WO2023072171A1 - 荆防制剂在制备预防或治疗丙型病毒性肝炎的药物中的用途 - Google Patents

荆防制剂在制备预防或治疗丙型病毒性肝炎的药物中的用途 Download PDF

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WO2023072171A1
WO2023072171A1 PCT/CN2022/127836 CN2022127836W WO2023072171A1 WO 2023072171 A1 WO2023072171 A1 WO 2023072171A1 CN 2022127836 W CN2022127836 W CN 2022127836W WO 2023072171 A1 WO2023072171 A1 WO 2023072171A1
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preparation
jingfang
virus
hepatitis
hcv
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PCT/CN2022/127836
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English (en)
French (fr)
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张贵民
赵文学
岳玲
闵姝君
姚景春
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山东新时代药业有限公司
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Publication of WO2023072171A1 publication Critical patent/WO2023072171A1/zh

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
    • A61K36/538—Schizonepeta
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/06—Fungi, e.g. yeasts
    • A61K36/07—Basidiomycota, e.g. Cryptococcus
    • A61K36/076—Poria
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
    • A61K36/232—Angelica
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
    • A61K36/233—Bupleurum
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
    • A61K36/236—Ligusticum (licorice-root)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
    • A61K36/237—Notopterygium
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
    • A61K36/238—Saposhnikovia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/34—Campanulaceae (Bellflower family)
    • A61K36/346—Platycodon
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
    • A61K36/484—Glycyrrhiza (licorice)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/75—Rutaceae (Rue family)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/75—Rutaceae (Rue family)
    • A61K36/752—Citrus, e.g. lime, orange or lemon
    • 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
    • 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
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Definitions

  • the invention belongs to the technical field of medicine, and relates to a new medical application of Jingfang preparation, in particular to the application of Jingfang granules in the preparation of medicines for preventing or treating hepatitis C virus.
  • Hepatitis C is an infectious disease caused by hepatitis C virus (HCV) and mainly transmitted by blood, with acute and chronic inflammation of the liver. Hepatitis C virus infection can lead to chronic inflammation, necrosis and fibrosis of the liver, and some patients may develop liver cirrhosis or even hepatocellular carcinoma, which is extremely harmful to the health and life of patients.
  • HCV infection rate is 3%, and there are about 170 million infected people.
  • the positive rate of anti-HCV is 0.43%, and there are more than 5.6 million HCV-infected people nationwide. Therefore, the prevention and treatment of hepatitis C has become a serious social and public health problem, and it is also one of the key diseases in the field of infectious disease prevention and control in my country in the future.
  • NS3/4A serine protease inhibitors to make it unable to produce edited and modified peptide chains, and block the production of viruses, such as telaprevir, boceprevir, vociprevir, Asunaprevir, etc.
  • NS5A protease inhibitors block virus assembly, release and transport, such as daclatasvir, velpatasvir, ledipasvir, etc.
  • NS5B polymerase inhibitors Nucleoside analogs and non-nucleoside analogs, the former terminates RNA synthesis, such as sofosbuvir, and the latter disables the enzyme, such as dasabuvir.
  • Host-targeted drugs exert anti-HCV effects by targeting and inhibiting pathogenicity-related cytokines in the host or enhancing the host's innate immune response, such as cyclophilin A and aripasvir.
  • New antiviral drugs have clear targets, high efficiency, and short treatment cycle, but they have many drug-resistant sites and large adverse reactions. The combined use of drugs can greatly reduce adverse reactions, but they still cause fatigue, headache, and nausea , diarrhea, etc. Therefore, hepatitis C is still a difficult problem in clinical treatment, and it is an urgent clinical need to further find effective drugs and programs for the treatment of hepatitis C.
  • Traditional Chinese medicine is showing its uniqueness in the treatment of hepatitis C with its individualized treatment advantages based on syndrome differentiation.
  • Jingfang Preparation is derived from the classic ancient prescription Jingfangbaidu Powder, which is prepared by modern pharmaceutical technology from the eleven raw materials of Schizonepeta, Fangfeng, Notopterygium, Duhuo, Bupleurum, Qianhu, Chuanxiong, Citrus aurantium, Poria, Platycodon grandiflorum, and licorice. It has the effects of sweating, dispelling wind and dampness, and is mainly used clinically to treat symptoms such as wind-cold cold, headache and body pain, aversion to cold without sweating, nasal congestion and runny nose, cough and white phlegm.
  • the monarch drug Nepeta Nepeta, Fangfeng pungent and warm surface powder, sweating to relieve the surface and disperse wind pathogens are the first of all diseases; Huxin dissolves muscles, helps notopterygia, solitary exogenous evils, and relieves pain; Citrus aurantium lowers qi, Platycodon grandiflorum opens lungs, Peucedanum expells phlegm, Poria oozes dampness, and is used as an adjuvant drug, and licorice is blended with other drugs as an envoy. All medicines are combined, sweating and heat subside, blood flow and wind relieve pain, lung qi is sharp, phlegm and dampness are removed, cough is stopped, cold symptoms are eliminated and the disease is cured.
  • Jingfang preparation has the effect of treating hepatitis C virus.
  • Jingfang preparation of the present invention has a significant effect on anti-hepatitis C virus in vitro, can significantly reduce the expression of HCV-RNA in cells, and has a significant effect on the anti-hepatitis C virus in vitro, and the effect is better than Jingfang Baidu San modified formula; Jingfang preparation has a significant effect on the anti-hepatitis C virus activity in vivo, and can significantly reduce the serum DHCV-DNA level of infected ducks, and the effect is better than Jingfang Baidu San and Jingfang Baidu San Modified square.
  • the Jingfang preparation of the invention provides a new medication option for the clinical treatment of viral hepatitis C, and reflects the curative effect characteristics of integrity, multi-targets and multi-component synergistic effects of the traditional Chinese medicine compound.
  • the invention provides the use of Jingfang preparation in the preparation of medicines for preventing or treating hepatitis C virus;
  • Hepatitis C virus is a kind of viral hepatitis caused by infection with HCV virus, and the main routes of transmission are blood transmission, sexual transmission and mother-to-child transmission.
  • the initial stage of HCV virus infection can cause chronic inflammation, necrosis and fibrosis of the liver, and further develop into end-stage liver diseases such as cirrhosis and liver cancer.
  • HCV treatment is to eliminate the virus in the patient's body, control or reduce the phenomenon of liver tissue fibrosis or inflammation and necrosis, and avoid the development of liver cirrhosis, thereby reducing the incidence of primary liver cancer.
  • HCV HCV infects the human body, it can cause acute hepatitis and chronic hepatitis, and a few can cause severe hepatitis and liver failure.
  • Symptoms in the acute phase are fatigue, anorexia, dark urine, and pain in the liver area; chronic hepatitis is mostly non-specific symptoms, such as fatigue, abdominal distension, dull pain in the right upper quadrant, loss of energy for study or work, etc. If it continues to develop continuously, it can develop into cirrhosis, with symptoms related to decreased liver reserve function and portal hypertension.
  • Some HCV carriers although there are signs of viral infection, but no obvious clinical symptoms and abnormal biochemical indicators, are called asymptomatic carriers.
  • hepatitis C virus refers to anti-hepatitis C virus
  • Hepatitis C virus belongs to the Flaviviridae family and its genome has a positive single-stranded RNA strand.
  • the intermediate coding region, envelope, and nonstructural proteins of the entire negative strand can be replicated, and the envelope region includes a hypervariable region, which is related to sequence variation.
  • HCV is currently divided into 6 genotypes and different subtypes, and each genotype has a different geographical distribution. HCV genotypes 1, 2, and 3 are prevalent all over the world, among which HCV genotype 1 is the most widespread.
  • HCV 1a is mainly endemic in Western Europe and North America; HCV 1b is mainly endemic in Japan, China, Southern and Eastern Europe; HCV 1c is only found in Indonesia; HCV 2c is only endemic in northern Italy; HCV 3a is common in young populations in Western countries , especially intravenous drug addicts; HCV type 3b is found in Japan, Nepal, Thailand and Indonesia; HCV types 3c, 3d, 3e and 3f are found in Nepal; HCV type 4 is mainly prevalent in Africa; HCV type 5 is the main genotype in South Africa; HCV type 6 is mainly prevalent in Asia. China mainly has HCV genotypes 1b and 2a, of which 1b type accounts for about 80%. In the south, it is basically 1b type. From south to north, 2a type gradually increases. In some northern areas, the proportion of 1b and 2a is basically similar.
  • anti-HCV refers to inhibiting the expression of HCV-RNA in cells.
