CN105943538A - Sobering medicinal composition, and preparation method and application thereof - Google Patents

Abstract

The invention discloses a pharmaceutical composition for awakening. The composition comprises the following components in parts by weight: 1-8 parts of ligustrazine and 0.5-5 parts of a-asarone. The composition of the invention has remarkable effects in treating vascular dementia, especially vascular senile dementia and cognitive impairment.

Description

A wake-up aiding pharmaceutical composition and its preparation method and application

technical field

The invention belongs to the technical field of traditional Chinese medicine, and in particular relates to a "wake-up" medicinal composition for neurodegenerative diseases and vascular senile dementia and a preparation method thereof.

Background technique

Vascular dementia (VD for short) is the second most common cause of dementia next to Alzheimer's disease in Europe and the United States, with a prevalence rate between 0.9% and 3.0%, accounting for about 10% to 50% of all dementias. %. In Asian developing countries such as Japan, South Korea, and India, the prevalence of VD is not different from that of Western countries, generally between 2.0-3.8%, but the ratio between VD and AD is different. Epidemiological studies have shown that, The incidence of VD increases linearly with age, and there are great differences between countries. After adjusting age and sex, the incidence rate of the elderly over 65 years old is 1.2-4.2%. /1000 people, the average course of disease is 5 years, and the survivors are lower than the general population and AD patients. The prevalence rate of VD in my country is about 1.1-3.0%, and the incidence rate is between 5-9 (cases)/1000 (persons). Accompanied by vascular dementia, or cognitive impairment, or cerebral infarction, has become one of the biggest diseases threatening human health.

At present, for this disease, the side effects of Western medicine are large, and there is a lack of effective and safe therapeutic drugs.

Contents of the invention

At present, for the α-asarone component, there are tablets on the market, which have the functions of relieving asthma, relieving cough, expectorant, sedative, antispasmodic, and anticonvulsant, and are mainly used for the treatment of chronic bronchitis. Ligustrazine has tablets and injections on the market, which are used for ischemic cerebrovascular diseases, such as cerebral infarction caused by cerebral insufficiency, cerebral thrombosis, and cerebral embolism.

The present invention mainly combines α-asarone and ligustrazine for the treatment of vascular dementia, especially the treatment of vascular senile dementia or cognitive impairment, which has remarkable curative effect.

The object of the present invention is to provide a pharmaceutical composition for awakening.

Another object of the present invention is to provide a preparation method of the pharmaceutical composition.

Another object of the present invention is to provide the application of the pharmaceutical composition in the preparation of medicines for treating vascular senile dementia, cognitive impairment or neurodegeneration.

The purpose of the present invention is achieved in the following manner:

A pharmaceutical composition for aiding in awakening, the composition comprises the following components in parts by weight:

Ligustrazine 1 to 8 parts, a-asarone 0.5 to 5 parts.

The above-mentioned composition preferably comprises the following components by weight:

Ligustrazine 1 to 4 parts, a-asarone 1 to 4 parts.

Said composition further preferably comprises the following components by weight:

Ligustrazine 1 to 2 parts, a-asarone 1 to 2 parts.

Above-mentioned composition most preferably comprises the component of following parts by weight to make:

Ligustrazine 1 part, a-asarone 1 part.

The composition is prepared into preparations with pharmaceutically acceptable auxiliary materials, and the preparations are preferably tablets, capsules, soft capsules, dropping pills or granules.

The above traditional Chinese medicine composition is prepared through the following steps: separately pulverize ligustrazine and α-asarone and mix them uniformly.

The application of the pharmaceutical composition of the invention in the preparation of medicines for treating vascular dementia has remarkable effects.

The pharmaceutical composition of the invention has remarkable effects in the preparation of medicines for treating memory impairment caused by vascular dementia.

The pharmaceutical composition of the invention has remarkable effects in the preparation of medicines for treating vascular senile dementia, cognitive impairment or neurodegeneration.

Compared with prior art, the beneficial effect of the present invention:

The present invention mainly combines α-asarone and ligustrazine for the treatment of vascular dementia, especially the treatment of vascular senile dementia or cognitive impairment has a remarkable effect.

