Application of lulutonic acid in the preparation of anti-hepatitis B virus drugs

Abstract

The present invention discloses the use of passutonic acid in the preparation of anti-hepatitis B virus drugs. Passutonic acid can inhibit the replication of hepatitis B virus, inhibit the production and replication of hepatitis B virus antigens, and inhibit the expression of hepatitis B virus mRNA and HBV transcription factors, and has a significant inhibitory effect on hepatitis B virus. It provides a new solution for the development of new anti-hepatitis B virus drugs. Moreover, as a traditional Chinese medicinal material, passutonic acid has abundant medicinal resources and low cost, and is of great significance to the research and development of new anti-hepatitis B virus drugs.

Description

Technical Field

[0001] The present invention belongs to the field of biomedicine technology, and specifically relates to the use of the traditional Chinese medicine compound lulutong acid in the preparation of anti-hepatitis B virus drugs. Background Art

[0002] Hepatitis B is a contagious liver disease caused by the hepatitis B virus (HBV). Its main transmission routes include blood, mother-to-child transmission, and sexual transmission. After the HBV enters liver cells, it undergoes viral replication, transcription, and assembly. The virally replicated hepatitis B surface antigen (HBsAg), HBsAg, and HBsAg are released onto the liver cell membrane, stimulating the body's immune system to recognize and react. This antigen-antibody reaction on the liver cell membrane can damage and destroy liver cells, leading to a range of clinical symptoms and potentially chronic infection, with a high risk of developing cirrhosis and liver cancer.

[0003] Currently, commonly used drugs for the treatment of hepatitis B virus include nucleoside analogs and interferon drugs. However, these drugs either have long treatment cycles, are prone to causing drug-resistant mutations in the HBV virus, or have a number of adverse reactions. Therefore, there is an urgent need to continuously develop new therapies and safer and more effective drugs based on existing ones to achieve a functional cure for HBV. As an effective option for disease treatment, Chinese herbal medicines, whether used as prescriptions or monomeric compounds, have a significant role in disease treatment. Currently, various anti-hepatitis B virus prescriptions or monomeric compounds have been proposed in various schemes. These can not only improve patients' liver function and regulate the body's immune function, but also have relatively few side effects and good patient compliance and tolerance.

[0004] Betulonic acid is a triterpenoid compound isolated from the Chinese herbal medicine Liquidambar formosana Hance (the dried mature infructescence of Liquidambar formosana Hance, a plant of the Hamamelidaceae family). Its molecular formula is C 30 H 46 O3, molecular weight is 454.34, and the structural formula is as follows:

[0005]

[0006] Studies have shown that lulutong acid has multiple biological effects such as anti-inflammatory, analgesic, antibacterial, and anti-tumor.

[0007] However, there are currently no research reports on the inhibitory effect of HBV replication and transcription, as well as the anti-hepatitis B virus effect of lumefantrine. Summary of the Invention

[0008] In view of this, the primary purpose of the present invention is to provide the use of passutonic acid in the preparation of anti-hepatitis B virus drugs. The present invention determines that passutonic acid has a significant inhibitory effect on hepatitis B virus (HBV), providing a new solution for the development of new drugs against hepatitis B virus. Moreover, as a traditional Chinese medicinal material, passutonic acid has abundant medicinal resources and low cost, and is of great significance to the development of anti-hepatitis B virus drugs.

[0009] In order to achieve the above object, the present invention adopts the following technical solutions:

[0010] One aspect of the present invention provides the use of lulutong acid in the preparation of anti-hepatitis B virus drugs.

[0011] The drug has at least one of the following effects:

[0012] a: Inhibit the replication of hepatitis B virus;

[0013] b: Inhibit the production and replication of hepatitis B virus antigen;

[0014] c: Inhibit the expression of hepatitis B virus mRNA;

[0015] d: Inhibit the expression of HBV transcription factors;

[0016] e: Treatment of hepatitis B.

[0017] Another aspect of the present invention provides an anti-hepatitis B virus drug containing an effective concentration of lulutong acid.

[0018] Beneficial effects of the present invention:

[0019] Extensive experiments have confirmed that passutonic acid has a significant inhibitory effect on hepatitis B virus (HBV). Passutonic acid can inhibit the production and replication of HBV antigens, the expression of HBV mRNA, and the expression of HBV transcription factors. Furthermore, using a HBV mouse model, passutonic acid has been shown to be effective in treating and controlling HBV, providing new insights into the development of HBV medications.