  • the Jingfang preparation of the present invention can significantly reduce the relative expression of HCV-RNA in cells, and has a significant anti-hepatitis C virus effect in vitro.
  • the anti-hepatitis C virus refers to reducing the level of DHCV-DNA in HCV-infected serum.
  • Jingfang preparation of the present invention can significantly reduce the DHCV-DNA level in the serum of HCV-infected ducks, and has a significant effect on inhibiting the activity of duck hepatitis C virus, and the effect is better than Jingfang Baidu Powder and Jingfang Addition and subtraction of Baidu powder.
  • the jingfang preparation of the present invention is mainly prepared from the following ingredients: Schizonepetae, Fangfeng, Notopterygium, Duhuo, Poria, Chuanxiong, Campanulaceae, Bupleurum, Peucedanum, Fructus Aurantii and Licorice.
  • the Jingfang preparation is mainly prepared from the following components by weight:
  • the Jingfang preparation is mainly prepared from the following ingredients in parts by weight:
  • the Jingfang preparation is mainly prepared from the following ingredients in parts by weight:
  • the Jingfang preparation is mainly prepared from the following ingredients in parts by weight:
  • the Jingfang preparation is mainly prepared from the following ingredients in parts by weight:
  • the Jingfang preparation is mainly prepared from the following ingredients in parts by weight:
  • the Jingfang preparation is mainly prepared from the following ingredients in parts by weight:
  • the Jingfang preparation is mainly prepared from the following ingredients in parts by weight:
  • the above components are proportioned by weight, and can be increased or decreased according to the corresponding proportion during production, but the proportion by weight of the components remains unchanged.
  • Schizonepeta Relieves exterior and disperses wind, penetrates rash and eliminates sores.
  • Windproof expelling wind and relieving exterior syndrome, dehumidifying and relieving pain, relieving spasm.
  • Notopterygium Relieving exterior and dispelling cold, expelling wind and dampness, relieving pain.
  • Bupleurum soothing the liver and relieving stagnation, reducing fever and tonifying yang.
  • Rhizoma Chuanxiong promoting blood circulation and removing blood stasis, expelling wind and relieving pain, calming down.
  • Fructus Aurantii Regulates Qi, relieves stagnation, relieves swelling.
  • Poria cocos invigorating the spleen, calming the mind, diuresis and expelling dampness.
  • Platycodon grandiflora clears the lung, relieves the throat, eliminates phlegm, and drains pus.
  • Licorice Tonifies spleen and Qi, eliminates phlegm, relieves cough, and relieves pain.
  • the invention provides a preparation method of Jingfang preparation, and the preparation method mainly includes the following steps:
  • Step A distill Nepeta, Fangfeng, Notopterygium, Duhuo, Peucedanum, Chuanxiong, and Citrus aurantium respectively to extract volatile oils, and distilled medicinal residues, distilled Chuanxiong, and Citrus aurantium aqueous solutions for future use;
  • Step B preparing the distilled aqueous solution of Ligusticum Chuanxiong and Fructus Fructus Fructus obtained in Step A into a 10-40% ethanol solution for subsequent use;
  • Step C mixing Poria cocos, the distilled Rhizoma Chuanxiong and Citrus aurantii herb residues obtained in step A, percolating and extracting with the ethanol solution obtained in step B, and the percolating liquid is set aside;
  • Step D decoct Bupleuri, Platycodon grandiflorum, licorice, Nepeta nepeta, Fangfeng, Qianghuo, Duhuo and Peucedanum obtained in step A after distillation, add water to decoct, and concentrate the decoction for later use;
  • Step E Mix the percolation liquid obtained in step C and the decoction liquid obtained in step D, concentrate into an extract, add the volatile oil obtained in step A, and obtain.
  • the preparation method mainly includes the following steps:
  • Step A Distill Nepeta, Fangfeng, Notopterygium, Duhuo, Peucedanum, Rhizoma Chuanxiong, and Citrus aurantium, respectively, to extract volatile oils for later use, and distilled medicinal residues, distilled Chuanxiong, and Citrus aurantii for later use;
  • Step B preparing the distilled aqueous solution of Rhizoma Chuanxiong and Fructus Fructus Fructus obtained in Step A into a 15-30% ethanol solution for subsequent use;
  • Step C mixing Poria cocos, the distilled Rhizoma Chuanxiong and Citrus aurantii herb residues obtained in step A, percolating and extracting with the ethanol solution obtained in step B, and the percolating liquid is set aside;
  • Step D decoct Bupleuri, Platycodon grandiflorum, licorice, nepeta, Fangfeng, Qianghuo, Duhuo and Peucedanum obtained in step A after distillation, add water to decoct, and condense the decoction into a thick paste for later use;
  • Step E Mix the percolation liquid obtained in step C and the thick paste obtained in step D, concentrate into a clear paste, add the volatile oil obtained in step A, and obtain.
  • the amount of water added, the extraction time and the number of extractions are not absolute, that is, the corresponding parameter values outside the range and close to the end values of the range are used. It is also possible to achieve the object of the present invention. Accordingly, all obvious variations of the above-described embodiments are intended to be within the scope of the invention.
  • the Jingfang preparation of the present invention is prepared into a clinically acceptable dosage form by adding other pharmaceutically acceptable auxiliary materials.
  • the clinically acceptable dosage forms are granules, oral solvents, mixtures, pills, syrups, capsules, and tablets.
  • the clinically acceptable dosage form is granule or mixture.
  • the pharmaceutically acceptable adjuvant refers to any substance that does not interfere with the pharmacological effects of the components of the Jingfang preparation and is non-toxic to subjects including humans.
  • the pharmaceutical excipients used in the preparation of the present invention are commonly used excipients known to those skilled in the art, as long as the excipients do not adversely affect the quality and performance of the traditional Chinese medicine composition of the present invention.
  • pharmaceutically acceptable excipients include conventional diluents, carriers, fillers, binders, wetting agents, disintegrants, absorption accelerators, surfactants, adsorption carriers and lubricants in the pharmaceutical field.
  • Commonly used diluents mainly include sucrose, dextrin, starch, lactose, mannitol, xylitol, bifidosaccharide, etc.
  • Commonly used wetting agents mainly include water, ethanol of different concentrations, etc.; commonly used binders include polymer binders such as ethyl cellulose, polyvinylpyrrolidone, sodium carboxymethyl cellulose, polyethylene glycol, alginic acid, etc. Sodium etc.
  • Commonly used disintegrants include microcrystalline cellulose, sodium carboxymethyl starch, etc.
  • a particular excipient will depend on the mode of administration or the type and state of the disease being used to treat the particular patient. If necessary, flavoring agents, preservatives and sweeteners can also be added to the Jingfang preparation.
  • suitable Chinese herbal compositions for a particular mode of administration is well within the knowledge of those skilled in the art. Those skilled in the art can select and determine the suitable excipients and their content in the fenugreek preparation of the present invention according to the content disclosed in this specification.
  • the antifungal formulations of the present invention may also contain suitable additives known in the art, such as emulsifiers, fragrances, solubilizers, anticaking agents, defoamers, binders, buffers, pH regulators Agents, propellants, chelating agents, and preservatives.
  • suitable additives such as emulsifiers, fragrances, solubilizers, anticaking agents, defoamers, binders, buffers, pH regulators Agents, propellants, chelating agents, and preservatives.
  • the dose of the sting preparation for humans or animals is 0.05g/kg/d-3.5g/kg/d.
  • the human or animal dose of the venom preparation is 0.1 g/kg/d-2.5 g/kg/d.
  • Jingfang preparation of the present invention has significant anti-hepatitis C virus effect in vitro, and compared with the normal control group, it can obviously reduce the expression level of HCV-RNA in cells, and there is a very significant statistical difference (P ⁇ 0.01), with Significant anti-hepatitis C virus effect, the effect is better than Jing Fang Bai Du powder addition and subtraction.
  • Jingfang preparation of the present invention has a significant effect on the anti-hepatitis C virus activity in vivo, and can obviously reduce the serum DHCV-DNA level of infected ducks, with significant or extremely significant statistical differences (p ⁇ 0.05, P ⁇ 0.01), and the effect is excellent Yu Jing Fang Bai Du San and Jing Fang Bai Du San Modified and Subtracted Prescriptions can be used to treat Hepatitis C Virus, and have broad clinical application prospects.
