Application of gastrodia elata active ingredient in preparation of medicine for treating Alzheimer's disease

Abstract

The invention belongs to the technical field of medicines for treating Alzheimer's disease, and particularly relates to application of gastrodia elata active ingredients in preparation of medicines for treating Alzheimer's disease, the gastrodia elata active ingredients are gastrodin and gastrodia elata polysaccharide, and the gastrodin and the gastrodia elata polysaccharide are compounded with known treatment preparations for treating Alzheimer's disease. The mass ratio of the gastrodin to the gastrodia elata polysaccharide to the known treatment preparation for treating the Alzheimer's disease is (50-100): (150-200): (2-3). The invention clarifies the application of the gastrodia elata active ingredient in preparation of the medicine for treating the Alzheimer's disease.

Description

Technical Field

[0001] The present invention belongs to the technical field of Alzheimer's disease drugs, and specifically relates to an application of a Gastrodia elata active ingredient in the preparation of a drug for treating Alzheimer's disease. Background Art

[0002] Alzheimer's disease, also known as senile dementia, mostly occurs in the elderly and is a disorder of higher nervous function activity. The main clinical manifestations are memory impairment, thinking disorder, visual-spatial recognition disorder and emotional disorder. The cause of Alzheimer's disease is complex, so many drugs in the existing technology can only improve related clinical symptoms and slow down the aggravation of the disease. Patients usually need to take medication for a long time.

[0003] Traditional Chinese medicine is considered to be a safe drug, suitable for long-term use, with few or even no side effects. Therefore, there are many traditional Chinese medicines for treating Alzheimer's disease in the prior art, such as Xuefu Zhuyu Decoction (the main ingredients include angelica, Chuanxiong, raw rehmannia, peach kernel, safflower, bitter orange peel, red peony root, bupleurum, cyathula, notoginseng, earthworm, and licorice), Tianma Gou Teng Yin prescription (Gastrodia, Uncaria, Semen Cassiae, Gardenia, Eucommia, Pueraria, Viscum, Cyathula, Chrysanthemum, Vitex, Lycium barbarum, and raw licorice), etc. However, these prescriptions contain many types of traditional Chinese medicines and more active ingredients, and it is not clear which specific active ingredients play a role in treating Alzheimer's disease. Summary of the invention

[0004] In order to solve the above technical problems, the present invention provides an application of an active ingredient of Gastrodia elata in preparing a drug for treating Alzheimer's disease.

[0005] The purpose of the present invention is to provide an application of an active ingredient of Gastrodia elata in the preparation of a drug for treating Alzheimer's disease. The active ingredients of Gastrodia elata are gastrodin and gastrodia elata polysaccharide, which are compounded with a known therapeutic preparation for treating Alzheimer's disease, and the mass ratio of gastrodin, gastrodia elata polysaccharide and the known therapeutic preparation for treating Alzheimer's disease is 50-100:150-200:2-3.

[0006] Gastrodin and Gastrodia polysaccharide are both known active ingredients of Gastrodia elata, and many related products can be purchased on the market. For example, the Gastrodia polysaccharide used in the experiment of the present invention was purchased from Yangling Ciyuan Biotechnology Co., Ltd., with an active ingredient content of 95%; Gastrodin was purchased from Xi'an Youshuo Biotechnology Co., Ltd., with an active ingredient content of 98%, white powder, 80 mesh.

[0007] Prior art studies have shown that although gastrodin is a neuroprotectant, it has no therapeutic effect on Alzheimer's disease. Gastrodia polysaccharides are often used as antioxidants, anti-tumor, liver protectors and immunity enhancers, and have not been used to treat Alzheimer's disease. However, given that these two substances are active ingredients in Gastrodia and are highly safe, we compound them with known drugs for treating Alzheimer's disease to enhance their efficacy. The present invention is the first to discover that gastrodin and gastrodia polysaccharides can be used to prepare drugs for treating Alzheimer's disease.

