A Chinese medicine composition for preventing and treating Alzheimer's disease and / or osteoporosis, preparation method and application thereof
By using traditional Chinese medicine compositions of nylon, monsolicin and echinobacterium, the problems of strong toxic side effects and potential adverse reactions of combined medications in the treatment of Alzheimer's disease and osteoporosis were solved, safer and more effective treatment effects were achieved, and the quality of life of patients was improved.
Patent Information
- Application Number
- CN202310631402.0
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2021-12-16
- Publication Date
- 2025-04-29
- Estimated Expiration
- 2041-12-16
AI Technical Summary
The existing drugs used to treat Alzheimer's disease and osteoporosis have strong toxic side effects, and the combination of different drugs may cause adverse reactions or toxic side effects.
The traditional Chinese medicine compositions of nylon, monsolica and echinobacter are prepared by extraction, concentration, impurity removal and HPLC preparation, forming a multi-component synergistic composition for improving memory and improving cognition, and treating Alzheimer's disease, osteoporosis and comorbidities.
The composition has no obvious toxicity and can significantly improve the survival rate of osteoblasts and LPS-induced microglia after oxidative stress, improve the proliferation ability of osteoblasts and the formation of bone mineralized nodules, have good anti-inflammatory activity, reduce the mineralization area and mineralization density of zebrafish skulls, and restore movement disorders and reaction efficiency.
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Figure CN116492362B_ABST
Abstract
Description
Technical Field
[0001] The invention relates to a traditional Chinese medicine composition for preventing and treating Alzheimer's disease and / or osteoporosis, and also relates to a preparation method and application thereof. Background Art
[0002] Osteoporosis (OP) and Alzheimer's disease (AD) are two diseases with completely different pathological manifestations, but they often co-occur in clinical practice, which belongs to the category of "co-morbidity". At present, there are many kinds of drugs used to treat OP and AD in clinical practice: for example, drugs for treating AD include estrogen that inhibits the formation of Aβ protein, non-steroidal anti-inflammatory drugs, drugs that act on the cholinergic nervous system, etc. for treating AD; drugs for treating OP include bone resorption inhibitors bisphosphonates, bone formation promoting drugs statins and fluoride, etc. for treating OP, but the above drugs all have certain disadvantages, such as non-steroidal anti-inflammatory drugs are metabolized quickly in the body and have a short maintenance time; most statins are metabolized by drug enzymes in the liver, and long-term use may cause abnormal liver biochemical indicators, etc.; and the two diseases need to be treated with drugs for different purposes, and the combination of different types of drugs may have potential adverse reactions or toxic side effects. Summary of the invention
[0003] Purpose of the invention: The purpose of the present invention is to provide a new treatment scheme of multi-component synergistic combination to treat Alzheimer's disease, osteoporosis and the comorbidity of the two diseases, aiming to provide safer and more effective treatment and improve the quality of life of patients.
[0004] Content of the invention: The Chinese medicine composition of the present invention is composed of notopterygium alcohol, verbascoside and echinacoside. Calculated by mass percentage, the ratio of notopterygium alcohol: verbascoside: echinacoside is 30-70%: 20-40%: 20-40%.
[0005] The method for preparing the above-mentioned Chinese medicine composition for preventing and treating Alzheimer's disease and / or osteoporosis comprises the following steps:
[0006] (1) taking Radix Notopterygii and Herba Cistanches, adding solvent to extract, filtering, and combining the extracts;
[0007] (2) Concentrating under reduced pressure until the relative density of the remaining material is between 0.8 and 1.2, adding ethanol for alcohol precipitation, and collecting the supernatant after standing;
[0008] (3) removing impurities from the supernatant obtained in step (2) by passing it through a macroporous resin and water, and then eluting it with 20-90% ethanol solution, and drying and concentrating the eluate to obtain a crude extract;
[0009] (4) Dissolve the crude extract in methanol, prepare the liquid phase using HPLC, collect the target components, and dry them.
[0010] Preferably, in step (1), the solvent is water or ethanol, the solid-liquid ratio is 4:1 to 50:1, and the number of extractions is 1 to 5 times.
