WO2011130892A1 - Traditional chinese medicinal composition for treating influenza and preparation method and use thereof - Google Patents
Traditional chinese medicinal composition for treating influenza and preparation method and use thereof Download PDFInfo
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- WO2011130892A1 WO2011130892A1 PCT/CN2010/001734 CN2010001734W WO2011130892A1 WO 2011130892 A1 WO2011130892 A1 WO 2011130892A1 CN 2010001734 W CN2010001734 W CN 2010001734W WO 2011130892 A1 WO2011130892 A1 WO 2011130892A1
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
- A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
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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)
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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)
- A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
- A61K36/484—Glycyrrhiza (licorice)
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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)
- A61K36/57—Magnoliaceae (Magnolia family)
- A61K36/575—Magnolia
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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)
- A61K36/61—Myrtaceae (Myrtle family), e.g. teatree or eucalyptus
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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)
- A61K36/70—Polygonaceae (Buckwheat family), e.g. spineflower or dock
- A61K36/704—Polygonum, e.g. knotweed
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
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- 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
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- 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
- A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
Definitions
- the invention relates to a traditional Chinese medicine composition, a pharmaceutical preparation, a preparation method and application thereof for combating influenza, especially anti-cluform H1N1 influenza. Background technique
- Influenza A (H1N1) virus is a subtype of influenza virus and one of the most common influenza (flu) in humans. Some of the H1N1 strains cause seasonal pandemics. From the end of March to mid-April 2009, the outbreak of influenza A (H1N1) (formerly known as H1N1 swine flu) broke out in many countries in the Americas and spread to the world. According to the World Health Organization, as of August 23, 2009, there were 209,438 cases worldwide and at least 2,185 deaths.
- H1N1 flu vaccine According to reports, by the end of 2009, the production capacity of China's H1N1 flu vaccine can only cover about 5% of the country's population. Anti-influenza specific drugs (such as oseltamivir) have also been reported to be resistant to the H1N1 influenza virus worldwide. At the same time, the risk of influenza A (H1N1) flu is more than that of HIV. The mutated influenza A (H1N1) virus may be more toxic, and all existing vaccines and targeted drugs may fail.
- the invention combines traditional Chinese medicine theory with modern molecular biology and drug design methods, strictly derives anti-A type from the structural characteristics of the H1N1 influenza virus protein, using modern structural biology, bioinformatics, and chemical informatics.
- the pharmacophore of the H1N1 influenza virus molecule, and the molecular group of the active constituents of the traditional Chinese medicine anti- ⁇ H1N1 influenza virus are derived from the pharmacophores, and according to the molecular structure group, the world traditional medicine patent database and the traditional Chinese medicine structure are used.
- Chinese herbal medicine-prescription-activity-chemical composition comprehensive database deducing the Chinese herbal medicine group containing the molecular structure group, and based on the data of the Chinese herbal medicine group, deriving a new special response to the H1N1 from the database of Chinese herbal medicines.
- An object of the present invention is to provide an anti-influenza traditional Chinese medicine composition which adopts the following original
- the drug preparation is made up: 10-20 parts by weight of Astragalus, 20-60 parts by weight of Polygonum cuspidatum, 5-10 parts by weight of Magnolia, and 5-10 parts by weight of licorice.
- xanthine may be used in an amount of 12 to 18 parts by weight, for example, 12 to 16 parts by weight.
- the knotweed may be used in an amount of 20 to 50 parts by weight, for example, 24 to 45 parts by weight, particularly 25 to 40 parts by weight.
- the orchid may be used in an amount of 5 to 9 parts by weight, for example, 5 to 8 parts by weight, particularly 5 to 7 parts by weight.
- the licorice may be used in an amount of 5 to 9 parts by weight, for example, 5 to 8 parts by weight, particularly 5 to 7 parts by weight.
- the traditional Chinese medicine composition may further comprise 15-30 parts by weight, for example 18-25 parts by weight or 15-20 parts by weight, of Houttuynia cordata.
- a second object of the present invention is to provide a pharmaceutical preparation comprising the traditional Chinese medicine composition of the present invention or an active extract thereof and a pharmaceutically acceptable carrier.
- the preparation may be in various dosage forms for use in the pharmaceutical field, such as tablets, capsules, oral solutions and the like.
- a third object of the present invention is to provide a process for the preparation of the traditional Chinese medicine composition and pharmaceutical preparation.
- a fourth object of the present invention is to provide use of the above-mentioned traditional Chinese medicine composition or a pharmaceutical preparation thereof for the preparation of a medicament for preventing or treating influenza, particularly an anti-H1N1 influenza.
- Individuals here may include people, dogs, cats, horses, pigs or monkeys.
- the invention is based on the following prescription principles: the selection is reasonable, clinically effective, resource-rich, economical and practical, and easy to promote. Therefore, the types of Chinese herbal medicines used should be minimized. If influenza occurs, especially in the case of a large-scale epidemic of influenza A (H1N1), the invention can be widely spread nationwide, with effective economic and resource costs. The spread of the flu.
- the drug substance is a form widely used in the art, which can be produced by a method well known in the art or commercially available.
- Scutellaria baicalensis Georgi, Polygonum cuspidatum Sieb.et Eucc, Magnolia biondii, Radix glycyrrhiza, Houttuynia cordata Thumb can be used as a raw material for Chinese herbal medicines. form.
- the anti-influenza traditional Chinese medicine composition of the present invention can be prepared by a method well known in the art, for example, pulverizing each raw material into fine powder, mixing in proportion or mixing in proportion, and pulverizing into fine
- the powder may also be prepared by separately extracting the raw materials with a solvent and mixing them in proportion or mixing them in a ratio and then extracting them with a solvent, for example, preparing a filtrate, an extract or a dry powder.
- the solvent include water and/or ethanol. .
- the traditional Chinese medicine composition of the present invention can be further prepared into various clinically acceptable dosage forms together with a pharmaceutically acceptable carrier by a conventional method in the art, that is, by the pharmaceutical preparation of the present invention, for example, by combining the traditional Chinese medicine composition of the present invention.