[0008] Preferably, the use of the above-mentioned Gastrodia elata active ingredients in the preparation of drugs for treating Alzheimer's disease, the known therapeutic preparations for treating Alzheimer's disease are acetylcholinesterase inhibitors, N-methyl-D-aspartate receptor antagonists or brain metabolism activators, mainly to improve cognitive function. For example, the known therapeutic preparations for treating Alzheimer's disease use donepezil hydrochloride, rivastigmine bitartrate, memantine hydrochloride, and oxiracetam, such as the corresponding prior art drugs named donepezil hydrochloride tablets, rivastigmine bitartrate capsules, memantine hydrochloride sustained-release capsules or oxiracetam capsules.

[0009] Preferably, the above-mentioned Gastrodia elata active ingredient is used in the preparation of a drug for treating Alzheimer's disease, and the Alzheimer's disease drug is an oral preparation.

[0010] Preferably, the above-mentioned Gastrodia elata active ingredients are used in the preparation of drugs for treating Alzheimer's disease, and the oral preparation is a capsule or tablet, which is composed of gastrodin, Gastrodia elata polysaccharide, a known therapeutic preparation for treating Alzheimer's disease and a first excipient.

[0011] Preferably, in the use of the above-mentioned Gastrodia elata active ingredient in the preparation of a drug for treating Alzheimer's disease, the first auxiliary material is one or more of starch, aluminum oxide and calcium stearate.

[0012] Preferably, the above-mentioned Gastrodia elata active ingredients are used in the preparation of drugs for treating Alzheimer's disease. First, gastrodin, gastrodia elata polysaccharide and a second auxiliary material are made into an oral preparation, and then the preparation is compounded with a known therapeutic preparation for treating Alzheimer's disease.

[0013] Preferably, in the use of the above-mentioned Gastrodia elata active ingredient in the preparation of a drug for treating Alzheimer's disease, the second excipient is one or more of starch, methyl cellulose, dextrin, aluminum oxide, magnesium stearate and calcium stearate.

[0014] Preferably, the above-mentioned Gastrodia elata active ingredients are used in the preparation of drugs for treating Alzheimer's disease, wherein the subjects suffering from Alzheimer's disease are naturally sick humans, mice, or constructed animal models of Alzheimer's disease.

[0015] Preferably, the above-mentioned Gastrodia elata active ingredient is used in the preparation of a drug for treating Alzheimer's disease, wherein the drug for treating Alzheimer's disease is used to reduce the activity of acetylcholinesterase.

[0016] Compared with the prior art, the present invention has the following beneficial effects:

[0017] The present invention provides an application of an active ingredient of Gastrodia elata in the preparation of a drug for treating Alzheimer's disease, which has good safety and efficacy. The active ingredients of Gastrodia elata are gastrodin and gastrodia polysaccharide, which are compounded with a known therapeutic preparation for treating Alzheimer's disease, and the mass ratio of gastrodin, gastrodia polysaccharide and the known therapeutic preparation for treating Alzheimer's disease is 50-100:150-200:2-3. The present invention develops a new application of the gastrodin and gastrodia polysaccharide for reducing acetylcholinesterase activity and treating Alzheimer's disease, thereby providing an application of an active ingredient of Gastrodia elata in the preparation of a drug for treating Alzheimer's disease.

[0018] In the experiment of the present invention, the known drugs for treating Alzheimer's disease were compounded with gastrodin and / or gastrodia polysaccharide, which can significantly reduce acetylcholinesterase and improve Alzheimer's disease. The research results of the present invention show that gastrodin and gastrodia polysaccharide have the effect of reducing acetylcholinesterase, and after being compounded with the known drugs for treating Alzheimer's disease, the effect of improving Alzheimer's disease is better. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 This is the statistical result of the central grid residence time.

[0020] Figure 2 This is the standing number statistics result.

[0021] Figure 3 The total walking distance statistics are shown in Figure 2.

[0022] Figure 4 Results were recorded for escape latency.

[0023] Figure 5 For swimming distance.