[0011] Preferably, in step (2), the alcohol precipitation has a final concentration of the alcohol solution of 50-80%.
[0012] Preferably, the Chinese medicine composition for preventing and treating Alzheimer's disease and / or osteoporosis is mixed with pharmaceutically acceptable excipients to form ointments, liniments, patches, lotions, solutions, powders, sprays, syrups, suppositories, tablets, pills, granules, capsules, injections or gastrointestinal sustained-release preparations.
[0013] The present invention combines notopterygium alcohol, verbascoside and echinacoside into a new composition, utilizes the notopterygium alcohol in the composition to be good at anti-inflammatory, and utilizes the effects of echinacoside and verbascoside in regulating immunity, protecting nerves and promoting the growth of osteoblasts, and exerts the integrated effect of multi-component synergistic enhancement, and is used for improving memory and enhancing cognition, and treating Alzheimer's disease, osteoporosis and the comorbidity of the two diseases, thereby constructing a new treatment plan combining traditional Chinese medicine with combined medication.
[0014] Cistanche deserticola and Notopterygium incisum are often used in combination in the clinical treatment of diseases in the category of "weakness" and "arthritis" in traditional Chinese medicine, such as Alzheimer's disease, osteoporosis or rheumatoid arthritis. Notopterygium incisum alcohol is one of the chemical components of Notopterygium incisum or Notopterygium latifolium, and echinacoside and verbascoside are chemical components of Cistanche deserticola or Cistanche tubulosa. During the research process, the inventors found that the notopterygium alcohol component in Notopterygium is good at exerting anti-inflammatory effects, while echinacoside and verbascoside have significant effects on regulating immunity, neuroprotection and promoting osteoblast growth. Therefore, notopterygium alcohol is combined with echinacoside and verbascoside to form component drugs, so that the synergistic and integrated effects of multiple components and multiple targets can be better exerted, which is used to improve memory and enhance cognition. While exerting anti-inflammatory effects, it can also promote osteoblast growth. It can be used to treat Alzheimer's disease, osteoporosis and the comorbidity of these two diseases. A new treatment regimen of component combination medication based on traditional Chinese medicine compound for the treatment of complex diseases and their comorbidities has been constructed.
[0015] Component Chinese medicine has the advantages of clear ingredients and ratios, and is an important development direction for compound Chinese medicine. It is consistent with or more effective than traditional Chinese medicine in terms of efficacy, and its quality is controllable, so it can be used for industrial promotion. Studies have found that OP and AD have the same pathogenic factors, such as advanced age, female, vitamin D and estrogen levels, and the common signaling pathways between the two also verify the correlation between the two diseases. The use of a combination of notopterygium alcohol, echinacea glycoside and verbascoside for the treatment of Alzheimer's disease, osteoporosis, especially the comorbidity of Alzheimer's disease and osteoporosis has important social significance and clinical value.
[0016] Beneficial effects: Compared with the prior art, the present invention has the following significant advantages:
[0017] (1) Each composition of the present invention is composed of active monomer components of traditional Chinese medicine, has a relatively clear mechanism of action, has the same or more significant therapeutic effect as traditional Chinese medicine, and has controllable quality;
[0018] (2) All compositions of the present invention have no obvious toxicity, and in vitro cell experiments show that they can significantly improve the survival rate of osteoblasts and LPS-induced microglia after oxidative stress;
[0019] (3) The results of the osteoblast and BV2 cell in vitro models showed that each composition of the present invention can improve the proliferation ability of osteoblasts, promote the formation of alkaline phosphatase and bone mineral nodules and the differentiation of osteoblasts; down-regulate the level of inflammatory factor NO in BV2 cells induced by LPS, and have good anti-inflammatory activity;
[0020] (4) The composition of the present invention can reduce the mineralized area and mineralized density of the zebrafish skull, restore movement disorders and reaction efficiency, and has the potential to resist Alzheimer's disease and osteoporosis. BRIEF DESCRIPTION OF THE DRAWINGS
[0021] Figure 1 It is a schematic diagram of the preparation and verification of the composition of the present invention;
[0022] Figure 2 It is the structural formula of Qianghuo alcohol;
[0023] Figure 3 It is the structural formula of verbascoside;
[0024] Figure 4 It is the structural formula of echinacoside;
[0025] Figure 5 The skull development of zebrafish in different drug-administered groups;
[0026] Figure 6 The following are representative movement trajectories of fry in different drug-treated groups under lighting conditions. DETAILED DESCRIPTION
[0027] The technical solution of the present invention is further described below in conjunction with the accompanying drawings.
