Traditional Chinese medicine composition for treating cognitive impairment

Abstract

The invention discloses a traditional Chinese medicine composition for treating cognitive impairment. The traditional Chinese medicine composition is prepared from the following raw material medicines in parts by weight: 2-5 parts of ginseng, 6-10 parts of astragalus membranaceus, 2-5 parts of angelica sinensis, 2-5 parts of bighead atractylodes rhizome, 3-7 parts of ligusticum wallichii, 1-4 parts of polygala tenuifolia, 2-5 parts of rhizoma acori graminei, 1-4 parts of earthworm, 0.5-2.5 parts of leech and 3-7 parts of kudzu vine root. The traditional Chinese medicine composition has a good effect on treating cognitive impairment diseases such as vascular cognitive impairment, Alzheimer's disease and the like with symptoms such as learning and memory deterioration, amnesia, slow response and the like caused by adverse spirit and machine due to insufficiency of qi and blood, internal resistance of phlegm and blood stasis and brain halfway disharmony.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine preparations, and specifically relates to a traditional Chinese medicine composition for treating cognitive impairment. Background Technology

[0002] Cognitive impairment (CI) refers to damage to one or more cognitive functions, such as speech, learning, memory, executive function, visuospatial function, and reasoning, leading to abnormalities in the brain's higher-level intelligent processing. Cognitive impairment-related diseases range from mild cognitive impairment (MCI) to various degrees and types of cognitive impairment, and it has now become the fourth leading cause of disease threatening the health of the elderly, after stroke, cardiovascular disease, and cancer.

[0003] Alzheimer's disease (AD) is the most common cause, accounting for 70-80% of all cases. The prevalence increases with age, roughly doubling every 5 years: <65 years old 4%, 65-74 years old 15%, 75-84 years old 44%, and ≥85 years old 58%. Vascular cognitive impairment (VCI) is the second most common cause, accounting for 15-20%. These two are the most common types of cognitive impairment in the elderly, characterized by high incidence, high disability rate, high mortality rate, and a trend towards affecting younger people. They place a heavy economic burden on patients, their families, and society.

[0004] The core pathological features of Alzheimer's disease (AD) include the deposition of β-amyloid (Aβ), hyperphosphorylation of tau protein, and the formation of neurofibrillary tangles (NFTs). In addition, neuroinflammation, oxidative stress, and gut microbiota dysbiosis are also important driving factors for AD. Currently, acetylcholinesterase (AChE) inhibitors and N-methyl-D-aspartate receptor (NMDAR) blockers are mainly used clinically. However, these have single targets and cannot improve the systemic causes of Alzheimer's disease, are insufficient to reverse the disease course, and both can cause gastrointestinal side effects. Long-term use can lead to drug resistance and mental health problems. For ventricular insufficiency (VCI), there is currently no definitive recommended treatment; treatment remains primarily focused on secondary prevention of cerebrovascular diseases and symptomatic treatment. Traditional Chinese medicine (TCM) has advantages in treating complex diseases due to its multi-target and multi-pathway effects. Increasing research focuses on the treatment of cognitive impairment with TCM formulas such as Xiaoyao San and Congrong San. However, the efficacy of these TCM formulas varies significantly among individuals, and some patients have experienced adverse reactions such as palpitations, diarrhea, and skin itching. Patent CN 101757573 B discloses a drug for treating memory decline. Although it has shown good memory-improving effects in clinical practice, its composition is complex, containing as many as 50 kinds of Chinese herbal raw materials. The numerous components make quality control difficult, resulting in high costs for patients. This complexity also leads to low international acceptance and hinders its widespread market application. Therefore, it is necessary to provide a Chinese herbal formula with a simpler composition, clearer pharmacology, lower cost, and easier clinical application. Summary of the Invention

[0005] To achieve the above objectives, the present invention provides a traditional Chinese medicine composition for treating cognitive impairment, which is prepared from raw materials comprising the following parts by weight:

[0006] Ginseng 2-5 parts, Astragalus 6-10 parts, Angelica sinensis 2-5 parts, Atractylodes macrocephala 2-5 parts, Ligusticum chuanxiong 3-7 parts, Polygala tenuifolia 1-4 parts, Acorus tatarinowii 2-5 parts, Pheretima aspergillum 1-4 parts, Hirudo medicinalis 0.5-2.5 parts, Pueraria lobata 3-7 parts.

