NL2034947A

NL2034947A - Application of scutellarein in the preparation of drugs for treating pancreatic cancer

Info

Publication number: NL2034947A
Application number: NL2034947A
Authority: NL
Inventors: Su Jia; Li Yan; Kong Lingmei; Bai Xue; Dong Zejun
Original assignee: Kunming Inst Botany Cas; Yunnan Univ Of Chinese Medicine
Priority date: 2022-05-27
Filing date: 2023-05-30
Publication date: 2023-12-05
Also published as: CN114788822A

Abstract

The present disclosure discloses an application of scutellarein in the preparation of drugs for treating pancreatic cancer. According to the present disclosure, scutellarein is applied to the treatment of pancreatic cancer for the first time. The pancreatic cancer cell line PANC-l is chosen to evaluate the activity of scutellarein. The results show that scutellarein can signiﬁcantly inhibit the proliferation and colony formation of PANC-l cells. In the in Vivo experiment, BALB/c nude mice are inoculated with PANC-l cells, and treated with scutellarein by intraperitoneal injection. The results show that scutellarein can inhibit the growth of transplanted tumors in nude mice, and the tumor inhibition rate is signiﬁcantly different from that in the control group.

Description

APPLICATION OF SCUTELLAREIN IN THE PREPARATION OF DRUGS

FOR TREATING PANCREATIC CANCER

TECHNICAL FIELD

[0001] The present disclosure belongs to the technical field of medicine, and particularly relates to an application of scutellarein in the preparation of drugs for treating pancreatic cancer.

BACKGROUND

[0002] Pancreatic cancer is characterized by strong invasiveness, difficulty in early diagnosis, high metastasis and high mortality rate, and is the malignant tumor with the highest mortality rate. At present, the clinical treatment of pancreatic cancer is mainly surgical resection and chemotherapy. Surgical radical resection is the most effective treatment for pancreatic cancer, and it is almost the only chance for patients with pancreatic cancer to achieve long-term survival. However, 80% of newly diagnosed patients often have developed to the middle or advanced stages when they are diagnosed because of local progression and distant metastasis. Only 10% to 20% of patients can receive surgical treatment when they are diagnosed. However, it cannot fundamentally improve the clinical prognosis of patients with pancreatic cancer. As a systemic disease, morphological resection cannot radically cure pancreatic cancer biologically. Even if surgical resection is possible, the median survival time of patients with pancreatic cancer is less than 2 years.

[0003] Chemotherapy is not only an important method to improve the quality of life and prognosis of patients with pancreatic cancer at the middle and advanced stage, but also plays an important role in the preoperative and postoperative treatment of pancreatic cancer. Due to its special biological behavior, the drug development and treatment progress of pancreatic cancer has been lagging behind other gastrointestinal tumors. Pancreatic cancer is rich in interstitial tissue, and the tumor microenvironment formed by a large amount of fibrous connective tissues is a barrier to the action of chemotherapy drugs, which results in a low local drug concentration in pancreatic cancer tissues and poor chemotherapy sensitivity, thus bringing great limitation to the chemotherapy of pancreatic cancer.

[0004] The first-line drug for the clinical treatment of pancreatic cancer is gemcitabine, and the targeted drugs for pancreatic cancer that have been marketed include erlotinib targeting EGFR and everolimus targeting mTOR. Since the clinical chemotherapeutic drugs alone have low effective rate, limited improvement in patient survival rate and frequent occurrence of drug resistance in the existing applications, the chemotherapeutics-based combination chemotherapy strategy is the main strategy for the treatment of pancreatic cancer. However, although the current combined chemotherapy regimen can improve the efficacy of pancreatic cancer to a certain extent, it still has the disadvantages of obvious toxic and side effects, poor tolerance nd overall prognosis of patients. The novel drug therapies, such as molecular targeted therapy and cancer immunotherapy, are the hotspots in the field of treatment of hepatobiliary and pancreatic cancers. The combination of lenvatinib and pembrolizumab has brought remarkable progress in the treatment of liver cancer, but pancreatic cancer, as a cold tumor, has a low response to the cancer immunotherapy. In addition, in terms of heterogeneity of pancreatic cancer and the characteristics of molecular targeted therapies, it is also difficult to carry out individualized treatment of pancreatic cancer through molecular targets. Based on the above clinical and treatment status of pancreatic cancer, there is no satisfactory drug treatment regimen for pancreatic cancer at present, suggesting the urgency and necessity of new strategies for pancreatic cancer treatment and the development of new drugs, especially the research and development of novel drugs with high-efficacy and low-toxicity for the treatment of pancreatic cancer are of great significance.

