CN114642688A - Application of ganoderma lucidum spore oil in preparing medicine for prolonging life of tumor patient - Google Patents
Application of ganoderma lucidum spore oil in preparing medicine for prolonging life of tumor patient Download PDFInfo
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- ganoderma lucidum
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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
- A61K36/06—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
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
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- C—CHEMISTRY; METALLURGY
- C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
- C11B—PRODUCING, e.g. BY PRESSING RAW MATERIALS OR BY EXTRACTION FROM WASTE MATERIALS, REFINING OR PRESERVING FATS, FATTY SUBSTANCES, e.g. LANOLIN, FATTY OILS OR WAXES; ESSENTIAL OILS; PERFUMES
- C11B9/00—Essential oils; Perfumes
- C11B9/02—Recovery or refining of essential oils from raw materials
- C11B9/022—Refining
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- C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
- C11B—PRODUCING, e.g. BY PRESSING RAW MATERIALS OR BY EXTRACTION FROM WASTE MATERIALS, REFINING OR PRESERVING FATS, FATTY SUBSTANCES, e.g. LANOLIN, FATTY OILS OR WAXES; ESSENTIAL OILS; PERFUMES
- C11B9/00—Essential oils; Perfumes
- C11B9/02—Recovery or refining of essential oils from raw materials
- C11B9/025—Recovery by solvent extraction
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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
- A61K2236/37—Extraction at elevated pressure or temperature, e.g. pressurized solvent extraction [PSE], supercritical carbon dioxide extraction or subcritical water extraction
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Abstract
The invention relates to the technical field of medicines, and provides application of ganoderma lucidum spore oil in preparation of a medicine for prolonging the life of a tumor patient.
Description
Technical Field
The invention relates to the technical field of medicines, in particular to application of ganoderma lucidum spore oil in preparing a medicine for prolonging the life of a tumor patient.
Background
Ganoderma lucidum is a precious product in Chinese medical treasury, has the reputation of 'immortal grass', and can be used for treating restlessness, insomnia and palpitation, cough and asthma due to lung deficiency, consumptive disease and shortness of breath, and poor appetite. The ganoderma lucidum spores are tiny spores ejected from a pileus in the growth and maturation period of the ganoderma lucidum, are germ cells of the ganoderma lucidum, and have all genetic active substances of the ganoderma lucidum. The Ganoderma spore powder has complicated chemical components, and contains polysaccharides, triterpenes, nucleosides, vitamins, sterols, alkaloids, inorganic trace elements, etc. The Ganoderma spore oil is liposoluble active substance obtained by breaking cell wall of Ganoderma spore powder and extracting with supercritical carbon dioxide, and contains triterpenes, sterols and triglycerides as main ingredients. Research shows that the material bases of the ganoderma lucidum spore oil and the ganoderma lucidum spore powder which exert the drug effect are obviously different, the ganoderma lucidum spore polysaccharide, the triterpenoid and the ganoderma lucidum spore protein in the ganoderma lucidum spore powder exert good immunoregulation activity, the anti-tumor activity of the ganoderma lucidum spore powder mainly plays a key role by the polysaccharide and the triterpenoid, wherein the polysaccharide is the main functional component of the ganoderma lucidum spore powder, and the content of the triterpenoid is lower. The ganoderma lucidum spore oil also has the effects of resisting tumors, enhancing immunity, protecting liver and the like, contains more triterpenes and a small amount of sterols, does not contain polysaccharide, and contains a large amount of triglyceride.
