CN112675162A - Application of loganin aglycone in preparation of medicine for preventing and treating viral hepatitis B - Google Patents
Application of loganin aglycone in preparation of medicine for preventing and treating viral hepatitis B Download PDFInfo
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Abstract
The invention belongs to the field of medicines, and relates to application of loganin aglycone in preparation of a medicine for preventing and treating viral hepatitis B. In order to overcome the defects of large toxic and side effects, easy occurrence of tolerance in the treatment process and the like of the existing medicaments for treating the viral hepatitis B, the invention provides an effective medicament for treating the viral hepatitis B. The treatment medicine takes loganin aglycone as an active ingredient, has the function of directly resisting hepatitis B virus when being used for treating patients with hepatitis B virus, can inhibit the hepatitis B virus from secreting HBsAg and HBeAg, can repair liver injury caused by virus infection, has definite curative effect and small toxic and side effects, has good safety and tolerance, and has very wide medical application prospect.
Description
Technical Field
The invention belongs to the field of medicines, relates to medical application of loganin aglycone, and particularly relates to application of loganin aglycone in preparation of a medicine for preventing and treating viral hepatitis B.
Background
Hepatitis B is a disease caused by the Hepatitis B Virus (HBV) and mainly caused by hepatitis virus infection and can cause multiple organ damage. The disease is widely spread in all countries of the world, mainly infringing children and young and middle-aged people, and a few patients can be converted into liver cirrhosis or liver cancer. Therefore, it has become a worldwide disease seriously threatening human health, and is also a disease which is most popular and most serious in China at present. Viral hepatitis B has no epidemic stage, can be developed all the year round, but is diffused mostly. In recent years, the incidence rate of the hepatitis B virus is obviously increased.
The aim of chronic viral hepatitis B treatment is to inhibit HBV replication before significant liver damage occurs. The primary goal of treatment is to inhibit viral replication and prevent liver damage; the long-term aim of treatment is to eliminate virus, prevent the disease from developing into cirrhosis and liver cancer and prolong the life. Antiviral treatments are also used to prevent viral hepatitis b virus replication after liver transplantation, during chemotherapy or immunosuppressive therapy. Since all current antiviral drugs are not able to effectively eliminate HBV DNA, achieving the goal of long-term HBV clearance is nearly impossible. There are two ways to treat chronic viral hepatitis b: immunomodulating and virus inhibiting. Liver transplantation can be used for patients with end-stage liver disease who are not effective in drug treatment.
The method for treating viral hepatitis B in the market at present mainly comprises three modes of injecting interferon drugs, taking nucleoside analogue drugs such as adefovir dipivoxil, entecavir and the like and injecting viral hepatitis B vaccines. However, the three modes have the defects of large size, and the long-term administration of the interferon can cause influenza-like symptoms of patients and possibly cause adverse reactions such as digestive tract symptoms, alopecia and the like of the patients. Also, in severe cases, bone marrow suppression leads to leukopenia and thrombocytopenia, which leads to decreased blood coagulation in patients. And taking nucleoside analogs such as adefovir dipivoxil, entecavir and the like can cause lactic acidosis and severe fatty liver swelling, and many patients can resist the drug for about half a year and cannot stop the drug at any time, otherwise the patients can be rapidly worsened and even become cirrhosis and liver cancer. Although the hepatitis B vaccine can inhibit the replication of HBV and has good safety and tolerance, the immune tolerance state of the hepatitis B is not enough to be broken so as to eliminate the HBV, and the anti-hepatitis B medicine is still required to be used for treatment.
Cornus officinalis (Cornus officinalis Sieb.) & Zucc.) is deciduous tree or shrub of Cornus genus of cornaceae family, and is widely distributed in shanxi, gansu, shandong, jiangsu, zhejiang, anhui, jiangxi, fluvial, Hunan, etc., and also distributed in korean and japan. The dried mature pulp is the Chinese medicine cornus officinalis, also named cornus officinalis, cornus officinalis and the like, and is collected in the 2010 version of the Chinese pharmacopoeia. Can be used for treating vertigo, tinnitus, soreness of waist and knees, sexual impotence, spermatorrhea, enuresis, frequent micturition, metrorrhagia, leukorrhagia, sweating, internal heat, and diabetes. The traditional Chinese medicine composition is widely used clinically, is the main medicine of various compounds or patent medicines such as a pill of six ingredients with rehmannia, a pill of Zhibai with rehmannia, a pill of Jinkui with kidney qi, a pill of Zuogui, a pill of medlar, chrysanthemum and rehmannia, a pill of Guifu with rehmannia, a pill of Yiming with rehmannia, a pill of Jiyin with rehmannia and the like, and is a medicine for tonifying liver and kidney with great research and development values. Iridoid glycoside is one of the main active ingredients of the traditional Chinese medicine dogwood, and the biological activity of the iridoid glycoside is mainly focused on the aspects of immunoregulation, blood sugar reduction, anticoagulation, memory improvement and the like. Through systematic chemical composition research, 19 iridoid glycoside compounds are found in the traditional Chinese medicine dogwood at present.
