Application of a Ganoderma lucidum lanostane triterpenoid compound in preparing a CYP metabolic enzyme inhibitor

Abstract

The present invention discloses the application of Ganoderma lucidum lanostane triterpenoids in the preparation of CYP metabolic enzyme inhibitors, belonging to the technical field of pharmaceuticals. The structural formula of this compound is as follows: #imgabs0# The present invention also provides the application of lanostane triterpenoids in the preparation of CYP metabolic enzyme inhibitors, and evaluates their inhibitory effects on various subtypes of CYP enzymes and the intervention of drug metabolism. The lanostane triterpenoids provided by the present invention can effectively inhibit the activities of various CYP metabolic enzymes, and can be used as combination drugs in inhibiting the hepatic metabolism of clinical drugs, providing a reference for the clinical use of Ganoderma lucidum.

Description

Technical Field

[0001] The present invention relates to the technical field of pharmaceuticals, and particularly to the use of ganoderma lanostane triterpenoids in the preparation of CYP metabolic enzyme inhibitors. Background Art

[0002] The traditional Chinese medicine Ganoderma lucidum is the dried fruiting body of the fungus Ganoderma lucidum (Leyss. ex Fr.) Karst. or Ganoderma sinense Zhao, Xu & Zhang of the family Polyporaceae, and is widely distributed in Shandong, Anhui, Zhejiang, Jiangsu, Jiangxi, Fujian and other places in China. It has the effects of replenishing qi, calming the mind, relieving cough and asthma. It is mainly used for treating restlessness of mind, insomnia, palpitation, cough and excessive phlegm, consumptive disease, etc. It was first recorded in "Shennong Ben Cao Jing" and has been used in Asian countries for improving health and treating various diseases for more than 2,000 years, and has various effects such as anti-tumor, anti-angiogenesis, anti-inflammatory, anti-herpes, anti-hypertension, low cholesterol, anti-histamine, anti-complement, liver protection and radiation protection. Therefore, Ganoderma lucidum has been widely used in the prevention and treatment of various types of diseases, especially in liver protection, immune regulation and clinical anti-tumor applications. So far, hundreds of compounds have been isolated and identified from Ganoderma lucidum, such as triterpenoids, alkaloids, polysaccharides, nucleosides, and a small amount of amino acids and proteins. Among them, water-soluble polysaccharides and triterpenoids are the main active ingredients of Ganoderma lucidum. Ganoderma triterpenoids have attracted much attention due to their good pharmacological properties. The chemical structures of these compounds are relatively complex. At present, 7 different parent nucleus structures are known, and there are multiple different substituents on the parent nucleus, commonly including hydroxyl, carboxyl, ketone, acetyl, methyl, etc.

[0003] CYP enzymes are a superfamily of heme proteins that are widely present in animals, plants, fungi and bacteria. In mammals, CYP enzymes are expressed almost ubiquitously in all tissues, but are most abundant in the liver and small intestine. In the human body, CYP enzymes are considered to be a superfamily of blood proteins and play a crucial role in the oxidative metabolism of endogenous and exogenous substances such as vitamins, cholesterol, prostaglandins, hormones and clinical drugs. In addition, CYP enzymes distributed in liver and intestinal tissues are important drug-metabolizing enzymes and play an important role in the efficacy and detoxification processes of drugs.

[0004] Interactions among numerous inducers, substrates, and inhibitors of CYP enzymes can alter the metabolic behavior of drugs, leading to poor therapeutic efficacy or the induction of drug adverse reactions. Therefore, substances including natural products may interfere with the clinical drug metabolism process mediated by CYP enzymes. Ganoderma lucidum-related drugs and health foods are widely used in medical care and are often used in combination with multiple drugs. The effects of Ganoderma lucidum on the activity of liver CYP enzymes and the resulting drug-drug interactions are still unclear. Therefore, studying the effects of Ganoderma lucidum on CYP metabolic function and evaluating CYP enzyme-mediated drug-drug interactions are of great significance for the safe and rational use of Ganoderma lucidum. Summary of the Invention

[0005] The object of the present invention is to provide an application of Ganoderma lucidum lanostane-type triterpenoids in the preparation of CYP metabolic enzyme inhibitors to solve the problems existing in the above-mentioned prior art. The lanostane-type triterpenoids provided by the present invention can effectively inhibit the activity of CYP metabolic enzymes, providing a reference for the rational use of Ganoderma lucidum.

