WO2022237007A1 - Utilisation de grande berce en tant que principe actif dans la préparation d'un médicament pour le traitement de l'hépatite b - Google Patents

Utilisation de grande berce en tant que principe actif dans la préparation d'un médicament pour le traitement de l'hépatite b Download PDF

Info

Publication number
WO2022237007A1
WO2022237007A1 PCT/CN2021/115274 CN2021115274W WO2022237007A1 WO 2022237007 A1 WO2022237007 A1 WO 2022237007A1 CN 2021115274 W CN2021115274 W CN 2021115274W WO 2022237007 A1 WO2022237007 A1 WO 2022237007A1
Authority
WO
WIPO (PCT)
Prior art keywords
hbv
hepatitis
bovine
preparation
parsnip
Prior art date
Application number
PCT/CN2021/115274
Other languages
English (en)
Chinese (zh)
Inventor
陈娟
黄爱龙
任放
程胜桃
任吉华
Original Assignee
重庆医科大学
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 重庆医科大学 filed Critical 重庆医科大学
Publication of WO2022237007A1 publication Critical patent/WO2022237007A1/fr

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365—Lactones
    • A61K31/366—Lactones having six-membered rings, e.g. delta-lactones
    • A61K31/37—Coumarins, e.g. psoralen
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/20—Antivirals for DNA viruses