Loganin is the main component of iridoid glycoside in the Chinese medicine dogwood, is one of the main effective components of Liuwei Dihuang Wan and the like which play pharmacological actions, has the content of 0.37 to 1.22 percent in the medicinal materials, has the functions of immunoregulation, anti-inflammation, antibiosis, cough relieving, phlegm eliminating and the like, and is also an important raw material of some Chinese patent medicines.
Loganin aglycone is loganin aglycone (loganin), and has the following structure:
the loganin aglycone was obtained by extraction from leaves of Desfontainia spinosa plants using conventional column chromatography techniques (Peter J. Houghton. Iridoids from Desfontinania spinosa. phytochemistry,1985,24(8): 1841-1842). The method is complicated to operate, long in time consumption, high in price and not economically feasible. Anupam Maurya and the like optimize a preparation method of loganin aglycone, which takes a chickenaf as a raw material and adopts a rapid centrifugal separation chromatography technology to prepare the loganin aglycone with high purity. The document discloses that loganin itself has no antibacterial activity, but the use in combination with nalidixic acid can significantly reduce the minimum inhibitory concentration of nalidixic acid-resistant and nalidixic acid-sensitive strains of escherichia coli. Loganin aglycone is useful in the treatment of multidrug resistant gram negative bacterial infections (Anupam Maurya. preparative Isolation of Bioenhancer loganin from Alstonia scholaris by Fast Central functional Partition chromatography separation Science and Technology,2014,49(5):773 + 777).
So far, no research on the prevention and treatment effect or clinical application of loganin on viral hepatitis B is available.
Disclosure of Invention
The invention mainly aims to provide the application of loganin aglycone in preparing the medicine for preventing and treating viral hepatitis B.
The purpose of the invention is realized by the following technical scheme:
the in vitro anti-HBV drug effect determination result of loganin aglycone shows that:
(1) loganin has obvious cell inhibition effect on HepG2.2.15 cells, so that loganin has potential effect of inhibiting hepatitis B virus.
(2) HBsAg and HBeAg are main markers in serum of a patient with viral hepatitis B, and the experimental result shows that loganin has obvious inhibition effect on HBSAg and HBeAg secreted by HepG2.2.15 cells, and the inhibition rates of loganin on HBsAg and HBeAg are 77.9% and 65.0% respectively when the loganin concentration is 100 mu g/ml, so that the loganin has obvious inhibition effect. The loganin is suggested to have the function of resisting HBSAg and HBeAg secretion of HBV cells in vitro.
The treatment result of loganin on the viral hepatitis B virus infection in ducks shows that:
each treatment group of loganin aglycone has obvious inhibition effect on DHBV-DNA of infected duck serum, wherein the loganin aglycone high-dose group (5mg/kg) has obvious inhibition effect on DHBV-DNA of infected duck serum and has the characteristic of inhibiting drug withdrawal rebound, and the loganin aglycone still has inhibition effect on viral hepatitis B virus after drug administration is stopped.
The experimental result of the effect of loganin on the liver injury of mice caused by sword bean protein A (ConA) shows that:
(1) compared with a normal control group, the serum ALT and AST of the mouse of the model control group are obviously increased.
(2) Compared with a model control group, the serum ALT and AST of the mice of each administration group are obviously reduced, and the statistical difference (P <0.05 or P <0.01) is achieved, wherein the difference between each dosage group of loganin aglycone and the loganin aglycone group is obvious (P <0.01), and the effect of loganin aglycone on treating liver injury is better than that of loganin aglycone.
Another object of the present invention is to provide a specific pharmaceutical preparation for loganin aglycone used in the treatment of immunological liver injury.
