CN1596944A - Medicine for treating senile dementia and application of related Chinese medicinal composition - Google Patents

Abstract

The invention relates to a medicine for treating senile dementia, which comprises: 9-30 parts by weight of Radix Paeoniae Alba, 9-10 parts by weight of Angelica sinensis, 6-10 parts by weight of Rhizoma Chuanxiong, 3 parts by weight of Saffron, 12-15 parts by weight of Atractylodes macrocephala, 10-12 parts by weight of diarrhea, 12 parts by weight of Poria cocos, and 12 parts by weight of motherwort. Grind the crude drug into powder to make oral dosage form, make compound preparation with western medicine and other traditional Chinese medicine, or add it to food to make health food. The effect of the present invention on senile dementia includes the following aspects: 1. Improving learning and memory ability. 2. Promote the collateral sprouting of central cholinergic neurons. 3. Improve synaptic plasticity 4. Anti-free radical damage. 5. Improve the microcirculation of the central nervous system.

Description

Application of medicine for treating senile dementia and related traditional Chinese medicine composition

[technical field]

The invention relates to a medicine for treating senile dementia and the application of the new formula of Danggui Shaoyao Powder in preparing the medicine for treating senile dementia.

[Background technique]

Alzheimer's Disease (AD) is a degenerative disease of the central nervous system characterized by progressive cognitive impairment and memory loss, which will eventually lead to patients being unable to take care of themselves. So far, no effective treatment for AD has been found. The purpose of existing treatment is mainly to control abnormal symptoms in behavior, improve cognitive functions such as language and memory, slow down the development of the disease and delay the occurrence of symptoms. The application of drugs mainly includes the following aspects: ① Acetylcholinesterase inhibitors, in view of the large loss of cholinergic neurons in the brain of AD patients and the severe lack of acetylcholine transmitters, the use of acetylcholinesterase inhibitors can increase the content of acetylcholine in the brain, Promotes the recovery of neuronal function. ② Excitatory amino acid receptor antagonists, which protect cells from the cytotoxicity of excitatory transmitters. ③ anti-inflammatory drugs, because there are reactive glial cells around the core of senile plaque amyloidosis, some people put forward the theory of chronic inflammation in AD, and use appropriate anti-inflammatory drugs to achieve the purpose of prevention and treatment. ④ Neurotrophic factors, which can specifically act on neurons, stimulate the plasticity of neurons, promote the growth and survival of neurons, and maintain cell functions. ⑤Others, such as estrogen replacement therapy, brain cell metabolism activators, application of calcium ion antagonists, etc. Although the above-mentioned drugs have shown certain curative effects in clinical application, due to the serious unavoidable side effects in the long-term use process, the application of this class of drugs needs further research.

At present, the toxic and side effects of chemically synthesized drugs are seriously perplexing the medical field. Returning to nature and returning to simplicity have become people's new desires for their own living conditions. People are paying more attention to natural medicines than ever before. In recent years, people have used these medicines Since a lot of effective experience has been accumulated in the prevention and treatment of AD, the use of natural medicines in the treatment of AD has at least two advantages: (1) multi-target action and overall regulation of human body functions; (2) less side effects. Therefore, for AD, a chronic degenerative disease of the nervous system, the development and application of natural medicines have greater advantages and broader development prospects.

Danggui Shaoyao San (DSS) comes from "Synopsis of the Golden Chamber". It is a commonly used ancient prescription for treating gynecological diseases. It has the functions of nourishing blood, promoting blood circulation, removing dampness, and diuresis. The DSS formula contained in the 95th edition of the Pharmacopoeia is: Radix Paeoniae Alba, Radix Hngelicae Sinenisis 9 grams each, Rhizoma Chuan Xiong 6 grams, Atractylodes Rhizoma Atractyodis Macrocephalae, Rhizoma Alismatis, Poria cocos ( Poria) each 12 grams. In the past, a large amount of clinical and experimental data have shown that DSS is an effective prescription for the treatment of various gynecological diseases. Studies have shown that DSS has a wide range of pharmacological effects. ① Anti-free radical damage; ② Regulate immune function; ③ Promote the function of the hypothalamus-pituitary-ovary axis; ④ Improve the sleep of the elderly; ⑤ Auxiliary anti-cancer effects, etc. In the late 1980s, Japanese scholar Nobuaki Mizushima first used it to treat AD and achieved preliminary curative effect. Later, some people found that this prescription could stimulate the synthesis of central acetylcholine and receptors, and improve the learning and memory ability of rats. The clinical and experimental studies of DSS in the treatment of AD, over the past two decades, more than 200 clinical reports and experimental studies of different cases in more than ten domestic and foreign research institutions have proved that DSS has the effect of treating senile dementia, which is enough to show that DSS is There are effective prescriptions for treating AD. It has been reported that different doses of each drug in the DSS prescription have different curative effects on AD. However, since this prescription comes from a commonly used ancient prescription for treating gynecological diseases, although it has been established that it is effective in treating AD. However, gynecological diseases and AD diseases are very different from the understanding of them in traditional Chinese medicine and the research of modern technology. Using DSS to treat AD, It is necessary to add or subtract corresponding drugs according to AD symptoms and TCM theory to achieve greater therapeutic effect.

