CN114984097A - Preparation method and application of antidepressant composition - Google Patents
Preparation method and application of antidepressant composition Download PDFInfo
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- CN114984097A CN114984097A CN202210664686.9A CN202210664686A CN114984097A CN 114984097 A CN114984097 A CN 114984097A CN 202210664686 A CN202210664686 A CN 202210664686A CN 114984097 A CN114984097 A CN 114984097A
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/72—Rhamnaceae (Buckthorn family), e.g. buckthorn, chewstick or umbrella-tree
- A61K36/725—Ziziphus, e.g. jujube
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/06—Fungi, e.g. yeasts
- A61K36/07—Basidiomycota, e.g. Cryptococcus
- A61K36/074—Ganoderma
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/31—Extraction of the material involving untreated material, e.g. fruit juice or sap obtained from fresh plants
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/54—Improvements relating to the production of bulk chemicals using solvents, e.g. supercritical solvents or ionic liquids
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- Microbiology (AREA)
- Medical Informatics (AREA)
- Biotechnology (AREA)
- Alternative & Traditional Medicine (AREA)
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- Bioinformatics & Cheminformatics (AREA)
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Abstract
The invention discloses a preparation method and application of an antidepressant composition. Belongs to the field of medicine; the antidepressant composition comprises semen Ziziphi Spinosae oil and wall-broken Ganoderma spore powder; the preparation method comprises the following steps: preparing wild jujube kernel oil; preparing wall-broken ganoderma lucidum spore powder; mixing the prepared wild jujube kernel oil and the wall-broken ganoderma lucidum spore powder, adding a small amount of the powder into the oil for multiple times, and circulating for 30 minutes by using a colloid mill to finally prepare the antidepressant composition. In the composition, the spina date seed oil and the wall-broken spore powder are fully and uniformly ground, so that the wall-broken ganoderma lucidum spore powder can be completely wrapped, and the oxidation resistance of the wall-broken ganoderma lucidum spore powder is enhanced; the composition can be used for preparing medicaments for treating and preventing depression, wherein the medicaments can be prepared into oral preparations such as soft capsules.
Description
Technical Field
The invention belongs to the field of medicines, and relates to a preparation method and application of an antidepressant composition.
Background
Depression is also known as depressive disorder, often mistakenly interpreted by a person as a common mood swing, which is actually a psychological disorder. According to World Health Organization (WHO) data, more than 3.2 million people worldwide have depression. However, the pathophysiological mechanisms of depression are complex, and the central mental disorder presented by patients involves pathological changes of multiple systems and involves metabolic and microstructural abnormalities in vivo. The existing treatment method for depression mainly comprises antidepressant drugs and assists physical therapy and psychological therapy. There are dozens of drugs for depression, mainly monoamine oxidase inhibitors, tricyclic drugs and selective serotonin reuptake inhibitors. However, the medicines have the problems of long effective time, strong side effect, different drug sensitivity of people and the like.
The traditional Chinese medicine puts depression into the category of depression syndrome, and indicates that the cause of depression is mainly emotional damage or extreme seven emotions, so that liver failure and liver depression and qi stagnation are caused. Different from the traditional body diseases, the exterior syndrome refers to stagnation of qi and blood and the disease is caused by the coexistence of mental symptoms and body symptoms. During treatment, the liver should be soothed and depressed, and qi should be regulated and tranquilized.