[0024] Figure 6 is the swimming speed.

[0025] Figure 7 is the statistical result of acetylcholinesterase activity. DETAILED DESCRIPTION

[0026] In order to enable those skilled in the art to better understand and implement the technical solution of the present invention, the present invention is further described below in conjunction with specific embodiments and drawings.

[0027] In the description of the present invention, unless otherwise specified, all reagents used are commercially available and all methods used are conventional techniques in the art.

[0028] The structural formula of gastrodin is shown in formula (1), and the molecular formula is C 13 H18 O7, CAS number is 62499-27-8. The existing technology of gastrodin includes acetyl gastrodin tablets, which are used for insomnia, neurasthenia, vascular headache and neuralgic headache; gastrodin injection, which is mainly used in neurology, can be used to treat vertigo, such as vestibular nerve dysfunction, Meniere's syndrome and vertebral-basilar artery insufficiency. Existing technology research shows that although gastrodin is a neuroprotective agent, it has no therapeutic effect on Alzheimer's disease.

[0029]

[0030] The common ingredients in Gastrodia elata polysaccharide are L-rhamnose, L-fucose, D-xylose, D-mannose and D-glucose. Existing studies have shown that Gastrodia elata polysaccharide has a variety of biological activities, such as anti-oxidation, scavenging free radicals in the body, delaying aging, improving immunity, etc. These biological activities make Gastrodia elata polysaccharide have a wide range of application prospects in the fields of medicine and health care. However, the existing technology has not found that Gastrodia elata polysaccharide has no therapeutic effect on Alzheimer's disease.

[0031] Newly prepared compound drugs need to undergo multiple tests such as molecular formula design, structural formula design, animal experiments, clinical trials, safety tests, etc. The process is very complicated and consumes high manpower, time and economic costs. In contrast, the development of new indications for known drugs requires fewer tests, which saves costs and resources and is an energy-saving and environmentally friendly approach. In the prior art, researchers have published many patents or papers on the discovery of new indications, such as CN200610104629.6, CN200810041513.1, "Li Ni. Development of new drug indications-Efficacy evaluation and mechanism study against enterovirus EV71 [D]. Hubei University of Technology [2024-10-11]", etc.

[0032] Gastrodin and Gastrodia polysaccharide are both known active ingredients of Gastrodia, with clear ingredients, high safety, and suitable for long-term use. Therefore, it is necessary to continue to develop new uses for them. In addition, there are many traditional Chinese medicines for treating Alzheimer's disease in the existing technology, which are compounded from multiple medicinal materials and contain more active ingredients. It is unclear which specific active ingredients play a role in treating Alzheimer's disease, which poses a safety risk.

[0033] Based on the above reasons, the present invention provides an application of an active ingredient of Gastrodia elata in the preparation of a drug for treating Alzheimer's disease. The active ingredients of Gastrodia elata are gastrodin and gastrodia polysaccharide, which are compounded with a known therapeutic preparation for treating Alzheimer's disease. The mass ratio of gastrodin, gastrodia polysaccharide and the known therapeutic preparation for treating Alzheimer's disease is 50-100:150-200:2-3.

[0034] Example 1

[0035] A drug for treating Alzheimer's disease, wherein the active ingredients of Gastrodia elata are gastrodin and gastrodia elata polysaccharide, which are compounded with a known therapeutic preparation for treating Alzheimer's disease to prepare the drug for treating Alzheimer's disease, wherein the mass ratio of gastrodin, gastrodia elata polysaccharide and the known therapeutic preparation for treating Alzheimer's disease is 50:150:2. The known therapeutic preparation for treating Alzheimer's disease is donepezil hydrochloride.

[0036] Example 2

[0037] A drug for treating Alzheimer's disease, wherein the active ingredients of Gastrodia elata are gastrodin and gastrodia elata polysaccharide, which are compounded with a known therapeutic preparation for treating Alzheimer's disease to prepare the drug for treating Alzheimer's disease, wherein the mass ratio of gastrodin, gastrodia elata polysaccharide and the known therapeutic preparation for treating Alzheimer's disease is 80:150:2. The known therapeutic preparation for treating Alzheimer's disease is donepezil hydrochloride.

