CN106138135B - Medicine for preventing and treating vascular cognitive disorder and preparation method thereof - Google Patents
Medicine for preventing and treating vascular cognitive disorder and preparation method thereof Download PDFInfo
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
- A61K36/236—Ligusticum (licorice-root)
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/333—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using mixed solvents, e.g. 70% EtOH
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/37—Extraction at elevated pressure or temperature, e.g. pressurized solvent extraction [PSE], supercritical carbon dioxide extraction or subcritical water extraction
Abstract
The invention discloses a medicine for preventing and treating vascular cognitive impairment and a preparation method thereof. The medicine is cnidium oil with ligustilide content higher than 10 wt%. The preparation method comprises the following steps: the method comprises the following steps: extracting the pulverized rhizoma Ligustici Chuanxiong by supercritical carbon dioxide circulation countercurrent mode, and separating to obtain rhizoma Ligustici Chuanxiong oil; or the second method: extracting rhizoma Ligustici Chuanxiong with ethanol solution with volume percentage of 60% or more, removing ethanol from the extractive solution, and separating to obtain rhizoma Ligustici Chuanxiong oil. The medicine has beneficial effects on treating mild, moderate and severe vascular cognitive impairment, has obviously better effect than similar products in the market, and has good development prospect.
Description
Technical Field
The invention relates to the field of medicines, in particular to a medicine for preventing and treating vascular cognitive impairment and a preparation method thereof.
Background
Vascular Cognitive Impairment (VCI) is a syndrome characterized by cerebrovascular injury with or without overt clinical stroke symptoms accompanied by cognitive impairment affecting at least one cognitive region. VCI includes the whole process from non-dementing vascular cognitive impairment to mild dementia vascular cognitive impairment to vascular dementia (VaD), with VaD being the most severe VCI.
Epidemiological studies have shown that: the incidence of VCI has risen year by year, with dementia occurring in affluent countries in the population greater than or equal to 65 years at 5% -10%, with the incidence of alzheimer's disease AD doubling every 4.3 years and the incidence of VaD doubling every 5.3 years. The situation in china is also not optimistic: the combined values of VaD prevalence, morbidity and mortality in the population over 55 years of age were 0.8%, 0.27/100, and 14.6/100 years, respectively. The prevalence rate of VaD increases year by year between 1980 and 2011, specifically from 0.14/100 person year to 0.57/100 person year. Memory decline was seen in 84.5% of the Shanghai population with an average age of 72.8 years with mild cognitive impairment MCI of 25%, AD of 4.7%, VaD of 2.5%, mixed 1.3%. With the increasing level of detection technology, it has been found that VaD accounts for a greater proportion of patients with dementia. The patients with dementia above 50 years old were sub-classified to find that AD accounted for 35.4%, VaD accounted for 21.2%, AD and VaD were present in a mixture of 13.3%, and other dementias accounted for 30.1%. Compared to AD, VCI and particularly VaD are more hazardous: its 50% average life cycle is shorter, more healthcare costs are required, the concomitant disease rate is higher, and the costs to care givers are also higher.
At present, the occurrence and development of VCI are widely considered to be closely related to the imbalance of homeostasis in the brain microenvironment. Although the close relationship between cerebral infarction and dementia has been recognized since a long time ago, the relationship between infarct size, number of infarcts, and location of infarcts and dementia remains to be further elucidated, since cerebral infarction is very common among the elderly, some of whom are dementia-causing, but none of them.
Western medicine has performed a great deal of research in preventing VCI, including: the effectiveness of the above methods has yet to be further verified from the current results of studies, by changing the lifestyle, treating diseases such as hypertension, diabetes, hyperlipidemia, hypercholesterolemia, etc., and performing anti-inflammatory and anti-coagulation treatments. Partial clinical studies show that Memantine, Galantamine, Donepezil, Rivastigmine and Nimodipine have certain improvement effects on behaviors, executive functions and cognitive abilities of patients with VaD, but only stay at the improvement level of symptoms, and have no obvious prevention and treatment effects on the essence of diseases. It has also been suggested that the use of cholinesterase inhibitors is not recommended for the treatment of VaD, based on the uncertainty of their efficacy and toxic side effects. Therefore, at present, no medicine for effectively preventing and treating VCI exists in Western medicine.