  • the inventors carried out corresponding animal experiments. It should be noted that the following animal experiments are selected from the representative formulations of the present invention and the medicines obtained by the preparation methods thereof, and the tests and results related to the products obtained by other formulations and preparation methods included in the present invention, the inventors Experiments were also carried out, and the experimental results showed that the medicines obtained by other formulations and preparation methods had the same or similar effects. Due to space limitations, they are not listed here.
  • the following experimental studies are carried out on the basis of acute toxicity test and long-term toxicity test to prove the safety of the drug, and the dosages in the experimental studies are all within the safe dosage range. Any equivalent replacements will be apparent to those skilled in the art and are included in the present invention.
  • Embodiment 1 granule preparation
  • Step A distill Nepeta, Fangfeng, Notopterygium, Duhuo, Peucedanum, Chuanxiong, and Citrus aurantium respectively to extract volatile oils, and distilled medicinal residues, distilled Chuanxiong, and Citrus aurantium aqueous solutions for future use;
  • Step B preparing the distilled aqueous solution of Rhizoma Chuanxiong and Fructus Aurantii obtained in Step A into a 25% ethanol solution for subsequent use;
  • Step C mixing Poria cocos, the distilled Rhizoma Chuanxiong and Citrus aurantii herb residues obtained in step A, percolating and extracting with the ethanol solution obtained in step B, and the percolating liquid is set aside;
  • Step D decoct Bupleurum chinensis, Platycodon grandiflorum, Radix Glycyrrhizae, distilled Schizonepetae, Fangfeng, Notopterygium, Duhuo, and Peucedanum dregs obtained in Step A, decocting twice for 1.5 hours each time, combining the two decoction liquids, Concentrate into a thick paste after filtering and set aside;
  • Step E Mix the percolation liquid obtained in step C and the thick paste obtained in step D, let it stand, filter and concentrate into a clear paste with a relative density of 1.30 (80-85°C), take 1 part of the clear paste, add 6 parts of sucrose powder , mixed evenly, made into granules, dried, added the volatile oil obtained in step A, mixed evenly, and obtained.
  • Nepeta 50g Fangfeng 100g, Notopterygium 50g, Duhuo 100g, Bupleurum 15g, Peucedanum 100g, Chuanxiong 50g, Citrus aurantium 100g, Poria cocos 50g, Campanulaceae 100g, Licorice 5g;
  • the preparation method is the same as in Example 1.
  • Embodiment 3 granule preparation
  • the preparation method is the same as in Example 1.
  • Step A distill Nepeta, Fangfeng, Notopterygium, Duhuo, Peucedanum, Chuanxiong, and Citrus aurantium respectively to extract volatile oils, and distilled medicinal residues, distilled Chuanxiong, and Citrus aurantium aqueous solutions for future use;
  • Step B preparing the distilled aqueous solution of Rhizoma Chuanxiong and Fructus Aurantii obtained in Step A into a 10% ethanol solution for subsequent use;
  • Step C mixing Poria cocos, the distilled Rhizoma Chuanxiong and Citrus aurantii herb residues obtained in step A, percolating and extracting with the ethanol solution obtained in step B, and the percolating liquid is set aside;
  • Step D decoct Bupleurum chinensis, Platycodon grandiflorum, Radix Glycyrrhizae, distilled Schizonepetae, Fangfeng, Notopterygium, Duhuo, and Peucedanum dregs obtained in Step A, decocting twice for 1.5 hours each time, combining the two decoction liquids, Concentrate into a thick paste after filtering and set aside;
  • Step E Mix the percolation liquid obtained in step C and the thick paste obtained in step D, let it stand, filter and concentrate into a clear paste, add an appropriate amount of sucrose, mix well, add the volatile oil obtained in step A, mix well, add water to 1000ml, and get .
  • Step A distill Nepeta, Fangfeng, Notopterygium, Duhuo, Peucedanum, Chuanxiong, and Citrus aurantium respectively to extract volatile oils, and distilled medicinal residues, distilled Chuanxiong, and Citrus aurantium aqueous solutions for future use;
  • Step B preparing the distilled aqueous solution of Rhizoma Chuanxiong and Fructus Aurantii obtained in Step A into a 40% ethanol solution for subsequent use;
  • Step C mixing Poria cocos, the distilled Rhizoma Chuanxiong and Citrus aurantii herb residues obtained in step A, percolating and extracting with the ethanol solution obtained in step B, and the percolating liquid is set aside;
  • Step D decoct Bupleurum chinensis, Platycodon grandiflorum, Radix Glycyrrhizae, distilled Schizonepetae, Fangfeng, Notopterygium, Duhuo, and Peucedanum dregs obtained in Step A, decocting twice for 1.5 hours each time, combining the two decoction liquids, Concentrate into a thick paste after filtering and set aside;
  • Step E Mix the percolation liquid obtained in step C and the thick paste obtained in step D, let stand, filter and concentrate into a clear paste, add an appropriate amount of sucrose, mix well, add 500ml of volatile oil and simple syrup obtained in step A, mix well, let stand , filter, add water to 1000ml, that is.
  • Step A distill Nepeta, Fangfeng, Notopterygium, Duhuo, Peucedanum, Chuanxiong, and Citrus aurantium respectively to extract volatile oils, and distilled medicinal residues, distilled Chuanxiong, and Citrus aurantium aqueous solutions for future use;
  • Step B preparing the distilled aqueous solution of Rhizoma Chuanxiong and Fructus Aurantii obtained in Step A into a 15% ethanol solution for subsequent use;
  • Step C mixing Poria cocos, the distilled Rhizoma Chuanxiong and Citrus aurantii herb residues obtained in step A, percolating and extracting with the ethanol solution obtained in step B, and the percolating liquid is set aside;
  • Step D decoct Bupleurum chinensis, Platycodon grandiflorum, Radix Glycyrrhizae, distilled Schizonepetae, Fangfeng, Notopterygium, Duhuo, and Peucedanum dregs obtained in Step A, decocting twice for 1.5 hours each time, combining the two decoction liquids, Concentrate into a thick paste after filtering and set aside;
  • Step E Mix the percolation liquid obtained in step C and the thick paste obtained in step D, let stand, filter and concentrate into a clear paste, add an appropriate amount of sucrose, mix well, make granules, dry, add the volatile oil obtained in step A, mix well, Make into granules, add appropriate amount of auxiliary materials, mix evenly, and compress into tablets.
  • Step A distill Nepeta, Fangfeng, Notopterygium, Duhuo, Peucedanum, Chuanxiong, and Citrus aurantium respectively to extract volatile oils, and distilled medicinal residues, distilled Chuanxiong, and Citrus aurantium aqueous solutions for future use;
  • Step B the aqueous solution of Ligusticum Chuanxiong and Fructus Fructus Fructus Aurantii after distillation obtained in Step A is prepared into a 30% ethanol solution for subsequent use;
  • Step C mixing Poria cocos, the distilled Rhizoma Chuanxiong and Citrus aurantii herb residues obtained in step A, percolating and extracting with the ethanol solution obtained in step B, and the percolating liquid is set aside;
  • Step D decoct Bupleurum chinensis, Platycodon grandiflorum, Radix Glycyrrhizae, distilled Schizonepetae, Fangfeng, Notopterygium, Duhuo, and Peucedanum dregs obtained in Step A, decocting twice for 1.5 hours each time, combining the two decoction liquids, Concentrate into a thick paste after filtering and set aside;
  • Step E Mix the percolation liquid obtained in step C and the thick paste obtained in step D, let stand, filter and concentrate into a clear paste, add an appropriate amount of sucrose, mix well, make granules, dry, add the volatile oil obtained in step A, mix well, Made into granules, dried, pulverized, and packed into capsules.
  • Step A distill Nepeta, Fangfeng, Notopterygium, Duhuo, Peucedanum, Chuanxiong, and Citrus aurantium respectively to extract volatile oils, and distilled medicinal residues, distilled Chuanxiong, and Citrus aurantium aqueous solutions for future use;
  • Step B preparing the distilled aqueous solution of Rhizoma Chuanxiong and Fructus Aurantii obtained in Step A into a 25% ethanol solution for subsequent use;
  • Step C mixing Poria cocos, the distilled Rhizoma Chuanxiong and Citrus aurantii herb residues obtained in step A, percolating and extracting with the ethanol solution obtained in step B, and the percolating liquid is set aside;
  • Step D decoct Bupleurum chinensis, Platycodon grandiflorum, Radix Glycyrrhizae, distilled Schizonepetae, Fangfeng, Notopterygium, Duhuo, and Peucedanum dregs obtained in Step A, decocting twice for 1.5 hours each time, combining the two decoction liquids, Concentrate into a thick paste after filtering and set aside;
  • Step E Mix the percolation liquid obtained in step C and the thick paste obtained in step D, let stand, filter and concentrate into a clear paste, add an appropriate amount of sucrose, mix well, make granules, dry, add the volatile oil obtained in step A, mix well, Dry, crush, sieve, add 40-60g of refined honey, appropriate amount of water to flood the pills, and dry to obtain.
