WO2023142317A1 - Composition pharmaceutique pour le traitement de l'hépatite virale - Google Patents

Composition pharmaceutique pour le traitement de l'hépatite virale Download PDF

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WO2023142317A1
WO2023142317A1 PCT/CN2022/094169 CN2022094169W WO2023142317A1 WO 2023142317 A1 WO2023142317 A1 WO 2023142317A1 CN 2022094169 W CN2022094169 W CN 2022094169W WO 2023142317 A1 WO2023142317 A1 WO 2023142317A1
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pharmaceutical composition
hepatitis
pharmaceutically acceptable
proton pump
steroidal anti
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PCT/CN2022/094169
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English (en)
Chinese (zh)
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李瑛颖
陈明键
仇思念
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中以海德人工智能药物研发股份有限公司
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Publication of WO2023142317A1 publication Critical patent/WO2023142317A1/fr

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    • 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
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
    • 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
    • A61K31/63—Compounds containing para-N-benzenesulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonyl hydrazide
    • A61K31/635—Compounds containing para-N-benzenesulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonyl hydrazide having a heterocyclic ring, e.g. sulfadiazine
    • 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
    • A61P31/14—Antivirals for RNA viruses
    • 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 present disclosure relates to the technical field of antiviral drugs, in particular, to a compound for treating or preventing viral hepatitis, a pharmaceutical composition and applications thereof.
  • Hepatitis B infection Human hepatitis B virus (HBV) infection is an important public health problem worldwide. After acute hepatitis B virus infection, about 8% still develop into chronic hepatitis B infection, and persistent HBV infection will lead to liver cirrhosis and even liver cancer. Hepatitis B transmission is mainly through vertical transmission and horizontal transmission. Vertical transmission refers to mother-to-child transmission; horizontal transmission is mainly through blood.
  • hepatitis B is also a long-term process.
  • the goal of treatment is to suppress or eliminate HBV to the greatest extent, reduce inflammation and necrosis of liver cells and liver fibrosis, delay and prevent disease progression, reduce and prevent liver decompensation, liver cirrhosis, occurrence of HCC and its complications, thereby improving quality of life and prolonging survival time.
  • hepatitis B therapeutic drugs mainly through the use of interferon or nucleoside analogues for antiviral treatment.
  • interferon recombinant DNA leukocyte interferon (IFN- ⁇ ) can inhibit the replication of HBV.
  • IFN- ⁇ recombinant DNA leukocyte interferon
  • it is often accompanied by strong adverse reactions, including bone marrow suppression, affecting thyroid function and depression.
  • Nucleoside analogs mainly inhibit HBV production by inhibiting the reverse transcriptase activity during HBV replication.
  • Clinically available drugs include the following categories: lamivudine, famciclovir, such as acyclovir, adefovir, entecavir, tenox Fovir, foscarnet sodium, etc., these drugs have a certain inhibitory effect on HBV.
  • Lansoprazole is a new type of drug that inhibits gastric acid secretion. Inhibitory effect, its acid suppression effect is obviously better than that of H2 receptor blockers, and the degree of inhibition has a significant dependence on concentration. Under acidic conditions, Lansoprazole can quickly pass through the parietal cell membrane and transform into sulfenic acid and sulfenyl derivatives to exert its medicinal effect. It has an inhibitory effect on Helicobacter pylori (Hp), which is 4 times that of omeprazole . It is clinically used in the treatment of duodenal ulcer, gastric ulcer, anastomotic ulcer, reflux esophagitis, and Zoller-Ellison syndrome, with remarkable curative effect.
  • Hp Helicobacter pylori
  • NSAIDs Nonsteroidal Antiinflammatory Drugs, NSAIDs
  • NSAIDs are a class of anti-inflammatory drugs that do not contain a steroidal structure. Since aspirin was first synthesized in 1898, more than 100 kinds of NSAIDs have been listed on the market for more than 100 years. Such drugs include aspirin, acetaminophen, indomethacin, naproxen, naproxen, diclofenac, ibuprofen, nimesulide, rofecoxib, celecoxib, etc.