[Content of the invention]

The object of the present invention is to improve the curative effect of DSS in treating senile dementia, and to provide a new DSS formula with better curative effect and no side effects—the application of Danggui Shaoyao San modified prescription in the preparation of medicaments for treating AD.

The present invention is realized in the following way: according to the theory of traditional Chinese medicine for treating emotionally aware diseases, two herbs of saffron (Crocus Sativus L) and motherwort (Herba Leonuri) are added on the basis of the original prescription. The former is a medicine for promoting blood circulation and removing blood stasis, while the latter can regulate menstruation and activate blood circulation, diuresis and swelling, lower blood pressure and expand the crown. The two medicines are added to the original prescription to play the role of ministerial drug and adjuvant drug. By increasing the proportion of the original prescription of monarch and minister medicine, a new formula of traditional Chinese medicine for the treatment of AD was formed. The formula is: 9-30 parts by weight of white peony, 9-10 parts by weight of angelica, 6-10 parts by weight of Chuanxiong, 3 parts by weight of saffron, 12-15 parts by weight of Atractylodes Rhizome, 10-12 parts by weight of Alisma, 12 parts by weight of Poria cocos, Motherwort 12 parts by weight.

The following formula is more effective: 30 parts of white peony, 10 parts of angelica, 10 parts of Chuanxiong, 3 parts of saffron, 15 parts of Atractylodes macrocephala, 10 parts of Alisma, 12 parts of Poria cocos, and 12 parts of motherwort.

The behavioral and morphological observation experiments on senile dementia model mice show that the effects of the modified Danggui Shaoyao San on senile dementia model mice include the following aspects: 1. Improving the learning and memory ability of senile dementia model mice. 2. Promote the collateral sprouting of central cholinergic neurons. 3. Improve synaptic plasticity 4. Anti-free radical damage. 5. Improve the microcirculation of the central nervous system.

According to the theory of traditional Chinese medicine for treating emotionally-aware diseases, the invention adds two herbs of saffron and motherwort on the basis of the original prescription, and forms a new prescription medicine for treating senile dementia. The new formula of Danggui Shaoyao Powder is more effective than the original formula in treating senile dementia.

[Detailed ways]

The modified Danggui Shaoyao Powder of the present invention can be prepared as a medicine for treating AD. Since Danggui Shaoyao Powder is a traditional Chinese medicine prescription, the therapeutic effect can be achieved through oral administration. It can be made into oral dosage forms, including powders, tablets, granules, capsules, Oral liquid, etc., can also be added to food for consumption, or added to food for consumption as health food.

The Danggui Shaoyao San modified prescription of the present invention can also be made into a compound preparation with the current Western medicine for treating AD such as cholinesterase inhibitors such as Tacrine, so that the purpose of treating both symptoms and root causes can be achieved when treating AD; it can also be combined with Other traditional Chinese medicines such as tea polyphenols are made into compound preparations.

The following examples are only used to illustrate the present invention, without any limitation to the protection scope of the present invention.

Example 1. Preparation of Danggui Shaoyao San Jiawei decoction: According to the recipe, take 30g of Radix Paeoniae Alba, 10g of Angelica sinensis, 10g of Rhizoma Chuanxiong, 3g of Saffron, 15g of Atractylodes macrocephala, 10g of Alisma, 12g of Poria cocos, 12g of motherwort, add 900ml of water, and simmer for 2 hours , concentrated to 300ml. That is, the same preparation process as the traditional Chinese medicine decoction.

Example 2

Danggui Shaoyao San Modified Prescription Powder.