  • Step A Distill Nepeta, Fangfeng, Notopterygium, Duhuo, Peucedanum, Chuanxiong, and Fructus Citrus Fructus respectively to extract volatile oils for later use, and collect the aqueous solution in another device after distillation;
  • Step B preparing the distilled aqueous solution of Rhizoma Chuanxiong and Fructus Aurantii obtained in Step A into a 25% ethanol solution for subsequent use;
  • Step C mixing Poria cocos, the distilled Rhizoma Chuanxiong and Citrus aurantii herb residues obtained in step A, percolating and extracting with the ethanol solution obtained in step B, and the percolating liquid is set aside;
  • Step D decoct Bupleurum chinensis, Platycodon grandiflorum, Radix Glycyrrhizae, distilled Schizonepetae, Fangfeng, Notopterygium, Duhuo, and Peucedanum dregs obtained in Step A, decocting twice for 1.5 hours each time, combining the two decoction liquids, Concentrate into a thick paste after filtering and set aside;
  • Step E Mix the percolation liquid obtained in step C and the thick paste obtained in step D, let stand, filter and concentrate into a clear paste, add an appropriate amount of sodium benzoate, mix well, add the volatile oil obtained in step A, mix well, add water to 1000ml, that is have to.
  • Step A Distill Nepeta, Fangfeng, Notopterygium, Duhuo, Peucedanum, Chuanxiong, and Fructus Citrus Fructus respectively to extract volatile oils for later use, and collect the aqueous solution in another device after distillation;
  • Step B the aqueous solution of Ligusticum Chuanxiong and Fructus Fructus Fructus Aurantii after distillation obtained in Step A is prepared into a 30% ethanol solution for subsequent use;
  • Step C mixing Poria cocos, the distilled Rhizoma Chuanxiong and Citrus aurantii herb residues obtained in step A, percolating and extracting with the ethanol solution obtained in step B, and the percolating liquid is set aside;
  • Step D decoct Bupleurum chinensis, platycodon grandiflorum, licorice, distilled Nepeta chinensis, Fangfeng, Qianghuo, Duhuo, and Peucedanum herbaceous residues obtained in step A twice, each time for 2.5 hours, and combine the decoctions twice, Concentrate into a thick paste after filtering and set aside;
  • Step E Mix the percolation liquid obtained in step C and the thick paste obtained in step D, let stand, filter and concentrate into a clear paste, add the volatile oil obtained in step A, mix well, make granules, dry, pulverize to obtain a fine powder, and set aside ;
  • Drug effect embodiment 1 Jingfang granule compares the anti-hepatitis C virus effect in vitro
  • Jingfang granule provided by Shandong New Times Pharmaceutical Co., Ltd., specification: 15g per bag;
  • Jingfangbaidu San Nepeta 30g, Fangfeng 30g, Notopterygium 25g, Duhuo 25g, Bupleurum 25g, Peucedanum 25g, Rhizoma Chuanxiong 20g, Citrus aurantium 25g, Poria cocos 45g, Campanulaceae 30g, Licorice 15g, Forsythia 30g, Mint 30g, Hawthorn 60g, Liuqu 60g. According to the above prescription, it is prepared into granules according to conventional methods in the art.
  • Huh7.5 cells were infected with chimera hepatitis C virus in vitro to investigate the antiviral effect of each group.
  • the granules prepared by adding and subtracting Jingfang Granules and Jingfang Baidu Powder were prepared into a 50 mg/ml mother solution with dimethyl sulfoxide DMSO for later use. During the experiment, it was diluted to the corresponding concentration according to the needs of the experiment.
  • the hepatitis C virus infection Huh7.5 cells were normally subcultured, and the Huh7.5 cells in the logarithmic growth phase were taken to make a cell suspension of 1 ⁇ 10 5 cells/ml, and 500 ⁇ l of the cell suspension was added to each well of a 24-well culture dish and shaken well.
  • Drug effect embodiment 2 Jingfang granule is to the therapeutic effect of hepatitis C virus infection in duck body
  • the invention adopts domestic and foreign recognized experimental models, and conducts experiments in ducks infected with hepatitis C virus. 1.
  • Jingfang granule provided by Shandong New Times Pharmaceutical Co., Ltd., specification: 15g per bag;
  • Jingfangbaidu Powder Modified Group Nepeta 30g, Fangfeng 30g, Notopterygium 25g, Duhuo 25g, Bupleurum 25g, Peucedanum 25g, Chuanxiong 20g, Citrus aurantium 25g, Poria cocos 45g, Campanulaceae 30g, Licorice 15g, Forsythia 30g, Mint 30g, Hawthorn 60g, Liuqu 60g. According to the above prescription, it is prepared into granules according to conventional methods in the art. 2. Experimental method
  • DHCV infection 48 ducklings were injected with DHCV-DNA positive duck serum through the tibial vein, 0.2ml each. Blood was collected 7 days after infection, serum was separated, and stored at -70°C until testing.
  • Detection method take the above-mentioned duck serum to be tested, spot the membrane at the same time for each batch, and measure the dynamic level of DHCV-DNA in the duck serum.
  • the instructions of the Promega gap translation kit use 32 p to label the DHCV-DNA probe, do duck serum dot hybridization, autoradiograph the membrane spots, measure the OD value (490nm) with an enzyme label detector, and calculate the serum DHCV-DNA density , take the OD value of the hybridization spot as the sample DHCV-DNA level value.
  • DHCV-DNA inhibition rate (OD value before administration-OD value after administration)/OD value before administration ⁇ 100%.
  • Drug effect embodiment 3 Jingfang granule is to the therapeutic effect of hepatitis C virus infection in duck body
  • Jingfangbaidu Powder According to the following prescription, it is prepared into granules according to the conventional method in this field. Nepeta, Fangfeng, Duhuo, Poria, and Bupleurum each 10g, Peucedanum, Chuanxiong, Hovenia, Notopterygium, Platycodon grandiflorum each 6g, Jiaosanxian 15g, mint (back part), licorice 3g each. The results are shown in Table 3.
  • Jingfang preparation of the present invention such as Jingfang mixture, pills, tablets, syrups, and capsules can also significantly reduce the expression of HCV-RNA in cells and reduce the serum DHCV-DNA level of infected ducks through animal experiments.
  • the effect of inhibiting the activity of hepatitis C virus is remarkable, which is superior to Jingfang Baidu powder and Jingfang Baidu powder, and can be used for the treatment of hepatitis C virus.
  • the specific description will not be listed one by one here.