[0006] To achieve the above object, the present invention provides the following solutions:

[0007] Technical Solution 1: A lanostane-type triterpenoid compound with the following structural formula:

[0008]

[0009] Technical Solution 2: A preparation method of the lanostane-type triterpenoid compound described above, comprising the following steps:

[0010] a. Crush the dried Ganoderma lucidum, reflux extract it with ethanol three times, combine the ethanol extracts, and then concentrate to obtain a Ganoderma lucidum extract. Disperse the Ganoderma lucidum extract with water to obtain an aqueous dispersion of the extract, and extract the aqueous dispersion of the extract with dichloromethane to obtain a dichloromethane extract;

[0011] b. Subject the dichloromethane extract to silica gel column chromatography, using a petroleum ether-acetone eluent, and elute successively according to the volume ratio of petroleum ether to acetone of 15:1, 14:1, 13:1, 12:1, 11:1, 10:1, 8:1, 6:1, 4:1, 3:1, 2:1 gradients. Collect 4 elution fractions for each gradient, and the 44 elution fractions obtained successively are respectively denoted as A1 to A44;

[0012] c. Separate the elution fraction A29 by reverse-phase ODS medium-pressure column chromatography, and elute with methanol-water according to the volume ratio of methanol to water of (10:90)-(100:0) gradients to obtain 23 elution fractions. The 29 elution fractions obtained successively are denoted as A29-1 to A29-23 in turn;

[0013] d. Subject the elution fraction A29-15 to semi-preparative C 18 chromatographic column HPLC separation to obtain the lanostane-type triterpenoid compound.

[0014] Technical solution three: Application of the lanostane-type triterpenoid compound in the preparation of CYP metabolic enzyme inhibitors.

[0015] Furthermore, the CYP metabolic enzyme inhibitor further includes pharmaceutical excipients.

[0016] Furthermore, the pharmaceutical excipients include flavoring agents, disintegrants, preservatives, lubricants, wetting agents, binders, solvents, thickeners or solubilizers.

[0017] Technical solution four: Application of the lanostane-type triterpenoid compound in the preparation of drugs for inhibiting the hepatic metabolism of clinical drugs.

[0018] Furthermore, the clinical drugs include phenacetin, coumarin, diclofenac, dextromethorphan, midazolam, bupropion, S-mephenytoin, melatonin, clozapine, riluzole, artemisinin, sertraline, efavirenz, imatinib, diltiazem, simvastatin, valsartan, glimepiride and glibenclamide.

[0019] Technical solution five: A drug combination for inhibiting the hepatic metabolism of clinical drugs, comprising the lanostane-type triterpenoid compound and the clinical drug.

[0020] The present invention discloses the following technical effects:

[0021] The present invention systematically and deeply studies Ganoderma lucidum extracts using modern chromatography and spectroscopy techniques, evaluates the inhibitory effects of Ganoderma lucidum bioactive substances on multiple subtypes of CYP enzymes and the intervention of drug metabolism, and clarifies the main bioactive substances of Ganoderma lucidum that intervene in CYP enzymes and their effects on clinical drug metabolism, providing a reference for the rational use of Ganoderma lucidum.

