TW200927155A - Composition and method for prevention and treatment of alzheimer's disease - Google Patents

Abstract

This invention presented is a composition and method for prevention and treatment of Alzheimer's disease, the composition comprising monacolins, anti-inflammation agents and anti-oxidant compounds is made by the method of the invention. The composition of the invention has effect on prevention and treatment of Alzheimer's disease without noticeable side effects caused to patients.

Description

200927155 IX. Description of the Invention: [Technical Field] The present invention relates to a composition for treating and preventing Alzheimer's disease and a preparation method thereof, and more particularly to a monacolin- (from a red glutinous rice) Monaco1 ins), an anti-inflammatory substance and an antioxidant substance for the treatment and prevention of Alzheimer's disease, can be applied to tablets, capsules, powders, drinks and the like for consumers to take. Ο [Prior Art] Alzheimer’s disease (AD), also known as Alzheimer's disease, is a persistent neurological disorder. People who get Alzheimer's disease will gradually lose their memory and have language and emotional barriers. The gradual loss of intelligence is called dementia. When the disease becomes more and more serious, the patient needs the help of his Q people in all aspects of life, such as taking a bath, eating, going to the toilet, and so on. Because people with Alzheimer's disease need day and night care, the lives of their relatives and friends are often greatly affected. The loss of memory may be the most common symptom of Alzheimer's disease, especially the recent events that have occurred or have only recently been obtained. The initial symptoms appear subtle and gradual as 'unrecognizable, and these symptoms may also occur in other dementias that are not specific to Alzheimer's disease. For example: Lost in a familiar place: If something has been done, it is always a matter of old things or can't learn new things. : 5 200927155 When the situation worsens, the patient may not be able to find the appropriate word or make a major decision when the 衽拄 衽拄 _ ” ” ” ” ” ” ” ” ” One of the most painful things is that patients sometimes have no way to cut it, and they can help their relatives and friends in a hundred times. The patient's personality may also become abnormally irritating, paranoid and suspicious, and do not like to interact with people. The patient may appear on the street and get lost in the home. The new study shows that the area of the brain that deals with visual and spatial information in Alzheimer's disease may be damaged. This may explain why the patient has no Ways to recognize where you are or where you can't figure out the direction. Patients may also become unfocused and therefore unable to care for their daily physical needs. Other areas of the brain that are important for memory in Alzheimer's patients are also Affected, such as basal forebrain and hippocampus. Many people suffering from Alzheimer's disease die from their cause, such as pneumonia. From the beginning, patients with Alzheimer's disease generally have a life span of 6-8 years, but still more than 20 years of survival. There are currently about five drugs for the treatment of Alzheimer's disease in the United States. Approved by the US Food and Drug Administration (FDA). These drugs are cholinesterase inhibitors (non-trade name tacrine and donepezil). Cholinesterase is the acetylcholine decomposition. 6 200927155 The key enzymes in these medicines, these drugs are blocked by yinyangling and still choline esterase