[0038] Example 3

[0039] A drug for treating Alzheimer's disease, wherein the active ingredients of Gastrodia elata are gastrodin and gastrodia elata polysaccharide, which are compounded with a known therapeutic preparation for treating Alzheimer's disease to prepare the drug for treating Alzheimer's disease, wherein the mass ratio of gastrodin, gastrodia elata polysaccharide and the known therapeutic preparation for treating Alzheimer's disease is 100:150:2. The known therapeutic preparation for treating Alzheimer's disease is donepezil hydrochloride.

[0040] Example 4

[0041] A drug for treating Alzheimer's disease, wherein the active ingredients of Gastrodia elata are gastrodin and gastrodia elata polysaccharide, which are compounded with a known therapeutic preparation for treating Alzheimer's disease to prepare the drug for treating Alzheimer's disease, wherein the mass ratio of gastrodin, gastrodia elata polysaccharide and the known therapeutic preparation for treating Alzheimer's disease is 50:170:2. The known therapeutic preparation for treating Alzheimer's disease is donepezil hydrochloride.

[0042] Example 5

[0043] A drug for treating Alzheimer's disease, wherein the active ingredients of Gastrodia elata are gastrodin and gastrodia elata polysaccharide, which are compounded with a known therapeutic preparation for treating Alzheimer's disease to prepare the drug for treating Alzheimer's disease, wherein the mass ratio of gastrodin, gastrodia elata polysaccharide and the known therapeutic preparation for treating Alzheimer's disease is 50:200:2. The known therapeutic preparation for treating Alzheimer's disease is donepezil hydrochloride.

[0044] Example 6

[0045] A drug for treating Alzheimer's disease, wherein the active ingredients of Gastrodia elata are gastrodin and gastrodia elata polysaccharide, which are compounded with a known therapeutic preparation for treating Alzheimer's disease to prepare the drug for treating Alzheimer's disease, wherein the mass ratio of gastrodin, gastrodia elata polysaccharide and the known therapeutic preparation for treating Alzheimer's disease is 50:150:3. The known therapeutic preparation for treating Alzheimer's disease is donepezil hydrochloride.

[0046] Example 7

[0047] A drug for treating Alzheimer's disease, wherein the active ingredients of Gastrodia elata are gastrodin and gastrodia elata polysaccharide, which are compounded with a known therapeutic preparation for treating Alzheimer's disease to prepare the drug for treating Alzheimer's disease, wherein the mass ratio of gastrodin, gastrodia elata polysaccharide and the known therapeutic preparation for treating Alzheimer's disease is 50:150:2. The known therapeutic preparation for treating Alzheimer's disease is memantine hydrochloride.

[0048] Comparison 1

[0049] A drug for treating Alzheimer's disease, wherein the active ingredient of Gastrodia elata is gastrodin, the active ingredient of Gastrodia elata is compounded with a known therapeutic preparation for treating Alzheimer's disease to prepare the drug for treating Alzheimer's disease, the mass ratio of gastrodin to the known therapeutic preparation for treating Alzheimer's disease is 200:2. The known therapeutic preparation for treating Alzheimer's disease is donepezil hydrochloride. That is, compared with Example 1, an equal mass of gastrodin is used to replace Gastrodia elata polysaccharide.

[0050] Comparison 2

[0051] A drug for treating Alzheimer's disease, wherein the active ingredient of Gastrodia elata is Gastrodia elata polysaccharide, the active ingredient of Gastrodia elata is compounded with a known therapeutic preparation for treating Alzheimer's disease to prepare the drug for treating Alzheimer's disease, the mass ratio of Gastrodia elata polysaccharide to the known therapeutic preparation for treating Alzheimer's disease is 200:2. The known therapeutic preparation for treating Alzheimer's disease is donepezil hydrochloride. That is, compared with Example 1, an equal mass of Gastrodia elata polysaccharide is used to replace gastrodin.