  • Anti-inflammatory, anti-rheumatic, analgesic, antipyretic and anti-coagulant effects are widely used clinically to relieve osteoarthritis, rheumatoid arthritis, various fevers and various pain symptoms.
  • the present disclosure provides a pharmaceutical composition, including a proton pump inhibitor and a non-steroidal anti-inflammatory drug, and also provides a proton pump inhibitor and a non-steroidal anti-inflammatory drug used in the preparation of a drug for treating or preventing viral hepatitis Use, especially for reducing HBsAg and/or HBeAg levels.
  • the inventors unexpectedly found that the combination of proton pump inhibitors and non-steroidal anti-inflammatory drugs can produce a synergistic effect, especially in reducing the level of HBsAg and/or HBeAg, which is stronger than any one of the two, and better than the combination of the two. Effect.
  • the composition of the present disclosure is expected to achieve the effect of eliminating hepatitis B virus, and even achieve complete cure.
  • the proton pump inhibitor includes at least one of omeprazole, lansoprazole, pantoprazole, rabeprazole, esomeprazole, and the non-steroidal Anti-inflammatory drugs include at least one of aspirin, acetaminophen, indomethacin, naproxen, naproxen, diclofenac, ibuprofen, nimesulide, rofecoxib, and celecoxib.
  • the pharmaceutical composition is administered by a route selected from oral, rectal, nasal, pulmonary, topical, buccal and sublingual, vaginal, parenteral, subcutaneous, intramuscular, intravenous, dermal Intrathecal, intrathecal and epidural.
  • the pharmaceutical composition is administered orally, preferably in the form of tablets or capsules.
  • the present disclosure also provides the use of the proton pump inhibitor and the non-steroidal anti-inflammatory drug in the preparation of a medicament for treating viral hepatitis.
  • the present disclosure provides the use of lansoprazole or a pharmaceutically acceptable salt thereof and celecoxib or a pharmaceutically acceptable salt thereof in the preparation of a medicament for treating viral hepatitis.
  • the present disclosure further provides the use of proton pump inhibitors and non-steroidal anti-inflammatory drugs in the preparation of drugs for reducing HBV DNA, HBsAg and/or HBeAg levels.
  • the present disclosure provides the use of lansoprazole or a pharmaceutically acceptable salt thereof and celecoxib or a pharmaceutically acceptable salt thereof in the preparation of a medicament for reducing HBV DNA, HBsAg and/or HBeAg levels.
  • the present disclosure provides a pharmaceutical composition comprising a proton pump inhibitor and a non-steroidal anti-inflammatory drug for use in the treatment of viral hepatitis.
  • the pharmaceutical composition comprises lansoprazole or a pharmaceutically acceptable salt thereof and celecoxib or a pharmaceutically acceptable salt thereof.
  • the present disclosure further provides a pharmaceutical composition
  • a pharmaceutical composition comprising a proton pump inhibitor and a non-steroidal anti-inflammatory drug for reducing HBV DNA, HBsAg and/or HBeAg levels.
  • the pharmaceutical composition comprises lansoprazole or a pharmaceutically acceptable salt thereof and celecoxib or a pharmaceutically acceptable salt thereof.
  • the proton pump inhibitor and the non-steroidal anti-inflammatory drug in the pharmaceutical composition or medicine of the present disclosure may exist independently in different dosage forms, or co-exist in one dosage form.
  • the present disclosure also provides a method of treating viral hepatitis using a proton pump inhibitor and a non-steroidal anti-inflammatory drug, comprising administering a therapeutically effective amount of a proton pump inhibitor and a non-steroidal anti-inflammatory drug to a patient in need thereof individual.
  • the proton pump inhibitor is lansoprazole or a pharmaceutically acceptable salt thereof
  • the non-steroidal anti-inflammatory drug is celecoxib or a pharmaceutically acceptable salt thereof.