In recent years, the incidence of cancer shows a trend of rising year by year, and with the transformation of a novel medical mode, medical workers pay more attention to the prolongation of the tumor-bearing life cycle of patients on the basis of the tumor treatment effect, the life cycle of cancer patients in China is far lower than the international level, and the improvement of the life cycle is the problem which needs to be urgently solved in the cancer treatment in China and is the most concerned problem of the cancer patients. With the continuous and deep understanding of the tumor problems, the method for examining the curative effect by only shrinking the tumor body has more and more limitations. In malignant tumors, especially in advanced stages, patients have poor general conditions and low quality of life even if the tumor lesions are reduced or even completely relieved. As a result, the survival time is not substantially prolonged and does not actually benefit the patient. Therefore, the medical community proposes that the treatment of malignant tumor cannot simply pursue the killing rate of tumor cells, but the improvement of the life quality and the prolonging of the survival time of the patient must be concerned so as to more scientifically evaluate the actual curative effect of treating malignant tumor.
How to better improve the life quality of tumor patients, particularly patients with advanced tumors, and effectively prolong the survival time of the patients becomes an urgent problem to be solved.
Disclosure of Invention
The invention aims to provide application of ganoderma lucidum spore oil in preparing a medicament for prolonging the life of a tumor patient. Based on the reasons and the requirements, the ganoderma lucidum spore oil is found to have the new performance of prolonging the life cycle of the tumor patients, and further provides a new application of the ganoderma lucidum spore oil as a medicament, namely the application in the aspect of medicaments for prolonging the life cycle of the tumor patients.
In order to solve the technical problem, the invention adopts the following technical scheme:
application of Ganoderma spore oil in preparing medicine for prolonging life of tumor patients is provided.
The combination of chemotherapy drugs and traditional Chinese medicine is a hotspot of tumor treatment research in recent years. The research shows that the ganoderma lucidum spore oil obtained by extracting the ganoderma lucidum spore powder by supercritical carbon dioxide has the effect of obviously improving the life cycle of a tumor patient after being combined with chemotherapeutic drugs, and no relevant report is found at present.
Preferably, the tumor comprises one or more of liver cancer tumor, lung cancer tumor, gastric cancer tumor, intestinal cancer tumor, breast cancer tumor and ascites cancer tumor.
Preferably, the tumor patient is treated with a chemotherapeutic drug.
Preferably, the chemotherapeutic drug comprises one or more of cyclophosphamide and paclitaxel.
Preferably, the ganoderma spore oil contains ergosterol, triterpene, and triglyceride.
Preferably, in the ganoderma lucidum spore oil, the mass content of triglyceride is more than 70%, the mass content of triterpene is 25% -40%, the mass content of ergosterol is 0.1% -0.5%, and the water content is less than 0.25%.
A method for preparing the ganoderma lucidum spore oil comprises the following steps: and (3) taking wall-broken ganoderma lucidum spore powder, and extracting and refining by supercritical carbon dioxide to obtain the ganoderma lucidum spore oil.
Preferably, the wall-breaking rate of the wall-broken ganoderma lucidum spore powder is more than 95%.
Preferably, the extraction refining is carried out by secondary separation, and only a first-stage separation sample is reserved, so that the ganoderma lucidum spore oil is obtained.
Preferably, the conditions of the extraction essence comprise: the extraction pressure is 25-35 MPa, the extraction temperature is 40-45 ℃, the extraction time is 1-2 h, and CO is added2The flow is 40L/h, the first-stage separation pressure is 10-15 MPa, the separation temperature is 40-45 ℃, the second-stage separation pressure is 5-8 MPa, and the separation temperature is 40-45 ℃.
The invention only keeps the sample obtained by the first-stage separation, and the ganoderma lucidum spore oil is obtained. And a large amount of impurities and water are removed through separation and refining, and the obtained ganoderma lucidum spore oil is clear and transparent and has stable component content. Experiments show that the sample after the second-stage separation contains more impurities, has turbid appearance and high moisture content (about 10 percent), is easy to deteriorate and is not reserved.