According to the formula, take 30g of white peony root, 10g of angelica, 10g of Chuanxiong, 3g of saffron, 15g of Atractylodes macrocephala, 10g of Alisma, 12g of poria cocos, 12g of motherwort, mix all the crude drugs and grind them into fine powder, which is Danggui Shaoyao powder.

Example 3

Danggui Shaoyao San Modified Capsules.

Take Danggui Shaoyao powder with flavored formula and pack it in a capsule machine to obtain capsules.

Example 4

Modified Danggui Shaoyao San improved the learning and memory ability of senile dementia model mice.

1. Materials and methods

8-month-old accelerated aging mice (SAMP-8) were selected, and the new formula group was fed with 3ml of water decoction of Danggui Shaoyao powder and modified prescription every day (1g crude drug/1ml and 0.25g crude drug/1ml group, the new formula was white peony 30g, angelica 10g, Chuanxiong 10g, saffron 3g, Atractylodes macrocephala 15g, Alisma 10g, Poria cocos 12g, Motherwort 12g), the original prescription group was given 3ml of Angelica Shaoyao powder decoction every day (1g crude drug/1ml original prescription was 9 grams each of Radix Paeoniae Alba and Angelica sinensis, Chuanxiong 6 grams, Atractylodes macrocephala, Alisma, Poria cocos each 12 grams), a total of 4 weeks after gavage Morris water maze test. A total of 5 days were tested, with morning and afternoon twice a day, and the time from entering the water in the four quadrants to finding the platform was recorded each time, that is, the escape latency period. If the platform cannot be found within 120 seconds, the rat is led onto the platform, and the escape latency is recorded as 120 seconds. In the afternoon of the 5th day, the platform was removed, and the swimming track of the rats after entering the water from a certain quadrant was recorded, the number of ring penetrations was counted, and the percentage of the swimming distance in the T quadrant was calculated.

2. Results

The average escape latency was: 62.23±18.33 seconds in the control group, 49.19±21.15 seconds in the original formula group, 53.19±21.15 seconds in the low-dose new formula group, and 33.21±15.12 seconds in the high-dose new formula group. Compared with the control group and the original prescription group, the average escape latency of the high-dose new formula group was significantly reduced (P<0.01). Compared with the control group, the average escape latency of the original prescription group was significantly reduced (P<0.01).

The number of piercings and the percentage of swimming distance in T quadrant in each group are shown in Table 1. It can be seen from the table: compared with the control group and the original prescription group, the number of piercings and the percentage of T quadrant swimming distance in the high-dose new formula group were significantly increased (P<0.01). Compared with the control group, the average escape latency of the original prescription group was significantly increased (P<0.01).

            Table 1 The average number of piercings and the percentage of swimming distance in the T quadrant of each group

Average number of piercings % of swimming distance in T quadrant

Control group 1.8±0.32 30.45±7.23

Original group 3.2±0.38 ^* 41.49±8.45 ^*

Low-dose new formula group 2.4±0.38 31.15±7.31

High-dose new formula group 4.6±0.41 ^*# 55.02±5.78 ^*#

^* P<0.01 compared with the control group#P<0.01 compared with the original prescription group

Example 5

Effects of Danggui Shaoyao powder on the cholinergic system in the basal forebrain of senile dementia model mice.

1. Materials and methods

1. Grouping of experimental animals

8-month-old accelerated aging mice (SAMP-8) were selected, and the new formula group was fed with 3ml of water decoction of Danggui Shaoyao powder and modified prescription every day (1g crude drug/1ml and 0.25g crude drug/1ml group, the new formula was white peony 30g, angelica 10g, Chuanxiong 10g, saffron 3g, Atractylodes macrocephala 15g, Alisma 10g, Poria cocos 12g, Motherwort 12g), the original prescription group was given 3ml of Angelica Shaoyao powder decoction every day (1g crude drug/1ml original prescription was 9 grams each of Radix Paeoniae Alba and Angelica sinensis, Chuanxiong 6 grams, Atractylodes macrocephala, Alisma, and Poria each 12 grams), after a total of 4 weeks of intragastric administration, all mice were anesthetized with 1% pentobarbital sodium intraperitoneally (35-40 mg/kg), after perfusion and fixation, the calvaria was removed, Place the animal on a brain locator, and make a transverse cut at 2mm and 4mm posterior to bregma, respectively, and divide it into three pieces, A, B, and C from head to tail. Keep the B organization block. Coronal frozen serial sections were made, and two out of five were selected, and adjacent sections were randomly selected for ChAT immunohistochemical staining and acetylcholinesterase (AchE) histochemical staining. The number of ChAT-positive cells in the medial septum and the number of AchE-positive fibers in the prefrontal cortex were tested under a light microscope.