[0022] The present invention screened the CYP enzyme inhibitory activity of the traditional Chinese medicine Ganoderma lucidum in China, found that the dichloromethane extract of Ganoderma lucidum is its effective part, and through further activity tracking and component separation, identified a lanostane-type triterpenoid compound ganodrol C, and carried out a systematic evaluation of its inhibitory effect on CYP enzymes. It was found that the compound ganodrol C has inhibitory effects on CYP3A4, 2B6 and 2C19, IC 50The values are 4.775 ± 0.32 μΜ, 25.28 ± 3.7 μM, and 15.40 ± 1.44 μM respectively. The present invention further studied its potential drug-drug interactions with clinical drugs. The research showed that ganodrol C generally inhibited the 16 selected clinical drugs. The research results of the present invention not only indicate that lanostane-type triterpenoids are the main active components of Ganoderma lucidum in inhibiting liver CYP enzymes, but also provide research ideas for systematically and deeply elaborating the drug-drug interactions caused by Ganoderma lucidum, and have reference value for the scientific and reasonable use of Ganoderma lucidum. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] In order to more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the following will briefly introduce the drawings required in the embodiments. Obviously, the drawings in the following description are only some embodiments of the present invention. For those of ordinary skill in the art, without creative efforts, other drawings can be obtained based on these drawings.

[0024] Figure 1 is the chemical structure of ganoderic triterpenoid compound 1;

[0025] Figure 2 is the dose-dependent inhibitory effect of compound ganodrol C on CYP enzymes, where A is CYP3A4, B is CYP2B6, C is CYP2C19, and D is CYP2C9;

[0026] Figure 3 is the key HMBC (A) of compound ganodrol C, 1 H- 1 H COSY (A) and NOESY (B) correlation signal analysis. DETAILED DESCRIPTION OF THE EMBODIMENTS

[0027] The various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as a limitation of the present invention, but rather as a more detailed description of certain aspects, characteristics, and embodiments of the present invention.

[0028] It should be understood that the terms described in the present invention are only for describing specific embodiments and are not used to limit the present invention. Additionally, for the numerical ranges in the present invention, it should be understood that each intermediate value between the upper and lower limits of the range is also specifically disclosed. Each intermediate value within any stated value or stated range, as well as each smaller range between any other stated value or intermediate value within the stated range, is also included in the present invention. The upper and lower limits of these smaller ranges may be independently included or excluded from the range.

[0029] Unless otherwise specified, 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 invention pertains. Although this invention only describes preferred methods and materials, any methods and materials similar or equivalent to those described herein may also be used in the practice or testing of this invention. All documents mentioned in this specification are incorporated by reference to disclose and describe the methods and / or materials related to the documents. In case of conflict with any incorporated document, the content of this specification shall prevail.

[0030] Without departing from the scope or spirit of this invention, various improvements and changes can be made to the specific embodiments of the specification of this invention, which are obvious to those skilled in the art. Other embodiments obtained from the specification of this invention are obvious to those skilled in the art. The specification and examples of this invention are merely exemplary.

[0031] Regarding the use of "comprising", "including", "having", "containing", etc. herein, they are all open-ended terms, meaning including but not limited to.

[0032] Example 1

[0033] 1.1 Extraction and Isolation Process of Ganoderma lucidum Lanostane-Type Triterpenoid 1

[0034] The dried Ganoderma lucidum is pulverized and refluxed with ethanol three times. The volume-mass ratio of ethanol to Ganoderma lucidum is 100 L:10 kg. The ethanol extracts are combined and concentrated under reduced pressure to obtain a Ganoderma lucidum extract. The Ganoderma lucidum extract is dispersed in water. The mass ratio of the Ganoderma lucidum extract to water is 1:5, and the pH is adjusted to 2 to obtain a dispersed liquid of the extract in water. The dispersed liquid of the extract in water is extracted with dichloromethane three times. The dichloromethane layers of the three extractions are combined and concentrated under reduced pressure until no distillate distills out to obtain the dichloromethane extract. Petroleum ether / acetone (15:1 - 2:1) is used as the eluent, and gradient elution is carried out in sequence according to the volume ratios of petroleum ether to acetone of 15:1, 14:1, 13:1, 12:1, 11:1, 10:1, 8:1, 6:1, 4:1, 3:1, 2:1. The dichloromethane extract (164 g) is separated into 44 fractions by silica gel column chromatography. Using methanol:water (10:90 - 100:0) (0.03% trifluoroacetic acid) as the mobile phase, fraction 29 (16 g) is further separated into 23 fractions (A29-1 to A29-23) by medium-pressure column chromatography (ODS column); fraction A29-15 is separated and purified by semi-preparative HPLC (C18 column; mobile phase of methanol-water (55:45) (0.03% CF3COOH)) to obtain compound 1 (3.2 mg).