[0007] Furthermore, it is prepared from the following active pharmaceutical ingredient in parts by weight:

[0008] Ginseng 3 parts, Astragalus 8 parts, Angelica sinensis 3 parts, Atractylodes macrocephala 3 parts, Ligusticum chuanxiong 5 parts, Polygala tenuifolia 3 parts, Acorus tatarinowii 3 parts, Pheretima aspergillum 2 parts, Hirudo medicinalis 1 part, Pueraria lobata 5 parts.

[0009] Furthermore, the Atractylodes macrocephala mentioned is stir-fried Atractylodes macrocephala.

[0010] Furthermore, it is a formulation prepared by adding pharmaceutically acceptable excipients to a powdered active pharmaceutical ingredient or an aqueous or organic solvent extract of the active pharmaceutical ingredient.

[0011] Furthermore, the formulation is an oral formulation; the oral formulation includes solutions, granules, pills, powders, ointments, or tablets.

[0012] The present invention also provides a method for preparing the aforementioned traditional Chinese medicine composition, which includes the following steps:

[0013] (1) Weigh the raw materials according to the aforementioned proportions;

[0014] (2) The active pharmaceutical ingredient is ground into powder, or the active pharmaceutical ingredient is extracted with water or organic solvent, and then excipients or auxiliary ingredients commonly used in pharmaceuticals are added to obtain the product.

[0015] Finally, this invention provides the use of the aforementioned traditional Chinese medicine composition in the preparation of a medicament for treating cognitive impairment.

[0016] Furthermore, the drug is a treatment for Alzheimer's disease.

[0017] Furthermore, the drug is a drug that improves memory, cognition, and / or learning abilities.

[0018] Furthermore, the drug is a drug for improving memory acquisition and memory retrieval disorders.

[0019] In this invention, ginseng and astragalus are the principal herbs in the herbal composition: they greatly replenish vital energy, and when vital energy is abundant, blood flows smoothly, and blood stasis is eliminated without harming the body's vital energy. The intention is to replenish while simultaneously attacking. "When blood and qi are not in harmony, all kinds of diseases will arise. The normal functioning of qi mechanism cannot be separated from the nourishment of qi, blood and body fluids. When qi is deficient and blood is stagnant, qi and blood are blocked, then the xuanfu (a point on the body's internal organs) will be blocked, and the function of the xuanfu will be disordered. Only when there is a foundation of qi and blood can the 'spirit' be generated. Therefore, astragalus and ginseng are used as the principal herbs to greatly replenish vital energy.

[0020] Chuanxiong, Danggui, stir-fried Baizhu, and Yuanzhi are the assistant herbs: Chuanxiong is pungent and aromatic, and is a "qi-regulating herb in the blood". It ascends to the top of the head and descends to the blood sea, promoting qi and blood circulation; Danggui nourishes and harmonizes the blood; stir-fried Baizhu strengthens the spleen to provide the source of qi and blood production, and also prevents phlegm from being generated; Yuanzhi resolves phlegm and opens the orifices.

[0021] Earthworm and leech are used as adjuvant medicines: leech removes blood stasis without harming the body's vital energy; earthworm moves freely and promotes circulation, calms wind; it invigorates blood, removes blood stasis, and regulates qi and blood.

[0022] Kudzu root and Acorus tatarinowii are used as guiding herbs: Kudzu root is sweet, cool, pungent and moistening. It is used to treat the obstruction of the five sense organs in the head, face and other parts of the body. It is light and dispersing, opens the mind and reaches the spirit, and restores the proper opening and closing of the brain. Acorus tatarinowii is pungent and warm. It is aromatic and can resolve phlegm and guide other herbs into the brain. It is pungent and fragrant. It can resolve phlegm and calm the mind and improve intelligence. It can "open the heart orifices and benefit the nine orifices", and "use it to clear the knots in the mind and connect with the spirit".

[0023] This formula is both effective in clearing and tonifying, without causing stagnation, working together to invigorate qi, resolve phlegm, promote blood circulation, clear the meridians, and improve intelligence. It is well-suited for treating vascular cognitive impairments such as memory loss, forgetfulness, and slow reaction time caused by qi and blood deficiency, phlegm and blood stasis obstructing the brain, and disharmony of the brain's internal organs, leading to impaired mental function. It is also effective for treating cognitive impairments such as Alzheimer's disease.