2. Data recording

Get two groups of slices of each rat 5, ChAT immunohistochemical staining slices were recorded under the light microscope (200 times) and calculated: the number of ChAT-positive cells in the medial septum on both sides of each slice; Observe under the microscope (10×40 times) and count: the number of intersections between the AchE positive fibers and the test grid line in the three visual fields of the bilateral prefrontal cortex molecular layer of each slice.

2. Results

1. Effect of modified Danggui Shaoyao San on the number of ChAT positive cells in the medial septum nucleus

The number of ChAT-positive cells in the medial septum of mice in each group: 28.1±7.9 cells/slice in the control group, 38.8±9.6 cells/slice in the original prescription group, 33.8±9.8 cells/slice in the low-dose new formula group, and 48.1±8.5 cells in the high-dose new formula group pieces/slice. Compared with the control group and the original prescription group, the number of ChAT-positive cells in the medial septal nucleus in the high-dose administration group was significantly increased (P<0.01), and compared with the control group, the number of ChAT-positive cells in the medial septal nucleus in the original prescription group was significantly increased (P<0.01).

2. Modified formula of Danggui Shaoyao San on the changes of AchE-positive fiber density in hippocampal CA1 area and prefrontal cortex

The measurement results of AchE-positive fibers in hippocampal CA1 area and prefrontal cortex of mice in each group are shown in Table 2.

The table shows: compared with the control group and the original formula group, the density of AchE-positive fibers in the hippocampus CA1 area and prefrontal cortex of the high-dose new formula group increased significantly (P<0.01). Compared with the control group, the density of AchE-positive fibers in the hippocampus CA1 area and prefrontal cortex in the original prescription group increased significantly (P<0.01).

Table 2 Density of AchE-positive fibers in CA1 region of rat hippocampus and prefrontal cortex (X±SD) Unit: number of intersections/1000μm2

            Hippocampal CA1 area     Prefrontal cortex

Control group 115.3±16.7 33.2±7.9

Original group 158.7±27.9 ^* 59.2±8.1 ^*

Low-dose new formula group 138.2±29.1 45.3±8.7

High-dose new formula group 187.5±37.1 ^*# 63.6±14.7 ^*#

^* P<0.01 compared with the control group#P<0.01 compared with the original prescription group

Claims (10)

1, a kind of medicine for the treatment of alzheimer disease comprises: Radix Paeoniae Alba 9-30 part is heavy, and Radix Angelicae Sinensis 9-10 part is heavy, and Rhizoma Chuanxiong 6-10 part is heavy, 3 parts of weights of Stigma Croci, and Rhizoma Atractylodis Macrocephalae 12-15 part is heavy, and Rhizoma Alismatis 10-12 part is heavy, 12 parts of weights of Poria, 12 parts of weights of Herba Leonuri.

2,, it is characterized in that 30 parts of weights of the Radix Paeoniae Alba, 10 parts of weights of Radix Angelicae Sinensis, 10 parts of weights of Rhizoma Chuanxiong, 3 parts of weights of Stigma Croci, 15 parts of weights of the Rhizoma Atractylodis Macrocephalae, 10 parts of weights of Rhizoma Alismatis, 12 parts of weights of Poria, 12 parts of weights of Herba Leonuri according to the described medicine of claim 1.

3, according to claim 1 or 2 described medicines, it is characterized in that adopting peroral dosage form.

4, according to claim 1 or 2 described medicines, it is characterized in that making compound preparation with Western medicine.

5,, it is characterized in that making compound preparation with cholinesterase inhibitor according to the described medicine of claim 4.

6,, it is characterized in that making compound preparation with tacrine (Tacrine) according to the described medicine of claim 4.

7, according to claim 1 or 2 described medicines, it is characterized in that making compound preparation with Chinese medicine extract.

8,, it is characterized in that making compound preparation with tea polyphenols according to the described medicine of claim 7.

9,, it is characterized in that being added into and make health food in the food according to claim 1 or 2 described medicines.

10, the Radix Paeoniae Alba, Radix Angelicae Sinensis, Rhizoma Chuanxiong, Stigma Croci, the Rhizoma Atractylodis Macrocephalae, Rhizoma Alismatis, Poria, the application of Herba Leonuri in preparation treatment alzheimer disease medicine.