[0005] The traditional Chinese medicinal herb Scutellaria barbata D.Don is the dried whole herb of Scutellaria barbata D.Don, a plant of the Labiatae family. Flavonoids are the effective pharmacological components of Scutellaria barbata D.Don. There are more than 50 types of flavonoids in Scutellaria barbata D.Don, including flavonoids, dihydroflavones and flavonoid glycosides. The Chinese Pharmacopoeia (2010)

stipulates that the content of flavonoids in Scutellaria barbata D.Don should be not less than 1.50%. As an important flavonoid component in Scutellaria barbata D.Don, scutellarein has a variety of biological activities and good safety within its activity range. Until now the activity of scutellarein in pancreatic cancer has not been reported, and there 1s no relevant literature and patent disclosure of scutellarein in the treatment of pancreatic cancer.

SUMMARY

[0006] An object of the present disclosure is to provide an application of scutellarein in the preparation of drugs for treating pancreatic cancer.

[0007] The present disclosure is achieved through the following technical solutions: the application of the scutellarein or the medicinal salt thereof as the sole active ingredient or one of the active ingredients in the preparation of drugs for treating pancreatic cancer.

[0008] The structural formula of scutellarein is represented by the following formula (I):

[0009] °

[0010] The present disclosure can achieve the following beneficial effects.

[0011] According to the present disclosure, scutellarein is applied to the treatment of pancreatic cancer for the first time. The pancreatic cancer cell line PANC-1 is treated with scutellarein. The results show that scutellarein can significantly inhibit the proliferation and colony formation of pancreatic cancer cells in vitro; while treatment with scutellarein by intraperitoneal injection in PANC-1 xenograft BALB/c nude mice resulted in inhibition of tumor growth. The results show that scutellarein can inhibit the growth of transplanted tumors in nude mice, and the tumor inhibition rate is significantly different from that in the control group. In summary, scutellarein has inhibitory effects on pancreatic cancer both in vitro and in vivo, and there is no obvious toxicity at the doses in the in vivo experiment, indicating that scutellarein has potential in the treatment of pancreatic cancer. Therefore, scutellarein and its medicinal salts are applicable in the treatment and prevention of pancreatic cancer.

BRIEF DESCRIPTION OF THE DRAWINGS

[0012] FIG. 1 shows the inhibitory effect of scutellarein on the proliferation of

PANC-1 pancreatic cancer cells;

[0013] FIG. 2 shows the inhibition of scutellarein in the clony formation of PANC-1 cells, of which FIG. 2A represents the inhibition of scutellarein in the clony formation of PANC-1 cells, and FIG. 2B indicates the statistical analysis of three independent experiments of colony formation of PANC-1 cells with inhibition of scutellarein;

[0014] FIG. 3 shows the effect of scutellarein on the migration of PANC-1 pancreatic cancer cells, of which FIG. 3A shows cell fusion of wound healing assay,

FIG. 3B shows the bar graph and statistical analysis of cell fusion distance;

[0015] FIG. 4 shows the result of acute toxicity test of scutellarein, of which, FIG. 4A shows the result of the measurement of body weights of mice, FIG. 4B shows the changes in the kidney indexes of mice, FIG. 4C shows the changes in the lung indexes of mice, FIG. 4D shows the changes in the liver indexes of mice, FIG. E shows the changes in the heart indexes of mice;