Supercritical carbon dioxide extraction is a novel green extraction and separation technology which is particularly suitable for extracting fat-soluble, high-boiling point and thermosensitive substances. The Ganoderma spore oil is liposoluble active substance obtained by breaking cell wall of Ganoderma spore and extracting with supercritical carbon dioxide, and contains sterol, triterpene, triglyceride, etc. In order to obtain the target ganoderma lucidum spore oil with stable quality, the invention removes a large amount of impurities and moisture by separation and refining, the obtained ganoderma lucidum spore oil is clear and transparent, has few impurities and stable component content, ensures the stability of the material base of the ganoderma lucidum spore oil, and obviously ensures the effect.
Compared with the prior art, the implementation of the invention has the following beneficial effects:
experiments and researches on tumor-bearing mice using chemotherapeutic drugs show that the ganoderma lucidum spore oil has a remarkable effect of prolonging the life cycle of the tumor-bearing mice. The ganoderma lucidum spore oil has the beneficial effect of being used for preparing the medicine for prolonging the life cycle of a tumor patient.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention clearer, the present invention will be further described in detail with reference to specific examples so that those skilled in the art can better understand the present invention and can implement the present invention, but the examples are not intended to limit the present invention. Modifications or substitutions to methods, procedures, or conditions of the invention may be made without departing from the spirit and scope of the invention. Unless otherwise specified, the technical means used in the examples are conventional means well known to those skilled in the art.
Example 1
Preparation of ganoderma spore oil
The preparation method of the ganoderma lucidum spore oil comprises the following steps:
breaking cell wall of Ganoderma spore powder 500g to a cell wall breaking rate of more than 95%, and performing supercritical CO extraction2Extracting, and separating and refining to obtain the ganoderma lucidum spore oil. The extraction pressure is 25-35 MPa, the extraction temperature is 40-45 ℃, the extraction time is 1-2 h, and CO is added2The flow is 40L/h, the primary separation pressure is 10-15 MPa, the separation temperature is 40-45 ℃, the secondary separation pressure is 5-8 MPa, and the separation temperature is 40-45 ℃. Only retaining the sample obtained by the first-stage separation to obtain the ganoderma lucidum spore oil. Separating and refining to remove a large amount of impurities and water, and obtaining the Ganoderma spore oilBright and stable component content. Experiments show that the sample obtained after the second-stage separation contains more impurities, has turbid appearance and high moisture content (about 10 percent), is easy to deteriorate and is not reserved.
Example 2
Effect of Ganoderma spore oil on survival of mice with ascites carcinoma cell transplantable tumors treated with cyclophosphamide
1. Laboratory animal
ICR mice, males, weight 26 ± 2 g. Animals are raised in an SPF animal room with alternating light and shade (12h:12h) and are free to eat and drink water. The experiment was started 7 days after the animals had acclimatized in the animal house.
2. Experimental Material
The ganoderma spore oil is prepared into solution with corresponding concentration by using corn oil before administration, and is prepared for use. Cyclophosphamide (CTX), is prepared into a solution with a corresponding concentration by using normal saline before administration, and is prepared for use.
Cell lines: EAC cell line (mouse Ehrlich ascites carcinoma cell line).
3. Experimental methods
(1) Establishing a tumor-bearing mouse animal model: culturing EAC cells, selecting cells in optimal growth state, and adjusting cell concentration to 5 × 106Perml, the abdominal cavity of mice was injected under sterile conditions, and 0.2ml was injected per mouse. Subculturing in abdominal cavity for 10-12 days, collecting healthy tumor-bearing mouse with swollen abdomen, vigorous growth and no rupture, placing on a clean bench, sterilizing abdominal skin, penetrating abdominal muscle with hollow needle, extracting ascites, placing into sterile container, storing on ice block, washing with normal saline, centrifuging for 2 times, diluting with normal saline, counting, and adjusting cell concentration to 5 × 107Each mouse was injected subcutaneously with 0.2mL of the above tumor cell suspension per mouse in the axilla of the right anterior limb. At 24h post-inoculation, the group administration was started.