The present invention is further described by drug effect test below:

Efficacy evaluation of each component of Chinese medicine compound CX on memory impairment mice caused by vascular dementia mice:

1 Experimental materials

1.1 Test drugs and reagents

CX components: CX1: α-asarone; CX2: ligustrazine; CX3: α-asarone + ligustrazine; CX4: Tongsai Yinao oral liquid.

CX1 (α-asarone): use physiological saline to prepare 700mg/10ml of α-asarone.

CX2 (Ligustrazine): Use normal saline to prepare 700mg/10ml of Ligustrazine.

CX3 (α-asarone + ligustrazine): use physiological saline to prepare the active ingredients α-asarone and ligustrazine (the weight ratio of the two is 1:1) at a concentration of 700mg/10ml, which is equivalent to containing asarum Brain 350mg, Ligustrazine 350mg.

CX4 (α-asarone + ligustrazine): Use physiological saline to prepare the active ingredients α-asarone and ligustrazine (the weight ratio of the two is 4:3) at a concentration of 700mg/10ml. Equivalent to asarone 400mg, ligustrazine 300mg

CX5 (α-asarone + ligustrazine): Use physiological saline to prepare the active ingredients α-asarone and ligustrazine (the weight ratio of the two is 3:4) at a concentration of 700mg/10ml. Equivalent to asarone 300mg, ligustrazine 400mg

CX6 (α-asarone + ligustrazine): Use physiological saline to prepare the active ingredients α-asarone and ligustrazine (the weight ratio of the two is 2.5:4.5) at a concentration of 700mg/10ml. Equivalent to asarone 250mg, ligustrazine 450mg

CX7 (α-asarone + ligustrazine): Use physiological saline to prepare the active ingredients α-asarone and ligustrazine (the weight ratio of the two is 4.5:2.5) at a concentration of 700mg/10ml. Equivalent to asarone 450mg, ligustrazine 250mg

CX8 Tongsai Yinao Oral Liquid (Lot No.: R20121001): Prepared with normal saline at a concentration of 700mg/10ml.

Chloral hydrate, A.R, Shanghai Wulian Chemical Factory, batch number: 20000218.

Sodium nitroprusside for injection, specification: 50mg/bottle, Beijing Shuanghe Modern Medical Technology Co., Ltd., batch number: 110820.

Oxiracetam (batch number: 20110901), all raw materials, white crystal-like powder, provided by Nanjing Youke Biomedical Co., Ltd.

1.2 Experimental animals and feeding conditions

Clean-grade ICR mice, male, weighing 18-22 g, certificate number: SCXK (Su) 2012-0004, were purchased from the Comparative Medicine Center of Yangzhou University, Jiangsu Province.

Before and after administration, the experimental mice were kept in separate cages in the Experimental Animal Center of Nanjing University of Traditional Chinese Medicine (experimental animal use license number: SYXK (Su) 2012-0042), and fed with full-price pellet feed (purchased from Qinglong Mountain Animals in Tangshan, Jiangning County). Breeding plant), free drinking water, room temperature 20±2°C, humidity 55-65%.

2 Experimental methods and results

2.1 Protective effect on vascular dementia induced by global cerebral ischemia-reperfusion in mice ^[1-3]

2.1.1 Experimental method

Before the test, the learning ability of the mice was tested using a platform tester, and mice with similar memory abilities were selected. After being anesthetized with 10% chloral hydrate (125 mg/kg), the mice were fixed on the mouse board in a supine position. Disinfect the skin of the neck with povidone iodine, make an incision along the middle of the neck, and bluntly dissect the neck muscles to expose the bilateral common carotid arteries (CCA). The silk thread was passed under the common carotid artery, and sodium nitroprusside (dissolved in normal saline, at a dose of 2.5 mg/kg) was injected intraperitoneally to cause hypotension, and then the bilateral common carotid arteries were clamped with noninvasive arterial clips for 10 minutes, and then released for 10 minutes. Repeat 3 times. In the sham operation, only the bilateral CCAs were separated without clipping or injection of sodium nitroprusside. Postoperative intramuscular injection of penicillin 02,000 U/cause for 3 consecutive days.