Disclosure of Invention
[ problem to be solved ]
The invention aims to solve the technical problems and provides a medicament for preventing and treating vascular cognitive impairment and a preparation method thereof.
[ solution ]
In order to achieve the technical effects, the invention adopts the following technical scheme:
a medicine for preventing and treating vascular cognitive disorder is cnidium oil whose ligustilide content is greater than 10%.
The medicine is ligusticum oil with ligustilide content of 10-60 wt%.
The medicine is ligusticum oil with 30-60% of ligustilide by mass percent.
The ligusticum oil with the ligustilide mass percentage of more than 10 percent is applied to preparing the medicine for treating mild, moderate or severe vascular cognitive impairment. Wherein, the ligusticum oil with the ligustilide mass percentage of more than 10 percent has the best effect on treating the severe vascular cognitive disorder.
According to a further technical solution of the present invention, the preparation method is as follows:
the method comprises the following steps: extracting pulverized rhizoma Ligustici Chuanxiong by supercritical carbon dioxide circulation countercurrent method, separating
Obtaining the oil of rhizoma ligustici wallichii;
or the second method: extracting rhizoma Ligustici Chuanxiong with ethanol solution with volume percentage of 60% or more, removing extractive solution
After ethanol extraction, the chuanxiong rhizome oil is obtained by separation.
According to a further technical scheme of the invention, the first method is that under the condition that the extraction pressure is 40-60 MPa, the extraction temperature is 60-70 ℃, and the mass ratio of the rhizoma ligustici wallichii to the carbon dioxide used in each hour is 1: 10-20, and performing supercritical carbon dioxide circulation countercurrent extraction under the condition that the extraction time is 5 hours; then, the ligusticum wallichii oil is separated under the conditions that the resolving pressure of a separator is 9-12 MPa and the resolving temperature is 48-55 ℃.
According to a further technical scheme of the invention, the first method is that when the extraction pressure is 40MPa, the extraction temperature is 60 ℃, the mass ratio of the hourly dosage of the ligusticum wallichii to the carbon dioxide is 1: 10, performing supercritical carbon dioxide circulation countercurrent extraction under the condition that the extraction time is 5 hours; then separating at a separation temperature of 50 ℃ under a separation pressure of 10MPa in a separator to obtain the ligusticum wallichii oil.
According to a further technical scheme of the invention, the ligusticum wallichii oil prepared by the method II is subjected to molecular distillation under the vacuum condition of the pressure of 1-80 MPa and the temperature of 20-300 ℃ to obtain the ligusticum wallichii oil with the ligustilide mass percentage of more than 30%. The molecular distillation is to separate and remove low-boiling point and high-boiling point components and non-volatile components to obtain the ligusticum oil with the ligustilide mass percentage of more than 30%.
According to a further technical scheme of the invention, the ligusticum wallichii oil prepared by the method II is subjected to molecular distillation to separate and remove low-boiling point and high-boiling point components and non-volatile components under the vacuum condition of the pressure of 1-50 MPa and the temperature of 30-200 ℃ to obtain the ligusticum wallichii oil with the ligustilide mass percentage of more than 30%.
The present invention will be described in detail below.
