TW202033212A - Use of agarwood extract - Google Patents

Abstract

The present invention relates to a novel use of agarwood extract. The use is to treat a living body suffering from neurological diseases, to improve neurological symptoms of the living body, to prevent neurological diseases in the living body, to enhance or activate a brain performance of the living body, or to enhance the neuronal outgrowth of the living body. The ability of learning and memory of the organism is improved by using the agarwood extract.

Description

Uses of agarwood extract

The present invention provides a new use of Agarwood extract, especially as a health product or medicine for the treatment, amelioration or prevention of cranial nerve-related diseases.

According to epidemiological statistics, in North America before 2040, neurodegenerative diseases will replace cancer as the second leading cause of death. Neurodegenerative diseases are also called "silent epidemics", which usually occur in the elderly. Because patients will gradually be isolated from the society during the onset, coupled with the current lack of relevant medical knowledge, the public rarely understands And attention. With the aging of the population structure, the number of patients with neurodegenerative diseases is also increasing. For the families, patients and the general public, the economic, psychological and lifestyle impacts are really hard to estimate and bear.

According to epidemiological studies, 5% of people over 65 have dementia, and this increases to 20% over 85. Studies have also shown that 89% of people over 100 have dementia, and every 5 years of age increases their chance of suffering from dementia doubles. Among the patients with dementia, 50%-70% are patients with Alzheimer's disease (AD). Alzheimer's disease is a persistent neurological dysfunction that progresses slowly and deteriorates over time.

The initial symptoms of Alzheimer's disease are often mistaken for aging or stress, but a detailed neuropsychological examination may reveal mild cognitive difficulties. These early symptoms can affect most complex activities of daily living, the most obvious defect is amnesia, the main It is difficult to remember recent events and unable to absorb new information. Other symptoms include problems in attention management, planning, flexibility, and abstraction, or semantic memory disorders. In some patients in the early stage, language impairment, control dysfunction, perceptual impairment (cognitive inability, or agnosia), or mobility impairment (inability to use, or apraxia) will be more obvious than memory impairment.

As the condition gradually deteriorates, the patient loses independence and is unable to perform most of the daily activities. Language barriers become obvious, leading to frequent incorrect vocabulary substitutions; complex movements become uncoordinated, and memory problems will worsen. End-stage patients with Alzheimer’s disease need to rely entirely on the assistance of their caregivers. Their language skills degenerate to simple words or even completely lose the ability to speak, unable to carry out any tasks independently, and degeneration of muscle mass and mobility will eventually lead to long-term bed rest and inability to eat on their own.

Neurological problems do not only occur in the elderly; attention deficit disorder (ADD), hyperactivity disorder (Hyperkinetic disorder, HD) or hyperactivity disorder (Attention deficient hyperactivity disorder, ADHD) is a neurological development related Psychological disorders usually occur in children and adolescents. There are about 200,000 children in Taiwan who meet the diagnostic criteria for ADHD. Most boys show impulsive and hyperactive behaviors, and most girls show inattention.

At present, most other cranial nerve-related diseases and symptoms are treated the same as Alzheimer's disease, and cannot prevent or reverse the course of the disease. There are only a few methods that may temporarily relieve or improve symptoms. Although ADHD has a chance to recover in adulthood, if it is not treated in time during childhood, it is easy to cause problems in learning and interpersonal relationships. Therefore, there is an urgent need for a substance that can effectively nourish degenerative nerves and repair damaged nerves to treat, prevent, and ameliorate brain diseases.

In view of this, the present invention proposes an agarwood extract that can be used to improve and prevent cranial nerve diseases and symptoms; even, the present invention also proposes that agarwood extract used in normal people can also improve memory and concentration, and improve brain nerve performance The efficacy.

"Agarwood" in the present invention refers to all trees that can produce agarwood resin, and agarwood extract is a compound component extracted from agarwood. The shade-dried agarwood containing resin is a kind of Chinese herbal medicine. A report on the medicinal properties of agarwood provided by the Chinese Medicine Committee of the Department of Health of the Republic of China Executive Yuan pointed out that agarwood mainly treats: vomiting, hiccups, abdominal pain, stagnation of the large intestine, cold waist and knees, thoracic congestion, and asthma. Agarwood is also a traditional medicine in the Middle East and India.

It is recorded in the Compendium of Materia Medica: "Agarwood, pungent smell, mild temperature and non-toxic. Indications of feng shui and swelling to remove nausea; abdominal pain, cholera evil, evil spirits, qi, clear human spirit; adjust the five internal organs, nourish essence and impotence, warm waist and knees , Relieving vomiting, vomiting and diarrhea of cold, broken syndrome, cold wind paralysis, irresponsible joints, rheumatic skin pruritus, dysentery; invigorating the spleen and stomach, replenishing qi and mind. Treating qi and reversing asthma, large intestine deficiency, urinary puffiness, men’s coldness "However, there is no ancient book or scientific document that proves that Agarwood has the desired effect.