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Abstract

荆防制剂在制备预防或治疗丙型病毒性肝炎的药物中的用途，荆防制剂由羌活、独活、茯苓、防风、荆芥、川芎、桔梗、柴胡、前胡、枳壳、甘草制成，可抑制丙型肝炎病毒的活性和HCV-RNA在细胞中的表达，降低体内HCV病毒感染鸭血清中DHCV-DNA的水平。

Description

[根据细则37.2由ISA制定的发明名称]　荆防制剂在制备预防或治疗丙型病毒性肝炎的药物中的用途 技术领域
本发明属于医药技术领域，涉及荆防制剂的一种新的医药用途，具体地，涉及荆防颗粒在制备预防或治疗丙型病毒性肝炎药物中的用途。
背景技术
丙型肝炎是一种由丙型肝炎病毒(hepatitis C virus，HCV)引起，主要经血液传播的肝脏急、慢性炎症的传染性疾病。丙型肝炎病毒感染可导致肝脏慢性炎症坏死和纤维化，部分患者可发展为肝硬化甚至肝细胞癌，对患者的健康和生命危害极大。目前，全球HCV感染率为3％，感染者约1.7亿。我国最新流行病学调查显示，抗HCV阳性率为0.43％，全国HCV感染者有560多万。因此，丙肝的防治已成为严重的社会和公共卫生问题，也是未来我国传染病防治领域的重点疾病之一。
由于HCV基因组存在高突变性，目前尚无有效的疫苗进行预防，所以应用抗病毒药物是治疗的重点。国际上的早期标准治疗方案是长效干扰素+利巴韦林，因不具备靶向性，其有效率不到50％，且不良反应大，治疗周期长。目前新型抗病毒药物主要有两大类：新型直接抗病毒药物和宿主靶向药物。直接抗病毒药物有三种：(1)NS3/4A丝氨酸蛋白酶抑制药—使其不能产生编辑和修饰肽链，阻断病毒的生成，如特拉匹韦、博赛匹韦、伏西瑞韦、阿舒瑞韦等；(2)NS5A蛋白酶抑制药—阻断病毒的组装、释放和转运，如达拉他韦、维帕他韦、来迪派韦等；(3)NS5B聚合酶抑制药—核苷类似物和非核苷类似物，前者终止RNA的合成，如索磷布韦，后者使酶失去作用，如达塞布韦。宿主靶向药物：通过靶向抑制宿主体内致病相关的细胞因子或增强宿主的固有免疫应答而发挥抗HCV作用，如亲环素A、阿立帕韦属。新型抗病毒药物靶向明确，有效率较高，治疗周期短，但其耐药位点多，不良反应大，药物联合使用协同发挥作用可大大降低不良反应，但还是会引起疲劳、头痛、恶心、腹泻等。因此，丙型病毒性肝炎依然是临床治疗的难题，进一步寻找治疗丙型病毒性肝炎的有效药物和方案是临床的 迫切需求。中医药以其辨证论治的个体化治疗优势，在丙型病毒性肝炎的治疗中正日益显示出其独特性。
荆防制剂来源于经典古方荆防败毒散，由荆芥、防风、羌活、独活、柴胡、前胡、川芎、枳壳、茯苓、桔梗、甘草十一味原料药材采用现代制药工艺制备而成，具有发汗解表，散风祛湿的功效，临床上主要用于治疗风寒感冒、头痛身痛、恶寒无汗、鼻塞流涕、咳嗽白痰等症状。方中君药荆芥、防风辛温表散、发汗解表散风邪，为祛百病之首；臣药羌活、独活辛温发散，通治一身上下之风寒湿邪，川芎行血祛风，柴胡辛散解肌，助羌活，独活祛外邪，止疼痛；枳壳降气，桔梗开肺，前胡祛痰，茯苓渗湿，并为佐药，甘草调合诸药为使药。诸药合用，汗出而热退，血行而风消痛止，肺气利，痰湿除，咳嗽止，感冒诸症状消除而病愈。
近年来，随着中药制剂研究的深入发展，越来越多的荆防制剂功效被发掘。发明人在临床应用过程中，发现荆防制剂具有治疗丙型病毒性肝炎的功效。药理实验研究结果表明：本发明的荆防制剂对体外抗丙型肝炎病毒效果显著，能明显降低HCV-RNA在细胞中的表达量，具有显著的抗体外丙型肝炎病毒的作用，效果优于荆防败毒散加减方；荆防制剂对体内抗丙型肝炎病毒活性效果显著，可明显降低感染鸭血清DHCV-DNA水平，效果优于荆防败毒散和荆防败毒散加减方。本发明的荆防制剂为临床治疗丙型病毒性肝炎提供了新的用药选择，体现出中药复方具有整体性、多靶点和多组分协同作用的疗效特点。
发明内容
本发明提供了荆防制剂在制备预防或治疗丙型病毒性肝炎药物中的用途；
丙型病毒性肝炎是由于感染HCV病毒引起的一种病毒性肝炎，传播途径主要血液传播、性传播和母婴传播。
HCV病毒感染初期可引起肝脏慢性炎症坏死和纤维化，进一步发展成为肝硬化、肝癌等终末期肝病。
HCV治疗的目的是清除患者体内病毒，控制或减轻肝组织纤维化或炎症坏死现象，避免发展成肝硬化，从而降低原发性肝癌发生几率。
HCV感染人体后可造成急性肝炎、慢性肝炎，少数可发生重症肝炎、肝衰竭。急性期的症状为乏力、厌食、尿色加深、肝区疼痛；慢性肝炎大多为非特异性症状，如乏力、腹胀、右上腹隐痛、学习或工作精力减退等。如继续持续发展， 可发展至肝硬化，出现肝脏储备功能下降和门静脉高压的相关症状。部分HCV携带者，虽有病毒感染的标志，但无明显临床症状和生化指标的异常，称为无症状携带者。
进一步的，所述的预防或治疗丙型病毒性肝炎是指抗丙型肝炎病毒；
丙型肝炎病毒(HCV)属于黄病毒科，其基因组单股RNA正链。整条负链的中间编码区域、包膜、非结构蛋白都可以进行复制，包膜区包括超变量区域，与序列的变异有关。HCV目前分为6各基因型及不同亚型，每个基因型具有不同的地理分布。HCV基因1，2，3型呈全世界流行，其中HCV基因1型流行最为广泛。HCV 1a型主要流行于西欧和北美；HCV 1b型主要流行于日本、中国、南欧和东欧；HCV 1c型仅见于印度尼西亚；HCV 2c型仅见于意大利北部流行；HCV 3a型常见于西方国家的年轻人群，特别是静脉药瘾者；HCV 3b型见于日本、尼泊尔、泰国和印度尼西亚；HCV 3c，3d，3e和3f型见于尼泊尔；HCV 4型主要流行于非洲；HCV 5型是南非的主要基因型；HCV 6型则主要流行于亚洲。中国主要是HCV基因1b型和2a型，其中1b型占80％左右，南方基本上为1b型，从南向北2a型逐渐增多，至北方部分地区，1b和2a比例基本接近。
进一步的，所述的抗丙型肝炎病毒是指抑制HCV-RNA在细胞中的表达。
药效实施例1研究发现，本发明的荆防制剂可明显降低HCV-RNA在细胞中的相对表达量，具有显著的体外抗丙型肝炎病毒的作用。
进一步的，所述的抗丙型肝炎病毒是指降低HCV感染的血清中DHCV-DNA的水平。
药效实施例2和3研究发现，本发明的荆防制剂可明显降低HCV感染鸭血清DHCV-DNA水平，抑制鸭丙型肝炎病毒活性效果显著，且效果优于荆防败毒散和荆防败毒散加减方。
本发明所述荆防制剂主要由如下成分制备而成：荆芥、防风、羌活、独活、茯苓、川芎、桔梗、柴胡、前胡、枳壳、甘草。
其中，所述荆防制剂主要由如下重量份的成分制备而成：
荆芥5-30份 防风5-30份。
所述荆防制剂主要由如下重量份的成分制备而成：
荆芥10-20份 防风15-25份。
所述荆防制剂主要由如下重量份的成分制备而成：
荆芥5-30份 防风5-30份 羌活5-30份
独活5-30份 柴胡3-25份 前胡3-25份。
所述荆防制剂主要由如下重量份的成分制备而成：
荆芥5-30份 防风5-30份 羌活5-30份
独活5-30份 柴胡3-25份 前胡3-25份
川芎5-30份 枳壳3-25份 茯苓5-30份
桔梗3-25份。
所述荆防制剂主要由如下重量份的成分制备而成：
荆芥5-30份 防风5-30份 羌活5-30份
独活5-30份 柴胡3-25份 前胡3-25份
川芎5-30份 枳壳3-25份 茯苓5-30份
桔梗3-25份 甘草1-10份。
所述荆防制剂主要由如下重量份的成分制备而成：