Preferably, the preparation of loganin aglycone for treating immunological liver injury is oral preparation or injection preparation.
The oral preparation is tablets, capsules or granules, the injection preparation is composed of loganin and pharmaceutic adjuvants, and the pharmaceutic adjuvants are one or more of ethanol, propylene glycol, PEG400, PEG600 and Tween 80. In addition, the injection can be used for subcutaneous injection.
The human dosage of loganin aglycone is 0.01-100 mg/kg/d, and the dosage can be adjusted according to the dosage contained in each unit of specific preparation when the loganin aglycone is taken, which is easy to realize by a person skilled in the art.
Compared with the method for treating the viral hepatitis B in the prior art, the technical scheme provided by the invention has the following advantages:
1. loganin has strong antiviral activity, and can not generate drug resistance: the results of the in vitro pharmacodynamic test of the invention show that loganin not only can directly inhibit the proliferation of hepatitis B virus, but also has the obvious function of inhibiting HBsAg and HBeAg secretion of hepatitis B virus,
2. loganin aglycone has definite curative effect on in vivo anti-hepatitis B virus, and does not rebound after drug withdrawal; the pharmacodynamic embodiment of the invention proves that loganin has a remarkable inhibiting effect on the level of DHBV-DNA of the infected duck serum and has the characteristic of inhibiting the rebound of drug withdrawal.
3. Loganin can repair liver damage caused by hepatitis B virus infection: the loganin aglycone can repair liver injury caused by hepatitis B virus, can remarkably reduce serum ALT and AST of mice, and has remarkable difference compared with loganin group, which shows that loganin aglycone has excellent effect of treating liver injury.
DETAILED DESCRIPTION OF EMBODIMENT (S) OF INVENTION
The present invention is further illustrated below by specific examples in order to provide those skilled in the art with a full understanding of the present invention, but it should be understood by those skilled in the art that the examples of the present invention are not to be construed as limiting the present invention in any way.
Formulation example 1 loganin aglycone injection
The preparation process comprises the following steps: mixing ethanol and tween-80, adding loganin, stirring for dissolving, adding water for injection to 10L, stirring, adding 0.5% injectable active carbon, stirring, and removing carbon.
Formulation example 2 loganin aglycone injection
Loganin aglycone 10g
Ethanol 3.3L
Adding water for injection to 10L
The preparation process comprises the following steps: adding loganin into ethanol, stirring to dissolve, adding water for injection to 10L, stirring, adding 0.5% injectable activated carbon, stirring, and removing carbon.
Formulation example 3 loganin aglycone injection
The preparation process comprises the following steps: uniformly mixing the propylene glycol and the ethanol according to the prescription amount, adding loganin aglycone, stirring and dissolving, adding the sodium chloride solution with the concentration of 0.9% according to the prescription amount, uniformly stirring, adding the activated carbon for injection with the concentration of 0.5%, stirring, and removing carbon to obtain the product.
Formulation example 4 loganin aglycone injection
The preparation process comprises the following steps: adding loganin aglycone into PEG-400, stirring for dissolving, adding 0.9% sodium chloride solution to 10L, stirring, adding 0.5% active carbon for injection, stirring, and removing carbon.
Formulation example 5 loganin aglycone injection
The preparation process comprises the following steps: adding loganin aglycone into PEG-400, stirring for dissolving, adding 0.9% sodium chloride solution to 10L, stirring, adding 0.5% active carbon for injection, stirring, and removing carbon.
Formulation example 6 loganin aglycone tablets
Sodium carboxymethyl starch 8g
Magnesium stearate 1.5g
Proper amount of 8 percent starch slurry
The preparation process comprises mixing loganin aglycone with adjuvants including microcrystalline cellulose and sodium carboxymethyl starch, adding appropriate amount of starch slurry to make soft mass, sieving with 16 mesh sieve, and granulating. Drying wet granules at 60 deg.C, sieving dry granules with 20 mesh sieve, grading, sieving to obtain fine powder, mixing with magnesium stearate, mixing with dry granules, and tabletting to obtain tablet of about 200 mg.
Formulation example 7 loganin aglycone capsule
Loganin aglycone 10g
Microcrystalline cellulose 300g
Silica gel micropowder 12g
The preparation process comprises the following steps: pulverizing loganin, microcrystalline cellulose and silica gel micropowder, sieving with 100 mesh sieve, mixing, and directly encapsulating.