  • the present disclosure also provides a method of reducing HBV DNA, HBsAg and/or HBeAg levels using a proton pump inhibitor and a non-steroidal anti-inflammatory drug, comprising administering a proton pump inhibitor and a non-steroidal anti-inflammatory drug to the individual in need.
  • the proton pump inhibitor is lansoprazole or a pharmaceutically acceptable salt thereof
  • the non-steroidal anti-inflammatory drug is celecoxib or a pharmaceutically acceptable salt thereof.
  • the proton pump inhibitor and the non-steroidal anti-inflammatory drug may be administered separately, sequentially or simultaneously.
  • the viral hepatitis is hepatitis B or hepatitis D
  • the pharmaceutical composition is preferably used to reduce the level of HBsAg and/or HBeAg in patients with hepatitis B.
  • the combination of proton pump inhibitors and non-steroidal anti-inflammatory drugs, especially lansoprazole and celecoxib, is applied to the treatment or prevention of viral hepatitis, thus providing a novel treatment option for viral hepatitis .
  • the combination of lansoprazole and celecoxib has a synergistic effect on effectively reducing the level of hepatitis B virus HBsAg and/or HBeAg, and is expected to become a follow-up drug combination for the functional cure of hepatitis B.
  • the combination of proton pump inhibitor and non-steroidal anti-inflammatory drug can significantly improve the effect of removing hepatitis B virus, and has good synergistic effect.
  • Figure 1 Inhibition results of HD017, HD017 and HD042 combination on HBeAg.
  • Figure 2 Inhibition results of HD017, HD017 and HD042 combination on HBsAg.
  • Figure 3 Analysis of the synergistic inhibitory effect of the combination of HD017 and HD042 on HBeAg.
  • Figure 4 Analysis of the inhibitory synergistic effect of the combination of HD017 and HD042 on HBsAg.
  • the inventors of the present disclosure have screened out a composition with therapeutic effects on hepatitis B through multiple experiments, and further verified by biological experiments that the composition has the effect of potentially eliminating HBsAg and/or HBeAg, and is expected to functionally cure hepatitis B, eliminate Hepatitis B virus.
  • the present disclosure provides a pharmaceutical composition
  • a pharmaceutical composition comprising a proton pump inhibitor and a non-steroidal anti-inflammatory drug, particularly for reducing HBsAg and/or HBeAg levels.
  • the proton pump inhibitor includes at least one of omeprazole, lansoprazole, pantoprazole, rabeprazole, esomeprazole, and the non-steroidal Anti-inflammatory drugs include at least one of aspirin, acetaminophen, indomethacin, naproxen, naproxen, diclofenac, ibuprofen, nimesulide, rofecoxib, and celecoxib.
  • the pharmaceutical composition is administered by a route selected from oral, rectal, nasal, pulmonary, topical, buccal and sublingual, vaginal, parenteral, subcutaneous, intramuscular, intravenous, dermal Intrathecal, intrathecal and epidural.
  • the pharmaceutical composition is administered orally, for example in the form of a tablet or capsule.
  • the present disclosure also provides the use of the above-mentioned pharmaceutical composition in preparing a medicine for treating viral hepatitis.
  • the viral hepatitis is hepatitis B or hepatitis D, and the use is for reducing the level of HBsAg and/or HBeAg in patients with hepatitis B.
  • Lansoprazole is a new type of drug that inhibits gastric acid secretion. It has a significant inhibitory effect on gastric acid secretion caused by basic gastric acid secretion and all stimulants (such as histamine, carbachol, etc.). It is obviously better than H2 receptor blockers, and the degree of inhibition has a significant dependence on concentration. Lansoprazole can rapidly pass through the parietal cell membrane to convert Chemicalbook into sulfenic acid and sulfenyl derivatives under acidic conditions to exert its drug effect, and has inhibitory effect on Helicobacter pylori (Hp). 4 times. It is clinically used in the treatment of duodenal ulcer, gastric ulcer, anastomotic ulcer, reflux esophagitis, and Zollinger-Ellison syndrome (Gastrinoma), with remarkable curative effect.