- the medicinal carrier is mixed to prepare.
- the pharmaceutical preparation of the present invention can be prepared by pulverizing the raw material of the traditional Chinese medicine composition of the present invention into a powder, or extracting the raw material medicinal solvent in the traditional Chinese medicine composition of the present invention to obtain an active extract (for example, with water)
- an active extract for example, with water
- the drug substance is extracted in a ratio of 1 part of the drug substance to 10 parts of water, and then the powder or active extract is thoroughly mixed with a pharmaceutically acceptable carrier.
- the pharmaceutical preparations include, but are not limited to, pellets, oral liquids, granules, powders, capsules, tablets, dropping pills or decoctions.
- the tablet may comprise a coated tablet or a tablet.
- the traditional Chinese medicine composition of the invention not only conforms to the informatical analysis report of the authoritative database, but also conforms to the principle of Chinese medicine and the law of clinical efficacy.
- Astragalus membranaceus, Houttuynia cordata and Polygonum cuspidatum are high-frequency selective drugs provided by information retrieval.
- Magnolia sinensis has anti-allergic effects
- licorice has hormone-like effects, and it can clear lungs and relieve cough.
- pharmaceutical carriers include, but are not limited to, diluents, excipients (such as water, etc.); fillers (such as starch, sucrose, etc.); binders (such as cellulose derivatives, alginate, gelatin) Or polyvinylpyrrolidone); wetting agent (such as glycerin); disintegrant (such as agar, calcium carbonate or sodium bicarbonate); absorption enhancer (such as quaternary ammonium compound); surfactant (such as cetyl alcohol); absorption Carriers (such as kaolin and soap clay); lubricants (such as talc, calcium stearate or polyethylene glycol).
- other adjuvants such as flavoring agents, sweeteners such as sucrose, and the like may be added as needed.
- compositions of the present invention can be administered orally, nasally or parenterally, for use in patients in need of such treatment.
- oral administration it may be formulated into a conventional solid preparation such as a tablet, a powder, a granule, a capsule or the like, or a liquid preparation such as a water and oil suspension or other liquid preparation such as syrup or the like.
- parenteral administration it can be formulated into solutions for injection, water or oily suspensions, and the like.
- a preferred form is a tablet, capsule or injection.
- the pharmaceutical preparation of the present invention is prepared by the following method: 1) preparing various raw materials in the traditional Chinese medicine composition into extracts such as granules, or preparing two or more kinds of raw materials together An extract such as a granule; 2) optionally mixing the various extracts in proportion; 3) combining the mixture with a pharmaceutically acceptable carrier.
- the medicament of the present invention can be used for the prevention or treatment of various influenzas, including sputum H1N1 influenza.
- the invention provides a method of preventing or treating influenza, particularly type A
- a method of H1N1 influenza which comprises administering a pharmaceutical preparation of the present invention to a subject having or at risk of developing influenza, particularly influenza A H1N1, in a prophylactically or therapeutically effective amount.
- suitable amounts can be readily determined by one of ordinary skill in the art in accordance with conventional techniques, for example 0.22 g/kg body weight, preferably 0.44 g/kg body weight.
- “individual” includes various animals such as poultry, mammals, especially humans, dogs, cats, horses, pigs, monkeys and the like.
- administration includes any suitable route, such as oral administration, sublingual administration, nasal mucosal administration, intravenous administration, and the like. detailed description
- the anti-influenza composition of the present invention is embodied as follows:
- Influenza virus rat lung adaptation forest FM1 (H1N1 virus), provided by the Institute of Virology, Chinese Academy of Preventive Medicine. Chicken embryo passage, BSL-3 (Biosafety Laboratory Level 3) Laboratory test, sub-package, -80 °C preservation.
- mice weighing 20 - 22g 72 were purchased from Beijing Weitong Lihua Experimental Animal Technology Co., Ltd., and the animal room was kept under clean conditions.
- the experimental drugs were the drugs of Examples 1, 2 and 5.
- the positive control drug was a commercially available ribavirin (0.15 g once for adults, 3 times a day for 7 days).
- SFDA approved standard (Sichuan Baili Pharmaceutical lot: 081017).
- mice were randomly divided into 6 groups, namely, a blank control group, a virus infection group, a positive drug control (0.15 g once per adult, 3 times daily conversion), the drug of Example 1, the drug of Example 2, and the drug of Example 5.
- the drug (0.04 g/20 g mouse), the drugs of Examples 1 and 2 were ground before the experiment and the appropriate amount of distilled water was added to form a suspension, 10-12 per group.
- the administration was started by intragastric administration on the day before infection, 0.4 ml/mouse (O.lg drug substance/ml) once a day for 5 days.
- the blank control group and the virus-infected group were given an equal volume of distilled water.
- Animal Infected Virus After each mouse was lightly anesthetized with ether, nasal infection was carried out with the influenza virus mouse lung adaptation strain FM1. Except normal Except the control group, the other groups were infected with FM1, 50ul/only (10 LD50).
- the data is represented by f s s, and the data is processed using SAS software.
- Lung index value ⁇ lung weight / weight. The greater the lung index value, the more severe the pneumonia. The mean values of the lung indices of each group were determined and SD, and the differences between the groups were compared for statistical analysis.
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Abstract
A traditional Chinese medicinal composition for treating influenza, in especial influenza A (H1N1), and the preparation method and use thereof, said traditional Chinese medicinal composition is prepared by using Radix Scutellariae, Rhizoma Polygoni Cuspidati, Flos Magnoliae and Radix Glycyrrhizae. In addition to above described raw medicinal materials, the composition can also comprise Herba Houttuyniae as raw medicinal material.