Definitions

  • the invention relates to the technical field of biomedicine, in particular to the use of bovine parsnip as an active ingredient in the preparation of hepatitis B therapeutic drugs.
  • Hepatitis B virus is a member of the Hepadnaviridae family, and HBV infection is closely related to the occurrence and development of acute and chronic hepatitis, liver cirrhosis and liver cancer. According to statistics, about 2 billion people in the world have been infected with HBV, of which about 350 million people are chronically infected, and about 1 million people die every year from serious diseases such as liver failure, liver cirrhosis and primary hepatocellular carcinoma caused by HBV infection . my country is a high-incidence area of hepatitis B. Although the hepatitis B vaccine has entered the national basic immunization range, it cannot completely eliminate HBV.
  • hepatitis B surface antigen HBsAg
  • the carrier rate of hepatitis B surface antigen HBsAg in the general population aged 1 to 59 was 7.18%. Due to the large population in our country, it is estimated that there are still HBsAg in our country. Approximately 93 million people are carriers. Mother-to-child transmission is difficult to prevent, and 10% of adults and 5% of minors cannot be immunized by the vaccine, making them the group with the greatest potential infection risk. Hepatitis B virus infection and the resulting diseases not only seriously endanger people's health, but also a serious social public health problem. Therefore, treating chronic HBV infection and preventing the progression of hepatitis B-related diseases is an important task related to global public health.
  • NAs drugs have a strong ability to inhibit viral DNA, NAs cannot completely remove HBsAg in patients and the source of HBV replication-HBV covalently closed circular DNA (cccDNA), and NAs need to be taken for a long time. HBV polymerase mutations may lead to drug resistance, and the viral load of most NAs drugs will rebound after drug withdrawal, which greatly limits the application of such drugs. Therefore, it is necessary to develop anti-HBV drugs with new mechanisms of action and targets.
  • HBV has a complex life cycle.
  • virus particles contact the liver cell membrane, enter the cell under the mediation of the receptor (NTCP), and release the relaxed circular DNA (rc) wrapped by the viral nucleocapsid protein (core protein) after internalization.
  • rcDNA undergoes a series of excision repair reactions under the action of host DNA polymerase and topoisomerase, and finally forms cccDNA with a supercoiled structure.
  • cccDNA is the key molecule to establish persistent infection. Under the action of host RNA polymerase II, it is transcribed to produce four RNA transcripts.
  • the precore RNA is responsible for the coding of HBV core protein and the formation of HBeAg; the 2.4/2.1-kb RNA is responsible for the formation of envelope protein (L, M, S); the 0.7-kb RNA finally forms HBx.
  • the largest pregenomic RNA (PregenomicRNA, pgRNA) forms rcDNA under the action of HBV polymerase, and continues to supplement the cccDNA pool. HBV is difficult to cure, which is closely related to the long-term stable existence of cccDNA.
  • the envelope protein can be integrated into the host genome DNA, so there is a large amount of HBsAg in the patient's serum, which is difficult to reverse. Based on this, the present invention intends to find out new anti-HBV drugs that can effectively reduce HBsAg and shut down cccDNA transcription.
  • the object of the present invention is to provide the purposes of bovine parsnipin as active ingredient in the preparation of hepatitis B treatment medicine, for effectively reducing HBsAg and shutting down cccDNA transcription to provide a kind of new anti-HBV medicine and treatment approach.
  • the first aspect of the present invention provides the use of bovine parsnip as an active ingredient in the preparation of a medicine for treating hepatitis B.
  • hepatitis B treatment drug has at least one of the following functions:
  • the hepatitis B treatment drug must include bovine parsnips, and use bovine parsnips as the active ingredient for the aforementioned functions.
  • the active ingredient that exerts the aforementioned functions may only be boprenin, and may also contain other molecules that can perform similar functions.
  • bovine parsnip is used as one or the only active ingredient of the hepatitis B treatment drug.
  • the hepatitis B therapeutic drug can be a single-component substance or a multi-component substance.
  • the form of the hepatitis B treatment drug is not particularly limited, and may be in various forms such as solid, liquid, gel, semi-fluid, and aerosol.
  • the hepatitis B therapeutic drug is mainly targeted at mammals, such as rodents, primates and the like.
