WO2010096987A1 - Use of patchouli alcohol in medicament preparation - Google Patents

Use of patchouli alcohol in medicament preparation Download PDF

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Publication number
WO2010096987A1
WO2010096987A1 PCT/CN2009/074811 CN2009074811W WO2010096987A1 WO 2010096987 A1 WO2010096987 A1 WO 2010096987A1 CN 2009074811 W CN2009074811 W CN 2009074811W WO 2010096987 A1 WO2010096987 A1 WO 2010096987A1
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Prior art keywords
influenza
patchouli
alcohol
virus
preparation
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PCT/CN2009/074811
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French (fr)
Chinese (zh)
Inventor
赖小平
苏子仁
张奉学
彭绍忠
胡家敏
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东莞广州中医药大学中医药数理工程研究院
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Publication of WO2010096987A1 publication Critical patent/WO2010096987A1/en

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/53Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/045Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12Antivirals
    • A61P31/14Antivirals for RNA viruses
    • A61P31/16Antivirals for RNA viruses for influenza or rhinoviruses

Definitions

  • the invention relates to the use of patchouli carbon dioxide supercritical extract, patchouli oil or baicaleol in the preparation of medicaments, and belongs to the field of medicine. Background technique
  • Patchouli Pogostemon cabl in (Blanco) Benth., also known as sorrel, musk, is a genus of the genus Labia, a perennial herb, used in whole herbs. It is native to subtropical regions such as Asia and the Philippines. China mainly produces Guangdong and Hainan. Its taste, tenderness, spleen, stomach, lungs. It has aroma, turbidity, appetizing and vomiting, and publishes heat-removing effects, etc. It is mostly used for wet turbidity, vomiting, vomiting, stagnation, chest tightness, cold and dampness, abdominal pain, vomiting and diarrhea, and nasal pain.
  • the medicinal ingredient of patchouli is mainly its volatile oil, which is called patchouli oil.
  • Patchouli oil promotes gastric juice secretion, enhances digestive function, and relieves gastric mucosal muscles and antibacterial effects.
  • patchouli oil The main ingredient of patchouli oil is patchoul alcohol, which is about 52% 57%. It is a tricyclic sesquiterpenoid compound with a molecular formula of C 15 H 26 0 and a molecular weight of 222. 37.
  • the chemical name is (1R-(lalpha, 4beta, 4aalpha, 6beta, 8aalpha) ) - octahydro-4, 8a, 9 9_tetramethyl_l 6- meth 1-1 (2H) -naphthol , and its structural formula is shown below:
  • Influenza is an acute respiratory infection caused by influenza virus. It is a highly infectious and fast-transmitting disease. It is mainly transmitted by droplets in the air, or by contact.
  • Human influenza viruses are classified into three types: A, B, and C. Their antigenicity and virulence are highly susceptible to mutation, especially the type A virus. Therefore, influenza is highly prone to occur and is highly contagious. China is a country with frequent influenza, and three world pandemics since 1957 have originated in China. In 1917-1919, the outbreak of flu in Europe killed 20 million people and was the worst flu outbreak in history.
  • Avian influenza (Bird Flu or Avian Influenza), also known as avian influenza, is a syndrome caused by avian influenza virus (AIV) in avian animals from a respiratory system to the body with severe sepsis. .
  • Avian influenza has been designated as a Class A animal disease by the World Organisation for Animal Health (0IE). It is classified as a type of animal disease in China, also known as "true chicken” or "European chicken”.
  • the highest number of cases and the highest mortality rate is the 3 ⁇ 4 avian influenza virus. At present, it has occurred in many countries and regions in the world, causing huge economic losses to the poultry industry.
  • antiviral drugs are mainly aimed at preventing the adsorption of viruses, preventing the replication of viral nucleic acids, and preventing the translation of viral messenger RNA into viral proteins, neuraminidase inhibitors and other metabolic pathways.
  • Currently developed drugs are amantadine (remantadine), ribavirin (tibavirin), ⁇ -interferon, zanamivir (zanamivir) and osmivir (o seltamivir).
  • Existing drugs not only have side effects, but also have drug resistance. Therefore, there is an urgent need to develop new highly effective anti-cold drugs that can effectively prevent, treat influenza, and have a safer source and lower price.
  • the present invention finds that the patchouli oil and the patchouli carbon dioxide supercritical extract group have obvious effects on influenza A virus, influenza B virus and avian influenza virus. Inhibition and killing effect.
  • one of the objects of the present invention is to provide an application of baicalol in the preparation of a medicament for treating or preventing influenza or a health care product.
  • the second object of the present invention is to provide a patchouli carbon dioxide supercritical extract group for the preparation or treatment of influenza drugs. Application in food or health care products.
  • a third object of the present invention is to provide a use of a patchouli carbon dioxide supercritical extract group for the preparation of a medicament for the treatment or prevention of influenza or a health care product.
  • a fourth object of the present invention is to provide an application of the pharmaceutical composition of the present invention for the preparation of a medicament for treating or preventing influenza or a health care product.
  • the technical scheme of the present invention is as follows: The application of the baicalin in the preparation of a medicament for treating or preventing influenza.
  • patchouli oil in the preparation of a medicament for treating or preventing influenza.
  • composition comprising the active active ingredient, baicaleol, and a pharmaceutically acceptable carrier for the preparation of a medicament for the treatment or prevention of influenza.
  • Baiqiu Li alcohol in the preparation of a medicament for treating or preventing influenza A caused by influenza A virus.
  • Baiqiu Li alcohol in the preparation of a medicament for treating or preventing influenza caused by influenza B virus.
  • Baiqiu Li alcohol in the preparation of influenza drugs caused by the treatment or prevention of avian influenza virus.
  • An anti-influenza drug composition comprising the active active ingredient, baicalol, and/or a pharmaceutically acceptable carrier.
  • the anti-influenza drug composition the active active ingredient baqiuli alcohol raw material is derived from patchouli carbon dioxide supercritical extract, Guanghuo sesame oil or Guanghuoxiang.
  • composition for an anti-influenza drug which may be formulated into a tablet, a capsule, a granule, an oral solution, an injection, a dropping pill, an inhalant, a spray or a drop.
  • reagent Baiqiu Li alcohol, purchased from China National Institute for the Control of Pharmaceutical and Biological Products, purity 98%; patchouli carbon dioxide supercritical (SPE-C0 2 ) extract (homemade); Baiqiu Li alcohol (homemade), Purity 90%; patchouli oil, commercially available.
  • SPE-C0 2 patchouli carbon dioxide supercritical
  • mice NIH mice, single sex, provided by the Guangdong Medical Laboratory Animal Center, SPF level.
  • Mouse feed is a multi-ingredient formula. Feeding environment: room temperature 23 ⁇ 2 ° C, relative humidity 75 ⁇ 10%.
  • the patchouli is pulverized into coarse powder, passed through a 10-mesh sieve, and taken in 2000g.
  • supercritical extraction is carried out with C0 2 .
  • the extraction conditions are: extraction pressure 12-30Mpa; extraction temperature 55_60°C ; analytical pressure 5_6Mpa The analytical temperature was 40-45 ° C.
  • the patchouli SPE-C0 2 extract containing patchouli alcohol was obtained and placed in a clean container for use.
  • the extract of patchouli SPE-C0 2 was subjected to column chromatography separation: column chromatography was activated by silica gel G at 110 ° C for 1 hour, cooled to room temperature, and then wet-packed with petroleum ether (60-90 ° C). The fraction was eluted with petroleum ether: ethyl acetate: formic acid (20: 1: 0.1). The petroleum ether is recovered under reduced pressure and recrystallized to obtain patchouli alcohol, which is stored at low temperature and protected from light.
  • Sample GC analysis American Phenomenex ZB-WAX capillary column (30mX 0. 25mmX 0. 25um), fixed solution polyethylene glycol (Polyethylene Glycol), coating concentration of 100%; temperature programming; initial temperature 150 ° C, keep 23 minutes, ramp up to 230 ° C at 8 ° C per minute for 2 minutes; inlet temperature is 280 ° C, detector temperature is 280 ° C; split ratio is 20 : 1 ; column flow: L OmL Min- 1 ; Carrier gas: N2: 25 mL. min-1 ; Detector: FID, H2: 30mL. min-l, Air: 300mL. min-1 ; Injection volume 2 ⁇ , internal standard correction factor method The internal standard is n-octadecane. 5% ⁇ The content of the sample was 94. 65%.
  • Baiqiu Li alcohol purchased from China National Institute for the Control of Pharmaceutical and Biological Products
  • added a proper amount of excipients to prepare a suspension with a concentration of 7%.
  • mice were randomly divided into normal control group, positive drug group (ribavirin), virus control group (ie model group), Baiqiuli alcohol group, Baiqiu Li alcohol (home made) group, patchouli 3?5-(3 ⁇ 4 Extract, patchouli oil group, 10 in each group.
  • each group of mice was lightly anesthetized with ether, and 15 LD50 virus concentrations of the lung-adapted strain of influenza A virus were used to infect mice. 4 drops per dose, about 0. 05 ml.
  • the intragastric administration was started 1 day before infection, and the dose was: 0. lmL/10g, once a day for 4 days, the virus infected control group was steamed in equal volume. Water drenching. Day 5
  • the body weight of the mice was weighed, the lung lesions were observed by the naked eye, the degree of liver liver consolidation was recorded, the whole lung was weighed, the lung index value was calculated with body weight, and the lung index and inhibition rate were determined. 1.