Description
治疗流感的中药组合物及其制备方法和应用 技术领域 Traditional Chinese medicine composition for treating influenza, preparation method and application thereof
本发明涉及一种抗流感一一尤其是抗曱型 H1N1 流感一一的中药 组合物、 药物制剂、 其制备方法及应用。 背景技术 The invention relates to a traditional Chinese medicine composition, a pharmaceutical preparation, a preparation method and application thereof for combating influenza, especially anti-cluform H1N1 influenza. Background technique
甲型 H1N1流感病毒( Influenza A (H1N1) virus )是一种亚型流感 病毒, 也是人类最常见的流行性感冒 (流感)之一, 其中一些 H1N1 病毒株会引起季节性的大流行。 2009年 3月底至 4月中旬,甲型 H1N1 流感(以前称 H1N1 型猪流感)疫情在美洲多国陆续爆发, 随后蔓延全 球。据世界卫生组织报告,截至 2009年 8月 23日,全球已经有 209438 病例, 至少 2185人死亡。 Influenza A (H1N1) virus is a subtype of influenza virus and one of the most common influenza (flu) in humans. Some of the H1N1 strains cause seasonal pandemics. From the end of March to mid-April 2009, the outbreak of influenza A (H1N1) (formerly known as H1N1 swine flu) broke out in many countries in the Americas and spread to the world. According to the World Health Organization, as of August 23, 2009, there were 209,438 cases worldwide and at least 2,185 deaths.
据报道, 到 2009年年底我国曱型 H1N1流感疫苗的生产能力只能 覆盖全国约 5%的人口。 已经报道的抗流感特效药 (如奥斯它韦)也 在全球对甲型 H1N1流感病毒出现抗药性。 同时, 甲型 H1N1流感病 毒变异几率超过艾滋病病毒, 变异后的甲型 H1N1流感病毒的毒性可 能更大, 现有的疫苗和靶向药有可能全都失效。 According to reports, by the end of 2009, the production capacity of China's H1N1 flu vaccine can only cover about 5% of the country's population. Anti-influenza specific drugs (such as oseltamivir) have also been reported to be resistant to the H1N1 influenza virus worldwide. At the same time, the risk of influenza A (H1N1) flu is more than that of HIV. The mutated influenza A (H1N1) virus may be more toxic, and all existing vaccines and targeted drugs may fail.
因此,开发一种有效防治曱型 H1N1流感的新型药物变得重要而急 迫。 发明内容 Therefore, it has become important and urgent to develop a new type of drug that is effective in preventing and treating sputum-type H1N1 influenza. Summary of the invention
本发明将传统中医药理论与现代分子生物学和药物设计方法结合, 从曱型 H1N1流感病毒蛋白质的结构特点, 运用现代结构生物学、 生 物信息学、 化学信息学, 严格地推导出抗甲型 H1N1流感病毒分子的 药效团, 由此类药效团导出相应的中药抗曱型 H1N1流感病毒的活性 成分分子结构群组, 根据这种分子结构群组, 运用世界传统药物专利 数据库、 中药结构数据库、 中药药材-方剂-活性-化学成分综合数据库, 推导出含有分子结构群组的中药材組, 再根据这种中药材組数据, 从 海量的中药方剂数据库推导出新的专门应对甲型 H1N1流感病毒的中 药组合物。 这种组合物经过中医专家的分析, 完全符合中医的医理。 The invention combines traditional Chinese medicine theory with modern molecular biology and drug design methods, strictly derives anti-A type from the structural characteristics of the H1N1 influenza virus protein, using modern structural biology, bioinformatics, and chemical informatics. The pharmacophore of the H1N1 influenza virus molecule, and the molecular group of the active constituents of the traditional Chinese medicine anti-曱H1N1 influenza virus are derived from the pharmacophores, and according to the molecular structure group, the world traditional medicine patent database and the traditional Chinese medicine structure are used. Database, Chinese herbal medicine-prescription-activity-chemical composition comprehensive database, deducing the Chinese herbal medicine group containing the molecular structure group, and based on the data of the Chinese herbal medicine group, deriving a new special response to the H1N1 from the database of Chinese herbal medicines. Traditional Chinese medicine composition of influenza virus. This composition has been analyzed by Chinese medicine experts and is fully in line with the medical principles of Chinese medicine.
本发明的一个目的是提供了一种抗流感中药组合物,其采用下列原
料药制成: 黄芩 10-20重量份、 虎杖 20-60重量份、 辛夷花 5-10重量 份、 甘草 5-10重量份。 An object of the present invention is to provide an anti-influenza traditional Chinese medicine composition which adopts the following original The drug preparation is made up: 10-20 parts by weight of Astragalus, 20-60 parts by weight of Polygonum cuspidatum, 5-10 parts by weight of Magnolia, and 5-10 parts by weight of licorice.
在一个优选的方案中,黄芩的用量可以是 12-18重量份,例如 12-16 重量份。 In a preferred embodiment, xanthine may be used in an amount of 12 to 18 parts by weight, for example, 12 to 16 parts by weight.
在另一个优选的方案中, 虎杖的用量可以是 20-50 重量份, 例如 24-45重量份, 特别是 25-40重量份。 In another preferred embodiment, the knotweed may be used in an amount of 20 to 50 parts by weight, for example, 24 to 45 parts by weight, particularly 25 to 40 parts by weight.
在又一个优选的方案中,辛夷花的用量可以是 5-9重量份,例如 5-8 重量份, 特别是 5-7重量份。 In still another preferred embodiment, the orchid may be used in an amount of 5 to 9 parts by weight, for example, 5 to 8 parts by weight, particularly 5 to 7 parts by weight.
在又一个优选的方案中, 甘草的用量可以是 5-9重量份, 例如 5-8 重量份, 特别是 5-7重量份。 In still another preferred embodiment, the licorice may be used in an amount of 5 to 9 parts by weight, for example, 5 to 8 parts by weight, particularly 5 to 7 parts by weight.
更为优选地, 该中药组合物中还可包含鱼腥草 15-30重量份, 例如 18-25重量份或 15-20重量份。 More preferably, the traditional Chinese medicine composition may further comprise 15-30 parts by weight, for example 18-25 parts by weight or 15-20 parts by weight, of Houttuynia cordata.
本发明的第二个目的是提供了一种药物制剂,其包含本发明的中药 组合物或其活性提取物和可药用栽体。 该制剂可以是药学领域中应用 的各种剂型, 例如片剂、 胶嚢、 口服液等。 A second object of the present invention is to provide a pharmaceutical preparation comprising the traditional Chinese medicine composition of the present invention or an active extract thereof and a pharmaceutically acceptable carrier. The preparation may be in various dosage forms for use in the pharmaceutical field, such as tablets, capsules, oral solutions and the like.
