Application of a heteroterpenoid compound and / or a pharmaceutically acceptable salt thereof in the preparation of a drug for treating triple-negative breast cancer

Abstract

The present invention belongs to the field of biomedicine technology, and specifically relates to the use of a heteroterpenoid compound and / or a pharmaceutically acceptable salt thereof in the preparation of a drug for treating triple-negative breast cancer. The present invention provides an application of a heteroterpenoid compound and / or a pharmaceutically acceptable salt thereof in the preparation of a drug for treating triple-negative breast cancer, wherein the heteroterpenoid compound has a structure shown in Formula 1. In the present invention, the compound (clavilactone A) shown in Formula 1 has a good inhibitory effect on the human triple-negative breast cancer MDA-MB-231 cell line, and its IC 50 The inhibitory effect of clavilactoneA on the triple-negative breast cancer MDA-MB-231 cell line is stronger than that of paclitaxel (the main drug currently used to treat triple-negative breast cancer), providing a new option for the development of therapeutic drugs for triple-negative breast cancer.

Description

Technical Field

[0001] The present invention belongs to the field of biomedicine technology, and specifically relates to the use of a heteroterpenoid compound and / or a pharmaceutically acceptable salt thereof in the preparation of a drug for treating triple-negative breast cancer. Background Art

[0002] Malignant tumors are common and frequently occurring diseases that seriously threaten human health and life. Breast cancer, as the malignant tumor with the highest incidence and mortality rate in women worldwide, has always received widespread attention. Triple-negative breast cancer is a special type of breast carcinoid, with an incidence of about 15-20% of all breast cancers. Compared with other breast cancer subtypes, triple-negative breast cancer lacks immunohistochemical expression of estrogen receptors, progesterone receptors, and human epidermal growth factor receptor-2. Triple-negative breast cancer is more invasive, develops rapidly, has a high recurrence rate, and has a poor prognosis. Triple-negative breast cancer is the most malignant type of breast cancer. Triple-negative breast cancer lacks suitable therapeutic targets, and the commonly used endocrine therapy and targeted therapy are relatively ineffective. The available treatments are relatively limited, and chemotherapy remains the main method of systemic treatment. At present, it is necessary to study and develop drugs that can effectively inhibit the activity of triple-negative breast cancer. Summary of the invention

[0003] In view of this, the present invention provides an application of a heteroterpenoid compound and / or a pharmaceutically acceptable salt thereof in the preparation of a drug for inhibiting the activity of a triple-negative breast cancer MDA-MB-231 cell line. In the present invention, the structural compound shown in Formula 1 and / or a pharmaceutically acceptable salt thereof can effectively inhibit the activity of a triple-negative breast cancer MDA-MB-231 cell line, providing support for the treatment of triple-negative breast cancer.

[0004] In order to solve the above technical problems, the present invention provides a use of a heteroterpenoid compound and / or a pharmaceutically acceptable salt thereof in the preparation of a drug for treating triple-negative breast cancer, wherein the heteroterpenoid compound has a structure shown in Formula 1:

[0005]

[0006] Preferably, the method for preparing the compound having the structure shown in Formula 1 comprises the following steps:

[0007] The roots of Lithospermum officinale are soaked in a low-grade alcohol aqueous solution for extraction to obtain an alcohol extract;

[0008] The alcohol extract is subjected to a first silica gel column chromatography to collect the fourth component, which is recorded as Fr.4; the eluent used in the first silica gel column chromatography is a mixed solution of petroleum ether and ethyl acetate and a mixed solution of ethyl acetate and methanol; the elution method of the first silica gel column chromatography is to use a mixed solution of petroleum ether and ethyl acetate and a mixed solution of ethyl acetate and methanol for gradient elution in sequence; the volume ratios of petroleum ether and ethyl acetate in the gradient elution process using the mixed solution of petroleum ether and ethyl acetate are 100:0, 99:1, 98:2, 90:10, 80:20, 70:30, 60:40, 50:50 and 0:100 in sequence; the volume ratios of ethyl acetate and methanol in the gradient elution process using the mixed solution of ethyl acetate and methanol are 90:10, 80:20, 50:50 and 0:100 in sequence;

