Application of traditional Chinese medicine composition in preparation of medicine for preventing and / or treating schizophrenia

Abstract

The invention relates to the technical field of traditional Chinese medicines, relates to new application of a traditional Chinese medicine composition, and in particular relates to application of the traditional Chinese medicine composition in preparation of a medicine for preventing and / or schizophrenia. The traditional Chinese medicine composition is prepared from cassia twig, white peony root, honey-fried licorice root, ginger, jujube, ginseng, Chinese angelica, salted morinda officinalis and dwarf lilyturf tuber. The composition disclosed by the invention can be used for remarkably inhibiting impairment of social competence of schizophrenia mice and abnormal increase of glutamic acid concentration of prefrontal cortex, and has a relatively good treatment effect on the schizophrenia mice.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of traditional Chinese medicine, and relates to a new use of a traditional Chinese medicine composition, in particular to application of the traditional Chinese medicine composition in preparation of a medicine for preventing and / or treating schizophrenia. BACKGROUND

[0002] Schizophrenia is a common mental illness characterized by personality change, split thinking, emotion and behavior, and the main symptoms are diverse, but can be attributed to the incoordination of mental activities and environment. The causes of schizophrenia are diverse, including heredity, external factors and trauma. The incidence of schizophrenia is high, and the international statistics show that the annual incidence of general population is about 0.3 per thousand, and due to the disability and common mania characteristics, it brings heavy burden to family and society.

[0003] In addition to emotional and psychological treatment, the current treatment drugs for schizophrenia mainly include sedatives, certain nerve receptor inhibitors and the like, and these drugs have narrow effective time and effective population, and moreover, long-term use is impossible. For the chronic disease of schizophrenia with unknown causes, it is a promising treatment method to exert the low toxicity, root treatment and conditioning characteristics of traditional Chinese medicine. In view of the above problems, the field of traditional Chinese medicine should actively intervene in the prevention and treatment of schizophrenia, and develop and research a symptomatic prescription.

[0004] Therefore, it is of important practical significance to provide the traditional Chinese medicine composition for preventing and / or treating schizophrenia. SUMMARY

[0005] Therefore, it is of important practical significance to provide the traditional Chinese medicine composition for preventing and / or treating schizophrenia.

[0006] In order to achieve the above-mentioned application purposes, the present application provides the following technical scheme:

[0007] The present application provides application of the traditional Chinese medicine composition in preparation of a medicine for preventing and / or treating schizophrenia, and the main active ingredients, in terms of mass parts, include 10-25 parts of Ramulus Cinnamomi, 10-25 parts of Radix Paeoniae Alba, 5-25 parts of Radix Glycyrrhizae, 10-30 parts of Rhizoma Zingiberis Recens, 15-30 parts of Fructus Jujubae, 10-30 parts of Radix Ginseng, 10-30 parts of Radix Angelicae Sinensis, 10-30 parts of Radix Morindae Officinalis and 10-30 parts of Radix Ophiopogonis.

[0008] The prescription takes Ba Ji Tian of Foot-Shaoyin Channel and Renshen of Hand-Shaoyin Channel as the monarch drugs. Ba Ji Tian is sweet and warm, and it can tonify both fire and water without impairing the latter. It can promote the primordial yang from the bottom of the cauldron, and it can also consolidate essence and guard spirit. Renshen is sweet and bitter in taste, and it is slightly warm in nature. It enters Hand-Shaoyin Channel, and it can tonify five Zang organs, calm the spirit, and it can also calm the soul, stop palpitation, open the heart and benefit the intelligence, greatly tonify primordial qi, benefit qi and nourish blood, and nourish the heart and calm the spirit. The two drugs enter heart and kidney respectively, and they are one up and one down, one south and one north, and they communicate between heart and kidney. The assistant drugs, Dang Gui and Gui Zhi, can assist the monarch drugs, and they can also nourish liver blood, and they can also promote liver qi. At the same time, the assistant drugs, Mai Dong and Bai Shao, can also astringe lung metal, and Mai Dong can enter lung channel, and it can astringe lung metal, and it can also descend at night. Bai Shao can also astringe heart qi, and it can also descend at night. The two drugs are one left and one right, and one east and one west, and they can ascend liver and descend lung. The accompanying drugs, Sheng Jiang, Gan Cao, and Da Zao, can also turn the qi of middle-Jiao, and they can also make the ascending and descending coordinated, and they can also rotate the four dimensions, and they can also nourish body fluid, and they can also transport the body fluid of spleen and stomach to harmonize Ying and Wei. In the prescription, Renshen and Ba Ji Tian can jointly exert the function of "making the official strong and the skill excellent", and they can also promote the essence during the day, and Dang Gui and Bai Shao can also exert the function of "the base of stopping extreme", and they can also descend at night. The whole prescription can warm middle-Jiao and tonify deficiency, ascend liver and descend lung, communicate between heart and kidney, regulate qi and blood, and lead yang into yin.