荆芥10-20份 防风10-20份 羌活10-20份
独活10-20份 柴胡3-20份 前胡3-20份
川芎10-20份 枳壳3-20份 茯苓10-25份
桔梗3-20份 甘草1-8份。
所述荆防制剂主要由如下重量份的成分制备而成：
荆芥15份 防风15份 羌活15份
独活15份 柴胡15份 前胡15份
川芎15份 枳壳15份 茯苓15份
桔梗15份 甘草5份。
所述荆防制剂主要由如下重量份的成分制备而成：
荆芥10份 防风10份 羌活12份
独活12份 柴胡5份 前胡5份
川芎12份 枳壳5份 茯苓20份
桔梗5份 甘草3份。
以上各成分是按重量作为配比的，在生产时可按照相应比例增大或减少，但各成分之间的重量配比的比例不变。
其中荆防制剂各成分的功效如下：
荆芥：解表散风、透疹消疮。
防风：祛风解表、除湿止痛、止痉。
羌活：解表散寒、祛风胜湿、止痛。
独活：祛风除湿、止痛。
柴胡：疏肝解郁、退热、补阳。
前胡：降气化痰、散风清热。
川芎：活血祛瘀、祛风止痛、镇静。
枳壳：理气宽中、行滞消胀。
茯苓：健脾、宁心、利水渗湿。
桔梗：宣肺、利咽、祛痰、排脓。
甘草：补脾益气、祛痰止咳、止痛。
本发明提供了荆防制剂的制备方法，所述制备方法主要包括以下步骤：
步骤A：将荆芥、防风、羌活、独活、前胡、川芎、枳壳分别蒸馏提取挥发油备用，蒸馏后的药渣、蒸馏后的川芎、枳壳水溶液备用；
步骤B：将步骤A所得川芎、枳壳蒸馏后的水溶液配制成10-40％的乙醇溶液，备用；
步骤C：将茯苓、步骤A所得蒸馏后的川芎、枳壳药渣混合，以步骤B所得乙醇溶液渗漉提取，渗漉液备用；
步骤D：将柴胡、桔梗、甘草、步骤A所得荆芥、防风、羌活、独活、前胡蒸馏后的药渣，加水煎煮，煎煮液浓缩后备用；
步骤E：将步骤C所得渗漉液和步骤D所得煎煮液混合，浓缩成浸膏，加入步骤A所得挥发油，即得。
进一步地，所述制备方法主要包括以下步骤：
步骤A：将荆芥、防风、羌活、独活、前胡、川芎、枳壳，分别蒸馏提取挥发油备用，蒸馏后的药渣、蒸馏后的川芎、枳壳水溶液备用；
步骤B：将步骤A所得川芎、枳壳蒸馏后的水溶液配制成15-30％的乙醇溶液，备用；
步骤C：将茯苓、步骤A所得蒸馏后的川芎、枳壳药渣混合，以步骤B所得乙醇溶液渗漉提取，渗漉液备用；
步骤D：将柴胡、桔梗、甘草、步骤A所得荆芥、防风、羌活、独活、前胡蒸馏后的药渣，加水煎煮，煎煮液浓缩成稠膏，备用；
步骤E：将步骤C所得渗漉液和步骤D所得稠膏混合，浓缩成清膏，加入步骤A所得挥发油，即得。
本领域技术人员知道，在该方面的任何一种实施方案中，所述的加水量、提取时间和提取次数不是绝对的，即使用在所述范围以外且接近所述范围端值的相应参数值也可能实现本发明的目的。因此，上述实施方案的所有显而易见的变化形式都在本发明的范围之内。
本发明所述荆防制剂为加入其他药学上可接受的辅料制备成临床上可接受的剂型。
进一步的，所述的临床上可接受的剂型为颗粒剂、口服溶剂、合剂、丸剂、糖浆剂、胶囊剂、片剂。
进一步优选的，所述的临床上可接受的剂型为颗粒剂或合剂。
进一步地，所述药学上可接受的辅料是指不干扰荆防制剂各组分的药理作用，且对包括人类在内的受试者没有毒性的任何物质。本发明制剂所用的药用辅料为本领域技术人员已知的常用辅料，只要该辅料不对本发明的中药组合物的质量和性能产生不利影响即可。如可以作为制药上可接受的赋形剂包括药学领域常规的稀释剂、载体、填充剂、粘合剂、湿润剂、崩解剂、吸收促进剂、表面活性剂、吸附载体和润滑剂等。常用的稀释剂主要有蔗糖、糊精、淀粉、乳糖、甘露醇、木糖醇、双歧糖等。常用的润湿剂主要有水、不同浓度的乙醇等；常用的粘合剂包括高分子粘合剂如乙基纤维素、聚乙烯吡咯烷酮、羧甲基纤维素钠、聚乙二醇、海藻酸钠等。常用的崩解剂包括微晶纤维素、羧甲基淀粉钠等。本领域技术人员根据本说明书公开的内容能够选择和确定本发明的荆防制剂中适用的辅料。特定赋形剂的选择将取决于用于治疗特定患者的给药方式或疾病类型和状态。必要时，还可以在荆防制剂中加入香味剂、防腐剂和甜味剂等。用于特定给药模式的合适 中药组合物的制备方法完全在本领域技术人员的知识范围内。本领域技术人员根据本说明书公开的内容能够选择和确定本发明的荆防制剂中适用的辅料及其含量。
本发明的荆防制剂还可以包含适用的添加剂，这些添加剂是本领域中已知的，例如乳化剂、芳香剂、增溶剂、抗结剂、消泡剂、粘合剂、缓冲剂、pH调节剂、推进剂、螯合剂以及防腐剂等。
进一步的，所述的荆防制剂人或动物用剂量为0.05g/kg/d-3.5g/kg/d。
进一步优选的，所述荆防制剂人或动物用剂量为0.1g/kg/d-2.5g/kg/d。
与现有技术相比，本发明的有益成果如下：
1.本发明荆防制剂对体外抗丙型肝炎病毒效果显著，与正常对照组比较，能明显降低HCV-RNA在细胞中的表达量，有极显著性统计学差异(P＜0.01)，具有显著的抗体外丙型肝炎病毒的作用，效果优于荆防败毒散加减。
2.本发明荆防制剂对体内抗丙型肝炎病毒活性效果显著，可明显降低感染鸭血清DHCV-DNA水平，有显著或极显著的统计学差异(p＜0.05，P＜0.01)，效果优于荆防败毒散和荆防败毒散加减方，可用治疗丙型病毒性肝炎，临床应用前景广阔。
具体实施方式
为验证本发明荆防制剂预防和治疗丙型病毒性肝炎的作用，发明人开展了相应动物试验研究。需要说明的是，下述动物试验研究所选取的是本发明具有代表性的配方及其制备方法所得的药品，本发明所包含的其它配方及制备方法所得产品涉及的试验及其结果，发明人同样进行了实验，实验结果显示其他配方及制备方法所得药品具有相同或类似的效果，由于篇幅限制，在此不一一穷举。以下实验研究均是在急性毒性试验和长期毒性试验证明药物安全性基础之上开展的，实验研究中的给药剂量均在安全剂量范围之内。任何等同替换对于本领域的技术人员来说都是显而易见的，且包含在本发明之中的。
实施例1颗粒剂制备
处方：
荆芥75g、防风75g、羌活75g、独活75g、柴胡75g、前胡75g、川芎75g、枳壳75g、茯苓75g、桔梗75g、甘草25g。
制备方法：
步骤A：将荆芥、防风、羌活、独活、前胡、川芎、枳壳分别蒸馏提取挥发油备用，蒸馏后的药渣、蒸馏后的川芎、枳壳水溶液备用；
步骤B：将步骤A所得蒸馏后的川芎、枳壳水溶液配制成25％的乙醇溶液，备用；
步骤C：将茯苓、步骤A所得蒸馏后的川芎、枳壳药渣混合，以步骤B所得乙醇溶液渗漉提取，渗漉液备用；
步骤D：将柴胡、桔梗、甘草、步骤A所得蒸馏后的荆芥、防风、羌活、独活、前胡药渣，加水煎煮两次，每次1.5小时，合并两次的煎煮液，过滤后浓缩成稠膏，备用；
步骤E：将步骤C所得渗漉液、步骤D所得稠膏混合，静置，过滤后浓缩成相对密度为1.30(80～85℃)的清膏，取清膏1份，加蔗糖粉6份，混匀，制成颗粒，干燥，加入步骤A所得挥发油，混匀，即得。
实施例2颗粒剂制备
处方：
荆芥50g、防风100g、羌活50g、独活100g、柴胡15g、前胡100g、川芎50g、枳壳100g、茯苓50g、桔梗100g、甘草5g；
制备方法同实施例1。
实施例3颗粒剂制备
处方：
荆芥100g、防风50g、羌活100g、独活50g、柴胡100g、前胡15g、川芎100g、枳壳125g、茯苓125g、桔梗15g、甘草40g；
制备方法同实施例1。
制备实施例4口服液制备
处方：
荆芥75g、防风75g、羌活75g、独活75g、柴胡75g、前胡75g、川芎75g、枳壳75g、茯苓75g、桔梗75g、甘草25g；