The spina date seed is a dry and mature seed collected in late autumn and early winter of Rhamnaceae plant Ziziphus jujube, has the effects of nourishing heart and liver, calming heart and tranquilizing mind, and is an important medicinal material for treating palpitation and insomnia. In recent years, due to the opening of the medicinal material market, the mixed filling of other plant seeds is continuously found in the commercial medicinal materials of the spina date seeds, and the spina date seeds are commonly mixed and filled with the same names of the Yunnan jujube kernels, the Burma jujube kernels or the Liziren of the same family, so that the quality of the spina date seeds and the preparation thereof is unstable. The spina date seeds are distributed in Hebei, Jilin, Liaoning, Shandong, Shanxi, Shaanxi, Henan, Gansu and other places, are one of the medicinal materials in the Taoism of Hebei, and the spina date seeds produced in the Hebei have the advantages of good quality, good quality and the like. The wild jujube kernel oil is a hydrophobic oil substance extracted from wild jujube seeds, mainly comprises palmitic acid, oleic acid, linoleic acid, eicosenoic acid, arachidic acid and the like, and can obviously reduce the levels of total cholesterol, low-density lipoprotein and triglyceride and reduce fatty liver degeneration.
The ganoderma lucidum is a traditional famous and precious traditional Chinese medicine, is recorded in ancient books such as Shennong's herbal Jing and Ben Cao gang mu, has the efficacies of benefiting heart qi, entering heart and generating blood, assisting heart and invigorating pulse, soothing the nerves, benefiting vital essence and strengthening muscles and bones, and is listed as the top grade. The traditional medicinal part of ganoderma is limited to the fruit body, while ganoderma lucidum spore is the tiny egg-shaped germ cell, namely the seed of ganoderma lucidum, which is shot from the fold of ganoderma lucidum in the mature period of ganoderma lucidum. Each Ganoderma spore is 4-6 μm and is living organism. The ganoderma lucidum spore powder has all genetic materials and health care functions of ganoderma lucidum, and researches show that the ganoderma lucidum spore has the functions of enhancing the immunity of organisms, inhibiting tumors, protecting liver from being damaged and protecting radiation.
The ganoderma lucidum spores are of a double-wall structure and are surrounded by hard chitin cellulose, so that the ganoderma lucidum spores are difficult to fully absorb by a human body and are more suitable for direct absorption of intestines and stomachs of the human body after wall breaking. After the wall breaking of the prior art is utilized, the effective components in the ganoderma lucidum spores are easy to oxidize due to improper preservation, the quality of the ganoderma lucidum spore powder can be influenced, various auxiliary materials and additives are added in the production process to prevent oxidation in the prior art, and the actual using effect of the wall breaking ganoderma lucidum spore powder can be influenced.
Disclosure of Invention
The purpose of the invention is as follows: the invention aims to provide a composition for treating depression, a preparation method and application thereof.
The technical scheme is as follows: the preparation method of the antidepressant composition comprises the following raw materials in parts by weight: 10-15 parts of wild jujube kernel oil and 4-5 parts of wall-broken ganoderma lucidum spore powder.
Further, the antidepressant composition comprises the following raw materials in parts by weight: 10 parts of wild jujube kernel oil and 4 parts of wall-broken ganoderma spore powder.
Further, the antidepressant composition comprises the following raw materials in parts by weight: 15 parts of wild jujube kernel oil and 4.5 parts of wall-broken ganoderma spore powder.
Further, the antidepressant composition comprises the following raw materials in parts by weight: 5 parts of wild jujube kernel oil and 2 parts of wall-broken ganoderma lucidum spore powder.
Further, the preparation method of the antidepressant composition is characterized by comprising the following specific preparation steps of:
(1) preparing wild jujube kernel oil;
(2) preparing wall-broken ganoderma lucidum spore powder;
(3) mixing the prepared wild jujube kernel oil and the wall-broken ganoderma lucidum spore powder, adding a small amount of the powder into the oil for multiple times, and circulating for 30 minutes by using a colloid mill to finally prepare the antidepressant composition.
Further, in the step (1), the preparation process of the wild jujube kernel oil is as follows:
firstly, selecting spina date seeds; cleaning and drying;
then, crushing the cleaned and dried spina date seeds into powder, and sieving the powder by a 80-mesh sieve, wherein the water content is controlled to be less than or equal to 10 percent in the process;
and finally, putting the spina date seed powder into a CO2 supercritical extraction kettle for extraction to obtain the spina date seed oil.
