerve tissues of mammals, so it was named nervonic acid. Research at home and abroad has shown that nervonic acid is the core natural component of brain nerve cells and nerve tissues. It is the only substance discovered in the world so far that can prevent demyelination, repair and dredge damaged brains, that is, nerve fibers; it is an essential material for the growth and development and maintenance of health of all nerve cells, including brain nerve cells, optic nerve cells, and peripheral nerve cells; it is a miraculous substance that can promote the regeneration of nerve cells and enhance brain function. When nervonic acid is ingested, it can synthesize glycosphingolipids (cerebrosides, gangliosides) and sphingomyelin in the body, which are used as materials for myelin regeneration, promoting the myelination and repair of nerve fibers; thus supplementing the brain's white matter, improving the structure of neuron cell membranes, enhancing the functions of neuron cells, increasing cell and body vitality, and effectively preventing the occurrence of cardiovascular and cerebrovascular diseases and Alzheimer's disease and other diseases.

[0006] After retrieval, no research on the combination of magnesium L-threonate and nervonic acid has been found yet. Summary of the Invention

[0007] The main purpose of the present invention is to provide a nervonic acid magnesium composite preparation, which uses magnesium L-threonate and nervonic acid as the core raw materials and is compounded with components such as PQQ, NMN, SOD, dihydroquercetin, nicotinamide (NAM), gamma-aminobutyric acid (GABA), etc. It has good effects of nourishing nerves and regulating emotions.

[0008] To achieve the above purpose, the present invention adopts the following technical solutions:

[0009] Nervonic acid magnesium composite preparation, the weight parts of the composite preparation are: 8-13 parts of magnesium L-threonate, 8-13 parts of nervonic acid.

[0010] Preferably, the weight parts of the composite preparation are: also including 2-6 parts of PQQ, 2-6 parts of NMN, 2-6 parts of SOD, 2-6 parts of dihydroquercetin, 2-6 parts of nicotinamide (NAM), 2-6 parts of gamma-aminobutyric acid.

[0011] Preferably, the preparation can be any one of tablets, compressed tablet candies, solid beverage agents, capsules, granules, and aqueous agents.

[0012] The preparation method of the above-mentioned nervonic acid magnesium composite preparation includes the following steps:

[0013] S1. Weigh the formulated amount of magnesium L-threonate and crush it to 600 meshes, add the formulated amount of nervonic acid, and use spray drying to dry and granulate, controlling the inlet air temperature to be 83-85°C to make a microcapsule preparation with a mesh number of 1000 meshes;

[0014] S2. First, add the microcapsules of S1 above into a wet granulator, and then add the formula amounts of PQQ, NMN, SOD, dihydroquercetin, niacinamide, and gamma-aminobutyric acid. Start the machine and mix for 5 minutes.

[0015] S3. Add 5 parts by weight of water, stir at 40°C for 1 hour at a rotation speed of 1360 rpm, filter, dry with hot air at 35°C for 6 hours, turn on the stirring and chopping knives to make soft materials, pass through a 16-mesh sieve, dry at 60°C until the moisture content is less than 3%, and screen with a 16-mesh sieve.

[0016] The innovation of the present invention is the combined application of nervonic acid and magnesium L-threonate. The product of their combination is called magnesium nervonate. The importance of magnesium nervonate is that its curative effect is better than the simple addition of the curative effects of single nervonic acid or magnesium L-threonate used alone. Because when they are used alone, only the curative effect of the product used can be guaranteed, while the supply of the other product is in an uncontrollable state and is very likely to become a short board and affect the curative effect. Just like a machine gun and bullets configured separately on the battlefield, it is easy to cause a situation where there is a gun but no bullets or there are bullets but no gun; when the bullets of the front-line machine gun are used up, there may or may not be bullets in the rear, or the bullets may still be on the transportation line; the situation where the front-line machine gunner fails the battle due to the lack of available bullets often occurs. And magnesium nervonate is like a machine gun with infinite quantum bullets that is still expected, and there will be no situation where there are no bullets available. MgT and NA can enhance each other's role in protecting neurotransmitters in the brain. Brief Description of the Drawings

[0017] In order to more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the following will briefly introduce the drawings required for the description of the embodiments or the prior art. Obviously, the drawings in the following description are only some embodiments of the present invention. For those of ordinary skill in the art, without creative efforts, other drawings can be obtained based on the structures shown in these drawings.

