Application of traditional Chinese medicine composition in preparation of medicine for treating insomnia

Abstract

The invention relates to application of a traditional Chinese medicine composition in preparation of a medicine for treating insomnia. The traditional Chinese medicine composition is prepared from the following raw material medicines in parts by weight: 5-25 parts of ligusticum wallichii and 1.5-8 parts of gastrodia elata. The traditional Chinese medicine composition disclosed by the invention has certain sedative and hypnotic effects and can exert a curative effect on insomnia.

Description

Technical Field

[0001] The invention belongs to the technical field of traditional Chinese medicines, relates to a new use of a traditional Chinese medicine composition, and specifically relates to the use of the traditional Chinese medicine composition in preparing a medicine for treating insomnia. Background Art

[0002] Insomnia is a sleep disorder and one of the common clinical symptoms in modern society, which has a serious impact on people's physical and mental health and quality of life. More and more evidence shows that insomnia is related to a series of health problems, including mental disorders, cardiovascular dysfunction, type 2 diabetes and obesity. With the rapid development of society, high work pressure and irregular life have led to an increase in the incidence of insomnia year by year and a trend of younger age, which has attracted great attention from all walks of life. Insomnia is controlled by many pathogenic factors, but its specific pathogenesis is not very clear. At present, sedative hypnotic drugs are often used in clinical treatment of insomnia, but the side effects are large, and there is tolerance and dependence. Traditional Chinese medicine mainly relieves insomnia by nourishing yin and qi, nourishing the heart and calming the mind, and regulating the body, with fewer adverse reactions. Therefore, choosing traditional Chinese medicine to treat insomnia has become the preferred treatment option for more and more people. Summary of the invention

[0003] The purpose of the present invention is to provide an application of a Chinese medicine composition in the preparation of a drug for treating insomnia, characterized in that the Chinese medicine composition is prepared from the following raw materials in the following weight proportions: 5-25 parts of Chuanxiong and 1.5-8 parts of Gastrodia. Wherein, Chuanxiong is the dried rhizome of the plant Ligusticum chuanxiong Hort. of the Apiaceae family; and Gastrodia is the dried tuber of the plant Gastrodia elata Bl. of the Orchidaceae family.

[0004] Furthermore, the Chinese medicine composition is made of raw materials in the following weight ratios: 8-15 parts of Chuanxiong and 2-6 parts of Gastrodia elata.

[0005] Furthermore, the Chinese medicine composition is made of raw materials in the following weight ratios: 8-10 parts of Chuanxiong and 2.5-5 parts of Gastrodia elata.

[0006] Furthermore, the Chinese medicine composition is made of raw materials in the following weight ratios: 9-10 parts of Chuanxiong and 2.5-3 parts of Gastrodia elata.

[0007] Furthermore, the Chinese medicine composition is made of raw materials in the following weight ratio: 10 parts of Chuanxiong and 2.5 parts of Gastrodia elata.

[0008] Furthermore, the Chinese medicine composition is made of raw materials in the following weight ratio: 9 parts of Chuanxiong and 5 parts of Gastrodia elata.

[0009] Specifically, the drug is selected from an oral dosage form, an injection dosage form or an external administration preparation.

[0010] Specifically, the medicine is selected from decoctions, tablets, capsules, granules, pills, injections, powders, decoctions, suspensions, dispersants, syrups, suppositories, gels, aerosols, patches, and oral liquids.

[0011] The composition of the present invention described above can be prepared by directly grinding several medicinal materials into powder according to traditional methods, or by obtaining extracts through conventional means so as to be prepared into different dosage forms, thereby obtaining better therapeutic effects and being more conducive to the preparation of modern pharmaceutical dosage forms.

[0012] The present invention also proposes the use of any of the above-mentioned traditional Chinese medicine compositions in the preparation of sedative and / or hypnotic and / or antianxiety drugs, wherein the traditional Chinese medicine composition is made of raw materials in the following weight proportions: 8-15 parts of Chuanxiong and 2-6 parts of Gastrodia elata.

[0013] Furthermore, the Chinese medicine composition is made of raw materials in the following weight ratios: 8-10 parts of Chuanxiong and 2.5-5 parts of Gastrodia elata.

[0014] Furthermore, the Chinese medicine composition is made of raw materials in the following weight ratios: 9-10 parts of Chuanxiong and 2.5-3 parts of Gastrodia elata.