Further, in the CO2 supercritical extraction kettle, the extraction temperature is 40-50 ℃, the pressure is 18-25MPa, the flow rate of CO2 is 20kg/h, and the extraction time is 2-4 hours.
Further, in the step (2), the preparation process of the wall-broken ganoderma lucidum spore powder is as follows:
firstly, selecting ganoderma lucidum spore powder;
then, breaking the wall of the ganoderma lucidum spore powder to prepare wall-broken ganoderma lucidum spore powder;
wherein the wall-breaking rate of the wall-broken ganoderma lucidum spore powder is more than or equal to 95 percent.
Furthermore, the antidepressant composition prepared by the preparation method is applied to the medicaments for treating depression.
Has the beneficial effects that: compared with the prior art, animal experiments prove that the composition can shorten the immobility time of tail suspension and forced swimming of mice and has the effect of resisting depression; in the composition, the spina date seed oil and the wall-broken spore powder are fully and uniformly ground, so that the wall-broken ganoderma lucidum spore powder can be completely wrapped, and the oxidation resistance of the wall-broken ganoderma lucidum spore powder is enhanced; the composition can be used for preparing medicaments for treating and preventing depression, wherein the medicaments can be prepared into oral preparations such as soft capsules.
Detailed Description
The present invention will be further described with reference to the following examples.
The invention relates to a process for extracting ganoderma lucidum and ganoderma lucidum spores rich in ganoderic acid components, which comprises the following steps:
the invention provides a composition for treating depression, which comprises the following raw materials in parts by weight: 10-15 parts of wild jujube kernel oil and 4-5 parts of wall-broken ganoderma spore powder; preferably 5 parts of wild jujube kernel oil and 2 parts of wall-broken ganoderma lucidum spore powder.
1. The optimized wild jujube seed oil is prepared by the following process:
1.1, preferably spina date seeds;
1.2, crushing clean and dry spina date seeds into powder, and sieving the powder by a 80-mesh sieve, wherein the water content is controlled to be below 10 percent;
1.3, putting the wild jujube seed powder into a CO2 supercritical extraction kettle, extracting for 2-4 hours at the temperature of 40-50 ℃, under the pressure of 18-25MPa and under the flow rate of 20kg/h of CO2 to obtain the wild jujube seed oil, wherein the yield is 2-3%.
The preferred extraction temperature is 45-48 ℃;
the preferred extraction pressure is 20-25 MPa;
the preferred extraction time is 3-4 hours.
The preferred wall-broken ganoderma lucidum spore powder has the wall-broken rate of more than or equal to 95 percent.
Mixing 10-15 parts of optimized wild jujube kernel oil and 4-5 parts of wall-broken ganoderma lucidum spore powder, adding a small amount of the powder into the oil for multiple times, and circulating for about 30 minutes by using a colloid mill to obtain the composition.
The composition can be used for preparing a medicament for treating depression, and the dosage form of the medicament is preferably soft capsules.
Comparative example 1:
1. the optimized wild jujube seed oil is prepared by the following process:
1.1, preferably spine date seed, from the hebeichen stage;
1.2, crushing clean and dry spina date seeds into powder, and sieving the powder by a 80-mesh sieve, wherein the water content is controlled to be below 10 percent;
1.3, putting the spina date seed powder into a CO2 supercritical extraction kettle, extracting for 3-4 hours at the temperature of 40-45 ℃, under the pressure of 20-25Mpa and under the flow rate of 20kg/h of CO2 to obtain the spina date seed oil, wherein the yield is 2-3 percent.
2. The wall-broken ganoderma lucidum spore powder is preferably selected, and the wall-broken rate is more than or equal to 95 percent;
3. mixing 5 parts of optimized wild jujube kernel oil and 2 parts of wall-broken ganoderma lucidum spore powder, adding a small amount of the powder into the oil for multiple times, and circulating for about 30 minutes by using a colloid mill to obtain the composition.