[0009] The raw materials of the prescription are as follows:

[0010] Gui Zhi: the dried tender branch of Cinnamomum cassia Presl of Lauraceae. It enters heart, lung, and bladder channels. It is pungent and sweet, and it is warm in nature.

[0011] Bai Shao: the dried root of Paeonia lactiflora Pall. of Ranunculaceae. It enters liver and spleen channels. It is bitter and sour, and it is cold in nature.

[0012] Gan Cao: the dried root of Glycyrrhiza uralensis Fisch., Glycyrrhiza inflata Bat., or Glycyrrhiza glabra L. of Leguminosae. It enters heart, lung, spleen, and stomach channels. It is sweet, and it is neutral in nature. Zhi Gan Cao is the processed product of Gan Cao, and the processing method can be as follows: take clean Gan Cao slices, add refined honey and a little water, mix well, and then steam for a while. Fry until yellow to dark yellow, and then take out when it is not sticky. Cool down.

[0013] Sheng Jiang: the fresh rhizome of Zingiber officinale Rosc. of Zingiberaceae. It enters lung, spleen, and stomach channels. It is pungent, and it is slightly warm in nature.

[0014] Da Zao: the dried mature fruit of Ziziphus jujuba Mill. var. inermis (Bunge) Rehd. of Rhamnaceae. It enters spleen and stomach channels. It is sweet, and it is warm in nature.

[0015] Ginseng: the dried root of Panax ginseng C. A. Mey. of Araliaceae, the cultivated one is called "garden ginseng", the garden ginseng is dried by sunning or drying, and is called "raw sun-dried ginseng". It belongs to the meridians of spleen, lung and heart. It is sweet and slightly bitter in taste, and is flat.

[0016] Angelica: the dried root of Angelica sinensis (Oliv.) Diels of Umbelliferae. It belongs to the meridians of liver, heart and spleen. It is sweet and pungent, and is warm.

[0017] Morinda: the dried root of Morinda officinalis How of Rubiaceae. It belongs to the meridians of kidney and liver. It is sweet and pungent, and is slightly warm.

[0018] Ophiopogon: the dried tuber of Ophiopogon japonicus (Thunb.) Ker-Gawl. of Liliaceae. It belongs to the meridians of heart, lung and stomach. It is sweet, slightly bitter and cold.

[0019] In some specific embodiments of the present application, the main active ingredients include, in mass parts, 15 parts of Ramulus Cinnamomi, 15 parts of Radix Paeoniae Alba, 12 parts of Glycyrrhizae, 18 parts of Zingiber officinale, 18 parts of Fructus Jujubae, 10 parts of Panax ginseng, 15 parts of Angelica, 10 parts of Morinda, and 10 parts of Ophiopogon.

[0020] In some specific embodiments of the present application, the Glycyrrhizae is Glycyrrhizae Radix Baked, and the Morinda is Morinda officinalis How. The Glycyrrhizae Radix Baked is sweet in taste and warm in nature, and has stronger effects of strengthening the spleen and tonifying qi, warming the middle and invigorating the body. The Morinda officinalis How is warm but not dry, has relatively weak toxicity, and has stronger effects.

[0021] In some specific embodiments of the present application, the medicine further includes a medically acceptable excipient. Specifically, the excipient used is a carrier or excipient commonly used in the art, including but not limited to starch, lactose, glucose, sodium carboxymethyl cellulose, ethyl cellulose, methyl cellulose, malt, gelatin, polyhydric alcohols (such as propylene glycol, glycerol, mannitol), tablet pressing agents, etc., to help improve the stability or activity of the medicine, or produce an acceptable taste or smell in the case of oral administration.

[0022] In some specific embodiments of the present application, the dosage form of the medicine is a decoction, a tablet, a capsule, a granule, an oral liquid or a dripping pill. Thus, the clinical administration is facilitated.