The present invention proposes the use of agarwood extract for enhancing the growth of neurites, repairing nerves and improving and preventing the degeneration of brain nerves in organisms, and further proves its efficacy with experimental data.

The agarwood extract of the present invention is obtained by extracting and concentrating from an agarwood. Furthermore, the agarwood extract is extracted and concentrated from the agarwood resin. The extraction method can be distillation, supercritical carbon dioxide, solvent extraction, cold pressing, liposuction, dipping, or carbon dioxide extraction. The chemical components of agarwood include phenyl ethyl chromenone derivatives, terpenoids, flavonoids and so on.

The present invention is to administer agarwood extract to the organism to treat the cranial nerve diseases of the organism, improve the cranial nerve symptoms of the organism, prevent the organism from cranial nerve diseases, Enhance or activate one of the organism's brain nerve performance or enhance the organism's nerve growth. The method of administering the agarwood extract to the organism is to further mix the agarwood extract with water and an emulsifier to form the essential oil to be atomized, and then atomize the essential oil to be atomized so that the organism absorbs the agarwood extract from its respiratory tract.

In summary, the agarwood extract of the present invention is extracted from agarwood, and the agarwood extract is administered to the organism. The use of the agarwood extract disclosed in the present invention is to enhance the nerve growth of the organism and treat, improve and prevent the degeneration of the brain nerve of the organism.

10‧‧‧Cerebral Cortex

11‧‧‧Skull

12‧‧‧Hippocampus back

2‧‧‧Nerve cells

20‧‧‧Cell body

211‧‧‧Axon

212‧‧‧Secondary axon

213‧‧‧ Tertiary axon

221‧‧‧First-degree dendrites

222‧‧‧Secondary dendrites

Figure 1 shows the fluorescence imaging of the hippocampal gyrus neurons of the rat brain in an experiment of the present invention.

Figure 2A is a schematic diagram showing the various levels of neurites in the brain nerve cells of the organism.

Figure 2B shows the fluorescence imaging of the hippocampal gyrus neurons of the mouse in the experiment of the present invention.

Fig. 3 is a bar graph showing the axon length of the hippocampal gyrus neurons of the mouse brain in the experiment of the present invention.

Fig. 4 is a bar graph showing the number of dendrites in the hippocampal gyrus of the rat brain in the experiment of the present invention.

Figure 5 is an image diagram showing the damage and repair of rat brain nerve cells in the experiment of the present invention.

Fig. 6 is a broken line diagram showing the time spent in swimming for the rats in the experiment of the present invention to perform the hydrazine experiment.

Fig. 7 is a histogram showing the white box residence time of the mouse in the black and white box experiment in the experiment of the present invention.

8A and 8B show the MRI images of the rat brain in the experiment of the present invention.

In order to make the advantages, spirit and features of the present invention easier and clearer to understand, the following embodiments will be used for detailed and discussion with reference to the accompanying drawings. It is worth noting that these embodiments are only representative embodiments of the present invention, and the specific methods, devices, conditions, materials, etc. exemplified therein are not intended to limit the present invention or corresponding embodiments.

In addition, the indefinite articles "a", "one" and "one" before the device or element of the present invention have no limitation on the quantity requirement (ie, the number of occurrences) of the device or element. Therefore, "a" should be read as including one or at least one, and a device or element in the singular form also includes the plural form, unless the number clearly refers to the singular form.

The term "improving, enhancing, enhancing, activating" as used herein refers to the cell sample or animal sample that uses the agarwood extract of the present invention, which has a higher survival rate and nerves compared to the cell sample or animal sample that does not use the agarwood extract of the present invention. Differentiation ability, nerve nourishment ability, cognition, learning and memory ability, etc.; and has more items to achieve normal physiological function and normal behavior performance indicators.

The term "treatment and prevention" as used herein refers to the cell sample or animal sample before the use of the Agarwood extract of the present invention, the cell sample or animal sample after the use of the Agarwood extract of the present invention can prevent or partially prevent diseases, symptoms, A condition, at least partially cures or alleviates a disease, symptom, condition, or adverse effect caused by the disease. The term "disorder" as used herein refers to diseases, genetic diseases, symptoms, focus, pathogenesis, etc.