[0028] Embodiment 1
[0029] Preparation of active ingredients of traditional Chinese medicine
[0030] Take appropriate amount of Notopterygium wilfordii and Cistanche tubulosa, crush them and place them in a round-bottom flask, add 15 times the amount of water, soak for 1 hour, heat and reflux to extract twice, each time for 1 hour. Combine the filtrate, concentrate under reduced pressure, and then add 95% ethanol for alcohol precipitation (the final concentration of the alcohol solution is 65%). After standing, take the supernatant and pass it through HPD-300 macroporous resin, elute with water until colorless, and then elute with 25% and 70% ethanol respectively, collect the 25% and 70% ethanol eluates, dry and concentrate the eluates respectively, and obtain the crude extract. Take an appropriate amount of crude product and dissolve it in methanol, filter it at 0.22μM, and prepare the sample for injection using HPLC. The chromatographic column filler is C 18 The column was prepared by using acetonitrile-water solution as the mobile phase and the ultraviolet detection wavelength as 320 nm. The target component solution was collected and dried to obtain the product.
[0031] Osteoblast activity verification
[0032] Osteoporosis is a metabolic disease in which bone brittleness increases, bone mass decreases, bone tissue microstructure is destroyed, and fractures are prone to occur. Osteoblasts are the main functional cells of bone formation. When bone tissue is damaged, osteoblasts proliferate in large quantities under the regulation of many factors and secrete bone matrix. Bone matrix maturation and mineralization form new bone tissue, which is an important means for preventing and treating osteoporosis. Therefore, the present invention sets up an in vitro osteoporosis cell model, and investigates the influence of the composition of the present invention on the early and late marker alkaline phosphatase (ALP) of osteoblasts by bone metabolism biochemical index inspection and bone tissue morphometry, and etidronate disodium (Ed) is a positive control drug.
[0033] 1 Experimental methods
[0034] 1.1CCK-8 assay for cell viability
[0035] Take MC3T3-E1 cells in the logarithmic growth phase, inoculate them in a 96-well plate, add 100 μL of cell suspension to each well, and after culturing for 24 hours, replace the DMEM medium containing H2O2, H2O2+etidronate disodium (Ed) and H2O2+different compositions of the present invention (5-100 μM) for intervention culture. Each group of cells is set up with 5 replicate wells at the same time. After continuing to culture in an incubator for 24 hours, add 10 μL of CCK-8 reagent to each well in the dark and continue to culture for 1 hour. Measure OD with an enzyme marker 450 , calculate the cell survival rate.
[0036] 1.2 Alkaline phosphatase (ALP) detection
[0037] Take MC3T3-E1 cells in the logarithmic growth phase, inoculate them in a 96-well plate, and culture them in an incubator for 24 hours. Then discard the supernatant and treat the cells differently according to the following groups: Ctrl group, Model group, Ed (1μM) group, and different combination groups (total concentration 30μM, combined at 1:1 and 1:1:1, respectively). Each group has 5 replicate wells. After continuing to culture in the incubator for 24 hours, discard the culture medium, wash twice with PBS, add 100μL of RIPA strong lysis solution to each well, transfer to a 1.5mL EP tube, and place on ice for lysis for 30 minutes. According to the instructions of the Bioday Alkaline Phosphatase (ALP) Activity Assay Kit, use an enzyme reader to measure OD 405 , taking the Ctrl group as the control, the changes of ALP activity in different drug-administered groups were calculated.
[0038] 2 Experimental results
[0039] After different dosing groups were given the positive control drug Ed and different combinations, the experimental results showed that after drug intervention, the ALP activity of osteoblasts increased to varying degrees, indicating that different combinations have different degrees of promoting osteoblast proliferation and increasing ALP activity. The specific results are shown in Table 1 below.
