Juncinate as well as preparation method and application thereof

Abstract

The invention relates to a cinnabarine salt and a preparation method and application thereof, and belongs to the technical field of chemical medicines. According to the present invention, the cinnabarine salt comprises the basic salt and the acidic salt, the cinnabarine salt is prepared by using cinnabarine through the one-step reaction, the purity is more than or equal to 95%, the yield is more than 70%, the reaction condition requirement is not high, the equipment requirement is simple, the dependence on the special equipment is avoided, the production process is simple and controllable, and the method is suitable for the industrial production. The rhodobrylic acid salt disclosed by the invention has anti-inflammatory activity, and has an obvious inhibiting effect on inflammatory response of microglial cells; the compound also has anti-tumor activity, and can significantly inhibit proliferation of large cell lung cancer cells, triple negative breast cancer cells, colon cancer cells and prostate cancer cells.

Description

Technical Field

[0001] The invention belongs to the technical field of chemical medicine and relates to vermilionate and a preparation method and application thereof. Background Art

[0002] In recent years, with the continuous development of drug molecular entities, the structure of drug molecules has become more and more complex, and the solubility of drugs has become worse and worse. The recently reported development of a synthesis process for cinnabaric acid has relatively poor solubility of the finished product cinnabaric acid, which is difficult to dissolve in water, with a solubility in water of <10mg / 100mL.

[0003] Drug salt formation is an important means to improve solubility and bioavailability, and is also a common approach for researchers to optimize the final structure of candidate drugs. Drug salt formation can also increase drug stability, hygroscopicity, and melting point, improve drug crystal form, and play an important role in further developing drug dosage forms. In addition, drug salt formation also has many benefits, such as masking the taste of drugs, improving patient compliance, and extending the shelf life of drugs.

[0004] Therefore, studying the salt forms of cinnamic acid compounds is of great practical significance. Salt formation can improve certain undesirable physical, chemical or biopharmaceutical properties of drugs, such as changing the solubility or dissolution rate of drugs, polymorphism, etc.

[0005] The synthesis process of cinnamic acid has been reported recently, but the synthesis process and application of cinnamic acid salts have not been reported yet. Summary of the invention

[0006] In view of the deficiencies of the prior art, the present invention provides vermilionate and a preparation method and application thereof, wherein the vermilionate has anti-inflammatory and anti-tumor activities.

[0007] The technical solution of the present invention is as follows:

[0008] Vermilionate, whose structural formula is shown in Formula Ⅰ or Formula Ⅱ:

[0009]

[0010] Where R1 is Li + 、Na + , K + 、Zn 2+ , Cs + or Ca 2+ ;

[0011] R2 is hydrochloric acid, acetic acid, trifluoroacetic acid, hydrobromic acid, hydroiodic acid, sulfuric acid, maleic acid, fumaric acid, phosphoric acid, tartaric acid, lactic acid, L-pyroglutamic acid, malic acid, citric acid or methanesulfonic acid.

[0012] The preparation method of the vermilionate represented by the above formula I comprises the following steps:

[0013] The cinnabaric acid is added to an organic solvent 1, and a salt-forming reagent is added to perform a salt-forming reaction. After the reaction is completed, activated carbon is added for decolorization treatment, and then the organic solvent 1 is removed by concentration to dryness, and then an organic solvent 2 and deionized water are added to dissolve, and then a crystallization reagent is added to perform a crystallization treatment, and the cinnabaric acid salt is obtained after filtering and drying.

[0014] Preferably according to the present invention, the organic solvent one is methanol, ethanol or isopropanol, and the amount of the organic solvent one is 5-20 times the weight of cinnabaric acid.

[0015] Preferably according to the present invention, the salt-forming agent is lithium hydroxide, sodium methoxide, sodium hydroxide, sodium carbonate, potassium carbonate, potassium hydroxide, cesium carbonate, zinc hydroxide or calcium hydroxide, and the molar ratio of the salt-forming agent used to vermilion acid is (0.9-1.5):1.

[0016] Further preferably, when the salt-forming reagent is lithium hydroxide, cesium carbonate or calcium hydroxide, the salt-forming reaction conditions are: reacting at 23-27° C. under shaking conditions for 0.5-0.7 h.