[0024] Animal experiments have demonstrated that the herbal composition of this invention can significantly prolong the latency of jumping off the platform in mice with scopolamine-induced memory acquisition impairment; significantly prolong the latency of jumping off the platform in mice with ethanol-induced memory retrieval impairment, and reduce the number of incorrect jumps off the platform; shorten the latency of orientation navigation and platform finding in rats with Aβ+LPS-induced learning impairment, and increase the distance traveled in the water maze, the number of times the platform is crossed, the number of times the platform is crossed in the quadrant, and the time spent in the quadrant where the platform is located.

[0025] The scopolamine-induced memory acquisition impairment model is a model that simulates some early cognitive impairment characteristics of Alzheimer's disease; the ethanol-induced mouse memory retrieval impairment model is also considered a model that can partially simulate Alzheimer's disease; the cognitive dysfunction model constructed by the combination of Aβ (amyloid-β) and LPS (lipopolysaccharide) is mainly used to study Alzheimer's disease. The herbal composition of this invention, acting on each of the three models, showed good efficacy, specifically improving the memory acquisition and memory retrieval impairment models; it also had a certain improving effect on the learning and memory impairment caused by the combined factors of Aβ and LPS. The herbal composition of this invention has broad application prospects for the treatment of AD.

[0026] Obviously, based on the above description of the present invention, and according to common technical knowledge and conventional methods in the field, various other modifications, substitutions or alterations can be made without departing from the basic technical concept of the present invention.

[0027] The following detailed embodiments further illustrate the above-described content of the present invention. However, this should not be construed as limiting the scope of the present invention to the following examples. All technologies implemented based on the above-described content of the present invention fall within the scope of the present invention. Attached Figure Description

[0028] Figure 1 Effects of Shenxiong Yizhi Pill on the pathological damage of Aβ+LPS-induced hippocampal tissue in rats (HE×40, black arrows represent tissue necrosis and inflammatory cell infiltration lesions; A: normal group; B: model group; C: donepezil; D: Shenxiong Yizhi Pill 2.4g / kg; E: Shenxiong Yizhi Pill 2.4g / kg; F: Shenxiong Yizhi Pill 2.4g / kg) Detailed Implementation

[0029] The raw materials and equipment used in the specific embodiments of the present invention are all known products and are obtained by purchasing commercially available products. The preparation process of modern Chinese medicine preparations made from the Chinese medicine composition of the present invention is mature and can be prepared by referring to conventional methods in the prior art.

[0030] Example 1: Preparation of the drug of the present invention

[0031] Formula: Ginseng 3g, Astragalus 8g, Angelica sinensis 3g, stir-fried Atractylodes macrocephala 3g, Ligusticum chuanxiong 5g, Polygala tenuifolia 3g, Acorus tatarinowii 3g, earthworm 2g, leech 1g, kudzu root 5g;

[0032] Preparation method: Weigh the above raw materials according to the ratio, add 300ml of water and decoct for 20-30 minutes, filter, concentrate the filtrate, and add pharmaceutically acceptable excipients to make pills.

[0033] Example 2: Preparation of the drug of the present invention

[0034] Formula: Ginseng 5g, Astragalus 10g, Angelica sinensis 5g, stir-fried Atractylodes macrocephala 5g, Ligusticum chuanxiong 7g, Polygala tenuifolia 4g, Acorus tatarinowii 5g, Pheretima aspergillum 4g, Hirudo medicinalis 2.5g, Pueraria lobata 7g;

[0035] Preparation method: Weigh the above raw materials according to the ratio, add 300ml of water and decoct for 20-30 minutes, filter, concentrate the filtrate, and add pharmaceutically acceptable excipients to make granules.

[0036] Example 3: Preparation of the drug of the present invention

[0037] Formula: Ginseng 2g, Astragalus 6g, Angelica sinensis 2g, stir-fried Atractylodes macrocephala 2g, Ligusticum chuanxiong 3g, Polygala tenuifolia 1g, Acorus tatarinowii 2g, Pheretima aspergillum 1g, Hirudo medicinalis 0.5g, Pueraria lobata 3g.

[0038] Preparation method: Weigh the above raw materials according to the ratio, add 300ml of water and decoct for 20-30 minutes, filter, concentrate the filtrate, and add pharmaceutically acceptable excipients to make tablets.

[0039] The following experimental examples illustrate the beneficial effects of the present invention.