本发明的第三个目的是提供了所述中药组合物和药物制剂的制备 方法。 A third object of the present invention is to provide a process for the preparation of the traditional Chinese medicine composition and pharmaceutical preparation.
本发明的第四个目的是提供所述中药组合物或其药物制剂在制备 预防或者治疗个体流感, 特别是抗曱型 H1N1流感药物中的应用。 这 里的个体可包括人、 狗、 猫、 马、 猪或猴。 A fourth object of the present invention is to provide use of the above-mentioned traditional Chinese medicine composition or a pharmaceutical preparation thereof for the preparation of a medicament for preventing or treating influenza, particularly an anti-H1N1 influenza. Individuals here may include people, dogs, cats, horses, pigs or monkeys.
本发明依据下述处方原则: 选方有理、 临床有效、 资源丰富、 经济 实用、 便于推广。 因此, 尽量减少所使用的中药材的种类, 如果发生 流感, 尤其是甲型 H1N1流感大规模流行的情况下, 本发明能够在全 国范围内普及, 以最小的经济代价和资源代价, 有效地防治流感的蔓 延。 The invention is based on the following prescription principles: the selection is reasonable, clinically effective, resource-rich, economical and practical, and easy to promote. Therefore, the types of Chinese herbal medicines used should be minimized. If influenza occurs, especially in the case of a large-scale epidemic of influenza A (H1N1), the invention can be widely spread nationwide, with effective economic and resource costs. The spread of the flu.
在本发明中,原料药是本领域内广泛采用的形式,其可通过本领域 内熟知的方法生产或通过商业途径获得。 例如, 黄芩 ( Scutellaria baicalensis Georgi ),虎杖 ( Polygonum cuspidatum Sieb.et Eucc ),辛夷 花 ( Magnolia biondii ),廿草 ( Radix glycyrrhiza ) , 鱼腹草 ( Houttuynia cordata Thumb )可为其作为原料中药材通常使用的形式。 In the present invention, the drug substance is a form widely used in the art, which can be produced by a method well known in the art or commercially available. For example, Scutellaria baicalensis Georgi, Polygonum cuspidatum Sieb.et Eucc, Magnolia biondii, Radix glycyrrhiza, Houttuynia cordata Thumb can be used as a raw material for Chinese herbal medicines. form.
本发明的抗流感中药組合物可以采用本领域内熟知的方法制备,例 如将各原料药粉碎成细粉后按比例混合或者按比例混合后粉碎成细
粉, 也可以将各原料药分别采用溶剂进行提取并按比例混合或者按比 例混合后采用溶剂进行提取来制备, 例如制成滤液、浸膏或者干膏粉, 溶剂的例子包括水和 /或乙醇。 The anti-influenza traditional Chinese medicine composition of the present invention can be prepared by a method well known in the art, for example, pulverizing each raw material into fine powder, mixing in proportion or mixing in proportion, and pulverizing into fine The powder may also be prepared by separately extracting the raw materials with a solvent and mixing them in proportion or mixing them in a ratio and then extracting them with a solvent, for example, preparing a filtrate, an extract or a dry powder. Examples of the solvent include water and/or ethanol. .
在此基础上可以进一步采用本领域常规方法将本发明中药组合物 与可药用载体一起制成各种临床可接受的剂型,即本发明的药物制剂, 例如通过将本发明中药组合物与可药用栽体混合来制备。 优选地, 本 发明的药物制剂可通过如下方法制备: 将本发明的中药组合物的原料 药粉碎成粉末, 或将本发明中药组合物中原料药用溶剂提取得到活性 提取物(例如, 以水为溶剂, 按照 1份原料药 10份水的比例提取所述 原料药), 然后将所述粉末或活性提取物与一种可药用栽体充分混合。 所述药物制剂包括但不限于: 微丸、 口服液、 颗粒剂、 散剂、 胶嚢、 片剂、 滴丸或者汤剂。 所述片剂可包括包衣片或者含片。 On the basis of this, the traditional Chinese medicine composition of the present invention can be further prepared into various clinically acceptable dosage forms together with a pharmaceutically acceptable carrier by a conventional method in the art, that is, by the pharmaceutical preparation of the present invention, for example, by combining the traditional Chinese medicine composition of the present invention. The medicinal carrier is mixed to prepare. Preferably, the pharmaceutical preparation of the present invention can be prepared by pulverizing the raw material of the traditional Chinese medicine composition of the present invention into a powder, or extracting the raw material medicinal solvent in the traditional Chinese medicine composition of the present invention to obtain an active extract (for example, with water) For the solvent, the drug substance is extracted in a ratio of 1 part of the drug substance to 10 parts of water, and then the powder or active extract is thoroughly mixed with a pharmaceutically acceptable carrier. The pharmaceutical preparations include, but are not limited to, pellets, oral liquids, granules, powders, capsules, tablets, dropping pills or decoctions. The tablet may comprise a coated tablet or a tablet.
本发明中药组合物既符合权威数据库信息学分析报告,又符合中医 原理和临床疗效规律。 黄芩、 鱼腥草、 虎杖是信息检索提供的高频优 选药, 辛夷花抗过敏, 甘草有激素样作用, 又能清肺止咳。 The traditional Chinese medicine composition of the invention not only conforms to the informatical analysis report of the authoritative database, but also conforms to the principle of Chinese medicine and the law of clinical efficacy. Astragalus membranaceus, Houttuynia cordata and Polygonum cuspidatum are high-frequency selective drugs provided by information retrieval. Magnolia sinensis has anti-allergic effects, licorice has hormone-like effects, and it can clear lungs and relieve cough.