制备方法：
步骤A：将荆芥、防风、羌活、独活、前胡、川芎、枳壳分别蒸馏提取挥发油备用，蒸馏后的药渣、蒸馏后的川芎、枳壳水溶液备用；
步骤B：将步骤A所得蒸馏后的川芎、枳壳水溶液配制成10％的乙醇溶液，备用；
步骤C：将茯苓、步骤A所得蒸馏后的川芎、枳壳药渣混合，以步骤B所得乙醇溶液渗漉提取，渗漉液备用；
步骤D：将柴胡、桔梗、甘草、步骤A所得蒸馏后的荆芥、防风、羌活、独活、前胡药渣，加水煎煮两次，每次1.5小时，合并两次的煎煮液，过滤后浓缩成稠膏，备用；
步骤E：将步骤C所得渗漉液、步骤D所得稠膏混合，静置，过滤后浓缩成清膏，加蔗糖适量，混匀，加入步骤A所得挥发油，混匀，加水至1000ml，即得。
实施例5糖浆剂制备
处方：
荆芥75g、防风75g、羌活75g、独活75g、柴胡75g、前胡75g、川芎75g、枳壳75g、茯苓75g、桔梗75g、甘草25g；
制备方法：
步骤A：将荆芥、防风、羌活、独活、前胡、川芎、枳壳分别蒸馏提取挥发油备用，蒸馏后的药渣、蒸馏后的川芎、枳壳水溶液备用；
步骤B：将步骤A所得蒸馏后的川芎、枳壳水溶液配制成40％的乙醇溶液，备用；
步骤C：将茯苓、步骤A所得蒸馏后的川芎、枳壳药渣混合，以步骤B所得乙醇溶液渗漉提取，渗漉液备用；
步骤D：将柴胡、桔梗、甘草、步骤A所得蒸馏后的荆芥、防风、羌活、独活、前胡药渣，加水煎煮两次，每次1.5小时，合并两次的煎煮液，过滤后浓缩成稠膏，备用；
步骤E：将步骤C所得渗漉液、步骤D所得稠膏混合，静置，过滤后浓缩成清膏，加蔗糖适量，混匀，加入步骤A所得挥发油和单糖浆500ml，混匀，静置，滤过，加水至1000ml，即得。
实施例6片剂制备
处方：
荆芥75g、防风75g、羌活75g、独活75g、柴胡75g、前胡75g、川芎75g、枳壳75g、茯苓75g、桔梗75g、甘草25g；
制备方法：
步骤A：将荆芥、防风、羌活、独活、前胡、川芎、枳壳分别蒸馏提取挥发油备用，蒸馏后的药渣、蒸馏后的川芎、枳壳水溶液备用；
步骤B：将步骤A所得蒸馏后的川芎、枳壳水溶液配制成15％的乙醇溶液，备用；
步骤C：将茯苓、步骤A所得蒸馏后的川芎、枳壳药渣混合，以步骤B所得乙醇溶液渗漉提取，渗漉液备用；
步骤D：将柴胡、桔梗、甘草、步骤A所得蒸馏后的荆芥、防风、羌活、独活、前胡药渣，加水煎煮两次，每次1.5小时，合并两次的煎煮液，过滤后浓缩成稠膏，备用；
步骤E：将步骤C所得渗漉液、步骤D所得稠膏混合，静置，过滤后浓缩成清膏，加蔗糖适量，混匀，制成颗粒，干燥，加入步骤A所得挥发油，混匀，制成颗粒，加入辅料适量，混匀，压片，即得。
实施例7胶囊剂制备
处方：
荆芥75g、防风75g、羌活75g、独活75g、柴胡75g、前胡75g、川芎75g、枳壳75g、茯苓75g、桔梗75g、甘草25g；
步骤A：将荆芥、防风、羌活、独活、前胡、川芎、枳壳分别蒸馏提取挥发油备用，蒸馏后的药渣、蒸馏后的川芎、枳壳水溶液备用；
步骤B：将步骤A所得蒸馏后的川芎、枳壳水溶液配制成30％的乙醇溶液，备用；
步骤C：将茯苓、步骤A所得蒸馏后的川芎、枳壳药渣混合，以步骤B所得乙醇溶液渗漉提取，渗漉液备用；
步骤D：将柴胡、桔梗、甘草、步骤A所得蒸馏后的荆芥、防风、羌活、独活、前胡药渣，加水煎煮两次，每次1.5小时，合并两次的煎煮液，过滤后浓缩成稠膏，备用；
步骤E：将步骤C所得渗漉液、步骤D所得稠膏混合，静置，过滤后浓缩成清膏，加蔗糖适量，混匀，制成颗粒，干燥，加入步骤A所得挥发油，混匀，制成颗粒，干燥，粉碎，装入胶囊，即得。
实施例8丸剂制备
处方：
荆芥75g、防风75g、羌活75g、独活75g、柴胡75g、前胡75g、川芎75g、枳壳75g、茯苓75g、桔梗75g、甘草25g；
制备方法：
步骤A：将荆芥、防风、羌活、独活、前胡、川芎、枳壳分别蒸馏提取挥发油备用，蒸馏后的药渣、蒸馏后的川芎、枳壳水溶液备用；
步骤B：将步骤A所得蒸馏后的川芎、枳壳水溶液配制成25％的乙醇溶液，备用；
步骤C：将茯苓、步骤A所得蒸馏后的川芎、枳壳药渣混合，以步骤B所得乙醇溶液渗漉提取，渗漉液备用；
步骤D：将柴胡、桔梗、甘草、步骤A所得蒸馏后的荆芥、防风、羌活、独活、前胡药渣，加水煎煮两次，每次1.5小时，合并两次的煎煮液，过滤后浓缩成稠膏，备用；
步骤E：将步骤C所得渗漉液、步骤D所得稠膏混合，静置，过滤后浓缩成清膏，加蔗糖适量，混匀，制成颗粒，干燥，加入步骤A所得挥发油，混匀，干燥，粉碎，过筛，加炼蜜40～60g，适量的水泛丸，干燥，即得。
实施例9合剂制备
处方：
荆芥97g、防风97g、羌活97g、独活97g、柴胡97g、前胡97g、川芎97g、枳壳97g、茯苓97g、桔梗97g、甘草32.4g；
制备方法：
步骤A：将荆芥、防风、羌活、独活、前胡、川芎、枳壳分别蒸馏提取挥发油备用，蒸馏后水溶液另器收集；
步骤B：将步骤A所得蒸馏后的川芎、枳壳水溶液配制成25％的乙醇溶液，备用；
步骤C：将茯苓、步骤A所得蒸馏后的川芎、枳壳药渣混合，以步骤B所得乙醇溶液渗漉提取，渗漉液备用；
步骤D：将柴胡、桔梗、甘草、步骤A所得蒸馏后的荆芥、防风、羌活、独活、前胡药渣，加水煎煮两次，每次1.5小时，合并两次的煎煮液，过滤后浓缩成稠膏，备用；
步骤E：将步骤C所得渗漉液、步骤D所得稠膏混合，静置，过滤后浓缩成清膏，加苯甲酸钠适量，混匀，加入步骤A所得挥发油，混匀，加水至1000ml，即得。
实施例10微囊制备
处方：
荆芥75g、防风75g、羌活75g、独活75g、柴胡75g、前胡75g、川芎75g、枳壳75g、茯苓75g、桔梗75g、甘草25g；
制备方法：
步骤A：将荆芥、防风、羌活、独活、前胡、川芎、枳壳分别蒸馏提取挥发油备用，蒸馏后水溶液另器收集；
步骤B：将步骤A所得蒸馏后的川芎、枳壳水溶液配制成30％的乙醇溶液，备用；
步骤C：将茯苓、步骤A所得蒸馏后的川芎、枳壳药渣混合，以步骤B所得乙醇溶液渗漉提取，渗漉液备用；
步骤D：将柴胡、桔梗、甘草、步骤A所得蒸馏后的荆芥、防风、羌活、独活、前胡药渣，加水煎煮两次，每次2.5小时，合并两次的煎煮液，过滤后浓缩成稠膏，备用；
步骤E：将步骤C所得渗漉液、步骤D所得稠膏混合，静置，过滤后浓缩成清膏，加入步骤A所得挥发油，混匀，制成颗粒，干燥，粉碎，得细粉，备用；
步骤F：称取步骤E荆防提取物细粉，络蛋白酸钠：麦芽糊精＝3:2混合物为囊材，十八醇：二氧化钛＝3：1为抗粘剂，聚乙二醇：柠檬酸＝3：1为增塑剂，将上述囊材、抗粘剂和增塑剂加入纯化水，加热搅拌使溶解，配置成质量分数为33％的囊材溶液，冷却至室温，搅拌状态下加入荆防提取物细粉，加入制剂配方总量的1.18％蔗糖脂肪酸酯：大豆磷脂＝8∶5的复合乳化剂，均质乳化，得乳化液，备用；将乳化液进行喷雾干燥，收集微囊，冷却，即得。
药效实施例1荆防颗粒在体外抗丙型肝炎病毒效果比较
1.材料
实验药物：
荆防颗粒：由山东新时代药业有限公司提供，规格：每袋15g；
荆防败毒散加减：荆芥30g，防风30g，羌活25g，独活25g，柴胡25g，前胡25g，川芎20g，枳壳25g，茯苓45g，桔梗30g，甘草15g，连翘30g，薄荷30g，山楂60g，六曲60g。根据以上组方按照本领域常规的方法制备成颗粒剂。
2.实验方法