[0016] FIGs. 5A-G show the inhibitory effect of 50 mg/kg scutellarein on the growth of pancreatic cancer xenografts in nude mice. FIG. SA shows the images of tumor-bearing nude mice after given 50 mg/kg scutellarein, FIG. 5B shows the results of weigh monitoring in nude mice, FIG. SC shows the spleen indexes of mice, FIG. 5D shows the images of xenografts of the control group and the scutellarein treated group,

FIG. SE shows the average weight of xenografts of the control group and the scutellarein treated group, FIG. 5F shows the changes in the tumor volume of xenografts, FIG. SG shows tumor inhibition rate of 50mg/kg scutellarein;

[0017] FIG. 6 shows a schematic diagram of the chemical structure of scutellarein.

DETAILED DESCRIPTION OF THE EMBODIMENTS

[0018] The present disclosure will be further described in detail below in 5 conjunction with the accompanying drawings and embodiments, but they are not intended to limit the present disclosure in any way. Any changes or improvements based on the teaching of the present disclosure shall fall within the protection scope of the present disclosure.

[0019] In the present disclosure, the application of scutellarein is an application of scutellarein or a medicinal salt thereof as the sole active ingredient or one of the active ingredients in the preparation of drugs for treating pancreatic cancer.

[0020] The structure of scutellarein is shown in the formula (I) below:

OH a

[0021] MH

[0022] The dosage of scutellarein is 5.54 mg/kg-22.16 mg/kg.

[0023] The present disclosure further provides a pharmaceutical composition for treating pancreatic cancer, which is prepared with a therapeutically effective dose of scutellarein or a medicinal salt thereof as an active ingredient, and pharmaceutically acceptable excipients or carriers.

[0024] The medicinal salt is a pharmaceutically acceptable salt formed by the compound scutellarein and an organic acid, or an inorganic acid, or an inorganic base, organic base, the inorganic acid is hydrochloric acid, phosphoric acid, sulfuric acid,

nitric acid, the organic acid is formic acid, acetic acid, propionic acid, butyric acid, hexanoic acid, heptanoic acid, oxalic acid, maleic acid, tartaric acid, citric acid, oxalic acid, adipic acid, aspartic acid, benzenesulfonic acid, camphoric acid, camphorsulfonic acid, digluconic acid, succinic acid, cyclopentanepropionic acid, laurylsulfuric acid, ethanesulfonic acid, glucoheptonic acid, glycerophosphoric acid, hemisulfuric acid, fumaric acid, 2-hydroxyethanesulfonic acid, lactic acid, methanesulfonic acid, nicotinic acid, 2-naphthalenesulfonic acid, pamoic acid, pectinic acid, 3-phenylpropionic acid, picric acid, pivalic acid, the inorganic base and organic base are sodium hydroxide, tris(hydroxymethyl)aminomethane, N-methyl-glucosamine.

[0025] Pharmaceutically acceptable carriers include, but are not limited to, lecithin, vitamin E, polyethylene glycol, propylene glycol, glycerin, Tween or other surfactants for pharmaceutical preparation, aluminum oxide, aluminum stearate, an ion exchange material, a buffer substance such as phosphate, sorbic acid, polyvinylpyrrolidone, a cellulosic substance, polyvinyl alcohol, sodium carboxymethylcellulose, lanolin, cyclodextrin, etc., which can be used to promote the compound of the present disclosure, the medicinal salt thereof or prodrug/drug delivery.

[0026] Pharmaceutically acceptable excipients include, but are not limited to, disintegrants such as sodium carboxymethyl starch, cross-linked sodium carboxymethylcellulose, low-substituted hydroxypropyl cellulose, cross-linked polyvinylpyrrolidone, sodium alginate, etc., binders such as povidone K30, microcrystalline cellulose, sodium alginate, etc, fillers such as anhydrous lactose, starch, glucose, lactose beads, etc., lubricants such as magnesium lauryl sulfate, magnesium stearate, etc., and other excipients, solubilizers, flavoring agents, coloring agents, etc.