[0018] Figure 1 It is a graph showing the determination results of cell viability (measured by the MTT assay) provided by an embodiment of the present invention;

[0019] Figure 2 It is a graph showing the determination results of malondialdehyde (MDA) provided by an embodiment of the present invention.

[0020] The realization, functional features, and advantages of the object of the present invention will be further described in conjunction with the embodiments and with reference to the drawings. Detailed Embodiments

[0021] The technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all embodiments. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without creative efforts shall fall within the protection scope of the present invention.

[0022] The preparation in the embodiments of the present invention uses magnesium L-threonate and nervonic acid as core raw materials, and is compounded with components such as PQQ, NMN, SOD, dihydroquercetin, nicotinamide (NAM), gamma-aminobutyric acid, etc.

[0023] Both nervonic acid and magnesium L-threonate play crucial roles in the brain nervous system. However, further research will reveal that their action points are significantly different. Simply put, nervonic acid is the structural raw material of the brain nervous system and is a component of the basic structure of the body, like the steel of a machine gun; while magnesium L-threonate is the functional consumable of the brain nervous system and is an indispensable trace element for the brain to perform various functions, like the ammunition in a bullet. A machine gun relies on bullets and ammunition to kill enemies, but bullets and ammunition are not part of the machine gun and need to be supplemented additionally. Similarly, the nervous system formed by nervonic acid, especially the brain nervous system, needs to rely on the neurotransmitters it produces to function, and magnesium L-threonate is the essential trace element for the formation and transmission of neurotransmitters.

[0024] Magnesium L-threonate has many functions and mainly has the following effects on the brain and nervous system.

[0025] 1. Repair nerves. Magnesium can help repair damaged nerve synapses. A synapse is the connection point for information transmission between nerve cells and is used to transmit information. Imagine that the cells in the brain need to communicate with each other, and the synapse is the tool for their communication, helping them transmit information and tell the body what to do and how to do it. If there are many synapses in the brain, just like having many communication tools, the communication will be very smooth, the brain will work better, and the memory and thinking abilities will be stronger. However, if there is a nervous system disease, these synapses will become fewer, just like the number of communication tools decreases, and the communication will be blocked, affecting the communication of the brain. The good news is that magnesium can help the brain repair those damaged synapses, just like repairing damaged communication tools, so that the functions of the brain can return to normal.

[0026] 2. Optimize memory. Magnesium is also important for memory. Imagine an organ called the hippocampus in the brain, which is the memory center of the brain. It helps the brain remember things. Whether it's something that just happened, i.e., short-term memory; or something that happened a long time ago, i.e., long-term memory; or even remembering places one has been to, i.e., spatial orientation. Studies have shown that the hippocampus is related to whether a person is prone to forgetting things, feeling anxious, depressed, or having poor stress resistance. Magnesium is like an umbrella for the hippocampus. Without enough magnesium, the hippocampus cannot work well, which may lead to memory decline. For example, not being able to remember things or getting lost even in familiar places. Therefore, magnesium is very important for maintaining memory and sense of direction. The role of magnesium L-threonate in neuroplasticity, learning, and memory depends on its interaction with the N-methyl-D-aspartic acid (NMDA) receptor. The NMDA receptor is located on neurons and receives signals from incoming neurotransmitters here, and then allows calcium to rush in by opening channels, thereby transmitting the signal to the host neuron. The role of magnesium L-threonate is like a signal valve switch. Only when receiving an appropriate amount of nerve signals can it allow calcium to enter, thereby blocking the interference of chaotic signals to the receptor on the one hand; and preventing over-strong signals from inducing cell death and inflammatory reactions in the brain on the other hand. In several studies on the effect of magnesium L-threonate on the brain, the experimental mice showed significantly better performance in long-term and short-term memory tasks only one month after orally taking magnesium L-threonate. The elderly are particularly prone to magnesium deficiency, and studies have found that this may be a possible mechanism for triggering Alzheimer's disease. For Alzheimer's disease, special studies have been conducted using magnesium L-threonate in a mouse model, and a small human pilot study has been carried out. Both of these studies have shown the potential positive effect of magnesium L-threonate in optimizing cognition. As observed in mice, the number of neural connections will increase after taking magnesium L-threonate.