2.1.2 Grouping and administration

Mice were given different concentrations of drugs by intragastric administration, with a volume of 10ml/kg. The sham operation group and the model group were given the same amount of normal saline. 200 mice successfully modeled were randomly divided into 6 groups, i.e. model group, CX1～CX4 group (700mg/kg), oxiracetam positive group (600mg/kg), plus sham operation group (10 mice ) a total of 7 groups. The mice in each group were intragastrically administered with drugs of corresponding concentration, and the injection volume was 10 ml/kg. The sham operation group and the model group were given the same amount of normal saline. Dosing once a day in the morning for 2 weeks.

2.1.3 Determination of learning and memory ability of mice

2.1.3.1 Passive avoidance conditioned reflex-platform jumping test started training test 0.5h after administration every day. During training, the mice were put into the platform test box to adapt to it for 5 minutes, and then energized. When the mice received the electric shock, they could jump back to the platform to avoid the electric shock. Most of the animals could jump up and down the platform again or several times. The second time the mouse jumped off the platform was recorded as the first error. The training time is 3 minutes, and the number of errors within 3 minutes is recorded. After 24 hours, the memory test was carried out, and the mice were directly placed on the safety platform and powered on, and the time the mice stayed on the platform (ie, the latency period) and the number of wrong responses within 3 minutes were recorded.

2.1.3.2 Passive avoidance conditioned reflex-darkness avoidance experiment The training test started 0.5h after administration every day. During training, the mice were placed in the bright chamber with their heads facing the chamber wall, and the latency period of the mice receiving the first electric shock was recorded. After 24 hours, record the incubation period of entering the dark room and the number of errors in entering the dark room and receiving electric shocks within 5 minutes.

2.1.3.3 Active avoidance conditioned reflex-Y-type electric maze training test started 0.5h after administration every day. In a quiet dark room, put the mice into the maze for 5 minutes to adapt, randomly determine the safe zone, and use a Y-shaped power-on radial maze to determine the correct response (the mouse escapes into the safe zone after the light is on), otherwise it is a wrong response . 9 out of 10 consecutive times are correct in order to meet the learning standard, record the number of training required to reach the standard. The same method was tested for 24 hours, and each mouse was subjected to 10 electric shock changes, and the correct number of times was recorded (escape into the safe area after the light was turned on). Calculate the correct rate to evaluate the animal's 24-hour memory retention rate.

Correct rate = correct times/10×100%

2.1.3.4 Spatial Learning and Memory Ability--Morris Water Maze Experiment

Positioning and navigation experiment: training is carried out after administration every day, once in the morning and once in the afternoon, and lasts for 3 days. Put the mouse facing the pool wall, put it into the water from the fixed entry point in the diagonal quadrant of the platform, record the time to find the platform within 120s, if it fails to find the platform, lead it to stay on it for 10s, and then put it back into the cage, the incubation period is recorded as 120s.

Space exploration experiment: 24 hours after the positioning navigation experiment, move out of the platform, still fix the water entry point from the diagonal quadrant of the platform, put the mouse into the water facing the pool wall, and record the number of times the mouse crosses the original platform position within 120s to measure the mouse’s response to the water maze. The ability to acquire memory.

2.1.4 Experimental results

2.1.4.1 The results of platform jumping test in vascular dementia model mice showed that the CX3-CX7 group could reduce the number of learning errors of the model mice and prolong the memory latency of the model mice, which was significantly different from the model group (P<0.05). The results are shown in Table 1.

Table 1 Effect of each component of CX on learning and memory of cerebral ischemia-reperfusion mice (stepping method) ( n=9～10)

Note: Compared with the model group, ^▲ P＜0.05;

2.1.4.2 The results of vascular dementia model mice avoiding the dark test showed that: CX3, CX4, CX7 can significantly prolong the memory latency of the model mice and reduce the number of mistakes within 5 minutes, and the difference is significant compared with the model group (P<0.05, P< 0.01). The results are shown in Table 2.

Table 2 Effects of CX components on learning and memory in mice with cerebral ischemia-reperfusion (avoiding the dark) ( 9～10)

Note: Compared with the model group, ^▲ P＜0.05, ^▲▲ P＜0.01;

2.1.4.3 The results of the Morris water maze experiment on vascular dementia model mice showed that: CX3-CX6 can significantly increase the number of crossing times of the original platform in the space exploration experiment, and the difference is significant compared with the model group (P<0.05). The results are shown in Table 3.