The traditional Chinese medicine has relatively deep knowledge on dementia for a long time, and doctors in different generations discuss a lot. The theory of classics syndrome, amnesia and treatment includes that the patients are poor in quality and forgetfulness, or lack of essence and blood, or excessive thoughts, or short spirit, or prosperity and asthenia, or prosperity and prosperity, or heart fire does not fall, kidney water does not rise, uneasiness, or phlegm retention, or phlegm-induced mental confusion, or fatigue and reading, absentmindedness, or heart-qi deficiency, severe palpitation amnesia, or congenital deficiency, absentmindedness, or heart-qi deficiency disturbing, or old age and prosperity drinking spirit. If blood stasis is in the interior, it is easy to forget. The Qing Dynasty Chen Shi ze (entry & entry of dull disease) written in the book "the liver-qi stagnation and the stomach-qi deficiency will be caused. Liver depression means wood-restriction of earth, while phlegm cannot be transformed; stomach deficiency can not produce water, but phlegm can not, so phlegm accumulates in the chest and is recumbent outside the heart, leading to dull disease . "
Chuan Xiong is the dried rhizome of Ligusticum chuanxiong Hort, an Umbelliferae plant, Chuan Xiong, recorded in Shen nong Ben Cao Jing. It is warm in nature, pungent and slightly bitter in taste; has effects in promoting blood circulation, activating qi-flowing, dispelling pathogenic wind, and relieving pain. Can be used for treating menoxenia due to blood stasis and qi stagnation, dysmenorrhea, amenorrhea, blood stagnation due to stagnation of liver-qi, chest and hypochondriac pain, headache, arthralgia due to wind-cold-dampness, and swelling and pain due to traumatic injury. The Chinese medicinal composition is mainly used for treating cardiovascular and cerebrovascular diseases, respiratory diseases, urinary system diseases and gynecological diseases in clinic. Research shows that the chuanxiong rhizome contains a great amount of compounds such as phthalides, phenolic acids, alkaloids and the like. Has effects in inhibiting platelet aggregation, inhibiting venous bypass thrombosis, resisting atherosclerosis, scavenging free radicals, enhancing immunity, relieving convulsion, resisting platelet aggregation and thrombosis, lowering blood viscosity, regulating heart function, inhibiting learning and memory impairment, inhibiting smooth muscle cell proliferation, preventing cerebral ischemia, tranquilizing mind, promoting sleep, relaxing smooth muscle, and inducing heme oxygenase-1 (HO-1) expression.
The research shows that the mouse is injected with the amyloid A β in the hippocampus1-42Then, the contents of learning, memory and brain tissue Ach are obviously reduced, the endoplasmic reticulum of neuron cells in the hippocampus CA1 area is expanded, and the mitochondria are seriously swollen, so that the A β can be obviously improved after the ligusticum wallichii extract is treated1-42Learning and memory ability and Ach content in brain tissue of mice, and for A β1-42A β is closely related to AD and also closely related to the functional state of blood vessels, and the research shows that A β 0 can shrink blood vessels of isolated brain and whole body system, and the application of A β to cerebral cortex of mice can reduce CBF, the vasodilation effect and functional congestion caused by damaged endothelial cell dependence, on the other hand, cerebral ischemia and hypoxia can accelerate the generation of A β by activating APP lyase- β secretase, and can also increase the formation of A β polymer and the phosphorylation of tau protein, and thirdly, the role of A β in shrinking the local blood vessels of brain can also prevent the self-clearing of the brain1-42The toxic effects of (A) are related.
The invention is used for preventing and treating vascular cognitive disorder, namely the ligusticum oil with the ligustilide mass percentage of more than 10 percent, and is suitable for preparing the medicine for preventing and treating mild, moderate and severe vascular cognitive disorder. Has obvious effect on preventing and treating mild, moderate and severe vascular cognitive disorder, in particular to preventing and treating early and middle stage cognitive disorder which is called as mild vascular cognitive disorder and moderate vascular cognitive disorder.
[ advantageous effects ]
Compared with the prior art, the invention has the following beneficial effects:
the ligusticum oil with the ligustilide mass percentage of more than 10 percent obtained from different ways has better prevention and treatment effects on vascular dementia animals, and the effects of the ligusticum oil are obviously superior to those of like products in the market, so that the ligusticum oil has good development prospect.