[0017] Further preferably, when the salt-forming agent is sodium hydroxide, the salt-forming reaction conditions are: stirring until the system is clear.

[0018] Further preferably, when the salt-forming reagent is potassium hydroxide, the salt-forming reaction conditions are: ultrasonic vibration until the system is clear.

[0019] More preferably, when the salt-forming agent is zinc hydroxide, the salt-forming reaction conditions are: reacting at 33-37° C. under shaking conditions for 1-1.5 hours.

[0020] Preferably according to the present invention, the concentration condition is: concentration to dryness at 35-55°C.

[0021] Preferably according to the present invention, the second organic solvent is dichloromethane, chloroform or dichloroethane, and the amount of the second organic solvent is 2-3 times the weight of vermilion acid.

[0022] Preferably according to the present invention, the amount of deionized water used is 5% to 10% of the weight of vermilionic acid.

[0023] Preferably according to the present invention, the crystallization reagent is ethyl acetate, butyl acetate, amyl acetate, methyl formate, isoamyl acetate, isoamyl isovalerate, ethyl benzoate or ethyl butyrate, and the amount of the crystallization reagent used is 10 to 20 times the weight of vermilionic acid.

[0024] Preferably according to the present invention, the crystallization treatment condition is: crystallization at 5-10°C.

[0025] Preferably according to the present invention, the drying treatment conditions are: drying at 45-50° C. under vacuum conditions.

[0026] The preparation method of the vermilionate represented by the above formula II comprises the following steps:

[0027] Dissolve cinnabaric acid in solvent I, maintain the temperature at -10 to 10°C, add the corresponding acid dropwise, solid will precipitate continuously until the solid is completely precipitated, then stir, at which time the solid particles become tiny needle-shaped crystals, filter and dry to obtain cinnabaric acid salt.

[0028] Preferably according to the present invention, the solvent I is one or more of methanol, ethanol, isopropanol, ethyl acetate, butyl acetate, amyl acetate, methyl formate, isoamyl acetate, isoamyl isovalerate, ethyl benzoate, and ethyl butyrate, and the amount of the solvent I is 5-10 times the weight of cinnamic acid.

[0029] Preferably according to the present invention, the acid is hydrochloric acid, acetic acid, trifluoroacetic acid, hydrobromic acid, hydroiodic acid, sulfuric acid, maleic acid, fumaric acid, phosphoric acid, tartaric acid, lactic acid, L-pyroglutamic acid, malic acid, citric acid, and the molar ratio of the acid used to vermilion acid is (1-4):1.

[0030] More preferably, the acid is dissolved in an alcohol solvent to form an alcohol solution of the acid, which is then added dropwise to the reaction system.

[0031] More preferably, the alcohol solvent is one or more of methanol, ethanol or isopropanol.

[0032] More preferably, the acid concentration in the alcoholic acid solution is 6 to 50 mol / L.

[0033] Preferably according to the present invention, in order to better precipitate the solid, refrigeration crystallization is performed before stirring and / or solvent II is added before stirring, and the solvent II is acetone, methyl isobutyl ketone, anhydrous ethyl ether, isopropyl ether or methyl tert-butyl ether.

[0034] More preferably, the amount of the solvent II is 2-10 times the weight of rubellonic acid.

[0035] The application of the above-mentioned vermilionate in the preparation of drugs for treating neuroinflammation.

[0036] The application of the above-mentioned vermilionate in the preparation of drugs for treating tumors.

[0037] Preferably according to the present invention, the tumors include: large cell lung cancer, triple-negative breast cancer, colon cancer, and prostate cancer.

[0038] Beneficial effects:

[0039] 1. The cinnamate salt in the present invention includes alkaline salt and acidic salt. The cinnamate salt is prepared by one-step reaction using cinnamate acid, with a purity of ≥95% and a yield of more than 70%. The reaction conditions are not demanding, the equipment requirements are simple, there is no dependence on special equipment, the production process is simple and controllable, and it is more suitable for industrial production.