[0020] In addition, as a traditional Chinese medicine compound, lulutong acid is widely available, easy to extract, and low in cost. More importantly, it has low cytotoxicity and has a significant inhibitory effect on HBV at lower drug concentrations, which is of great significance for the development of new anti-hepatitis B virus drugs. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Figure 1 This is the result of the CCK8 cytotoxicity test in Example 1 to detect the toxicity of lulutong acid on HepG2.215 cells.

[0022] Figure 2The results of flow cytometry determination of the drug toxicity of lulutong acid on HepG2.215 cells in Example 2 are shown.

[0023] Figure 3 The results of enzyme-linked immunosorbent assay in Example 3 show the inhibition of HBsAg and HBeAg production by HepG2.215 cells using lulutong acid.

[0024] Figure 4 This is the result of real-time fluorescence quantitative determination of the inhibition of mRNA expression in HepG2.215 cells by lulutong acid in Example 4.

[0025] Figure 5 This is the Western blot analysis result of the inhibition of HBV transcription factor expression by lulutong acid in Example 5.

[0026] Figure 6 These are the results of the changes in HBsAg expression in the mouse serum after the hepatitis B mouse model was treated with lulutong acid in Example 6.

[0027] Figure 7 These are the immunohistochemical detection results of HBcAg and HBsAg in the liver of mice after the hepatitis B mouse model was treated with lulutong acid in Example 6. DETAILED DESCRIPTION

[0028] The embodiments of the present invention are described in detail below. The embodiments described below are exemplary and are only used to explain the present invention, and are not to be construed as limiting the present invention.

[0029] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those commonly understood by those skilled in the art of the present invention. The terms used in the specification of the present invention herein are only for the purpose of describing specific embodiments and are not intended to limit the present invention.

[0030] The first aspect of the present invention provides the use of lulutong acid in the preparation of anti-hepatitis B virus drugs.

[0031] Traditional Chinese medicine ingredients have natural advantages in treating hepatitis B and combating the hepatitis B virus. They are widely available, relatively inexpensive, have minimal toxic side effects, and offer improved patient tolerance and compliance. Therefore, screening for traditional Chinese medicine ingredients with anti-hepatitis B virus effects is crucial for the development of drugs for the treatment of the virus. The inventors conducted extensive drug screening experiments and ultimately determined that lulutong acid exhibits a significant inhibitory effect against the hepatitis B virus, suggesting its potential application in the development of anti-hepatitis B virus drugs.

[0032] The second aspect of the present invention further provides an anti-hepatitis B virus drug, which contains an effective concentration of lulutonic acid.

[0033] In the present invention, the drug is an anti-hepatitis B virus drug, which has at least one of the following effects a to e:

[0034] a: Inhibit the replication of hepatitis B virus;

[0035] b: Inhibit the production and replication of hepatitis B virus antigen;

[0036] c: Inhibit the expression of hepatitis B virus mRNA;

[0037] d: Inhibit the expression of HBV transcription factors;

[0038] e: Treatment of hepatitis B.

[0039] The present invention demonstrates, through in vitro cell and animal model experiments, that lulutong acid can inhibit the replication of the hepatitis B virus (HBV), the production and replication of HBV antigens, the expression of HBV mRNA, and the expression of HBV transcription factors, thereby exerting a significant HBV inhibitory effect. The present invention demonstrates a clear mechanism for the anti-HBV effect of lulutong acid, demonstrating its ability to treat hepatitis B and slow the progression of the disease.

[0040] In the present invention, the hepatitis B virus antigen is at least one of HBsAg, HBeAg, and HBcAg.

[0041] The HBV transcription factor is at least one of PPARγ, PGC1α, HNF4α and HNF1α.

[0042] The term "effective concentration" refers to the lowest concentration at which a drug component begins to exert a therapeutic effect. In the present invention, the effective concentration is preferably the concentration at which the drug component exerts a therapeutic effect with minimal toxicity. The term "exerting a therapeutic effect" refers to the suppression or alleviation of the subject's condition after administration. In the present invention, this refers to the slowing or pausing of HBV replication; or the cessation of HBV antigen production, slowing or cessation of replication; or the decrease or elimination of HBV mRNA expression; or the decrease or elimination of HBV transcription factor expression; thereby controlling, alleviating, or even curing the subject's HBV condition.