(cholinesterase) acts to inhibit the decomposition of acetylcholine. Both drugs can increase the content of acetylcholine in the brain. Both drugs can delay the loss of memory and help the patient perform the actions required for daily living. But it is important that these drugs do not cure Alzheimer's disease. They can only alleviate the symptoms of Alzheimer's disease. In addition, these drugs can cause some side effects to patients, such as nausea, headache, ventral side, Z sleep, pain, hallucinations or dizziness, etc., so it is not a practical treatment for Alzheimer's disease. As described above, as effective treatment and prevention of Alzheimer's disease, without any obvious adverse side effects, it is a practical thinking. 〇 [Summary of the Invention] The main object of the present invention is to provide a composition for treating and preventing Alzheimer's disease to achieve the effect of actually treating and preventing Alzheimer's disease. Another object of the present invention is to provide a composition for treating Alzheimer's which is effective in treating and preventing Alzheimer's disease without causing any significant adverse side effects. A group for treating and preventing Alzheimer's disease 200927155 according to the present invention. The composition, which comprises a combination of m〇nac〇lins, an anti-inflammatory substance and an antioxidant substance, can be applied to a consumer in a tablet, a capsule, or the like. The composition formed by the three types of substances is used to treat and prevent Alzheimer's disease. In addition, in the practice of the present invention, the effective minimum content of monacolin (_ac〇l ins) is at least greater than ΙΟΟ/zg, and the resistance is The effective minimum content of inflammatory substances is at least greater than ❹40 "g and the effective minimum content of antioxidants is at least greater than that of Monacol ins, the optimal ratio of inflammatory substances to antioxidants is 4 0 · 2 · 1 It will be achieved by the treatment and prevention of Ace, and the effect of not causing any obvious adverse side effects. Furthermore, a composition for treating and preventing Alzheimer's disease disclosed in the present invention is a composition comprising monac, an anti-inflammatory substance, and monacolin (M〇nac〇lins). The effective minimum content is less than 20〇eg, and the effective minimum content of anti-inflammatory substances is required to be >, greater than 60#g' and the optimal weight ratio of M〇nac〇iins to inflammatory substances is 1 〇: 1 'In this composition, it is also possible to achieve the treatment and prevention of Alzheimer's disease without any obvious adverse side effects. Further, in the present invention, a method for treating and preventing Alzheimer's disease and a composition is as follows: 200927155 First clean one meter and sterilize under high pressure and high temperature environment, then inoculate a specific red sputum strain Into a culture medium and inoculation in a specific temperature and humidity environment, a specific oscillating environment and a first specific time limit, after the completion of the sterilization, stirring the inoculum culture medium in a first specific temperature environment and continuing for a second specific time limit Providing a specific proportion of moisture, and performing appropriate agitation at a fixed time in the first specific temperature environment for a post-ripening in a third specific time limit, and collecting the red mash fermentation after completion of the fermentation and in the fourth specific period Maintaining a second specific temperature to dry it, grinding the dried red peony fermentate into a powder and analyzing whether it meets the one-component ratio condition, when it is in accordance with the present invention for treating and preventing Alzheimer's disease composition , the prepared powder of the red sorghum fermented product is added into an edible beverage in a specific ratio to prepare a medicinal In combination with the prevention of Alzheimer's disease, the powder of the red sorghum fermented product can be filled into a capsule or made into a tablet, and the composition can be implemented in this manner. It does treat and prevent Alzheimer's disease and does not produce any obvious adverse side effects. The details and techniques of the present invention are as follows: [Embodiment] The present invention is a composition for treating and preventing Alzheimer's disease, and prior to introducing the composition of the present invention, the concept of the present invention is 9 200927155 Description. The main factor in the formation of Alzheimer's disease is the amyloid /5-protein, which is caused by a large amount of deposition in the brain, and causes the lack of neurotransmitters and oxidative inflammation to make the disease gradually worsen. The production of Ay5 That is, the fragmented protein produced by the cutting enzyme (amyl〇id precursor protein, APP) is a fragment of the specific position. The sheared enzyme contains α, no secretase. /g means that the amino acid bond of the 671, 672 can be cleaved by the ® Θ -secretase and the 7-secretase can be cut after the 713 is cleavable on the APP. When the enzyme is cleaved on the amino acid sequence In addition to the Bu 40 and Bu 42 fragments, the remaining fragments are generated. If the APP is cleaved by a-secretase to produce a fragment of sAPP-α and pl〇kDa, and pl〇 can be cleaved by γ-secretase to generate ρ 3 and P? fragment, where ρ3 is a small fragment. In addition, if ❹APP is cleaved by yS-secretase to generate sAPP-0 and pl2 kDa fragments, pl2 fragment can be cleaved again by 7-secretase to produce A泠 and p7. Fragment Evin et al. 2003; Shoji et al. 1 9 92). These small fragments have no ability to aggregate in the brain, but can demonstrate the cleavage activity of different types of secretase. When APP passes 泠-secretase and 7-secretase Decomposition produces all types of A / 3, where soluble A is not toxic and must be polymerized to form 10 200927155 fiber bundles (fibri 1 s ) which are toxic to nerve cells. Soluble vermiculite is not toxic 'must After polymerization to form fibri for 1 s, the nerve cells can be transfected by disrupting intracellular calcium ion balance and inducing oxidative stress. A cold polymer can also interfere with the promotion of intracellular tau protein hyperphosphorylation. The extension of the axons causes cell death. In addition, the A-fiber bundle can be activated by binding to the special receptors on the microglia and astrocyte membranes in the brain, which release a variety of neurotoxins, including interleukin ( Inflammatory substances such as IL-1), interleukin-6 (il-6), tumor necrosis factor (TNF_a), and free radicals such as nitric oxide and superoxide anion attack the nerve cells, causing their death. In recent years, it has been found that the apoE (ApoE, apol ipoprotein E) gene on the chromosome 9 is associated with Alzheimer's disease, and the ApoE and A/S are rapidly combined and deposited in the brain to form plaques for the elderly. Will cause necrosis of nerve cells. 〇 In addition, many literatures have pointed out that cardiovascular disease and Alzheimer's disease have a certain correlation. According to Martha et al., the elderly who are over 65 years old are surveyed, and the diet is rich in saturated fatty acids that cause cardiovascular disease. After tracking, the majority of the elderly will suffer from Alzheimer's disease after 4 years. In contrast, the diet rich in polyunsaturated fatty acids is inversely related to the elderly with monounsaturated fatty acids (Freund-Levi et al. 2006). There are many studies that have shown that the production of A stone in Alzheimer's disease is related to intracellular lipid metabolism (Frears et al. 1 999; Kuo et al. 1 998; Roher and Kuo 1999). In recent years, studies have shown that a cold is altered by the distribution of intracellular cholesterol and cholesterol acetification (Frearsetal. 1 999). ApoE promotes elevated levels of cholesterol in the plasma and is one of the risk factors for cardiovascular disease. PuglieUi et al. found that the activity of acetylcholine in the cells of hamsters was positively correlated with the content of cholesterol lipids in 2 years (Puglielli et al. 200 1; Zhao et al. 20 05) The disease is positively associated with Alzheimer's disease. Thus, the composition of the present invention focuses on reducing the deposition of point A in the brain and reducing the saturated fatty acids that cause cardiovascular diseases for the treatment of Alzheimer's disease. In recent years, research on the number of red sputum bacteria (such as; Species) has been increasing. In the future development, Hung Hom will be developed into a compound health food. M〇nac〇Hn κ, r-aminobutyric acid (GABA) and antioxidant substances in red peony have been confirmed by the present invention to greatly improve the feasibility of improving Alzheimer's disease for treatment and prevention. The alias of Monacol in K contains lovastatin, a rate-limiting enzyme for cholesterol synthesis - hydroxymethylglutarate coenzyme A cyclase 12 200927155 (3-hydroxy-3- Inhibitors of methylg1utary1-coenzyme A reductase, HMG CoA reductase, which are statin-like compounds, have been clinically proven to be effective in improving cardiovascular disease (CAD). Epidemiological studies in recent years have also pointed out that the treatment of Alzheimer's patients with s t a t i η drugs does have a good improvement effect. UK General Practitioners Research Ο

Database) pointed out that 70% of patients with statin drugs have a significant improvement (Jick et al. 2000); similar experiments include 2000 Wolozin et al. The elderly with Alzheimer's disease as a subject are diagnosed according to the criteria of NINCDS-ADRDA (National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease oand R e ated D isorders A ssociation ) In this trial, subjects were divided into three groups, group A was the control group, group B was treated with statins, and group C was treated with other cardiovascular diseases (including blood pressure lowering drugs). Surprisingly, when statins are used to treat patients, the degree of Alzheimer's disease can be reduced by 70%, with Lovastatin (1 〇vastat i η) and palavastatin (pravastatin) The best effect (Wolozin et al. 13 200927155 2000) nicotinic, muscarinic, serotonin in the brain of patients with Alzheimer's disease Surface leucine (glutamate) receptors, and 7 " - aminobutyric acid (T -aminobutyric acid, GABA), norepinephrine

Nerve impulse transfer factors such as norepinephrine have defects. The brain will be reduced by 10% during aging, mainly due to the decrease in the number of neurons in the cerebral cortex. In some areas, it will even decrease by 30-50%, and the amount of neurotransmitters will also decrease, such as B. Choline, GABA, catecholamine, etc. Because of the reduction in these substances, the brain's cognitive function is reduced or memory capacity is impaired. The earliest symptoms are memory loss, which loses the ability to judge things and is easy to lose. In the advanced stage, the patient may have language problems, abnormal behavior, paralysis, and life cannot take care of themselves (Mohr et al. 1994). When the glandular gland is deficient in 2 or H2〇2 and 〇H. is too large, it leads to the formation of highly reactive 0H·. The cold oxidation of A cold radicals leads to the formation of insoluble Αβ, which worsens Alzheimer's disease. Experiments have found that oral antioxidants such as vitamin C and vitamin E are effective in slowing the symptoms caused by Alzheimer's disease (Yallampalli et al. 1998; Yamada et al. 1999) (in addition to neuronal amine (ceramlde), a natural The neurogenicity 14 200927155 is resistant to A/3 and FeS (h causes hippocampal regurgitation) (Abousalham et al. 2002). The antioxidant capacity of red peony was proposed by Aniya et al. in 1999. The antioxidant mechanism of dimerumic acid is known to eliminate 〇H, · 〇2_, ferryl-Mb, peroxyi radicals and inhibition of lipid peroxidation (Lp〇), which provides an electron The oxide oxidizes itself to a nitr oxide radical, and the nitroxide radical is removed again to achieve an antioxidant effect (Taira et al. 2002). The antioxidant effect can be applied to the prevention of Alzheimer's disease to avoid the disease being aggravated by the attack of oxidative free radicals. The present invention was published on July 30, 2007 in journalof