[0052] Comparison 3

[0053] A drug for treating Alzheimer's disease, wherein the active ingredient of Gastrodia elata is a mixture of gastrodin and gastrodia elata polysaccharide, and the mass ratio of gastrodin and gastrodia elata polysaccharide is 50:150. That is, compared with Example 1, the known therapeutic preparation for treating Alzheimer's disease is removed.

[0054] Comparison 4

[0055] A drug for treating Alzheimer's disease is gastrodin.

[0056] Comparison 5

[0057] A drug for treating Alzheimer's disease is Gastrodia elata polysaccharide.

[0058] The present invention provides an application of an active ingredient of Gastrodia elata in preparing a drug for treating Alzheimer's disease, and the relevant effect demonstration experiment is as follows.

[0059] 1. Experimental Animals

[0060] Healthy 6-week-old C57 female mice were selected and adaptively fed for 4 days. Aβ was injected into the brain on the 5th day. 25-35 , Aβ 25-35 The concentration was 35pmol / μL, and 5μL was injected into the brain of each C57 female mouse to construct an Alzheimer's disease animal model.

[0061] Among them, the brain injection method is:

[0062] (1) C57 female mice were anesthetized by intraperitoneal injection of 0.4% sodium pentobarbital (0.2 mL / 10 g body weight) and then fixed on a stereotaxic apparatus.

[0063] (2) The scalp was incised longitudinally and the coordinates for bilateral ventricular catheterization were 0.8 mm from the anterior bregma, 1.1 mm from the midline, and 3.6 mm below the dura mater.

[0064] (3) Slowly inject 5 μL of freshly prepared 35 pmol / μL Aβ into each lateral ventricle. 25-35 , a total of 5 μL for the whole brain, the injection rate was about 1 μL / min, and the interval between each injection was 2 hours.

[0065] (4) After leaving the needle in place for 2 minutes, the tube was removed, the skull hole was sealed with bone wax, and the incision was sutured.

[0066] 2. Drug administration and modeling

[0067] Model group: Starting from the 6th day, 100 μL of 0.9wt% saline was gavaged daily.

[0068] Group 1 of Example 1: Starting from the 6th day, 100 μL of the drug solution prepared from the drug of Example 1 was intragastrically administered every day, wherein 100 μL of the drug solution contained 2 μg of donepezil hydrochloride.

[0069] Group 2 of Example: Starting from the 6th day, 100 μL of the drug solution prepared from the drug of Example 2 was intragastrically administered every day. Based on the total weight of the drug, 100 μL of the drug solution contained the same amount of drug as that of Group 1 of Example.

[0070] Group 3 of Example: Starting from the 6th day, 100 μL of the drug solution prepared from the drug of Example 3 was intragastrically administered every day. Based on the total weight of the drug, 100 μL of the drug solution contained the same amount of drug as that of Group 1 of Example.

[0071] Group 4 of Example: Starting from the 6th day, 100 μL of the drug solution prepared from the drug of Example 4 was intragastrically administered every day. Based on the total weight of the drug, 100 μL of the drug solution contained the same amount of drug as that of Group 1 of Example.

[0072] Group 5 of Example: Starting from the 6th day, 100 μL of the drug solution prepared from the drug of Example 5 was intragastrically administered every day. Based on the total weight of the drug, 100 μL of the drug solution contained the same amount of drug as that of Group 1 of Example.

[0073] Group 6 of Example: Starting from the 6th day, 100 μL of the drug solution prepared from the drug of Example 6 was intragastrically administered every day. Based on the total weight of the drug, 100 μL of the drug solution contained the same amount of drug as that of Group 1 of Example.

[0074] Group 7 of Example: Starting from the 6th day, 100 μL of the drug solution prepared from the drug of Example 7 was intragastrically administered every day. Based on the total weight of the drug, 100 μL of the drug solution contained the same amount of drug as that of Group 1 of Example.