[0035] 1.2 Physicochemical Properties and Spectral Data of Ganoderma lucidum Lanostane-Type Triterpenoid 1

[0036] Compound 1 is a yellow powder; (-)-HRESIMSm / z 533.3489 [M+COOH] - (Calcd for C 31 H 49 O7 - , 533.3484); [α] 20 D +101.2 (c 0.20, CHCl3); 1 1H NMR (CDCl3, 600 MHz) data are shown in Table 1; 13 13C NMR (CDCl3, 150 MHz) data are shown in Table 1, and the chemical structure of ganoderic triterpenoid 1 is shown in Figure 1 .

[0037] Table 1 1H NMR (600 MHz) (δ 1 ppm, J Hz) and H 13C NMR (150 MHz) (δ 13 ppm) C of compound 1

[0038]

[0039]

[0040] 1.3 Structural identification of ganoderma lanostane triterpenoid 1

[0041] The structure of compound 1 was confirmed by comprehensive analysis of its NMR data (shown in Table 1), indicating that compound 1 was similar in structure to 24S,25R-dihydroxy-3,7-dioxo-5α-lanost-8-en-26-ol (Peng X, Liu J, Xia J et al. Lanostane triterpenoids from ganoderma hainanensej.D.Zhao. Phytochemistry. 2015; 114: 137-145). The main difference between the two was that there was a carbonyl group at C-21 and the carbonyl group at C-7 was replaced by a hydrogen atom in compound 1. In the HMBC spectrum, the key long-range correlation signals of H2-7 / C-9 and H2-12 / C-11 confirmed the above inference (see Figure 3 ). The three characteristic oxygenated carbons δC 79.4 (C-24), 74.0 (C-25), 67.8 (C-26) and the HMBC long-range correlation signals of H-24 / C-25, C-26 indicated that compound 1 had the same side chain part as ganodrol B. Based on the above information, the structure of compound 1 was determined as shown in Figure 1 and named ganodrol C.

[0042] 1.4 Evaluation of the inhibitory effect of ganodrol C on CYP enzymes

[0043] The inhibitory effect of ganodrol C, a triterpenoid compound from Ganoderma lucidum, on seven subtypes of CYP enzymes (CYP1A2, 2A6, 2D6, 2B6, 2C9, 2C19, 3A4) was determined using an in vitro metabolic incubation method with liver microsomes.

[0044] Experimental method: The inhibitory effect of ganodrol C on seven subtypes of CYP enzymes (CYP1A2, 2A6, 2D6, 2B6, 2C9, 2C19, 3A4) was evaluated by the reaction of specific substrate probes (Table 2). The total volume of the in vitro metabolic incubation system was 200 μL. The concentrations of the probe substrates in the system are shown in Table 2, 100 mM potassium phosphate buffer (pH adjusted to 7.4 with K2HPO4 / KH2PO4), NADPH generating system (consisting of 1 unit / mL G-6-P-DH, 1 mM NADP, 10 mM G-6-P), HLM (0.5 mg / mL), 4 mM MgCl2, and ganodrol C (50 μg / mL). The reaction samples were preheated thoroughly in a thermostatic mixer at 37 °C, and then NADP was added to initiate the reaction. The reaction time was 30 minutes. After the time reached, 100 μL of acetonitrile was added on time, and the reaction was terminated immediately by vortex oscillation and then centrifuged at 4 °C and 20,000 g for 20 minutes. The supernatant was analyzed by liquid chromatography-tandem mass spectrometry (LC-MS / MS), and the CYP enzyme activity was evaluated by the production amount of the probe metabolites. The mass spectrometry information of the probe substrates is shown in Table 2. + The inhibitory effects of ganodrol C on four subtypes of CYP enzymes (CYP1A2, 2B6, 2C9, 3A4) were studied. By selecting a variety of clinical drugs metabolized by CYP enzymes, DDI studies with ganodrol C were carried out, and the IC50 values were determined. The results are shown in

[0045] Table 2 Probe substrate information

[0046]

[0047] The inhibitory effects of ganodrol C on four subtypes of CYP enzymes (CYP1A2, 2B6, 2C9, 3A4) were studied. By selecting a variety of clinical drugs metabolized by CYP enzymes, DDI studies with ganodrol C were carried out, and the IC50 values were determined. The results are shown in Figure 2 .