[0040]

[0041] 2. The cinnamate of the present invention has anti-inflammatory activity and has a significant inhibitory effect on the inflammatory response of microglia. Among them, the anti-inflammatory effect of alkaline cinnamate is better than that of acidic cinnamate, but the anti-inflammatory effects of both are better than resveratrol, and the best anti-inflammatory effect is cesium cinnamate. The cinnamate of the present invention also has anti-tumor activity and can significantly inhibit the proliferation of large cell lung cancer cells, triple-negative breast cancer cells, colon cancer cells and prostate cancer cells, among which cesium cinnamate has the best effect on triple-negative breast cancer cells. The above results show that the cinnamate of the present invention can be used for the research and development and preparation of drugs for treating neuroinflammation and tumors. BRIEF DESCRIPTION OF THE DRAWINGS

[0042] Figure 1 This is the hydrogen spectrum of vermilionic acid.

[0043] Figure 2 It is the HPLC chromatogram of cinnamic acid lithium salt.

[0044] Figure 3 This is the hydrogen spectrum of lithium salt of vermilionate. DETAILED DESCRIPTION

[0045] The present invention will be further described below in conjunction with specific embodiments so that those skilled in the art can better understand the present invention, but the present invention is not limited thereby.

[0046] The reagents and materials involved in the examples are all common commercially available products unless otherwise specified. Vermilion acid can be prepared according to the prior art, such as the preparation described in Example 1 of patent document CN 118440025 A. The hydrogen spectrum of vermilion acid is as follows: Figure 1 shown.

[0047] Embodiment 1:

[0048] 200 mg of cinnabaric acid was added to 4.7 mL of methanol, and 17 mg of lithium hydroxide was added. The system was placed in a constant temperature oscillator (shaker) JCOZ-300J, and the reaction temperature was set to 25°C. The reaction was carried out for 0.5 h. Activated carbon was added for decolorization, and the filtrate was filtered. The filtrate was concentrated to dryness at 35-40°C, 0.5 g of dichloroethane and 10 mg of deionized water were added to dissolve the material, and then 4 g of amyl acetate was added to crystallize at 5-10°C, and the mixture was filtered. The cinnabaric acid lithium salt of 194 mg was obtained, with a yield of 95% and a purity of 97%. The HPLC chromatogram of the obtained cinnabaric acid lithium salt is as follows: Figure 2 As shown, the hydrogen spectrum is Figure 3 shown.

[0049] Embodiment 2:

[0050] 200 mg of cinnabaric acid was added to 5 mL of methanol, 28 mg of sodium hydroxide was added, and the mixture was stirred until clear, activated carbon was added for decolorization, and the mixture was filtered. The filtrate was concentrated to dryness at 40-45° C., 0.6 g of dichloromethane and 20 mg of deionized water were added to dissolve the material, and then 3 g of ethyl acetate was added to crystallize at 5-10° C., filtered, and dried at 45-50° C. under vacuum conditions to obtain 206 mg of cinnabaric acid sodium salt, with a yield of 96% and a purity of 98%. The solubility of cinnabaric acid sodium salt was greatly improved, and it was easily soluble in water. At room temperature and normal pressure, the solubility in water was about 10 g / 100 mL.

[0051] Embodiment 3:

[0052] 200 mg of cinnabaric acid was added to 4.5 mL of ethanol, 40 mg of potassium hydroxide was added, ultrasonic vibration was performed until clarified, activated carbon was added for decolorization, and the filtrate was concentrated to dryness at 40-45° C., 0.5 g of dichloromethane and 15 mg of deionized water were added to dissolve the material, and then 4 g of butyl acetate was added to crystallize at 5-10° C., the mixture was filtered off, and dried at 45-50° C. under vacuum conditions to obtain 218 mg of cinnabaric acid potassium salt, with a molar yield of 96% and a purity of 97%.

[0053] Embodiment 4:

[0054] 200 mg of cinnabaric acid was added to 4.7 mL of isopropanol, and 68 mg of zinc hydroxide was added. The system was placed in a constant temperature oscillator (shaker) JCOZ-300J, and the reaction temperature was set to 35°C. The reaction was carried out for 1 hour, and activated carbon was added for decolorization. The mixture was filtered and the filtrate was concentrated to dryness at 40-55°C. 0.5 g of chloroform and 14 mg of deionized water were added to dissolve the material, and then 4 g of amyl acetate was added to crystallize at 5-10°C, and the mixture was filtered and dried at 45-50°C under vacuum to obtain 212 mg of cinnabaric acid zinc salt with a yield of 96% and a purity of 95%.