  • the second aspect of the present invention provides a pharmaceutical preparation for treating hepatitis B, including a safe and effective dose of parsnip.
  • the pharmaceutical preparation for treating hepatitis B also includes pharmaceutically acceptable carriers and/or adjuvants.
  • the pharmaceutical preparation for treating hepatitis B must include bovine parsnips, and use bovine parsnips as the active ingredient for the aforementioned functions.
  • the active ingredient that exerts the aforementioned functions may only be parsnip, or may contain other molecules that can perform similar functions.
  • bovine parsnip is used as one or the only active ingredient of the pharmaceutical preparation for treating hepatitis B.
  • the pharmaceutical preparation for treating hepatitis B can be a single-component substance or a multi-component substance.
  • the form of the pharmaceutical preparation for treating hepatitis B is not particularly limited, and may be in various forms such as solid, liquid, gel, semi-fluid, and aerosol.
  • the pharmaceutical preparation for treating hepatitis B is mainly aimed at mammals, such as rodents, primates and the like.
  • the third aspect of the present invention provides a method for treating hepatitis B, which is to administer bovine parsnips to a subject.
  • the subject may be a mammal or a mammalian hepatitis B cell.
  • the mammal is preferably a rodent, an artiodactyla, a perissodactyla, a lagomorpha, a primate or the like.
  • the primate is preferably a monkey, ape or human.
  • the hepatitis B cells may be isolated hepatitis B cells.
  • the subject may be a patient suffering from hepatitis B or an individual with hepatitis B who is expected to be treated.
  • the subject is a hepatitis B cell from a hepatitis B patient or an individual desiring treatment for hepatitis B.
  • bovine parsnips can be administered to the subject before, during and after receiving hepatitis B treatment.
  • the fourth aspect of the present invention provides a drug combination for combined treatment of hepatitis B, which includes a safe and effective dose of parsnip and at least one other drug for treating hepatitis B, and the balance is pharmaceutically acceptable carriers and/or adjuvants.
  • hepatitis B combination therapy drug combination can be any one of the following forms:
  • Preparing bovine parsnips and other drugs for treating hepatitis B into separate preparations the dosage forms of the preparations may be the same or different, and the routes of administration may also be the same or different.
  • parenteral administration is generally used.
  • other drugs for treating hepatitis B are chemical drugs, the administration forms can be relatively rich, and can be gastrointestinal or parenteral. Dosing by the known route of administration for each chemical is generally recommended.
  • Bovine parsnip and other hepatitis B therapeutic drugs are formulated into a compound preparation.
  • the bovine parsnip and other hepatitis B therapeutic drugs are administered through the same route of administration and applied simultaneously, the two can be configured into a compound preparation. Form of compound preparation.
  • the fifth aspect of the present invention provides a method for treating hepatitis B, which is to administer an effective amount of bovine parsnip to a subject and administer an effective amount of other hepatitis B treatment drugs to the subject and/or implement other hepatitis B treatment methods to the subject .
  • an effective dose of parsnip and at least one effective dose of other hepatitis B therapeutic drugs can be administered synchronously or sequentially.
  • bovine parsnip is the hepatitis B therapeutic drug discovered for the first time in the present invention
  • at least the effect of adding curative effect can be achieved, further enhancing the effect on hepatitis B Therapeutic effect.
  • hepatitis B treatment drugs include but are not limited to: antibody drugs, chemical drugs or targeted drugs, etc.
  • bovine parsnips can be administered gastrointestinally or parenterally, and the other drugs for treating hepatitis B can be administered gastrointestinally or parenterally.
  • parenteral administration is generally used.
  • Use for preparing a substance that inhibits HBV from secreting HBsAg use for preparing a substance that inhibits the transcription level of HBV RNAs, use for preparing a substance that inhibits the replication level of HBV core DNA, and for preparing a substance that inhibits cccDNA transcription activity
  • the purposes of the invention the purposes of preparing substances for inhibiting the levels of HBV RNAs, HBV DNA, HBV S protein and X protein in liver tissue.