[0015] Furthermore, the Chinese medicine composition is made of raw materials in the following weight ratio: 10 parts of Chuanxiong and 2.5 parts of Gastrodia elata.

[0016] Furthermore, the Chinese medicine composition is made of raw materials in the following weight ratio: 9 parts of Chuanxiong and 5 parts of Gastrodia elata.

[0017] Furthermore, the method for preparing the Chinese medicine composition comprises the following steps:

[0018] (1) taking Chuanxiong and Gastrodia elata in a weight ratio of 5-25 of Chuanxiong and 1.5-8 of Gastrodia elata, drying, crushing and mixing them to obtain a mixture;

[0019] (2) extracting the mixture by reflux with 70%-90% ethanol for 2-3 times, each time for 1-3 hours, to obtain an extract and a medicinal residue;

[0020] (3) combining the extracts and filtering to obtain a filtrate;

[0021] (4) The filtrate is concentrated to a clear paste having a relative density of 1.21-1.30 at 55-65°C.

[0022] Furthermore, the preparation method of the Chinese medicine composition also includes:

[0023] (5) decocting the medicinal residue with water for 1-2 hours, combining the decoction, filtering, and concentrating the filtrate after the decoction to a clear paste with a relative density of 1.21-1.30 at 55-65° C., preferably decocting for 1 hour;

[0024] (6) Combine the clear pastes obtained in step (4) and step (5).

[0025] Specifically, step (2) is to extract the mixture by reflux using 90% ethanol twice to obtain an extract, each time for 2 hours.

[0026] Furthermore, the drug is selected from capsules, and the preparation method, in addition to the above steps, further comprises: adding drug-acceptable excipients, such as an appropriate amount of dextrin, to the clear paste obtained in step (4) and / or step (5), vacuum drying, mixing evenly, sieving, granulating, granulating, and encapsulating.

[0027] Experimental studies have shown that the composition of the present invention can significantly reduce the total activity distance and the number of standing times of autonomous activities of rats with insomnia model induced by PCPA, and up-regulate the content of 5-HT in the hypothalamus; significantly reduce the number of activities and the number of standing times of autonomous activities of mice with insomnia model induced by PCPA, significantly shorten the sleep latency of insomnia mice, and significantly prolong the sleep time, indicating that the traditional Chinese medicine composition has a certain sedative and hypnotic effect, and can be used to treat insomnia. DETAILED DESCRIPTION

[0028] The present invention discloses an application of a Chinese medicine composition, and those skilled in the art can refer to the content of this article and appropriately improve the process parameters to achieve it. It is particularly important to point out that all similar substitutions and modifications are obvious to those skilled in the art, and they are all considered to be included in the present invention. The method and application of the present invention have been described through preferred embodiments, and relevant personnel can obviously modify or appropriately change and combine the methods and applications described herein without departing from the content, spirit and scope of the present invention to implement and apply the technology of the present invention.

[0029] As used herein, the term "treat" refers to any indicator of success in treating or ameliorating an injury, condition, disorder or symptom (e.g., pain), including any objective or subjective parameter, such as elimination; improvement; reduction of symptoms or making symptoms, injuries, conditions or disorders more tolerable to the patient; reduction of symptom or disorder frequency or duration; or, in some cases, prevention of the onset of symptoms or disorders. Treatment or amelioration of symptoms can be based on any objective or subjective parameter, including, for example, the results of a physical examination.

[0030] The raw materials and reagents used in the following examples can all be purchased from the market.

[0031] Example 1 Preparation of Chinese medicine composition capsules

[0032] Take 784g of Chuanxiong and 196g of Gastrodia elata, dry, crush and mix them; then use 90% ethanol to reflux and extract twice to obtain an extract and medicinal residues, each time for 2 hours, combine the extracts, and filter to obtain a filtrate; the filtrate is concentrated to a clear paste with a relative density of 1.27 at 55-65°C; the medicinal residues are decocted with water twice, each time for 1 hour, the decoctions are combined, filtered, and the filtrate after the decoction is concentrated to a clear paste with a relative density of 1.27 at 55-65°C, and the clear paste is combined with the above-mentioned clear paste to obtain a traditional Chinese medicine composition; add drug-acceptable excipients to the clear paste of the traditional Chinese medicine composition, vacuum dry, mix evenly, and sieve; granulate, granulate, and encapsulate to make 1000 capsules for standby use, with each capsule containing 0.34g, equivalent to 0.98g of the original medicinal material.