Neuroscience Research (Lee CL, Kuo TF, Wang JJ, Pan TM: Red mold rice ameliorates impairment of memory

J and learning ability in intracerebroventricu1ar amyloid beta-infused rat via repressing amyloid beta accumulation. J Neurosci Res. 2007, 85, 3171-7182.), the animal used in the study of the present invention is purchased from the National Taiwan University School of Medicine Experimental Animal Center. Wistar strain male rats, 8 weeks old, weighing about 250 g, 7 in each group, kept in air-conditioned space 'temperature maintained at 23 ± 1 〇 c lighting control 12 15 200927155 ❹ Ο hours 12 hours Dark (08:00 light, 2: dark light), food and water are not limited. Rats were pre-fostered to the weight of the 3 uterus, and the experimental scalpel group and the brain infusion pump were implanted. The daily intake of red glutinous rice and the injection volume of A/3 40 in each group were as shown in Table 3_2eVehicle. Surgical Ren not lost the left A-call 40 as a normal memory learning ability of the rats A cold group for surgical infusion of A cold 40 as a memory learning dysfunction of Alzheimer's disease rats, the red glutinous rice diet dose is Formulated by the FDA for human body surface area conversion (B〇yd, sF〇rmuia〇f

Body Surface Area) (B〇yd 1935; Lee et al 2006) This study is equivalent to an adult (170 cm, 65 kg) of 2g of red glutinous rice, RH group. For the high-dose red glutinous rice, the Ls group was the same dose of lQVastatin (1. 43 mg/kg ra〇) for each silver food and RL group, for comparing monacolin K with Mona. The effect of the combination of colin, anti-oxidant and anti-inflammatory substances in the treatment and prevention of Alzheimer's disease. 2 8 days of infusion in Alzheimer's disease rats with A call 40 consecutive rat brain. , >f吏A/S 40 directly in the brain to cause Alzheimer's disease during the test, daily intake of red peony fermentation products or the same concentration of 1 〇VaStatin to explore the inhibition of Λβ toxicity The effect and assessment of the impact on memory learning ability. The results of the test of the present invention show that for 24 consecutive days, 汴Λ O O 勒 勒 勒 于 40 40 40 40 40 40 40 40 40 40 40 40 40 40 40 40 40 40 40 40 40 40 40 Activity, active oxygen Ο species (R0S) production and lipid peroxidation, and reduce Antioxidant power and super 〇xide dismutase (S0D) activity and red glutinous rice foraging can significantly inhibit these damage caused by 40 points of brain infusion, and the effect is better than the treatment group. By inhibiting the oxidative lovastatin inflammatory response, the infusion of A "can not be deposited in the hippocampus back to the tissue. Red glutinous rice was first confirmed to reduce the risk factors of Alzheimer's disease and improve memory learning ability, and The effect is more significant than the l〇vastatin drug. The test grouping of the present invention is shown in Table 1: Group Αβ injection RMR (monacolin K) (mg/kg only days) Lovastatin (mg/kg only days) Vehicle - Αβ + LS + - 1.43 RL + 151 (1.44) RH + 755 (7.20) Table 1 试验 The test apparatus of the present invention is as shown in Fig. 1, the test apparatus 1 〇 includes the bright room 11 and the dark room 12 of the same size, two In the center of the room, there is a gate 13 of 10 (W) x 10 (D) cm. When the gate 13 is opened, the bright room 11 17 200927155 can communicate with the dark room 12. The bright room i has illumination, and the dark room i2 has no illumination, and The bottom is provided with a spacing of 1 era parallel The wire array 14 'and the current through the experimental flow rat of each group of first turns into the light compartment 11, while the shutter 13 is open. After the rat enters the darkroom 12, the gate 13 is immediately closed, and current is applied to the metal wire 14 (1 〇〇V, 0.3 mA, 2 sec), and 5 seconds after the electrical stimulation, the rat is taken out from the dark room. ' Return to the cage. If the rat does not enter the darkroom 12 after 300 seconds, the rat is forced into the darkroom 12 and the gate 13' is closed while the current of the metal wire 14 at the bottom of the darkroom 12 is returned to the home cage. Measurement period: At 24 hours and 48 hours after the training, the rats were placed in the bright room 11 while the gate 13 was opened, and the step_through latency of the rats in the bright room 11 was recorded. When the residence time in the bright room 11 is more than 300 seconds, the learning and memory ability of the rat is said to be normal. The time when the rat stayed in the bright room 11 until entering the dark room 12 can be regarded as an indicator for evaluating the memory learning ability in the passive avoidance test. As shown in Fig. 2, all the rats immediately entered the dark room 12 during the first test due to the darkening characteristics, and the electric shock stimulated in the dark room 12 caused the rats with normal memory learning ability to be next. During the test, I was afraid to enter the darkroom 12 again. Therefore, in the second experiment, the time of each group of experimental animals staying in the bright room 11 will be significantly different due to the difference in memory learning ability. The results of the second test show that the time of the A point group staying in the bright room will Significantly lower than 18 200927155 veh ic 1 e group. The RL and RH groups in the experimental group were significantly longer than the Αβ group (/?<〇.〇5). The effect of the lovastatin group was not as good as that of the RL group with the same monacol in K content. The effect is still significantly higher than the A cold group. 〇