  • bovine parsnipin of the present invention as an active ingredient in the preparation of hepatitis B therapeutic drugs has the following beneficial effects:
  • the present invention finds for the first time that bovine parsnipin (Sphondin, referred to as Sph) can inhibit the secretion of HBsAg by HBV, inhibit the transcription level of HBV RNAs, inhibit the replication level of HBV core DNA, inhibit the transcription activity of cccDNA, and inhibit HBV RNAs, HBV DNA, and HBV in liver tissue.
  • the level of S protein and X protein has obvious therapeutic function for hepatitis B, and can be used to prepare new anti-HBV drugs that can reduce HBsAg level and inhibit cccDNA transcription, and has broad application prospects in hepatitis B treatment.
  • Fig. 1 is a graph showing the experimental results of verifying the toxic effect of Sph in vitro by MTT experiment.
  • Fig. 2 is a diagram showing the experimental results of verifying the inhibitory effect of Sph on extracellular and extracellular HBsAg by ELISA experiment.
  • Figure 3 shows the experimental results of the verification of the inhibitory effect of Sph on HBV RNAs by qRT-PCR and Northern blot experiments.
  • Figure 4 shows the experimental results of Sph's inhibitory effect on HBV core DNA verified by q-PCR and Southern blot experiments.
  • Fig. 5 shows the experimental results of the verification of the effect of Sph on cccDNA level and transcriptional activity by Taq-Man probe PCR experiment and RNA-Seq.
  • Fig. 6 is a graph showing the experimental results of verifying the antiviral activity of Sph in vivo through the human liver chimeric mouse model experiment.
  • Bovine parsnip, Sphondin referred to as Sph, also known as 6-methoxy angelica.
  • the present invention finds through high-throughput ELISA experiments that Sph can effectively inhibit HBsAg secreted by HBV, and does not show obvious toxicity on multiple liver cancer cell lines and primary human liver cells (PHH). It was confirmed again by Western blot and Dot blot that Sph can effectively reduce intracellular and extracellular HBsAg. RT-PCR experiments and Northern blot experiments proved that Sph can inhibit the level of HBV RNA. Simultaneously, the present invention also finds that Sph also has concentration-dependent inhibitory effect on HBV core DNA.
  • the present invention does not find that Sph has an obvious inhibitory effect on the HBV transcription template cccDNA, but interestingly, the present invention finds that it can effectively reduce the transcriptional activity of cccDNA.
  • the present invention uses the human liver chimeric mouse model to conduct in vivo experiments. After the mice are infected with HBV, they are continuously cultured for 8 weeks to make them stably replicate HBV and then give Sph treatment. By detecting the virus indicators in serum and liver tissue, it is found that Sph It can significantly reduce the levels of HBsAg and HBV DNA in mouse serum, as well as the levels of HBV RNAs, HBV DNA, HBV S protein and X protein in liver tissue.
  • bovine parsnipin Sph affects the production of HBV RNAs by inhibiting the transcription activity of cccDNA, and further leads to the decrease of virological indicators such as viral protein and DNA. Anti-HBV drugs.
  • the present invention provides the preparation of a medicine for treating hepatitis B with bovine parsnip as an active ingredient.
  • the hepatitis B treatment drug will also include one or more pharmaceutically acceptable carriers or adjuvants according to the requirements of different drug dosage forms.
  • “Pharmaceutically acceptable” means that the molecular entities and compositions do not produce adverse, allergic or other adverse reactions when properly administered to animals or humans.
  • the "pharmaceutically acceptable carrier or excipient” should be compatible with parsnip, that is, it can be blended with it without greatly reducing the effect of the pharmaceutical composition under normal circumstances.
  • Specific examples of some substances that can be used as pharmaceutically acceptable carriers or excipients are sugars, such as lactose, glucose and sucrose; starches, such as corn starch and potato starch; cellulose and its derivatives, such as sodium methylcellulose, Ethyl cellulose and methyl cellulose; Gum tragacanth powder; Malt; Gelatin; Talc; Solid lubricants such as stearic acid and magnesium stearate; Calcium sulfate; Vegetable oils such as peanut oil, cottonseed oil, sesame oil, olive Oils, corn oil, and cocoa butter; polyols, such as propylene glycol, glycerin, sorbitol, mannitol, and polyethylene glycol; alginic acid; emulsifiers, such as Tween; wetting agents,
  • the pharmaceutical dosage form is not particularly limited, and can be made into dosage forms such as injections, oral liquids, tablets, capsules, dripping pills, sprays, etc., and can be prepared by conventional methods.