[0040] Table 1 Experimental results of the effects of different drug combinations on osteoblast ALP activity (%, n=5, )
[0041]
[0042] Note: Compared with the blank group, * P<0.05, ** P<0.01, *** P<0.001.
[0043] The results of this example show that the composition provided by the present invention can increase ALP activity, and the effect is better than that of a single compound, suggesting that it may promote bone differentiation, improve the symptoms of osteoporosis, have anti-osteoporosis activity and the possibility of being used as an anti-osteoporosis drug.
[0044] Embodiment 2
[0045] Effects of different samples on BV2 cells
[0046] The two most characteristic pathological changes in patients with Alzheimer's disease are extracellular β-amyloid deposition and neurofibrillary tangles. Studies have found that β-amyloid is crucial to the inflammatory response of AD: it activates microglia (BV2) to produce inflammatory factors, which can damage various cells including neurons and induce their apoptosis; these factors can further activate BV2 cells, leading to a vicious cycle. Therefore, the present invention uses lipopolysaccharide (LPS)-induced BV2 cells to establish an in vitro inflammatory model, and uses the CCK-8 method and Griess experiment to investigate the effect of the composition of the present invention on LPS on cell viability and the effect of the inflammatory factor NO, and berberine hydrochloride (BBR) is a positive control drug.
[0047] 1 Experimental methods
[0048] 1.1 CCK-8 assay to detect cell viability
[0049] BV-2 cells in the logarithmic growth phase were taken and inoculated into 96-well plates. 100 μL of cell suspension was added to each well. After culturing for 24 hours, DMEM medium containing lipopolysaccharide (LPS), lipopolysaccharide + berberine hydrochloride (BBR) and lipopolysaccharide + different compositions of the present invention (5-100 μM) was replaced for intervention culture. Five replicate wells were set for each group. After continuing to culture in an incubator for 24 hours, 10 μL of CCK-8 reagent was added to each well in the dark and continued to culture for 1 hour. OD was measured using an enzyme marker 450 , calculate the cell survival rate.
[0050] 1.2 Griess experiment
[0051] BV-2 cells in the logarithmic growth phase were taken and inoculated in a 48-well plate, 200 μL per well, and placed in an incubator for 24 hours. The supernatant was discarded and the cells were treated differently according to the following groups: Ctrl group, LPS group, LPS+BBR (1 μM) group, LPS+different combinations (total concentration 30 μM, combined at 1:1 and 1:1:1, respectively) group, and 5 replicate wells were set for each group. After continued culturing in the incubator for 24 hours, 100 μL of the supernatant was taken from each well and transferred to a clean 96-well plate. 100 μL of Griess reagent was added to each well, mixed thoroughly, and color was developed for 10 minutes in the dark, and the OD was measured. 540 The measured OD 540 Substitute the standard equation drawn with sodium nitrite standard solution to calculate the content of NO released in the supernatant of BV-2 cells.
[0052] The NO inhibition rate was calculated according to the following formula:
[0053] NO inhibition rate (%) = (C 模型 -C 给药 ) / (C 模型 -C空白 )×100%
[0054] C 模型 , C 给药 , C 空白 Represent the concentration values of the model group, drug-treated group and blank group, respectively.
[0055] 2 Experimental results
[0056] The results of this example are shown in Table 2: Different compositions can inhibit the production of NO and have certain anti-neuroinflammatory activity, and the effect of the composition is better than that of a single drug, suggesting that it may have anti-Alzheimer's disease activity.
[0057] Table 2 Experimental results of different drugs on LPS-induced BV-2 cell viability and NO release (n=5, )
[0058]
[0059] Note: Compared with the model group, * P<0.05, ** P<0.01, *** P<0.001.