Another test device of the present invention is shown in Fig. 3, which is a water labyrinth device 20 having a circular swimming pool 21 having a diameter of 140 cm and a height of 45 cm. The swimming pool contains a movable rest platform ρι ( Or escape platform, escape platform). The platform has a diameter of 12 cm and a height of 25 cm. Before the experiment, the circular swimming pool 21 must be filled with water to a liquid level of 27 cm. The circular pool 21 is divided into four quadrants (Ι, Π, ιη and IV zones), and five starting points are set, and the rest platform ρι is placed at the center of any quadrant. During the test, a camera was placed directly above the center point of the pool to record the swimming path of the experimental animals. The effect of red glutinous rice on the impairment of reference memory learning ability in Alzheimer's rats with brain infusion is shown in Fig. 4. The time from the start of the water maze device 20 to the finding of the resting platform ρι is considered as an indicator for evaluating the reference memory test. From the results of the 2nd: ninth to the 9th memory training, it was shown that the Alzheimer's disease in the A stone infusion always takes a longer time to find the resting platform P1' than the vehicle group with normal memory ability. Alzheimer's disease a large red glutinous rice (RL and RH group can significantly reduce the time of search (Q5) 〇LQvastatin diet 19 200927155 Although it can take a shorter search time than the A / 3 group, but the effect is Below the RL group and the rh group, the same search time will show a similar swimming path length. In addition, there is no significant difference in the swimming speed between the experimental animals (data not shown) (p>〇.〇5) The spatial detection test is followed by the last reference e-review test on the 24th day. The rest platform P1 will be removed from the water-lulu device 20 after the end of the reference memory test, and the experimental animal will be placed on the resting platform P1. The time in the quadrant is regarded as the memory learning ability index of the spatial detection test. As shown in Fig. 4A, the time of the Λ/3 group searching in the target quadrant will be significantly lower than that of the vehicle group (/?<〇. 〇5). The RL group and the RH group are at the target. The search time in the quadrant increased by 38.2% (/7<〇.〇5) and 48.0% (/?<〇.〇1), respectively, which proved that red glutinous rice can improve the memory of Alzheimer's disease rats. Learning ability impairment. The ice path can help to judge the authenticity of the memory learning ability of experimental animals in the spatial detection test. Figure 4 shows that the A/S group has no directionality and no target in the spatial detection test. Looking for the target quadrant' and swimming the path throughout the circular pool 21. Conversely, the RL group, the RH group and the vehi c 1 e group with better memory learning ability will swim directly into the target quadrant' and take longer Time was in the target area. However, the 'lovastatin diet group still showed an improvement in memory learning ability between the rl group and the Αβ group (Fig. 4 and Fig. 4 20 200927155 Fig. c). Working memory test * Gu η &gt m January § Recalling the learning ability evaluation method's results as shown in Figure 5, the Αλ Α泠 group will be significantly longer than the vehicle ^ (n?) However, the ^ group and the RH group are at work minutes & ^___ „ In the hidden test, the memory of the vehicle group like normal memory can be expressed as μ ... 丨 丨 I 效果 并 并 并 并 并 并 并 Ο Ο Ο Ο Ο Ο Ο Ο Ο Ο Ο 57.3% and 58.9% of the search time (p < 〇〇 1) Although the cLs group was significantly shorter than the A/3 group by 26 7% of the search time 〇 < 〇〇 5), the effect was lower than the RL group and the RH group (/? < 〇〇 5). Κβ has been shown to be a major risk factor for memory learning in patients with Alzheimer's disease (Hashimoto et al. 2005; Stephan and Phillips 2005). Infusion of A;34 in the lateral ventricle of the rat brain has been shown to successfully establish an animal model of Alzheimer's disease (Stephan and Phillips 2005). The model animals established in this way also have the characteristics of memory behavior and lack of learning ability (Kar et al. 1998, Schubert et al. 1995; Townsend and

Pratico 2005). Infusion of A/5 induces free radicals and reactive oxygen species and causes neuronal damage and synaptic elongation to be inhibited, resulting in a lack of memory learning (Townsend and Pratico 2005). Therefore, there are several studies that have used antioxidant and anti-inflammatory substances to reduce the risk of oxidative inflammation in the brains of these Alzheimer's diseases and to reduce the ability to learn memory (Chauhan et al. 2004; Cordle et al. 21 200927155 2005) The Morris water maze test is one of the main methods for evaluating memory learning. The test of the 4α ^ test of the participant is represented by the ~ estimate method of ~ δ 己 忆 ' ' force and working memory The test is a method of assessing the ability of the wing. According to the results of the above-mentioned memory learning test, it is recalled that the Alzheimer's disease rats fed with a double dose and a five-fold dose of Λ舳 ' 麴 麴 缩短 缩短 缩短 shortened the search time η of the reference memory test and the working memory test ( ρ<το· 〇5). In addition, the red glutinous rice dumplings + έ-卞 diet group can be extended to the target quadrant search time in the space exploration test. These results clearly protect the feeding of red glutinous rice to improve the memory learning ability and find the resting platform of the labyrinth in a short time. Conversely, untreated Alzheimer's rats searched the entire water maze in an untargeted manner, and both of them took more time in both the reference memory and the work § recall test. Monacolin κ is one of the main functional ingredients of red glutinous rice to lower blood fat, and statin compound has been considered to treat Alzheimer's because it has the effect of inhibiting the formation and anti-inflammatory of brain A. New drug for the disease (Chauhan et al 9 η η /i τ. • Li et al. 2006). Most studies on Alzheimer's disease use statins to reduce the formation of brain A in mice with Alzheimer's disease (Yamada et al. 1 999). In the current study, lovastatin has not been used to alleviate the impairment of memory learning ability in A/3 infusion of Alzheimer's disease model rats 2009 2009155155. This ..,, 1 ovastat i η replaces m〇nacolinK in red glutinous rice to detect whether monacolin K in 7 red sputum water is the only substance that alleviates the memory of Alzheimer's disease. However, the results of the above memory learning experiments indicated that the loss of memory learning ability and injury in the 1ovastati η feeding group were weaker than those in the RL group with the same monacolin Κ concentration. Four confirmed that the monacolin K in red glutinous rice is not the only effective component to alleviate the memory impairment of P W.

Monacolin K is one of the main functional ingredients of red glutinous rice mites and blood stasis I ,, and statin compounds have been recognized by rabbits because they have the effect of inhibiting the formation and anti-inflammatory of brain A. An emerging drug for Alzheimer's disease (Chauhan et al. 2004. τ ΐ

Ll et al. 2006). Most of the treatments for Alzheimer's disease use ..."乂 to reduce the brain Μ 生成 gene production in mice with Alzheimer's disease (Yamada et al. 1 999). In the current known studies, ι〇ν oil (1) has not been used to alleviate the impairment of memory learning ability of AM-injected A. In this study, l〇vastatin was used to replace monacoiinK in red glutinous rice to explore whether m〇nac〇UnK in red glutinous rice is the only substance that can alleviate the impairment of memory learning in Alzheimer's disease. However, the results of the above memory learning experiments indicated that the 丨〇vastaUn feeding group was less effective in reducing the impairment of sufficiency learning ability than the same 23 200927155. Therefore, Tian Guan used Monacol in κ to cause Alzheimer's disease monacol. In K concentration of rl group. Indeed, it can be effectively improved because of the current treatment of Alzheimer's disease, which focuses on inhibiting acetylcholine activity to increase acetylcholine concentration and improve cognitive and memory behavior.