[0027] 3. Soothe the nerves and calm the mind. Magnesium is like a relaxation button in the brain. It binds to some receptors in the brain that can produce a calming effect, just like inserting a key into a lock. When magnesium binds to those receptors, the body will feel calm and relaxed. This is why when there is enough magnesium in the body, one feels calmer and less anxious. Because magnesium helps activate the relaxation mode of the brain. Therefore, in addition to possibly helping with memory formation and cognition, magnesium L-threonate may also have the effects of calming the mind, relieving anxiety, and optimizing sleep.

[0028] 4. Reduce stress. There is an interactive relationship between magnesium and mental health. Increasing magnesium intake helps relieve stress and anxiety. On the contrary, stress causes the kidneys to release more magnesium into the urine, thus reducing the magnesium content in the body. Therefore, it is particularly important to supplement magnesium when facing stress or feeling anxious. Another study found that compared with mice that did not receive magnesium L-threonate, mice that took magnesium L-threonate could overcome fear faster and remain anxiety-free for a longer time. This mechanism seems to be similar to the memory mechanism. Mice that ingested magnesium L-threonate were more likely to form new thought associations and retain new information, and adapt to the new reassuring environment faster. There are also several other theoretical supports for how magnesium relieves anxiety, including reducing excessive excitatory signals from the brain by blocking NMDA receptors, and enhancing the activity of receptors that receive and transmit sedative signals of GABA (the main inhibitory neurotransmitter in the brain).

[0029] 5. Alleviate depression. Magnesium L-threonate can relieve depression by increasing serotonin production and enhance the efficacy of antidepressant prescriptions. Research shows that for elderly subjects with depression and type 2 diabetes and low magnesium levels in the body, continuous magnesium supplementation for 12 weeks may help regulate depressive symptoms, with the same efficacy as taking antidepressant prescriptions.

[0030] 6. Concentrate. A small pilot study involving 15 adults with attention deficit hyperactivity disorder (ADHD) showed that after 12 weeks of supplementing magnesium L-threonate, the symptoms of the subjects were significantly improved. The potential of magnesium as a supportive therapy for attention deficit hyperactivity disorder cannot be underestimated.

[0031] 7. Pain relief. It includes common pain and fibromyalgia. (1) A in-depth study shows that compared with the placebo group, the pain symptoms of fibromyalgia patients who took magnesium preparations for 8 consecutive weeks were significantly relieved. (2) In addition, if magnesium is taken in combination with amitriptyline, all parameters of fibromyalgia may be optimized. This result shows that the combination of magnesium supplementation and traditional treatment may bring many benefits to patients. (3) In a study on chemotherapy-induced neuropathic pain, the potential efficacy of magnesium L-threonate was observed. The research results show that the underlying mechanism of chemotherapy-induced neuropathic pain may be associated with low magnesium content in the body, which leads to inflammatory reactions and nerve damage. Supplementing magnesium L-threonate during chemotherapy helps to avoid common complications of chronic neuropathic pain. (4) In addition, in chronic pain related to menopause, magnesium L-threonate may play a protective or reparative role. (5) In a mouse model, magnesium L-threonate may also play a protective or reparative role against neuroinflammatory reactions caused by decreased estrogen levels, bringing hope for solving chronic pain problems related to menopause. These studies together illustrate that magnesium may have multiple potentials in preventing and relieving various types of pain related to inflammatory reactions, which undoubtedly expands new ideas for the research frontier of pain relief.

[0032] 7. Brain food. Magnesium is like a superfood for the brain. It helps the brain increase a brain-derived neurotrophic factor called BDNF. BDNF is like the fertilizer of the brain. It helps the brain grow new cells and makes the brain healthier. This is good for improving mood. BDNF can also make the brain better at learning new things and helps in the recovery of the nervous system after trauma. Simply put, BDNF makes the brain more flexible and better able to adapt to new environments and challenges. Therefore, magnesium L-threonate is a magnesium supplement specifically customized for the brain. It acts directly on the brain, just like directly feeding magnesium to the brain. This type of magnesium is particularly good at repairing various problems that may occur in the brain and helps maintain the health of the brain. Compared with other types of magnesium supplements, magnesium L-threonate is more like precision medicine, directly targeting the brain with more prominent effects.

[0033] The functions and effects of nervonic acid mainly include but are not limited to the following aspects:

[0034] 1. Promote the growth and development of brain tissue cells, improve memory, increase the intelligent response speed of the brain, enhance self-movement and sensory functions, improve the IQ (intelligence quotient) and thinking and memory functions of young people, and assist in the rehabilitation of cerebral palsy patients.

