New application of Jianjing bezoar heart-fire-clearing pill

Abstract

The invention relates to the technical field of traditional Chinese medicines, discloses a novel application of a Jianjing bezoar heart-fire clearing pill, and further discloses an application of the Jianjing bezoar heart-fire clearing pill in preparation of medicines for preventing and / or treating mild cognitive impairment. The invention provides the new application of the Jianjing bezoar heart-fire-clearing pill in the aspect of preventing and / or treating the mild cognitive impairment, the new application of the Jianjing bezoar heart-fire-clearing pill is expanded, safer and more effective treatment medicines and means are provided for clinical treatment of the mild cognitive impairment, and technical support can be provided for guiding clinical medication. Specifically, experiments find that the Jianjing bezoar heart-clearing pill can significantly improve the learning and memory ability of MCI model rats and reduce the expression level of AD7c-NTP (neurofilament protein) in the cerebrospinal fluid of the MCI model rats.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicines, and in particular to a new use of Tongren Niuhuang Qingxin Pills, and further to a use of Tongren Niuhuang Qingxin Pills in preparing a medicine for preventing and / or treating mild cognitive impairment. Background Art

[0002] Mild cognitive impairment (MCI) is an intermediate state between normal aging and clinical Alzheimer's disease, and is a syndrome of cognitive impairment. MCI patients have mild cognitive impairment (including memory and cognitive impairment), but their daily abilities are basically not significantly affected. MCI has a high risk of developing into Alzheimer's disease (AD). According to a meta-analysis of the prevalence of Alzheimer's disease in some populations around the world in recent years by the WHO, the prevalence of Alzheimer's disease in people over 60 years old in East Asia is between 0.7% and 28.7%, and increases with age. As a transitional stage before Alzheimer's disease, the prevalence of MCI in the elderly population over 65 years old is 3% to 19%, and the incidence rate is 5 to 58 cases per 1,000 person-years. Studies have shown that within a year, about 10% to 15% of MCI patients progress to AD patients, which is much higher than the normal population, and about 2 / 3 of AD patients progress from MCI patients. The damage caused by AD to the brain is irreversible, but there is currently no specific drug to treat AD.

[0003] Therefore, early detection, diagnosis and treatment of MCI, the precursor symptom of AD, are of great significance for delaying the transformation of MCI to AD and reducing the incidence of AD. Summary of the invention

[0004] In view of this, the present invention provides the use of Tongren Niuhuang Qingxin Pills in preparing a medicine for preventing and / or treating mild cognitive impairment.

[0005] In a first aspect, the present invention provides the use of Tongren Niuhuang Qingxin Pills in preparing a medicament for preventing and / or treating mild cognitive impairment.

[0006] The present invention provides a new use of Tongren Niuhuang Qingxin Pills in preventing and / or treating mild cognitive impairment, which not only expands the new use of Tongren Niuhuang Qingxin Pills, but also provides safer and more effective therapeutic drugs and means for the clinical treatment of mild cognitive impairment, and can provide technical support for guiding clinical medication. Specifically, it was found through experiments that Tongren Niuhuang Qingxin Pills can significantly improve the learning and memory ability of MCI model rats, and reduce the expression level of AD7c-NTP (neurofilament protein) in the cerebrospinal fluid of MCI model rats.

[0007] It should be noted that the Tongren Niuhuang Qingxin Pills described in the present invention are commercially available products, with the drug name: Tongren Niuhuang Qingxin Pills (Tongrentang); common name: Tongren Niuhuang Qingxin Pills; manufacturer: Tongrentang Pharmaceutical Factory of Beijing Tongrentang Co., Ltd.; main ingredients: 27 Chinese medicinal materials such as artificial bezoar, antelope horn, artificial musk, ginseng, Atractylodes macrocephala (fried with bran), angelica, white peony root, bupleurum, dried ginger, donkey-hide gelatin, platycodon, and buffalo horn concentrated powder; functions and indications: invigorating qi and nourishing blood, calming the mind, resolving phlegm and extinguishing wind. It is suitable for deficiency of qi and blood, phlegm-heat disturbance caused by: chest heat, palpitations, restlessness, dizziness, aphasia due to stroke, crooked mouth and eyes, hemiplegia, slurred speech, coma, and phlegm congestion.