The present invention proposes an agarwood extract that can be used to nourish nerve cells, enhance the growth of cranial nerves in organisms, and thereby improve and prevent cranial nerve diseases and symptoms; even, the present invention also proposes that agarwood extract can be used in normal people. Improve memory and concentration, and improve brain nerve performance. Enhancing the growth of brain nerves in an organism refers to increasing the number of dendrites or axons in an organism and increasing the length of dendrites or axons in an organism.

The agarwood extract of the present invention is obtained by extracting and concentrating an agarwood. Furthermore, the agarwood extract is extracted and concentrated from the agarwood resin. The extraction method can be distillation, supercritical carbon dioxide, solvent extraction, cold pressing, liposuction, immersion, or dioxide Carbon extraction method. In a preferred embodiment, the agarwood extract contains more than 1% by volume of α-Agarofuran or its derivatives and more than 3% by volume of α-Bulnesene or its derivatives. α-Agarofuran and α-Bulnesene are unique components of agarwood, which can be used as the characteristic index of agarwood extract. α-Agarofuran and α-Bulnesene exist in the whole plant of Agarwood, but it is easier to extract a high concentration of Agarwood extract from agarwood resin. The present invention does not limit that α-Agarofuran and α-Bulnesene must be effective ingredients in the use of nourishing nerve cells, and the effective ingredients may be one compound in agarwood extract or a synergistic effect of multiple compounds. Agarwood extract may also contain the following compounds: α-Copaene, γ-Muurolene, Cypera-2,4-diene, jinkoh-eremol, Kusunol, Dihydrokaranone, β-Patchoulene, oxo-agarospirol, Prezizaene, Aromandendrene, (-)-selina -3,11-dien-9-one, dehydrojinkoh-eremol, Agarospirol, 10,11-Himachala-3(12),4-diene.

In many specific embodiments of the present invention, the agarwood extract can be further diluted by 10 ³ to 10 ⁹ times for experimental, health care or medical applications.

Agarwood trees are native to Asia (from northern India to Vietnam and Indonesia). It appears especially in the rain forests of Indonesia, Thailand, Cambodia, Laos, Vietnam, Malaysia, northern India, the Philippines, Borneo and New Guinea. Agarwood trees are evergreen trees that grow to a height of 30-40 meters and have a diameter of 60 cm. Strictly speaking, agarwood is a plant belonging to the Aquilaria family (Aquilaria), but some tree species in the olive family (Burseracrae), camphor family (Lauraceae), and Euphorbiaceae (Euphorbiaceae) during the growth process, due to plant injury and simultaneous damage Fungal infection can also lead to incense, and eventually can bred agarwood. Therefore, the "Agarwood" in the present invention should cover the plant species recognized by those skilled in the art or related industries to produce "Aquilaria", including Aquilaria, Burseracrae, and Camphoraceae ( Lauraceae), Euphorbiaceae (Euphorbiaceae) Some of the tree species.

The "Aquilaria" in the present invention includes but is not limited to Aquilaria Agallocha, Aquilaria Ganadensis, Aquilaria Malaccensis, Aquilaria Vulgaris, Aquilaria Vulgaris Plants of Aquilaria Grassna, Aquilaria Moskowskii, Aquilaria Sinensis and Aquilaria Kajugaru; "Aquilaria" also includes but is not limited to Excoecaria formosana Hayata, Excoecaria bicolor Hassk, Agarwood (Excoecaria agallocha L.) and Excoecaria kawakamii Hayata (Excoecaria kawakamii Hayata); further, "Agarwood" also includes, but is not limited to, A. baillonii, A. hirta, and Agarwood. (A.rostrata), A. beccariana, A. cummingiana, A. filaria, A. khasiana, A. microcarpa , A. grandiflora (A. grandiflora), A. sinensis (A. sinensis), A. borneensis (A. borneensis) and A. bancana (A. bancana).

The method of administering the agarwood extract to the organism of the present invention may further be oral, smearing, inhalation, injection, sublingual administration and the like. In a specific embodiment, the method of administering the agarwood extract of the present invention is to mix the agarwood extract with water and an emulsifier to form the essential oil to be atomized, and then atomize the essential oil to be atomized so that the organism absorbs the agarwood extract from its respiratory tract . Compared with oral and intravenous injection methods, the respiratory tract absorption method can cross the blood-brain barrier (BBB) to reach the brain and obtain better nerve nourishing effects.