(2) Experiment grouping
CTX group: carrying out intragastric lavage on 16 tumor-bearing mice by using corn oil with equal volume; simultaneously, 50mg/Kg of cyclophosphamide is injected into the abdominal cavity, and the times are 2 times per week; the above administration was performed until the animal died.
Ganoderma spore oil + CTX group: intragastric administration of Ganoderma spore oil (5.1ml/Kg) in 20 tumor-bearing mice, and intraperitoneal injection of cyclophosphamide (50 mg/Kg) 2 times per week; the above administration was performed until the animal died.
(3) Influence of ganoderma lucidum spore oil on survival time and life prolonging rate of EAC solid tumor mice
The day of mouse molding is day 0, and the intragastric administration of ganoderma lucidum spore oil or corn oil is started from the first day after the molding, and the administration is continued until the death of animals. Cyclophosphamide or saline was administered to the abdominal cavity twice a week starting the first week after molding until the animals died. Counting the survival time of each group of mice, calculating the average survival time of each group, and calculating the life prolonging rate according to the following formula: the life extension rate (mean survival time of drug group-mean survival time of model group)/mean survival time of model group × 100%, and was statistically processed. .
4. Results of the experiment
The mean survival days for EAC tumor bearing mice after continuous gavage with corn oil and 2 intraperitoneal injections of cyclophosphamide (CTX group) per week was 31.5 ± 8.8 d. After continuous gavage administration of ganoderma spore oil (5.1ml/Kg) and 2 intraperitoneal injections of cyclophosphamide per week, the average survival days of mice were 37.9 ± 7.7d, which is statistically different from that of the CTX group, and the life prolongation rate was 20.2%. The results show that the ganoderma lucidum spore oil can obviously prolong the life cycle of tumor-bearing mice after the administration of chemotherapeutic drugs.
Example 3
Effect of Ganoderma spore oil on survival of H22 tumor-bearing mice receiving cyclophosphamide treatment
1. Laboratory animal
ICR mice, males, weight 26 ± 2 g. Animals are raised in an SPF animal room with alternating light and shade (12h:12h) and are free to eat and drink water. The experiment was started 7 days after the animals had acclimatized in the animal house.
2. Experimental Material
The ganoderma spore oil is prepared into solution with corresponding concentration by using corn oil before administration, and is prepared for use. Cyclophosphamide (CTX), is prepared into a solution with a corresponding concentration by using normal saline before administration, and is prepared for use.
Cell lines: h22 hepatoma carcinoma cell.
3. Experimental methods
(1) Establishing a tumor-bearing mouse animal model: culturing H22 cells, collecting cells in optimal growth state, and adjusting cell concentration to 2.5 × 106Perml, the abdominal cavity of mice was injected under sterile conditions, and 0.2ml was injected per mouse. Subculturing in abdominal cavity for 10-12 days, collecting healthy tumor-bearing mouse with swollen abdomen, vigorous growth and no rupture, placing on a clean bench, sterilizing abdominal skin, penetrating abdominal muscle with hollow needle, extracting ascites, placing into sterile container, storing on ice block, washing with normal saline, centrifuging for 2 times, diluting with normal saline, counting, and adjusting cell concentration to 2 × 107Each mouse was injected subcutaneously with 0.2mL of the above tumor cell suspension per mouse in the axilla of the right anterior limb. 5 days after inoculation, mice with accessible lumps in the axilla were selected and the group administration was started.
(2) Experiment grouping
Solvent control group: the gastric lavage is carried out on 25 tumor-bearing mice with corn oil with equal volume; simultaneously, 50mg/Kg of cyclophosphamide is injected into the abdominal cavity, and the times are 2 times per week; until the animal dies.
Ganoderma lucidum spore oil (2.72ml/Kg) + cyclophosphamide group: intragastric administration of 25 tumor-bearing mice (2.72ml/Kg) with Ganoderma spore oil once a day for 6 days, and stopping administration for 1 day; simultaneously, 50mg/Kg of cyclophosphamide is injected into the abdominal cavity, and the times are 2 times per week; the above administration was performed until the animal died.