Table 3 Effects of CX components on learning and memory in mice with cerebral ischemia-reperfusion (Morris water maze) ( 9～10)

Note: Compared with the model group, ^▲ P＜0.05, ^▲▲ P＜0.01;

3. Summary of results

The main pharmacodynamic test results show that:

The results of platform jumping test showed that the CX3-CX7 group could reduce the number of learning errors of the model mice and prolong the memory latency of the model mice, which was significantly different from the model group (P<0.05).

The results of the dark avoidance experiment showed that the CX3, CX4, and CX7 groups could significantly prolong the memory latency of the model mice and reduce the number of mistakes, which were significantly different from the model group (P<0.05, P<0.01).

The results of the Morris water maze experiment showed that: CX3-CX6 can significantly increase the number of crossing times of the original platform in the space exploration experiment, and the difference is significant compared with the model group (P<0.05).

The above results suggest that: CX3-CX7 components can significantly enhance the passive and active avoidance conditioned reflexes and spatial learning and memory abilities of vascular dementia model animals.

detailed description

The present invention is further elaborated below by specific examples.

Example 1

Take 100 parts by weight of ligustrazine and 100 parts by weight of a-asarone, pulverize them respectively and mix them uniformly to make a powder.

Example 2

Take 100 parts by weight of ligustrazine and 50 parts by weight of a-asarone, grind them separately, mix them uniformly with pharmaceutically acceptable auxiliary materials, and make granules.

Example 3

Take 100 parts by weight of ligustrazine and 500 parts by weight of α-asarone, pulverize them respectively, mix them uniformly with pharmaceutically acceptable auxiliary materials, and make tablets.

references

[1] Wang Beiying, Li Yikui. Research and development technology and method of new traditional Chinese medicine, Shanghai Science and Technology Press, 2001: 647-649.

[2] Zhang Juntian. The Second Volume of Modern Pharmacological Experimental Methods, Beijing Medical University and China Union Medical University Press, 1998: 1216-1217.

[3] Xu Shuyun. Pharmacological Experimental Methodology, People's Health Publishing House, 1991: 854-859

[4] Wang Hongli, Xue Lijun, Wan Dong, et al. Catalpol improves learning and memory impairment induced by scopolamine and its mechanism. Chinese Pharmacology Bulletin, 2011; 27(9): 1272-5.

Claims (10)

1. one kind is used for helping awake pharmaceutical composition, it is characterised in that said composition includes that the component of following weight portion is made: ligustrazine 1～8 parts, a-asarone 0.5～5 parts.

Pharmaceutical composition the most according to claim 1, it is characterised in that said composition includes that the component of following weight portion is made: ligustrazine 1～4 parts, a-asarone 1～4 parts.

Pharmaceutical composition the most according to claim 2, it is characterised in that said composition includes that the component of following weight portion is made: ligustrazine 1～2 parts, a-asarone 1～2 parts.

Pharmaceutical composition the most according to claim 2, it is characterised in that said composition includes that the component of following weight portion is made: ligustrazine 1 part, a-asarone 1 part.

5. according to the pharmaceutical composition described in claim 1,2,3 or 4, it is characterised in that preparation made by said composition and pharmaceutically acceptable adjuvant.

6. according to the pharmaceutical composition described in claim 1,2,3 or 4, it is characterised in that described preparation is tablet, capsule, soft capsule, drop pill or granule.

7. according to the pharmaceutical composition described in claim 1,2,3 or 4, it is characterised in that this Chinese medicine composition prepares through the following steps: mix homogeneously after ligustrazine and a-asarone are pulverized respectively.

8. the application in the medicine of preparation treatment vascular dementia of the pharmaceutical composition described in claim 1,2,3 or 4.

9. the application in dysmnesia medicine caused by preparation treatment vascular dementia of the pharmaceutical composition described in claim 1,2,3 or 4.

10. the application in the medicine of preparation treatment vascular senile dementia, cognitive competence damage or nerve retrograde affection of the pharmaceutical composition described in claim 1,2,3 or 4.