[0023] In some specific embodiments of the present application, the preparation method of the traditional Chinese medicine composition includes: mixing the raw medicinal materials according to the ratio, adding water to decoct twice, adding 10 times the amount of water to decoct for 1.5 hours the first time, adding 8 times the amount of water to decoct for 1 hour the second time, combining the decoction, filtering, and concentrating the filtrate to a relative density of 1.10-1.20 (60°C) of the extract, to obtain the traditional Chinese medicine composition.

[0024] In some embodiments of the present application, the preparation method of the medicine comprises: mixing the raw medicinal materials according to the proportion, decocting twice with water, decocting for 1.5 hours with 10 times the amount of water the first time and decocting for 1 hour with 8 times the amount of water the second time, combining the decoction, filtering, concentrating the filtrate to the relative density of 1.10-1.20 (60°C), and mixing with the excipients to obtain the medicine.

[0025] or mixing the raw medicinal materials according to the proportion, water extracting twice with 8-10 times the weight of water, combining the water extracts, and concentrating to 1 gram of crude drug / mL.

[0026] In some embodiments of the present application, when the dosage form of the medicine is a decoction, the preparation method comprises the following steps:

[0027] mixing the raw medicinal materials according to the proportion, decocting for 30-40 minutes with 8-10 times the weight of water, and obtaining the medicine.

[0028] In some embodiments of the present application, when the dosage form of the medicine is a tablet, a capsule, a granule, an oral liquid or a dripping pill, the preparation method comprises the following steps:

[0029] mixing the raw medicinal materials according to the proportion, water extracting twice with 8-10 times the weight of water, combining the water extracts, concentrating to 1 gram of crude drug / mL, adding excipients, and preparing the corresponding dosage form according to the conventional method in the art to obtain the medicine.

[0030] In some embodiments of the present application, the prevention and / or treatment of schizophrenia comprises: inhibiting the impairment of social interaction ability and the abnormal increase of glutamate concentration in the prefrontal cortex of schizophrenic mice.

[0031] The present application provides the application of the traditional Chinese medicine composition in the preparation of a medicine for preventing and / or treating schizophrenia. The composition of the present application can significantly inhibit the impairment of social interaction ability and the abnormal increase of glutamate concentration in the prefrontal cortex of schizophrenic mice, and has a good therapeutic effect on schizophrenic mice. DETAILED DESCRIPTION

[0032] The present application discloses the application of a traditional Chinese medicine composition in the preparation of a medicine for preventing and / or treating schizophrenia. Those skilled in the art can refer to the content herein and appropriately improve the process parameters for implementation. It is particularly pointed out that all similar substitutions and changes are obvious to those skilled in the art, and they are all regarded as included in the present application. The method and application of the present application have been described by 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 application, to realize and apply the present application technology.

[0033] The following experiments were carried out according to the conventional conditions or the conditions recommended by the manufacturer unless otherwise specified. The raw materials or excipients used, and the reagents or instruments used, are all conventional products that can be obtained commercially unless the manufacturer is specified. All percentages, ratios, proportions or parts are by weight unless otherwise specified.

[0034] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs. In addition, any method and material similar or equivalent to those described herein can be used in the present application.

[0035] The present application is further illustrated by the following examples:

[0036] Example 1 Preparation of granules of the traditional Chinese medicine composition in the present application

[0037] Take 250 g of cassia twig, 250 g of white peony root, 200 g of fried licorice root, 300 g of raw ginger, 300 g of jujube, 167 g of ginseng, 250 g of angelica, 167 g of baijiatian, and 167 g of ophiopogon japonicus. Add water and decoct twice. The first time, add 10 times the amount of water and decoct for 1.5 hours. The second time, add 8 times the amount of water and decoct for 1 hour. Combine the decoctions, filter, and concentrate the filtrate to a relative density of 1.10-1.20 (60°C) of extract. Add 200 g of maltodextrin, dry, and pulverize into fine powder. Mix with maltodextrin, and make granules. Dry to make 1000 g.

[0038] Experimental Example 2 Therapeutic effect of the traditional Chinese medicine composition on the schizophrenia model induced by dizocilpine maleate (MK-801) in mice

[0039] 1. Experimental materials

[0040] 1.1 Animals

[0041] C57BL / 6J mice, SPF level, 54, body weight 18-22 g, male.