[0055] Embodiment 5:

[0056] According to the preparation method of Example 1, cesium carbonate and calcium hydroxide were used as salt-forming reagents to prepare cesium cinnamate and calcium cinnamate respectively.

[0057] Embodiment 6:

[0058] 2 g of cinnabaric acid was dissolved in 20 mL of ethyl acetate, and the reaction system was placed in an ice-salt bath at 0-5°C. 1.5 mL of a methanol solution of hydrochloric acid was added dropwise to the system, wherein the concentration of hydrochloric acid in the methanol solution of hydrochloric acid was 6 mol / L. Solids were continuously precipitated. In order to better precipitate the solids, 5 g of acetone was added and stirred for 1-2 h. The cinnabaric acid hydrochloride was obtained by suction filtration and drying, with a yield of 70% and a purity of 95%.

[0059] Embodiment 7:

[0060] 1.5 g of cinnabaric acid was dissolved in 17 mL of butyl acetate, and the reaction system was placed in an ice-salt bath at -10 to -5°C. 1.6 mL of hydrochloric acid ethanol solution was added dropwise to the system so that the pH of the system was 1.0 to 2.0. The concentration of hydrochloric acid in the hydrochloric acid ethanol solution was 6 mol / L. Solids were continuously precipitated. The solution was placed in a freezer and refrigerated for crystallization. 15 g of anhydrous ether was added and stirred for 1 to 2 hours. The solution was filtered and dried to obtain cinnabaric hydrochloride with a yield of 72% and a purity of 96%.

[0061] Embodiment 8:

[0062] 2 g of cinnabaric acid was dissolved in a mixed solution of 24 mL of methanol and ethanol (1:1, v / v), the reaction system was placed in an ice-salt bath at -5 to 0° C., 0.5 mL of trifluoroacetic acid methanol solution was added dropwise to the system, the concentration of trifluoroacetic acid in the trifluoroacetic acid methanol solution was 50 mol / L, solids were continuously precipitated, the solution was placed in a freezer, refrigerated for crystallization, 10 g of methyl isobutyl ketone was added, stirred, filtered and dried to obtain cinnabaric acid trifluoroacetate, with a yield of 73% and a purity of 95%.

[0063] Example 9

[0064] The preparation methods of cinnamic acid methanesulfonate, cinnamic acid hydrobromide, cinnamic acid hydroiodide, cinnamic acid acetate, cinnamic acid sulfate, cinnamic acid maleate, cinnamic acid fumarate, cinnamic acid phosphate, cinnamic acid tartrate, cinnamic acid lactate, cinnamic acid L-pyroglutamate, and cinnamic acid malate are the same as those in Example 7.

[0065] The cinnamate prepared above or the cinnamate prepared by the above method are summarized and numbered as shown in the following table:

[0066] Table 1. Summary of cinnamate in this patent

[0067] Compound No. Salt-forming reagent Vermilionate 1 Lithium hydroxide Lithium cinnamate 2 Sodium hydroxide Vermilionic acid sodium salt 3 Potassium hydroxide Potassium cinnamate 4 Zinc Hydroxide Vermilionic acid zinc salt 5 Cesium carbonate Vermilionate cesium salt 6 Calcium hydroxide Vermilionic acid calcium salt 7 Methanesulfonic acid Vermilionic acid methanesulfonate 8 hydrochloric acid Vermilion hydrochloride 9 Hydrobromic acid Vermilionic acid hydrobromide 10 Hydroiodic acid Vermilionic acid hydroiodide 11 acetic acid Vermilionic acid acetate 12 Trifluoroacetic acid Vermilionic acid trifluoroacetate 13 sulfuric acid Vermilionic acid sulfate 14 Maleic acid Vermilionic acid maleate 15 Fumaric Acid Vermilionic acid fumarate 16 Phosphoric acid Vermilionic acid phosphate 17 tartaric acid Vermilionic acid tartrate 18 lactic acid Vermilionic acid lactate 19 L-Pyroglutamic acid Vermilionic acid L-pyroglutamate 20 Malic Acid Vermilionic acid malate