Formulation example 8 loganin aglycone granules
The preparation process comprises the following steps: weighing loganin, starch, dextrin and sucrose powder according to the prescription amount, and uniformly mixing. Adding appropriate amount of 80% ethanol into the mixed powder, mixing, making soft mass, sieving with 18 mesh nylon sieve to obtain wet granules, drying at about 60 deg.C, sieving with 20 mesh sieve, and packaging.
Pharmacodynamic example 1 in vitro anti-HBV pharmacodynamic assay of loganin aglycone
1. HepG2.2.15 cell culture
The experiment uses the currently accepted cell model HepG2.2.15 cell for researching HBV replication as a research object, and the HepG2.2.15 cell adopted in the experiment is purchased from China center for type microorganism preservation.
The cell culture solution is MEN culture solution, each 100ml contains 10ml of fetal calf serum, 1ml of glutamine solution with the mass percentage concentration of 3%, G418380 mu G/ml and gentamicin 50U/ml; the cell digestive juice is a pancreatin solution with the mass percent of 0.25 percent and is prepared by Hanks solution.
The cell culture method comprises the following steps: after thawing HepG2.2.15 cells, 25cm were inoculated2Culture flask with concentration of 1 × 105And (4) adding 0.25% pancreatin for digestion at 37 ℃ for 3-5 minutes after the cells grow full. Adding culture solution, blowing, passing through l:3 passages, collecting supernatant every day, continuously for 2 weeks, and refrigerating for detection.
2. Inhibition of HepG2.2.15 cell proliferation by loganin aglycone
Determining cytotoxicity of the medicine by MTT method, diluting loganin with DMEM culture solution 2 to obtain medicine-containing culture solution with concentration of 200 μ g/ml, 100 μ g/ml, 55 μ g/ml and 25 μ g/ml respectively; mu.l of HepG2.2.15 cells (cell concentration 3X 10) were added to each well of a 96-well plate5Individual cells/ml), 5% CO at 37 deg.C2Culturing in an incubator. Culturing for 24 hr, changing the culture solution containing medicine into 4 wells every 3 days, and changing the culture solution containing medicine into 5% CO at 37 deg.C2The cultivation was continued in the incubator for 8 days. After completion of the culture, 10. mu.l of MTT 5. mu.g/ml was added to the cells in each well, 100. mu.l of the supernatant was retained in each well, and 5% CO was added at 37 ℃2After culturing for 4h in the incubator, the OD value is measured by an enzyme-labeling instrument at the wavelength of 570/630 nm. Blank and cell controls were performed in 4 wells each. The percentage of cell inhibition was calculated according to the following formula.
Percent cell inhibition ═ 100% (cell control 0D value-drug action group OD value)/(cell control OD value-blank OD value) ].
TABLE 1 loganin aglycone inhibitory Effect on HepG2.2.15 cell proliferation
Preliminary cytological experiments show that loganin has obvious cell inhibition effect on HepG2.2.15 cells, so that loganin has potential effect of inhibiting hepatitis B virus.
3. Effect of loganin on secretion of HBSAg and HBeAg by HepG2.2.15 cells
100. mu.l (3X 10) of HepG2.2.15 cells per well of 96-well plate5Individual cells/ml), cultured in a 5% CO 2 incubator at 37 ℃. One day later, the drug-containing culture solution was changed to 4 wells per concentration, loganin aglycone was diluted with DMEM (100. mu.g/ml, 50. mu.g/ml, 25. mu.g/ml, 12.5. mu.g/ml) and the same concentration of drug-containing culture solution was changed every 3 days, and culture supernatant was collected on day 9 and stored frozen at-20 ℃. The ELISA detection kit is used for detecting HBsAg and HBeAg, and the enzyme-linked immunosorbent assay (ELISA) instrument is used for detecting an OD value at 540/630nm wavelength. Blank and cell controls were performed in 4 wells each.
Percent inhibition was ═ 100% (cell control OD value-drug action group OD value)/(cell control OD value-blank OD value) ]. The results are shown in Table 2.
TABLE 2 loganin aglycone vs. HepG2.2.15 cells secreting HBSEffect of Ag and HBeAg
HBsAg and HBeAg are main markers in serum of patients with viral hepatitis B, and the experimental result shows that loganin aglycone secretes HB to HepG2.2.15 cellsSThe Ag and HBeAg have obvious inhibiting effect, and the inhibition rates of loganin aglycone to HBsAg and HBeAg are 77.9% and 65.0% respectively when the loganin aglycone concentration is 100 mu g/ml, so that the obvious inhibiting effect is achieved. Suggesting that loganin has anti-HBV cell secretion HB in vitroSAg and HBeAg.