  • Pulmonary index inhibition rate (control group average lung index - experimental group mean lung index) I control group average lung index X 100% Table 1 Effect of Baiqiu Li alcohol on mouse influenza A virus pneumonia
  • Patchouli alcohol group 10 1.19 ⁇ 0 ⁇ 42** 29.23 patchouli alcohol (homemade) group 10 1.21 ⁇ 0 ⁇ 19** 28.34
  • mice were sacrificed after 5 days of influenza infection.
  • the lungs of the control group were found to have obvious lung lesions.
  • the lung index was significantly different from the normal control group (P ⁇ 0.01), indicating that the model was established.
  • the ribavirin group significantly inhibited lung inflammation, and the lung index was significantly improved compared with the virus control group (P ⁇ 0.01).
  • the anti-pulmonary inflammatory effects of patchouli and patchouli were similar.
  • the lung index was significantly improved (P ⁇ 0.01) .
  • the P. sylvestris SPE-C0 2 extract group and the patchouli oil group had lower lung index than the virus control group. ( ⁇ ⁇ 0 ⁇ 05).
  • mice were randomly divided into normal control group, positive drug group (ribavirin), virus control group (ie model group), Baiqiuli alcohol group, Baiqiu Li alcohol (home made) group, patchouli SPE-C0 2 extract Group, patchouli oil group, 15 per group. Except the normal control group, each group of mice was lightly anesthetized with ether, and 5 LD50 virus concentrations of the lung-adapted strain of influenza A virus were used, and mice were intranasally inoculated with 4 drops each, about 0.05 ml. The drug was administered by the dose shown in Table 2 from the pre-infection Id, once a day for 12 days, and the virus-infected control group was orally administered with an equal volume of distilled water.
  • Death protection rate (virus infection control group mortality - test group mortality)
  • I virus infection control group mortality life extension rate (test group average survival days - virus infection control group average survival days I virus infection control group average survival Number of days) X 100%
  • mice were infected with the influenza virus most of the symptoms occurred after 4 days.
  • the mice developed symptoms such as shrub, decreased activity, weight loss, and decreased body temperature. From the 6th day onwards, they died.
  • the ribavirin group has obvious death protection and prolongs survival time (P ⁇ 0.01)
  • the Baiqiuli alcohol group and Baiqiuli alcohol (homemade) group also have obvious death protection effects.
  • the patchouli SPE-C0 2 extract group and the patchouli oil group had the effect of prolonging the survival time of life (P ⁇ 0.05).
  • Baiqiu Liol has obvious therapeutic effect on influenza
  • the higher the content of Baiqiuli alcohol the more obvious the effect, whether it is pure Baiqiu Liol or homemade samples, the effect is Better than the patchouli SPE-C0 2 extract group.
  • This also explains from another aspect that the self-made Baiqiu Li alcohol has a higher purity and is equivalent to the antiviral effect of the pure Qiu Li Li alcohol.
  • patchouli oil and patchouli 5?5-(3 ⁇ 4 extract also have the effect of treating influenza.
  • Baiqiu Li alcohol purchased from China National Institute for the Control of Pharmaceutical and Biological Products, purity 98%; Baiqiu Li alcohol (homemade), purity 90%; patchouli oil, commercially available.
  • Influenza A virus strain is provided by the Virus Laboratory of Tropical Medicine Institute of Guangzhou University of Traditional Chinese Medicine, influenza B virus strain, avian influenza virus (H5N1), cell line MDCK, by Shenzhen Center for Disease Control and Prevention Provided by the Microbiology Laboratory. 2. Sample preparation
  • the patchouli is pulverized into coarse powder, passed through a 10-mesh sieve, and taken in 2000g.
  • supercritical extraction is carried out with C0 2 .
  • the extraction conditions are: extraction pressure 12-30Mpa; extraction temperature 55_60°C ; analytical pressure 5_6Mpa The analytical temperature was 40-45 ° C.
  • the patchouli SPE-C0 2 extract containing patchouli alcohol was obtained and placed in a clean container for use.
  • the extract of patchouli SPE-C0 2 was subjected to column chromatography separation: column chromatography was activated with silica gel G at 110 ° C for 1 hour, cooled to room temperature, and then wet-packed with petroleum ether (60-90 ° C). The fractions were collected by elution with petroleum ether: ethyl acetate: formic acid (20: 1: 0.1). The petroleum ether is recovered under reduced pressure and recrystallized to obtain patchouli alcohol, which is stored at low temperature and protected from light.
  • the SFE-C02 extract of patchouli, the Baiqiu Liol, the Baiqiu Liol (homemade), and the patchouli oil sample were made into a 100 mg/ml sample solution with DMS0, and then diluted with PBS (1:2, 1:8, 1:32, 1:64, 1:128)
  • a total of 4 tubes after dilution, add 50 ⁇ 1/well to MDCK cells that have grown into a single layer, then add 50 ⁇ 1/well of influenza virus solution, plus ⁇ / Maintenance solution for the well.
  • Make 4 wells per sample concentration set the cell control wells, place at 35 °C, 5% C0 2 incubator overnight, add 0.2ml% red blood cell suspension to each well, mix well and let stand for 30-60min at room temperature. . Observe the blood coagulation results. The results are shown in Table 3.
  • Microculture is used. MDCK cells were cultured in 96-well culture plates in advance, cultured in a 5% CO 2 incubator at 35 ° C, and after 24 hours of cell layering, the wells were discarded and diluted (1:20). , 1:40, 1:80, 1:160, 1:320, 1:640, 1:1280) ⁇ alcohol sample solution, respectively added to the MDCK cells that have grown into a single layer, each hole is added ⁇ /well maintenance solution. For each concentration of 4 wells, set the cell control wells, set at 35 °C, 5% CO2 incubator environment, record the cytopathic results every day, until the toxicity of the drug to the cells no longer progresses. The minimum dilution factor for drugs that do not have cytopathic effects is an infinite amount of toxicity.
  • Baiqiu Li alcohol has a toxic effect on influenza A virus, influenza B virus and avian influenza virus, and is not cytotoxic.
  • patchouli alcohol namely, baqiol
  • the advantages of the invention are as follows: (1) The present invention finds that the patchouli carbon dioxide supercritical extract group, patchouli oil or baiqiuol has significant inhibition and killing of influenza A virus, avian influenza virus and influenza B virus. The role of the virus has opened up a new field of application. (2) The patchouli carbon dioxide supercritical extract group, patchouli oil or baicale alcohol of the invention is safe and non-toxic, and has strong pharmacological action, indicating a good medicinal prospect. (3) The raw material of the invention is rich in source, low in price, and simple in preparation process. (4) The pharmaceutical composition of the present invention can be prepared into an oral dosage form, an injection dosage form, a tablet U, a capsule, etc., and is convenient to use. detailed description
  • the patchouli is pulverized into coarse powder, passed through a 10-mesh sieve, taken at 2000g, placed in a supercritical extraction device, and supercritically extracted with C02.
  • the extraction conditions are: extraction pressure 12-30Mpa; extraction temperature 55_60°C ; analytical pressure 5_6Mpa; Analytical temperature After extracting for 4 hours at 40-45 ° C, a patch of patchouli SFE-C02 containing patchouli alcohol was obtained and placed in a clean container for use.
  • Example 3 The extract of patchouli SFE-C0 2 prepared in Example 1 was added to a suitable excipient, dissolved in 1000 ml of water to prepare a 0.2% aqueous solution, dissolved, and uniformly mixed, sealed and sterilized. Used during the flu epidemic to inject, prevent or treat the flu.
  • Example 3 The extract of patchouli SFE-C0 2 prepared in Example 1 was added to a suitable excipient, dissolved in 1000 ml of water to prepare a 0.2% aqueous solution, dissolved, and uniformly mixed, sealed and sterilized. Used during the flu epidemic to inject, prevent or treat the flu.
  • Example 4 200 mg of patchouli SFE-C0 2 extract prepared in Example 1 was added, and appropriate excipients were added to prepare a soft capsule containing 5% of patchouli alcohol, sealed and sterilized. Used during oral flu, prevention or treatment of influenza.
  • Example 4 200 mg of patchouli SFE-C0 2 extract prepared in Example 1 was added, and appropriate excipients were added to prepare a soft capsule containing 5% of patchouli alcohol, sealed and sterilized. Used during oral flu, prevention or treatment of influenza.
  • Example 4 200 mg of patchouli SFE-C0 2 extract prepared in Example 1 was added, and appropriate excipients were added to prepare a soft capsule containing 5% of patchouli alcohol, sealed and sterilized. Used during oral flu, prevention or treatment of influenza.
  • Example 5 200 mg of the patchouli SFE-C0 2 extract prepared in Example 1 was tableted, tableted, sealed, and sterilized. Used during oral flu, prevention or treatment of influenza.
  • Example 5 200 mg of the patchouli SFE-C0 2 extract prepared in Example 1 was tableted, tableted, sealed, and sterilized. Used during oral flu, prevention or treatment of influenza.
  • the extract of patchouli SFE-C02 was prepared in Example 1 and subjected to column chromatography.
  • Column chromatography was carried out by using silica gel G at 110 ° C for 1 hour, and after cooling to room temperature, petroleum ether (60-90 ° C) was used. It was wet-packed and eluted with petroleum ether: ethyl acetate: formic acid (20: 1: 0.1) to collect fractions.
  • the petroleum ether is recovered under reduced pressure and recrystallized to obtain patchouli alcohol, which is stored at low temperature and protected from light.
  • Example 7 Take 150 mg of baicaleol prepared in Example 2, add suitable excipients, dissolve in 1000 ml of water to make a 0.1% aqueous solution, dissolve, mix well, seal and disinfect. During the flu epidemic, it is used for injection, prevention and treatment of influenza.