  • Hp Helicobacter pylori
  • NSAIDs Nonsteroidal Antiinflammatory Drugs, NSAIDs
  • NSAIDs are a class of anti-inflammatory drugs that do not contain a steroidal structure. Since aspirin was first synthesized in 1898, more than 100 brands of NSAIDs have been on the market for more than 100 years. Such drugs include aspirin, acetaminophen, indomethacin, naproxen, naproxen, diclofenac, ibuprofen, nimesulide, rofecoxib, celecoxib, etc.
  • Anti-inflammatory, anti-rheumatic, analgesic, antipyretic and anti-coagulant effects are widely used clinically to relieve osteoarthritis, rheumatoid arthritis, various fevers and various pain symptoms.
  • Lansoprazole and rofecoxib of the present disclosure include deuterated versions thereof.
  • hepatitis B virus is a DNA virus
  • RNA viruses The rest are RNA viruses.
  • Hepatitis caused by the above viruses are all viral hepatitis.
  • hepatitis caused by HBV is hepatitis B
  • hepatitis caused by HDV is hepatitis D.
  • Hepatitis B is an infectious disease mainly caused by hepatitis B virus with liver lesions. Clinically, the main manifestations are loss of appetite, nausea, upper abdominal discomfort, pain in the liver area, and fatigue. Some patients may have jaundice, fever and hepatomegaly with liver function damage. Some patients can become chronic and even develop into liver cirrhosis, and a few can develop into liver cancer.
  • hepatitis B virus The pathogenic factor of hepatitis B virus is hepatitis B virus, abbreviated as HBV, and hepatitis B virus is a DNA virus.
  • the genome is double-stranded, circular, partially closed DNA.
  • the outermost layer of the virus is the outer membrane or coat of the virus, and the inner layer is the core part.
  • the nucleoprotein is the core antigen (HBcAg), which cannot be detected in serum.
  • HBcAg core antigen
  • three types of particles can be seen under the electron microscope, round and filamentous particles with a diameter of 22 nm, and less spherical particles with a diameter of 42 angstroms, also known as Dane’s particles, which are complete HBV particles .
  • HBsAg positive indicates that HBV is currently in the infection stage, and anti-HBs is positive for immune protective antibodies, indicating that immunity to HBV has been produced.
  • Chronic HBsAg carriers are diagnosed on the basis of no clinical symptoms and signs, normal liver function, and HBsAg positive for more than 6 months.
  • HBeAg positive is an indicator of active HBV replication and strong infectivity. The change of tested serum from HBeAg positive to anti-HBe positive indicates that the disease has been relieved and the infectivity has weakened.
  • HBcAg and anti-HBc Positive HBcAg indicates the existence of complete HBV particle direct reaction, and the active replication of HBV is rarely used clinically due to the complicated detection method. Anti-HBc is a sign of HBV infection, and anti-HBc IgM positive indicates that it is in the early stage of infection and there is virus replication in the body. In chronic mild hepatitis B and HBsAg carriers, HBsAg, HBeAg and anti-HBc are all positive and highly contagious indicators are difficult to turn negative.
  • therapeutically effective amount refers to an amount effective at dosages and for periods of time required to achieve the desired therapeutic result.
  • a therapeutically effective amount of a hepatitis B therapeutic will depend on the nature of the disorder or condition and on the particular agent, and can be determined by standard clinical techniques known to those skilled in the art.
  • the outcome of treatment can be, for example, reduction of symptoms, prolongation of survival, improvement of mobility, and the like.
  • the result of treatment need not be a "cure.”
  • Treatment outcomes can also be preventative.
  • a medicament or pharmaceutical composition of the present disclosure is administered by any route appropriate for the condition to be treated. Suitable routes include oral, rectal, nasal, pulmonary, topical (including buccal and sublingual), vaginal and parenteral (including subcutaneous, intramuscular, intravenous, intradermal, intrathecal and epidural) and the like.
  • a medicament or pharmaceutical composition disclosed herein is administered by intravenous injection. It will be appreciated that the preferred route may vary depending, for example, on the condition of the recipient.