[0042] Housing environment: room temperature 20-26°C, relative humidity controlled at 40-70%, 5 / cage.

[0043] 1.2 Drugs

[0044] Traditional Chinese medicine composition prepared in Example 1 (Jiangsu Kangle Pharmaceutical Co., Ltd.); Dizocilpine maleate (MK-801, Sigma, CAS 77086-22-7); Risperidone tablets (Xi'an Yangsen Pharmaceutical Co., Ltd., batch number: KDJ2TPH); Glutamate test kit (Nanjing Jiancheng Biological Engineering Institute, A074-1-1)

[0045] 1.3 Instruments

[0046] Electronic balance (Sartorius Scientific Instruments Co., Ltd., model BS224S); electronic balance (G&G, model TC3K); UV spectrophotometer (Thermo, GENESYS TM 50UV-Vis spectrophotometer); behavioral software (Ravood, SMARTV3.0).

[0047] 2. Design of measurement

[0048] The daily dose of traditional Chinese medicine composition is 123g of crude drug per day, and according to the body surface area conversion method, the equivalent dose of mice is 123g / 60kg*12.3=25.22g of crude drug / kg. Set this dose as the medium dose group, then the low dose is 12.61g of crude drug / kg and the high dose is 50.44g of crude drug / kg. Gavage administration, once a day.

[0049] MK-801 was dissolved in 0.9% normal saline to prepare a 0.01mg / ml solution, injected intraperitoneally once a day, with a daily dose of 0.1mg / kg.

[0050] Risperidone tablets were dissolved in 0.9% normal saline to prepare a 0.01mg / ml solution, injected intraperitoneally once a day, with a daily dose of 0.1mg / kg.

[0051] 3. Experimental method

[0052] C57BL / 6J mice were adaptively fed for 7 days with free access to feed and water. According to the body weight, they were randomly divided into normal control group, model control group, risperidone control group, traditional Chinese medicine composition high, medium and low dose groups, each group of 9.

[0053] The normal control group was injected intraperitoneally with 200μl of normal saline per mouse, the model control group, risperidone control group, traditional Chinese medicine composition high, medium and low dose groups were injected intraperitoneally with 200μl of MK-801 per mouse, once a day for 14 consecutive days. After the last injection of MK-801, the risperidone group was injected intraperitoneally with 200μl of risperidone per mouse, once a day for 14 consecutive days; the traditional Chinese medicine composition high, medium and low dose groups were given 0.2ml / 10g gavage, once a day for 14 consecutive days; the normal control group and model group were given the same amount of distilled water under the same conditions.

[0054] After the last administration of positive drugs and traditional Chinese medicine composition, the following tests were performed:

[0055] 3.1 Three-box social interaction

[0056] The device consisted of an opaque white resin glass box, divided into a central chamber and two side chambers. Each side chamber contained a plastic cup, and an opening in the wall between the three chambers allowed mice to pass through. Mice were acclimatized for 20 minutes / day for two consecutive days prior to the test, allowing free exploration. On the test day, the mice initially explored the three-box area for 10 minutes, during which two black partitions completely covered the side chambers containing the cups. Afterward, the resin glass partitions were removed, and an unfamiliar male C57BL / 6 mouse was placed in one cup (social stimulus), while the other cup remained empty (no vital stimulus). The mice freely explored all chambers for 10 minutes, during which time the activity was recorded. During the subject-specific test, the position of the object mouse changed between the left and right chambers. The video files were analyzed using SMART 3.0 software. To calculate the results, we used the Social Preference Index (FS) / (F+S), where F is the time spent in the social chamber and S is the time spent in the non-social chamber.

[0057] 3.2 Determination of glutamate content in the prefrontal cortex of brain tissue

[0058] After the three-box social interaction test was completed, the prefrontal cortex of mouse brain tissue was taken and prepared into a homogenate for the detection of glutamate content. The detection method was carried out in accordance with the kit instructions.

[0059]

[0060]

[0061]

[0062] C 标准 Standard concentration: 200 μmol / L;

[0063] 4: Sample pretreatment (adding reagent one) dilution factor;

[0064] Cpr: Tissue homogenate protein concentration, gprot / L (prot refers to protein).

[0065] 4. Statistical Methods

[0066] The results were statistically analyzed using t-tests.