❾ U— and Nitta 1 994). Studies on the establishment of Alzheimer's disease model animals have also demonstrated that continuous infusion of the brain of M i rats will result in neurotoxicity of choline neuronal decline and deficiency. Studies have also shown that brain acetaminophen levels in brain-infused A/5 Alzheimer's rats are significantly lower than in normal rats (Arendtetal. 1984; Darvesh et al. 2004). A decrease in acetylcholine concentration and an increase in acetylcholine activity will exacerbate neuronal loss (stephan and Phillips 2005). In addition, an increase in the activity of acetylcholine enzymes was also indicated to result in a more severe degree of polymerization of A/3 and a more stable and more toxic fibrillar amyloid (AyS nbrils) (Stephan and Phillips 20 05) ). Therefore, inhibition of the activity of acetylcholine enzyme is considered to be an indirect mitigation of the neuroprotective effect of A not causing insufficient memory learning ability. Figure 6 shows the effect of red glutinous rice on the activity of enzyme B in the cerebral cortex and hippocampal gyrus of rats infused with 80,000 brains. The figure indicates that the acetylcholine activity of the cerebral cortex of the k β group will be Compared with ν ehic 1 e group, it is 50.5 percent, while in hippocampus, it is 24 200927155 high 179.1%. Rice + one " a five-fold dose of red glutinous rice can significantly inhibit g 1 by A /5. Acetylcholine activity, however, lovastatin has no inhibitory effect on the activity of cholinesterase in the cerebral and hippocampal gyrus. Slave ash, Fruit confirmed that the red glutinous rice has a substance that inhibits the activity of acetylcholine enzyme, and

The sputum substance should not be monac〇lin K but other functional metabolites. The preliminary study indicated that lovastatin can inhibit the activity of acetylcholine enzyme, and that the activity of lovastatin for acetamidine test enzymes does not have the inhibitory effect of 卜丹页. The results of this study are consistent with the trends of the present invention. In addition to monacolin K, the complex effects of red-faced rice are included! _ must A u I I contain other acetaminophen enzyme inhibitors. However, the metabolite GABA in red glutinous rice is also a neurotransmitter's ability to improve the cognitive and memory behavioral abilities of Alzheimer's disease. 0 A call has been shown to trigger brains in Alzheimer's patients. Oxidation pressure. Therefore, inhibition of A-induced oxidative stress is considered to be an important indicator for the development of Alzheimer's disease. As shown in Figure 7, brain infusion of A / 3 resulted in a decrease in total antioxidants status (TAS) in the cerebral cortex and hippocampus, 20.9% and 20.4%, respectively, compared to the vehicle group. Feeding l0Vastatin only has a T A S of 13.9% in the cerebral cortex of the South, but it is not effective in the hippocampus. In the RL group, cerebral cortex and hippocampal gyrus were found to be significantly increased by 24.6% and 46.2%. However, this study found that TAS in the cerebral cortex and hippocampus of rats fed Alzheimer's disease with a five-fold dose of red glutinous rice was significantly higher than that of the a million group. The effect of red glutinous rice on malondialdehyde (MDA) Hanta in the cerebral cortex and hippocampal gyrus is shown in Figure 8. MDA concentrations in the cerebral cortex and hippocampus were significantly increased by 95.3% and 112%, respectively, after AyS infusion in the brain, but this increase in MDA concentration was effectively reduced again by increasing the dose of red carp. The superoxide dismutase (SOD) activity in the cerebral cortex and hippocampal gyrus of the RL group and the RH group also showed similar neuroprotective effects, as shown in Fig. 9. Although the SOD activity in the cerebral cortex and hippocampus was reduced by 19.8% and 25.2%, respectively, the feeding of a double dose of red rice increased the hippocampus of the cerebral cortex and hippocampus. The S0D activity in the tissue was 27.2% and 52.7%, and the 5-fold red glutinous rice increased by 27.2% and 60.9%, respectively. From the above results, it was found that Alzheimer's disease rats with impaired memory learning ability had severe oxygen stress in the cerebral cortex and hippocampus. However, these oxidative stresses are improved by feeding red glutinous rice daily and the effect is not only dose-effect, but also better than the lovastatin silver food group. Anti-gasification negative in the fermentation product of red peony 26 200927155 Dimerumic acid, tannin, phenol, monounsaturated fatty acid have been mentioned before. ), superoxide dismutase and sterols (Aniya et al. 1999; Wang et al. 2006). Therefore, the antioxidant substance of the present invention can be derived from dimerumic acid, tannin, phenol, monounsaturated fatty acid, superoxide dismutase and sterol. (sterols) and any of superoxide dismutase (SOD). The results of the in vivo animal test of the present invention are shown in Fig. 10A.

A/3 brain infusion significantly increased the concentration of reactive oxygen species (ROS) in the rat cerebral cortex and hippocampus, respectively, by 39.8% and 28.7% (/?<0 05). The concentration of rOS 〇 in the cerebral cortex and hippocampus of rats with Alzheimer's disease fed daily was reduced. The RL group can be reduced by 16.0% (p < 〇. 〇5 ) and 21. 2% (/? < 〇. 〇5), respectively, and the RH group can be reduced by 35.4% (/?<;0.01) and 21.3% (/?<〇.05). The Lovastatin diet reduced the concentration of R0S in the cerebral cortex by 29.3%' and decreased by 15.7% in the hippocampus (组织5). The expression of inducible nitric oxide synthase (iN〇S) in hippocampal gyrus is shown in immunohistochemical staining in Figure 10B.