Pharmacodynamic example 2 therapeutic Effect of loganin on viral hepatitis B Virus infection in Duck bodies
The invention adopts a recognized experiment model at home and abroad to carry out experiments in duck bodies infected by the virus B hepatitis virus.
DHBV infection 50 ducklings injected with DHBV-DNA positive duck serum through the tibiovenous, 0.2ml each. Blood was taken 7 days after infection, serum was separated, and stored at 70 ℃ for examination.
2. Drug treatment test: DHBV infected 1-day-old Beijing ducks are randomly grouped, 3 doses of the components are administered, the loganin aglycone injection prepared in example 1 is administered by intraperitoneal injection, and the loganin aglycone injection is a loganin aglycone low dose group (0.5mg/kg), a loganin aglycone medium dose group (2.5mg/kg) and a loganin aglycone high dose group (5mg/kg), the doses are continuously administered for 10 days 2 times every day, and a blank control group replaces the drugs with physiological saline; the positive drug acyclovir group (50mg/kg) was administered 2 times daily for 10 consecutive days. Before administration, at 5d, 10d and 3d after drug withdrawal, blood is respectively taken from the tibial vein of the duck leg, serum is separated, and the blood is stored at-70 ℃ for detection.
3. The detection method comprises the following steps: and (3) taking the duck serum to be detected, and measuring the dynamic level of DHBV-DNA in the duck serum at the same time point of each batch of time films. According to the method of the instruction of the notch translation kit, a DHBV-DNA probe is marked by 32p and used as a duck serum spot for hybridization, a membrane spot is subjected to autoradiography, the OD value (490nm) is measured, the density of the DHBV-DNA in the serum is calculated, and the OD value of the hybridization spot is used as the level value of the DHBV-DNA in the sample.
4. Calculating the drug effect, namely calculating the DHBV-DNA level of each group of serum at different time points, comparing before and after each group of drugs by adopting paired t test, calculating the DHBV-DNA inhibition rate, and comparing the dynamic change of the DHBV-DNA inhibition rate of each group of duck serum. The dosing groups were compared to the virus control groups using a group t test. DHBV-DNA inhibition ═ (pre-dose OD value — post-dose OD value)/pre-dose OD value × 100%. The results are shown in Table 3.
TABLE 3 Effect of loganin aglycone injection on DHBV-DNA levels in duck blood serum infected with DHBV
In comparison with the blank set, the results,#p<0.05,##p<0.01；
compared with the acyclovir group, the method has the advantages that,﹩p<0.05,﹩﹩p<0.01。
the experiment proves that loganin has better activity of resisting duck virus B hepatitis virus through a duck virus B hepatitis model, each treatment group of loganin has obvious inhibition effect on the average of the water of DHBV-DNA of infected duck serum, wherein the inhibition effect of a loganin high-dose group (5mg/kg) on the DHBV-DNA level of the infected duck serum is especially obvious, the loganin has the characteristic of inhibiting drug withdrawal rebound, and the loganin still has inhibition effect on the virus B hepatitis virus after drug administration is stopped.
Pharmacodynamic example 3 Experimental study of the Effect of loganin aglycone on liver injury in mice caused by Canavalin A (ConA)
Canavalid protein (ConA) is a mitogen widely used for activating T cells, and after ConA is injected into mice intravenously, most of ConA accumulates in the liver, and immunological liver injury is caused by the activation of T lymphocytes, which indicates that the liver is a target organ for inducing toxicity by ConA. The experimental model well simulates diseases such as human viral hepatitis, autoimmune liver disease and the like, and is an ideal animal model for screening the treatment drugs for acute hepatitis and fulminant liver failure.
1. Animal grouping and administration
Healthy BALB/C mice, clean grade, 50 mice, half male and female, weight (20 +/-2) g, randomly dividing the mice into 5 groups according to the weight, and 10 mice in each group are respectively a normal control group, a model control group, a loganin low-dose group and a loganin high-dose group (tablets in preparation example 6).