[0043] In some specific embodiments of the present invention, the effective concentration of lululemon acid is 5 μM to 30 μM, for example, it can be any concentration of 5 μM, 10 μM, 15 μM, 20 μM, 25 μM or 30 μM.

[0044] Preferably, the effective concentration of the passutonic acid is 5 μM to 20 μM, for example, any concentration of 5 μM, 10 μM, 15 μM, or 20 μM.

[0045] Preferably, the effective concentration of the lulutong acid is 10 μM to 20 μM. Within this concentration range, it has a significant inhibitory effect on HBV and has extremely low toxicity.

[0046] In some specific embodiments of the present invention, the effective concentration of lulutonic acid is 10 μM or 20 μM.

[0047] More preferably, the effective concentration of the passutonic acid is 20 μM.

[0048] It is understood that the anti-HBV drug described in the present invention may also include any pharmaceutically acceptable excipients and / or carriers. These excipients and / or carriers are auxiliary components used in pharmaceutical formulations, and preferably, are components that can enhance drug absorption by a subject, increase the drug's biological activity, or mitigate the drug's side effects. For example, it can be a solvent (such as water, ethanol, etc.), a solubilizer or co-solvent (such as cyclodextrin, etc.), an emulsifier (such as lecithin, etc.), a colorant, a binder (such as starch, etc.), a disintegrant (such as cross-linked sodium carboxymethyl cellulose, etc.), a filler (such as lactose, etc.), a lubricant (such as magnesium stearate, etc.), a wetting agent (such as polysorbate, etc.), an osmotic pressure regulator (such as sodium chloride, etc.), a stabilizer (such as ascorbic acid, etc.), a glidant (such as colloidal silicon dioxide, etc.), an anti-caking agent (such as silicate, etc.), a flavoring agent (such as sodium saccharin, etc.), an antioxidant (such as tocopherol, etc.), a gelling agent (such as gelatin, etc.), a buffer (such as phosphate buffer, etc.), and a carrier material (such as microcrystalline cellulose, etc.), but is not limited thereto. Any pharmaceutically acceptable excipient and / or carrier in the art can be used, and those skilled in the art can make a selection based on pharmaceutical common sense in the art and the route of administration of the drug, so there is no particular limitation.

[0049] In the present invention, the administration routes of the anti-HBV drug include, but are not limited to, oral administration, injection, mucosal, transdermal or topical administration, nasal or inhalation administration, etc., and the corresponding dosage form is prepared according to the different administration routes. Preferably, it is an injection or oral preparation.

[0050] Furthermore, the anti-HBV drug of the present invention may also include other known active pharmaceutical ingredients with anti-HBV effects, thereby exerting a better anti-HBV effect. Preferably, these active pharmaceutical ingredients are traditional Chinese medicine ingredients, thereby preparing a traditional Chinese medicine compound. It is understandable that these active pharmaceutical ingredients should have an additive or synergistic promoting effect with lulutong acid, and will not produce toxic side effects with lulutong acid. The selection of specific drugs can be carried out by those skilled in the art by methods well known in the art. It should be noted that if it is a traditional Chinese medicine compound, it needs to be carried out in accordance with the traditional Chinese medicine prescription compatibility principle of "monarch, minister, assistant and envoy".

[0051] The present invention is described below by means of specific examples. It should be noted that the following specific examples are for illustrative purposes only and do not limit the scope of the present invention in any way. In addition, unless otherwise specified, methods without specific conditions or steps are conventional methods, and the reagents and materials used are all commercially available.

[0052] The cells, antibodies and reagents used in the examples of the present invention are shown in Tables 1 to 3.