[0009] The Fr.4 is subjected to a second silica gel column chromatography, and the third component is collected and recorded as Fr.4.3; the eluents used in the second silica gel column chromatography are dichloromethane and methanol; the elution method of the second silica gel column chromatography is gradient elution, and the volume ratios of dichloromethane and methanol in the second silica gel column chromatography are 60:1, 50:1, 25:1, 15:1 and 0:100 respectively;

[0010] The Fr.4.3 is subjected to a first gel column chromatography to collect the third component, which is recorded as Fr.4.3.3; the Fr.4.3.3 is subjected to a second gel column chromatography to collect the second component, which is recorded as Fr.4.3.3.2; the eluent used in the first gel column chromatography is a mixed solvent of dichloromethane and methanol, and the eluent used in the second gel column chromatography is methanol;

[0011] The Fr.4.3.3.2 is separated by a reverse phase chromatography column to obtain the structural compound represented by Formula 1; the eluent used for the reverse phase chromatography column separation is methanol-water solution.

[0012] Preferably, the particle sizes of the fillers for the first silica gel column chromatography and the second silica gel column chromatography are independently 200-300 meshes.

[0013] Preferably, the gels used for the first gel column chromatography and the second gel column chromatography respectively include hydroxypropyl dextran gel;

[0014] The volume ratio of dichloromethane to methanol in the mixed solvent of dichloromethane and methanol is 1:4 to 4:1.

[0015] Preferably, the volume fraction of methanol in the methanol aqueous solution is 83-87%.

[0016] Preferably, the volume fraction of the lower alcohol in the lower alcohol aqueous solution is 50-100%; the lower alcohol includes methanol and / or ethanol;

[0017] The volume ratio of the dry weight of the lithospermum root to the lower alcohol aqueous solution is 0.8-1.2 kg:7L.

[0018] Preferably, the extraction temperature is 15-40° C., the number of extractions is 2-4 times, and the time for a single extraction is 24-120 hours.

[0019] Preferably, the active ingredient of the drug is a terpenoid compound or a pharmaceutically acceptable salt thereof.

[0020] Preferably, the mass percentage of the active component in the medicine is 0.1 to 99 wt %.

[0021] Preferably, the dosage form of the drug includes oral preparation or injection.

[0022] The present invention provides the use of a compound of the structure shown in Formula 1 and / or a pharmaceutically acceptable salt thereof in the preparation of a drug for treating triple-negative breast cancer; In the present invention, the compound of formula 1 and / or its pharmaceutically acceptable salt can effectively inhibit the activity of triple-negative breast cancer cells, and its IC 50 The inhibitory effect of the structural compound shown in Formula 1 (clavilactoneA) on the activity of triple-negative breast cancer cells is higher than that of paclitaxel (the main drug currently used to treat triple-negative breast cancer), providing a new option for the development of therapeutic drugs for triple-negative breast cancer. DETAILED DESCRIPTION

[0023] The present invention provides an application of a heteroterpenoid compound and / or a pharmaceutically acceptable salt thereof in the preparation of a drug for treating triple-negative breast cancer, wherein the heteroterpenoid compound has a structure as shown in Formula 1;

[0024]

[0025] In the present invention, the structural compound represented by Formula 1 is clavilactoneA.

[0026] In the present invention, the method for preparing the compound having the structure shown in Formula 1 comprises the following steps:

[0027] The roots of Lithospermum officinale are soaked in a low-grade alcohol aqueous solution for extraction to obtain an alcohol extract;

[0028] The alcohol extract is subjected to a first silica gel column chromatography to collect the fourth component, which is recorded as Fr.4; the eluent used in the first silica gel column chromatography is a mixed solution of petroleum ether and ethyl acetate and a mixed solution of ethyl acetate and methanol; the elution method of the first silica gel column chromatography is to use a mixed solution of petroleum ether and ethyl acetate and a mixed solution of ethyl acetate and methanol for gradient elution in sequence; the volume ratios of petroleum ether and ethyl acetate in the gradient elution process using the mixed solution of petroleum ether and ethyl acetate are 100:0, 99:1, 98:2, 90:10, 80:20, 70:30, 60:40, 50:50 and 0:100 in sequence; the volume ratios of ethyl acetate and methanol in the gradient elution process using the mixed solution of ethyl acetate and methanol are 90:10, 80:20, 50:50 and 0:100 in sequence;