[0068] Experimental Example 1: Anti-inflammatory Activity

[0069] The cinnamate prepared in the example was applied to BV2 cells (mouse microglia, purchased from Shanghai Lianmai Biotechnology Co., Ltd. (LMAl Bio)), and lipopolysaccharide (LPS) was used to induce cell inflammation, and the anti-inflammatory activity of different cinnamate was detected. The specific steps are as follows:

[0070] 1. NO generation rate detection

[0071] BV2 cells were inoculated on a 96-well culture plate, and the culture medium used was DMEM culture medium, and the cells were cultured in a 37°C constant temperature incubator containing 5% CO2. The cells were divided into a drug administration group, a positive control group, and an LPS model group. After culturing for 24 hours, the corresponding concentration (1 μM or 10 μM) of vermilionate prepared in the embodiment was added to the drug administration group, and the corresponding concentration (20 μM) of resveratrol was added to the positive control group. After incubation for 2 hours, LPS (purchased from Sigma-Aldrich) with a final concentration of 100 ng / mL was added to the drug administration group, the positive control group, and the LPS model group, respectively, to induce cellular inflammatory response. The culture was continued for 24 hours in the incubator, and the supernatant of each group was reacted with an equal volume of Griess buffer (purchased from Sigma-Aldrich). The OD value of each group at a wavelength of 540 nm was detected by an enzyme marker (BioTek), wherein the NO generation rate of the LPS model group was set to 100% (n=3), and the NO generation rate of the other groups was calculated on this basis.

[0072] 2. Cell viability assay

[0073] BV2 cells were inoculated on a 96-well culture plate, and the culture medium used was DMEM culture medium, which was placed in a 37°C constant temperature incubator containing 5% CO2. The cells were divided into a drug administration group and an LPS model group. After 24 hours of culture, the corresponding concentration (1 μM or 10 μM) of the cinnamate prepared in the embodiment was added to the drug administration group. After incubation for 2 hours, LPS with a final concentration of 100 ng / mL was added to the drug administration group and the LPS model group to induce cellular inflammatory response. Continue to culture for 24 hours, add a final concentration of 0.5 mg / mL MTT (purchased from Sigma-Aldrich) to each well for live cell staining. After incubation in the incubator, the culture solution was discarded, 100 μL DMSO was added to each well, and it was shaken on a shaker to fully dissolve it. The OD value of each group at a wavelength of 490 nm was detected by an enzyme marker (BioTek), wherein the cell survival rate of the LPS model group was set to 100% (n=3), and the cell survival rate of the other groups was calculated on this basis.

[0074] 3. Test results

[0075] (1) The results of NO generation rate detection are shown in Table 2. It can be found that alkaline vermilionate has a very obvious effect on inhibiting NO generation. It is further found that this is because the carboxyl group can have a stronger chelating ability with metals under alkaline conditions, and by chelating with the ferrous ions of heme in the IDO1 target, it inhibits IDO1 activity, thereby reducing inflammation and inhibiting NO release. The results are: alkaline vermilionate is better than acidic vermilionate and better than resveratrol, and the higher the concentration of vermilionate, the stronger the NO inhibition effect, among which the best is cesium vermilionate.

[0076] Table 2. NO generation rate test results

[0077]

[0078]

[0079] (2) The results of cell viability test are shown in Table 3. It can be found that compared with LPS, alkaline cinnamate is basically non-toxic to BV2 cells, and its cell viability is higher than 100%, but the cell viability of the acidic cinnamate treatment group is lower than 100%. In short, the cytotoxicity of alkaline cinnamate is weaker than that of LPS, which is weaker than that of acidic cinnamate. The lower the concentration of cinnamate, the weaker the cytotoxicity. Among them, cesium cinnamate is the best.

[0080] Table 3. Cell viability test results. Results of toxic effects of compounds on BV2 cells.