[0053] Table 1 Information on cells, viruses and experimental animals

[0054] name source HepG2.215 cell line Enzyme Research Biotechnology AAV8[HBV-D,ayw](D#2012) Paizhen Bio C57BL / 6 mice Jicui Yaokang

[0055] Table 2 Antibody information

[0056] Antibody name Item No. Manufacturer β-actin Sc-4778 Santa cruz PGC1alpha+beta Antibody ET1702-96 Hua an PPARγ Sc-7273 Santa cruz HNF-4α Sc-374229 Santa cruz HNF-1α Sc-393925 Santa cruz Ubiquitin rabbit mAb R26024 Positive Energy Biology Goat anti-mouse IgG(H+L)Antibody 31430 Invitrogen Goat anti-rabbit IgG(H+L)Antibody 31460 Invitrogen Rabbit anti-HBsAg NB100-62652 Novus Biologicals Mouse anti-HBcAg C010103 Selvi

[0057] Table 3 Reagent information

[0058]

[0059]

[0060] It should be noted that the above information listed in the present invention is merely an example for the full disclosure of the technical solution, and does not mean that the technical solution of the present invention can only be implemented using the above reagents, cells or antibodies. The specific scope of protection shall be subject to the claims.

[0061] Example 1 Toxicity test of lulutong acid on HepG2.215 cells

[0062] In this example, the CCK8 cytotoxicity test was used to detect the toxicity of different concentrations of passutonic acid on HepG2.215 cells to preliminarily determine the safe concentration range of passutonic acid on HepG2.215 cells. The specific steps are as follows:

[0063] HepG2.215 cells were seeded in 96-well plates at a rate of 20,000 cells per well using DMEM growth medium containing 10% fetal bovine serum and cultured in a 37°C, 5% CO2 incubator. When the cells reached approximately 70% confluency, a 10mM stock solution of passepartout acid prepared by dissolving passepartout acid dry powder in DMSO was diluted with DMEM growth medium to different concentrations of 5μM, 10μM, 15μM, 20μM, 25μM, 30μM, 35μM, and 40μM. The medium in the 96-well plate was replaced with 100μL of drug-containing growth medium per well. A control group (given an equal volume of DMSO) and a blank group (without cells) were set up, with three replicates per group. The cells were cultured in a 37°C, 5% CO2 incubator for 48 hours. After 48 hours, discard the supernatant and add 100 μL of DMEM growth medium containing 10% CCK8 cytotoxicity detection solution. Continue to culture in a 37°C, 5% CO2 incubator for a suitable time. After that, measure the OD value at 450 nm using a microplate reader. The results are shown in the table. Figure 1 .

[0064] pass Figure 1 It can be seen that lulutong acid has low drug toxicity to HepG2.215 cells within the dosage concentration of 30 μM.

[0065] Example 2 Drug toxicity of thiazolinone to HepG2.215 cells at safe concentrations

[0066] Based on the results in Example 1, flow cytometry was used in this example to further determine the drug toxicity of lulutong acid on HepG2.215 cells at a safe dosing concentration. The specific steps were as follows:

[0067] HepG2.215 cells were plated in a six-well plate in DMEM growth medium containing 10% fetal bovine serum, with approximately 500,000 cells per well. When the HepG2.215 cells reached approximately 70% confluency in the six-well plate, 10mM lipoic acid stock solution was diluted with the above medium to different drug concentrations of 5μM, 10μM, 15μM, and 20μM. 100μL of lipoic acid-containing medium was added to the six-well plate. A control group (an equal volume of DMSO) was also set up, with 3 replicates per group. The cells were cultured in a 37°C, 5% CO2 incubator for 48 hours. After 48 hours, the cell supernatant and cells were collected, centrifuged and the supernatant discarded. The cells were resuspended in 200μL PBS buffer and stained with 2μL PI dye. The cells were then subjected to flow cytometry to detect cell viability. For results, see [see ]. Figure 2 .

[0068] pass Figure 2 It can be seen that compared with the control group, lulutong acid has extremely low cytotoxicity to HepG2.215 cells at a dosage concentration of less than 20 μM.

[0069] Example 3 Inhibitory effect of different concentrations of lulutong acid on the production of HBsAg and HBeAg in HepG2.215 cells

[0070] Hepatitis B surface antigen (HBsAg) is the earliest and most important marker of hepatitis B virus infection, and hepatitis B e antigen (HBeAg) is a marker of hepatitis B virus replication. In this example, the inhibitory effect of lulutong acid on the production of HBsAg and HBeAg in HepG2.215 cells at different dosage concentrations was detected by enzyme-linked immunosorbent assay. The specific steps are as follows:

[0071] HepG2.215 cells were plated in 12-well plates and cultured in the same manner as in Example 1. When the HepG2.215 cells grew to a confluency of about 70% in the 12-well plate, the culture medium was discarded and the thiazolinone was diluted to 10 μM and 20 μM with new DMEM growth medium. A control group (DMSO with the same drug volume) was set up at the same time, with 3 replicates per group. The cells were cultured in an incubator at 37°C and 5% CO2 for 48 hours. The supernatant of the culture medium was then aspirated and the OD value was measured on a microplate reader according to the instructions of the enzyme-linked immunosorbent assay kit. The results can be found in the table below. Figure 3 .