[0029] The Fr.4 is subjected to a second silica gel column chromatography, and the third component is collected and recorded as Fr.4.3; the eluents used in the second silica gel column chromatography are dichloromethane and methanol; the elution method of the second silica gel column chromatography is gradient elution, and the volume ratios of dichloromethane and methanol in the second silica gel column chromatography are 60:1, 50:1, 25:1, 15:1 and 0:100 respectively;

[0030] The Fr.4.3 is subjected to a first gel column chromatography to collect the third component, which is recorded as Fr.4.3.3; the Fr.4.3.3 is subjected to a second gel column chromatography to collect the second component, which is recorded as Fr.4.3.3.2; the eluent used in the first gel column chromatography is a mixed solvent of dichloromethane and methanol, and the eluent used in the second gel column chromatography is methanol;

[0031] The Fr.4.3.3.2 is separated by a reverse phase chromatography column to obtain the structural compound represented by Formula 1; the eluent used for the reverse phase chromatography column separation is methanol-water solution.

[0032] In the present invention, unless otherwise specified, the materials and equipment used are conventional commercially available products.

[0033] The present invention soaks the lithospermum root in a low-grade alcohol aqueous solution for extraction to obtain an alcohol extract. In the present invention, the soaking preferably further includes: drying the lithospermum root and then cutting it into sections. In the present invention, the drying temperature is preferably 20 to 35°C, more preferably 25°C; the drying time is preferably 8 to 20 days, more preferably 10 days. In the present invention, the length of the lithospermum root after cutting is preferably 0.5 to 2 cm, more preferably 1 cm.

[0034] In the present invention, the volume fraction of the lower alcohol in the lower alcohol aqueous solution is preferably 50-100%, more preferably 90-95%; the lower alcohol preferably includes methanol and / or ethanol, more preferably methanol or ethanol, further preferably methanol.

[0035] In the present invention, the volume ratio of the dry weight of the lithospermum root to the lower alcohol aqueous solution is preferably 4-6kg:6-7L, more preferably 4-5kg:6L.

[0036] In the present invention, the extraction temperature is preferably 15-40°C, more preferably 20-30°C; the number of extractions is preferably 2-4 times, more preferably 3 times; the time for a single extraction is preferably 24-120h, more preferably 30-100h, and further preferably 40-50h.

[0037] In the present invention, after the extraction, the step preferably further comprises: combining the extracts obtained from each extraction and concentrating them to obtain an alcohol extract. The present invention has no special limitation on the concentration, and a concentration method well known to those skilled in the art can be used until the volume does not change, such as reduced pressure concentration.

[0038] After obtaining the alcohol extract, the present invention performs the first silica gel column chromatography on the alcohol extract to collect the fourth component, which is recorded as Fr.4. In the present invention, the particle size of the filler for the first silica gel column chromatography is preferably 200-300 meshes. In the present invention, the eluent used in the first silica gel column chromatography is a mixed solution of petroleum ether and ethyl acetate and a mixed solution of ethyl acetate and methanol; the elution method of the first silica gel column chromatography is to use a mixed solution of petroleum ether and ethyl acetate and a mixed solution of ethyl acetate and methanol for gradient elution in sequence; the volume ratio of petroleum ether to ethyl acetate in the gradient elution process using a mixed solution of petroleum ether and ethyl acetate is 100:0, 99:1, 98:2, 90:10, 80:20, 70:30, 60:40, 50:50 and 0:100 in sequence; the volume ratio of ethyl acetate to methanol in the gradient elution process using a mixed solution of ethyl acetate and methanol is 90:10, 80:20, 50:50, 0:100 in sequence.