[0048] 1.5 Study on the inhibitory effect of ganodrol C on clinical drugs

[0049] Clinical drug selection: Four drugs, namely phenacetin, melatonin, clozapine, and riluzole, are metabolized by CYP1A2; four drugs, namely bupropion, artemisinin, efavirenz, and sertraline, are metabolized by CYP2B6; four drugs, namely diclofenac, valsartan, glimepiride, and glibenclamide, are metabolized by CYP2C9; four drugs, namely midazolam, imatinib, simvastatin, and diltiazem, are metabolized by CYP3A4. The clinical drug information is shown in Table 3. The experimental method is the same as that in 1.4.

[0050] Table 3 Clinical drug information

[0051]

[0052]

[0053] 1.6 Mass spectrometry analysis method

[0054] The LC-MS / MS used is ExionLC AD HPLC-AB SCIEX QTRAP 5500 MS, and the analytical column is Luna Omega PS C18 (2.1×100 mm, 3 μm). The LC-MS analysis methods for the metabolites of phenacetin, coumarin, diclofenac, dextromethorphan, midazolam, bupropion, S-mephenytoin, melatonin, clozapine, riluzole, artemisinin, sertraline, efavirenz, imatinib, diltiazem, simvastatin, valsartan, glimepiride, and glibenclamide refer to the following existing technologies: 1. Sarkar M, Grossman RG, Toups EG et al. Uplc-ms / ms assay of riluzole in human plasma and cerebrospinal fluid (csf): Application in samples from spinal cord injured patients. J Pharm Biomed Anal. 2017;146:334-340; 2. Couchman L, Fisher DS, Subramaniam K et al. Ultra-fast lc-ms / ms in therapeutic drug monitoring: Quantification of clozapine and norclozapine in human plasma. Drug Test Anal. 2018;10(2):323-329; 3. Magliocco G, Le Bloc'h F, Thomas A et al. Simultaneous determination of melatonin and 6-hydroxymelatonin in human overnight urine by lc-ms / ms. J Chromatogr B Analyt Technol Biomed Life Sci. 2021;1181:122938.4; 4. Liu T, Du F, Wan Y et al.Rapid identification of phasei and ii metabolites of artemisinin antimalarials using ltq-orbitrap hybridmass spectrometer in combination with online hydrogen / deuterium exchangetechnique.J Mass Spectrom.2011;46(8):725-733;5、Kobayashi K,Ishizuka T,ShimadaN,et al.Sertraline n-deme thylation is catalyzed by multiple isoforms ofhuman cytochrome p-450in vitro.Dru g Metabolism and Disposition.1999;27(7):763-766;6、Selvan R.Metabolic profile of glyburide in human liver microsomesusing lc-dad-q-trap-ms / ms.Biomedical chromato graphy:BMC.2013;27(5):575-582;7、Dai DP,Wang SH,Geng PW et al.In vitro assessment of 36cyp2c9 allelicisoforms found in the chinese population on the meta bolism ofglimepiride.Basic Clin Pharmacol Toxicol.2014;114(4):305-310;8、Yuan L J,QianJC,Li XY et al.Enzymatic activity on valsartan of 38cyp2c9 variants from thechinese population.Chem Biol Interact.2022;353:109799;9、Zhuang W,Qiu HB,ChenXM et al.Simultaneous quantification of imatinib and its main metabolite n-demethyl-imatinib in human plasma by liquid chromatography-tandem mass spectrometry and its application to therapeutic drug monitoring in patients with gastrointestinal stromal tumor. Biomed Chromatogr. 2017;31(12):e4022; 10, H, Wang, Y, Wu, Z, Zhao. Fragmentation study of simvastatin and lovastatin using electrospray ionization tandem mass spectrometry. Journal of mass spectrometry: JMS. 2001;36(1):58-70; 11, Dasandi B, Shah S, Shivprakash. Development and validation of a high throughput and robust lc-ms / ms with electrospray ionization method for simultaneous quantitation of diltiazem and its two metabolites in human plasma: Application to a bioequivalence study. J Chromatogr B Analyt Technol Biomed Life Sci. 2009;877(8-9):791-798。