The agarwood extract of the present invention mainly has the function of nourishing nerve growth, helping neurite growth and repair. This can further improve, treat or prevent neurological diseases or neurological symptoms, including but not limited to attention deficit, hyperactivity or hyperactivity disorders, memory impairment, mental Can decline, impaired motor coordination, decreased neuron or glial cell survival rate, nerve fiber breakage, central nervous system disease, Parkinson's disease, Alzheimer's disease, diseases affecting sensory neurons, and cortical limbic system diseases , Conditions related to developmental delay and learning disabilities, Down's syndrome, neuronal death induced by oxidative stress, mood-related conditions, depression, conditions due to aging, conditions due to chronic alcoholism, and drug abuse Symptoms, pathological changes caused by local trauma, and symptoms caused by negative side effects of therapeutic drugs and treatments. The above-mentioned diseases can be improved and prevented by nourishing nerve growth, so agarwood extract with the effect of nourishing nerve growth can improve and prevent the above-mentioned diseases.

In some embodiments, the neurological disorder is memory impairment, intellectual decline, impaired motor coordination, decreased survival rate of nerve cells or glial cells, insomnia, sleep disorders, Parkinson’s disease or Alzheimer’s disease, mood Related illnesses, depression. In some specific embodiments, compared with the negative control group, the above-mentioned symptoms have been significantly improved after the experimental mice are administered the present invention for a period of time.

As used herein, the term "one of the biological manifestations of cranial nerve disorders" refers to the manifestations of brain nerve abnormality, damage or degeneration, such as brain nerve damage, brain nerve degeneration, motor dysfunction, memory degeneration, neuron Or decreased survival rate of glial cells, deterioration of cognitive or learning ability, mood-related disorders, depression, etc.

The term "an organism suffering from a neurological disorder" as referred to herein refers to a disorder or symptom related to damage or degeneration of nerve cells or glial cells. Specifically, it can refer to symptoms that include neuropathy that leads to the death of neurons or glial cells and/or that are not yet lethal, including: Central nervous system diseases, including degenerative diseases that affect the basal ganglia (eg Huntington’s disease, Wilson’s disease, striatal substantia nigra degeneration, cortical basal ganglia degeneration Chemical), Tourette’s disease, Parkinson’s disease, progressive supranuclear palsy, progressive bulbar palsy, hereditary spastic paralysis, spinal muscular atrophy, amyotrophic lateral sclerosis, and changes Body, dentate nucleus red nucleus pallidus subthalamic nucleus atrophy, olive pontine cerebellar atrophy, mood-related disorders, depression, paraneoplastic cerebellar degeneration, and dopamine toxicity; Diseases affecting sensory neurons, such as Friedreich's ataxia, diabetes, peripheral neuropathy, and retinal neuron degeneration; diseases of the cortical limbic system, such as cerebral amyloid angiopathy, Pick’s atrophy, Leiter Syndrome Neurodegenerative diseases involving the nervous system and/or brain stem, including Alzheimer's disease, AIDS-related dementia, childhood cerebrospinal disease, diffuse Lewy body disease, epilepsy, multiple system atrophy, Guillain-Barr Li syndrome, lysosomal storage disease, brown fat storage disease, infantile spongiform encephalopathy (Alpers disease), dizziness caused by central nervous system degeneration; Conditions related to developmental delay and learning disabilities, Down’s syndrome, and neuronal death induced by oxidative stress; conditions due to aging, chronic alcoholism or drug abuse, including, for example, the locus coeruleus, cerebellum, Degeneration of neurons in the cholinergic basal forebrain, dementia caused by aging, cognitive and motor damage caused by the degeneration of cerebellar neurons and cortical neurons, and neuronal damage in the basal ganglia caused by long-term amphetamine abuse Sports injury, attention deficit, hyperactivity or hyperactivity disorder caused by degeneration; Pathological changes caused by local trauma, such as: stroke, ischemia, insufficient blood supply, hypoxic ischemic encephalopathy, hyperglycemia, hypoglycemia, closed head trauma, or direct trauma, nerve fiber damage; and Diseases caused by the negative side effects of therapeutic drugs and treatments (for example, response to N-methyl-D-aspartate (N-methyl-D-aspartate, NMDA) glutamine receptor antagonists Degeneration of the cingulate cortex and entorhinal cortex caused by the spasm dose).

According to some medical literature, depression and mood disorders are also a phenomenon of neurological disorders.

In order to illustrate that the agarwood extract of the present invention has the above-mentioned effects, the following will describe the completed cell experiments and animal experiments. In the cell experiment in vitro, different concentrations of agarwood extract were added to the culture medium of nerve cells, and the changes of nerve cells were observed after culturing in a constant temperature incubator at 37°C and 5% CO _{2 for} three days. When administering agarwood extract to the cell experiment, add 1/30M, 1/10M, 1/5M (1/30,000,000, 1/10,000,000, 1/5,000,000) ratio of the agarwood extract to the culture solution Process for three days.