[0039] The present invention obtains 12 components through the first silica gel column chromatography, and collects the fourth component.

[0040] After obtaining Fr.4, the present invention performs a second silica gel column chromatography on Fr.4 to collect the third component, which is recorded as Fr.4.3. In the present invention, the particle size of the filler for the second silica gel column chromatography is preferably 200-300 mesh. In the present invention, the eluents used in the second silica gel column chromatography are dichloromethane and methanol; the elution method of the second silica gel column chromatography is gradient elution, and the volume ratios of dichloromethane and methanol in the second silica gel column chromatography are 60:1, 50:1, 25:1, 15:1 and 0:100, respectively.

[0041] The present invention obtains 6 components through the second silica gel column chromatography, and the present invention collects the third component.

[0042] After obtaining Fr.4.3, the present invention subjects Fr.4.3 to a first gel column chromatography to collect the third component, which is recorded as Fr.4.3.3; subjects Fr.4.3.3 to a second gel column chromatography to collect the second component, which is recorded as Fr.4.3.3.2. In the present invention, the gel used for the first gel column chromatography preferably includes hydroxypropyl dextran gel (Sephadex LH-20). In the present invention, the eluent used for the first gel column chromatography is a mixed solvent of dichloromethane and methanol. In the present invention, the volume ratio of dichloromethane and methanol in the mixed solvent of dichloromethane and methanol is preferably 1:4 to 4:1, more preferably 1:2 to 2:1, and further preferably 1:1. In the present invention, the elution mode of the first gel column chromatography is isocratic elution.

[0043] In the present invention, the gel for the second gel column chromatography preferably includes hydroxypropyl dextran gel (Sephadex LH-20). In the present invention, the eluent used in the second gel column chromatography is methanol. In the present invention, the elution method of the second gel column chromatography is isocratic elution.

[0044] After obtaining Fr.4.3.3.2, the present invention performs reverse phase chromatography column separation on Fr.4.3.3.2 to obtain the structural compound shown in Formula 1. In the present invention, the eluent for the reverse phase chromatography column separation is a methanol aqueous solution. In the present invention, the volume fraction of methanol in the methanol aqueous solution is preferably 83 to 87%, more preferably 85%. In the present invention, the elution method for the reverse phase chromatography column separation is isocratic elution.

[0045] In the present invention, the drug preferably includes an active ingredient and an excipient, and the active ingredient is preferably a terpenoid compound or a pharmaceutically acceptable salt of a terpenoid compound. In the present invention, the pharmaceutically acceptable salt of a terpenoid compound preferably includes a sodium salt or a potassium salt. In the present invention, the pharmaceutically acceptable salt of a terpenoid compound is preferably prepared by a terpenoid compound and a metal hydroxide through a salt-forming reaction; the terpenoid compound has a phenolic hydroxyl group as the salt-forming site. In the present invention, the metal hydroxide is preferably sodium hydroxide or potassium hydroxide. The present invention has no special restrictions on the conditions of the salt-forming reaction, and the conventional method in the art can be used.

[0046] In the present invention, the excipient preferably includes a pharmaceutical carrier or excipient. In the present invention, the excipient is preferably one or more of lactose, starch, magnesium stearate and sodium chloride solution. In the present invention, the excipient is non-toxic to humans and animals and is an inert excipient.

[0047] In the present invention, the mass percentage of the active component in the drug is preferably 0.1 to 99 wt%, more preferably 0.5 to 90 wt%, and further preferably 5 to 50 wt%.

[0048] In the present invention, the dosage form of the drug preferably includes an oral agent or an injection. In the present invention, the oral agent preferably includes a powder, tablet, sugar-coated agent, capsule, drop pill or solution syrup; the injection preferably includes a powder injection or a solution injection.

[0049] In the present invention, the tablet is preferably prepared according to the following method:

[0050] first mixing clavilactone A, lactose and starch to obtain a mixture;

[0051] Wetting the mixture with water and then sieving it to take the material under the sieve;

[0052] The sieve material and magnesium stearate are mixed for a second time and then tabletted to obtain the tablet.