  • Example 7 Take 150 mg of baicaleol prepared in Example 2, add suitable excipients, dissolve in 1000 ml of water to make a 0.1% aqueous solution, dissolve, mix well, seal and disinfect. During the flu epidemic, it is used for injection, prevention and treatment of influenza.
  • Example 8 Take 150 mg of Baiqi Li alcohol prepared in Example 2, add suitable excipients, and prepare soft capsules containing 5% of patchouli alcohol, sealed and disinfected. Used during oral flu, prevention or treatment of influenza.
  • Example 8 Take 150 mg of Baiqi Li alcohol prepared in Example 2, add suitable excipients, and prepare soft capsules containing 5% of patchouli alcohol, sealed and disinfected. Used during oral flu, prevention or treatment of influenza.
  • Example 14 The extract of patchouli SFE-C02 prepared in Example 1 was mixed with the chicken feed, and the daily dose was 0.16 g / of the extract of patchouli SFE-C02, which was taken twice in the morning and evening. Day, used to prevent bird flu.
  • Example 14 The extract of patchouli SFE-C02 prepared in Example 1 was mixed with the chicken feed, and the daily dose was 0.16 g / of the extract of patchouli SFE-C02, which was taken twice in the morning and evening. Day, used to prevent bird flu.
  • Example 15 Take the puppies prepared in Example 5, mix them well with the chicken feed, and use the daily dose of Baiqiu Li alcohol 0. lg / only, take it twice in the morning and evening, and take it for 3 days in a row to prevent bird flu.
  • Example 15 Take the puppies prepared in Example 5, mix them well with the chicken feed, and use the daily dose of Baiqiu Li alcohol 0. lg / only, take it twice in the morning and evening, and take it for 3 days in a row to prevent bird flu.

Abstract

New use of patchouli alcohol, CO2 supercritical extracts of herba pogostemonis or patchouli oil in medicament preparation is disclosed. Patchouli alcohol, having distinct inhibiting and killing effect on influenza virus H1N1, influenza virus B and avian influenza virus H5N1, can be found in both CO2 supercritical extracts of herba pogostemonis and patchouli oil.

Description

百秋李醇在药物制备中的用途 技术领域  Use of Baiqiu Li alcohol in drug preparation
本发明涉及广藿香二氧化碳超临界提取物、 广藿香油或百秋李醇在制备药物中的用 途, 属医药领域。 背景技术  The invention relates to the use of patchouli carbon dioxide supercritical extract, patchouli oil or baicaleol in the preparation of medicaments, and belongs to the field of medicine. Background technique
广藿香, Pogostemon cabl in (Blanco ) Benth. , 又称剌蕊草、 藿香, 是唇形科剌 蕊草属植物, 多年生草本, 全草药用。 原产亚洲菲律宾等亚热带地区, 我国主产广东、 海南等地。 其味辛, 微温, 归脾、 胃、 肺经。 具有芳香化浊, 开胃止呕, 发表解暑等功 效, 多用于湿浊中阻, 脘痞呕吐, 暑湿倦怠, 胸闷不舒, 寒湿闭暑, 腹痛吐泻, 鼻渊头 痛。 广藿香的药用成分主要是其挥发油, 称广藿香油, 其全草含有约 1. 5 %广藿香油, 其干品含有约 2 % 2. 8 %的广藿香油, 叶含 4. 5 %的广藿香油。 广藿香油具有促进胃液 分泌, 增强消化功能, 对胃平滑肌解痉作用和抗菌作用。  Patchouli, Pogostemon cabl in (Blanco) Benth., also known as sorrel, musk, is a genus of the genus Labia, a perennial herb, used in whole herbs. It is native to subtropical regions such as Asia and the Philippines. China mainly produces Guangdong and Hainan. Its taste, tenderness, spleen, stomach, lungs. It has aroma, turbidity, appetizing and vomiting, and publishes heat-removing effects, etc. It is mostly used for wet turbidity, vomiting, vomiting, stagnation, chest tightness, cold and dampness, abdominal pain, vomiting and diarrhea, and nasal pain. The medicinal ingredient of patchouli is mainly its volatile oil, which is called patchouli oil. Its whole grass contains about 1.5% patchouli oil, and its dry product contains about 2% 2.8% of patchouli oil, and the leaf contains 4. 5 % patchouli oil. Patchouli oil promotes gastric juice secretion, enhances digestive function, and relieves gastric mucosal muscles and antibacterial effects.
广藿香油的主要成份广藿香醇 (patchoul i alcohol, 百秋李醇) 约为 52 % 57 % 百秋李醇,是三环倍半萜类化合物, 分子式为 C15H260,分子量为 222. 37, 化学名称为 (1R- (lalpha, 4beta, 4aalpha, 6beta, 8aalpha) ) - octahydro-4, 8a, 9 9_tetramethyl_l 6- meth 1-1 (2H) -naphthol , 其结构式如下图所 示: The main ingredient of patchouli oil is patchoul alcohol, which is about 52% 57%. It is a tricyclic sesquiterpenoid compound with a molecular formula of C 15 H 26 0 and a molecular weight of 222. 37. The chemical name is (1R-(lalpha, 4beta, 4aalpha, 6beta, 8aalpha) ) - octahydro-4, 8a, 9 9_tetramethyl_l 6- meth 1-1 (2H) -naphthol , and its structural formula is shown below:
Figure imgf000002_0001
为结晶, 熔点 55 56%, 沸点 140°C (1· 06kPa) 1. 0284 1. 5029, 旋光度 -97. 4° (c=24 氯仿)。 不溶于水, 溶于醇、 醚和常用有机溶剂。 消旋体熔点 39 40%
Figure imgf000002_0001
For crystallization, melting point 55 56%, boiling point 140 ° C (1·06 kPa) 1. 0284 1. 5029, optical rotation -97. 4 ° (c = 24 chloroform). Do not dissolve in water, soluble in alcohol, ether and common organic solvents. Racemic melting point 39 40%
截至到目前, 人们对广藿香、 广藿香油及其主要成份百秋李醇的功能和用途的认识 仅限于作为一种传统香料, 添加在化妆品或精油中, 如欧洲专利 EP0409089A2, 揭示了 一种含百秋李醇的香水组分。专利 W02004110153A1也揭示了广藿香油,百秋李醇及其衍 生物可用于抑制真菌的无性繁殖及降低微生物的粘附作用, 愈合伤口或用于清洁剂等方 面的功效。中国专利 200710176344. 8揭示了百秋李醇在防治老年性痴呆症方面的功效和 用途。 然而, 对广藿香油及其主要成份百秋李醇在其他方面的功效和用途, 罕见报道。 Up to now, people's understanding of the function and use of patchouli, patchouli oil and its main ingredient, Baiqiu Liol, has been limited to being a traditional spice, added to cosmetics or essential oils, such as European Patent EP0409089A2, which reveals a A perfume component containing ubiquinol. Patent WO20041153153A1 also discloses that patchouli oil, Baiqiuliol and its derivatives can be used to inhibit the asexual reproduction of fungi and reduce the adhesion of microorganisms, heal wounds or use in detergents, etc. The effect of the face. Chinese patent 200710176344. 8 reveals the efficacy and use of Baiqiu Li alcohol in the prevention and treatment of senile dementia. However, the efficacy and use of patchouli oil and its main ingredient, Baiqiu Li alcohol, in other aspects are rarely reported.
流行性感冒 (Influenza, 简称流感)是流感病毒引起的急性呼吸道感染, 是一种传 染性强、 传播速度快的疾病。 主要通过空气中的飞沫, 或接触传播。  Influenza (Influenza) is an acute respiratory infection caused by influenza virus. It is a highly infectious and fast-transmitting disease. It is mainly transmitted by droplets in the air, or by contact.
人流感病毒分为甲、 乙、 丙三型, 其抗原性及其致病力极易发生变异, 尤其是甲型 病毒, 因此流感极易发生, 具有高度传染性。 我国是流感多发国, 而且自 1957年以来的 3 次世界性大流行都起源于我国。 1917-1919年, 欧洲爆发流感, 导致 2000万人死亡, 是历 史上最严重的一次流感爆发。  Human influenza viruses are classified into three types: A, B, and C. Their antigenicity and virulence are highly susceptible to mutation, especially the type A virus. Therefore, influenza is highly prone to occur and is highly contagious. China is a country with frequent influenza, and three world pandemics since 1957 have originated in China. In 1917-1919, the outbreak of flu in Europe killed 20 million people and was the worst flu outbreak in history.
禽流感(Bird Flu或 Avian Influenza) , 也就是禽类的流行性感冒, 是由禽流感病毒 (AIV)引起禽类动物的一种从呼吸系统到全身都出现严重败血症为主的多种症状的综合 症。 禽流感被世界动物卫生组织 (0IE)定为 A类动物疫病, 我国将其列为一类动物疫病, 又称 "真性鸡瘟" 或 "欧洲鸡瘟"。 全球禽流感患者中发病人数最多、 病死率最高的是 ¾ 型禽流感病毒。 目前, 在世界上许多国家和地区都有发生, 给养禽业造成了巨大的经 济损失。  Avian influenza (Bird Flu or Avian Influenza), also known as avian influenza, is a syndrome caused by avian influenza virus (AIV) in avian animals from a respiratory system to the body with severe sepsis. . Avian influenza has been designated as a Class A animal disease by the World Organisation for Animal Health (0IE). It is classified as a type of animal disease in China, also known as "true chicken" or "European chicken". Among the global avian influenza patients, the highest number of cases and the highest mortality rate is the 3⁄4 avian influenza virus. At present, it has occurred in many countries and regions in the world, causing huge economic losses to the poultry industry.