[0075] Control group 1: Starting from the 6th day, 100 μL of the drug solution prepared from the drug of control group 1 was intragastrically administered every day. Based on the total weight of the drug, 100 μL of the drug solution contained the same amount of drug as that of the Example 1 group.

[0076] Control group 2: Starting from the 6th day, 100 μL of the drug solution prepared from the drug of control group 2 was intragastrically administered every day. Based on the total weight of the drug, 100 μL of the drug solution contained the same amount of drug as that of the Example 1 group.

[0077] Control group 3: Starting from the 6th day, 100 μL of the drug solution prepared from the drug of control group 3 was intragastrically administered every day. Based on the total weight of the drug, 100 μL of the drug solution contained the same amount of drug as that of the Example 1 group.

[0078] Control group 4: Starting from the 6th day, 100 μL of the drug solution prepared from the drug of control group 4 was intragastrically administered every day. Based on the total weight of the drug, 100 μL of the drug solution contained the same amount of drug as that of the Example 1 group.

[0079] Control group 5: Starting from the 6th day, 100 μL of the drug solution prepared from the drug of control group 5 was intragastrically administered every day. Based on the total weight of the drug, 100 μL of the drug solution contained the same amount of drug as that of the Example 1 group.

[0080] Control group 6: Starting from the 6th day, 100 μL of the suspension prepared by donepezil hydrochloride was gavaged daily. Based on the total weight of the drug, 100 μL of the drug solution contained the same amount of the drug as that of the Example 1 group.

[0081] Blank control: healthy C57 female mice.

[0082] In the present invention, the model group is used to reflect the condition of C57 female mice that have not been treated with drugs, the blank control is used to reflect the condition of healthy C57 female mice, and Example 1 to Example 7 are used to reflect the efficacy of the drugs corresponding to Example 1 to Example 7 in treating Alzheimer's disease. Control Group 1 is used to reflect the efficacy of gastrodin combined with known therapeutic preparations for treating Alzheimer's disease, Control Group 2 is used to reflect the efficacy of gastrodia polysaccharides combined with therapeutic preparations for treating Alzheimer's disease, and Control Group 3 is used to reflect the efficacy of gastrodin combined with gastrodia polysaccharides. Control Group 4 is used to reflect the efficacy of gastrodin alone. Control Group 5 is used to reflect the efficacy of gastrodia polysaccharides alone. Control Group 6 is used to reflect the efficacy of known drugs for treating Alzheimer's disease.

[0083] The treatment was continued for 7 days. On the 8th day, open field test and Morris water maze test were performed to test acetylcholinesterase activity.

[0084] 3. Data Processing Method

[0085] Three parallel experiments were performed in each group, and the results were averaged for significance analysis.

[0086] 4. Open field experiment and results

[0087] The time spent in the central grid, the number of standing times and the total walking distance of the female mice in each group were observed, and the average value (n = 6) was taken. Figure 1 to Figure 3 Specifically, Figure 1 This is the statistical result of the central grid residence time. Figure 2 This is the standing number statistics result. Figure 3 The total walking distance statistics are shown in Figure 2.

[0088] from Figure 1 It can be seen that compared with the blank control, the female mice in the model group stayed in the central grid for a significantly longer time (P<0.05); the number of standing times was significantly reduced (P<0.05); and the total walking distance was significantly shortened (P<0.05). Compared with the model group, the central grid stay time of each embodiment group was significantly shortened (P<0.05), and the number of standing times and total walking distance were significantly increased (P<0.05). The comparison results with the blank control group and the model group show that the drug for treating Alzheimer's disease provided by the embodiment of the present invention can effectively alleviate Alzheimer's disease.

[0089] The control group 1 was a combination of gastrodin and a known therapeutic preparation for treating Alzheimer's disease, and the control group 2 was a combination of gastrodia polysaccharide and a therapeutic preparation for treating Alzheimer's disease. After comparison with the model group and the blank control, they were shown to have a certain effect in alleviating Alzheimer's disease, but there were still significant differences between them and the drugs in the embodiments of the present application.