Comparative example 2:
1. the optimized wild jujube kernel oil is prepared by the following process:
1.1, preferably, wild jujube seed, from the hechen platform;
1.2, crushing clean and dry spina date seeds into powder, and sieving the powder by a 80-mesh sieve, wherein the water content is controlled to be below 10 percent;
1.3, putting the wild jujube seed powder into a CO2 supercritical extraction kettle, extracting for 3-4 hours at the temperature of 45-48 ℃, under the pressure of 18-20MPa and under the flow rate of 20kg/h of CO2 to obtain the wild jujube seed oil.
2. The preferred wall-broken ganoderma lucidum spore powder has the wall-broken rate of more than or equal to 95 percent
3. Mixing 5 parts of optimized wild jujube kernel oil and 2 parts of wall-broken ganoderma lucidum spore powder, adding a small amount of the powder into the oil for multiple times, and circulating for about 30 minutes by using a colloid mill to obtain the composition.
Comparative example 3:
1. the optimized wild jujube kernel oil is prepared by the following process:
1.1, preferably, wild jujube seed, from the hechen platform;
1.2, crushing clean and dry spina date seeds into powder, and sieving the powder by a 80-mesh sieve, wherein the water content is controlled to be below 10 percent;
1.3, putting the wild jujube seed powder into a CO2 supercritical extraction kettle, extracting for 2-3 hours at the temperature of 45-48 ℃, under the pressure of 20-25MPa and under the flow rate of 20kg/h of CO2 to obtain the wild jujube seed oil, wherein the yield is 2-3 percent.
2. The wall-broken ganoderma lucidum spore powder is preferably selected, and the wall-broken rate is more than or equal to 95 percent;
3. mixing 5 parts of optimized wild jujube kernel oil and 2 parts of wall-broken ganoderma lucidum spore powder, adding a small amount of the powder into the oil for multiple times, and circulating for about 30 minutes by using a colloid mill to obtain the composition.
Comparative example 4:
1. the optimized wild jujube kernel oil is prepared by the following process:
1.1, preferably, wild jujube seed, from the hechen platform;
1.2, crushing clean and dry spina date seeds into powder, and sieving the powder by a 80-mesh sieve, wherein the water content is controlled to be below 10 percent;
1.3, putting the wild jujube seed powder into a CO2 supercritical extraction kettle, extracting for 3-4 hours at the temperature of 45-48 ℃, under the pressure of 20-25MPa and under the flow rate of 20kg/h of CO2 to obtain the wild jujube seed oil, wherein the yield is 2-3%.
2. The wall-broken ganoderma lucidum spore powder is preferably selected, and the wall-broken rate is more than or equal to 95 percent;
3. mixing 10 parts of optimized wild jujube kernel oil and 3 parts of wall-broken ganoderma lucidum spore powder, adding a small amount of the powder into the oil for multiple times, and circulating for about 30 minutes by using a colloid mill to obtain the composition.
Animal experiments:
the beneficial effects of the invention are further illustrated by animal experiments.
1. Laboratory animal
ICR male mice, weight 18 + -22 g, provided by the animal laboratory of certain university of medicine, were fed with conventional pellet feed, and the feeding conditions were: air-conditioning room, temperature 18-24 deg.C, relative humidity 70%; animals were acclimatized for 1 week at 22 ℃, 50% relative humidity and 12 hours light-12 hours dark; the animals had free access to food and water.
2. Tail suspension experiment of mice
The tail suspension experiment is a classic method capable of rapidly evaluating the drug effects of antidepressant drugs, stimulants and sedatives; the principle is that the mouse tries to escape after hanging the tail but cannot escape, so that struggle is abandoned and the special depression immobility state is entered, the animal immobility time is recorded in the experimental process to reflect the depression state, and antidepressant drugs and exciting drugs can obviously shorten and change the state.
