Pharmaceutical composition for improving memory impairment and application thereof

文档序号:1480599 发布日期:2020-02-28 浏览:26次 中文

阅读说明:本技术 一种改善记忆损伤的药物组合物及其应用 (Pharmaceutical composition for improving memory impairment and application thereof ) 是由 宋采 张才 张永平 唐海婷 杨隆恩 李晓红 刘白平 于 2019-11-29 设计创作,主要内容包括:本发明公开了一种改善记忆损伤的药物组合物及其应用。所述组合物包含EPA、红景天和远志。本发明建立小鼠记忆损伤模型,给小鼠饲喂含有EPA、红景天和远志的饲料,通过避暗行为实验和跳台行为实验评价EPA、红景天和远志联合使用在改善记忆损伤的效果以及改善乙醇诱导小鼠记忆损伤的作用机制,研究发现,EPA、红景天和远志联合使用可显著降低小鼠血清促炎因子IL-6和海马区乙酰胆碱酯酶的水平,能显著延长乙醇诱导小鼠的潜伏期,显著降低错误次数,对记忆损伤有着明显的改善效果。本发明提供的食源性药物组合物高效且无毒副作用,对于改善记忆损伤具有重要的应用价值。(The invention discloses a pharmaceutical composition for improving memory impairment and application thereof. The composition comprises EPA, rhodiola rosea and polygala tenuifolia. According to the invention, a mouse memory impairment model is established, a mouse is fed with a feed containing EPA, rhodiola rosea and polygala tenuifolia, the effect of the combined use of EPA, rhodiola rosea and polygala tenuifolia on improving memory impairment is evaluated through a dark avoidance behavior experiment and a diving platform behavior experiment, and the action mechanism of the combined use of EPA, rhodiola rosea and polygala tenuifolia on improving the memory impairment of the mouse induced by ethanol is found through researches, the combined use of EPA, rhodiola rosea and polygala tenuifolia can obviously reduce the levels of proinflammatory factor IL-6 in mouse serum and acetylcholinesterase in hippocampal region, the incubation period of the mouse induced by ethanol can be obviously prolonged, the error times. The food-borne pharmaceutical composition provided by the invention is efficient and has no toxic or side effect, and has an important application value for improving memory impairment.)

1. A pharmaceutical composition for improving memory impairment, comprising EPA, rhodiola rosea and polygala tenuifolia.

2. The pharmaceutical composition according to claim 1, wherein the weight ratio of EPA, rhodiola rosea and polygala tenuifolia is 8-10: 1-3: 5-8.

3. The pharmaceutical composition according to claim 1, wherein the weight ratio of EPA, rhodiola rosea and polygala tenuifolia is 10: 1-3: 5.

4. The pharmaceutical composition of claim 1, wherein the weight ratio of EPA, rhodiola rosea and polygala tenuifolia is 10:3: 5.

5. The pharmaceutical composition according to any one of claims 1 to 4, further comprising a pharmaceutically acceptable carrier.

6. Use of the pharmaceutical composition of any one of claims 1 to 5 for the preparation of a medicament for improving memory impairment.

7. The use of claim 6, wherein the memory impairment is ethanol-induced memory impairment.

8. Use of the pharmaceutical composition of any one of claims 1 to 5 in the preparation of a medicament for reducing the level of the proinflammatory factor IL-6 in serum.

9. Use of a pharmaceutical composition according to any one of claims 1 to 5 in the manufacture of a medicament for reducing the level of acetylcholinesterase in the hippocampal region of the brain.

10. The use according to claim 8 or 9, wherein the reduction of the serum level of the proinflammatory factor IL-6 is a reduction of an abnormally elevated serum level of the proinflammatory factor IL-6 induced by ethanol; the step of reducing the level of acetylcholinesterase in the hippocampal brain region is to reduce the abnormal increase of the level of acetylcholinesterase in the hippocampal brain region induced by ethanol.

Technical Field

The invention belongs to the technical field of medicines. More particularly, relates to a pharmaceutical composition for improving memory impairment and application thereof.

Background

The memory impairment is the core of cognitive function impairment, and at the present stage, with the change of social environment and the increase of various pressures, different groups of light teenagers, middle-aged people and old people have great demands on improving memory, so that active substances with the functions of improving memory function, promoting learning ability and treating memory impairment caused by various factors are researched and developed, and the application prospect is great.

The marine lipid eicosapentaenoic acid (EPA), which belongs to n-3 polyunsaturated fatty acids, is also one of the essential fatty acids of the human body. The substance has antiinflammatory, anticancer, blood lipid reducing, and memory improving effects, and can be widely used in food and medicine, and has regulating and controlling effects on multiple physiological functions of human body, especially important effects on maintaining cardiovascular health, brain development, visual system and nervous system. The human body can produce a small amount of EPA by itself through the conversion of linolenic acid, but the synthesis rate is too slow to provide daily needs, and thus, people need to supplement EPA through external ingestion.