采用体外嵌合体丙肝病毒感染Huh7.5细胞考察各组的抗病毒作用。将荆防颗粒和荆防败毒散加减制备的颗粒剂采用二甲基亚砜DMSO配制成50mg/ml的母液备用，实验时根据实验需要稀释成相应的浓度，另将丙型肝炎病毒感染Huh7.5细胞正常传代培养，取对数生长期的Huh7.5细胞制成1×10 5个/ml的细胞悬液，在24孔培养皿中每孔加入500μl的细胞悬液，摇匀，放至37℃5％CO 2培养箱中，培养12h，将24孔培养皿中细胞上清液吸弃100μl，各组取100μl药液加入到对应浓度标记的细胞中，每个样品重复4个，摇匀，放入37℃5％CO 2中继续培养12h后，抽提丙肝病毒RNA，采用PCR扩增后设定病毒的量。结果见表1。
表1各组HCV-RNA在细胞中的相对表达量的比较
Figure PCTCN2022127836-appb-000001
Figure PCTCN2022127836-appb-000002
与正常对照组相比， **p＜0.01；与荆防败毒散加减组相比， #p＜0.05， ##p＜0.01；
由表1知，与正常对照组比较，各给药组HCV-RNA在细胞中的相对表达量明显降低，均有极显著统计学差异(p＜0.01)；与荆防败毒散加减组比较，荆防颗粒中、高剂量组HCV-RNA在细胞中的相对表达量明显降低，有显著或极显著统计学差异(p＜0.05或p＜0.01)。由此可知，荆防颗粒可明显降低HCV-RNA在细胞中的相对表达量，具有显著的体外抗丙型肝炎病毒的作用，效果优于荆防败毒散加减方。
药效实施例2荆防颗粒在鸭体内对丙型肝炎病毒感染的治疗效果
本发明采用国内外公认的实验模型，在丙型肝炎病毒感染的鸭体内进行实验。1.材料
实验药物：
荆防颗粒：由山东新时代药业有限公司提供，规格：每袋15g；
荆防败毒散加减组：荆芥30g，防风30g，羌活25g，独活25g，柴胡25g，前胡25g，川芎20g，枳壳25g，茯苓45g，桔梗30g，甘草15g，连翘30g，薄荷30g，山楂60g，六曲60g。根据以上组方按照本领域常规的方法制备成颗粒剂。2.实验方法
2.1.DHCV感染：48只雏鸭经胫静脉注射DHCV-DNA阳性鸭血清，每只0.2ml。在感染后7天取血，分离血清，-70℃保存待检。
2.2.药物治疗试验：DHCV感染1日龄北京鸭后随机分组，给药组分3个剂量灌胃给予市售荆防颗粒，分别为荆防颗粒低剂量组(1.4g/kg)、荆防颗粒中剂量组(2.8g/kg)、荆防颗粒高剂量组(5.6g/kg)，模型对照组，以生理盐水代替药物；荆防败毒散加减组给予荆防败毒散加减方制备的颗粒剂(5.6g/kg)，每天3次，连续给药7d。给药前、给药第3d、7d分别自鸭腿胫静脉取血，分离血清，于-70℃保存待检。
2.3.检测方法：取上述待检鸭血清，每批同时点膜，测定鸭血清中DHCV-DNA的动态水平。按Promega缺口翻译试剂盒说明书方法，用 32p标记DHCV-DNA探针，作鸭血清斑点杂交，放射自显影膜片斑点，用酶标检测仪测定OD值 (490nm)，计算血清DHCV-DNA密度，以杂交斑点OD值作为标本DHCV-DNA水平值。
2.4.药效计算：计算每组不同时间点血清DHCV-DNAOD值的平均值，计算DHCV-DNA抑制率，比较各组不同时间点的鸭血清DHCV-DNA抑制率。给药组与模型对照组比较，采用成组t检验。结果见表2。
DHCV-DNA抑制率＝(给药前OD值-给药后OD值)/给前OD值×100％。
表2荆防颗粒对DHCV感染鸭血清DHCV-DNA水平的影响
Figure PCTCN2022127836-appb-000003
Figure PCTCN2022127836-appb-000004
与模型对照组相比， *p＜0.05， **p＜0.01；与荆防败毒散加减组相比， #p＜0.05， ##p＜0.01..
由表2知，与模型对照组比较，荆防颗粒各剂量组感染鸭血清DHCV-DNA水平明显降低，均有极显著统计学差异(p＜0.01)；与荆防败毒散加减组比较，荆防颗粒中高剂量组感染鸭血清DHCV-DNA水平明显降低，有极显著统计学差异(p＜0.01)。以上结果说明，荆防颗粒可显著降低感染鸭血清DHCV-DNA水平，抑制鸭丙型肝炎病毒活性效果显著，优于荆防败毒散加减，可用于治疗丙型病毒性肝炎。
药效实施例3荆防颗粒在鸭体内对丙型肝炎病毒感染的治疗效果
采用药效实施例2相同的实验方法，验证荆防败毒散对DHCV感染鸭血清DHCV-DNA水平的影响。荆防败毒散组方：根据以下组方按照本领域常规的方法制备成颗粒剂。荆芥、防风、独活、茯苓、柴胡各10g，前胡、川芎、枳売、羌活、桔梗各6g，焦三仙15g，薄荷(后下)、甘草各3g。结果见表3。
表3荆防颗粒对DHCV感染鸭血清DHCV-DNA水平的影响
Figure PCTCN2022127836-appb-000005
Figure PCTCN2022127836-appb-000006
Figure PCTCN2022127836-appb-000007
与模型对照组相比， *p＜0.05， **p＜0.01；与荆防败毒散组相比， #p＜0.05， ##p＜0.01。
由表3知，与模型对照组比较，荆防颗粒各剂量组鸭血清DHCV-DNA水平明显降低，均有极显著统计学差异(p＜0.01)；与荆防败毒散组比较，荆防颗粒各剂量组鸭血清DHCV-DNA水平明显降低，有显著或极显著统计学差异(p＜0.05，p＜0.01)。以上结果说明，荆防颗粒明显降低感染鸭血清DHCV-DNA水平，抑制鸭丙型肝炎病毒活性效果显著，优于荆防败毒散，可用于治疗丙型病毒性肝炎。
本发明荆防制剂的其他剂型如荆防合剂、丸剂、片剂、糖浆剂、胶囊剂经动物实验验证，同样能明显降低HCV-RNA在细胞中的表达量，降低感染鸭血清DHCV-DNA水平，抑制丙型肝炎病毒活性效果显著，优于荆防败毒散和荆防败毒散加减，可用于治疗丙型病毒性肝炎。具体描述在此不再一一列举。

Claims (10)

  1. 荆防制剂在制备预防或治疗丙型病毒性肝炎药物中的医药用途。
  2. 根据权利要求1所述的用途，其特征在于，所述预防或治疗丙型病毒性肝炎是指抗丙型肝炎病毒。
  3. 根据权利要求2所述的用途，其特征在于，所述的抗丙型肝炎病毒是指抑制HCV-RNA在细胞中的表达。
  4. 根据权利要求2中所述的用途，其特征在于，所述抗丙型肝炎病毒是指体内降低HCV病毒感染的血清中DHCV-DNA的水平。
  5. 根据权利要求1-4任一项所述的用途，其特征在于，所述荆防制剂由以下成分制备而成：羌活、独活、茯苓、防风、荆芥、川芎、桔梗、柴胡、前胡、枳壳、甘草。
  6. 根据权利要求5所述的用途，其特征在于，所述荆防制剂成分可加入其他药学上可接受的辅料制备成临床上可接受的剂型。
  7. 据权利要求6所述的用途，其特征在于，所述临床上可接受的剂型为颗粒剂、口服溶液剂、合剂、丸剂、糖浆剂、胶囊剂、片剂。
  8. 根据权利要求7所述的用途，其特征在于，临床上可接受的剂型为颗粒剂或合剂。
  9. 根据权利要求1所述的用途，其特征在于，所述荆防制剂人用剂量为0.05g/kg/d-3.5g/kg/d。
  10. 根据权利要求9所述的用途，其特征在于，所述荆防制剂人用剂量为0.1g/kg/d-2.5g/kg/d。
PCT/CN2022/127836 2021-10-29 2022-10-27 荆防制剂在制备预防或治疗丙型病毒性肝炎的药物中的用途 WO2023072171A1 (zh)

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