由于流感的传播速度极快, 病毒又极易发生变异, 故每年流感都会发生不同规模的 流行。 据 WHO公布的数据, 估计全球每年流感病例达 6亿〜 12亿。  Because the spread of the flu is extremely fast, the virus is highly susceptible to variability, so the flu will occur at different scales every year. According to data released by the WHO, it is estimated that there are 600 to 1.2 billion cases of influenza worldwide each year.
数十年来, 世界各国均投入大量的人力物力进行抗流感病毒的研究, 希望能找到更 为有效的预防以及治疗流感病毒的方法。 抗病毒药物的研发主要针对阻止病毒吸附、 阻 止病毒核酸的复制、 阻止病毒信使 RNA翻译成病毒蛋白质、 神经氨酸酶抑制剂等几个病 毒的代谢环节。 目前开发的药物有金刚烷(amantadine ^ 甲基金刚烷胺(rematadine)、 利巴韦林 ( tibavirin), λ -干扰素、扎那米韦 ( zanamivir)与奥斯米韦 (o seltamivir)。 但现有的药物, 不但有副作用, 而且存在耐药性。 因此, 急需开发新的可有效预防, 治 疗流感, 来源更安全, 价格低廉的高效抗感冒药物。 发明内容  For decades, countries around the world have invested a lot of manpower and resources in research on anti-influenza viruses, hoping to find more effective ways to prevent and treat influenza viruses. The development of antiviral drugs is mainly aimed at preventing the adsorption of viruses, preventing the replication of viral nucleic acids, and preventing the translation of viral messenger RNA into viral proteins, neuraminidase inhibitors and other metabolic pathways. Currently developed drugs are amantadine (remantadine), ribavirin (tibavirin), λ-interferon, zanamivir (zanamivir) and osmivir (o seltamivir). Existing drugs not only have side effects, but also have drug resistance. Therefore, there is an urgent need to develop new highly effective anti-cold drugs that can effectively prevent, treat influenza, and have a safer source and lower price.
本发明在筛选抗流行性感冒药物的过程中, 发现广藿香油, 广藿香二氧化碳超临界 提取物组, 百秋李醇对甲 1型流感病毒、 乙型流感病毒及禽流感病毒具有明显的抑制及 杀灭作用。  In the process of screening anti-influenza drugs, the present invention finds that the patchouli oil and the patchouli carbon dioxide supercritical extract group have obvious effects on influenza A virus, influenza B virus and avian influenza virus. Inhibition and killing effect.
为此, 本发明的目的之一是提供百秋李醇在制备治疗或预防流感药物或保健品中的 应用。  To this end, one of the objects of the present invention is to provide an application of baicalol in the preparation of a medicament for treating or preventing influenza or a health care product.
本发明的目的之二是提供广藿香二氧化碳超临界提取物组在制备治疗或预防流感药 物或保健品中的应用。 The second object of the present invention is to provide a patchouli carbon dioxide supercritical extract group for the preparation or treatment of influenza drugs. Application in food or health care products.
本发明的目的之三是提供广藿香二氧化碳超临界提取物组在制备治疗或预防流感药 物或保健品中的应用。  A third object of the present invention is to provide a use of a patchouli carbon dioxide supercritical extract group for the preparation of a medicament for the treatment or prevention of influenza or a health care product.
本发明的目的之四是提供本发明药物组合物制备治疗或预防流感药物或保健品中的 应用。  A fourth object of the present invention is to provide an application of the pharmaceutical composition of the present invention for the preparation of a medicament for treating or preventing influenza or a health care product.
本发明的技术方案如下: 百秋李醇在制备治疗或预防流感药物中的应用。  The technical scheme of the present invention is as follows: The application of the baicalin in the preparation of a medicament for treating or preventing influenza.
广藿香二氧化碳超临界提取物在制备治疗或预防流感药物中的应用。  The application of patchouli carbon dioxide supercritical extract in the preparation of a medicament for treating or preventing influenza.
广藿香油在制备治疗或预防流感药物中的应用。  The use of patchouli oil in the preparation of a medicament for treating or preventing influenza.
由活性有效成份百秋李醇和药学上可接受的载体组成的组合物在制备治疗或预防流 感药物中的应用。  The use of a composition comprising the active active ingredient, baicaleol, and a pharmaceutically acceptable carrier for the preparation of a medicament for the treatment or prevention of influenza.
百秋李醇在制备治疗或预防甲 1型流感病毒引起的流感药物中的应用。  The use of Baiqiu Li alcohol in the preparation of a medicament for treating or preventing influenza A caused by influenza A virus.
百秋李醇在制备治疗或预防乙型流感病毒引起的流感药物中的应用。  The use of Baiqiu Li alcohol in the preparation of a medicament for treating or preventing influenza caused by influenza B virus.
百秋李醇在制备治疗或预防禽流感病毒 引起的流感药物中的应用。  The use of Baiqiu Li alcohol in the preparation of influenza drugs caused by the treatment or prevention of avian influenza virus.
一种抗流感药物的组合物,所述组合物包含活性有效成份百秋李醇和 /或药学上可接 受的载体。  An anti-influenza drug composition comprising the active active ingredient, baicalol, and/or a pharmaceutically acceptable carrier.
所述的抗流感药物的组合物, 所述活性有效成份百秋李醇原料来源于广藿香二氧化 碳超临界提取物、 广霍香油或广霍香。  The anti-influenza drug composition, the active active ingredient baqiuli alcohol raw material is derived from patchouli carbon dioxide supercritical extract, Guanghuo sesame oil or Guanghuoxiang.
所述的抗流感药物的组合物, 所述药物的组合物可制成片剂、 胶囊剂、 颗粒剂、 口 服液、 注射液、 滴丸、 吸入剂、 喷雾剂或滴剂。  The composition for an anti-influenza drug, which may be formulated into a tablet, a capsule, a granule, an oral solution, an injection, a dropping pill, an inhalant, a spray or a drop.
为了更好的理解本发明的实质, 下面将结合广藿香二氧化碳超临界提取物组、 广藿 香油、 百秋李醇各自的药理实验及结果来说明其在制备抗流感药物及抗禽流感药物中的 作用。 实验例一 动物实验——广藿香二氧化碳超临界提取物组、 广藿香油、 百秋李醇抗 流感病毒作用的研究  In order to better understand the essence of the present invention, the following pharmacological experiments and results of the patchouli carbon dioxide supercritical extract group, patchouli oil, and baicaleol are described to illustrate the preparation of anti-influenza drugs and anti-avian influenza drugs. The role of. Experimental Example 1 Animal Experiment——Study on the Anti-influenza Virus Effect of Patchouli Carbon Dioxide Supercritical Extract Group, Patchouli Oil and Baiqiu Liol
1材料与仪器 1 materials and instruments
1. 1试药: 百秋李醇, 购于中国药品生物制品检定所, 纯度 98%; 广藿香二氧化碳超临 界 (SPE-C02 ) 提取物 (自制); 百秋李醇 (自制), 纯度 90%; 广藿香油, 市售。 1. 1 reagent: Baiqiu Li alcohol, purchased from China National Institute for the Control of Pharmaceutical and Biological Products, purity 98%; patchouli carbon dioxide supercritical (SPE-C0 2 ) extract (homemade); Baiqiu Li alcohol (homemade), Purity 90%; patchouli oil, commercially available.
1. 2 仪器: 1-5L超临界二氧化碳萃取装置,购于广州市轻工业研究所;常压分离层析柱; 挥发油提取装置; 美国 VARIAN-3900气相色谱仪。 1. 2 Instrument: 1-5L supercritical carbon dioxide extraction device, purchased from Guangzhou Light Industry Research Institute; atmospheric separation chromatography column; volatile oil extraction device; US VARIAN-3900 gas chromatograph.
1. 3 毒株甲 1型流感病毒鼠肺适应株由广州中医药大学热带医学研究所病毒室提供, 给 小鼠增强毒力后, 于鸡胚尿囊腔传代 2次 1. 3 strain of influenza A virus mouse lung adaptation strain provided by the Virus Room of Institute of Tropical Medicine, Guangzhou University of Chinese Medicine, After the mice increased their virulence, they were passaged twice in the chicken embryoal allantoic cavity.
1. 4 动物:: NIH小鼠, 单一性别, 由广东省医学实验动物中心提供, SPF级别。 小鼠饲料 为富含多种成分的配方。 饲养环境: 室温 23 ± 2° C , 相对湿度 75 ± 10%。  1. 4 Animals:: NIH mice, single sex, provided by the Guangdong Medical Laboratory Animal Center, SPF level. Mouse feed is a multi-ingredient formula. Feeding environment: room temperature 23 ± 2 ° C, relative humidity 75 ± 10%.
2 样品制备 2 sample preparation
2. 1 百秋李醇 (自制) 样品的制备: 2. 1 Preparation of Baiqiu Liol (Homemade) Sample:
广藿香粉碎成粗粉, 过 10 目筛, 取 2000g, 置超临界提取装置中, 用 C02进行超临 界萃取, 萃取条件是: 萃取压力 12-30Mpa; 萃取温度 55_60°C ; 解析压力 5_6Mpa; 解析 温度为 40-45 °C, 萃取 2小时后, 得到含广藿香醇的广藿香 SPE-C02提取物, 置洁净容器 中备用。 The patchouli is pulverized into coarse powder, passed through a 10-mesh sieve, and taken in 2000g. In a supercritical extraction device, supercritical extraction is carried out with C0 2 . The extraction conditions are: extraction pressure 12-30Mpa; extraction temperature 55_60°C ; analytical pressure 5_6Mpa The analytical temperature was 40-45 ° C. After 2 hours of extraction, the patchouli SPE-C0 2 extract containing patchouli alcohol was obtained and placed in a clean container for use.