The market is full of various EPA memory improving health care products, which are declared to have the effect of prevention or adjuvant therapy, but the actual purity, dosage and the proportion of mixed preparations are very different. At present, there are also related researches on the treatment of memory impairment, and patents CN104256585A and CN104187727A both disclose EPA-containing soft capsule of seal oil capable of improving memory, but there is no definite experimental data to confirm that it can effectively improve memory impairment of individuals. Patent CN108904779A discloses that triptorelin has obvious protective effect on learning and memory impairment of mice induced by LPS, and patent CN1336930A discloses a bridged heterocyclic derivative capable of treating memory impairment, but long-term use of chemical drugs can cause negative effects on organisms. Therefore, research on food-derived memory improvement becomes an important research field, and the current research situation and trend of the structural characteristics and physiological activity of food-derived bioactive peptides [ J ] Chinese food bulletin, 2011,11(09):69-81] summarize the application of food-derived polypeptides in the aspect of memory improvement, but still more problems exist in the aspects of raw material selection, raw material utilization rate, memory improvement evaluation methods, action mechanisms and the like at present.

Therefore, aiming at the existing problems, the finding of the food-borne memory improving formula which is efficient and has no toxic or side effect has important application value.

Disclosure of Invention

Aiming at the defects of the existing medicines for improving memory impairment, the invention aims to provide a medicine composition for improving memory impairment and application thereof in improving memory impairment.

The invention aims to provide a pharmaceutical composition for improving memory impairment.

The invention also aims to provide application of the pharmaceutical composition in preparing a medicine for improving memory impairment.

Another object of the present invention is to provide the use of the above pharmaceutical composition in the preparation of a medicament for reducing the level of the proinflammatory factor IL-6 in serum.

The invention also aims to provide the application of the pharmaceutical composition in preparing a medicine for reducing the acetylcholinesterase level in the hippocampal region of the brain.

The above purpose of the invention is realized by the following technical scheme:

the invention establishes a mouse memory impairment model, feeds a mouse with a feed containing EPA, rhodiola rosea and polygala tenuifolia, evaluates the effect of the combined use of the EPA, the rhodiola rosea and the polygala tenuifolia on improving memory impairment through a dark-avoidance behavior experiment and a diving platform behavior experiment, and improves the action mechanism of ethanol-induced mouse memory impairment.

Therefore, a pharmaceutical composition for improving memory impairment, which consists of EPA, rhodiola rosea and polygala tenuifolia, is within the scope of the present invention.

Preferably, the weight ratio of the EPA, the rhodiola rosea and the polygala tenuifolia is 8-10: 1-3: 5-8.

More preferably, the weight ratio of the EPA, the rhodiola rosea and the polygala tenuifolia is 10: 1-3: 5.

Most preferably, the weight ratio of the EPA, the rhodiola rosea and the polygala tenuifolia is 10:3: 5.

Preferably, the above pharmaceutical composition further comprises a pharmaceutically acceptable carrier.

In addition, the application of the pharmaceutical composition in preparing the medicine for improving the memory impairment, the application in preparing the medicine for reducing the level of the proinflammatory factor IL-6 in serum and the application in preparing the medicine for reducing the level of the acetylcholinesterase in the hippocampal region of the brain are all within the protection scope of the invention.

Preferably, the memory impairment is ethanol-induced memory impairment.

Preferably, the reduction of the serum proinflammatory factor IL-6 level refers to the reduction of the abnormal increase of the serum proinflammatory factor IL-6 level induced by ethanol; the step of reducing the level of acetylcholinesterase in the hippocampal brain region is to reduce the abnormal increase of the level of acetylcholinesterase in the hippocampal brain region induced by ethanol.

The invention has the following beneficial effects:

the pharmaceutical composition capable of improving memory impairment is developed and obtained, namely EPA, rhodiola rosea and polygala tenuifolia are compounded for use, the levels of a proinflammatory factor IL-6 in serum of a mouse and acetylcholinesterase in a hippocampal region can be obviously reduced, the latency of the mouse can be obviously prolonged in a dark-avoiding behavior experiment and a diving platform behavior experiment, the error times are reduced, and the pharmaceutical composition has an obvious effect of improving memory impairment.

Drawings

FIG. 1 shows the results of experiments on the latency (A) and the number of errors (B) of mice in different experimental groups in a diving platform behavior experiment;

FIG. 2 shows the results of experiments on the latency (A) and the number of errors (B) of mice in different experimental groups in the dark behavior avoidance experiment;

FIG. 3 is a graph showing the change of the levels of proinflammatory factor IL-6(A) and intracerebral acetylcholinesterase (B) in mice of different experimental groups.

Detailed Description

The invention is further described with reference to the drawings and the following detailed description, which are not intended to limit the invention in any way. Reagents, methods and apparatus used in the present invention are conventional in the art unless otherwise indicated.

1. Experimental animals and breeding

Sexually mature Kunming mice, purchased from Tianqin Biotechnology Ltd of Changsha (certification: No.43006700016542), rearing environment: mice were housed in 12 per cage (30 × 19 × 16cm), temperature: 23 ± 1 ℃, humidity: under the feeding environment of 50 +/-10 percent, the standard experimental animal house with 12h of light-dark cycle is sufficient in water source and feed. The EPA traditional Chinese medicine compound feed is prepared by mixing according to the mass ratio of 1%, is prepared once every 2 days and is stored in a refrigerator at the temperature of 20 ℃ below zero. The raising and handling process of the experimental animals complies with the relevant regulations of the Guangdong university of oceans for raising and using the experimental animals.

2. Experimental reagent

Figure BDA0002297237100000031

Figure BDA0002297237100000041

3. Main apparatus and equipment

4. Data processing

Data processing was performed using SPSS 19.0, and results were expressed as mean. + -. standard error (Average. + -. SEM), and group differences were compared using 1-Way analysis of variance, and LSD post-analysis. The statistical chart was manufactured by Graphpad Prism 6. P <0.05 was significantly different.

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