在本发明中, 药用载体包括但不限于: 稀释剂、赋形剂(如水等)'; 填充剂 (如淀粉、 蔗糖等) ; 粘合剂 (如纤维素衍生物、 藻酸盐、 明 胶或聚乙烯吡咯烷酮) ; 湿润剂 (如甘油) ; 崩解剂 (如琼脂、 碳酸 钙或碳酸氢钠) ; 吸收促进剂 (如季铵化合物) ; 表面活性剂 (如十 六烷醇) ; 吸收载体(如高岭土和皂黏土) ; 润滑剂 (如滑石粉、 硬 脂酸钙或聚乙二醇等)。此外还可以根据需要加入其它辅剂如香味剂、 甜味剂 (如蔗糖) 等。 In the present invention, pharmaceutical carriers include, but are not limited to, diluents, excipients (such as water, etc.); fillers (such as starch, sucrose, etc.); binders (such as cellulose derivatives, alginate, gelatin) Or polyvinylpyrrolidone); wetting agent (such as glycerin); disintegrant (such as agar, calcium carbonate or sodium bicarbonate); absorption enhancer (such as quaternary ammonium compound); surfactant (such as cetyl alcohol); absorption Carriers (such as kaolin and soap clay); lubricants (such as talc, calcium stearate or polyethylene glycol). In addition, other adjuvants such as flavoring agents, sweeteners such as sucrose, and the like may be added as needed.
本发明的组合物可以通过口服、鼻吸入或肠胃外的方式给药, 以便 适用于需要这种治疗的患者。 用于口服时, 可将其制成常规的固体制 剂如片剂、 粉剂、 颗粒剂、 胶嚢等, 或者制成液体制剂如水和油混悬 剂或其它液体制剂如糖浆等。 用于肠胃外给药时候, 可将其制成注射 用的溶液、 水或油性混悬剂等。 优选的形式是片剂、 胶囊或注射剂。 The compositions of the present invention can be administered orally, nasally or parenterally, for use in patients in need of such treatment. For oral administration, it may be formulated into a conventional solid preparation such as a tablet, a powder, a granule, a capsule or the like, or a liquid preparation such as a water and oil suspension or other liquid preparation such as syrup or the like. For parenteral administration, it can be formulated into solutions for injection, water or oily suspensions, and the like. A preferred form is a tablet, capsule or injection.
在一个实施方案中, 本发明药物制剂通过以下方法制备: 1 )将所 述中药組合物中的各种原料药分别制成提取物如颗粒, 或者将其中的 两种或多种原料药一起制成提取物如颗粒; 2 )任选地按比例混合各种 提取物; 3 )将所述混合物与可药用载体相组合。 In one embodiment, the pharmaceutical preparation of the present invention is prepared by the following method: 1) preparing various raw materials in the traditional Chinese medicine composition into extracts such as granules, or preparing two or more kinds of raw materials together An extract such as a granule; 2) optionally mixing the various extracts in proportion; 3) combining the mixture with a pharmaceutically acceptable carrier.
本发明的药物可用于预防或治疗各种流感, 包括曱型 H1N1流感。
在一个实施方案中, 本发明提供了一种预防或治疗流感、 尤其是甲型The medicament of the present invention can be used for the prevention or treatment of various influenzas, including sputum H1N1 influenza. In one embodiment, the invention provides a method of preventing or treating influenza, particularly type A
H1N1 流感的方法, 其中包括以预防或治疗有效量对患有或有风险患 流感、 尤其是甲型 H1N1流感的个体施用本发明的药物制剂。 合适的 用量是本领域普通技术人员根据常规技术可以容易确定的, 例如 0.22 克 /千克体重, 优选 0.44克 /千克体重。 在本发明中, "个体 "包括各种 动物, 例如禽类、 哺乳类, 尤其是人、 狗、 猫、 马、 猪、 猴等。 在本 发明中, "施用 "包括任何合适的途径, 例如口服给药、 舌下给药、 鼻 黏膜给药、 静脉注射给药等。 具体实施方式 A method of H1N1 influenza, which comprises administering a pharmaceutical preparation of the present invention to a subject having or at risk of developing influenza, particularly influenza A H1N1, in a prophylactically or therapeutically effective amount. Suitable amounts can be readily determined by one of ordinary skill in the art in accordance with conventional techniques, for example 0.22 g/kg body weight, preferably 0.44 g/kg body weight. In the present invention, "individual" includes various animals such as poultry, mammals, especially humans, dogs, cats, horses, pigs, monkeys and the like. In the present invention, "administration" includes any suitable route, such as oral administration, sublingual administration, nasal mucosal administration, intravenous administration, and the like. detailed description
本发明抗流感组合物实施例如下: The anti-influenza composition of the present invention is embodied as follows:
1) 按以上表格中所示重量份换算的量称取鱼腥草, 适当粉碎, 过 筛, 置于挥发油提取装置中, 加 10倍量水, 温浸 0.5 h后, 加热, 水 蒸汽蒸馏, 4h后收集馏出液。 馏出液用***萃取 3次, 萃取液加无水 硫酸钠干燥 24h后过滤, 滤液用旋转蒸发仪挥去***, 收集挥发油, 挥发油呈现淡黄绿色。残渣再煎煮两次,每次加 5倍量的水, 煎煮 lh, 过滤, 滤液合并备用, 残渣弃去。 1) Weigh the houttuynia according to the amount shown in the above table, smash it properly, sieve it, place it in the volatile oil extraction device, add 10 times of water, immerse for 0.5 h, heat, steam distillation, The distillate was collected after 4 h. The distillate was extracted with diethyl ether three times. The extract was dried over anhydrous sodium sulfate and filtered for 24h, then filtered and evaporated. The residue is further boiled twice, each time adding 5 times the amount of water, boiling for lh, filtering, and the filtrate is combined for use, and the residue is discarded.