[0072] pass Figure 3 It can be seen that with the increase of the concentration of lulutong acid, the amount of HBsAg and HBeAg produced by HepG2.215 cells decreased ( Figure 3 a and Figure 3 b) showed significant differences compared to the control group. These results indicate that lulutong acid at 10μM and 20μM concentrations significantly inhibited the production of HBsAg and HBeAg in HepG2.215 cells. Compared to the control group, * indicates a significant difference (P<0.05); ** indicates an extremely significant difference (P<0.01); *** indicates an even more significant difference (P<0.001); and **** indicates an extremely significant difference (P<0.0001).

[0073] Example 4 Inhibitory effect of different concentrations of lulutong acid on mRNA expression in HepG2.215 cells

[0074] The level of HBV mRNA reflects the activity of HBV infection. A high level of HBV mRNA indicates active viral replication and strong infectivity. In this example, the inhibitory effect of different concentrations of lulutonic acid on mRNA expression in HepG2.215 cells was determined by real-time fluorescence quantitative PCR. The specific steps are as follows:

[0075] The same cell plating and culture method as in Example 3 was used to extract RNA from HepG2.215 cells 48 hours after administration, and then the reverse transcription kit ( Reverse transcription was performed according to the instructions for the Plus All-in-one 1st Strand cDNA Synthesis SuperMix (gDNA Purge). The cDNA was diluted tenfold and used as a template. The qPCR system was configured as follows: 2 μL of diluted cDNA, 7 μL of ddH2O, 10 μL of SYBR, and 0.5 μL of each upstream and downstream primer per well of a 96-well plate. The primer information involved is shown in the following table:

[0076]

[0077] According to the kit ( Real-time fluorescence quantitative PCR was performed using the qPCR protocol in the SYBR qPCR SuperMix Plus manual. The relative expression of total RNA and pgRNA was calculated using the non-administered control group as a reference to evaluate changes in mRNA expression. For results, see Figure 4 .

[0078] pass Figure 4 It can be seen that compared with the control group, lulutong acid at a concentration of 20 μM has a significant inhibitory effect on the mRNA expression of HepG2.215 cells ( Figure 4 a and Figure 4 b). * indicates significant difference (P<0.05); ** indicates extremely significant difference (P<0.01).

[0079] Example 5 Inhibitory effect of lulutong acid on the expression of HBV transcription factors.

[0080] HBV transcription factors play a very important role in the replication and expression of hepatitis B virus. High or active expression of HBV transcription factors promotes the replication and expression of HBV virus, thereby promoting the development of hepatitis B. In this example, Western blot was used to study the inhibitory effect of lulutonic acid on the expression of HBV transcription factors (PPARγ, PGC1α, HNF4α, and HNF1α). The specific steps are as follows:

[0081] HepG2.215 cells were cultured and administered using the same method as in Example 2. After 48 hours, the cells were harvested, washed twice with PBS, and the supernatant was discarded. 200 μL of protein lysis buffer NP-40 was added to lyse the cells on ice for 40 to 60 minutes, centrifuged at 12,000 rpm for 15 minutes, and the supernatant was transferred to another clean EP tube. After the concentration of the supernatant was determined using a BCA kit, protein samples of equal concentration were prepared. The different transcription factor protein bands were then detected by Western blot. The test results are shown in Figure 2. Figure 5 .

[0082] pass Figure 5 It can be seen that lulutong acid has a significant inhibitory effect on the protein expression of HBV transcription factors at the dosage concentration of 10μM and 20μM, and has a certain dose-effect relationship.