[0040] Experimental Example 1: Pharmacodynamic Study of the Ginseng and Ligusticum chuanxiong Yizhi Pill of the Present Invention

[0041] 1. Experimental Materials

[0042] 1.1 Drugs and Reagents

[0043] Ginseng and Ligusticum striatum pills: The pills prepared according to Example 1 were ground into powder, appearing as a brownish-gray powder. 1g of powder is equivalent to 1.43g of raw herb. Southwest Medical University Affiliated Traditional Chinese Medicine Hospital, batch number: 20241111. The dosage in this experiment was calculated based on raw herb g / kg. Before use, add 0.5% CMC-Na solution and grind thoroughly until homogeneous, preparing a suspension of the appropriate concentration for later use.

[0044] Piracetam tablets: 0.4g / tablet, batch number: 6230420, Northeast Pharmaceutical Group Shenyang First Pharmaceutical Co., Ltd. Before use, grind thoroughly with 0.5% CMC-Na solution to prepare a suspension of the appropriate concentration.

[0045] Scopolamine hydrobromide: 50mg / vial; Batch No.: S2250805; Selleck Biotechnology Co., Ltd. Prepare with physiological saline before use.

[0046] Donepezil hydrochloride tablets: 5mg / tablet, batch number: 2207092, Eisai (China) Pharmaceutical Co., Ltd. Before use, grind thoroughly with 0.5% CMC-Na solution to prepare a suspension of the appropriate concentration.

[0047] Anhydrous ethanol: 500mL / bottle, batch number: 20231106; Chengdu Changlian Chemical Reagent Co., Ltd.

[0048] Sodium chloride injection: 250mL / bottle, batch number: N24070220, Sichuan Kelun Pharmaceutical Co., Ltd.

[0049] β-Amyloid peptide 1-42 (Aβ1-42): 1 mg / vial, batch number: N11IS231984, Shanghai Yuanye Biotechnology Co., Ltd. Add physiological saline for injection to Aβ powder to prepare a 2 μg / μL solution, incubate at 37℃ for 7 days, and use later.

[0050] Lipopolysaccharide (LPS): L2880-100MG, batch number: 0000189842, Escherichia coli O55:B5, SIGMA.

[0051] Add 1 mg LPS to 500 μL of Aβ solution, which is 2 μg / μL.

[0052] Rat Tumor Necrosis Factor-Tumor (TNF-α) ELISA Kit: Batch No.: A16036661, Wuhan Huamei Biotechnology Co., Ltd.

[0053] Rat Interleukin-6 (IL-6) ELISA Kit: Batch No.: A09036662, Wuhan Huamei Biotechnology Co., Ltd.

[0054] 1.2 Animals

[0055] C57BL / 6 mice and SD rats, both of SPF grade, were provided by Sichuan Viton Laboratory Animal Technology Co., Ltd. The animal certificate number is: SCXK(Sichuan) 2024-0040. The ethical resolution number for animal experiments is: DWSYLL-2024-195.

[0056] 1.3 Main instruments

[0057] SDT-8X Mouse Step-Down Test Video Analysis System, Chengdu Taimeng Technology Co., Ltd.

[0058] ST-120 Animal Behavior Stimulator, Chengdu Taimeng Technology Co., Ltd.

[0059] Microplate Reader, VARIOSKAN FLASH, Thermo

[0060] JA1003A Electronic Analytical Balance, d = 1mg, e = 10d, Shanghai Jingtian Electronic Instrument Co., Ltd.

[0061] Desktop Centrifuge, TD5Z, Hunan Kaida Scientific Instrument Co., Ltd.

[0062] CX21FS1C Biological Microscope, Olympus (Guangzhou) Industrial Co., Ltd.

[0063] Brain Stereotaxic Instrument, Sichuan Reword Life Science and Technology Co., Ltd.