2.1, experimental grouping: after 1 week of acclimation, male ICR mice were randomized into 5 groups of 12 mice each, divided into: the blank control group, the drug group, the high dose group, the medium dose group and the low dose group were continuously administered for 14 days according to the following schedule.
Blank control group: edible oil 2.4 g/(kg. d)
Drug group: venlafaxine hydrochloride 0.05 g/(kg. d), venlafaxine is suitable for treating various depression (including depression accompanied by anxiety) and generalized anxiety disorder, and is a common antidepressant drug.
High, medium and low dose groups: the composition of the present invention is administered in an amount of 2.4 g/(kg. d), 1.4 g/(kg. d), and 0.7 g/(kg. d) in this order.
2.2 Experimental methods
After the mice are dosed for 1 hour for the last time, the LCm part of the mouse tail tip is pasted on a suspension hook, the mouse is hung in an open observation box by a hand-held mouse, the despair behavior of the mouse within 6min is recorded, and the immobility time of the mouse within 4min after analysis.
3. Forced swimming test of mice
The experimental method is a behavior despair experimental method, the mice are limited in water, the mice struggle and struggle to try to escape and cannot escape, and after a period of time, the mice give up struggling and only leave the water surface, so that the behavior despair 'immobility state' is shown; by observing the duration of the recording of the immobility, the antidepressant effect of the drug can be evaluated.
The experiment is divided and administered according to 2.1, the mice are placed in an organic glass jar with the height of 25cm, the diameter of 10cm and the water depth of 15cm after the mice are administered for 1 hour for the last time, the water temperature is (23 +/-2) DEG C, the swimming behavior of the mice is observed in an open observation box within 6min, and the immobility time of forced swimming of the mice within 4min after analysis.
4. Results and analysis
4.1 Effect on immobility time in mouse Tail suspension experiment
Compared with a blank control group, the medicine group and the high, medium and low dose group have significant difference (P is less than 0.01), which shows that the composition can significantly shorten the immobility time in a tail suspension experiment of mice, and shows that the composition has an antidepressant effect.
Table 1: influence on immobility time in mouse tail suspension experiment (x + -s, n ═ 12)
Compared with a blank control group, the Tp is less than 0.01, and has significant difference
4.2 influence on immobility time in forced swimming experiment of mice
Table 2: influence on immobility time in forced swimming experiments of mice (x + -s, n ═ 12)
Compared with a blank control group, the product has the advantages that the phosphorus P is less than 0.01 and has significant difference
Compared with a blank control group, the medicine group and the high, medium and low dose group have significant difference (P is less than 0.01), which shows that the composition can significantly shorten the immobility time in a forced swimming experiment of a mouse, and shows that the composition has an antidepressant effect.
Clinical efficacy study
1. 125 depression patients are randomly selected to participate in the experiment, the main manifestations of the patients are low mood and low vigor, and the patients are accompanied with the manifestations of appetite reduction, self-attitude, remorse and the like, and the patients are diagnosed as depression by means of a Berth depression list;
2. 125 patients were randomly divided into 5 groups, blank control group, drug control group, high dose group, medium dose group, low dose group and were administered for 30 days according to the following schedule:
blank control group: 5g of edible oil, once a day.
Drug control group: venlafaxine hydrochloride is 75mg/d, and venlafaxine is suitable for treating various depression (including depression accompanied by anxiety) and generalized anxiety disorder and is a common antidepressant drug.
High, medium and low dose groups: the composition of the invention is taken at the dose of 10g/d, 8g/d and 5g/d in sequence, and is taken once a day.