取广藿香 SPE-C02提取物进行柱层析分离: 柱层析用硅胶 G在 110°C活化 1小时, 冷 却至室温后, 用石油醚(60-90°C )湿法装住, 以石油醚: 乙酸乙酯: 甲酸(20: 1: 0. 1 ) 洗脱,收集流分。 减压回收石油醚, 并经重结晶处理, 得广藿香醇, 低温、 避光保存。 The extract of patchouli SPE-C0 2 was subjected to column chromatography separation: column chromatography was activated by silica gel G at 110 ° C for 1 hour, cooled to room temperature, and then wet-packed with petroleum ether (60-90 ° C). The fraction was eluted with petroleum ether: ethyl acetate: formic acid (20: 1: 0.1). The petroleum ether is recovered under reduced pressure and recrystallized to obtain patchouli alcohol, which is stored at low temperature and protected from light.
样品 GC分析:美国 Phenomenex公司 ZB-WAX毛细管柱(30mX 0. 25mmX 0. 25um) ,固定 液聚乙二醇 (Polyethylene Glycol ) ,涂布浓度为 100 % ; 程序升温; 初始温度 150°C, 保持 23分钟, 以每分钟 8°C的速率升温至 230°C, 保持 2分钟; 进样口温度为 280°C, 检测器温度为 280°C ; 分流比为 20 : 1 ; 柱流量: L OmL. min- 1 ; 载气: N2: 25 mL. min-1 ; 检测器: FID, H2: 30mL. min-l, Air: 300mL. min-1 ; 进样量 2μί, 内标校正因子法计算 含量, 内标物为正十八烷。 结果得到, 百秋李醇(自制)样品含量为 94. 65%。  Sample GC analysis: American Phenomenex ZB-WAX capillary column (30mX 0. 25mmX 0. 25um), fixed solution polyethylene glycol (Polyethylene Glycol), coating concentration of 100%; temperature programming; initial temperature 150 ° C, keep 23 minutes, ramp up to 230 ° C at 8 ° C per minute for 2 minutes; inlet temperature is 280 ° C, detector temperature is 280 ° C; split ratio is 20 : 1 ; column flow: L OmL Min- 1 ; Carrier gas: N2: 25 mL. min-1 ; Detector: FID, H2: 30mL. min-l, Air: 300mL. min-1 ; Injection volume 2μί, internal standard correction factor method The internal standard is n-octadecane. 5%。 The content of the sample was 94. 65%.
2. 2 试药的制备 2. 2 Preparation of reagents
称取百秋李醇 (购于中国药品生物制品检定所) 70mg, 加入适量辅料后, 配制成浓 度为 7%的混悬液。  Weighed 70mg of Baiqiu Li alcohol (purchased from China National Institute for the Control of Pharmaceutical and Biological Products), and added a proper amount of excipients to prepare a suspension with a concentration of 7%.
称取百秋李醇 (自制) 70mg , 加入适量辅料后, 配制成浓度为 7%的混悬液。  Weighed 70mg of Baiqiu Li alcohol (home-made), and added a proper amount of excipients to prepare a suspension with a concentration of 7%.
称取广藿香 SPE-C02提取物 100mg, 加入适量辅料后, 配制成浓度为 10%的混悬液。 称取广藿香油 30mg, 加入适量辅料后, 配制成浓度为 3%的混悬液。 Weigh 100 mg of patchouli SPE-C0 2 extract, and add a suitable amount of excipients to prepare a suspension with a concentration of 10%. Weigh 30mg of patchouli oil and add a proper amount of excipient to prepare a suspension with a concentration of 3%.
3 方法与结果 3 Methods and results
3. 1 对小鼠流感病毒性肺炎的影响  3. 1 Effect on mouse influenza virus pneumonia
将小鼠随机分成正常对照组、 阳性药物组(病毒唑)、 病毒对照组(即模型组)、 百 秋李醇组, 百秋李醇 (自制) 组, 广藿香 3?5-(¾提取物, 广藿香油组, 每组 10只。 除 正常对照组外,各组小鼠用乙醚轻度麻醉,选用甲 1型流感病毒鼠肺适应株 15个 LD50 病 毒浓度, 滴鼻感染小鼠, 每只 4滴, 约 0. 05 ml。 从感染前 1 d开始灌胃给药, 给药剂 量为: 0. lmL/10g, 每天 1次, 连续 4 d, 病毒感染对照组以等体积蒸熘水灌胃。 第 5天 称取小鼠体重后解剖, 肉眼观察肺部病变, 记录肺部肝样实变的程度, 摘取全肺称重, 与体重计算肺指数值, 并求出肺指数与抑制率, 结果见表 1。 The mice were randomly divided into normal control group, positive drug group (ribavirin), virus control group (ie model group), Baiqiuli alcohol group, Baiqiu Li alcohol (home made) group, patchouli 3?5-(3⁄4 Extract, patchouli oil group, 10 in each group. In addition to the normal control group, each group of mice was lightly anesthetized with ether, and 15 LD50 virus concentrations of the lung-adapted strain of influenza A virus were used to infect mice. 4 drops per dose, about 0. 05 ml. The intragastric administration was started 1 day before infection, and the dose was: 0. lmL/10g, once a day for 4 days, the virus infected control group was steamed in equal volume. Water drenching. Day 5 The body weight of the mice was weighed, the lung lesions were observed by the naked eye, the degree of liver liver consolidation was recorded, the whole lung was weighed, the lung index value was calculated with body weight, and the lung index and inhibition rate were determined. 1.
肺指数 =小鼠肺重 (g) /小鼠体重 (g) X 100%  Lung Index = Mouse Lung Weight (g) / Mouse Body Weight (g) X 100%
肺指数抑制率 = (对照组平均肺指数-实验组平均肺指数) I对照组平均肺指数 X 100% 表 1 百秋李醇对小鼠甲 1型流感病毒肺炎的影响  Pulmonary index inhibition rate = (control group average lung index - experimental group mean lung index) I control group average lung index X 100% Table 1 Effect of Baiqiu Li alcohol on mouse influenza A virus pneumonia
动物数 /只 肺指数 / x±s 抑制率 / % 正常对照组 10 0.81±0.14 Number of animals / lung index / x ± s inhibition rate / % Normal control group 10 0.81 ± 0.14
病毒对照组 10 1.52±0· 17##  Virus control group 10 1.52±0· 17##
病毒唑对照组 10 1.09±0.36** 42.69 广藿香 SFE-C02提取物组 10 1.27±0· 28* 15.90 Ribavirin control group 10 1.09±0.36** 42.69 Patchouli SFE-C0 2 extract group 10 1.27±0· 28* 15.90
广藿香醇组 10 1.19±0· 42** 29.23 广藿香醇 (自制) 组 10 1.21±0· 19** 28.34  Patchouli alcohol group 10 1.19±0· 42** 29.23 patchouli alcohol (homemade) group 10 1.21±0· 19** 28.34
广藿香油组 10 1.25±0· 47* 20.06  Patchouli oil group 10 1.25±0· 47* 20.06
(与正常对照组比较, ##·· Ρ<0.01; 与病毒对照组比较:  (Compared with the normal control group, ##·· Ρ<0.01; compared with the virus control group:
小鼠感染流感病毒 5d后被处死,解剖发现病毒对照组小鼠的肺部病变明显,其肺指 数与正常对照组比较具有显著性差别(P〈0.01),表明此模型成立。 实验表明, 病毒唑组 具有明显抑制肺部炎症作用, 与病毒对照组相比, 肺指数有明显好转(P〈0.01); 广藿香 醇、 广藿香醇 (自制) 的抗肺部炎症作用相似, 与病毒对照组相比, 肺指数均有明显好 转 ((P〈0.01)); 广藿香 SPE-C02提取物组、 广藿香油组与病毒对照组相比, 肺指数低于 病毒对照组 (Ρ〈0· 05)。 The mice were sacrificed after 5 days of influenza infection. The lungs of the control group were found to have obvious lung lesions. The lung index was significantly different from the normal control group (P<0.01), indicating that the model was established. Experiments showed that the ribavirin group significantly inhibited lung inflammation, and the lung index was significantly improved compared with the virus control group (P<0.01). The anti-pulmonary inflammatory effects of patchouli and patchouli (home-made) were similar. Compared with the virus control group, the lung index was significantly improved (P<0.01) . The P. sylvestris SPE-C0 2 extract group and the patchouli oil group had lower lung index than the virus control group. (Ρ <0· 05).