[0064] Mouse and Rat Water Maze, EV-RMWM-SYS, Shanghai Fanbi Intelligent Technology Co., Ltd. ​​​​​​​​​​​​​​​​​​​​​Sixty male C57BL / 6 mice weighing 18-22g were randomly divided into four groups: a normal group, a model group, and four other groups (n=10 each): donepezil 2mg / kg, Shenxiong Yizhi Wan 3.0g / kg, Shenxiong Yizhi Wan 6.0g / kg, and Shenxiong Yizhi Wan 12.0g / kg. Except for the normal and model groups, which were administered an equal volume of 0.5% CMC-Na solution by gavage, the other groups were administered the corresponding drugs by gavage once daily for 7 days. On day 6, 30 minutes after administration, except for the normal group which received an intraperitoneal injection of saline, the experimental groups received an intraperitoneal injection of scopolamine hydrobromide 3mg / kg. Twenty minutes later, the mice underwent jumping training. They were placed in a reaction chamber for 3 minutes to acclimatize, then powered by a 36V AC power source for 5 minutes before being returned to their cages. Thirty minutes after administration on day 7, mice were gently placed on a platform with the bottom copper grid electrified. The time from when the mouse was placed on the platform to when it jumped off for the first time was recorded as the latency period and the number of errors within 5 minutes were recorded as memory scores. The results were then statistically analyzed.

[0072] Table 1. Effects of Shenxiong Yizhi Pill on Scopolamine-Induced Memory Acquisition Impairment in Mice (n=10, )

[0073]

[0074] Compared with the model group, *p<0.05, the same applies below.

[0075] As shown in Table 1, 6.0 g / kg of raw Ginseng and Ligusticum striatum pills significantly prolonged the latency period for mice to jump off the platform, showing a statistically significant difference compared with the model group.

[0076] 4.2 Effects of Shenxiong Yizhi Pills on Ethanol-Induced Memory Retrieval Impairment in Mice

[0077] Sixty male C57BL / 6 mice weighing 18-22g were randomly divided into four groups: a normal control group, a model group, and four other groups (n=10 each): a piracetam group (0.6g / kg), a Shenxiong Yizhi Wan group (3.0g / kg), a Shenxiong Yizhi Wan group (6.0g / kg), and a Shenxiong Yizhi Wan group (12.0g / kg). Except for the normal control and model groups, which were administered an equal volume of 0.5% CMC-Na solution via gavage, the other groups were administered the corresponding drugs via gavage once daily for 7 consecutive days. One hour after administration on day 6, acclimatization training was initiated. The mice were placed on a jumping platform for 3 minutes, followed by a 36V AC power supply for 5 minutes, after which they were removed and returned to their cages. Thirty minutes after administration on day 7, each animal in the model group and the drug administration group was given 10 mL / kg of 40% ethanol solution by gavage. Thirty minutes later, the mice were placed on the platform of the jumping device, and the copper grid at the bottom was energized. The time from when the mouse was placed on the platform to the first jump was recorded as the latency period, and the number of errors within 5 minutes was recorded as the memory score. Statistical analysis was then performed.

[0078] Table 2. Effects of Shenxiong Yizhi Pills on Ethanol-Induced Memory Retrieval Impairment in Mice (n=10, )

[0079]

[0080] Compared with the model group, **p<0.01, the same applies below.

[0081] As shown in Table 2, 6.0 g / kg and 12.0 g / kg of raw Ginseng and Ligusticum striatum pills significantly prolonged the latency period for mice to jump off the platform; 12.0 g / kg of raw Ginseng and Ligusticum striatum pills also significantly reduced the number of errors in jumping off the platform, which was statistically different from the model group.

[0082] 4.3 Effects of Shenxiong Yizhi Pill on Aβ+LPS-induced Learning Impairment in Rats

[0083] Seventy male SD rats weighing 180-200g were fasted for 12 hours before modeling, but allowed free access to water. After anesthesia, the rats' heads were fixed on a stereotaxic apparatus, and the apparatus was adjusted to ensure the rats' heads were horizontal. The apparatus was disinfected with iodine, and the scalp was cut open to expose the skull. Using the anterior fontanelle as the zero point, small holes were drilled 3.5mm posterior to the anterior fontanelle and 2.0mm lateral to the midline on either side using a skull drill. A syringe was inserted vertically 3.5mm into the hippocampus, and 5μL of a solution containing 2μg / μL Aβ and 2μg / μL LPS was injected bilaterally over 5 minutes. To ensure sufficient diffusion of the solution, the injection was allowed to remain for 3 minutes after injection before the needle was slowly withdrawn. The wounds were sutured, disinfected, and each rat was given an intraperitoneal injection of 100,000 U of penicillin for 3 consecutive days. Ten normal rats were injected bilaterally with an equal volume of sodium chloride injection. The day after surgery, the rats were randomly divided into a model group, a donepezil hydrochloride group (1.6 mg / kg), a Shenxiong Yizhi Wan (2.4 g / kg), a Shenxiong Yizhi Wan group (4.8 g / kg), and a Shenxiong Yizhi Wan group (9.6 g / kg), respectively, and administered the corresponding drugs by gavage. The model group and normal group were administered an equal volume of 0.5% CMC-Na solution by gavage once daily for 7 consecutive days. On the fourth day of administration, the Morris water maze was used to assess their learning and memory abilities. At the end of the experiment, the animals were anesthetized and euthanized. One hippocampal tissue was fixed for pathological examination. Based on references and the actual situation of this experiment, "necrosis of the hippocampus and parahippocampal brain tissue with inflammatory cell infiltration" was proposed as the detection index. The degree of lesion was scored semi-quantitatively, and the diagnostic criteria are shown in Table 3. The other hippocampus was used to detect memory-related inflammatory factors TNF-α and IL-6.