3. And (3) evaluating the clinical effect:
HAMD scoring is carried out on depression patients before the first administration and after the last administration; evaluation of therapeutic efficacy
HAMD score reduction was the criterion: the reduction rate is more than or equal to 25 is effective, and less than or equal to 25 is ineffective, wherein the reduction rate is more than or equal to
The medicine is cured in 75%, the reduction rate of 50-70 is obviously improved, and the reduction rate of 25-50 is improved.
Table 3: HAMD scores (x ± s, n ═ 25) in groups before initial dosing
Comparing the groups, i.e. P is more than 0.05, without difference
Table 4: evaluation of clinical effects of groups after last administration
Before the medicine is taken for the first time, the difference of the HAMD scores of all groups of people has no statistical significance, the effective rate of the HAMD score reduction rate of the high, medium and low dose groups after the medicine is taken for the last time is 68 percent at the lowest, and the effective rate of the HAMD score reduction rate is far higher than 16 percent of that of a blank control group, wherein the number of significant progress cases of the high dose group is higher than that of the medicine group, and the result shows that the medicine has an anti-depression effect.
The above is only a preferred embodiment of the present invention, and the protection scope of the present invention is not limited to the above-mentioned embodiments, and all technical solutions belonging to the idea of the present invention belong to the protection scope of the present invention. It should be noted that modifications and embellishments within the scope of the invention may be made by those skilled in the art without departing from the principle of the invention.
Claims (9)
1. The preparation method of the antidepressant composition is characterized in that the antidepressant composition comprises the following raw materials in parts by weight: 10-15 parts of wild jujube kernel oil and 4-5 parts of wall-broken ganoderma lucidum spore powder.
2. The method for preparing an antidepressant composition according to claim 1,
the antidepressant composition comprises the following raw materials in parts by weight: 10 parts of wild jujube kernel oil and 4 parts of wall-broken ganoderma spore powder.
3. The method for preparing an antidepressant composition according to claim 1,
the antidepressant composition comprises the following raw materials in parts by weight: 15 parts of wild jujube kernel oil and 4.5 parts of wall-broken ganoderma spore powder.
4. The method for preparing an antidepressant composition according to claim 1,
the antidepressant composition comprises the following raw materials in parts by weight: 5 parts of wild jujube kernel oil and 2 parts of wall-broken ganoderma lucidum spore powder.
5. The preparation method of the antidepressant composition according to claims 1-4, characterized in that it comprises the following specific preparation steps:
(1) preparing wild jujube kernel oil; (2) preparing wall-broken ganoderma lucidum spore powder;
(3) mixing the prepared wild jujube kernel oil and the wall-broken ganoderma lucidum spore powder, and circulating for 30 minutes by using a colloid mill to finally prepare the antidepressant composition.
6. The method for preparing an antidepressant composition according to claim 5,
in the step (1), the preparation process of the wild jujube kernel oil is as follows:
firstly, selecting spina date seeds; cleaning and drying; then, crushing the cleaned and dried spina date seeds into powder, and sieving the powder by a 80-mesh sieve, wherein the water content is controlled to be less than or equal to 10 percent in the process;
and finally, putting the wild jujube seed powder into a CO2 supercritical extraction kettle for extraction, thereby preparing the wild jujube seed oil.
7. The method for preparing an antidepressant composition according to claim 6,
in the CO2 supercritical extraction kettle, the extraction temperature is 40-50 ℃, the pressure is 18-25MPa, the flow of CO2 is 20kg/h, and the extraction time is 2-4 hours.
8. The method for preparing an antidepressant composition according to claim 5,
in the step (2), the preparation process of the wall-broken ganoderma lucidum spore powder is as follows:
firstly, selecting ganoderma lucidum spore powder; then, breaking the wall of the ganoderma lucidum spore powder to prepare wall-broken ganoderma lucidum spore powder;
wherein the wall-breaking rate of the wall-broken ganoderma lucidum spore powder is more than or equal to 95 percent.
9. Use of the antidepressant composition prepared by the preparation method according to any of claims 5 to 8 in a medicament for treating depression.
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