Example one

Please refer to Figure 1. Figure 1 shows the fluorescence imaging of the hippocampal gyrus neurons of the rat brain in an experiment of the present invention. β-Ⅲ tubulin is a skeletal protein unique to nerve cells. After β-Ⅲ tubulin is stained, it can be seen that the neurites of nerve cells are green under a fluorescent microscope. DAPI can penetrate cell membranes and bind to DNA. When viewed under a fluorescent microscope, DAPI appears blue, representing the location of the nucleus of nerve cells. In this experiment, nerve cells were stained with β-Ⅲ tubulin antibody and DAPI respectively, and the observed growth of neurite cells is shown in Figure 1. It can be seen that when the concentration of agarwood extract (AEO) is 1/5M (1 in 5,000,000), the growth of its neurites is significantly better than that of the control group (control) without the agarwood extract (AEO), such as nerve The length of the neurites and the number of neurites.

Example two

See Figure 2A. Figure 2A is a schematic diagram showing the various levels of neurites in the brain nerve cells of the organism. In this cell experiment, observe the neurites extending from the cell body 20 in the nerve cell 2. The neurites are divided into axons and dendrites, and the axons are divided into primary axons 211, secondary axons 212, and tertiary axons. 213. The dendrites are divided into primary dendrites 221 and secondary dendrites 222. Axons and dendrites are responsible for The transmission and reception of electrochemical signals between different nerve cells 2 is also the most important purpose of nerve cell 2 conduction. Therefore, the greater the number and length of neurites, the more opportunities and distances that nerve cells 2 can contact with other nerve cells, and the greater the number of synapses that may be formed. When the network connection between nerve cells in the brain tissue increases, When it is strong, the performance of the brain nerves will also be improved.

The above-mentioned brain nerve performance includes biological instinct performance such as memory, concentration, spatial memory, cognitive ability, learning ability, emotional balance, language ability, and athletic ability. In addition, it can also delay brain atrophy and increase brain cell mass or brain volume.

See Figure 2B. Fig. 2B shows a fluorescent image of a rat brain hippocampal gyrus after staining in another experiment of the present invention. Furthermore, in order to know whether the length and number of neurites increased after treating nerve cells with agarwood extract act on axons or dendrites, the following experiment was performed. Different antibodies are added to the nerve cells, which can then be used to distinguish the types of neurites under a fluorescent microscope. Use Tau5 protein antibody to define axons, add Tau5 antibody and then add a green fluorescent secondary antibody to distinguish axons (green); use MAP2 protein antibody to define dendrites, add MAP2 antibody and then Add a secondary antibody that emits red fluorescence to distinguish dendrites (red). From this figure, you can roughly distinguish the length and number of axons and dendrites. The length and number of axons and dendrites in the treatment groups with each concentration of agarwood extract were greater than those in the control group without the agarwood extract. Then, the length and number of axons and dendrites were quantified by computer software (ImageJ) and statistically analyzed (One-way ANOVA, followed by Post hoc Newman-Keuls test).

Please refer to Figure 2B, Figure 3 and Figure 4. Fig. 3 is a bar graph showing the axon length of rat brain nerve cells in the experiment of the present invention. Fig. 4 is a bar graph showing the number of dendrites of rat brain nerve cells in the experiment of the present invention. The number of each group in this experiment is greater than or equal to twenty (*p<0.05, **p<0.01). After the length and number of neurites observed in FIG. 2B are separately counted, the histograms in FIGS. 3 and 4 are drawn. As shown in Figure 3, compared with the control group, the length of the primary and secondary axons in the treatment group added with agarwood extract increased significantly, and as the concentration of agarwood extract increased (1 in 30,000,000) ~ 1 out of 5,000,000), the degree of growth tends to be higher. As shown in Figure 4, in the treatment group added with agarwood extract, as the concentration of agarwood extract increases, the number of dendrites tends to gradually increase. Especially under the treatment with agarwood extract concentration of 1/5,000,000, compared with the control group, the number of primary dendrites and secondary dendrites reached a significant level of improvement. As the length of the axon increases, it means that the number of synapses that can be formed on the axon can be greatly increased, and the increase in the number of dendrites also means that the points that can form synapses will increase, which shows that the agarwood extract acts on Cranial nerve cells will increase the connections and synapses of the cranial nerves, achieve the effect of nourishing nerves, and then enhance the performance of the cranial nerves. It is proved that agarwood extract has the effect of nourishing nerves and can improve or regulate the plasticity of nerve cells, which means that agarwood extract has the potential to improve, treat or prevent neurological diseases or neurological symptoms.