[0081]

[0082] Experimental Example 2: Antitumor Activity

[0083] Four cell lines were used to determine the antitumor activity of the vermilionate prepared in the example, and the four cell lines were H460 cells (human large cell lung cancer cells), MDB-MA-231 cells (human triple-negative breast cancer cells), Caco-2 cells (human colon cancer cells), and PC-3 cells (prostate cancer cells), all purchased from Sigma-Aldrich. The specific steps are as follows:

[0084] (1) Cell culture: Tumor cells were cultured using RPMI-1640 medium (complete medium) containing 10% fetal bovine serum (FBS) in a 10-cm-diameter culture dish. 10 mL of complete medium was added to each dish and the dishes were placed in a 37°C, 5% CO2 cell culture incubator for culture.

[0085] (2) Cell passaging: When the cell density reaches 80%, discard the old culture medium and wash the cells twice with PBS buffer (10 mL each time); add 1 mL of trypsin to digest the cells and observe under a microscope. When the cells become round, discard the trypsin and add a certain amount of fresh complete culture medium to beat the cells into single cells. Then, divide the cell suspension into two and add them to two new 10 cm cell culture dishes. Finally, fill up the complete culture medium to 10 mL and culture in a 37°C, 5% CO2 cell culture incubator;

[0086] (3) Determination of cell number: When the cells are subcultured to a density of 80%, wash, digest, and blow the cells according to step (2) to prepare a cell suspension, inoculate the cell suspension in a 96-well plate at 100 μL / well, pre-incubate the 96-well plate in a saturated humidity incubator (37°C, 5% CO2) for 60 min, add 10 μL of CCK8 solution to each well of the 96-well plate, continue to incubate the culture plate in the incubator for 1 to 4 hours, and use a microplate reader to measure the absorbance at 450 nm to determine the cell concentration of the cell suspension;

[0087] (4) Cell proliferation and cytotoxicity assay: Adjust the cell concentration of the cell suspension to 10 3 ~10 4 Cells / well were inoculated in a 96-well plate, 100 μL / well, and the cells were cultured in a 37°C, 5% CO2 incubator for 24 hours. The cells were divided into a drug-treated group and a positive control group. The drug-treated group was divided into a positive control group according to the IC 50 The prepared vermiculate in the example was added to a 96-well plate, 5-fluorouracil (1 μM) was added to the positive control group, and 6 replicates were performed in each group. The 96-well plate was incubated in an incubator for 24 hours, and 10 μL of CCK8 solution was added to each well of the 96-well plate using a repeating pipette. The 96-well plate was incubated in the incubator for 4 hours, and the absorbance at 450 nm was measured using a microplate reader to calculate the cell survival rate.

[0088] The cell survival rate results are shown in Table 4. The cinnamic acid salt of the present invention showed good inhibitory effects on cell proliferation in 4 tumor cell lines, and was superior to cinnamic acid. Among them, cesium cinnamic acid salt had the best effect on triple-negative breast cancer.

[0089] Table 4. Cell viability results

[0090]

[0091]

[0092] The invention improves the solubility of the natural product in water by forming salts of different cinnabaric acids, is beneficial to the transmembrane transport and drug delivery of the compound, and has better activity on inflammatory cells and tumor cells than the natural product.

Claims

1. Vermilionate, characterized in that Its structural formula is shown in Formula I or Formula II: Where R1 is Li + 、Na + , K + 、Zn 2+ , Cs + or Ca 2+ ; R2 is hydrochloric acid, acetic acid, trifluoroacetic acid, hydrobromic acid, hydroiodic acid, sulfuric acid, maleic acid, fumaric acid, phosphoric acid, tartaric acid, lactic acid, L-pyroglutamic acid, malic acid, citric acid or methanesulfonic acid.

2. The method for preparing the vermilionate represented by formula I in claim 1, characterized in that: The steps include: The cinnabaric acid is added to an organic solvent 1, and a salt-forming reagent is added to perform a salt-forming reaction. After the reaction is completed, activated carbon is added for decolorization treatment, and then the organic solvent 1 is removed by concentration to dryness, and then an organic solvent 2 and deionized water are added to dissolve, and then a crystallization reagent is added to perform a crystallization treatment, and the cinnabaric acid salt is obtained after filtering and drying.