2) 按以上表格中所示重量份换算的量称取黄芩、 虎杖、 辛夷花和 甘草。 适当粉碎, 过筛, 加水煎煮 2次, 每次加 5倍量水, 每次煎煮 2h, 提取液过滤, 合并滤液, 同时加入鱼腥草提取挥发油后的水溶液, 浓缩至 10g药材 /ml, 加入 95%乙醇, 边加边搅拌, 至醇浓度 80%, 冷藏放置 24小时, 过滤, 滤液回收乙醇至无醇味, 然后喷雾干燥, 鱼 腥草挥发油加入适量乙醇溶解, 喷入细粉中, 混和均匀, 即得干膏粉,
出膏率控制在 5%。 2) Weigh the amount of scutellaria, Polygonum cuspidatum, Magnolia and licorice according to the amount of weight shown in the table above. Properly smash, sift, add water to cook twice, add 5 times the amount of water each time, decoct for 2 h each time, filter the extract, combine the filtrate, add the aqueous solution of the volatile oil after the extract of Houttuynia cordata, concentrate to 10 g of medicinal material/ml Add 95% ethanol, stir while stirring, to 80% alcohol concentration, refrigerate for 24 hours, filter, recover the ethanol from the filtrate to a non-alcoholic taste, then spray dry, add the appropriate amount of ethanol to the volatile oil of Houttuynia cordata, and spray it into the fine powder. , mixing evenly, that is, getting dry powder, The creaming rate is controlled at 5%.
3) 制剂工艺: 干膏粉 1.5重量份, 淀粉 1重量份。 将干膏粉和淀 粉混和均匀, 加入 85%乙醇制粒, 60-65。C烘干, 用 16目筛网整粒。 实施例 5的制备方法: 3) Formulation process: 1.5 parts by weight of dry powder, 1 part by weight of starch. The dry powder and the starch were mixed uniformly, and granulated with 85% ethanol, 60-65. C is dried and sized with a 16 mesh screen. Preparation method of Example 5:
1) 按以上表格中所示重量份换算的量称取黄芩、 虎杖、 辛夷花和 甘草。 适当粉碎, 过筛, 加 10倍量水, 煎煮 2次, 每次 2h, 提取液 过滤, 合并滤液, 每毫升相当于 0.1克原料药。 1) Weigh the scutellaria, Polygonum cuspidatum, Magnolia and Licorice according to the amount of weight indicated in the table above. Properly smash, sift, add 10 times the amount of water, decoct 2 times, each time 2h, extract the filtrate, combine the filtrate, equivalent to 0.1 gram of drug substance per ml.
3) 制剂工艺: 在合并的滤液中加入适量的蔗糖, 然后分装, 每瓶 10毫升, 即得口服制剂。 应用实施例 3) Formulation process: An appropriate amount of sucrose is added to the combined filtrate, and then dispensed, 10 ml per bottle, to obtain an oral preparation. Application example
一、 材料与方法 I. Materials and methods
1、 病毒 1, the virus
流感病毒鼠肺适应林 FM1 (甲型 H1N1病毒) , 由中国预防医学 科学院病毒学研究所提供。 鸡胚传代, BSL-3 (生物安全实验室三级) 实验室内检测, 分装, -80°C保存。 Influenza virus rat lung adaptation forest FM1 (H1N1 virus), provided by the Institute of Virology, Chinese Academy of Preventive Medicine. Chicken embryo passage, BSL-3 (Biosafety Laboratory Level 3) Laboratory test, sub-package, -80 °C preservation.
2、 实验动物 2, experimental animals
BALB/c小鼠体重 20 - 22g 72只,购自北京维通利华实验动物技术 有限公司, 本所动物室清洁级条件下饲养。 BALB/c mice weighing 20 - 22g 72 were purchased from Beijing Weitong Lihua Experimental Animal Technology Co., Ltd., and the animal room was kept under clean conditions.
3、 实验药物 3, experimental drugs
实验用药为实施例 1、 2和 5的药物。 阳性对照药为市售的利巴韦 林(成人一次 0.15g, 一日 3次, 连用 7天) SFDA认可标准(四川百 利药业 lot:081017 ) 。 The experimental drugs were the drugs of Examples 1, 2 and 5. The positive control drug was a commercially available ribavirin (0.15 g once for adults, 3 times a day for 7 days). SFDA approved standard (Sichuan Baili Pharmaceutical lot: 081017).
4、 实验方法 4, the experimental method
将小鼠随机分为 6组即空白对照組、 病毒感染组、 阳性药对照(按 照成人一次 0.15g, —日 3次换算)、 实施例 1的药物、 实施例 2的药 物和实施例 5的药物(0.04g/20g小鼠) , 实施例 1和 2的药物实验前 需研碎并加适量蒸馏水成混悬液, 每组 10-12只。 感染前一天开始灌 胃给药, 0.4ml/只 (O.lg原料药 /ml ) , 1次 /天, 连续给药 5天。 空白 对照组、 病毒感染组给予等体积蒸馏水。 动物感染病毒: 每只小鼠经 ***轻度麻醉后, 用流感病毒鼠肺适应株 FM1进行滴鼻感染。 除正常
对照组以外, 其余各组均感染 FM1 , 50ul/只 (10个 LD50 ) 。 The mice were randomly divided into 6 groups, namely, a blank control group, a virus infection group, a positive drug control (0.15 g once per adult, 3 times daily conversion), the drug of Example 1, the drug of Example 2, and the drug of Example 5. The drug (0.04 g/20 g mouse), the drugs of Examples 1 and 2 were ground before the experiment and the appropriate amount of distilled water was added to form a suspension, 10-12 per group. The administration was started by intragastric administration on the day before infection, 0.4 ml/mouse (O.lg drug substance/ml) once a day for 5 days. The blank control group and the virus-infected group were given an equal volume of distilled water. Animal Infected Virus: After each mouse was lightly anesthetized with ether, nasal infection was carried out with the influenza virus mouse lung adaptation strain FM1. Except normal Except the control group, the other groups were infected with FM1, 50ul/only (10 LD50).
给药的第 5天后, 小鼠称体重后,进行轻度麻醉,放血,取肺组织, 称重。 计算肺指数(肺指数值 =100x肺重 /体重, SFDA公布公式) 。 进行统计学处理, 比较各組肺指数的差异。 After the fifth day of administration, after the mice were weighed, mild anesthesia was performed, blood was taken, lung tissue was taken, and weighed. Calculate the lung index (pulmonary index value = 100 x lung weight / body weight, SFDA published formula). Statistical analysis was performed to compare the differences in lung index between the groups.