[0060] Embodiment 3
[0061] Effects of different compositions on osteoporosis and Alzheimer's disease in zebrafish models
[0062] 1. Experimental Methods
[0063] 1.1 Zebrafish embryo collection
[0064] Male and female zebrafish were raised separately in a 28°C circulating water system, maintained at 14h light and 10h dark per day, and fed Artemia twice. 3-4 pairs (female: male = 1:2) of zebrafish around 6 months old were taken for mating and spawning, and normal embryos were collected into zebrafish embryo culture medium and placed in a 28°C constant temperature incubator to maintain the same lighting conditions for culture.
[0065] 1.2 Experimental Grouping
[0066] The zebrafish larvae in good condition at 3 days after fertilization were selected and transferred to 6-well plates, with 30 fish in each well and 1 well in each group. The fish were randomly divided into the following groups: blank control group, model group (prednisolone or AlCl3), positive drug group (etidronate disodium or donepezil hydrochloride), and groups treated with notopterygium alcohol, verbascoside, echinacoside, and different combinations.
[0067] 1.3 Alizarin red staining observation
[0068] The juveniles were grouped and dosed as described in 1.2 and cultured until 7 dpf after fertilization. After anesthesia with 0.02% tricaine, they were fixed with 4% paraformaldehyde for 2 h. After removing the fixative, freshly prepared bleach (3% H2O2 and 0.5% KOH) was added to bleach the fish until the body was transparent. The bleach was removed, and the fish were dehydrated with 50% ethanol for 10 min, and then stained with 0.1% alizarin red dye prepared with 0.5% KOH overnight. The excess dye was washed off with pure water, and the fish were permeabilized in different ratios of 0.5% KOH and glycerol (3:1, 1:1, 1:3). Finally, the ventral surface of the zebrafish skull stained with alizarin red was observed under a stereomicroscope in a prone position, and images were collected using the same light intensity and exposure settings. Image-Pro Plus 6.0 image analysis software was used to calculate the area and cumulative optical density of the alizarin red stained area. 1.4 Detection of osteoblast-osteoclast biochemical indicators
[0069] The fry were divided into groups as described in 1.2 and cultured until 7 dpf after fertilization. The drug solution was removed, washed twice with PBS, and the fry were collected into 1.5 mL centrifuge tubes. Pre-cooled PBS was added at a ratio of fry: PBS (w / v) = 1:9 and ground. Centrifuged at 4°C and 3000r / min for 15min, and the supernatant was collected into a new centrifuge tube. According to the instructions of the kit, the enzyme-linked immunosorbent assay (ELISA) was used to determine the activities of zebrafish alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRAP).
[0070] 1.5 Behavioral Analysis
[0071] The zebrafish larvae at 6 dpf after fertilization were transferred to a 96-well plate. The experimental time was 60 min, the temperature was maintained at 28 °C, and 3 cycles of light / dark cycle (10 min light / 10 min dark) were set. The movement distance (D), average movement speed (AS), and light / dark cycle speed change (ΔS) of zebrafish larvae were recorded by Viewpiont behavior analyzer. AS was used to calculate the motor disorder recovery rate (DRR), and ΔS was used to calculate the reaction efficiency (RE).
[0072] 1.6 Nerve conduction biochemical index detection
[0073] The fry were divided into groups as described in 1.2 and cultured until 6 days after fertilization. The drug solution was removed, washed twice with PBS, and the fry were collected into a 1.5 mL centrifuge tube. Pre-cooled PBS was added at a ratio of fry: PBS (w / v) = 1:9 and ground. Centrifuged at 4°C and 3000r / min for 15 minutes, and the supernatant was collected into a new centrifuge tube. According to the instructions of the kit, the enzyme-linked immunosorbent assay (ELISA) was used to determine the activities of zebrafish acetylcholinesterase (AChE) and acetylcholine transferase (ChAT).
[0074] 2. Experimental results
[0075] In the Alizarin Red staining experiment, compared with the model group (prednisolone), the head bone development of zebrafish in the positive drug group (Ed) and different drug groups was significantly improved, and the mineralization area and mineralization density were increased to varying degrees (Table 3 and Figure 5 ), and the effect of the different combination administration groups was significantly better than that of the single administration group.
[0076] Table 3 Experimental results of the effects of different drugs on the mineralization area and mineralization density of zebrafish (n=10, )
[0077]
[0078] Note: Compared with the prednisolone model group, * P<0.05, ** P<0.01, *** P<0.001.