Example three

Please refer to Figure 5. Figure 5 is an image diagram showing the damage and repair of rat cerebral cortical nerve cells in the experiment of the present invention. In the third cell experiment, the basic principle of measuring the ability of cell migration and repair is: after separating and culturing the primary cerebral cortex cells, a blank area is artificially created on the overgrown single layer of cells, called "scratches". Or wound", cells on the damaged edge will stretch out axons to regenerate and enter the blank area to accelerate repair. This method is widely used to observe the effects of drugs on cell migration and axon regeneration and repair. Plant an equal amount of cells on a petri dish. After attaching, scratches are made on the petri dish (between the two dotted lines on the right side of Figure 5) to break the connection between neurite cells. After a while, observe the growth of nerve cells on the petri dish (the two empty lines on the left in Figure 5) Between lines). This can be used to observe whether there is any change in the repair of nerve cells under the treatment of different concentrations of agarwood extract. It can be seen from Figure 5 that only a small amount of nerve axons regenerate at the damaged scratches in the control group; in the 1/30,000,000 and 1/10,000,000 treatment groups, it can be seen that the neurites of nerve cells grow to the damaged area. ; In the 1/5,000,000 treatment group, it can be seen that the nerve cell axons on both sides of the dotted line have been connected to each other. This means that agarwood extract can nourish nerves and promote the repair of broken brain neurites.

Example four

The APP/PS1 gene transgenic mice was used as the verification of in vivo experiments. APP/PS1 gene transgenic mice are an animal model of Alzheimer’s disease mice. Because of their genetic defects, amyloid plaques are produced and deposited in the brain in large quantities. Glial cell degeneration occurs when mice are 8 weeks old. Synaptic damage occurs at the age of one week, and plaque A β deposition begins to occur in the cortex at 6 weeks of age and the hippocampus at 3-4 months of age, which may lead to Alzheimer’s disease. Therefore, this type of mouse is suitable for dementia animal models. the study. It is reported that the dendritic spines around the plaque will gradually disappear at about 4 weeks of age and continue for several months. It is reported that the mouse will have cognitive dysfunction at the age of seven months, especially the cognitive deficits in spatial learning and memory in the water maze pattern, which is regarded as a unique symptom of Alzheimer's disease. The long-term potentiation (LTP) in the CA1 region of the hippocampus was impaired at 8 and 15 months of age. In the following experiment, the agarwood extract of the present invention was formulated into agarwood oil to be atomized, and then the agarwood oil was inhaled by the method of atomized fragrance.

In the first animal experiment, APP/PS1 mice were divided into AEO (Agarwood Essential Oil, AEO) treatment group and Control group, and Morris water maze experiment was performed respectively. The AEO treatment group placed four-month-old Alzheimer’s rats in a box six times a week for 20 minutes of atomized agarwood oil treatment for three months; the Control group took four-month-old rats The Alzheimer's disease rat received aerosolized pure water treatment in a box for 20 minutes daily for three months. The water maze experiment was used to test spatial learning and memory capabilities and cognitive functions. The experimental mice were placed in a pool. A hidden platform was set up under the water surface of the pool. The mice would try to swim to a position where their feet could touch the bottom to avoid drowning. At the beginning, the mouse will swim aimlessly until it accidentally touches the position of the platform. The mouse can safely stay on the platform and remember its location based on the surrounding environment. After repeated training three times a day, mice with good spatial learning and memory will quickly find the location of the hidden platform under the water. In this way, recording the time from when the mouse is put into the pool until the platform is found can be regarded as a discriminant index of spatial learning and memory performance and cognitive function.

Please refer to Figure 6. Fig. 6 is a broken line diagram showing the time required for the mouse to find the platform under the water surface in the experiment of the present invention. The time required for the Alzheimer’s mouse group (diamond) and Alzheimer’s mouse treated with AEO to find the platform under the water in the Control group (circle) of the pure water treatment group. After five consecutive days, the mice arrived The time spent on the platform is drawn as a line graph. The number of replicates for each treatment in this experiment is greater than or equal to three. It can be seen from Figure 6 that the two groups of mice on the first and second days are still in the exploratory stage, and the time required for the two groups of mice to find an underwater platform on the second day can be reduced from an average of 55 seconds to an average of 35 seconds. About seconds. However, the time for the mice in the Control group to find the platform under the water every day from the second day to the fifth day was similar, ranging from 30 seconds to 40 seconds. On the other hand, the mice in the AEO group fell between 10 seconds and 20 seconds, which had better performance than the mice in the Control group. It can be inferred from this that the spatial learning and memory performance and cognitive function of mice with Alzheimer's disease in the brain can be improved after inhaling agarwood extract.