[0035] 2. Improve cerebral blood circulation, refresh the mind and strengthen the brain, nourish brain nerves, enhance the energy of brain cells and the full supply of blood oxygen and information transmission between brain cells, and ensure that middle-aged people have clear cognition, agile thinking and stable emotions.

[0036] 3. Repair nerve fibers, reduce the accumulation of lipofuscin in brain cells, and prevent and treat senile diseases such as brain tissue collapse, atrophy, sclerosis, nerve fiber atrophy, neurodegeneration, Parkinson's syndrome, and Alzheimer's disease in middle-aged and elderly people.

[0037] PQQ: Nerve growth factor (NGF) was the earliest discovered and most thoroughly studied among neurotrophic factors. It has dual biological functions of neuron nutrition and neuroprotection and plays an important regulatory role in the growth, development, differentiation, regeneration, and specific expression of biological functions of central and peripheral neurons. Experiments have shown that in vitro, PQQ can stimulate L-M cells and Schwann cells to produce NGF.

[0038] NMN: NMN mainly exerts its effects by being converted into NAD+. NAD+ is also known as coenzyme I, full name nicotinamide adenine dinucleotide. It is widely distributed in all cells of the human body and participates in thousands of biological catalytic reactions. It is an essential coenzyme in the human body. The decline of NAD+ during the aging process is considered to be the main cause of diseases and disabilities, such as hearing and vision loss, cognitive and motor function disorders, immune deficiencies, and arthritis, metabolic disorders, and cardiovascular diseases caused by dysregulation of autoimmune inflammatory responses. Therefore, supplementing NMN increases the content of NAD+ in the body, thereby delaying, improving, and preventing various phenotypes related to aging, or age-induced metabolic disorders and senile diseases.

[0039] Sirtuins is a NAD+-dependent deacylase, which has traditionally been considered to be related to caloric restriction and aging in mammals. These proteins also play an important role in maintaining the health of neurons during the aging process.

[0040] During neural development, SIRT1 plays an important structural role, promoting axonal growth, neurite growth, and dendritic branching through the Akt-GSK3 pathway. The development of synapses and the regulation of synaptic strength are crucial for memory formation, and sirtuins proteins play an important regulatory role in this process both physiologically and after injury. SIRT1 can exist in the form of an inhibitory complex in the hippocampus, and this complex contains the transcription factor YY1 that can regulate microRNA-134. The distribution of microRNA-134 is brain-specific and can regulate the expression of cAMP response element-binding protein (CREB) and brain-derived neurotrophic factor (BDNF). This is important for synapse formation and long-term potentiation.

[0041] In the occurrence and development of neurological diseases, SIRT1 plays a protective role in various neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and motor neuron disease. These diseases may be related to the functions of SIRT1 in metabolism, stress resistance, and genomic stability.

[0042] SOD: SOD can rapidly catalyze the disproportionation reaction of free radicals in the human body. When it encounters harmful free radicals (such as superoxide anion radicals, hydroxyl radicals, carbon tetrachloride, and some highly reactive oxygen-containing substances), it promotes the decomposition of superoxide radicals, turning them into water molecules and oxygen molecules harmless to the human body, eliminating lipid peroxidation of tissue cells. It protects some free radicals beneficial to life substances and physiological functions (such as nitric oxide), maintains the balance of free radicals in the body, deeply regulates sleep quality, enhances memory, improves the body's immunity, resists diseases, stimulates youthful vitality, and delays aging.

[0043] Dihydroquercetin: It has antioxidant effects, antioxidant protection of capillaries, which is 3 - 5 times stronger than quercetin, anti-lipid peroxidation to protect the liver, nerve cells, and red blood cells, and anti-myocardial necrosis, etc.

[0044] Nicotinamide: Nicotinamide can promote digestion and absorption, promote the synthesis of important substances such as choline and lecithin in the human body, and also has a certain protective effect on preventing nervous system diseases, liver diseases, etc.

[0045] Gamma-aminobutyric acid: Gamma-aminobutyric acid can enter the tricarboxylic acid cycle in the brain, promote brain cell metabolism, and at the same time increase the activity of glucose phosphatase during glucose metabolism, increase the production of acetylcholine, dilate blood vessels to increase blood flow, and reduce blood ammonia, promoting the metabolism of the brain and restoring brain cell function.