[0079] like Figure 5 As shown, the skull development of zebrafish in different drug-treated groups (A is the Pre model group, B is the Ed positive control group, C is the Not notoginseng alcohol group; D is the Ech echinacoside group; E is the Act verbascoside group; F is the notoginseng alcohol + verbascoside group; G is the notoginseng alcohol + echinacoside group; H is the verbascoside + echinacoside group; I is the notoginseng alcohol + verbascoside + echinacoside group.
[0080] The results of osteoblast-osteoclast biochemical index detection also showed that the positive drug group (Ed) and the drug-treated group both increased the ALP activity and reduced the TRAP activity, showing an opposite trend to the model group. The results were consistent with the results of Alizarin red staining. In particular, different drug combinations had a better alleviating effect on osteoporosis, and the effect was better than that of a single drug (Table 4).
[0081] Table 4 Experimental results of the effects of different drugs on the activity of zebra ALP and TRAP (n=10, )
[0082]
[0083] Note: Compared with the blank group, ### P<0.001; compared with the model group, * P<0.05, ** P<0.01, *** P<0.001.
[0084] like Figure 6As shown in the figure, the representative movement trajectory of the young fish in different drug groups under light conditions; in the behavioral analysis experiment, compared with the model group (AlCl3), the movement of zebrafish in the positive drug group (DPZ) and different drug groups was significantly improved. The calculation of the movement disorder recovery rate (DRR) and reaction efficiency (RE) showed that the movement disorder and reaction efficiency of zebrafish in the drug group were recovered to varying degrees, and the effect of the combination was better than that of a single drug (Table 5 and Figure 6 ).
[0085] Table 5 Experimental results of the effects of different drugs on the recovery rate and reaction efficiency of zebra dyskinesia (n=10, )
[0086]
[0087]
[0088] Note: Compared with the blank group, ### P<0.001; compared with the model group, * P<0.05, ** P<0.01, *** P<0.001.
[0089] The biochemical indices of nerve conduction were detected. The results showed that compared with the blank group, the AChE activity of the AlCl3 model group was significantly increased, and the ChAT activity was significantly decreased, while the positive drug group (DPZ) and the drug-treated group showed a trend opposite to that of the model group, and the effect of the combination was better than that of a single drug (Table 6), which was consistent with the results of behavioral analysis.
[0090] Table 6 Experimental results of different drugs on the activity of zebra AChE and ChAT (n=10, )
[0091]
[0092] Note: Compared with the blank group, ### P<0.001; compared with the model group, * P<0.05, ** P<0.01, *** P<0.001.
[0093] The results of this example show that the composition provided by the present invention has the effects of up-regulating the mineralization area and density of the zebrafish head bones, increasing the activities of ALP and TRAP, and improving the movement disorder and related biochemical indices of the zebrafish, and the effect is significantly better than that of a single drug, has a multi-component synergistic effect, and can significantly improve the symptoms of osteoporosis and Alzheimer's disease, proving that it has anti-osteoporosis and Alzheimer's disease activity and its possibility as an anti-osteoporosis and Alzheimer's disease drug.
[0094] Through cell experiments, in vitro models of osteoblasts and BV2 cells were established. The results showed that different compositions can improve the survival rate of osteoblasts under oxidative stress, increase the activity of alkaline phosphatase and the differentiation of osteoblasts; the composition can downregulate the level of inflammatory factor NO in BV2 cells induced by LPS, and has good anti-inflammatory activity. The results of cell experiments show that the composition of active ingredients of traditional Chinese medicine provided by the present invention can effectively prevent and treat Alzheimer's disease and osteoporosis, and the effect of the composition is significantly better than that of a single ingredient.
[0095] Through animal experiments, zebrafish models of OP and AD were established. Embryos of zebrafish spawned by mating at about 6 months of age were collected, and after culturing at 28°C for 3 days, the fry were divided into a blank control group, a model group (prednisolone or AlCl3), a positive drug group (etidronate disodium or donepezil hydrochloride), a group administered with notopthrasia alcohol, a group administered with verbascoside, a group administered with echinacoside, and a group administered with different combinations of notopthrasia alcohol, verbascoside, and echinacoside, and transferred to a 6-well plate, 30 per well, 1 well per group, and cultured for 3-4 days.