[0083] Example 6 Construction of a Hepatitis B Mouse Model to Study the Effect of Lulutong Acid in the Hepatitis B Mouse Model

[0084] In this example, a hepatitis B mouse model was constructed to further study and determine the therapeutic effect of lulutong acid on hepatitis B virus. The specific steps are as follows:

[0085] 1. Construction of Hepatitis B Mouse Model

[0086] 6-8 week-old CL57 mice were injected with HBV AAV8 [HBV-D, ayw] (D#2012) (diluted in PBS) in the orbital cavity twice weekly. Blood was then collected from the orbital cavity, and serum levels of HBsAg and HBeAg were measured to determine if the model was successfully established.

[0087] 2. Drug administration experiment

[0088] The successfully established hepatitis B mouse model was divided into an experimental group and a control group. The experimental group received an intraperitoneal injection of 20 μM 100 μL of a 10 μM stock solution of pamoate diluted in PBS, while the control group received the same volume of PBS once a week. Blood was collected from the mouse orbitals every 10 days to measure changes in HBsAg expression in the mouse serum.

[0089] 3. Immunohistochemical detection of HBcAg and HBsAg in mouse liver

[0090] Mice were sacrificed by cervical dislocation. Fresh livers from control and experimental groups were fixed in 4% paraformaldehyde and embedded in paraffin. The fixed tissue samples were embedded in paraffin, and 3-4 μm sections were prepared. Paraffin sections were deparaffinized in xylene and rehydrated through a gradient of alcohol to remove the paraffin and restore the tissue to its native state. Sections were treated with antigen retrieval solution. Endogenous peroxidases were inactivated with 3% aqueous hydrogen peroxide, and nonspecific binding sites were blocked with blocking solution. Sections were incubated with primary antibodies (rabbit anti-HbsAg and mouse anti-HbcAg) for 60 minutes at room temperature. Horseradish peroxidase (HRP)-conjugated secondary antibodies (goat anti-mouse IgG (H+L) antibody and goat anti-rabbit IgG (H+L) antibody) were then added to bind to the primary antibodies. DAB was used as a chromogen to visualize the location of the target antigen under a light microscope.

[0091] See the results Figure 6 and Figure 7 .

[0092] in, Figure 6 The graph shows the changes in HBsAg expression in mouse serum after a period of treatment with lulutong acid. It can be seen that compared with the control group, the HBsAg expression in the serum of hepatitis B mice in the experimental group has a significant decreasing trend.

[0093] Figure 7 The results show the detection of HBcAg and HBsAg in the liver of mice after administration of lulutong acid. It can be seen that compared with the control group, the color expression of cell membrane and cell nucleus in the liver cells of the experimental group of mice was weaker, which shows that the hepatitis B condition of the experimental group of mice treated with lulutong acid was controlled, indicating that lulutong acid has obvious anti-hepatitis B virus effect.

[0094] The technical features of the above-mentioned embodiments can be combined arbitrarily. In order to make the description concise, not all possible combinations of the technical features in the above-mentioned embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0095] The above-described embodiments merely illustrate several implementations of the present invention, and while their descriptions are relatively specific and detailed, they should not be construed as limiting the scope of the patent. It should be noted that a person skilled in the art would be able to make numerous variations and improvements without departing from the spirit of the present invention, all of which fall within the scope of protection of the present invention. Therefore, the scope of protection of the patent for this invention shall be determined by the appended claims.

Claims

1. Application of lulutong acid in the preparation of anti-hepatitis B virus drugs.

2. The use according to claim 1, characterized in that The effective concentration of the passepartout acid is 5 μM to 30 μM.

3. The use according to claim 1, characterized in that The effective concentration of the passepartout acid is 5 μM to 20 μM.

4. The use according to claim 1, wherein The effective concentration of the lulutonic acid is 10 μM to 20 μM.

5. The use according to claim 1, characterized in that The effective concentration of the passutonic acid is 10 μM or 20 μM.

6. The use according to claim 1, wherein The effective concentration of the passutonic acid is 20 μM.

7. The use according to claim 1, wherein The drug has at least one of the following effects: a: Inhibit the replication of hepatitis B virus; b: Inhibit the production and replication of hepatitis B virus antigen; c: Inhibit the expression of hepatitis B virus mRNA; d: Inhibit the expression of HBV transcription factors; e: Treatment of hepatitis B.

8. The use according to claim 7, characterized in that The hepatitis B virus antigen is at least one of HBsAg, HBeAg, and HBcAg.

9. The use according to claim 7, characterized in that The HBV transcription factor is at least one of PPARγ, PGC1α, HNF4α and HNF1α.

Images