[0033] Experimental Example 2 Therapeutic effect of Chinese medicine composition on insomnia rat model

[0034] 1. Experimental Materials

[0035] 1.1 Animals

[0036] SD rats, SPF grade, 60 rats, weighing 170-190g, half male and half female. Rearing environment: room temperature 20-26℃, relative humidity controlled at 40-70%. Male and female rats were raised in separate cages, 5 rats / sex / group per cage.

[0037] 1.2 Drugs and reagents

[0038] The Chinese medicine composition prepared in Example 1, Jiangsu Kangyuan Pharmaceutical Co., Ltd.;

[0039] Diazepam (2.5 mg / tablet, Shandong Xinyi Pharmaceutical Co., Ltd.); p-chlorophenylalanine (PCPA, Sigma, catalog number: 7474-00-2); 5-hydroxytryptamine (5-HT, Shanghai Jianglai Biotechnology Co., Ltd.).

[0040] 1.3 Instruments

[0041] Open field test box (Shanghai Xinruan Information Technology Co., Ltd., model: ANY-maze); homogenizer (US MP Company, model: FastPrep-24TM 5G); microplate reader (US Meigu Molecular, model: Flexstation 3); electronic balance (G&G, model: TC3K).

[0042] 2. Dosage design

[0043] The daily dosage of the Chinese medicine composition is 4.08 g / day. According to the body surface area conversion method, the equivalent dose for rats is 4.08 g / 60 kg*6.2=0.42 g / kg. According to the 1:2:4 dosing method, the medium dose is 0.84 g / kg and the high dose is 1.68 g / kg. Oral administration, 0.1 mL / 10 g, once a day.

[0044] Diazepam, the clinical daily dose for humans is 10 mg. Based on the body surface area conversion method, the equivalent dose for rats is 10 mg / 60 kg*6.2=1.03 mg / kg.

[0045] 3. Experimental Methods

[0046] SD rats were fed adaptively for 5 days and had free access to feed and water. According to body weight, they were randomly divided into normal control group, model control group, diazepam group, high-dose, medium-dose and low-dose groups of Chinese medicine combination, with 10 rats in each group. Except for the normal control group, rats in other groups were intraperitoneally injected with PCPA 400 mg / kg at the same time range every morning for 4 consecutive days. The normal control group was injected with an equal amount of normal saline. When the number of standing times of rats with autonomous activities increased significantly, the circadian rhythm was disordered, the sleep time was significantly reduced until it disappeared completely, and the excitability and aggressiveness were also significantly enhanced, it indicated that the model had been successfully established. After the modeling was completed, each group began to be gavaged once a day for 7 days. The normal control group and the model control group were gavaged with distilled water. One hour after the last administration of the experiment, the rats were placed in the center of the open field test box for 1 minute to adapt, and the moving distance and number of standing times of each rat within 5 minutes were recorded. After each experiment, the inner wall and bottom of the open field test box should be cleaned with 75% ethanol to prevent the smell left by the previous rat from affecting the next experiment. After the experimental box is completely dried, the next experiment can be carried out. After the observation, the rats are anesthetized, the hypothalamus is removed and frozen, and the 5-HT content in the hypothalamus is detected.

[0047] 4. Statistical methods

[0048] The results were statistically analyzed using t-test.

[0049] 5. Experimental Results

[0050] 5.1 Effects on the autonomic activity of insomnia model rats

[0051] Compared with the normal control group, the total distance of activity and the number of standing times of rats in the model control group increased significantly, indicating that the insomnia model was successfully established. Compared with the model control group, the total distance of activity and the number of standing times of rats in the diazepam group and the low, medium and high dose groups of the Chinese medicine composition decreased significantly (P<0.05, P<0.01), indicating that the Chinese medicine composition has a certain sedative and tranquilizing effect. The results are shown in Table 1.

[0052] Table 1 Effects on the autonomic activity of insomnia model rats

[0053]

[0054]

[0055] Note: Compared with the normal control group, P<0.01; compared with the model control group, P<0.05, P<0.01.