Detailed Description
The invention will be further elucidated and described with reference to the embodiments of the invention described hereinafter.
Preparation of ligusticum oil with ligustilide mass percentage more than 10%
The method comprises the following steps: collecting crude powder of rhizoma Ligustici Chuanxiong 100kg, and supercritical fluid CO2Circulating countercurrent extraction and separation are carried out, the extraction pressure is 40MPa, the extraction temperature is 60 ℃, and an extractant CO is2The dosage is 1000 kg/h, the extraction time is 5 hours, the resolving pressure of a separator is 10Mpa, the resolving temperature is 50 ℃, and the ligusticum wallichii volatile oil is obtained. The content of ligustilide is 21.3% by HPLC method.
The second method comprises the following steps: 100kg of crude powder of the medicinal raw material ligusticum wallichii is taken, the crude powder is subjected to percolation extraction by 80 percent ethanol, the ethanol is completely removed from the extract, and the ligusticum wallichii volatile oil is obtained by separating aqueous solution. The content of ligustilide is 12.7% by HPLC method.
The third method comprises the following steps: 100kg of crude powder of the medicinal raw material ligusticum wallichii is taken, the crude powder is subjected to percolation extraction by 90% ethanol, the ethanol is completely removed from the extract, and the ligusticum wallichii volatile oil is obtained by separating aqueous solution. Under the vacuum condition with the pressure of 10-50 Pa, firstly separating and removing low boiling point components in a molecular distillation mode at the temperature of 50-120 ℃, then heating to the temperature of 80-200 ℃, and collecting distillate in a molecular distillation mode to obtain the ligusticum oil with the weight content of ligustilide of more than 30%.
Secondly, carrying out pharmacodynamic evaluation on the ligusticum wallichii oil
1, test materials
1.1 Experimental drugs
And (3) ligusticum oil: the chuanxiong rhizome oil obtained by the first to third methods is named chuanxiong rhizome oil I, chuanxiong rhizome oil II and chuanxiong rhizome oil III in sequence;
ligustilide with purity of 92% is provided by institute of Chinese medicine and pharmacy of academy of Chinese medicine and sciences of Sichuan province;
before use, the chuanxiong rhizome oil and ligustilide are prepared into oil solution with required concentration by edible oil for standby;
memantine hydrochloride tablets: specification: 10 mg/tablet, ex Rottendorf Pharma GmbH, product lot No. 201503, approved literature: H20120268.
Aβ1-42batch number SLBG1637V from Sigma A β1-42Preparation of (1) A β1-42Adding 0.1mg of the powder into 100 mu L of sterile normal saline, uniformly mixing, and incubating in a constant temperature oven at 37 ℃ for a week to obtain a condensed state; the concentration was 1. mu.g/. mu.L.
1.2 Experimental instruments
A mouse diving platform instrument with model ZXC-5Q, produced by equipment maintenance supply station of Shandong province medical science institute;
DW-2000 brain stereotaxic instrument, Chengdu Tai Union science and technology Co., Ltd;
morris Water maze, model WMT-100, produced by union science and technology, Inc.
1.3 subjects
The production certification number of the SPF-grade Kunming mouse and the SPF-grade SD rat is SCXK (No. Sichuan 2013-19), and is provided by the experimental animal center of the academy of traditional Chinese medicine and pharmacology of Sichuan province.
1.4 Experimental Environment
An SPF animal experiment barrier system of a research institute of pharmacology and toxicology of the academy of traditional Chinese medicine and sciences of Sichuan province has the indoor temperature of 20-22 ℃, the relative humidity of about 52 percent, the illumination for 12 hours and the brightness for 12 hours and the darkness for 12 hours. The certificate number is SYXK (Chuan) 2013-100. The water is freely drunk. The total nutrient granulated feed is provided by the laboratory animal center of the academy of traditional Chinese medicine and pharmacology of Sichuan province.