[0084] Table 3. Histological Grading and Diagnostic Criteria for Hippocampal Injury

[0085]

[0086] Morris water maze navigation experiment: The pool was divided into four quadrants (1, 2, 3, and 4). A safety platform was placed in one of the quadrants. The water temperature was 22±2℃, and the water level was 1 cm above the platform. The time it took for the rat to find the platform after entering the water within 90 seconds was recorded; this was the escape latency. If the rat failed to find the platform or climb onto it within 90 seconds, it was guided to stay on the platform for approximately 10 seconds. This training was repeated for 3 consecutive days. The escape latency of the rats during the training period was recorded.

[0087] Morris water maze spatial exploration experiment: 24 hours after training, the safety platform was removed. During the test, the animals were placed in the pool at a location other than the training location. The swimming time of the animals after entering the water was limited to 60 seconds. The behavior of the rats was analyzed using a data acquisition system.

[0088] Table 4 shows that the latency to find the platform during orientation navigation tests was significantly prolonged after rats were injected with Aβ+LPS in the hippocampus, with statistically significant differences in latency on days 2 and 3 compared to the normal group. Ginseng and Ligusticum striatum pills at 2.4 g / kg and 4.8 g / kg shortened the latency to find the platform on days 2 and 3, with 4.8 g / kg significantly shortening the latency on day 2, showing a statistically significant difference compared to the model group.

[0089] Table 4. Effects of Shenxiong Yizhi Pill on the latency of Aβ+LPS rats to local navigation (n=10, )

[0090]

[0091] As shown in Table 5, compared with the model group, the dosages of Shenxiong Yizhi Pills 2.4 g / kg and 4.8 g / kg increased the movement distance, number of platform crossings, number of platform crossings in quadrants, and dwell time in quadrants of the platform in the water maze experiment in rats with Aβ+LPS-induced learning impairment; they also showed a trend of shortening the escape latency, but there was no statistical difference.

[0092] Table 5. Effects of Shenxiong Yizhi Pill on Spatial Exploration Ability in Aβ+LPS Rats (n=10, )

[0093]

[0094] As shown in Table 6, compared with the model group, Shenxiong Yizhi Pill had no effect on the levels of inflammatory cytokines IL-6 and TNF-α in the hippocampus of rats, and could not reduce the levels of IL-6 and TNF-α in the hippocampus of rats with Aβ+LPS-induced learning impairment.

[0095] Table 6. Effects of Shenxiong Yizhi Pill on cytokines in the hippocampus of rats with impaired learning ability (n=10, )

[0096]

[0097] from Figure 1 As shown in Table 7, the normal group ( Figure 1 A) The hippocampal tissue structure was clear, and the neuronal cell morphology was normal, with no tissue necrosis or inflammatory cell infiltration observed. (Model group) Figure 1 B) Extensive necrosis with inflammatory cell infiltration in the hippocampus and parahippocampal brain tissue was observed, showing a statistically significant difference compared to the control group. (The text then abruptly shifts to a discussion of different dosage groups of Shenxiong Yizhi Wan.) Figure 1 D, E, and F) The hippocampus and parahippocampal brain tissues showed extensive necrosis with inflammatory cell infiltration, and the pathological scores were not statistically different from those of the model group.