[0055] The ion pairs for quantitative analysis are shown in Table 4; the gas flow rate (CUR) is 35 L / min; the ion spray voltage and temperature are set at 5500 V and 550 °C respectively; the dwell time is 200 ms; Gas 1 and Gas 2 are 45 and 55 psi respectively; the analysis and detection mode is the positive mode, and only efavirenz is in the negative mode; liquid phase method: the mobile phase is A and B, A is 1‰ formic acid in water, and B is acetonitrile; the mobile phase flow rate is 0.30 mL / min, and the column temperature is 30 °C; the specific method is: 0 - 1.5 min (13 - 13% B), 1.5 - 5.0 min (18 - 83% B), 5.0 - 6.0 min (83 - 90% B); other relevant mass spectrometry parameters are shown in Table 4.

[0056] Table 4 Mass Spectrometry Information of Probe Drugs

[0057]

[0058]

[0059] LC-MS analysis method for determining the contents of four drugs, phenacetin, bupropion, midazolam, and diclofenac, in rat plasma: the ion pairs for quantitative analysis are shown in Table 5, and the ion spray voltage and temperature, dwell time, and Gas 1 and Gas 2 are the same as above; the analysis and detection mode is the positive mode, and only diclofenac is in the negative mode, and other relevant mass spectrometry parameters are shown in Table 5.

[0060] Table 5 Mass Spectrometry Parameters for In Vivo Pharmacokinetics Determination

[0061]

[0062]

[0063] 1.7 Experimental Results

[0064] 1.7.1 Isolation and Identification of Ganoderma Triterpenoids

[0065] The 95% ethanol extract of Ganoderma lucidum was extracted with dichloromethane, and one ganoderma triterpenoid compound 1 was isolated from the dichloromethane extract by silica gel column chromatography combined with medium-pressure chromatography and pre-HPLC chromatography techniques. Its structure, ganodrol C, was determined by spectroscopic techniques such as 1D NMR, 2D NMR, HRESIMS, and ESIMS, combined with ECD and SCD methods. The structure of the isolated and identified ganoderma triterpenoid compound 1 is shown in Figure 1 , and the key HMBC, 1 H- 1 H COSY and NOESY correlation signals of compound ganodrol C are shown in Figure 3 .

[0066] 1.7.2 Inhibitory Activity of Compound 1 (Ganodrol C) against CYP Enzymes

[0067] The ganoderma triterpenoid ganodrol C showed strong inhibitory effects on multiple subtypes of CYP3A4, 2B6, 2C9, and 2C19. The results are as Figure 2 shown. The results showed that compound ganodrol C exhibited concentration-dependent inhibitory effects on CYP3A4, 2B6, 2C19, and 2C9.

[0068] 1.7.3 Study on the Inhibitory Effects of Compound 1 (Ganodrol C) on Clinical Drugs

[0069] Sixteen clinical drugs such as clozapine, riluzole, and simvastatin were selected to evaluate the potential drug-drug interactions between the active triterpenoids and clinical drugs. The results are shown in Table 6. Compound ganodrol C had significant inhibitory effects on the in vitro metabolism of midazolam, simvastatin, diltiazem, imatinib, bupropion, artemisinin, efavirenz, sertraline, diclofenac, valsartan, glimepiride, and glibenclamide.