[0053] In the present invention, the mass ratio of clavilactone A to lactose is preferably 1:17-19, more preferably 1:18; the mass ratio of clavilactone A to starch is preferably 1:5.3-5.7, more preferably 1:5.5. The present invention has no special requirements for the first mixing, as long as it can be mixed evenly.

[0054] In the present invention, the water is preferably distilled water or sterile water, more preferably distilled water. In the present invention, the aperture of the sieve is preferably 75 to 85 meshes, more preferably 80 meshes.

[0055] In the present invention, the mass ratio of clavilactone A to magnesium stearate is preferably 1:0.4-0.6, more preferably 1:0.5. The present invention has no special requirements for the second mixing, as long as it can be mixed evenly. The present invention has no special requirements for the tableting, and the conventional method in the art can be used.

[0056] In the present invention, the weight of the tablet is preferably 240-260 mg, more preferably 250 mg, and the content of clavilactone A in the tablet is preferably 9-11 mg, more preferably 10 mg.

[0057] In the present invention, the capsule is preferably prepared according to the following method:

[0058] Mix clavilactone A and starch, sieve and take the sieve;

[0059] The sieve material is filled into magnesium stearate capsule shells to obtain the capsules.

[0060] In the present invention, the mass ratio of clavilactone A to starch is preferably 0.8 to 1.2:1, more preferably 1:1. The present invention has no special requirements for the mixing, as long as it can be mixed. In the present invention, the aperture of the sieve is preferably 75 to 85 mesh, more preferably 80 mesh.

[0061] In the present invention, the injection ampoule is preferably prepared according to the following method:

[0062] The clavilactone A and sodium chloride are dissolved in water for injection, filtered, and the filtrate obtained by filtration is aseptically filled into an ampoule bottle and sealed to obtain the ampoule for injection.

[0063] In the present invention, the mass ratio of clavilactone A to sodium chloride is preferably 1:9-11, more preferably 1: 10. In the present invention, the mass ratio of clavilactone A to water for injection is preferably 2 mg:90-110 mL, more preferably 2 mg:100 mL.

[0064] In the present invention, the drug is preferably used in the form of a dosage per unit body weight, and the administration method is preferably oral administration and / or injection, and the injection preferably includes intravenous injection or intramuscular injection.

[0065] The present invention first extracts the lithospermum root by cold soaking with methanol, and then separates the compound clavilactone A by silica gel column chromatography, gel chromatography and semi-preparative liquid chromatography; in the present invention, the silica gel column chromatography is simple to operate, has obvious separation effect and large sample carrying capacity. The gel chromatography has good separation degree, fast separation speed and convenient operation. The reverse phase chromatography column separation method has flexible sample quantity and can process samples from micrograms to milligrams, has high separation efficiency and prepares samples with high purity. The compound clavilactone A prepared according to the preparation method provided by the present invention has stronger inhibitory activity on human triple-negative breast cancer MDA-MB-231 cells than the positive control paclitaxel.

[0066] In order to further illustrate the present invention, the technical solutions provided by the present invention are described in detail below in conjunction with embodiments, but they should not be construed as limiting the protection scope of the present invention.

[0067] Example 1

[0068] S1: Dry 50 kg of lithospermum root at 25° C. for 10 days and cut into small segments of 1 cm in length; soak the cut lithospermum root in 95% methanol aqueous solution at 30° C. for extraction, repeat the extraction 3 times, the amount of methanol aqueous solution used for a single soaking extraction is 60 L, and the single soaking extraction time is 72 h; combine the extracts, and then concentrate the extracts by vacuum concentration at 40° C. to obtain 3.5 kg of alcohol extract;

[0069] S2: The alcohol extract was subjected to a first silica gel column chromatography; the filler used for the first silica gel column chromatography was silica gel with a particle size of 200-300 mesh; a mixed solution of petroleum ether and ethyl acetate and a mixed solution of ethyl acetate and methanol were used in turn for gradient elution to obtain 12 components, and the fourth component was collected and recorded as Fr.4; the volume ratios of petroleum ether and ethyl acetate in the gradient elution process using a mixed solution of petroleum ether and ethyl acetate were 100:0, 99:1, 98:2, 90:10, 80:20, 70:30, 60:40, 50:50 and 0:100, respectively; the volume ratios of ethyl acetate and methanol in the gradient elution process using a mixed solution of ethyl acetate and methanol were 90:10, 80:20, 50:50 and 0:100, respectively;