5、 数据处理与统计方法 5, data processing and statistical methods
数据用 f 士 s表示, 采用 SAS软件处理数据。 The data is represented by f s s, and the data is processed using SAS software.
二、 实验结果 Second, the experimental results
1.各组肺指数实验数据 1. Experimental data of lung index of each group
表 1 各实验组肺指数数据 组别 肺指数 Table 1 Pulmonary index data of each experimental group Group lung index
空白对照 0.5971 0.7030 0.6256 0.6226 0.6000 0.5971 0.7059 0.6923 0.8788 0.7419 0.7561 0.5805 病毒感染 1.6767 1.2886 1.3264 1.3169 1.5528 1.6772 1.5S02 1.9615 1.7188 1.4274 - 利巴韦林 0.8896 0.9416 0.9268 0.687S 0.8662 0.8305 0.9528 1.0662 0.9078 1.0000 0.8929 0.9306 实旄例 2 1.9653 1.2878 1.2980 1.3605 0.8742 1.5986 1.0000 1.3203 1.6290 1.6260 1.0952 0.9793 实施例 1 1.4493 1.3784 1.2914 1.4000 1.6689 0.9627 0.9448 1.4109 1.5167 1.1111 1.0873 1.0373 实施例 5 1.2566 1.4207 1.4375 1.5643 1.0920 1.1216 0.8369 1.6195 . 1.5537 1.5000 1.1060 1.0543 Blank control 0.5971 0.7030 0.6256 0.6226 0.6000 0.5971 0.7059 0.6923 0.8788 0.7419 0.7561 0.5805 Virus infection 1.6767 1.2886 1.3264 1.3169 1.5528 1.6772 1.5S02 1.9615 1.7188 1.4274 - Ribavirin 0.8896 0.9416 0.9268 0.687S 0.8662 0.8305 0.9528 1.0662 0.9078 1.0000 0.8929 0.9306 Example 2 1.9653 1.2878 1.2980 1.3605 0.8742 1.5986 1.0000 1.3203 1.6290 1.6260 1.0952 0.9793 Example 1 1.4493 1.3784 1.2914 1.4000 1.6689 0.9627 0.9448 1.4109 1.5167 1.1111 1.0873 1.0373 Example 5 1.2566 1.4207 1.4375 1.5643 1.0920 1.1216 0.8369 1.6195 . 1.5537 1.5000 1.1060 1.0543
2. 各组之间统计学分析 2. Statistical analysis between groups
肺指数值 =ιοοχ肺重 /体重。 肺指数值越大, 表示肺炎越严重。 求出 各组肺指数的均值与 SD, 比较组间差异, 进行统计分析。 Lung index value = ιοοχ lung weight / weight. The greater the lung index value, the more severe the pneumonia. The mean values of the lung indices of each group were determined and SD, and the differences between the groups were compared for statistical analysis.
表 2 药物对 H1N1小鼠流感的防治作用 Table 2 Prevention and treatment of drugs against H1N1 mouse influenza
组 别 N 肺指数 (JC±5rf) P 值 空白对照 12 0.6751±0.0861 Group N lung index (JC±5rf) P value blank control 12 0.6751±0.0861
病毒感乘 10 1.5527±0.2157 < 0.01 Λ 利巴韦林 12 0.9077±0.0926 < 0.01 Α 实施例 2 12 1.3062±0.3235 < 0.01 Α 实施例 1 12 1.2716±0.2362 < 0.01 Α 实施例 5 11 1.3417±0.3765 <0·05Α 注: ▲与病毒感染组比较, △与正常对照组比较 表 1和 2的实验结果显示,本发明的药物对 H1N1流感呈现一定的 量效特征, 表明具有防治作用; 另外也表明本发明包含鱼腥草的药物 治疗效果更好, 是优选的方案。
Viral sensation by 10 1.5527 ± 0.2157 < 0.01 Λ ribavirin 12 0.9077 ± 0.0926 < 0.01 Α Example 2 12 1.3062 ± 0.3235 < 0.01 Α Example 1 12 1.2716 ± 0.2362 < 0.01 Α Example 5 11 1.3417 ± 0.3765 <0 · 05 Α Note: ▲ viral infection group, △ normal control group table 1 and the results of experiment 2 showed that the drug of the present invention on H1N1 influenza showed some dose-response characteristics shown to have preventive and therapeutic effects; There is also show that the The invention has a better therapeutic effect on the treatment of Houttuynia cordata, and is a preferred solution.
Claims
1. 一种抗流感中药组合物, 其是采用下列原料药制成: 黄芩 10-20 重量份、 虎杖 20-60重量、 辛夷花 5-10重量份、 甘草 5-10重量份。 An anti-influenza traditional Chinese medicine composition which is prepared by the following raw materials: 10-20 parts by weight of Astragalus, 20-60 parts of Polygonum cuspidatum, 5-10 parts by weight of Magnolia, and 5-10 parts by weight of licorice.
2. 权利要求 1所述的中药组合物, 其中原料药还包括鱼腥草 15-30 重量份。 2. The traditional Chinese medicine composition according to claim 1, wherein the raw material medicine further comprises 15-30 parts by weight of Houttuynia cordata.
3. 权利要求 1或 2的中药组合物, 其中黄芩为 12-18重量份。 3. The traditional Chinese medicine composition according to claim 1 or 2, wherein the xanthine is 12-18 parts by weight.
4. 权利要求 3的中药组合物, 其中黄芩为 12-16重量份。 4. The traditional Chinese medicine composition of claim 3, wherein the xanthine is 12-16 parts by weight.
5. 权利要求 1或 2的中药组合物, 其中虎杖为 20-50重量份。 The traditional Chinese medicine composition according to claim 1 or 2, wherein the knotweed is 20-50 parts by weight.
6. 权利要求 5的中药组合物, 其中虎杖为 24-45重量份。 6. The traditional Chinese medicine composition of claim 5, wherein the knotweed is 24-45 parts by weight.