[0070] Table 6 Dose-Dependent Inhibitory Effects of Compound ganodrol C on Clinical Drugs

[0071]

[0072]

[0073] 1.7.4 Determination of the Inhibitory Effects of Compound 1 (Ganodrol C) on CYP Enzymes

[0074] Through preliminary inhibitory screening in this invention, it was found that the ethanol extract of ganoderma and the dichloromethane extract had significant inhibitory effects on CYP1A2, 3A4, 2B6, and 2C9, and the aqueous layer had basically no inhibitory activity, indicating that the main inhibitory active substances were distributed in the dichloromethane extract. Through further research, a lanostane-type triterpenoid compound ganodrol C was discovered and isolated from ganoderma. This compound had significant inhibitory effects on CYP3A4, 2B6, and 2C19, and the IC 50 values were 4.775 ± 0.32 μΜ, 25.28 ± 3.7 μM, and 15.40 ± 1.44 μM respectively, and there was a general inhibitory effect on the 16 selected clinical drugs. This invention not only indicates that lanostane-type triterpenoids are the main active components of ganoderma that inhibit liver CYP enzymes, but also provides a research idea for systematically and deeply elaborating the drug-drug interactions caused by ganoderma, and has a reference value for the scientific and reasonable use of ganoderma.

[0075] The embodiments described above are only descriptions of the preferred embodiments of the present invention, and do not limit the scope of the present invention. Without departing from the spirit of the present invention's design, various deformations and improvements made by those of ordinary skill in the art to the technical solutions of the present invention should all fall within the protection scope determined by the claims of the present invention.

Claims

1. A lanostane - type triterpenoid compound, characterized in that, The structural formula is as follows: 。 2. A method for preparing the lanostane - type triterpenoid compound as described in claim 1, characterized in that, It includes the following steps: a. Crush the dried Ganoderma lucidum, reflux extract it three times with ethanol, combine the ethanol extracts, and then concentrate to obtain a Ganoderma lucidum extract. Disperse the Ganoderma lucidum extract with water to obtain an aqueous dispersion of the extract, and extract the aqueous dispersion of the extract with dichloromethane to obtain a dichloromethane extract; b. Subject the dichloromethane extract to silica gel column chromatography, using a petroleum ether-acetone eluent, and elute successively according to the volume ratios of petroleum ether to acetone of 15:1, 14:1, 13:1, 12:1, 11:1, 10:!8:1, 6:1, 4:1, 3:1, 2:1 in a gradient manner. Collect 4 elution fractions for each gradient, and the 44 elution fractions obtained successively are denoted as A1 to A44; d. Subject the elution fraction A29-15 to semi-preparative C 18 chromatographic column HPLC separation to obtain the lanostane-type triterpenoid compound. c. Separate the elution fraction A29 by reverse-phase ODS medium-pressure column chromatography, and elute with methanol-water according to the volume ratio of methanol to water from (10:90) to (100:0) in a gradient manner to obtain 23 elution fractions, which are successively denoted as A29-1 to A29-23; 4. The application according to claim 3, wherein 3. Use of the lanostane-type triterpenoid compound according to claim 1 in the preparation of a CYP metabolic enzyme inhibitor.

5. The application according to claim 4, wherein The CYP metabolic enzyme inhibitor further includes pharmaceutical excipients.

6. Use of the lanostane triterpenoid compound according to claim 1 in the preparation of a drug for inhibiting the hepatic metabolism of clinical drugs, characterized in that, The pharmaceutical excipients include flavoring agents, disintegrants, preservatives, lubricants, wetting agents, binders, solvents, thickeners or solubilizers.

7. A pharmaceutical composition for inhibiting the hepatic metabolism of clinical drugs, characterized in that, The clinical drugs are diclofenac, midazolam, bupropion, artemisinin, sertraline, efavirenz, imatinib, diltiazem, simvastatin, valsartan, glimepiride and glibenclamide. It includes the lanostane-type triterpenoid compound according to claim 1 and clinical drugs; the clinical drugs are diclofenac, midazolam, bupropion, artemisinin, sertraline, efavirenz, imatinib, diltiazem, simvastatin, valsartan, glimepiride and glibenclamide.

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