  • the choice of drug dosage form should match the mode of administration.
  • the present invention also provides a drug combination and administration method for combined treatment of hepatitis B.
  • the hepatitis B combination therapy drug combination can be any one of the following forms:
  • the dosage forms of the preparations may be the same or different, and the routes of administration may also be the same or different.
  • the routes of administration may also be the same or different.
  • several medicines can be used at the same time, or several medicines can be used successively.
  • other drugs should be administered to the body during the period when the first drug is still effective on the body.
  • hepatitis B treatment drugs are antibodies, they are generally administered parenterally, such as intravenous injection, intravenous drip or arterial infusion. Its usage and dosage can refer to the prior art.
  • the administration forms can be relatively rich, and can be gastrointestinal or parenteral. Dosing by the known route of administration for each chemical is generally recommended.
  • Bovine parsnip and other hepatitis B therapeutic drugs are formulated into a compound preparation.
  • the bovine parsnip and other hepatitis B therapeutic drugs are administered through the same route of administration and applied simultaneously, the two can be configured into a compound preparation. Form of compound preparation.
  • combination drug in the present invention refers to a rational combination drug, and the basic principle should be to improve the curative effect and/or reduce adverse reactions.
  • drug interactions should include interactions affecting pharmacokinetics and interactions affecting pharmacodynamics.
  • types of drugs should be reduced as much as possible to reduce adverse drug reactions caused by drug interactions, avoid affecting drug efficacy or increasing toxicity, and avoid producing opposite results.
  • the experimental methods, detection methods, and preparation methods disclosed in the present invention all adopt conventional molecular biology, biochemistry, chromatin structure and analysis, analytical chemistry, cell culture, recombinant DNA technology and related fields in the technical field conventional technology.
  • HepG2-NTCP cell line was cultured in DMEM medium containing 10% fetal bovine serum and 2 ⁇ g/mL doxycycline; PHH cells were cultured in HM medium; Huh-7 cell line was cultured in DMEM medium containing 10% fetal bovine serum Base. All cells were routinely cultured in a 37°C incubator containing 5% CO2.
  • Sph was dissolved in DMSO to prepare a 50 mM stock solution. Inoculate 1.5 ⁇ 10 4 Huh-7, PLC/PRF/5, PHH cells or 2 ⁇ 10 4 HepG2-NTCP cells in a 96-well plate. After 24 hours, dilute the Sph stock solution with growth medium , and sequentially obtained 9 concentrations of 500, 250, 125, 62.5, 31.25, 15.6, 7.8, 3.9, and 1.95 ⁇ M; and the no-drug treatment group was used as a control, and the pure medium was used as a blank, and each concentration was repeated in 3 wells. Add 100 ⁇ l of drug solution to each well.
  • total HBV RNAs forward 5'-ACCGACCTTGAGGCATACTT-3'(SEQ ID NO.1)
  • HBV 3.5-kb mRNA forward 5'- GCCTTAGAGTCTCCTGAGCA-3' (SEQ ID NO.3)
  • cell lysate (10mM Tris-HCl pH 8.0, 1mM EDTA, 1% NP-40, 2% sucrose), mix well, incubate at 37°C for 15min, collect the cell lysate, and centrifuge at 15000g for 5min .
  • HBV DNA primer, F CCTAGTAGTCAGTTATGTCAAC (SEQ ID NO.5)
  • R TCTATAAGCTGGAGGAGTGCGA (SEQ ID NO.6)
  • mice Purchased 15 male human liver chimeric mice, injected fresh patient serum into the mice through the tail vein, tested the level of HBV replication in the mice after 8 weeks of normal feeding, and randomly divided them into 3 groups: the control group (injection, etc. Volume does not contain drug solute), Sph group (2.5mg/kg/2days, intraperitoneal administration), ETV+Sph group (ETV: 0.02mg/kg/2days intragastric administration). Orbital blood was collected every 4 days to separate serum and frozen at -80°C. At the 7th week, the mice were sacrificed by cervical dislocation, and the liver of the mice was bluntly dissected. Larger and complete tissue pieces were cut out and embedded in paraffin for sectioning. The remaining tissues were ground and dried. Extract DNA and RNA.
  • Biospin virus DNA extraction kit (BioFlux)
  • 10 ⁇ l of serum in 190ul of normal saline add 10 ⁇ l of proteinase K into a new 1.5ml centrifuge tube, then add 200 ⁇ l of lysate, shake and mix for 5-10 seconds. Incubate at 56°C for 15 minutes. Add 200 ⁇ l of absolute ethanol to the above centrifuge tube, shake and mix well for 5-10 seconds.
  • the purification column in the kit to complete the extraction of viral DNA, and store the DNA sample at -20°C.