Ganoderma lucidum spore oil (0.34ml/Kg) + cyclophosphamide group: intragastric administration of 25 tumor-bearing mice (0.34ml/Kg) with Ganoderma spore oil once a day for 6 days, and stopping administration for 1 day; simultaneously, 50mg/Kg of cyclophosphamide is injected into the abdominal cavity for 2 times per week; the above administration was performed until the animal died.
(3) Influence of ganoderma lucidum spore oil on survival time and life prolonging rate of H22 solid tumor mice
After randomly grouping tumor-bearing mice, feeding ganoderma spore oil or corn oil for intragastric administration is started, and the administration is continued until the animals die. Intraperitoneal injections of Cyclophosphamide (CTX) or normal saline were started at the same time, twice a week, until the animals died. Counting the survival time of each group of mice, calculating the average survival time of each group, and calculating the life prolonging rate according to the following formula: the life extension rate (mean survival time of drug group-mean survival time of model group)/mean survival time of model group × 100%, and was statistically processed.
4. Results of the experiment
Solvent control group H22 tumor-bearing mice were continuously gavaged with corn oil for 21 days, and were also injected with Cyclophosphamide (CTX) intraperitoneally 2 times a week, and the average survival days of the mice was 41.12 + -2.77 d. The mice are continuously gavaged with ganoderma lucidum spore oil (2.72ml/Kg), and after 2 times of intraperitoneal injection of cyclophosphamide every week, the average survival days of the mice are 53.96 +/-3.81 days which are obviously longer than that of a solvent control group (P is less than 0.05), and the life prolonging rate is 31.23%. The mice are continuously gavaged with ganoderma lucidum spore oil (0.34ml/Kg), and after 2 times of intraperitoneal injection of cyclophosphamide every week, the average survival days of the mice are 54.68 +/-3.91 d which are obviously longer than that of a solvent group (P is less than 0.05), and the life prolonging rate is 32.99%. The results suggest that the ganoderma lucidum spore oil can significantly prolong the survival time of H22 tumor-bearing mice receiving CTX chemotherapy.
Example 4
Effect of Ganoderma spore oil on survival of Lewis lung cancer-bearing mice receiving paclitaxel treatment
1. Laboratory animal
C57BL/6 mice, male, with a body mass of 22 + -4 g at the time of the experiment (5-6 weeks old). Animals are raised in an SPF animal room with alternating light and shade (12h:12h) and are free to eat and drink water. The experiment was started 7 days after the animals had acclimatized in the animal house.
2. Experimental Material
The ganoderma spore oil is prepared into solution with corresponding concentration by using corn oil before administration, and is prepared for use. Paclitaxel injection (PTX).
Cell lines: lewis lung carcinoma cells.
3. Experimental methods
(1) Establishing a tumor-bearing mouse animal model: recovering and culturing Lewis lung cancer cells, collecting cells in optimal growth state, and adjusting cell concentration to 7.5 × 106One per ml, mice were injected subcutaneously with 0.2ml of the above tumor cell suspension per mouse in the right anterior axilla. On day 5 post inoculation, the tumorigenic mice were randomly grouped by body weight.
(2) Experimental groups
Paclitaxel single use group: corn oil + PTX (20mg/Kg)
Ganoderma spore oil (high dose) combination: ganoderma spore oil (3.4ml/Kg) + PTX (20mg/Kg)
Ganoderma lucidum spore oil (low dose) combination: ganoderma spore oil (0.34ml/Kg) + PTX (20mg/Kg)
(3) Influence of ganoderma lucidum spore oil on survival time and life prolonging rate of mice with Lewis solid tumors
The day of mouse molding is day 0, and the intragastric administration of ganoderma lucidum spore oil or corn oil is started from the first day after the molding, and the administration is continued until the death of animals. Paclitaxel or saline was administered intraperitoneally from the first week after molding twice a week until the animals died. Counting the survival time of each group of mice, calculating the average survival time of each group, and calculating the life prolonging rate according to the following formula: the life extension rate (mean survival time of drug group-mean survival time of model group)/mean survival time of model group × 100%, and was statistically processed.