3.2 对流感病毒感染小鼠的死亡保护实验 3.2 Death protection experiment in mice infected with influenza virus
将小鼠随机分成正常对照组、 阳性药物组 (病毒唑)、 病毒对照组 (即模型组)、 百 秋李醇组, 百秋李醇 (自制) 组, 广藿香 SPE-C02提取物组, 广藿香油组, 每组 15只。 除正常对照组外, 各组小鼠用乙醚轻度麻醉, 选用甲 1型流感病毒鼠肺适应株 5个 LD50 病毒浓度, 滴鼻感染小鼠, 每只 4滴, 约 0.05 ml。 从感染前 Id开始按表 2所示的剂量 灌胃给药, 每天 1次, 连续 12d, 病毒感染对照组以等体积蒸熘水灌胃。 逐日观察动物 发病症状与死亡数, 共观察 15d。 计算死亡率、 保护率、 平均存活天数及生命延长率。 死亡保护率 = (病毒感染对照组死亡率一试验组死亡率) I病毒感染对照组死亡率 生命延长率 = (试验组平均存活天数一病毒感染对照组平均存活天数 I病毒感染对照组平 均存活天数) X 100% The mice were randomly divided into normal control group, positive drug group (ribavirin), virus control group (ie model group), Baiqiuli alcohol group, Baiqiu Li alcohol (home made) group, patchouli SPE-C0 2 extract Group, patchouli oil group, 15 per group. Except the normal control group, each group of mice was lightly anesthetized with ether, and 5 LD50 virus concentrations of the lung-adapted strain of influenza A virus were used, and mice were intranasally inoculated with 4 drops each, about 0.05 ml. The drug was administered by the dose shown in Table 2 from the pre-infection Id, once a day for 12 days, and the virus-infected control group was orally administered with an equal volume of distilled water. The symptoms and deaths of the animals were observed daily for 15 days. Calculate mortality, protection, average survival days, and life extension rates. Death protection rate = (virus infection control group mortality - test group mortality) I virus infection control group mortality life extension rate = (test group average survival days - virus infection control group average survival days I virus infection control group average survival Number of days) X 100%
表 2 各样品对甲 1型流感病毒感染小鼠死亡保护结果 给药剂 死亡 存活 死亡率 死亡保 生命延 平均存活时间 Table 2 Results of death protection of mice infected with influenza A virus by each sample Give the drug death survival mortality death life-average survival time
(mg * g_l) 数(只) 数(只) (%) 护率(%) 长率(%) 病毒对照组 15 0 5.13±2.00 100 - - 病毒唑对照组 0.07 8 7 10.20±4.69** 53.33 46.67** 98.93 广藿香 SPE-C02  (mg * g_l) number (only) number (only) (%) protection rate (%) long rate (%) virus control group 15 0 5.13 ± 2.00 100 - - ribavirin control group 0.07 8 7 10.20 ± 4.69** 53.33 46.67** 98.93 Patchouli SPE-C02
0.1 12 3 7.00±4.42* 80 20 36.45 提取物组  0.1 12 3 7.00±4.42* 80 20 36.45 Extract group
广藿香醇组 0.07 10 5 8.73±4.85** 66.67 33.33** 70.18 广藿香醇 (自  Patchouli alcohol group 0.07 10 5 8.73±4.85** 66.67 33.33** 70.18 Patchouli alcohol (from
0.07 10 5 8.68±4.05** 66.67 33.33** 71.26 制) 组  0.07 10 5 8.68±4.05** 66.67 33.33** 71.26 system)
广藿香油组 0.03 14 1 6.20±3.00* 93.33 6.67 20.86 Patchouli oil group 0.03 14 1 6.20±3.00* 93.33 6.67 20.86
(与病毒对照组比较, **Ρ〈0· 01, *Ρ〈0· 05) (Compared with the virus control group, **Ρ<0· 01, *Ρ<0· 05)
小鼠感染流感病毒后, 大多发病在 4d以后, 小鼠出现耸毛、 活动减少、 体重减轻、 体温下降等症状, 从第 6日开始出现死亡。 从表 2可看出, 病毒唑组具有明显的死亡保 护作用及延长生命存活时间 (P〈0.01), 百秋李醇组、 百秋李醇(自制)组, 同样具明显 的死亡保护作用及延长生命存活时间 (P〈0.01)。 广藿香 SPE-C02提取物组、 广藿香油组 具有延长生命存活时间的作用 (P〈0.05)。 After the mice were infected with the influenza virus, most of the symptoms occurred after 4 days. The mice developed symptoms such as shrub, decreased activity, weight loss, and decreased body temperature. From the 6th day onwards, they died. It can be seen from Table 2 that the ribavirin group has obvious death protection and prolongs survival time (P<0.01), and the Baiqiuli alcohol group and Baiqiuli alcohol (homemade) group also have obvious death protection effects. Prolong survival time (P<0.01). The patchouli SPE-C0 2 extract group and the patchouli oil group had the effect of prolonging the survival time of life (P<0.05).
3.3小结  3.3 Summary
从以上两个动物实验可知, 百秋李醇具有明显的治疗流行性感冒作用, 且百秋李醇 的含量越高, 作用越明显, 无论是百秋李醇纯品还是自制样品, 其效果均优于广藿香 SPE-C02提取物组。这也从另一方面说明, 自制百秋李醇纯度较高, 与百秋李醇纯品抗病 毒效果相当。 同时, 广藿香油及广藿香 5?5-(¾提取物也具有治疗流行性感冒作用。 实验例二 体外实验——体外抑制了流感病毒作用 It can be seen from the above two animal experiments that Baiqiu Liol has obvious therapeutic effect on influenza, and the higher the content of Baiqiuli alcohol, the more obvious the effect, whether it is pure Baiqiu Liol or homemade samples, the effect is Better than the patchouli SPE-C0 2 extract group. This also explains from another aspect that the self-made Baiqiu Li alcohol has a higher purity and is equivalent to the antiviral effect of the pure Qiu Li Li alcohol. At the same time, patchouli oil and patchouli 5?5-(3⁄4 extract also have the effect of treating influenza. Experimental example 2 in vitro experiment - inhibition of influenza virus effect in vitro
1. 材料与仪器  1. Materials and instruments
1.1 试药: 百秋李醇, 购于中国药品生物制品检定所, 纯度 98%; 百秋李醇 (自制), 纯度 90%; 广藿香油, 市售。  1.1 Test: Baiqiu Li alcohol, purchased from China National Institute for the Control of Pharmaceutical and Biological Products, purity 98%; Baiqiu Li alcohol (homemade), purity 90%; patchouli oil, commercially available.
1.2 仪器: 1-5L超临界二氧化碳萃取装置,购于广州市轻工业研究所;常压分离层析柱; 挥发油提取装置; 美国 VARIAN-3900气相色谱仪。  1.2 Instrument: 1-5L supercritical carbon dioxide extraction device, purchased from Guangzhou Light Industry Research Institute; atmospheric separation chromatography column; volatile oil extraction device; US VARIAN-3900 gas chromatograph.
1.3 毒株与细胞: 甲 1型流感病毒株由广州中医药大学热带医学研所病毒室提供, 乙型 流感病毒毒株, 禽流感病毒 (H5N1), 细胞株 MDCK, 由深圳市疾病预防控制中心微生物 检验科提供。 2. 样品制备 1.3 Strain and cell: Influenza A virus strain is provided by the Virus Laboratory of Tropical Medicine Institute of Guangzhou University of Traditional Chinese Medicine, influenza B virus strain, avian influenza virus (H5N1), cell line MDCK, by Shenzhen Center for Disease Control and Prevention Provided by the Microbiology Laboratory. 2. Sample preparation
2.1 百秋李醇 (自制) 样品的制备:  2.1 Baiqiu Li alcohol (homemade) Sample preparation:
广藿香粉碎成粗粉, 过 10 目筛, 取 2000g, 置超临界提取装置中, 用 C02进行超临 界萃取, 萃取条件是: 萃取压力 12-30Mpa; 萃取温度 55_60°C; 解析压力 5_6Mpa; 解析 温度为 40-45 °C, 萃取 2小时后, 得到含广藿香醇的广藿香 SPE-C02提取物, 置洁净容器 中备用。 The patchouli is pulverized into coarse powder, passed through a 10-mesh sieve, and taken in 2000g. In a supercritical extraction device, supercritical extraction is carried out with C0 2 . The extraction conditions are: extraction pressure 12-30Mpa; extraction temperature 55_60°C ; analytical pressure 5_6Mpa The analytical temperature was 40-45 ° C. After 2 hours of extraction, the patchouli SPE-C0 2 extract containing patchouli alcohol was obtained and placed in a clean container for use.
取广藿香 SPE-C02提取物进行柱层析分离: 柱层析用硅胶 G在 110°C活化 1小时, 冷 却至室温后, 用石油醚(60-90°C)湿法装住, 以石油醚: 乙酸乙酯: 甲酸(20: 1: 0.1) 洗脱,收集流分。 减压回收石油醚, 并经重结晶处理, 得广藿香醇, 低温、 避光保存。 The extract of patchouli SPE-C0 2 was subjected to column chromatography separation: column chromatography was activated with silica gel G at 110 ° C for 1 hour, cooled to room temperature, and then wet-packed with petroleum ether (60-90 ° C). The fractions were collected by elution with petroleum ether: ethyl acetate: formic acid (20: 1: 0.1). The petroleum ether is recovered under reduced pressure and recrystallized to obtain patchouli alcohol, which is stored at low temperature and protected from light.
样品 GC分析:美国 Phenomenex公司 ZB-WAX毛细管柱(30mX0.25mmX0.25um) ,固定 液聚乙二醇 (Polyethylene Glycol) ,涂布浓度为 100%; 程序升温; 初始温度 150°C, 保持 23分钟, 以每分钟 8°C的速率升温至 230°C, 保持 2分钟; 进样口温度为 280°C, 检测器温度为 280°C; 分流比为 20:1; 柱流量: LOmL.min- 1; 载气: N2: 25 mL. min-1; 检测器: FID, H2: 30mL. min-l, Air: 300mL. min-1; 进样量 2μί, 内标校正因子法计算 含量, 内标物为正十八烷。 结果得到, 百秋李醇(自制)样品含量为 94.65%。  Sample GC analysis: American Phenomenex ZB-WAX capillary column (30mX0.25mmX0.25um), fixed solution polyethylene glycol (Polyethylene Glycol), coating concentration of 100%; temperature programming; initial temperature 150 ° C, for 23 minutes , ramp up to 230 ° C at 8 ° C per minute for 2 minutes; inlet temperature is 280 ° C, detector temperature is 280 ° C; split ratio is 20:1; column flow: LOmL.min- 1; Carrier gas: N2: 25 mL. min-1; Detector: FID, H2: 30mL. min-l, Air: 300mL. min-1; Injection volume 2μί, internal standard correction factor method to calculate content, internal standard The substance is n-octadecane. As a result, the sample content of Baiqiu Li alcohol (homemade) was 94.65%.