2, Experimental methods and results
2.1 influence of cnidium oil on mouse model of memory reproduction disorder caused by ethanol
The experimental method comprises the following steps: SPF-level Kunming mice with the weight of 18-22 g and half male and female are randomly divided into 10 groups according to the weight: control group, model group, memantine 10mg/kg, rhizoma Ligustici Chuanxiong oil I10 mg/kg, rhizoma Ligustici Chuanxiong oil 5mg/kg, rhizoma Ligustici Chuanxiong oil II 10mg/kg, rhizoma Ligustici Chuanxiong oil III 10mg/kg, rhizoma Ligustici oil III 5mg/kg, and ligustilide 10 mg/kg. The mice in each group were administered by intragastric administration in the afternoon according to the dose, 3 times continuously, and the control group and the model group were administered with the same volume of edible oil. Performing jump bench method training 50min after the last administration, putting the animal into a reaction box for adaptation for 3min, and immediately introducing 36V alternating current. Training for 5min, and recording the number of shocks received (number of errors) per mouse, thereby obtaining the learning performance. The test was carried out after 24h, 5min per mouse and 30min before the test, and the test was performed by molding each group except the control group with 40% ethanol 0.1ml/10 g. The test records the number of animals shocked and the latency to first jump off the platform and the number of errors within 5 min.
The results of this experiment were statistically analyzed and are shown in table 1.
Table 1 shows the effect of cnidium oil on mice with ethanol-induced memory disorder
Comparison with model groups:*P<0.05，**P<0.01，***P<0.001
as can be seen from Table 1, the mice molded by ethanol have memory reproduction disorder, the latency period of the mice in the model group is obviously shortened compared with that of the control group, the error times are obviously increased, and the statistical significance is realized when the model group is compared with the control group. Each sample of the ligusticum wallichii oil, the ligustilide and the memantine can obviously prolong the incubation period of the ethanol mice and reduce the error times, and has statistical difference compared with a model. The effect of the ligusticum wallichii oil is obviously better than that of ligustilide and memantine under the same dosage.
2.2 Effect of Ligusticum chuanxiong Hort oil on Long-term Low-perfusion vascular cognitive impairment in rats
The experimental method comprises the following steps: taking male rats with the weight of about 180-200 g, and randomly dividing the animals into a control group and a vascular cognitive disorder building group. After anaesthetizing, fixing the model-making rats, shaving the neck hairs, disinfecting with alcohol, cutting the neck skin under aseptic condition, carefully separating and ligating the bilateral common carotid arteries of the rats, suturing the skin, and after breeding normally for 1 month after disinfection, randomly dividing the model-making rats into model groups, namely 10mg/kg of memantine, 10mg/kg and 5mg/kg of ligusticum wallichii oil I, 10mg/kg and 5mg/kg of ligusticum wallichii oil II, 10mg/kg and 5mg/kg of ligusticum wallichii oil III and 10mg/kg of ligustilide. The administration was performed by gavage once a day for 4 weeks, and the model group and the control group were administered with an equal volume of edible oil. The Y maze experiment was performed 1 hour after the last dose. The rat is placed at the tail end of the Y maze arm to adapt for 3 minutes, the safety area is changed in a random order, the rat subjected to electric stimulation escapes to the safety area, the light stimulation is kept for 15 seconds, the rat is rested for 30 seconds after the light is turned off, 1 test is completed, and the arm where the rat is located serves as the starting point for the next test. This was repeated, 10 times per rat per day for one day. The test was carried out after 24 hours. Rats escape directly to the safe zone after receiving a shock as a correct response, otherwise as a false response. The correct and incorrect responses of the rats were recorded and the correct rate, i.e. the number of correct responses as a percentage of the total number tested, was calculated.