[0098] Table 7. Effects of Shenxiong Yizhi Pills on Histological Scores of Aβ+LPS-Induced Hippocampal Injury in Rats ( )

[0099]

[0100] 5. Summary

[0101] This study used animal models closely related to cognitive function to evaluate the effect of the traditional Chinese medicine compound preparation Shenxiong Yizhi Wan on improving cognitive impairment in Alzheimer's disease, providing a basis for the safe and rational use of drugs in clinical practice.

[0102] Scopolamine induces a model of memory acquisition impairment by competitively blocking the binding of acetylcholine to M-type cholinergic receptors and inhibiting cholinergic neurotransmission. A single high-dose ethanol induces memory retrieval impairment through multiple pathways, including neurotransmitter imbalances such as glutamate and γ-aminobutyric acid (GABA), oxidative stress, and synaptic plasticity damage. Aβ, a polypeptide fragment produced by enzymatic hydrolysis of amyloid precursor protein (APP), abnormally deposits in the brain to form senile plaques, exhibiting neurotoxicity and inducing inflammatory responses. In vitro and in vivo studies have shown that LPS-induced inflammation promotes neuroinflammatory responses by upregulating various pro-inflammatory mediators, such as NO, IL-6, prostaglandin E2, and cyclooxygenase, thereby impairing cognitive and learning functions. Therefore, this study also used the method of injecting Aβ and LPS into the hippocampus of rats to induce an animal model of cognitive and learning impairment.

[0103] The results showed that Shenxiong Yizhi Pills had a good effect on improving memory acquisition and memory retrieval impairments, and had a certain effect on improving the learning and memory abilities of rats with learning impairment caused by the combined factors Aβ and LPS, without any toxic side effects.

[0104] In summary, the traditional Chinese medicine composition of this invention has a good effect on improving memory acquisition and memory retrieval impairment models; it also has a certain effect on improving learning and memory impairment caused by the combined factors of Aβ and LPS. The traditional Chinese medicine composition of this invention has broad application prospects in the treatment of AD.

Claims

1. A traditional Chinese medicine composition for treating cognitive impairment, characterized in that: It is prepared from the following raw materials by weight: Ginseng 2-5 parts, Astragalus 6-10 parts, Angelica sinensis 2-5 parts, Atractylodes macrocephala 2-5 parts, Ligusticum chuanxiong 3-7 parts, Polygala tenuifolia 1-4 parts, Acorus tatarinowii 2-5 parts, Pheretima aspergillum 1-4 parts, Hirudo medicinalis 0.5-2.5 parts, Pueraria lobata 3-7 parts.

2. The traditional Chinese medicine composition according to claim 1, characterized in that: It is prepared from the following raw materials by weight: Ginseng 3 parts, Astragalus 8 parts, Angelica sinensis 3 parts, Atractylodes macrocephala 3 parts, Ligusticum chuanxiong 5 parts, Polygala tenuifolia 3 parts, Acorus tatarinowii 3 parts, Pheretima aspergillum 2 parts, Hirudo medicinalis 1 part, Pueraria lobata 5 parts.

3. The traditional Chinese medicine composition according to claim 1 or 2, characterized in that: The Atractylodes macrocephala mentioned is stir-fried Atractylodes macrocephala.

4. The traditional Chinese medicine composition according to claim 1, characterized in that: It is a formulation prepared by adding pharmaceutically acceptable excipients to a powdered active pharmaceutical ingredient or an aqueous or organic solvent extract of the active pharmaceutical ingredient.

5. The traditional Chinese medicine composition according to claim 4, characterized in that: The preparation is an oral preparation; the oral preparation includes solutions, granules, pills, powders, ointments or tablets.

6. A method for preparing the traditional Chinese medicine composition according to any one of claims 1 to 5, characterized in that: It includes the following steps: (1) Weigh the raw materials according to the proportions described in claim 1; (2) The active pharmaceutical ingredient is ground into powder, or the active pharmaceutical ingredient is extracted with water or organic solvent, and then excipients or auxiliary ingredients commonly used in pharmaceuticals are added to obtain the product.

7. Use of the traditional Chinese medicine composition according to any one of claims 1 to 5 in the preparation of a medicament for treating cognitive impairment.

8. The use according to claim 7, characterized in that: The drug in question is a medication for treating Alzheimer's disease.

9. The use according to claim 8, characterized in that: The drug is a medication that improves memory, cognition, and / or learning abilities.

10. The use according to claim 9, characterized in that: The drug is used to improve memory acquisition and memory recall disorders.

Images