[0056] 5.2 Effects on 5-HT content in the hypothalamus of insomnia model rats

[0057] 5-HT is an important transmitter involved in the body's sleep-wake cycle and an indispensable sleep regulator. Its content is negatively correlated with insomnia, anxiety and other diseases. The results show that compared with the normal control group, the 5-HT content in the hypothalamus of the insomnia model rats was significantly reduced (P<0.01); compared with the model control group, the 5-HT content in the hypothalamus of the diazepam group and the medium and high dose groups of the Chinese medicine composition was significantly increased (P<0.05). The results are shown in Table 2.

[0058] Table 2 Effects on 5-HT content in the hypothalamus of insomnia model rats

[0059]

[0060] Note: Compared with the normal control group, P<0.01; compared with the model control group, P<0.05.

[0061] 6. Experimental conclusion

[0062] The Chinese medicine composition can reduce the total distance of spontaneous activity and the number of standing times of insomnia model rats, and upregulate the content of 5-HT in the hypothalamus, indicating that the Chinese medicine composition has a certain sedative and hypnotic effect. Experimental Example 3 Effect of the Chinese medicine composition on spontaneous activity of insomnia mouse model

[0063] 1. Experimental Materials

[0064] 1.1 Animals

[0065] ICR mice, SPF grade, 60 mice, body weight 16-18 g, male.

[0066] Rearing environment: room temperature 20-26℃, relative humidity controlled at 40-70%. Males and females were reared in separate cages, 5 per cage / sex / group.

[0067] 1.2 Drugs

[0068] The Chinese medicine composition was prepared according to the method of Example 1 and provided by Jiangsu Kangyuan Pharmaceutical Co., Ltd.; estazolam (Shandong Xinyi Pharmaceutical Co., Ltd.); p-chlorophenylalanine (PCPA, Sigma); and pentobarbital sodium (Sigma).

[0069] 1.3 Instruments

[0070] Mouse locomotor activity instrument (Chengdu Taimeng); electronic balance (G&G, model TC3K).

[0071] 2. Dosage design

[0072] The daily dosage of the Chinese medicine composition is 4.08 g / day. According to the body surface area conversion method, the equivalent dose for mice is 4.08 g / 60 kg*12.3=0.84 g / kg. According to the 1:2:4 dosing method, the medium dose is 1.68 g / kg and the high dose is 3.36 g / kg. Oral administration, 0.2 mL / 10 g, once a day.

[0073] The clinical daily dose of estazolam for humans is 1 mg. Based on the body surface area conversion method, the equivalent dose for mice is 1 mg / 60 kg*12.3=0.2 mg / kg.

[0074] 3. Experimental Methods

[0075] After 5 days of adaptive feeding, the mice were randomly divided into a normal control group, a model control group, an estazolam group, and a low, medium, and high dose group of the Chinese medicine composition according to their body weight, with 10 mice in each group. Except for the normal control group, the mice in the other groups were intraperitoneally injected with PCPA 400 mg / kg at the same time every day for 2 consecutive days. The status of each group was observed. Except for the control group, the mice showed day and night disorders and mutual attacks, indicating that the insomnia model was successfully established. Starting from the third day, each group was gavaged with the corresponding drug, 0.2 mL / 10 g, once a day, for 7 consecutive days. 30 minutes after the last administration of each group, the mice were placed in the autonomic activity instrument, adapted to the environment for 3 minutes, and the number of activities and standing times of the mice within 5 minutes were measured. The inside of the instrument needs to be cleaned for each experiment to avoid affecting the next experiment. Sodium pentobarbital (45 mg / kg) was injected intraperitoneally 1 hour after the last administration, and the disappearance time of the righting reflex (sleep latency) and sleep time of the mice were observed and recorded.

[0076] 4. Statistical methods

[0077] The results were statistically analyzed using t-test.

[0078] 5. Experimental Results

[0079] 5.1 Effects on the autonomic activity of insomnia model mice

[0080] Compared with the normal control group, the number of activities and standing times of the model control group increased significantly (P<0.05, P<0.01); compared with the model control group, the number of activities and standing times of the mice in the estazolam group and the low, medium and high dose groups of the Chinese medicine composition decreased significantly (P<0.05, P<0.01). The results are shown in Table 3.