[0090] Control group 3 is a combination of gastrodin and gastrodia polysaccharide. Control group 4 is gastrodin alone. Control group 5 is gastrodia polysaccharide alone. Control group 6 is a known drug for the treatment of Alzheimer's disease. The results showed that when gastrodin and gastrodia polysaccharide were used alone, there was almost no effect on the treatment of Alzheimer's disease; when gastrodin and gastrodia polysaccharide were combined, there was a certain therapeutic effect, indicating that the combination of the two had a mutual enhancement effect. When one or both of gastrodin and gastrodia polysaccharide were used with known drugs for the treatment of Alzheimer's disease, the therapeutic effect was better than using the known drugs for the treatment of Alzheimer's disease alone, indicating that one or both of gastrodin and gastrodia polysaccharide can enhance the efficacy of known drugs for the treatment of Alzheimer's disease.

[0091] 5. Morris water maze experiment and results

[0092] ① Place the platform 0.5 cm below the water surface. The female mice enter the water from the middle of the four quadrants of the platform facing the pool wall. Record the escape latency, that is, the time it takes for the female mice to find the platform and stay on it for 20 seconds.

[0093] After five days of continuous training, the above experiment was conducted again, the escape latency was recorded, and the results were averaged (n=6).

[0094] Results Figure 4 Compared with the blank control, the escape latency of female mice in the model group was significantly prolonged, P<0.05. Compared with the model group, the escape latency of each embodiment group was significantly shortened, P<0.05.

[0095] ②On the sixth day of the experiment, the platform was removed and other conditions were the same as in ①. The swimming distance and speed of the female mice within 90 seconds were recorded.

[0096] Results Figure 5-6 Specifically, Figure 5 For the swimming journey, Figure 6 is the swimming speed.

[0097] The results of the Morris water maze test are consistent with those of the open field test, that is, the comparison results with the blank control group and the model group show that the drug for treating Alzheimer's disease provided by the embodiment of the present invention can effectively alleviate Alzheimer's disease. When gastrodin is compounded with a known therapeutic preparation for treating Alzheimer's disease, and when gastrodia polysaccharide is compounded with a therapeutic preparation for treating Alzheimer's disease, they are compared with the model group and the blank control, showing that they also have a certain effect of alleviating Alzheimer's disease, but there are still significant differences between them and the drugs in each embodiment of the present application. When gastrodin and gastrodia polysaccharide are used alone, there is almost no effect on the treatment of Alzheimer's disease; when gastrodin is compounded with gastrodia polysaccharide, it has a certain therapeutic effect, indicating that the combination of the two has a mutual enhancement effect. When one or both of gastrodin and gastrodia polysaccharide are used with known drugs for treating Alzheimer's disease, the therapeutic effect is better than the use of known drugs for treating Alzheimer's disease alone, indicating that one or both of gastrodin and gastrodia polysaccharide can enhance the efficacy of known drugs for treating Alzheimer's disease.

[0098] 5. Acetylcholinesterase activity test results

[0099] Most Alzheimer's patients have abnormal acetylcholinesterase activity, and acetylcholinesterase is often used as one of the diagnostic and treatment judgment indicators for Alzheimer's patients. Therefore, the present invention tests the acetylcholinesterase activity of female mice participating in the experiment to evaluate the efficacy of each group of drugs.

[0100] Results Figure 7 The acetylcholinesterase activity of the model group was significantly higher than that of the various example groups of the present invention. The acetylcholinesterase activity of the blank control was the lowest. Gastrodin and Gastrodia polysaccharide have the effect of reducing the activity of acetylcholinesterase, and when one or both of Gastrodin and Gastrodia polysaccharide are combined with a known drug for treating Alzheimer's disease, the effect of reducing the activity of acetylcholinesterase is more obvious.