Example five

In the second animal experiment of the present invention, the mice were divided into Control group, AD treatment group and AD+AEO treatment group. AD treatment group refers to seven-month-old APP/PS1 gene transfer Rats with Hymer disease, and the AD+AEO treatment group refers to seven-month-old APP/PS1 gene transgenic mice that have been treated with agarwood incense for three months. This experiment also provided wild type mice (wild type) with only pure water mist as the Control group, and the Control group was the same age as the AD treatment group and AD+AEO treatment group but normal genes. The three groups of mice were subjected to a light-dark transition test. The black and white box experiment was used to test discrimination, memory, and emotional stability, also known as the passive one-way avoidance test. Rats feel uneasy and anxious when they are placed in a bright white box, and their nature drives them toward the dark black box. When the mouse enters the black box, a slight electric current foot shock (0.7mA/sec, for 2sec) is applied to make the mouse uncomfortable, and then the fear memory of the mouse is detected. 14 days after the electrical stimulation, the mice were put into the white box again, and the time the mice stayed in the bright area was recorded. The longer the stay, the better the memory ability of the mice. This is a long-term fear memory test. In this way, the elapsed time from when the mouse is put into the white box to when the mouse enters the black box can be regarded as a distinguishing indicator of memory, concentration and learning ability.

Refer to Figure 7. Fig. 7 is a histogram showing the white box residence time of the mouse in the black and white box experiment in the experiment of the present invention. The second animal experiment was carried out on the 14th day after suffering (training group) or not suffering (untrained group) foot electrodes. The time the rats stayed in the white box was counted, and the rats staying in the 14th day after the untrained and training Time and draw a histogram. The number of replicates for each treatment in this experiment is greater than or equal to three. It can be seen from Fig. 7 that, no matter what the group, the mice escaped from the white box to the black box in a very short time before being stimulated by the foot, which shows that the dark nature of the rats in each group is not affected. On the 14th day after receiving the foot electric shock, the rats of each treatment group were put into the white box, and the time the rats stayed in the white box was calculated. The control group rats stayed in the white box for about 500 seconds on average before entering the black box; the AD group rats stayed in the white box for an average of less than 200 seconds before entering the black box; the AD rats were treated with AEO and stayed in the white box for about 600 seconds before entering the black box. . This means that the AD group is indeed more memorable than the average mouse Memory and learning ability are insufficient; however, the rats in the AD+AEO group can recover to the level of memory equivalent to those in the control group after agarwood treatment, and even have a tendency to exceed the memory level of the control group. It can be inferred that the memory and learning ability of mice with Alzheimer's disease in the brain can be improved after inhaling agarwood extract.

Example Six

Please refer to Figures 8A and 8B. 8A and 8B show the MRI images of the rat brain in the experiment of the present invention. The wild type mice, Alzheimer's disease mice (AD group), and Alzheimer's mice were treated with agarwood treatment (AD+AEO group) to detect brain volume changes by MRI. Fig. 8A indicates the dorsal hippocampus 12, brain shell 11 and cerebral cortex 10 of the mouse, respectively. The brain shell 11 is bone tissue, and its shape is not easy to change. Under normal conditions, there is a slight gap between the skull 11 and the cerebral cortex 10. The cerebral cortex 10 of the wild-type mouse (control) of the same age is a smooth and full smooth brain structure. The gap 11 is shown in black in Figures 8A and 8B . When the cerebral cortex 10 of the mouse begins to shrink, the gap between the cerebral case 11 and the cerebral cortex 10 will become more obvious. Therefore, the MRI image can be used to determine whether the rat cerebral cortex 10 has atrophy.

The left, middle, and right images of Figure 8B are images taken by mice in different groups. From top to bottom in each group, the same mouse is sequentially detected from the brain stem to the frontal lobe. Figure 8B shows that the gap between the braincase 11 and the cerebral cortex 10 of the AD group of mice is more obvious than that of the Control group (wild-type) mice; and the edge of the cerebral cortex 10 of the AD group mice is more bumpy and shrunken (atrophy) Characterization 1), the cerebral cortex 10 of the mice in the Control group was relatively smooth and full. Compared with the AD group of mice, the gap between the braincase 11 and the cerebral cortex 10 of the AD+AEO group was narrower, and the cerebral cortex 10 was more full and round. The signs of cerebral cortex 10 and gaps in the AD+AEO group are also similar to those in the Control group, which means that the brains of the AD+AEO group are The degree of atrophy and degeneration will be suppressed, and the brain volume will increase. In addition, after computer software analysis, AD mice treated with agarwood will increase 12.5% in volume of dorsal hippocampus 12 tissues compared to AD mice not treated with agarwood. In other words, smoking agarwood extract of the present invention can prevent brain atrophy or increase brain cell volume in mice, thereby improving the symptoms of Alzheimer's disease.