  • paraffin-embedded sections were placed in an oven at 55°C overnight; the next day, they were baked in an oven at 95°C for 10 minutes; they were immediately placed in xylene and ethanol with gradient concentrations for dewaxing treatment.
  • SPSS 19.0 software was used for statistics, paired t-test was used for comparison between two groups and one-way analysis of variance was used for comparison between multiple groups, and P ⁇ 0.05 was considered statistically significant.
  • the HBV-infected PHH and HepG2-NTCP cells were treated with Sph, and the secretion level and intracellular expression level of HBsAg after drug treatment were detected.
  • the results showed that Sph decreased intracellular and extracellular HBsAg in a concentration-gradient-dependent and time-gradient-dependent manner, with EC50 of 18.08 ⁇ M and 13.17 ⁇ M, respectively ( Figure 2).
  • HBsAg is translated from HBV 2.4/2.1-kb RNA.
  • HBV-infected PHH and HepG2-NTCP cells were treated with different concentrations of Sph, and cells were collected at different time points to extract total RNA. .
  • Both qRT-PCR and Northern blot results showed that Sph reduced HBV RNAs (including 3.5-kb RNA and 2.4/2.1-kb RNA) in a concentration-gradient-dependent and time-gradient-dependent manner, with EC50 of 23.48 ⁇ M and 19.24 ⁇ M (PHHs) respectively , 9.26 ⁇ M and 6.14 ⁇ M (HepG2-NTCP cells) ( FIG. 3 ).
  • HBV 3.5-kb RNA can be further reverse-transcribed to generate HBV core DNA.
  • HBV-infected PHH and HepG2-NTCP cells were treated with Sph at a concentration gradient, q- PCR and Southern blot were used to detect the level of HBV core DNA in the cells. The results showed that: Sph decreased the level of HBV core DNA in a concentration gradient-dependent manner (Fig. 4).
  • mice Fifteen 6-8 week-old BALB/c mice were randomly divided into 3 groups, and were treated with different doses of Sph (respectively 0mg/kg group, 2.5mg/kg group, 5mg/kg group), every two The mice were administered intraperitoneally once every day while monitoring the body weight of the mice. After 28 days of continuous treatment, blood routine and blood biochemical indicators were detected by eyeball blood sampling.
  • Sph treatment had no significant effect on body weight, leukocytes, erythrocytes, hemoglobin, platelets, total protein, albumin, ALT, AST, GGT, total bilirubin, serum creatinine, and blood urea in mice. It shows that Sph is less toxic in vivo and has no obvious liver and kidney toxicity. Therefore, we adopted a concentration of 2.5 mg/kg for subsequent experiments (Table 1).
  • WBC white blood cell, white blood cell
  • RBC red blood cell, red blood cell
  • HGB Hemoglobin, hemoglobin
  • HCT Hematocrit, hematocrit
  • PLT Platelets, platelets
  • MCV Mean Corpusular Volume, average red blood cell Volume
  • MCH Mean Corpusular Hemoglobin, mean corpuscular hemoglobin content
  • BUN blood urea nitrogen, blood urea nitrogen
  • TP Total protein, serum total protein
  • ALB Albumin, albumin
  • ALT alanine transaminase, alanine aminotransferase
  • AST aspartate transaminase, aspartate aminotransferase
  • ALKP alkaline phosphatase, alkaline phosphatase
  • GGT ⁇ -glutamyl transpeptidase, urinary glutamyl transpeptidase
  • TBIL total bilirubin, total bilirubin.
  • mice 8 weeks after HBV infection were randomly divided into 3 groups (control group, 2.5mg/kg group, ETV+Sph group), 4 mice in each group. Administration was given once every 2 days, and orbital blood was collected every 4 days. After 7 weeks, the mice were sacrificed by cervical dislocation, and the livers were harvested. The levels of HBsAg and HBV DNA in serum of mice, and the levels of HBV RNAs, HBV DNA, HBs and HBx proteins in liver tissue were detected.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Virology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Biotechnology (AREA)
  • Molecular Biology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne l'utilisation de grande berce en tant que principe actif dans la préparation d'un médicament pour le traitement de l'hépatite B. La grande berce peut inhiber la sécrétion de l'antigène de surface de l'hépatite (HBsAg) par le virus de l'hépatite B (VHB), inhiber le niveau de transcription des ARN du VBH, inhiber le niveau de réplication de l'ADN du noyau du VHB, inhiber l'activité transcriptionnelle de l'ADN circulaire du VHB, inhiber les ARN du VHB, l'ADN du VHB, les niveaux de la protéine S et de la protéine X du VHB dans les tissus hépatiques.
PCT/CN2021/115274 2021-05-11 2021-08-30 Utilisation de grande berce en tant que principe actif dans la préparation d'un médicament pour le traitement de l'hépatite b WO2022237007A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN202110514966.7 2021-05-11
CN202110514966.7A CN113069445A (zh) 2021-05-11 2021-05-11 牛防风素作为有效成分在制备乙型肝炎治疗药物中的用途