[0070] S3: Fr.4 was subjected to a second silica gel column chromatography; the filler used for the second silica gel column chromatography was silica gel with a particle size of 200-300 mesh; dichloromethane and methanol were used as eluents for gradient elution to obtain 6 components, and the third component was collected and recorded as Fr.4.3; the volume ratios of dichloromethane and methanol during the gradient elution were 60:1, 50:1, 25:1, 15:1 and 0:100, respectively;

[0071] S4: using a mixed solvent of dichloromethane and methanol in a volume ratio of 1:1 as an eluent to perform the first gel column chromatography on Fr.4.3, and collecting the third component, which is recorded as Fr.4.3.3;

[0072] S5: Perform a second gel column chromatography on Fr.4.3.3 using methanol as the eluent, and collect the second component, which is recorded as Fr.4.3.3.2;

[0073] S6: Fr.4.3.3.2 was separated by a reverse phase column using a methanol aqueous solution with a methanol volume fraction of 85% as an eluent to obtain a light yellow powder compound clavilactone A.

[0074] The clavilactone A prepared in Example 1 was subjected to mass spectrometry analysis, specific rotation analysis, UV analysis and NMR analysis, and the results were as follows:

[0075] Molecular formula: C 16 H 16 O 5 ; ESIMS: m / z 311[M+Na] + ; [α] 20 D +115.2(c 0.11,MeOH); UV(MeOH) max :194,308nm. 1 H NMR (500MHz, Methanol-d 4 )δ:6.75(1H,d,J=8.7Hz,H-2),6.64(1H,d,J=8.7Hz,H-3),6.26(1H,s,H-6),5.25(1H,t,J=8.5Hz,H-11),4.08(1H,s,H-7),3.64(1H,d,J=15 .3Hz,H-13a),2.93(1H,d,J=15.3Hz,H-13b),2.58(1H,ddd,J=13.4,5.0,2.3Hz,H-9a),2.41(1H,m,H-10a),2.14(1H,m,H-10b),1.56(3H,s,H 3 -15),1.28(1H,td,J=13.8,2.9Hz,H-9b); 13 C NMR (151MHz, Methanol-d 4)δ:174.7(C-16),150.9(C-1),150.8(C-4),139.7(C-12),128.2(C-14),122.5(C-11),120.9(C-5),118.6 (C-2),115.3(C-3),77.0(C-6),65.0(C-7),62.7(C-8),28.2(C-13),26.1(C-9),23.4(C-10),21.7(C-15).

[0076] From the above test results, it can be seen that the compound prepared in Example 1 is clavilactone A.

[0077] Test Case

[0078] Anti-triple negative breast cancer MDA-MB-231 cell viability assay:

[0079] Triple negative breast cancer MDA-MB-231 cells were placed in 96-well plates at a density of 5000 cells per well. The cells were exposed to different concentrations of the test compounds for 48 h. After the incubation, 10 μL of CCK-8 solution was added to each well and incubated at 37 °C for 2 h. The absorbance was then measured at 450 nm using a microplate reader (Molecular Devices, USA). Relative cell viability was calculated, and IC was calculated using GraphPad Prism 9.0.0 50 The results are listed in Table 1. Paclitaxel and β,β-dimethylacrylshikonin were used as positive control drugs.

[0080] Table 1 IC of inhibition of MDA-MB-231 cell activity 50 value

[0081] Test compound <![CDATA[IC 50 (μM) <!-- 6 -->]]> clavilactoneA 0.18 β,β-dimethylacrylshikonin 2.45 Paclitaxel 0.48

[0082] Paclitaxel is a commonly used drug for treating triple-negative breast cancer. The compound clavilactoneA prepared in Example 1 of the present invention has stronger inhibitory activity on triple-negative breast cancer MDA-MB-231 cells than paclitaxel.