The results are shown in table 2:
table 2 shows the effect of cnidium oil on the behaviourology of Y maze in rat with long-term low-perfusion vascular cognitive impairment
Comparison with model groups:*P<0.05，**P<0.01，***P<0.001
as shown in Table 2, the learning accuracy and the memory accuracy of the rats were significantly reduced by the long-term low perfusion, which was statistically different from those of the control group. The learning accuracy and the memory accuracy of the rats with long-term low perfusion can be obviously improved by each sample of the ligusticum wallichii oil, the ligustilide and the memantine, and the statistical difference is compared with a model. The effect of the ligusticum wallichii oil is obviously better than that of ligustilide and memantine under the same dosage.
2.3 Effect of Ligusticum chuanxiong Hort oil on mice with vascular cognitive impairment caused by long-term low perfusion and beta-amyloid protein injection from Hippocampus
The experimental method comprises the steps of randomly dividing an SPF-grade Kunming male mouse into a control group and a vascular cognitive disorder mouse model building group by 18-22 g, injecting condensed A β in a cerebral hippocampus (3 mm behind bregma, 2mm on the right side of a midline and 2mm in depth as coordinates) of a dementia model building group by using a brain stereotaxic instrument after ligating common carotid arteries on both sides for 3 months in the model building mouse1-42Keeping the needle for 5min after 2 μ g/injection (injection time is 2min), slowly withdrawing the needle, injecting equal volume of normal saline into the control group, suturing wound after operation, injecting penicillin intramuscularly to prevent infection, injecting A β on the next day of injecting β -amyloid protein1-42The mice are randomly divided into a model group, 10mg/kg of memantine, 10mg/kg and 5mg/kg of ligusticum oil I, 10mg/kg and 5mg/kg of ligusticum oil II, 10mg/kg and 5mg/kg of ligusticum oil III and 10mg/kg of ligustilide. The administration was performed by gavage once a day for 4 weeks, and the model group and the control group were administered with an equal volume of 0.05% CMC-Na. Three weeks after dosing mice were tested for learning and memory using the Morris water maze procedure.
Morris water maze positioning navigation test: dividing the water pool into quadrants 1,2,3 and 4, placing the platform at a fixed position in a positioning navigation experiment and keeping the position unchanged, adding water into the water pool, keeping the water temperature at 22 +/-2 ℃, and adding a proper amount of milk powder to make the water pool become opaque white. Hiding the platform, enabling the water surface to submerge by 2cm, and recording the time required by the mouse from entering the water to finding the platform within 90s, namely the escape latency. The mice were allowed to find the platform within 90s and remain on the platform for 10s, if they failed to find the platform within 90s or did not climb up the platform, the mice were led to the platform and left for 10s, and the animals were trained 3 times a day for 3 consecutive days. The escape latency for each training of mice to find the platform was recorded, etc.
Morris water maze space exploration experiment: and (5) removing the platform 24h after the positioning navigation experiment is finished. And then, optionally selecting the same water inlet point, putting the animal into water, recording the swimming path, the effective region entering times and the like of the mouse, and performing data analysis by using WUDITAIN WMT-100Morris water maze video tracking system software.
The results are shown in tables 3 and 4:
table 3 shows that the chuanxiong rhizome oil is applied to mice with vascular cognitive impairment caused by long-term low perfusion and beta-amyloid protein injection from hippocampus
Influence of Morris water maze positioning navigation
Comparison with model groups:*P<0.05，**P<0.01，***P<0.001
as can be seen from Table 3, the long-term low perfusion plus beta-amyloid injection from the hippocampus can cause the incubation period of the mice in the Morris directional navigation experiment to be obviously prolonged, and compared with the control group, the incubation period is statistically different. Each sample of the ligusticum wallichii oil, the ligustilide and the memantine can obviously shorten the incubation period of mice injected with beta-amyloid protein by long-term low perfusion and hippocampi, and has statistical difference compared with a model. The effect of the ligusticum wallichii oil is obviously better than that of ligustilide and memantine under the same dosage.