[0027] The pharmaceutical composition can be administered by enteral or parenteral route, and the dosage form may be, but not limited to, injection, powder injection, powder, granule, capsule, tablet or implant.

[0028] Example 1 Effect of scutellarein on pancreatic cancer in vivo and in vitro

[0029] 1. The inhibitory effect of scutellarein on the proliferation of pancreatic cancer PANC-1 cells in vitro.

[0030] Experimental method: (1) PANC-1 cells of the logarithmic growth phase are seeded in a 24-well culture plate(1x10* cells in each well), and the cells are cultured in a carbon dioxide cell incubator.

[0031] (2) Scutellarein(0, 12.5, 25, 50, 100, 200 uM) are added to to each well respectively after cell adhesion, cell number of each well are counted at the indicated time points(7 days).

[0032] (3) Cells of each treatment group are counted at 0, 1, 2, 3, 4, 5, 6, and 7 days after treating with or without scutellarein. Each counting is repeated for three times, and the experiment is repeated for three times independently.

[0033] (4) Perform statistical analysis of data with the SPSS software , and graphs are created with GraphPad Prism 9.

[0034] Test results: As shown in FIG. 1, compared with the control group, the proliferation ability of PANC-1 cells in the scutellarein treatment groups are reduced significantly, and the inhibitory activity of scutellarein on the proliferation of PANC-1 cells is dose-dependent. The proliferation inhibition can be observed at lower doses of 12.5 and 25 uM, and the inhibitory activity of scutellarein at doses of 50 uM and higher on the cell proliferation is significant, suggesting that scutellarein has inhibitory activity on pancreatic cancer growth.

[0035] Inhibitory effect of scutellarein on the colony formation of pancreatic cancer

PANC-1 cells in vitro.

[0036] Experimental method: (1) Inoculate PANC-1 cells in the logarithmic growth phase in a 24-well culture plate, 1,000 cells in each well, and culture the cells in a carbon dioxide cell incubator.

[0037] (2) Add 0, 1.57, 3.13, 6.25, 12.5, and 25 uM scutellarein to each well respectively after cell adhesion.

[0038] (3) After 24 h of treatment, remove the drug-containing medium and use 2 mL of ordinary complete medium to continue culturing.

[0039] (4) After cells are cultured for 14 days, remove the medium of each well, and rinse with PBS, then add 4% paraformaldehyde fix solution for 30 min.

[0040] (5) Remove the fix solution, rinse with PBS, add 0.5% crystal violet staining solution for 15 min. Discard the staining solution, rinse slowly to remove the excess stain.

[0041] (6) Dry in the air and capture images, use Image] to analyze the number of colonies formed in each well, statistical analysis is perform with SPSS software and graphs are created with GraphPad Prism 9.

[0042] Test results: As shown in FIG. 2, scutellarein can effectively inhibit the colony formation of pancreatic cancer PANC-1 cells at a lower dose, and it is almost impossible to form colonies at a concentration of 12.5 pM, which further proves that scutellarein has anti-proliferation activity on pancreatic cancer, and suggests that scutellarein can inhibit the invasiveness of pancreatic cancer to a certain extent.

[0043] Inhibitory effect of scutellarein on the migration of pancreatic cancer

PANC-1 cells in vitro.

[0044] Experimental method: (1) Place the culture insert (specification: 2 wells) in a 6-well culture plate, with the standard wound width of 500 uM, prepare the PANC-1 cell suspension at 1.25x10° cells/mL. 100 pL of PANC-1 cell suspension is added to each part of the insert, and culture overnight in a carbon dioxide cell incubator.

[0045] (2) Add 0, 12.5, 25, 50, 100, 200 uM scutellarein to treat cells after cell adhesion.