  • One advantage of the disclosed medicaments or pharmaceutical compositions is that they are orally bioavailable and can be administered orally.
  • the composition is administered by a route selected from the group consisting of: oral, rectal, nasal, pulmonary, topical, buccal and sublingual, vaginal, parenteral, subcutaneous, intramuscular, intravenous, dermal Intrathecal, intrathecal and epidural.
  • the composition is formulated for oral administration, preferably in the form of a tablet or capsule.
  • compositions of the present disclosure can be formulated with conventional carriers and excipients which will be selected according to ordinary practice. Tablets will contain excipients, glidants, fillers, binders, and the like. Aqueous formulations are prepared in sterile form and, when intended for delivery by parenteral administration, are generally isotonic. All formulations will optionally contain excipients such as those described in the "Handbook of Pharmaceutical Excipients" (1986).
  • Formulations include those suitable for the aforementioned routes of administration.
  • the composition of the present disclosure can be that two or more drugs are present in unit dosage form separately, and these drugs can also be combined together to form a unit dosage form.
  • Such formulations or dosage forms may be prepared by any of the methods well known in the art of pharmacy. Techniques and formulations are generally found in Remington's Pharmaceutical Sciences (Mack Publishing Co., Easton, PA). Such methods include the step of bringing into association the active ingredient with the carrier which constitutes one or more accessory ingredients. In general, the formulations are prepared by uniformly and intimately bringing into association the active ingredient with liquid carriers or finely divided solid carriers or both, and then shaping the product if necessary.
  • Formulations of the present disclosure suitable for oral administration may be presented as discrete units, such as capsules or tablets, each containing a predetermined amount of the active ingredient; powders or granules; solutions or suspensions in aqueous or non-aqueous liquids; or aqueous Oil-in-liquid emulsion or water-in-oil liquid emulsion.
  • the pharmaceutical compositions of the present disclosure may also be in the form of sterile injectable preparations, such as sterile injectable aqueous or oleaginous suspensions.
  • the compositions can also be in sustained or controlled release dosage forms.
  • HepG2-NTCP cells were used to evaluate the synergistic effect of lansoprazole and celecoxib against HBV in vitro.
  • Celecoxib No. HD042
  • Lansoprazole No. HD017
  • the volume of solvent DMSO ( ⁇ l) sample mass (mg) ⁇ purity ⁇ molecular weight ⁇ 20 ⁇ 10 6
  • the control compound was entecavir (ETV, batch number: P1214012; 99.0% purity), which was purchased from Shanghai Titan Technology Co., Ltd.
  • the concentrations of the mother solutions of the above compounds were all 20 mM and stored at -20°C.
  • HepG2-NTCP cells provided by Shanghai WuXi PharmaTech New Drug Development Co., Ltd.
  • Freezing PHH culture medium mainly DMEM medium (Gibco product number 11960051) containing 10% fetal bovine serum (FBS, Hyclon product number SV3008703) and 1% penicillin-streptomycin, mainly used for cell culture.
  • DMEM medium Gibco product number 11960051
  • FBS Hyclon product number SV3008703
  • penicillin-streptomycin mainly used for cell culture.
  • Cryopreserved PHH plating medium mainly containing 10% fetal bovine serum (FBS, Hyclon product number SV3008703) and 1% penicillin-streptomycin InvitroGRO CP Medium (BIOIVT product number S03316), mainly used for cell plating.
  • FBS fetal bovine serum
  • BIOIVT product number S03316 penicillin-streptomycin InvitroGRO CP Medium
  • Virus infection medium mainly containing 1% penicillin-streptomycin Williams' Medium E (SIGMA product number W1878), mainly used for HBV virus infection.
  • HepG2-NTCP cells were seeded into 48-well cell plates (7.5 ⁇ 10 4 cells/well).
  • the compound was added to pretreat the cells for 2 hours, and then type D HBV was added to infect the HepG2-NTCP cells (the compound was added at the same time as the infection).
  • the concentration of the test compound is shown in Table 2, and the combined medication is set in pairs.