3. 方法与结果  3. Methods and results
3.1体外抑制甲型和乙型流感病毒及禽流感病毒的作用  3.1 Inhibition of influenza A and B viruses and avian influenza virus in vitro
将广藿香的 SFE-C02提取物、 百秋李醇、 百秋李醇 (自制)、 广藿香油样品用 DMS0制 成 100mg/ml的样液后, 用 PBS作对倍稀释 (1:2, 1:8, 1:32, 1:64, 1:128)共 4管, 稀释 后按 50μ1/孔加入已长成单层的 MDCK细胞中, 再加入流感病毒液 50μ1/孔, 再加上 ΙΟθμΙ/ 孔的维持液。 每个样品浓度做 4孔重复, 同时设细胞对照孔, 置 35°C, 5%C02孵箱环境培 养过夜, 于每孔中加入 0.2mll%红细胞悬液, 混合均匀后室温放置 30-60min。观察血凝结 果。 结果见表 3。 The SFE-C02 extract of patchouli, the Baiqiu Liol, the Baiqiu Liol (homemade), and the patchouli oil sample were made into a 100 mg/ml sample solution with DMS0, and then diluted with PBS (1:2, 1:8, 1:32, 1:64, 1:128) A total of 4 tubes, after dilution, add 50μ1/well to MDCK cells that have grown into a single layer, then add 50μ1/well of influenza virus solution, plus ΙΟθμΙ / Maintenance solution for the well. Make 4 wells per sample concentration, set the cell control wells, place at 35 °C, 5% C0 2 incubator overnight, add 0.2ml% red blood cell suspension to each well, mix well and let stand for 30-60min at room temperature. . Observe the blood coagulation results. The results are shown in Table 3.
结果显示, 两种百秋李醇样品对甲 1型流感病毒、 乙型流感病毒、 禽流感病毒 均 有灭毒作用, 广藿香 SFE-C02提取物、 广藿香油也有抗流感病毒作用, 但效果比百秋李醇 弱。 表 3 百秋李醇抗流感病毒的最大稀释度The results showed that the two kinds of Baiqiuli alcohol samples had anti-virus effects on influenza A virus, influenza B virus and avian influenza virus. The extract of patchouli SFE-C0 2 and patchouli oil also had anti-influenza virus effect. But the effect is weaker than Baiqi Li alcohol. Table 3 Maximum dilution of Baiqiu Liol against influenza virus
Figure imgf000009_0001
Figure imgf000009_0001
广藿香 SFE-C02提取物 1 :640 1 :640 1 :640 Patchouli SFE-C0 2 Extract 1: 640 1 : 640 1 : 640
百秋李醇 1: 1280 1: 1280 1: 1280 百秋李醇 (自制) 1: 1280 1: 1280 1: 1280  Baiqiu Li alcohol 1: 1280 1: 1280 1: 1280 Baiqiu Li alcohol (homemade) 1: 1280 1: 1280 1: 1280
广藿香油 1: 640 1: 640 1: 640  Patchouli oil 1: 640 1: 640 1: 640
3.2百秋李醇对细胞毒性的测定 3.2 Determination of cytotoxicity of Baiqiu Li alcohol
采用微量培养法。预先将 MDCK细胞培养于 96孔培养板内, 置 35°C, 5%C02孵箱环境中 培养,约 24小时细胞成层后,弃去孔内培养液,再将递倍稀释(1:20, 1:40, 1:80, 1:160, 1:320, 1:640, 1:1280) 的 ΙΟθμΙ百秋李醇样品液, 分别加入已长成单层的 MDCK细胞中, 每孔再加 Ιθθμΐ/孔的维持液。 每个浓度 4孔, 同时设细胞对照孔, 置 35°C, 5%C02孵箱环 境培养, 每天记录细胞病变结果, 直至药物对细胞的毒性不再继续进展时判结果。 以不 出现细胞病变的药物最小稀释倍数为无限毒量。  Microculture is used. MDCK cells were cultured in 96-well culture plates in advance, cultured in a 5% CO 2 incubator at 35 ° C, and after 24 hours of cell layering, the wells were discarded and diluted (1:20). , 1:40, 1:80, 1:160, 1:320, 1:640, 1:1280) ΙΟθμΙ百秋李 alcohol sample solution, respectively added to the MDCK cells that have grown into a single layer, each hole is added Ιθθμΐ/well maintenance solution. For each concentration of 4 wells, set the cell control wells, set at 35 °C, 5% CO2 incubator environment, record the cytopathic results every day, until the toxicity of the drug to the cells no longer progresses. The minimum dilution factor for drugs that do not have cytopathic effects is an infinite amount of toxicity.
结果显示, 各浓度作用下细胞均无发现病变, 表明百秋李醇无细胞毒性。  The results showed that no lesions were found in the cells under the respective concentrations, indicating that cytotoxicity was not cytotoxic.
3.3小结  3.3 Summary
体外实验表明, 百秋李醇对甲 1型流感病毒、 乙型流感病毒、 禽流感病毒 均有灭 毒作用, 且无细胞毒性。  In vitro experiments have shown that Baiqiu Li alcohol has a toxic effect on influenza A virus, influenza B virus and avian influenza virus, and is not cytotoxic.
从以上实验可以推断, 广藿香, 广藿香油, 广藿香 SPF-C02提取物中发挥抗感冒病毒 作用的主要成份为广藿香醇, 即百秋李醇。 It can be inferred from the above experiments that the main component of the extract of patchouli, patchouli oil, and patchouli SPF-C0 2 which exerts anti-cold virus action is patchouli alcohol, namely, baqiol.
本发明的优点是: (1) 本发明发现广藿香二氧化碳超临界提取物组、 广藿香油或百 秋李醇具有明显的抑制和杀灭甲 1型流感病毒、 禽流感病毒、 乙型流感病毒的作用, 开 拓了一个新的应用领域。 (2) 本发明的广藿香二氧化碳超临界提取物组、 广藿香油或百 秋李醇安全无毒, 药理作用强, 预示着很好的药用前景。 (3) 本发明的原料来源丰富, 价格低廉, 制备工艺简单。 (4)本发明的药物组合物可制成口服剂型、 注射剂型、 片齐 U、 胶囊等, 使用方便。 具体实施方式  The advantages of the invention are as follows: (1) The present invention finds that the patchouli carbon dioxide supercritical extract group, patchouli oil or baiqiuol has significant inhibition and killing of influenza A virus, avian influenza virus and influenza B virus. The role of the virus has opened up a new field of application. (2) The patchouli carbon dioxide supercritical extract group, patchouli oil or baicale alcohol of the invention is safe and non-toxic, and has strong pharmacological action, indicating a good medicinal prospect. (3) The raw material of the invention is rich in source, low in price, and simple in preparation process. (4) The pharmaceutical composition of the present invention can be prepared into an oral dosage form, an injection dosage form, a tablet U, a capsule, etc., and is convenient to use. detailed description
实施例 1 Example 1
广藿香粉碎成粗粉, 过 10目筛, 取 2000g, 置超临界提取装置中, 用 C02进行超临界 萃取, 萃取条件是: 萃取压力 12-30Mpa; 萃取温度 55_60°C; 解析压力 5_6Mpa; 解析温度 为 40-45°C,萃取 2小时后,得到含广藿香醇的广藿香 SFE-C02提取物,置洁净容器中备用。 取上述制得的广藿香 SFE-C02提取物 2000mg, 加入适当辅料, 溶于 1000ml水中制成水 溶液, 溶解, 混合均匀后, 分装成配成 2mg/lml/支浓度的滴丸, 密封、 消毒。 在流感疫 情期间, 用于滴入鼻腔, 预防治疗流感。 实施例 2 The patchouli is pulverized into coarse powder, passed through a 10-mesh sieve, taken at 2000g, placed in a supercritical extraction device, and supercritically extracted with C02. The extraction conditions are: extraction pressure 12-30Mpa; extraction temperature 55_60°C ; analytical pressure 5_6Mpa; Analytical temperature After extracting for 4 hours at 40-45 ° C, a patch of patchouli SFE-C02 containing patchouli alcohol was obtained and placed in a clean container for use. Take the above-prepared extract of patchouli SFE-C0 2 2000mg, add appropriate excipients, dissolve in 1000ml of water to make an aqueous solution, dissolve, mix well, and then dispense into a pellet of 2mg/lml / concentration, seal , disinfection. During the flu epidemic, it is used to drip into the nasal cavity to prevent and treat the flu. Example 2
取实施例 1制得的广藿香 SFE-C02提取物 200mg, 加入适当辅料, 溶于 1000ml水中制 成 0. 2 %浓度的水溶液, 溶解, 混合均匀后, 密封、 消毒。 在流感疫情期间, 用于注射, 预防或治疗流感。 实施例 3 The extract of patchouli SFE-C0 2 prepared in Example 1 was added to a suitable excipient, dissolved in 1000 ml of water to prepare a 0.2% aqueous solution, dissolved, and uniformly mixed, sealed and sterilized. Used during the flu epidemic to inject, prevent or treat the flu. Example 3
取实施例 1制得的广藿香 SFE-C02提取物 200mg, 加入适当辅料, 配成内含广藿香醇 5%的软胶囊, 密封、 消毒。 在流感疫情期间, 用于口服, 预防或治疗流感。 实施例 4 200 mg of patchouli SFE-C0 2 extract prepared in Example 1 was added, and appropriate excipients were added to prepare a soft capsule containing 5% of patchouli alcohol, sealed and sterilized. Used during oral flu, prevention or treatment of influenza. Example 4
取实施例 1制得的广藿香 SFE-C02提取物 200mg, 压片, 制成片剂, 密封、 消毒。 在 流感疫情期间, 用于口服, 预防或治疗流感。 实施例 5 200 mg of the patchouli SFE-C0 2 extract prepared in Example 1 was tableted, tableted, sealed, and sterilized. Used during oral flu, prevention or treatment of influenza. Example 5
取实施例 1制得广藿香 SFE-C02提取物, 进行柱层析分离: 柱层析用硅胶 G在 110°C活 化 1小时, 冷却至室温后, 用石油醚 (60-90°C ) 湿法装住, 以石油醚: 乙酸乙酯: 甲酸 ( 20: 1: 0. 1 )洗脱,收集流分。减压回收石油醚, 并经重结晶处理, 得广藿香醇, 低温、 避光保存。  The extract of patchouli SFE-C02 was prepared in Example 1 and subjected to column chromatography. Column chromatography was carried out by using silica gel G at 110 ° C for 1 hour, and after cooling to room temperature, petroleum ether (60-90 ° C) was used. It was wet-packed and eluted with petroleum ether: ethyl acetate: formic acid (20: 1: 0.1) to collect fractions. The petroleum ether is recovered under reduced pressure and recrystallized to obtain patchouli alcohol, which is stored at low temperature and protected from light.