[0101] In summary, in the experiment of the present invention, the known drugs for treating Alzheimer's disease are compounded with gastrodin and / or gastrodia polysaccharide, which can significantly reduce the activity of acetylcholinesterase and improve Alzheimer's disease. The research results of the present invention show that gastrodin and gastrodia polysaccharide have the effect of reducing the activity of acetylcholinesterase, and after being compounded with the known drugs for treating Alzheimer's disease, the effect of improving Alzheimer's disease is better.

[0102] It should be noted that when the present invention involves a numerical range, it should be understood that the two endpoints of each numerical range and any value between the two endpoints can be selected. Since the steps and methods used are the same as those in the embodiments, in order to avoid redundancy, the present invention describes a preferred embodiment. Although the preferred embodiments of the present invention have been described, once those skilled in the art know the basic inventive concept, they can make other changes and modifications to these embodiments, and these changes and modifications all fall within the scope of the present invention.

[0103] Obviously, those skilled in the art can make various changes and modifications to the present invention without departing from the spirit and scope of the present invention. If these modifications and variations of the present invention fall within the scope of the equivalent technology of the present invention, the present invention is also intended to include these modifications and variations.

Claims

1. An application of an active ingredient of Gastrodia elata in the preparation of a drug for treating Alzheimer's disease, characterized in that: The active ingredients of Gastrodia elata are gastrodin and gastrodia polysaccharide, which are compounded with a known therapeutic preparation for treating Alzheimer's disease. The mass ratio of gastrodin, gastrodia polysaccharide and the known therapeutic preparation for treating Alzheimer's disease is 50-100:150-200:2-3.

2. The use of the active ingredient of Gastrodia elata according to claim 1 in the preparation of a drug for treating Alzheimer's disease, characterized in that: The known therapeutic preparations for treating Alzheimer's disease are acetylcholinesterase inhibitors, N-methyl-D-aspartate receptor antagonists or brain metabolism activators.

3. The use of the active ingredient of Gastrodia elata according to claim 2 in the preparation of a drug for treating Alzheimer's disease, characterized in that: The acetylcholinesterase inhibitor is donepezil hydrochloride or rivastigmine bitartrate; the N-methyl-D-aspartate receptor antagonist is memantine hydrochloride; and the brain metabolism activator is oxiracetam.

4. The use of the active ingredient of Gastrodia elata according to claim 1 in the preparation of a drug for treating Alzheimer's disease, characterized in that: The drug for treating Alzheimer's disease is an oral preparation.

5. The use of the active ingredient of Gastrodia elata according to claim 1 in the preparation of a drug for treating Alzheimer's disease, characterized in that: The oral preparation is a capsule or a tablet, and is prepared from gastrodin, gastrodia polysaccharide, a known therapeutic preparation for treating Alzheimer's disease and a first auxiliary material.

6. The use of the active ingredient of Gastrodia elata according to claim 5 in the preparation of a drug for treating Alzheimer's disease, characterized in that: The first auxiliary material is one or more of starch, aluminum oxide and calcium stearate.

7. The use of the active ingredient of Gastrodia elata according to claim 1 in the preparation of a drug for treating Alzheimer's disease, characterized in that: Firstly, gastrodin, gastrodia polysaccharide and the second auxiliary material are made into an oral preparation, and then the preparation known for treating Alzheimer's disease is compounded.

8. The use of the active ingredient of Gastrodia elata according to claim 7 in the preparation of a drug for treating Alzheimer's disease, characterized in that: The second auxiliary material is one or more of starch, methyl cellulose, dextrin, aluminum oxide, magnesium stearate and calcium stearate.

9. The use of the active ingredient of Gastrodia elata according to claim 1 in the preparation of a drug for treating Alzheimer's disease, characterized in that: The Alzheimer's disease patient is a naturally ill human, mouse, or a constructed Alzheimer's disease animal model.

10. The use of the active ingredient of Gastrodia elata according to claim 1 in the preparation of a drug for treating Alzheimer's disease, characterized in that: The drug for treating Alzheimer's disease is used to reduce the activity of acetylcholinesterase.

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