[0046] (3) After 24 h of treatment, remove the insert, rinse once with PBS to remove floating cells, add 2 mL of complete medium to continue culturing, and observe the wound healing under a microscope at 0, 24, and 48 h.

[0047] (4) Capture images and quantify the wound width with Image] software, graphs are created with GraphPad Prism 9, and perform statistical analysis with the software SPSS.

[0048] Test results: As shown in FIG. 3, at the time point of 24 h, the wound of

PANC-1 cells in the control group are fully fused, while the wound of the cells in the scutellarein treatment group is inhibited obviously; at the time point of 48 h, the wound of PANC-1 cells treated with 100 uM and 200 uM scutellarein cannot be fully fused, suggesting that scutellarein can apparently inhibit the migration of pancreatic cancer cells and has the activity of inhibiting the metastasis of pancreatic cancer.

[0049] Evaluation of acute toxicity of scutellarein

[0050] Experimental steps:

[0051] (1) Grouping of experimental animals: Four-week-old ICR male mice (1842 g) are randomly divided into groups after 3 days of adaptive feeding, 5 animals in each group.

[0052] Solvent control group: 90% normal saline + 4% Tween 80 + 6% DMSO

[0053] Scutellarein 50 mg/kg group (low-dose group): Accurately weigh scutellarein powder, add 90% normal saline, 4% Tween 80 and 6% DMSO to prepare a working solution with a concentration of 5 mg/mL.

[0054] Scutellarein 100 mg/kg group (medium-dose group): Accurately weigh scutellarein powder, add 90% normal saline, 4% Tween 80 and 6% DMSO to prepare a working solution with a concentration of 10 mg/mL.

[0055] Scutellarein 200 mg/kg group (high-dose group): Accurately weigh scutellarein powder, add 90% normal saline, 4% Tween 80 and 6% DMSO to prepare a working solution with a concentration of 20 mg/mL.

[0056] The mice received the intraperitoneal injection of scutellarein according to the indicated dose, once a day for 7 consecutive days.

[0057] (2) Observe the signs of the mice every day (including the skin color, coat color, breathing, eye, mouth and nose secretions, activity and survival) and detect the body weights of mice. At the end of the experiment, sacrifice the animals, dissect and inspect the organs such as the heart, lungs, liver, and kidneys in each group; clean the organs with normal saline and dry, measure the weights of each group, then analyze data. The organ index = wet weight of the organ (mg) / body mass (g).

[0058] Test results: As shown in FIG. 4, (1) the signs and behaviors of mice in each group are normal after administration; (2) the body weights of mice in each group are normal within 7 days (FIG. 4A), and the body weights of mice show no trend of obvious decline in low-, medium- and high-dose groups of scutellarein comparing with the control group; (3) no abnormal changes in organs such as heart, liver, spleen, lungs, kidneys, and stomach are observed with the naked eyes after dissection (FIG. 4B-E).

Compared with the control group, there are no significant changes in the organ index in the low-, medium- and high-dose groups of scutellarein, suggesting that scutellarein has no obvious toxicity to the main organs of mice. According to the dosage conversion standard, the safe dose of scutellarein for human treatment is 5.54 mg/kg-22.16 mg/kg.

[0059] Inhibitory effect of scutellarein on tumor growth of pancreatic cancer xenografts in nude mice

[0060] Experimental method: (1) construction of tumor models: After BALB/c nude mice (4- week-old) are fed adaptively for 5 days, if no abnormality 1s observed, carry out the experiment. Culture the PANC-1 pancreatic cancer cells to the logarithmic growth phase, collect cells after trypsinization, resuspend in PBS, adjust the cell concentration to 8x107 cells/mL; mix the cell suspension with pre-cooled Matrix gel, and subcutaneously inject 200 uL to the right upper limb of each nude mouse, totally 810° cells for each mouse. After inoculation, observe the growth status and tumor formation of nude mice. When the tumor volume is about 80 mm’, the model is constructed successfully, and scutellarein treatment is started.