[0008] In an optional embodiment, the use is for preparing a drug for preventing and / or treating vascular mild cognitive impairment.

[0009] In an optional embodiment, the use is for preparing a drug for improving the learning and memory ability of a subject with mild cognitive impairment.

[0010] In an optional embodiment, the use is use in preparing a drug for reducing the expression level of neurofilament protein in cerebrospinal fluid.

[0011] In a second aspect, the present invention provides a method for constructing an animal model of mild cognitive impairment, the method comprising: taking a test animal and blocking blood transmission in its bilateral common carotid arteries.

[0012] In a third aspect, the present invention provides an animal model of mild cognitive impairment, wherein the blood transmission of bilateral common carotid arteries in the animal model is in a blocked state.

[0013] In an optional embodiment, the animal model is a rat animal model.

[0014] In an optional embodiment, the animal model is a vascular mild cognitive impairment animal model.

[0015] The invention constructs a simple, economical, stable and reliable vascular MCI animal model by blocking bilateral common carotid arteries, and administers Tongren Niuhuang Qingxin Pills on this basis, and comprehensively evaluates the therapeutic effect of Tongren Niuhuang Qingxin Pills on vascular MCI by detecting the learning and memory indexes of the model animals and the neurofilament protein (AD7c-NTP) in the cerebrospinal fluid. DETAILED DESCRIPTION

[0016] The following examples are provided for a better understanding of the present invention, but are not intended to limit the best mode of implementation, nor to limit the content and protection scope of the present invention. Any product identical or similar to the present invention obtained by anyone under the inspiration of the present invention or by combining the features of the present invention with other prior arts shall fall within the protection scope of the present invention.

[0017] If no specific experimental steps or conditions are specified in the examples, the conventional experimental steps or conditions described in the literature in the field can be used. If no manufacturer is specified for the reagents or instruments used, they are all conventional reagent products that can be obtained commercially.

[0018] The present invention is further described in detail below in conjunction with specific embodiments. These embodiments should not be construed as limiting the scope of protection claimed by the present invention.

[0019] The Tongren Niuhuang Qingxin Pills used in the embodiments of the present invention were provided by Tongrentang Pharmaceutical Factory of Beijing Tongrentang Co., Ltd., with batch number: 19010324.

[0020] Example

[0021] This example is used to verify the therapeutic effect of Tongren Niuhuang Qingxin Pills on vascular MIC.

[0022] (1) Animal model construction

[0023] Wistar male rats (SPF grade, weight 180-200g) were randomly divided into a sham operation group and a modeling group after adaptive feeding. After anesthesia, the rats in the modeling group were separated from the common carotid arteries on both sides, and surgical sutures were placed to permanently ligate the common carotid arteries on both sides. The skin was sutured and the rats were returned to the cage for feeding after disinfection. The sham operation group only separated the common carotid arteries on both sides without ligation.

[0024] (2) Experimental drug administration

[0025] After the modeling, the modeling rats were randomly divided into model group, nimodipine group (12 mg / kg), Tongren Niuhuang Qingxin Pills high-dose group (2.4 g / kg), Tongren Niuhuang Qingxin Pills medium-dose group (1.2 g / kg), and Tongren Niuhuang Qingxin Pills low-dose group (0.6 g / kg), with 11 rats in each group. Each drug group was given the corresponding drug by gavage every day according to the dosage, once a day, for a total of 4 weeks. Morris water maze test was performed in the fourth week after administration to evaluate the effect of the drug on the behavior of vascular mild cognitive impairment model rats. After the last administration, the rats were anesthetized, cerebrospinal fluid was collected, and the expression level of rat neurofilament protein (AD7C-NTP) in the cerebrospinal fluid was determined.