[0096] Alizarin red staining experiments showed that the mineralized area and density of the skull of zebrafish in the model group were significantly reduced, and the head bone development of zebrafish in the positive drug group (Ed) and different combination groups was significantly improved. The results of osteoblast-osteoclast biochemical index detection also showed that the positive drug group (Ed) and the combination group increased the ALP activity and reduced the TRAP activity, showing a trend opposite to that of the model group (prednisolone). The results of behavioral analysis experiments showed that compared with the model group (AlCl3), the movement of zebrafish in the positive drug group (DPZ) and different combination groups was significantly improved, and the movement disorder and reaction efficiency of zebrafish in the drug group were restored to varying degrees. The biochemical indicators of nerve conduction showed that the AChE and ChAT activity levels in the positive drug group (DPZ) and different combination groups showed a trend opposite to that of the model group.
[0097] Therefore, for patients with AD and OP in my country, especially patients with AD and OP co-morbidity, the composition of the present invention can replace multiple drugs that work alone with one drug that exerts dual effects, thereby reducing the physical burden and costs of patients with comorbidities caused by taking multiple drugs at the same time, and also avoiding the toxic side effects or adverse reactions caused by combined medication to a certain extent.
[0098] The component drugs of the Chinese medicine composition can play a synergistic role, and can also reduce the types and dosages of drugs to be taken. The efficacy of different combinations is better than that of single drugs, and can significantly improve the symptoms of OP and AD animal models in the present invention, and has anti-Alzheimer's disease and osteoporosis activity. Therefore, various forms of drugs prepared with Qianghuo alcohol, echinacoside and verbascoside and different combinations thereof as the main active ingredients can be used to prevent or treat Alzheimer's disease and osteoporosis.
Claims
1. A Chinese medicine composition for preventing and treating Alzheimer's disease and / or osteoporosis, characterized in that: The composition consists of notopterygium alcohol, verbascoside and echinacoside; in terms of mass percentage, notopterygium alcohol: verbascoside: echinacoside is 30-70%: 20-40%: 20-40%, and the total addition does not exceed 100%.
2. A method for preparing the Chinese medicine composition for preventing and treating Alzheimer's disease and / or osteoporosis according to claim 1, characterized in that: The following steps are involved: (1) Take Notopterygium root and Cistanche deserticola medicinal materials, add water or ethanol to extract, filter, and combine the extracts; (2) Concentrate under reduced pressure until the relative density of the remaining material is between 0.8 and 1.2, add ethanol for alcohol precipitation, let stand and take the supernatant; (3) The supernatant obtained in step (2) is passed through a macroporous resin and water to remove impurities, and then eluted with 20-90% ethanol solution, and the eluate is dried and concentrated to obtain a crude extract; (4) Dissolve the crude extract in methanol, prepare the liquid phase using HPLC, collect the target components separately, and dry them to obtain the product.
3. The method for preparing the Chinese medicine composition according to claim 2, characterized in that: In step (1), the solid-liquid ratio is 4:1-50:1, and the number of extractions is 1-5 times.
4. The method for preparing the Chinese medicine composition according to claim 2, characterized in that: In step (2), the alcohol precipitation has a final concentration of the alcohol solution of 50-80%.
5. The Chinese medicine composition for preventing and treating Alzheimer's disease and / or osteoporosis according to claim 1, characterized in that: The Chinese medicine composition is mixed with pharmaceutically acceptable excipients to form ointments, liniments, patches, lotions, solutions, powders, sprays, syrups, suppositories, tablets, pills, granules, capsules, injections or gastrointestinal sustained-release preparations.
6. Use of the Chinese medicine composition for preventing and treating Alzheimer's disease and / or osteoporosis according to claim 1, characterized in that: The traditional Chinese medicine composition is used for preparing medicines for preventing and / or treating Alzheimer's disease and osteoporosis.
Citation Information
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