[0083] Although the above embodiment describes the present invention in detail, it is only a part of the embodiments of the present invention, not all of the embodiments. People can also obtain other embodiments based on this embodiment without creativity, and these embodiments all fall within the protection scope of the present invention.

Claims

1. Use of a heteroterpenoid compound and / or a pharmaceutically acceptable salt thereof in the preparation of a drug for treating triple-negative breast cancer, wherein the heteroterpenoid compound has a structure as shown in Formula 1: Formula 1; The mass percentage of the terpenoid compound in the medicine is 0.1-99wt%.

2. The application according to claim 1, characterized in that: The method for preparing the compound having the structure shown in Formula 1 comprises the following steps: The roots of Lithospermum officinale are soaked in a low-grade alcohol aqueous solution for extraction to obtain an alcohol extract; The alcohol extract is subjected to a first silica gel column chromatography to collect the fourth component, which is recorded as Fr.4; the eluent used in the first silica gel column chromatography is a mixed solution of petroleum ether and ethyl acetate and a mixed solution of ethyl acetate and methanol; the elution method of the first silica gel column chromatography is to use a mixed solution of petroleum ether and ethyl acetate and a mixed solution of ethyl acetate and methanol for gradient elution in sequence; the volume ratios of petroleum ether and ethyl acetate in the gradient elution process using the mixed solution of petroleum ether and ethyl acetate are 100:0, 99:1, 98:2, 90:10, 80:20, 70:30, 60:40, 50:50 and 0:100 in sequence; the volume ratios of ethyl acetate and methanol in the gradient elution process using the mixed solution of ethyl acetate and methanol are 90:10, 80:20, 50:50 and 0:100 in sequence; The Fr.4 is subjected to a second silica gel column chromatography, and the third component is collected and recorded as Fr.4.3; the eluents used in the second silica gel column chromatography are dichloromethane and methanol; the elution method of the second silica gel column chromatography is gradient elution, and the volume ratios of dichloromethane and methanol in the second silica gel column chromatography are 60:1, 50:1, 25:1, 15:1 and 0:100 respectively; The Fr.4.3 is subjected to a first gel column chromatography to collect the third component, which is recorded as Fr.4.3.3; the Fr.4.3.3 is subjected to a second gel column chromatography to collect the second component, which is recorded as Fr.4.3.3.2; the eluent used in the first gel column chromatography is a mixed solvent of dichloromethane and methanol, and the eluent used in the second gel column chromatography is methanol; The Fr.4.3.3.2 is separated by a reverse phase chromatography column to obtain the structural compound represented by Formula 1; the eluent used for the reverse phase chromatography column separation is methanol-water solution.

3. The application according to claim 2, characterized in that: The particle sizes of the fillers for the first silica gel column chromatography and the second silica gel column chromatography are independently 200-300 meshes.

4. The use according to claim 2 or 3, characterized in that: The gels used for the first gel column chromatography and the second gel column chromatography respectively include hydroxypropyl dextran gel; The volume ratio of dichloromethane to methanol in the mixed solvent of dichloromethane and methanol is 1:4 to 4:

1.

5. The application according to claim 2, characterized in that: The volume fraction of methanol in the methanol aqueous solution is 83-87%.

6. The use according to claim 2, characterized in that: The volume fraction of the lower alcohol in the lower alcohol aqueous solution is 50-100%; the lower alcohol includes methanol and / or ethanol; The volume ratio of the dry weight of the lithospermum root to the lower alcohol aqueous solution is 0.8-1.2 kg:7 L.

7. The use according to claim 6, characterized in that: The extraction temperature is 15-40° C., the number of extractions is 2-4 times, and the time for a single extraction is 24-120 hours.

8. The use according to claim 1, characterized in that: The active component of the medicine is a terpenoid compound or a pharmaceutically acceptable salt thereof.

9. The use according to claim 1 or 8, characterized in that: The dosage form of the drug includes oral preparation or injection.

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