The A million infusion significantly increased the amount of iNOS expression. In the RL group and the RH 27 200927155 group, the expression of i N〇S was significantly inhibited. However, it was also found that the anti-inflammatory effect of l〇vas tat in槪 was worse than the 1x and 5x doses of the red scorpion feeding group. The concentration of R0S in the cerebral cortex and hippocampal gyrus of Alzheimer's disease rats was significantly reduced by increasing the dose of red glutinous rice. Although lovastat in has been shown to be effective in inhibiting the inflammatory response induced by A/5 in cell mode, this effect has not been demonstrated in animal models' and the anti-inflammatory effects of statins have not been applied to the reduction of brain infusion. A yS Alzheimer's disease in rats with impairment of memory learning ability. This study confirmed that l〇vas1:atin feeding significantly reduced ROS content and iNOS expression in brain tissue, but these effects were slightly worse than the red glutinous rice diet group. In recent years, the health benefits of secondary metabolites of red peony have been gradually developed, so 'many anti-inflammatory substances have been proposed', including various forms of monacol ins, 6 kinds of red-face metabolites ( Azaphilones). monascin, ankaf lavin, lubok, rubropunctatin, m〇nasc〇rburin, lumber punk Aromatic (rubropunctamine) and monascorburamine, 2 species of voroni i sophan i des: xanthomonasin A and simon monazin B ( Xanth〇m〇nasin 28 200927155 B); and 2 kinds of amino acids: ( + )-monascus citrate (( + )-monascumic acid) and (-)-monascu 糜Acid ((-)-monascumic acid) (Schubert et al. 1995). Therefore, raonacolin K is not the only metabolite that inhibits the inflammatory response caused by Ay3. Akihisa et al. (2005) used an anti-inflammatory agent (12-0-tetradecanoylphorbol-13-acetate; TPA) to inhibit the inflammatory response induced by red glutinous rice in a mouse model. It was also confirmed that the main anti-inflammatory substances are compounds of the azaphilones and furanoisophthalides. Based on the results of the in vitro and in vivo animal evaluation of this study and the anti-inflammatory effects of red peony, the inflammatory response caused by red glutinous rice inhibition is mainly from the synergistic mechanism of monacolin K and other anti-inflammatory substances. Therefore, the inflammatory substances mentioned in the present invention can be derived from T-aminobutyric acid (GABA), monascin, ankaflavin, lube punctan, and j (rubropunctatin). ), monascorburin, rubropunctamine, monascorburamine, xanthomonasin A, and xanthomonasin b (xanthomonasin) B), (+)-monascus citrate (( + )-monascumic acid) and (-)-monascu 糜 29 200927155 acid ((-)-monascumic acid). After 28 days of continuous infusion of 3A "hipi rat hippocampus back tissue, from the comparison of the vehicle level in Figure 11, it is known that there are a large number of sediments in the hippocampus of the W group. From the above results and the deaf Yan Jiu can know that the infusion of A cold 4 〇 will cause oxidative stress and inflammatory reaction in the brain 'and then make a &A; 54 〇 deposition. When deposited

The more A million 40 I, the more severe the oxidative stress and inflammatory reaction, and the continuous cycle, the vicious circle will cause the brain damage to continue to increase.

Lovastatm has the effect of inhibiting the inflammatory response caused by A/54 ,, but its ability to resist oxidative stress is weak. Therefore, it can be found from the results that A; S4〇 in the hippocampus of the LS group is slightly lower than

AyS group, but a large amount of Ay5 40 deposition can still be found. The RL group and the rH group fed with red glutinous rice had a significant effect of reducing the cumulative amount of a^4〇. The reason why red glutinous rice reduces the cumulative amount of A stone 4 〇 in the hippocampus back tissue is mainly due to its inhibition of oxidative stress and inflammatory reaction. A/540 infused into the brain is not deposited by oxidative inflammatory substances. The A / 9 40 can not cause damage to the brain, thereby effectively improving the ability of memory learning. The combination of Monaco lins, anti-inflammatory substances and antioxidant substances of the present invention for treating and preventing Alzheimer's disease can provide symptoms for improving Alzheimer's disease in red glutinous rice. In the first embodiment 30 200927155, the effective minimum content of monac〇lins per gram of red glutinous rice is at least greater than 100 yg' and the effective minimum content of antioxidants per gram of red glutinous rice is at least 40. /Zg' and the effective minimum content of anti-inflammatory substances in each gram of red glutinous rice is at least greater than 1〇#g; among them, monacolin (111〇11%〇1丨118), the best inflammatory substances and antioxidant substances The weight ratio of 40 : 2 : 1 is the best effect in the first embodiment, in addition to the effective weight ratio of monacolin (1 « 〇 11% 〇 1 丨 118), inflammatory substances and antioxidants 1〇: 4:1 to 90:2:1 can be implemented and applied to consumers in the form of tablets, capsules, powders, drinks, etc. In addition, in the second embodiment, monacolin is used. (Monacolins), a combination of anti-inflammatory substances, can also treat and prevent Alzheimer's disease The effective minimum content of Monacolins per gram of red glutinous rice is at least greater than 2 〇〇" g and each gram of red glutinous rice has an effective minimum content of anti-inflammatory substances of at least 6 〇 #g In the composition, the utility of the above process can also be used; wherein the optimal weight ratio of Monacolins to inflammatory substances is 1 〇: 丄 is the best effect in the second embodiment, and in addition, Monaco The effective weight ratio of forest (Monacolins) to inflammatory substances ranges from 1 (): 3 to 45 · 1, which can be implemented in the second embodiment, and applied in the form of tablets, capsules, powders, drinks, etc. Take it. 31 200927155 The anti-inflammatory substance contained in red glutinous rice is r-amin〇butyric acid (GABA), and red glutinous rice is a natural food, which can be fermented and refined in a specific way. Therefore, it will have any obvious adverse side effects on the human body. Therefore, if red glutinous rice is used as a conditioning food for the treatment of Alzheimer's disease, (4) the fruit will not only show I, but there is no such thing as a drug that will cause a variety of side effects for the patient.

Please refer to Figures 1 2 -1 to 1 2 - 3 for the prevention of Alzheimer's disease composition. The treatment and description of the present invention are as follows: ❹ First of all, 'clean first' - rice species and at a high pressure Sterilize in a high temperature environment (step 1〇〇), this one meter is a ryryzasati Va L., Japonica, which is in a pressure environment of 121 and 丄kg/cm2. Then, a specific red sputum strain is inoculated into a bacterium culture medium and sterilized in a first specific temperature and humidity environment, a specific oscillating environment and a first specific time limit (step 11 〇), the bacterium medium composition is at least 5g of the rice is immersed in 100ml of distilled sterile water. The first specific time limit means that the first specific temperature is maintained at 3 (TC) after 48 hours, and the specific oscillating environment is maintained at 100 to 150 rpm. (revoluti〇ns per “仙仙; rpm); that is, the red sputum strain was inoculated to the inoculum culture medium, and kept at 30 ° C, 125 rpm shaking culture for about 48 hours, then can be carried out 32 200927155 bacteria 'species solid medium 500 g, after washing Η hours. After filtering the water with cotton cloth, place it on the surface cloth, flatten it in the tray, sterilize (121., 20~25min), then sprinkle 1〇〇mL. Perform the second sterilization (lUtlGmin ) 'and after cooling, pick up the inoculum into the solid matrix (5%)' and stir the sentence. Then in the first