[0046] Example 1:

[0047] A magnesium nervonic acid composite preparation, and the weight parts of the composite preparation are as follows: 9 parts of magnesium L-threonate, 9 parts of nervonic acid, 3 parts of PQQ, 3 parts of NMN, 3 parts of SOD, 3 parts of dihydroquercetin, 3 parts of nicotinamide, and 3 parts of gamma-aminobutyric acid.

[0048] The preparation method of the above composite preparation is as follows:

[0049] S1. Weigh the formulated amount of magnesium L-threonate and crush it to 600 meshes, add the formulated amount of nervonic acid, and use spray drying to dry and granulate, controlling the inlet air temperature at 83 - 85°C to make a microcapsule preparation with a mesh number of 1000 meshes;

[0050] S2. First, add the microcapsules obtained in S1 above to a wet granulator, and then add the formulated amounts of PQQ, NMN, SOD, dihydroquercetin, nicotinamide, and gamma-aminobutyric acid, and start mixing for 5 minutes;

[0051] S3. Add 5 parts by weight of water, stir at 40°C for 1 h, with a rotation speed of 1360 rpm, filter, dry in a blast dryer at 35°C for 6 h, turn on the stirring and chopping knife to make soft materials, pass through a 16-mesh sieve, dry at 60°C until the moisture content is less than 3%, and perform 16-mesh sizing.

[0052] Example 2:

[0053] A magnesium nervonic acid composite preparation, the weight parts of the composite preparation are as follows: 10 parts of magnesium L-threonate, 10 parts of nervonic acid, 4 parts of PQQ, 4 parts of NMN, 4 parts of SOD, 4 parts of dihydroquercetin, 4 parts of nicotinamide, and 4 parts of gamma-aminobutyric acid.

[0054] The preparation method of the above composite preparation is as follows:

[0055] S1. Weigh the formulated amount of magnesium L-threonate and crush it to 600 mesh, add the formulated amount of nervonic acid, and use spray drying to dry and granulate, controlling the inlet air temperature at 83 - 85 °C to make a microcapsule preparation with a mesh number of 1000 mesh;

[0056] S2. First, add the microcapsules of S1 above to a wet granulator, then add the formulated amounts of PQQ, NMN, SOD, dihydroquercetin, nicotinamide, and gamma-aminobutyric acid, and turn on the machine to mix for 5 minutes;

[0057] S3. Add 6 parts by weight of water, stir at 40 °C for 1 h, with a rotation speed of 1360 rpm, filter, dry under blowing at 35 °C for 6 h, turn on the stirring and chopping knife to make soft materials, pass through a 16-mesh sieve, dry at 60 °C until the moisture content is less than 3%, and perform 16-mesh sizing.

[0058] Example 3:

[0059] A magnesium nervonic acid composite preparation, the weight parts of the composite preparation are as follows: 11 parts of magnesium L-threonate, 11 parts of nervonic acid, 5 parts of PQQ, 5 parts of NMN, 5 parts of SOD, 5 parts of dihydroquercetin, 5 parts of nicotinamide, and 5 parts of gamma-aminobutyric acid.

[0060] The preparation method of the above composite preparation is as follows:

[0061] S1. Weigh the formulated amount of magnesium L-threonate and crush it to 600 mesh, add the formulated amount of nervonic acid, and use spray drying to dry and granulate, controlling the inlet air temperature at 83 - 85 °C to make a microcapsule preparation with a mesh number of 1000 mesh;

[0062] S2. First, add the microcapsules of S1 above to a wet granulator, then add the formulated amounts of PQQ, NMN, SOD, dihydroquercetin, nicotinamide, and gamma-aminobutyric acid, and turn on the machine to mix for 5 minutes;

[0063] S3. Add 7 parts by weight of water, stir at 40 °C for 1 h, with a rotation speed of 1360 rpm, filter, dry under blowing at 35 °C for 6 h, turn on the stirring and chopping knife to make soft materials, pass through a 16-mesh sieve, dry at 60 °C until the moisture content is less than 3%, and perform 16-mesh sizing.

[0064] Example 4:

[0065] Magnesium L-threonate enhances the protective effect of nervonic acid on 6-hydroxydopamine-induced oxidative stress in PC-12 cells.