7. 权利要求 1或 2的中药组合物, 其中辛夷花为 5-9重量份。 The traditional Chinese medicine composition according to claim 1 or 2, wherein the orchid is 5-9 parts by weight.
8. 权利要求 7的中药组令物, 其中辛夷花为 5-8重量份。 8. The traditional Chinese medicine composition of claim 7, wherein the magnolia flower is 5-8 parts by weight.
9. 权利要求 1或 2的中药组合物, 其中甘草为 5-9重量份 9. The traditional Chinese medicine composition according to claim 1 or 2, wherein the licorice is 5-9 parts by weight
10. 权利要求 9的中药组合物, 其中甘草为 5-8重量份。 10. The traditional Chinese medicine composition of claim 9, wherein the licorice is 5-8 parts by weight.
11. 权利要求 2的中药组合物, 其中所述鱼腥草为 18-25重量份。 11. The traditional Chinese medicine composition of claim 2, wherein the Houttuynia cordata is 18-25 parts by weight.
12. 一种药物制剂, 其包含权利要求 1-11任一项的中药组合物和一 种可药用栽体。 A pharmaceutical preparation comprising the traditional Chinese medicine composition according to any one of claims 1 to 11 and a pharmaceutically acceptable carrier.
13. 权利要求 12的药物制剂, 所述制剂为微丸、 口服液、 颗粒剂、 散剂、 胶嚢、 片剂、 滴丸或汤剂形式。 13. The pharmaceutical preparation according to claim 12, which is in the form of a pellet, an oral solution, a granule, a powder, a capsule, a tablet, a dropping pill or a decoction.
14. 权利要求 13的药物制剂, 其中所述片剂为包衣片或含片。 14. The pharmaceutical preparation according to claim 13, wherein the tablet is a coated tablet or a tablet.
15. 一种制备权利要求 12的药物制剂的方法, 其特征在于: 将权利 要求 1-11任一项的中药组合物的原料药粉碎成粉末或将权利要求 1-11 任一项的中药组合物的原料药用溶剂提取得到活性提取物, 然后将所 述粉末或活性提取物与一种可药用载体充分混合。 A method of preparing the pharmaceutical preparation according to claim 12, characterized in that the raw material of the traditional Chinese medicine composition according to any one of claims 1 to 11 is pulverized into a powder or the combination of the traditional Chinese medicine according to any one of claims 1 to 11. The raw material pharmaceutically acceptable solvent is extracted to obtain an active extract, and then the powder or active extract is thoroughly mixed with a pharmaceutically acceptable carrier.
16. 权利要求 15的方法, 其中采用水作为溶剂, 按照 1份原料药 10份水的比例提取所述原料药而制备活性提取物。 The method according to claim 15, wherein the active drug is prepared by extracting the drug substance in a ratio of 1 part of the drug substance to 10 parts of water using water as a solvent.
17. 权利要求 1-11任一项的中药组合物或权利要求 12-14任一项的 药物制剂在制备预防或治疗个体流感的药物中的应用。 17. Use of a traditional Chinese medicine composition according to any one of claims 1 to 11 or a pharmaceutical preparation according to any one of claims 12 to 14 for the preparation of a medicament for preventing or treating influenza in a subject.
18. 权利要求 17的应用, 其中所述流感为甲型 H1N1流感。 18. The use of claim 17, wherein the influenza is influenza A H1N1.
19. 权利要求 17或 18的应用, 其中所述个体是人、 狗、 猫、 马、 猪或猴。 19. The use of claim 17 or 18, wherein the individual is a human, a dog, a cat, a horse, a pig or a monkey.
Applications Claiming Priority (2)
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CN2010101542184A CN101791338B (en) | 2010-04-23 | 2010-04-23 | Medicament for resisting influenza and preparation method and application thereof |
CN201010154218.4 | 2010-04-23 |
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WO2011130892A1 true WO2011130892A1 (en) | 2011-10-27 |
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PCT/CN2010/001734 WO2011130892A1 (en) | 2010-04-23 | 2010-11-01 | Traditional chinese medicinal composition for treating influenza and preparation method and use thereof |
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EP4293141A1 (en) | 2022-06-13 | 2023-12-20 | Dubai Aluminium PJSC | Anode servicing assembly for an aluminium electrolysis plant, and methods for operating the same |
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US20120231097A1 (en) * | 2009-11-26 | 2012-09-13 | James Zhou | Medicinal composition and usage |
CN101791338B (en) * | 2010-04-23 | 2012-04-25 | 苏州东方楷模医药科技有限公司 | Medicament for resisting influenza and preparation method and application thereof |
CN103191291B (en) * | 2013-04-09 | 2014-09-03 | 王金磊 | Traditional Chinese medicine composition for treating viral myocarditis |
Citations (2)
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CN1589857A (en) * | 2003-08-30 | 2005-03-09 | 昆明滇虹药业有限公司 | Nose drops agent for treating common cold and its preparation method |
CN101791338A (en) * | 2010-04-23 | 2010-08-04 | 苏州东方楷模医药科技有限公司 | Medicament for resisting influenza and preparation method and application thereof |
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CN1048176C (en) * | 1995-07-31 | 2000-01-12 | 李俊华 | Face-nurishing acne-diminishing capsule |
CN1167445C (en) * | 2001-08-15 | 2004-09-22 | 李咸珠 | Chinese medicine for treating rhinitis and nasosinusitis |
CN1589852A (en) * | 2003-08-28 | 2005-03-09 | 昆明滇虹药业有限公司 | External use nose drop agent for treating common cold and its preparation method |
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CN1589857A (en) * | 2003-08-30 | 2005-03-09 | 昆明滇虹药业有限公司 | Nose drops agent for treating common cold and its preparation method |
CN101791338A (en) * | 2010-04-23 | 2010-08-04 | 苏州东方楷模医药科技有限公司 | Medicament for resisting influenza and preparation method and application thereof |
Cited By (1)
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EP4293141A1 (en) | 2022-06-13 | 2023-12-20 | Dubai Aluminium PJSC | Anode servicing assembly for an aluminium electrolysis plant, and methods for operating the same |
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CN101791338B (en) | 2012-04-25 |
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