In summary, the present invention proposes that the agarwood extract extracted by distillation has the use of treating and preventing cranial nerve diseases and enhancing cranial nerve performance, and the said efficacy is proved by experimental data. The use of agarwood extract in the treatment and prevention of cranial nerve diseases in the prior art has not been reported, and it has not been proved by data; and the agarwood extract of the present invention has been confirmed in cell and animal experiments to repair brain nerves, The effect of improving memory.

Through the detailed description of the preferred embodiments above, it is hoped that the characteristics and spirit of the present invention can be described more clearly, and the scope of the present invention is not limited by the preferred embodiments disclosed above. On the contrary, its purpose is to cover various changes and equivalent arrangements within the scope of the patent application for the present invention. Therefore, the scope of the patent application for the present invention should be interpreted in the broadest way based on the above description, so that it covers all possible changes and equivalent arrangements.

Claims (10)

A kind of agarwood extract is used to enhance the performance of cranial nerves. An agarwood extract is administered to a living body to enhance the growth of the brain nerves of the organism, wherein the agarwood extract is extracted and concentrated from agarwood by an extraction method Therefore, the extraction method includes one selected from the group consisting of distillation, supercritical carbon dioxide, solvent extraction, cold pressing, liposuction, immersion, and carbon dioxide extraction. The use of the agarwood extract described in item 1 of the scope of patent application, wherein enhancing the growth of the brain nerves of the organism includes increasing the number of dendrites of the organism and increasing the length of the axons of the organism. The use of agarwood extract as described in item 1 of the scope of patent application, wherein the agarwood extract is further extracted and concentrated from agarwood resin of the agarwood. The use of the agarwood extract described in item 1 of the scope of patent application, wherein the method of administering the agarwood extract to the organism is further to mix the agarwood extract with water and an emulsifier to form an essential oil to be atomized, Re-atomizing the essential oil to be atomized allows the organism to absorb the agarwood extract from its respiratory tract. An agarwood extract is used to prepare a composition for improving cranial nerve diseases. An agarwood extract is administered to a living body to improve the organism suffering from a cranial nerve disorder, wherein the agarwood extract uses an extraction method It is extracted and concentrated from agarwood. The extraction method is selected from the group consisting of distillation, supercritical carbon dioxide, solvent extraction, cold pressing, liposuction, impregnation and carbon dioxide extraction One of them. The use of the agarwood extract described in item 5 of the scope of the patent application, wherein the cranial neuropathy includes selected from Down’s disease, Alzheimer’s disease, Parkinson’s disease, Tourette’s disease, epilepsy, and Mental illness, neurodegenerative diseases, central nervous system diseases, sensory neuron diseases, cortical limbic system diseases, cranial nerve damage, cranial nerve degeneration, motor dysfunction, memory deterioration, neuronal or glial cell survival rate decline, cognitive decline , At least one of the group consisting of deterioration in learning ability, mood-related disorders, and depression. An agarwood extract is used to prepare a composition for preventing cranial nerve diseases. An agarwood extract is administered to a living body to prevent the organism from suffering from a cranial nerve disorder, wherein the agarwood extract is obtained by an extraction method Agarwood is extracted and concentrated. The extraction method includes one selected from the group consisting of distillation, supercritical carbon dioxide, solvent extraction, cold pressing, liposuction, dipping, and carbon dioxide extraction. One. The use of the agarwood extract described in item 7 of the scope of patent application, wherein the cranial neuropathy includes selected from Down’s disease, Alzheimer’s disease, Parkinson’s disease, Tourette’s disease, epilepsy, and Mental illness, neurodegenerative diseases, central nervous system diseases, sensory neuron diseases, cortical limbic system diseases, cranial nerve damage, cranial nerve degeneration, motor dysfunction, memory deterioration, neuronal or glial cell survival rate decline, cognitive decline , At least one of the group consisting of deterioration in learning ability, mood-related disorders, and depression. An agarwood extract is used to prepare a composition for enhancing cranial nerve performance. An agarwood extract is administered to a living body to enhance or activate a brain nerve performance of the organism, wherein the agarwood extract uses an extract The method is obtained by extraction and concentration of agarwood. The extraction method is selected from the group consisting of distillation, supercritical carbon dioxide, solvent extraction, cold pressing, liposuction, dipping, and carbon dioxide extraction One of them. The use of agarwood extract as described in item 9 of the scope of patent application, wherein the brain nerve performance is selected from memory, concentration, sense of direction, cognitive ability, learning ability, language ability, emotional balance and motor ability. At least one of the formed groups.

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