[0066] In neurodegenerative diseases such as Parkinson's disease (PD) and Alzheimer's disease (AD), an increase in oxidative stress in the human brain has been observed and is considered a major cause of the progression of these disease states. Nervonic acid is a very long-chain fatty acid found in various sphingolipids of the central nervous system. Nervonic acid plays an important role in forming the lipid bilayer of the plasma membrane and maintaining normal myelin function. In this study, we examined the neuroprotective effects of nervonic acid alone and in combination with magnesium L-threonate (NA+MgT) on 6-hydroxydopamine (6-OHDA)-stimulated rat pheochromocytoma (PC-12) cells, a cellular model of PD.

[0067] Cell culture and treatment PC-12 cells were cultured in DMEM medium supplemented with 10% FBS, 20 U / mL penicillin, and 20 μg / mL streptomycin in a humidified incubator at 37 °C with 5% CO2. When 90% confluence was reached, the cells were digested with 0.025% trypsin and collected, and seeded into 96-well plates at a density of 2×10 5 cells / mL. The protective effects of NA (1 μM) and NA (1 μM)+MgT (1 mM) on PC-12 cells were investigated by pretreatment or co-treatment with 6-hydroxydopamine (6-OHDA, 50 μM). The experimental groups were as follows, with 3 replicates in each group:

[0068] (1) Normal control (NCT) group: normal medium;

[0069] (2) 6-OHDA group: 6-OHDA;

[0070] (3) 6-OHDA-NA group: 6-OHDA, NA;

[0071] (4) 6-OHDA-MgT group: 6-OHDA, MgT;

[0072] (5) 6-OHDA-MgT+NA group: 6-OHDA, NA, MgT.

[0073] The pretreatment procedure was to add NA alone or NA+MgT in DMSO to the medium and pre-incubate at 37 °C for 48 h. Then the pretreatment medium was replaced with fresh medium, and the cells were treated with an equal amount of NA or NA+MgT and 6-OHDA at 37 °C for 48 h, followed by incubation at 37 °C for 48 h. For the negative control group, the cells were treated with 6-OHDA only. All experiments were performed in triplicate.

[0074] Cell viability was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. The MTT labeling solution was prepared at a concentration of 5 mg / mL in sterile PBS. After treatment of PC-12 cells with 6-OHDA, each medium was replaced with fresh medium. Then, 50 μL of the MTT solution was added to each well, and the cell culture plates were incubated at 37 °C for 1.5 h. To dissolve the formed formazan salts, 50 μL of 3% SDS and 300 μL of 0.04 N hydrochloric acid in isopropanol were added. The absorbance of the solution was measured at 492 nm using a microplate reader.

[0075] PC-12 cells were pretreated with NA, MgT, or NA + MgT for 48 h and then co-treated with NA, MgT, or NA + MgT and 6-OHDA for 48 h to induce cellular oxidative stress. The results showed that both NA and MgT alone could increase PC-12 cell viability; the effect of NA + MgT was the best, exceeding the sum of the effects of the two alone. In cells treated with NA or MgT, the content of malondialdehyde (a marker of lipid peroxidation) decreased, and the content of malondialdehyde (a marker of lipid peroxidation) in cells treated with NA + MgT was lower (see Figure 1 ). It was shown that both NA and MgT pretreatment activated the cellular antioxidant defense system, and the antioxidant effect of NA + MgT was better. These results indicated that MgT and NA could enhance each other's role in protecting neurotransmitters in the brain.

[0076] Figure 1 Cell viability (determined by the MTT assay) was measured. Cells were pretreated with NA and MgT alone or in combination for 48 h, and then co-treated with NA, MgT alone or in combination and 6-OHDA for 48 h. Data are shown as mean ± SD. The effect of the NA + MgT group was significant compared with the groups of NA and MgT alone (p < 0.05).

[0077] Quantitative detection of malondialdehyde (MDA). Malondialdehyde (MDA) is a marker of lipid peroxidation. Cultured PC-12 cells were washed with PBS buffer and homogenized using an ultrasonic processor. The suspension was centrifuged at 12,000×g for 15 min, and the MDA level in the supernatant was measured. That is, 250 μL of the supernatant was added to a 1.5 mL Eppendorf tube, and then 10 μL of the BHT solution, 250 μL of 1 M phosphoric acid solution, and 250 μL of the TBA solution were added to the tube. The mixture was incubated at 60 °C for 1 h, and the absorbance at 514 nm was measured.