4. Results of the experiment
Lewis tumor-bearing mice in the paclitaxel-treated group alone were continuously gavaged with corn oil for 21 days, and were intraperitoneally injected with Paclitaxel (PTX) 2 times a week, with the average survival day of the mice being 17.68. + -. 1.42 d. The mice in the high-dose combination paclitaxel treatment group are continuously administered with ganoderma spore oil (3.4ml/Kg) by intragastric administration, and after 2 times of intraperitoneal injection of paclitaxel every week, the average survival days of the mice are 22.05 +/-1.49 days which are obviously higher than that of the solvent group (P <0.05), and the life prolonging rate is 22.89%. The low-dose combination of the ganoderma lucidum spore oil and the paclitaxel is used for mice in a paclitaxel treatment group to continuously administrate the ganoderma lucidum spore oil (0.34ml/Kg) through intragastric administration, and after 2 times of intraperitoneal injection of paclitaxel every week, the average survival days of the mice are 22.55 +/-1.43 d, which are obviously longer than that of a solvent group (P is less than 0.05), and the life prolonging rate is 27.55%. The results suggest that the ganoderma lucidum spore oil can obviously prolong the life cycle of PTX chemotherapy of tumor-bearing mice.
In conclusion, the ganoderma lucidum spore oil has the obvious effect of prolonging the life cycle of tumor-bearing mice after the administration of chemotherapeutic drugs. The ganoderma lucidum spore oil has the beneficial effect of being used for preparing the medicine for prolonging the life time of tumor-bearing mice after the chemotherapy medicine is given.
The above disclosure is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the scope of the present invention, therefore, the present invention is not limited by the appended claims.
Claims (10)
1. The application of ganoderma spore oil in pharmacy is characterized in that the ganoderma spore oil is used for prolonging the life of a tumor patient.
2. The use of claim 1, wherein the tumor comprises one or more of liver cancer tumor, lung cancer tumor, stomach cancer tumor, intestinal cancer tumor, breast cancer tumor, ascites cancer tumor.
3. The use of claim 1, wherein said patient is treated with a chemotherapeutic agent.
4. The use of claim 3, wherein the chemotherapeutic agent comprises one or more of cyclophosphamide and paclitaxel.
5. The use of claim 1, wherein the ganoderma lucidum spore oil comprises ergosterol, triterpenes, triglycerides.
6. The use according to claim 5, wherein the ganoderma lucidum spore oil contains more than 70% by mass of triglyceride, 25-40% by mass of triterpene, 0.1-0.5% by mass of ergosterol and less than 0.25% by mass of moisture.
7. A method for preparing the ganoderma lucidum spore oil as claimed in claim 5, comprising: and (3) taking wall-broken ganoderma lucidum spore powder, and extracting and refining by supercritical carbon dioxide to obtain the ganoderma lucidum spore oil.
8. The preparation method according to claim 7, wherein the wall-broken rate of the wall-broken ganoderma lucidum spore powder is more than 95%.
9. The method according to claim 7, wherein the ganoderma lucidum spore oil is obtained by subjecting the extractive refining to secondary separation and retaining only the primary separated sample.
10. The production method according to claim 9, wherein the conditions for the extractive purification include: the extraction pressure is 25-35 MPa, the extraction temperature is 40-45 ℃, the extraction time is 1-2 h, and CO is added2The flow is 40L/h, the first-stage separation pressure is 10-15 MPa, the separation temperature is 40-45 ℃, the second-stage separation pressure is 5-8 MPa, and the separation temperature is 40-45 ℃.
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