[0081] Table 3 Effects on the autonomic activity of insomnia model mice

[0082]

[0083] Note: Compared with the normal control group, # P<0.05, ## P<0.01; compared with the model control group, * P<0.05, ** P<0.01.

[0084] 5.2 Effects on sleep latency and sleep duration in insomnia model mice

[0085] Compared with the normal control group, the sleep latency of mice in the model control group was significantly prolonged, and the total sleep time was significantly reduced (P<0.05). Compared with the model control group, the sleep latency of the estazolam group and the low, medium, and high dose groups of the Chinese medicine composition was significantly reduced, and the sleep time was significantly increased (P<0.05, P<0.01). This shows that the Chinese medicine composition has the effect of shortening the sleep latency and prolonging the sleep time of insomnia mice. The results are shown in Table 4.

[0086] Table 4 Effects on sleep latency and sleep time of insomnia model mice

[0087]

[0088] Note: Compared with the normal control group, # P<0.05; compared with the model control group, * P<0.05, ** P<0.01.

[0089] 6. Experimental conclusion

[0090] The Chinese medicine composition can significantly reduce the number of activities and standing times of autonomous activities of insomnia mice, significantly shorten the sleep latency of insomnia mice, and prolong the sleep time, indicating that the Chinese medicine composition has a certain sedative and hypnotic effect.

[0091] The above embodiments of the present invention are merely examples for clearly illustrating the present invention, and are not intended to limit the embodiments of the present invention. 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 embodiments here. Any modifications, equivalent substitutions and improvements made within the spirit and principles of the present invention should be included in the protection scope of the claims of the present invention.

Claims

1. Use of a Chinese medicine composition in preparing a drug for treating insomnia, characterized in that: The traditional Chinese medicine composition is prepared from raw materials in the following weight proportions: 5-25 parts of Chuanxiong and 1.5-8 parts of Gastrodia elata.

2. The use according to claim 1, characterized in that: The traditional Chinese medicine composition is prepared from raw materials in the following weight proportions: 8-15 parts of Chuanxiong and 2-6 parts of Gastrodia elata.

3. The use according to claim 1, characterized in that: The traditional Chinese medicine composition is prepared from raw materials in the following weight proportions: 8-10 parts of Chuanxiong and 2.5-5 parts of Gastrodia elata.

4. The use according to claim 1, characterized in that: The traditional Chinese medicine composition is prepared from raw materials in the following weight proportions: 10 parts of Chuanxiong and 2.5 parts of Gastrodia elata.

5. The use according to any one of claims 1 to 4, characterized in that: The drug is selected from oral dosage forms, injection dosage forms or external administration preparations.

6. The use according to claim 5, characterized in that: The medicine is selected from decoctions, tablets, capsules, granules, pills, injections, powders, decoctions, suspensions, dispersants, syrups, suppositories, gels, aerosols, patches, and oral liquids.

7. The use according to claim 1, characterized in that: The method for preparing the Chinese medicine composition comprises the following steps: (1) Take two components, Chuanxiong and Gastrodia elata, in a weight ratio of 5-25 of Chuanxiong and 1.5-8 of Gastrodia elata. drying, crushing and mixing the obtained mixture; (2) extracting the mixture by reflux with 70%-90% ethanol for 2-3 times, each time for 1-3 hours, to obtain an extract and a medicinal residue; (3) combining the extracts and filtering to obtain a filtrate; (4) The filtrate is concentrated to a clear paste having a relative density of 1.21-1.30 at 55-65°C.

8. The use according to claim 7, characterized in that: The preparation method of the Chinese medicine composition also includes: (5) decocting the medicinal residue with water for 1-2 hours, combining the decoction, filtering, and concentrating the filtrate after the decoction to a clear paste with a relative density of 1.21-1.30 at 55-65° C., preferably decocting for 1 hour; (6) Combine the clear pastes obtained in step (4) and step (5).

9. The use according to claim 6 or 7, characterized in that: Step (2) is to extract the mixture by reflux with 90% ethanol twice to obtain an extract, each time for 2 hours.

10. Use of a Chinese medicine composition in the preparation of a sedative and / or anti-anxiety and insomnia drug, characterized in that: The traditional Chinese medicine composition is prepared from raw materials in the following weight proportions: 5-25 parts of Chuanxiong and 1.5-8 parts of Gastrodia elata.

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