Publications (1)

Publication Number Publication Date
WO2022237007A1 true WO2022237007A1 (fr) 2022-11-17

Family

ID=76616475

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2021/115274 WO2022237007A1 (fr) 2021-05-11 2021-08-30 Utilisation de grande berce en tant que principe actif dans la préparation d'un médicament pour le traitement de l'hépatite b

Country Status (3)

Country Link
CN (1) CN113069445A (fr)
AU (1) AU2021107213A4 (fr)
WO (1) WO2022237007A1 (fr)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113069445A (zh) * 2021-05-11 2021-07-06 重庆医科大学 牛防风素作为有效成分在制备乙型肝炎治疗药物中的用途
CN113304165B (zh) * 2021-07-15 2022-07-22 重庆医科大学 单体化合物Ciliatoside A在制备乙型肝炎治疗药物中的用途

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4939167A (en) * 1988-07-22 1990-07-03 Jean Jacques Goupil Use of 5-methoxypsoralen and other furocoumarins as jet lag suppressants
CN101904839A (zh) * 2010-08-06 2010-12-08 中国人民解放军第二军医大学 欧芹素乙在制备防治肝炎或肝损伤药物中的应用
CN103191105A (zh) * 2013-03-18 2013-07-10 中山大学 一类呋喃香豆素类化合物在制备抗乙型肝炎病毒（hbv）药物中的应用
CN105456517A (zh) * 2015-12-15 2016-04-06 彭国能 一种治疗慢性乙型肝炎的中药组合物、制剂及制备方法
CN105616463A (zh) * 2014-11-10 2016-06-01 南京浩鼎生物科技有限公司 一种抑制乙肝病毒用的无副作用调理药剂
CN113069445A (zh) * 2021-05-11 2021-07-06 重庆医科大学 牛防风素作为有效成分在制备乙型肝炎治疗药物中的用途

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6103706A (en) * 1997-04-29 2000-08-15 New York Blood Center, Inc. Methods for treating viral infections
US6242188B1 (en) * 1999-07-30 2001-06-05 Applied Gene Technologies, Inc. Sample processing to release nucleic acids for direct detection
US20060024691A1 (en) * 2004-03-25 2006-02-02 Buck Institute For Age Research Novel pathways in the etiology of cancer
US20090312406A1 (en) * 2008-06-12 2009-12-17 Hsing-Pang Hsieh Coumarin compounds and their use for treating viral infection
WO2011133879A2 (fr) * 2010-04-22 2011-10-27 University Of Massachusetts Polythérapies par agents antitumoraux ciblant la mitochondrie
CN107496476A (zh) * 2017-09-29 2017-12-22 北京健旭康技术有限公司 白云花的益肝作用及应用技术
CN109364074B (zh) * 2018-11-01 2021-05-07 重庆医科大学 6-氨基烟酰胺作为有效成分在制备乙型肝炎治疗药物中的用途
WO2020118159A1 (fr) * 2018-12-07 2020-06-11 The University Of Chicago Méthodes et compositions comportant un inhibiteur de nf-kb et un adjuvant
CN113304165B (zh) * 2021-07-15 2022-07-22 重庆医科大学 单体化合物Ciliatoside A在制备乙型肝炎治疗药物中的用途