[0026] (3) Experimental results

[0027] ① Water maze test results

[0028] The results of the water maze experiment are shown in Table 1. From the experimental results in Table 1, it can be seen that:

[0029] After modeling, the model group rats stayed in the test quadrant for a shorter time than the sham operation group, and the latency to reach the test quadrant was longer than that of the sham operation group, but there was no significant difference (p>0.05); the swimming path length and the number of crossing platforms of the model group rats in the test quadrant were significantly different from those of the sham operation group rats (p<0.05). It can be seen that the model construction method in this embodiment has obvious memory damage to rats, and the vascular mild cognitive impairment rat model was successfully constructed in this embodiment;

[0030] The high- and low-dose groups of Tongren Niuhuang Qingxin Pills can significantly increase the length of the swimming path of the model rats in the test quadrant, which is significantly different from the model group (all p<0.05); the high-dose group of Tongren Niuhuang Qingxin Pills can significantly increase the number of times the model rats cross the platform in the test quadrant, which is significantly different from the model group (all p<0.05). This shows that Tongren Niuhuang Qingxin Pills has a significant effect on improving the memory ability of rats with mild cognitive impairment caused by ischemia.

[0031] Table 1 Water maze test results (x±SD)

[0032]

[0033] Compared with the model group: *P<0.05. Special note: Some rats died during the experiment, and N in the table is the number of rats that finally survived in each experimental group.

[0034] ②Test results of neurofilament protein (AD7c-NTP) expression level in cerebrospinal fluid of rats with vascular MCI model

[0035] The test results of the expression level of neurofilament protein (AD7c-NTP) in the cerebrospinal fluid of vascular MCI model rats are shown in Table 2. From the experimental results in Table 2, it can be seen that:

[0036] The expression level of neurofilament protein (AD7c-NTP) in the cerebrospinal fluid of the model group rats was significantly increased, and there was a significant difference compared with the sham operation group (p<0.01), indicating that the model rats had neuronal or synaptic function degeneration, indicating that the model was successfully replicated;

[0037] The expression level of AD7c-NTP in the cerebrospinal fluid of rats in the high-dose and low-dose groups of Tongren Niuhuang Qingxin Pills was significantly reduced, which was significantly different from that in the model group (all p<0.01). This result shows that Tongren Niuhuang Qingxin Pills has a significant therapeutic effect on vascular MCI.

[0038] Table 2 Expression level of AD7c-NTP in cerebrospinal fluid (x±SD)

[0039]

[0040]

[0041] Compared with the model group: *P<0.05, **P<0.01. Special note: Some rats died during the experiment, and N in the table is the number of rats that finally survived in each experimental group.

[0042] In conclusion, Tongren Niuhuang Qingxin Pills can significantly improve the learning and memory abilities of model rats, reduce the expression level of AD7c-NTP in cerebrospinal fluid, and have a significant therapeutic effect on vascular MCI.

[0043] Obviously, the above embodiments are merely examples for the purpose of clear explanation, and are not intended to limit the implementation methods. For those skilled in the art, other different forms of changes or modifications can be made based on the above description. It is not necessary and impossible to list all the implementation methods here. The obvious changes or modifications derived therefrom are still within the scope of protection of the invention.

Claims

1. Use of Tongren Niuhuang Qingxin Pills in the preparation of a drug for preventing and / or treating mild cognitive impairment.

2. The use according to claim 1, characterized in that The use is use in preparing medicine for preventing and / or treating vascular mild cognitive impairment.

3. The use according to claim 1 or 2, characterized in that The use is use in preparing a medicine for improving the learning and memory ability of a subject with mild cognitive impairment.

4. The use according to any one of claims 1 to 3, characterized in that The use is use in preparing a drug for reducing the expression level of neurofilament protein in cerebrospinal fluid.

5. A method for constructing an animal model of mild cognitive impairment, characterized in that: The construction method comprises: taking a test animal and blocking blood transmission of its bilateral common carotid arteries.

6. A mild cognitive impairment animal model, characterized in that: The blood transmission of bilateral common carotid arteries in the animal model is in a blocked state.

7. The animal model according to claim 6, characterized in that: The animal model is a rat animal model.

8. The mild cognitive impairment animal model according to claim 6 or 7, characterized in that: The animal model is a vascular mild cognitive impairment animal model.

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