[0067] 5. Experimental Results

[0068] After 14 days of continuous intraperitoneal injection of MK-801 (0.1 mg / kg), compared with the normal control group, the social preference index of the model group mice was significantly reduced (P < 0.01), indicating that the social ability of the model group mice was impaired and the contact time with unfamiliar mice was reduced. Compared with the model group mice, the social preference index of the positive drug control group mice was significantly increased (P < 0.01), indicating that the positive drug was effective in treating the social ability impairment in schizophrenia model mice. Compared with the model group mice, the social preference index of the medium-dose group (P < 0.05) and high-dose group (P < 0.01) of the traditional Chinese medicine composition was significantly increased, indicating that the high dose of the traditional Chinese medicine composition was effective in treating the social ability impairment in schizophrenia model mice. See Table 1.

[0069] Table 1. Effects of traditional Chinese medicine composition on the three-box socialization test in schizophrenic mice (n=9)

[0070]

[0071]

[0072] Note: Compared with the normal control group, ##P < 0.01; compared with the model control group, *P < 0.05, **P < 0.01. ns P > 0.05.

[0073] Compared with the normal control group, the concentration of glutamate in the prefrontal cortex of the brain tissue of the model group mice was significantly increased (P < 0.001), indicating abnormal glutamate production in the model group mice. Compared with the model group mice, the concentration of glutamate in the prefrontal cortex of the brain tissue of the positive drug group mice was significantly decreased (P < 0.01), indicating that the positive drug was effective in treating the abnormally high concentration of glutamate in the prefrontal cortex of schizophrenia model mice. Compared with the model group mice, the concentration of glutamate in the medium-dose group (P < 0.001) and high-dose group (P < 0.001) of the traditional Chinese medicine composition was significantly decreased, indicating that the high dose of the traditional Chinese medicine composition was effective in treating the abnormally high concentration of glutamate in the prefrontal cortex of schizophrenia model mice. See Table 2.

[0074] Table 2. Effects of traditional Chinese medicine composition on glutamate concentration in the prefrontal cortex of schizophrenic mice (n=9)

[0075]

[0076] Note: Compared with the normal control group, ##P < 0.001; compared with the model control group, ***P < 0.001. ns P > 0.05.

[0077] 6. Experimental Conclusions

[0078] The traditional Chinese medicine composition at concentrations of 25.22g and 50.44g crude drug / kg significantly inhibited the decrease in social preference index and the abnormal increase in glutamate concentration in the prefrontal cortex of schizophrenia model mice, indicating that the traditional Chinese medicine composition has a certain therapeutic effect on MK-801-induced schizophrenia model mice.

[0079] Experimental Example 3: Therapeutic effect of traditional Chinese medicine composition on ketamine-induced mouse schizophrenia model

[0080] 1. Experimental Materials

[0081] 1.1 Animals

[0082] C57BL / 6J mice, SPF grade, 54 mice, weighing 18-22g, male.

[0083] Rearing environment: Room temperature 20-26℃, relative humidity controlled at 40-70%, 5 animals / cage.

[0084] 1.2 Drugs

[0085] The traditional Chinese medicine composition prepared in Example 1 is from Jiangsu Kangyuan Pharmaceutical Co., Ltd.; ketamine hydrochloride injection (Fujian Gutian Pharmaceutical Co., Ltd., National Drug Approval Number: H35020148); risperidone tablets (Xi'an Janssen Pharmaceutical Co., Ltd., Batch Number: KDJ2TPH); glutamate test kit (Nanjing Jiancheng Bioengineering Institute, A074-1-1).

[0086] 1.3 Instruments

[0087] Electronic balance (Sartorius Scientific Instruments, BS224S); Electronic balance (G&G, TC3K); Ultraviolet spectrophotometer (Thermo Fisher Scientific, GENESYS) TM 50UV-Vis spectrophotometer; behavioral software (Reward, SMART V3.0).

[0088] 2. Measurement Design

[0089] The daily dosage of the herbal composition is 123g of raw drug / day. Based on the body surface area calculation method, the equivalent dose for mice is 123g / 60kg * 12.3 = 25.22g of raw drug / kg. This dose is designated as the medium-dose group; the low-dose group is 12.61g of raw drug / kg, and the high-dose group is 50.44g of raw drug / kg. Administered by gavage once daily.

[0090] The concentration of ketamine is 10 mg / ml. It is diluted to 3 mg / ml and administered once daily via intraperitoneal injection. The daily dose is 30 mg / kg.