[0061] (2) Administration in groups:

[0062] Solvent control group: 90% normal saline+4% Tween 80+6% DMSO,

[0063] Scutellarein 50 mg/kg group:

[0064] Accurately weigh scutellarein powder, add 90% normal saline, 4% Tween 80 and 6% DMSO to prepare a working solution with a concentration of 5 mg/mL.

[0065] Tumor-bearing nude mice are randomly divided into the control group(vehicle) and the scutellarein group (50 mg/kg), 5 mice in each group.

Tumor-bearing nude mice are injected intraperitoneally with the vehicle or scutellarein containing working solution, once every 48 h for a dosing cycle of 14 days.

[0066] Test indicators: During the dosing period, the signs, body weights, and tumor sizes of nude mice are monitored; at the end of the experiment, animals are photographed; after animals are sacrificed, the tumor tissues were stripped off, the weights of the tumors are measured. The tumors are photographed and recorded according to the size and weight.

[0067] The tumor inhibition rate and spleen index are calculated according to the following formulas. Tumor inhibition rate (%) = (average tumor weight of the control group-average tumor weight of the scutellarein dose group)/ average tumor weight of the scutellarein dose group x 100; spleen index =Wgpieen (MZ) Wh w. (8).

[0068] Test results: As shown in FIGs. 5A-G, compared with the control group, after treatment with 50 mg/kg scutellarein, the tumor growth of pancreatic cancer xenografts is significantly inhibited, and the body weight(FIG. 5B) and organ index (FIG. 5C) of tumor-bearing mice show no obvious decrease comparing with the control group, indicating no obvious toxicity. The above results show that scutellarein exhibits potent inhibitory activity against the pancreatic cancer in vivo, and is safe and suitable for clinical application (based on the dosage conversion standard, the effective dose of scutellarein for human treatment is 5.54 mg/kg).

[0069] Example 2 Preparation of scutellarein

[0070] Take 10 kg of dried Scutellaria barbata D.Don decocting pieces, crush them and carry out cold extraction for three times with 95% ethanol at room temperature, combine the extraction, concentrate under reduced pressure to remove the organic solvent to obtain 723 g of Scutellaria barbata D.Don extraction; extract with petroleum ether, dichloromethane and ethyl acetate successively to obtain the petroleum ether fraction (238.8 g), dichloromethane fraction (32.5 g), ethyl acetate fraction (144.9 g), and aqueous phase fraction ( 146.1 g) respectively; carry out silica gel column chromatography for the petroleum ether fraction for further separation, perform gradient elution with chloroform-methanol in a volume ratio of (100:1)- (2:1), collect and combine the chloroform-methanol (20:1) fraction, then further separate, concentrate, and purify by normal phase silica gel column, reverse C18 column and recrystallization for multiple times to obtain the compound scutellarein.

[0071] Compound scutellarein: yellow powder, ESI-MS m/z 287 [M+H] *; molecular formula: Cys Hip Os. Spectral data: ! H-NMR (400 MHz, DMSO-d 6 ) 6.57 (s, 1H), 6.73 (s, 1H), 6.93 (d, J = 8.7Hz, 2H), 7.91 (d, J = 8.7 Hz, 2H), 8.74 (br s, 1H), 10.35 (br s, 2H), 12.79 (s, 1H),

[0072] Example 3

[0073] Prepare the compound scutellarein according to the method described in

Example 2, then prepare a salt by using organic acids (tartaric acid, citric acid, formic acid, oxalic acid, etc.) or inorganic acids (hydrochloric acid, sulfuric acid, phosphoric acid, etc.), add water for injection conventionally, perform refined filtration, fill and seal, and sterilize to make an injection.