3. The preparation method according to claim 2, characterized in that: Meet one or more of the following conditions: i. The organic solvent is methanol, ethanol or isopropanol, and the amount of the organic solvent is 5-20 times the weight of vermilion acid; ii. The salt-forming agent is lithium hydroxide, sodium methoxide, sodium hydroxide, sodium carbonate, potassium carbonate, potassium hydroxide, cesium carbonate, zinc hydroxide or calcium hydroxide, and the molar ratio of the salt-forming agent to vermilion acid is (0.9 to 1.5): 1; iii. The concentration conditions are: 35 to 55 ° C and concentrated to dryness; iv. The organic solvent II is dichloromethane, chloroform or dichloroethane, and the amount of the organic solvent II is 2-3 times the weight of vermilion acid; v. The amount of deionized water is 5% to 10% by weight of vermilion acid; vi. The crystallization agent is ethyl acetate, butyl acetate, amyl acetate, methyl formate, isoamyl acetate, isoamyl isovalerate, ethyl benzoate or ethyl butyrate, and the amount of the crystallization agent is 10 to 20 times the weight of vermilion acid; vii. The crystallization treatment conditions are: 5-10 ° C crystallization; viii. The drying process is carried out under vacuum conditions at 45-50°C.

4. The preparation method according to claim 3, characterized in that: When the salt-forming reagent is lithium hydroxide, cesium carbonate or calcium hydroxide, the salt-forming reaction conditions are: react at 23-27° C. for 0.5-0.7 h under shaking conditions; Preferably, when the salt-forming agent is sodium hydroxide, the salt-forming reaction conditions are: stirring until the system is clear; Preferably, when the salt-forming agent is potassium hydroxide, the salt-forming reaction conditions are: ultrasonic vibration until the system is clear; Preferably, when the salt-forming reagent is zinc hydroxide, the salt-forming reaction conditions are: reacting at 33-37° C. for 1-1.5 hours under shaking conditions.

5. A method for preparing the vermilionate represented by formula II in claim 1, characterized in that: The steps include: Dissolve cinnabaric acid in solvent I, maintain the temperature at -10 to 10°C, add the corresponding acid dropwise, solid will precipitate continuously until the solid is completely precipitated, then stir, at which time the solid particles become tiny needle-shaped crystals, filter and dry to obtain cinnabaric acid salt.

6. The preparation method according to claim 5, characterized in that: Meet one or more of the following conditions: a. The solvent Ⅰ is one or more of methanol, ethanol, isopropanol, ethyl acetate, butyl acetate, amyl acetate, methyl formate, isoamyl acetate, isoamyl isovalerate, ethyl benzoate, and ethyl butyrate, and the amount of the solvent Ⅰ is 5-10 times the weight of vermilion acid; b. The acid is hydrochloric acid, acetic acid, trifluoroacetic acid, hydrobromic acid, hydroiodic acid, sulfuric acid, maleic acid, fumaric acid, phosphoric acid, tartaric acid, lactic acid, L-pyroglutamic acid, malic acid, citric acid, and the molar ratio of the acid to vermilion acid is (1 to 4): 1; c. In order to better precipitate the solid, the mixture is refrigerated for crystallization before stirring and / or solvent II is added before stirring, wherein the solvent II is acetone, methyl isobutyl ketone, anhydrous ether, isopropyl ether or methyl tert-butyl ether; further preferably, the amount of the solvent II is 2-10 times the weight of cinnamic acid.

7. The preparation method according to claim 6, characterized in that: The acid is dissolved in an alcohol solvent to form an alcohol solution of the acid, and then added dropwise to the reaction system; Preferably, the alcohol solvent is one or more of methanol, ethanol or isopropanol; Preferably, the acid concentration in the alcoholic acid solution is 6 to 50 mol / L.

8. Use of the cinnamate of claim 1 in the preparation of a drug for treating neuroinflammation.

9. Use of the vermilionate according to claim 1 in preparing drugs for treating tumors.

10. The use according to claim 9, characterized in that The tumors include: large cell lung cancer, triple negative breast cancer, colon cancer, and prostate cancer.

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