Table 4 shows the effect of cnidium oil on the Morris water maze space exploration experiment of mice with vascular cognitive impairment caused by long-term low perfusion and β -amyloid protein injection from hippocampus
Comparison with model groups:*P<0.05，**P<0.01，***P<0.001
as can be seen from Table 4, the incubation period of the mice in the Morris space exploration experiment can be obviously prolonged by long-term low perfusion plus beta-amyloid injection from the hippocampus, the frequency of entering the escape platform area is obviously reduced, and the statistical difference is obtained compared with the control group. Each sample of the ligusticum wallichii oil, the ligustilide and the memantine can obviously shorten the incubation period of the mice and increase the times of entering an escape platform area, and compared with a model, the statistical difference exists. The effect of the ligusticum wallichii oil is obviously better than that of ligustilide and memantine under the same dosage.
N shown in tables 1 to 4 is the number of mice.
In conclusion, the ligusticum wallichii oil obtained from different ways has better prevention and treatment effects on vascular dementia animals, the effects of the ligusticum wallichii oil are obviously superior to those of similar products in the market, and the ligusticum wallichii oil has good development prospects.
Although the present invention has been described herein with reference to the illustrated embodiments thereof, which are intended to be preferred embodiments of the present invention, it is to be understood that the invention is not limited thereto, and that numerous other modifications and embodiments can be devised by those skilled in the art that will fall within the spirit and scope of the principles of this disclosure.
Claims (2)
1. The application of ligusticum oil with ligustilide mass percentage of 10-60% in preparing the medicine for preventing and treating vascular cognitive disorder is characterized in that the ligusticum oil is obtained by separating after extracting crushed ligusticum in a supercritical carbon dioxide circulation countercurrent mode, and the specific steps are as follows: under the conditions that the extraction pressure is 40MPa, the extraction temperature is 60 ℃, and the mass ratio of the rhizoma ligustici wallichii to the carbon dioxide used in each hour is 1: 10, performing supercritical carbon dioxide circulation countercurrent extraction under the condition that the extraction time is 5 hours; then separating at a separation temperature of 50 ℃ under a separation pressure of 10MPa in a separator to obtain the ligusticum wallichii oil.
2. The use as claimed in claim 1, wherein the ligustilide content of cnidium oil is 30-60% by weight.
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| CN1034911C (en) * | 1993-02-19 | 1997-05-21 | 田文 | Shixinling oral medicine and its preparation method |
| CN1291726C (en) * | 2002-07-19 | 2006-12-27 | 四川禾正制药有限责任公司 | Application of ligusticum oil in preparation of medicine for treating cerebral thrombosis |
| CN100404020C (en) * | 2003-06-11 | 2008-07-23 | 长春大政药业科技有限公司 | Chuanxiong rhizome volatile oil soft capsule and its preparation method |
| CN1321638C (en) * | 2003-08-18 | 2007-06-20 | 天津药物研究院 | Ligustilide oil and its preparation |
| CN100496482C (en) * | 2005-07-15 | 2009-06-10 | 钱忠明 | Application of ligustilide in preparation of medicine for preventing and treating cerebral ischemia diseases |
| CN100431575C (en) * | 2006-03-17 | 2008-11-12 | 四川省中药研究所 | Medicine composition for treating cardiac and cerebral vascular diseases |
| CN102295629B (en) * | 2011-07-01 | 2014-06-25 | 重庆工商大学 | Preparation method of ligustilide |
| CN102614234B (en) * | 2012-04-25 | 2013-08-14 | 湖南天济草堂制药有限公司 | Anti-stroke medicinal composition, tablet and preparation methods thereof |
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Non-Patent Citations (1)
| Title |
|---|
| 川芎、当归和藁本中挥发油成分比较研究;杨艳 等;《中药材》;20150630;第38卷(第6期);第1212-1216页 * |
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