The following drugs were administered to each group:
normal control group: the same volume of normal saline is used for gastric perfusion
Model control group: the same volume of normal saline is used for gastric perfusion
Loganin group: 50mg/kg loganin, and is administered by intragastric administration
Loganin low dose group: 5mg/kg loganin aglycone, and is administered by intragastric administration
Loganin high dose group: 10mg/kg loganin aglycone, and is administered by intragastric administration
The drug is administrated once a day for 10 days continuously according to the dose, 1h after the last drug administration, except a normal control group, each group is administrated with ConA to induce liver injury, and the specific method comprises the following steps: mice were injected intravenously with 15mg/kg ConA. After modeling, fasting, taking blood by taking eyeballs of the mice after 8 hours, and separating serum for measuring serum biochemical indexes; livers were removed to prepare liver homogenates and for histopathological examination. The determination method of the serum ALT and AST comprises the following steps: after the model is made, the mice are fasted for 8 hours without water prohibition, blood is taken after anesthesia, the blood is kept still for 1 hour and 3000r/min, serum is taken after centrifugation for 15 minutes, and the blood is refrigerated for 4 ℃ to be used for measuring ALT and AST by an automatic biochemical analyzer.
2. Data processing
Data of
Shown, analysis of variance was performed using SPSS15.0 software.
3. Results and discussion
From the results in Table 4, it can be seen that:
(1) compared with a normal control group, the serum ALT and AST of the mouse of the model control group are obviously increased.
(2) Compared with a model control group, the serum ALT and AST of the mice of each administration group are obviously reduced, and the statistical difference (P <0.05 or P <0.01) is achieved, wherein the difference between each dosage group of loganin aglycone and the loganin aglycone group is obvious (P <0.01), and the effect of loganin aglycone on treating liver injury is better than that of loganin aglycone.
TABLE 4 influence of loganin on ConA induced liver injury in mice
| Group of | n | ALT(U/L) | AST(U/L) |
| Normal control group | 10 | 44.67±6.66 | 99.05±10.12 |
| Model control group | 10 | 898.78±78.56## | 1001.46±109.53## |
| Loganin group | 10 | 698.78±67.23﹩ | 785.46±99.76﹩ |
| Loganin aglycone low dose group | 10 | 304.89±69.09﹩﹩&& | 201.15±67.89﹩﹩&& |
| Loganin aglycone high dose group | 10 | 101.04±23.45﹩﹩&& | 141.07±34.78﹩﹩&& |
Compared with the normal control group, the composition has the advantages that,##P<0.01；
compared with the model control group,﹩P<0.05，﹩﹩P<0.01；
compared with the loganin group, the method has the advantages that,&&P<0.01。
(2) the pathological detection result shows that a plurality of liver lobules can be seen in the liver of the normal control group mouse, the liver chordae are regularly arranged, the structure of the liver lobules is clear, the structure of the portal area is clear, and no obvious inflammatory cell infiltration and liver cell necrosis exist. The mouse in the model control group has disorganized liver cable arrangement, damaged liver lobule structure, more lymphocyte and monocyte infiltration and small-focus liver cell necrosis. The lobular structure of the livers of each group of mice of loganin aglycone is basically preserved, the arrangement of the liver cords is basically regular, a small amount of lymphocytes and monocytes are infiltrated in the portal area, obvious hepatocyte necrosis is not seen, and the pathological changes are obviously reduced compared with a model control group.
Claims (10)
1. Use of loganin aglycone in preparing medicine for preventing and treating viral hepatitis B is provided.
2. The use of claim 1, wherein loganin is capable of inhibiting the proliferation of hepatitis b virus.
3. The use of claim 1, wherein loganin is capable of inhibiting secretion of HBsAg and HBeAg by hepatitis B virus.
4. The use of claim 1, wherein loganin is capable of repairing liver damage caused by hepatitis b virus infection.
5. The use according to any one of claims 1 to 4, wherein loganin is in an oral or injectable form.
6. The use of claim 5, wherein the oral formulation comprising loganin is in the form of a tablet, capsule, granule.
7. The use of claim 5, wherein the loganin-containing injection is composed of loganin and a pharmaceutically acceptable excipient.
8. The use of claim 7, wherein the pharmaceutical excipient can be one or more of ethanol, propylene glycol, PEG400, PEG600, Tween 80.
9. The use according to claim 1, wherein the loganin is administered in a human dose of 0.01mg/kg.d to 100 mg/kg.d.
10. The use of claim 5, wherein the injectable formulation of loganin aglycone is suitable for subcutaneous injection.
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