[0074] Example 4

[0075] Prepare the compound scutellarein according to the method described in

Example 2, then prepare a salt by using organic acids (tartaric acid, citric acid, formic acid, oxalic acid, etc.) or inorganic acids (hydrochloric acid, sulfuric acid, phosphoric acid, etc.), dissolve it in sterile water for injection, stir to dissolve, filter with a sterile suction funnel, and then perform refined filtration aseptically, aliquot into 2 ampoules, freeze-dry at a low temperature, aseptically melt-seal to obtain a powder injection.

[0076] Example 5

[0077] Prepare the compound scutellarein according to the method described in

Example 2, then prepare a salt by using organic acids (tartaric acid, citric acid, formic acid, oxalic acid, etc.) or inorganic acids (hydrochloric acid, sulfuric acid, phosphoric acid, etc.), add an excipient in a weight ratio of the salt to the excipient at 9:1, to make a powder.

[0078] Example 6

[0079] Prepare the compound scutellarein according to the method described in

Example 2, then prepare a salt by using organic acids (tartaric acid, citric acid, formic acid, oxalic acid, etc.) or inorganic acids (hydrochloric acid, sulfuric acid, phosphoric acid, etc.), add an excipient in a weight ratio of the salt to the excipient at (1:5)- (1:10), then granulate and compress into tablets.

[0080] Example 7

[0081] Prepare the compound scutellarein according to the method described in

Example 2, add an excipient in a weight ratio of the salt to the excipient at 3:1 to make capsules, granules or infusion.

Claims

Conclusions l. Scutellarein compound represented by the following structural formula (I) or a medical salt thereof, \ HO , x,

a

Use of the scutellarein or its medical salt according to claim 1 as the sole active ingredient or one of the active ingredients in the preparation of medicaments for treating pancreatic cancer.

3. A pharmaceutical composition for treating pancreatic cancer, wherein the pharmaceutical composition is prepared with a therapeutically effective dose of scutellarein or a medical salt thereof as an active ingredient, and pharmaceutically acceptable excipients or carriers.

A pharmaceutical composition according to claim 3, wherein the medical salt is a pharmaceutically acceptable salt formed by the scutellarein compound and an organic acid, or an inorganic acid, or an inorganic base, wherein the inorganic acid is hydrochloric acid, phosphoric acid, sulfuric acid, nitric acid, the organic ACID is formic acid, acetic acid, propionic acid, butyric acid, hexanoic acid, heptanoic acid, oxalic acid, maleic acid, tartaric acid, citric acid, oxalic acid, adipic acid, aspartic acid, benzenesulfonic acid, camphoric acid, camphorsulfonic acid, digluconic acid, succinic acid, cyclopentanepropionic acid, laurylsulfuric acid, ethanesulfonic acid, gluco heptonic acid , glycerophosphoric acid, hemisulfuric acid, fumaric acid, 2-hydroxyethanesulfonic acid, lactic acid, methanesulfonic acid, nicotinic acid, 2-naphthalenesulfonic acid, pamoic acid, pectic acid, 3-phenylpropionic acid, picric acid,

pivalic acid, the inorganic base and organic base are sodium hydroxide, tris(hydroxymethyl)aminomethane, N-methylglucosamine.

A pharmaceutical composition according to claim 3, wherein the pharmaceutical composition can be administered enterally or parenterally, and the dosage form is injection, powder injection, powder, granule, capsule, tablet or implant.

6. Method of preparing scutellareine, which includes the following steps: grinding dried Scutellaria barhata D.Don decoctions in 400 meshes, leaching 3-4 times with 95% ethanol, combining the extraction solution, concentrating under reduced pressure pressure to remove the organic solvent to obtain Scutellaria barbata D.Don extract; extracting the extract with successively petroleum ether, dichloromethane and ethyl acetate, performing silica gel column chromatography for the ethyl acetate fraction, performing gradient elution with chloroform-methanol in a volume ratio of (100:1)-2:1), collecting and combining the eluents chloroform-methanol is a volume ratio of 20:1, then further separation, concentration, purification by normal phase silica gel column, inverted C18 column and recrystallization to obtain the scutellarein compound.