[0078] Determination of malondialdehyde (MDA) ( Figure 2) Pretreat with NA and MgT alone or in combination for 48 hours, and then co-treat with NA, MgT alone or in combination with 6-OHDA for 48 hours. Data are shown as mean ± SD. Compared with the groups of NA and MgT alone, the effect of the NA+MgT group was significant (p<0.05).

[0079] The innovation of the present invention is the combined application of nervonic acid and magnesium L-threonate. The product we call magnesium nervonate when used in combination. The importance of magnesium nervonate is that its efficacy is better than the simple addition of the efficacy of single nervonic acid or magnesium L-threonate alone. Because when used alone, only the efficacy of the product used can be guaranteed, while the supply of the other product is in an uncontrollable state and is very likely to become a short board and affect the efficacy. Just like a machine gun and bullets configured separately on the battlefield, it is easy to cause a situation where there is a gun but no bullets or there are bullets but no gun; when the bullets of the front-line machine gun are used up, there may or may not be bullets in the rear, or the bullets may still be on the transportation line; the situation where the front-line machine gunner fails the battle due to no bullets available often occurs. And magnesium nervonate is like a machine gun with infinite quantum bullets that is still awaited, and there will be no situation where there are no bullets available.

[0080] The above are only the preferred embodiments of the present invention, and do not limit the patent scope of the present invention accordingly. Any equivalent structural transformation made under the inventive concept of the present invention, or direct / indirect application in other related technical fields, is included in the patent protection scope of the present invention.

Claims

1. A magnesium neuraminic acid composite preparation, characterized in that: The weight proportions of the composite preparation are as follows: 8-13 parts of magnesium L-threonate (MgT) and 8-13 parts of neuraminic acid (NA); It also includes 2-6 parts of PQQ, 2-6 parts of NMN, 2-6 parts of SOD, 2-6 parts of dihydroquercetin, 2-6 parts of nicotinamide (NAM), and 2-6 parts of gamma-aminobutyric acid (GABA).

2. The magnesium neuraminic acid composite preparation according to claim 1, characterized in that: The weight proportions of the composite preparation are: 9 parts of magnesium L-threonate, 9 parts of neuraminic acid, 3 parts of PQQ, 3 parts of NMN, 3 parts of SOD, 3 parts of dihydroquercetin, 3 parts of nicotinamide, and 3 parts of gamma-aminobutyric acid.

3. The magnesium neuraminic acid composite preparation according to claim 1, characterized in that: The weight proportions of the composite preparation are: 10 parts of magnesium L-threonate, 10 parts of neuraminic acid, 4 parts of PQQ, 4 parts of NMN, 4 parts of SOD, 4 parts of dihydroquercetin, 4 parts of nicotinamide, and 4 parts of gamma-aminobutyric acid.

4. The magnesium neuraminic acid composite preparation according to claim 1, characterized in that: The weight proportions of the composite preparation are: 11 parts of L-magnesium threonate, 11 parts of neuraminic acid, 5 parts of PQQ, 5 parts of NMN, 5 parts of SOD, 5 parts of dihydroquercetin, 5 parts of nicotinamide, and 5 parts of gamma-aminobutyric acid.

5. The magnesium neuraminic acid composite preparation according to any one of claims 1-4, wherein the preparation can be any one of tablets, compressed candies, solid beverages, capsules, granules, and aqueous solutions.

6. A method for preparing a magnesium neuraminic acid composite preparation, characterized in that: The following steps are involved: S1. Weigh the formulated amount of magnesium L-threonate and grind it into 600 mesh, add the formulated amount of nervonic acid, dry and granulate it by spray drying, control the inlet air temperature to 83-85° C., and prepare a microcapsule preparation with a mesh size of 1000 mesh; S2, first add the microcapsules of S1 above into a wet mixing granulator, then add the formulated amount of PQQ, NMN, SOD, dihydroquercetin, nicotinamide, and gamma-aminobutyric acid, and start mixing for 5 minutes; S3, add 5 parts of water by weight, stir at 40℃ for 1h, rotation speed 1360rpm, filter, blow dry at 35℃ for 6h, stir and chop to make soft material, pass through 16-mesh sieve, dry at 60℃ until the moisture content is less than 3%, and granulate into 16-mesh granules.

7. The application of magnesium neuraminic acid compound preparation in protecting the brain nervous system, characterized in that: Use the magnesium neuraminic acid composite preparation or preparation method described in any one of claims 1 to 5.

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