[0091] Dissolve risperidone tablets in 0.9% saline to prepare a 0.01 mg / ml solution. Administer once daily via intraperitoneal injection. The daily dose is 0.1 mg / kg.

[0092] 3. Experimental Methods

[0093] C57BL / 6J mice were acclimatized for 7 days with free access to feed and water. They were then randomly divided into four groups according to body weight: a normal control group, a model control group, a risperidone control group, and high, medium, and low dose groups of the traditional Chinese medicine composition, with 9 mice in each group.

[0094] The normal control group received an intraperitoneal injection of 200 μl of physiological saline per animal. The model control group, risperidone control group, and the high, medium, and low dose groups of the traditional Chinese medicine composition received an intraperitoneal injection of 200 μl of ketamine per animal, once daily for 14 consecutive days. After the last ketamine injection, the risperidone group received an intraperitoneal injection of 200 μl of risperidone per animal, once daily for 14 consecutive days; the high, medium, and low dose groups of the traditional Chinese medicine composition received 0.2 ml / 10 g by gavage, once daily for 14 consecutive days; the normal control group and the model group were given the same volume of distilled water under the same conditions.

[0095] 3.1 Three-box social

[0096] The device consisted of an opaque white resin glass box, divided into a central chamber and two side chambers. Each side chamber contained a plastic cup, and an opening in the wall between the three chambers allowed mice to pass through. Mice were acclimatized for 20 minutes / day for two consecutive days prior to the test, allowing free exploration. On the test day, the mice initially explored the three-box area for 10 minutes, during which two black partitions completely covered the side chambers containing the cups. Afterward, the resin glass partitions were removed, and an unfamiliar male C57BL / 6 mouse was placed in one cup (social stimulus), while the other cup remained empty (no vital stimulus). The mice freely explored all chambers for 10 minutes, during which time the activity was recorded. During the subject-specific test, the position of the object mouse changed between the left and right chambers. The video files were analyzed using SMART 3.0 software. To calculate the results, we used the Social Preference Index (FS) / (F+S), where F is the time spent in the social chamber and S is the time spent in the non-social chamber.

[0097] 3.2 Determination of glutamate content in the prefrontal cortex of brain tissue

[0098] After the three-box social interaction test was completed, the prefrontal cortex of mouse brain tissue was taken and prepared into a homogenate for the detection of glutamate content. The detection method was carried out in accordance with the kit instructions.

[0099]

[0100]

[0101] C 标准 Standard concentration: 200 μmol / L;

[0102] 4: Sample pretreatment (adding reagent one) dilution factor;

[0103] Cpr: Tissue homogenate protein concentration, gprot / L (prot refers to protein).

[0104] 4. Statistical Methods

[0105] The results were statistically analyzed using t-tests.

[0106] 5. Experimental Results

[0107] After 14 days of continuous intraperitoneal injection of ketamine (30 mg / kg), the social preference index of mice in the model group was significantly lower than that of the normal control group (P < 0.01), indicating that the social ability of mice in the model group was impaired and the contact time with unfamiliar mice was reduced. Compared with the model group, the social preference index of mice in the positive drug control group was significantly higher (P < 0.01), indicating that the positive drug was effective in treating the social ability impairment of mice with schizophrenia. Compared with the model group, the social preference index of mice in the medium-dose group (P < 0.05) and high-dose group (P < 0.001) of the traditional Chinese medicine composition was significantly higher, indicating that the high-dose group of the traditional Chinese medicine composition was effective in treating the social ability impairment of mice with schizophrenia.

[0108] Table 3. Effects of traditional Chinese medicine compositions on the three-box socialization test in schizophrenic mice (n=9)

[0109]

[0110] Note: Compared with the normal control group, ##P < 0.001; compared with the model control group, *P < 0.05, ***P < 0.001. ns P > 0.05.

[0111] Compared with the normal control group, the concentration of glutamate in the prefrontal cortex of the brain tissue of the model group mice was significantly increased (P < 0.001), indicating that glutamate production in the model group mice was abnormal. Compared with the model group mice, the concentration of glutamate in the prefrontal cortex of the brain tissue of the positive drug group mice was significantly decreased (P < 0.001), indicating that the positive drug was effective in treating the abnormally high concentration of glutamate in the prefrontal cortex of schizophrenia model mice. Compared with the model group mice, the concentration of glutamate in the medium-dose (P < 0.001) and high-dose (P < 0.001) groups of the traditional Chinese medicine composition was significantly decreased, indicating that the high dose of the traditional Chinese medicine composition was effective in treating the abnormally high concentration of glutamate in the prefrontal cortex of schizophrenia model mice.