  • the medium containing the compound was replaced once.
  • cell supernatants were collected for detection of HBV DNA (qPCR), HBeAg and HBsAg (ELISA). After the cell supernatant was collected, CellTiter-Glo was added to detect cell viability, and the collected cells were cryopreserved (for later use).
  • the method refers to the kit instruction manual, and the method is briefly described as follows: take 50 ⁇ l of standard, sample and control substance and add them to the detection plate, then add 50 ⁇ l of enzyme conjugate to each well, incubate at 37°C for 60 minutes, wash the plate with washing solution and aspirate After drying, add 50 ⁇ l premixed luminescence substrate, incubate at room temperature in the dark for 10 minutes, and finally measure the luminescence value with a microplate reader.
  • the cell viability was determined according to the instructions of the CellTiter-Glo kit. The method is briefly described as follows: After collecting the cell culture supernatant, add CellTiter-Glo (1:1 dilution in medium) to each well, incubate at room temperature for 10 minutes, and measure the luminescence value with a microplate reader.
  • HBV DNA inhibition rate (%) (1-the HBV copy number of compound group sample/the HBV copy number of DMSO control group) ⁇ 100%
  • HBsAg inhibition rate (%) (1-HBsAg value of sample/HBsAg value of DMSO control group) ⁇ 100%
  • HBeAg inhibition rate (%) (1-HBeAg value of sample/HBeAg value of DMSO control group) ⁇ 100%
  • % cell viability (signal value of sample-signal value of medium control)/(signal value of DMSO control-signal value of medium control) ⁇ 100%
  • EC50 values were calculated using GraphPad Prism software (four parameter logistic equations).
  • Combination Index (CI) software CompuSyn software V1.0. software was used to analyze the synergistic effect of celecoxib and lansoprazole by Non-Constant Combo method.
  • control compound test in the experiment yields the expected results
  • other data in the experiment are considered to be valid and available. And the data will be analyzed and explained in the report.
  • the combination of celecoxib and lansoprazole can produce a synergistic effect and is expected to become a new combination of hepatitis B drugs.

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Abstract

Composition pharmaceutique pour le traitement de l'hépatite virale, son utilisation dans le traitement ou la prévention de l'hépatite virale, et son utilisation dans la préparation d'un médicament pour le traitement ou la prévention de l'hépatite virale, en particulier de l'hépatite B. La composition pharmaceutique comprend un inhibiteur de la pompe à protons et un médicament anti-inflammatoire non stéroïdien.
PCT/CN2022/094169 2022-01-27 2022-05-20 Composition pharmaceutique pour le traitement de l'hépatite virale WO2023142317A1 (fr)

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CN114159573B (zh) * 2022-01-27 2023-01-24 中以海德人工智能药物研发股份有限公司 一种用于治疗病毒性肝炎的药物组合物
CN114159572B (zh) * 2022-01-27 2023-01-24 中以海德人工智能药物研发股份有限公司 一种用于治疗病毒性肝炎的药物组合物

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CN102294031A (zh) * 2011-09-07 2011-12-28 沈阳亿灵医药科技有限公司 含质子泵抑制剂、nsaid和抗酸剂的药物制剂
CN103906506A (zh) * 2011-09-14 2014-07-02 波曾公司 氯吡格雷与胃酸抑制治疗的控制给药
JP2015145343A (ja) * 2014-01-31 2015-08-13 公立大学法人和歌山県立医科大学 ランソプラゾールの新規医薬用途
CN109069471A (zh) * 2016-03-01 2018-12-21 新兴病毒治疗（香港）公司 用于治疗流感病毒的组合物和方法
CN112933085A (zh) * 2020-12-28 2021-06-11 中以海德人工智能药物研发股份有限公司 一种化合物在制备治疗或预防病毒性肝炎用药物中的应用
CN114159573A (zh) * 2022-01-27 2022-03-11 中以海德人工智能药物研发股份有限公司 一种用于治疗病毒性肝炎的药物组合物

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