Stirring the culture medium in a specific temperature environment and continuously providing a specific proportion of water for a second specific time period (step 12〇), the second specific time limit means within 72 hours, and the specific ratio Moisture refers to 20% distilled water, and the culture medium is mixed every 24 hours within 72 hours and supplemented with steamed sterile water at 30. . Cultivating in a thermostat, and then appropriately agitating at a fixed time in the first specific temperature environment for a post-ripening in a third specific time period (step 130), and the post-ripening refers to the stage of metabolite formation. This third specific time limit means within 96 hours. This fixed time means every 1 hour. Within 96 hours, an appropriate agitation of the inoculum culture medium is performed every 1 hour on average. Then, one of the red alfalfa fermented materials after the completion of the fermentation is collected and dried at a first specific temperature for a fourth specific period. (Step 14A), this fourth specific period means that within 24 hours, this second specific temperature means that it is maintained at 5 5-6 0 °C. This step is for collecting, and the fermented red sorghum fermented product is subjected to a drying process for 24 hours and 60 seconds in an oven, and then the red sorghum fermented product which has been dried for 33 200927155 is ground into a powder and analyzed for compliance with a component. The proportional condition (step 150), the composition ratio condition means that the composition comprises a monac〇Hns, an anti-inflammatory substance and an antioxidant substance, and the effective weight ratio of the three substances ranges from 4.1 to 90 .2:1, in this range, it is confirmed that it is in the condition of the ratio of the component. If not, the process is terminated because it is a failure process. If it is confirmed that there are steps A and steps in the range. B, please refer to Figure 12-2 and Figure 12-3. After Step A, prepare the powder of the red sorghum fermented product into a edible beverage in a specific ratio to make a treatment and prevention. The sputum drink of Zhaimer's disease (step 160), and complete the production process.至〜4. 0%之间。 This particular ratio is between 1. 〇~4. 0%. After the step B, the prepared powder of the red sorghum fermented material is filled into a capsule or made into a tablet (step! 7 〇), and the production process is completed. The production method of the present embodiment can be cultured through a conventional tray to produce a smaller type of trays having a length, a width, and a height of about 20 X 30 X 5 cm. When the substrate is cultured, a cloth is wrapped around the solid substrate, which is advantageous for turning over, and at the same time ° X Maintain the humidity 'The upper layer is covered again' - layered cloth to isolate the external pollution while maintaining the humidity of the red rice in the fermentation process. The entire culture process is carried out in an open space. Therefore, the composition of the present invention can be applied by this production method, and can be applied to tablets, capsules, powders, drinks, and the like. The present invention has been described above in terms of the preferred embodiments thereof, and is not intended to limit the invention, and may be modified and modified, such as by those skilled in the art, without departing from the spirit and scope of the invention. Any other article that utilizes Monacol ins, anti-inflammatory substances, and anti-oxidative sputum substances to treat Alzheimer's disease, and therefore the scope of protection of the present invention is subject to the scope of the appended patent application. . BRIEF DESCRIPTION OF THE DRAWINGS Fig. 1 is a schematic view of a test apparatus of the present invention; Fig. 2 is a time chart of a rat staying in a bright room until entering a darkroom; Fig. 3 is a schematic diagram of a water labyrinth apparatus and a sub-area of the present invention Figure 4 is a graph showing the memory learning ability of red glutinous rice in the reference memory test and the PrPbe test in rats with amyloid-like protein 4 (A call 4). Figure 5 is the memory learning ability of red glutinous rice in rats with a stone infusion of 4 stone in the working memory test; Figure 6 is the red glutinous rice in the brain cerebral cortex of the brain infused with M4〇 Figure VIII shows the effect of acetylcholine activity in the hippocampus of the hippocampus; Figure 7 is a comparison of the total antioxidant status (TAS) in the cerebral cortex and hippocampus of the rat infusion; 35 200927155 Figure 8 shows the red glutinous rice The effect of malondialdehyde (MDA) concentration on rat cerebral cortex and hippocampus gyrus; Figure 9 is the effect of red glutinous rice on superoxide dismutase (SOD) activity in rat cerebral cortex and hippocampus Figure 10 shows red glutinous rice in Ay5 40 The effects of reactive oxygen species (R0S) content in the cerebral cortex and hippocampus of rat infusion and the expression of nitric oxide synthase (iNOS) in hippocampus. The 11th image shows continuous infusion of AiS 40 to rat hippocampus. After the reorganization, the deposition diagram of 40; and 12-1~12-3 are the preparation methods of the composition for treating and preventing Alzheimer's disease of the present invention. 〇 [Main component symbol description] 10 Test device 11 Ming room 12 Dark room 13 Gate 14 Metal wire 2 0 Water labyrinth device 21 Round pool 36 200927155 pi Rest platform Step 100 Step 110 Step 120 ❹ Step 130 Step 140

#步骤150 Step 160 Step 170 Clean one meter and sterilize in a high-pressure high-temperature environment. Inoculate a specific red peony strain into a culture medium and in a first specific temperature humidity environment, a specific earthquake environment and a first a specific time limit for inoculation in the first specific temperature environment to stir the culture medium and continue to provide for a second specific time period - a specific proportion of moisture within a third specific time limit and each of the first specific temperature environments Stirring is carried out at a fixed time to achieve a post-ripening charge of one of the red mash fermentations after completion of the fermentation and to be dried at a second specific temperature for a fourth specific period to dry the dried red mash fermentation Powdered and analyzed for compliance with one-component ratio conditions. The prepared powder of the red-fermented fermented product is added to an edible beverage in a specific ratio to prepare a red scorpion drink having treatment and prevention of Alzheimer's disease. The prepared powder of the red sorghum fermented material is filled into a capsule of 37 200927155 or made into a tablet 10, and the patent application is applied. A composition for treating and preventing Alzheimer's disease, which comprises a combination of _monacolins, an anti-inflammatory substance and an antioxidant substance, and is carried out from red glutinous rice. Refined. 2. The composition for treating and preventing Alzheimer's disease according to claim 1, wherein the effective minimum content of the monacol ins per gram of red glutinous rice is at least greater than 100/ Z g. 3. The composition for treating and preventing Alzheimer's disease according to claim 1, wherein the antioxidant is effective at a minimum of at least 40&g; g per gram of red glutinous rice. 4. The composition for treating and preventing Alzheimer's disease according to claim 1, wherein the antioxidant substance is derived from dimerum acid, tannin, and tannin. (Phenol), monounsaturated fatty acid, superoxide dismutase and sterols and superoxide dismutase (SOD) in any combination. 5. The composition for treating and preventing Alzheimer's disease according to claim 1, wherein the anti-inflammatory substance has an effective minimum content of at least 10/g in each gram of red glutinous rice. 6 · Treatment and prevention of Alzheimer's disease as described in claim 1