[0112] Table 4. Effects of traditional Chinese medicine composition on glutamate concentration in the prefrontal cortex of schizophrenic mice (n=9)

[0113]

[0114]

[0115] Note: Compared with the normal control group, ##P < 0.001; compared with the model control group, ***P < 0.001. ns P > 0.05.

[0116] 6. Experimental Conclusions

[0117] The traditional Chinese medicine composition at concentrations of 25.22 g and 50.44 g crude drug / kg significantly inhibited the decrease in social preference index and the abnormal increase in glutamate concentration in the prefrontal cortex of schizophrenia model mice, suggesting that the traditional Chinese medicine composition has a certain therapeutic effect on ketamine-induced schizophrenia model mice.

[0118] The above embodiments of the present invention are merely examples to clearly illustrate the present invention and are not intended to limit the implementation of the present invention. Those skilled in the art can make other variations or modifications based on the above description. It is neither necessary nor possible to exhaustively describe all embodiments here. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of the present invention should be included within the scope of protection of the claims of the present invention.

Claims

1. The application of a traditional Chinese medicine composition in the preparation of a medicament for the prevention and / or treatment of schizophrenia, characterized in that, The traditional Chinese medicine composition comprises, by weight:

2. The application as described in claim 1, characterized in that, The traditional Chinese medicine composition comprises, by weight:

3. The application as described in claim 1 or 2, characterized in that, The licorice mentioned is roasted licorice, and the Morinda officinalis mentioned is salt-processed Morinda officinalis.

4. The application as described in any one of claims 1 to 3, characterized in that, The drug includes the traditional Chinese medicine composition and pharmaceutically acceptable excipients.

5. The application as described in any one of claims 1 to 4, characterized in that, The dosage form of the drug is one or more of the following: granules, decoction, tablets, capsules, oral liquid, or pills.

6. The application as described in any one of claims 1 to 5, characterized in that, The preparation method of the traditional Chinese medicine composition includes: mixing the raw medicinal materials according to the ratio, adding water and decocting twice. The first decoction is decocted with 10 times the amount of water for 1.5 hours, and the second decoction is decocted with 8 times the amount of water for 1 hour. The decoctions are combined, filtered, and the filtrate is concentrated to an extract with a relative density of 1.10 to 1.20 (60°C).

7. The application as described in any one of claims 1 to 6, characterized in that, The preparation method of the drug includes: mixing the raw medicinal materials according to the ratio, adding water and decocting twice. The first decoction is decocted for 1.5 hours with 10 times the amount of water, and the second decoction is decocted for 1 hour with 8 times the amount of water. The decoctions are combined, filtered, and the filtrate is concentrated to an extract with a relative density of 1.10 to 1.20 (60°C). The extract is then mixed with excipients to obtain the final product. Alternatively, mix the raw medicinal materials according to the specified ratio, add 8 to 10 times the weight of water, extract twice with water, combine the water extracts, and concentrate to 1 gram of raw drug / mL.

8. The application as described in claim 7, characterized in that, When the dosage form of the drug is granules, its preparation method includes: mixing the raw medicinal materials according to the ratio, adding water and decocting twice, adding 10 times the amount of water for 1.5 hours for the first decoction, adding 8 times the amount of water for 1 hour for the second decoction, combining the decoctions, filtering, concentrating the filtrate to an extract with a relative density of 1.10 to 1.20 (60°C), adding maltodextrin, drying, pulverizing into fine powder, adding maltodextrin, mixing well, making granules, drying, and obtaining the drug. When the dosage form of the drug is a decoction, tablet, capsule, oral liquid or drop pill, its preparation method includes: mixing each raw medicinal material according to the ratio, adding 8 to 10 parts by weight of water, extracting twice with water, combining the water extracts, concentrating to 1 gram of crude drug / mL, adding excipients, and preparing the corresponding dosage form.

9. The application as described in any one of claims 1 to 8, characterized in that, The prevention and / or treatment of schizophrenia includes: inhibiting impaired social skills and abnormally elevated glutamate concentrations in the prefrontal cortex of schizophrenic mice.

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