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4939167A (en) * 1988-07-22 1990-07-03 Jean Jacques Goupil Use of 5-methoxypsoralen and other furocoumarins as jet lag suppressants
CN101904839A (zh) * 2010-08-06 2010-12-08 中国人民解放军第二军医大学 欧芹素乙在制备防治肝炎或肝损伤药物中的应用
CN103191105A (zh) * 2013-03-18 2013-07-10 中山大学 一类呋喃香豆素类化合物在制备抗乙型肝炎病毒（hbv）药物中的应用
CN105616463A (zh) * 2014-11-10 2016-06-01 南京浩鼎生物科技有限公司 一种抑制乙肝病毒用的无副作用调理药剂
CN105456517A (zh) * 2015-12-15 2016-04-06 彭国能 一种治疗慢性乙型肝炎的中药组合物、制剂及制备方法
CN113069445A (zh) * 2021-05-11 2021-07-06 重庆医科大学 牛防风素作为有效成分在制备乙型肝炎治疗药物中的用途

Also Published As

Publication number Publication date
AU2021107213A4 (en) 2021-12-09
CN113069445A (zh) 2021-07-06

Similar Documents

Publication Publication Date Title
Lan et al. Cordycepin ameliorates nonalcoholic steatohepatitis by activation of the AMP‐activated protein kinase signaling pathway
Wu et al. Relevance of the NLRP3 inflammasome in the pathogenesis of chronic liver disease
WO2022237007A1 (fr) Utilisation de grande berce en tant que principe actif dans la préparation d'un médicament pour le traitement de l'hépatite b
DK2694087T3 (en) The treatment of infection with Hepatitis B virus alone or in combination with hepatitis delta virus, and in connection with liver diseases
TWI732156B (zh) 用於治療和/或預防與肝炎病毒相關的疾病或病症的雙二氮雜雙環化合物
US11020392B2 (en) Use of trimetazidine as a hepatoprotective medicine in prevention and treatment of liver diseases and conditions
JP2013082726A (ja) 鉄が病因に関与する肝臓疾患の処置
CN107635566A (zh) 治疗hbv感染的组合物和方法
CN106902347A (zh) 亲环孢素抑制剂的用途
CN109364074B (zh) 6-氨基烟酰胺作为有效成分在制备乙型肝炎治疗药物中的用途
IL294161A (en) A method for treating virus infection using a tlr7 agonist
Zhu et al. Anti-hepatitis B virus activity of lithospermic acid, a polyphenol from Salvia miltiorrhiza, in vitro and in vivo by autophagy regulation
TWI631943B (zh) 治療脂肪肝疾病之方法
Lefebvre et al. Anti-fibrotic and anti-inflammatory activity of the dual CCR2 and CCR5 antagonist cenicriviroc in a mouse model of NASH: 30
Kuang et al. The NALP3 inflammasome is required for collagen synthesis via the NF‑κB pathway
CN101190211B (zh) 芳香硝基化合物在制备治疗病毒性肝炎药物中的应用
WO2023241179A1 (fr) Utilisation d'acide asiatique dans la préparation d'un médicament pour le traitement de l'hépatite b
WO2006043153A2 (fr) Utilisation de chelateurs d'ions de zinc et de cuivre pour le traitement d'infections causees par des virus vehicules par le sang
CN111671749A (zh) 双香豆素在制备HBx蛋白稳定性抑制剂中的用途
CN113304165B (zh) 单体化合物Ciliatoside A在制备乙型肝炎治疗药物中的用途
US20240226214A1 (en) Methods for treating inflammatory and fibrotic diseases and disorders
Yamashita et al. Virological effects and safety of combined double filtration plasmapheresis (DFPP) and interferon therapy in patients with chronic hepatitis C: A preliminary study
CN116617390A (zh) Asgr1抑制剂在促进胆固醇外排和治疗非酒精性脂肪性肝病中的应用
CN104780918B (zh) 用于预防和/或治疗丙型肝炎的氮杂环丁酮化合物及其组合物
CN116440272B (zh) Gpvi抑制剂在制备发热伴血小板减少综合征治疗药物中的应用

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 21941574

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 21941574

Country of ref document: EP

Kind code of ref document: A1