Claims (1)

200927155 A capsule can be made into a tablet. X. Patent application scope: 1 · A composition for treating and preventing Alzheimer's disease, which comprises _ monacolins, primary anti-inflammatory substances and one A composition of an antioxidant substance, which is obtained by refining from red glutinous rice. 2. The composition for treating and preventing Alzheimer's disease according to claim 1, wherein the effective minimum content of the monacol ins per gram of red glutinous rice is at least greater than 100/ Z g. 3. The composition for treating and preventing Alzheimer's disease according to claim 1, wherein the antioxidant is effective at a minimum of at least 40&g; g per gram of red glutinous rice. 4. The composition for treating and preventing Alzheimer's disease according to claim 1, wherein the antioxidant substance is derived from dimerum acid, tannin, and tannin. (Phenol), monounsaturated fatty acid, superoxide dismutase and sterols and superoxide dismutase (SOD) in any combination. 5. The composition for treating and preventing Alzheimer's disease according to claim 1, wherein the anti-inflammatory substance has an effective minimum content of at least 10/g in each gram of red glutinous rice. 6. The composition for treating and preventing Alzheimer's disease 38 200927155 according to claim 1, wherein the anti-inflammatory substance is derived from r-aminobutyric acid (GABA), Mo Monascin, ankaf lavin, rubropunctatin, monascorburi η, rubropunctamine, monascorburam i ne), xanthomonasin A and xanthomonasin 、, ( + )-monascusic acid (( + )-monascumic acid) and (-) - Any combination of Monascu citrate ((-)-monascumi c aci d). 7. The composition for treating and preventing Alzheimer's disease according to claim 1, wherein the optimal weight ratio of the monacolins to the anti-inflammatory substance to the antioxidant is 4 〇: 2: 1. 8. The group A for treating and preventing Alzheimer's disease as described in claim i, wherein the monacolin (M〇nac〇1丨ns), the anti-inflammatory substance and the antioxidant substance The effective weight ratio range is 丨〇: 4 : 1 to 90 : 2 : 1 . A composition for treating and preventing Alzheimer's disease, which comprises a monacolin (m〇nac〇lins) and a primary anti-inflammatory substance. The composition for treating and preventing Alzheimer's 39 200927155 according to claim 9, wherein the composition is red glutinous rice. The composition for treating and preventing Alzheimer's disease as described in claim 9 wherein the monacolins have an effective minimum content of at least greater than 2 μg per gram of the composition unit. 12. The composition for treating and preventing Alzheimer's disease according to claim 9 wherein the effective minimum level of the anti-inflammatory substance in each gram of the composition unit is at least greater than 6 〇"g. 13. The composition for treating and preventing Alzheimer's disease according to claim 9, wherein the anti-inflammatory substance is from 7-aminobutyric acid (GABA), Monas Monascin, ankafiavjn, rubropunctatin, monascorburin, rubropunctamine, monascorburamine, celery Xanthomonasin A and xanthomonasin B, ( + )-monascus citrate (( + )-m〇nascUmiC acid) and (-) _ mona Any combination of succinic acid ((-)-monascumic acid) 14. A method for producing a composition for treating and preventing Alzheimer's disease, the method comprising the following steps: 200927155 - sterilizing in a two-pressure high-temperature environment; inoculating a specific red sputum strain into a culture medium and inoculation in a specific temperature and humidity environment, a specific oscillating environment and a first specific time limit; Mixing the culture medium in a temperature environment - continuously providing a specific proportion of moisture during the second specific time limit; ❹ during the third specific time limit and the first specific temperature environment t every other time - the appropriate line is appropriate (four) to achieve the ripening; ;- red-faced fermented material and maintained in a fourth characteristic period - at a second specific temperature to be dried; the dried red sorghum fermented product is ground into a powder and analyzed for compliance with a component ratio condition; as well as The prepared powder of the red sorghum fermented product was added to an edible beverage in a specific ratio to prepare an Alzheimer's sorghum drink. The invention relates to a method for preparing a therapeutic and prophylactic composition according to claim 14, wherein the rice germplasm is - (Oryza satiVa L., Japonica). The method for producing a composition for treating sputum and top-proof Alzheimer's disease according to claim 14, wherein the high-pressure high environment refers to a pressure environment of 200927155 121C and 1 kg/cm2. The method for producing a composition for treating and preventing Alzheimer's disease according to claim 14, wherein the culture medium has a composition of at least 5 g of the rice seed soaked in distilled sterile water. The method for producing a composition for treating and preventing Alzheimer's disease according to claim 14, wherein the first specific temperature is maintained at 30 °C. ® 1 9 · A method for the treatment and prevention of Alzheimer's disease composition as described in claim i, wherein the specific oscillating environment is maintained at 100 to 150 rpm (rev〇iuti〇ns per Between minute; r pm). The method for producing a composition for treating and preventing Alzheimer's disease according to the invention of claim i, wherein the first specific time limit means after 48 hours. The method for producing a composition for treating and preventing Alzheimer's disease according to claim 14, wherein the second specific time limit means within 72 hours. 2 2. The method for producing a composition for treating and preventing Alzheimer's disease according to claim 14, wherein the specific proportion of water refers to 20% of steamed sterile water. 23. The method for producing a composition for the treatment and prevention of Alzheimer's 42 ❹ 10 : 200927155 according to claim 14, wherein the third specific time limit is within 9 hours. 24. A method of making a therapeutic and prophylactic composition according to claim 14 wherein the fixed time is an hour. 2. The method for producing a composition for treating and preventing p according to claim 14, wherein the fourth specific period is within an hour. 2. The method for producing a composition for treating and preventing p according to claim 14, wherein the second specific temperature 4 is between 55 ° C and 60 ° C. 27. The method according to claim 14, wherein the component ratio conditional compound comprises monac〇lins, primary antibody; The substance, the effective weight ratio of the three substances to 90: 2 8. The method for producing a composition for treating and preventing endogenous diseases according to claim 27, wherein the monacolins, the anti- The weight ratio of the inflammatory substance to the antioxidant is 40 ·· 2 : 1. 2 9. The treatment and prevention referred to in Article 14 of the patent application refers to the Z-Mermer: 10 Zimmerm refers to the retention of Zheme in the Gazheimer. 0%之间。 Between the 0. 0~4. 0% between the 0. The method for producing a composition for treating and preventing Alzheimer's disease according to claim 14, wherein the dried red sorghum fermented product is ground into a powder and analyzed for compliance with a component ratio. The step of the condition may further comprise the step of filling the prepared powder of the red peony fermentate into a capsule or making a tablet. 44