取上述制得的百秋李醇 1500mg, 加入适当辅料, 溶于 1000ml水中制成水溶液, 溶解, 混合均匀后, 分装成配成 3mg/2ml/支浓度的滴丸, 密封、 消毒。 在流感疫情期间, 用于 滴入鼻腔, 预防治疗流感。 实施例 6  Take 1500mg of Baiqi Lialol prepared above, add appropriate auxiliary materials, dissolve in 1000ml water to make an aqueous solution, dissolve, mix well, and then pack into 3ppm/2ml/dose dropping pills, seal and disinfect. During the flu epidemic, it is used to drip into the nasal cavity to prevent and treat the flu. Example 6
取实施例 2制得的百秋李醇 150mg,加入适当辅料,溶于 1000ml水中制成 0. 15 %浓度 的水溶液, 溶解, 混合均匀后, 密封、 消毒。 在流感疫情期间, 用于注射, 预防治疗流 感。 实施例 7 Take 150 mg of baicaleol prepared in Example 2, add suitable excipients, dissolve in 1000 ml of water to make a 0.1% aqueous solution, dissolve, mix well, seal and disinfect. During the flu epidemic, it is used for injection, prevention and treatment of influenza. Example 7
取实施例 2制得的百秋李醇 150mg, 加入适当辅料, 配成内含广藿香醇 5%的软胶囊, 密封、 消毒。 在流感疫情期间, 用于口服, 预防或治疗流感。 实施例 8  Take 150 mg of Baiqi Li alcohol prepared in Example 2, add suitable excipients, and prepare soft capsules containing 5% of patchouli alcohol, sealed and disinfected. Used during oral flu, prevention or treatment of influenza. Example 8
取实施例 2制得的百秋李醇 150mg, 加入适当辅料, 压片, 制成片剂, 密封、 消毒。 在流感疫情期间, 用于口服, 预防或治疗流感。 实施例 9  Take 150 mg of baicaleol prepared in Example 2, add suitable excipients, compress tablets, make tablets, seal and disinfect. Used during oral flu, prevention or treatment of influenza. Example 9
购买市售广藿香油 lOOOmg, 加入适当辅料, 溶于 1000ml水中制成水溶液, 溶解, 混 合均匀后, 分装成配成 lmg/lml/支浓度的滴丸, 密封、 消毒。 在流感疫情期间, 用于滴 入鼻腔, 预防治疗流感。  Buy commercially available patchouli oil lOOOOmg, add appropriate excipients, dissolve in 1000ml water to make an aqueous solution, dissolve, mix evenly, and then dispense into lmg/lml/dose dropping pills, seal and disinfect. During the flu epidemic, it is used to drip into the nasal cavity to prevent and treat the flu.
实施例 10 Example 10
购买市售广藿香油 100mg,加入适当辅料,溶于 1000ml水中制成 0. 1 %浓度的水溶液, 溶解, 混合均匀后, 密封、 消毒。 在流感疫情期间, 用于注射, 预防治疗。 实施例 11  Buy commercially available patchouli oil 100mg, add appropriate excipients, dissolve in 1000ml water to make 0.1% aqueous solution, dissolve, mix evenly, seal and disinfect. During the flu epidemic, it is used for injection, preventive treatment. Example 11
购买市售广藿香油 100mg, 加入适当辅料, 配成内含广藿香醇 5%的软胶囊, 密封、 消 毒。 在流感疫情期间, 用于口服, 预防或治疗流感。 实施例 12  Purchase 100mg of commercial patchouli oil, add appropriate excipients, and prepare soft capsules containing 5% of patchouli alcohol to seal and disinfect. Used during oral flu, prevention or treatment of influenza. Example 12
购买市售广藿香油, 加入适当辅料后, 压片, 制成片剂, 用于口服预防治疗流感。 实施例 13  Buy commercially available patchouli oil, add appropriate excipients, compress tablets, and make tablets for oral prevention and treatment of influenza. Example 13
取实施例 1制得的广藿香 SFE-C02提取物, 将其与鸡饲料拌匀, 每天用量为广藿香 SFE-C02提取物 0. 15g /只, 分早晚两次服用, 连续服 3天, 用于预防禽流感。 实施例 14  The extract of patchouli SFE-C02 prepared in Example 1 was mixed with the chicken feed, and the daily dose was 0.16 g / of the extract of patchouli SFE-C02, which was taken twice in the morning and evening. Day, used to prevent bird flu. Example 14
取实施例 5制得的百秋李醇, 将其与鸡饲料拌匀, 每天用量为百秋李醇 0. lg /只, 分早晚两次服用, 连续服 3天, 用于预防禽流感。 实施例 15 Take the puppies prepared in Example 5, mix them well with the chicken feed, and use the daily dose of Baiqiu Li alcohol 0. lg / only, take it twice in the morning and evening, and take it for 3 days in a row to prevent bird flu. Example 15
购买市售广藿香油, 将其与猪饲料拌匀, 每天用量为广藿香油 0. 5g /只, 分早晚两 次服用, 连续服 3天, 用于预防禽流感。 上述实施例, 只是本发明的较佳实施例, 并非用来限制本发明实施范围, 故凡以本 发明权利要求所述的特征及原理所做的等效变化或修饰, 均应包括在本发明权利要求范 围之内。  Buy the commercial patchouli oil, mix it with the pig's feed, use the patchouli sesame oil 0. 5g / day, take it twice in the morning and evening, and take it for 3 days in a row to prevent bird flu. The above-described embodiments are merely preferred embodiments of the present invention, and are not intended to limit the scope of the present invention, and equivalent changes or modifications made by the features and principles of the present invention should be included in the present invention. Within the scope of the claims.

Claims

权 利 要 求 Rights request
1、 百秋李醇在制备治疗或预防流感药物中的应用。 1. The application of Baiqiu Li alcohol in the preparation of a medicament for treating or preventing influenza.
2、 广藿香二氧化碳超临界提取物在制备治疗或预防流感药物的应用。 2. The application of patchouli carbon dioxide supercritical extract in the preparation of drugs for the treatment or prevention of influenza.
3、 广藿香油在制备治疗或预防流感药物中的应用。 3. The application of patchouli oil in the preparation of drugs for treating or preventing influenza.
4、由活性有效成份百秋李醇和药学上可接受的载体组成的组合物在制备治疗或预防 流感药物中的应用。 4. Use of a composition comprising the active active ingredient, baicaleol, and a pharmaceutically acceptable carrier for the preparation of a medicament for the treatment or prevention of influenza.
5、 百秋李醇在制备治疗或预防甲 1型流感病毒引起的流感药物中的应用。 5. The application of Baiqiu Li alcohol in the preparation of influenza drugs caused by treating or preventing influenza A virus.
6、 百秋李醇在制备治疗或预防乙型流感病毒引起的流感药物中的应用。 6. The application of Baiqiu Li alcohol in the preparation of influenza drugs caused by treating or preventing influenza B virus.
7、 百秋李醇在制备治疗或预防禽流感病毒 引起的流感药物中的应用。 7. The use of Baiqiu Li alcohol in the preparation of influenza drugs caused by the treatment or prevention of avian influenza virus.
8、一种抗流感药物的组合物, 其特征在于, 所述组合物包含活性有效成份百秋李醇 和 /或药学上可接受的载体。 A composition for an anti-influenza drug, characterized in that the composition comprises the active active ingredient, baicalol, and/or a pharmaceutically acceptable carrier.
9、如权利要求 8所述的抗流感药物的组合物, 其特征在于, 所述活性有效成份百秋 李醇原料来源于广藿香二氧化碳超临界提取物、 广霍香油或广霍香。 The composition for anti-influenza drugs according to claim 8, wherein the active ingredient octoberol raw material is derived from a patchouli carbon dioxide supercritical extract, a broad eucalyptus oil or a broad fragrant incense.
10、如权利要求 8所述的抗流感药物的组合物, 其特征在于, 所述药物的组合物可制 成片剂、 胶囊剂、 颗粒剂、 口服液、 注射液、 滴丸、 吸入剂、 喷雾剂或滴剂。 The anti-influenza drug composition according to claim 8, wherein the composition of the drug is formulated into tablets, capsules, granules, oral liquids, injections, dropping pills, inhalants, Spray or drop.
PCT/CN2009/074811 2009-02-27 2009-11-05 Use of patchouli alcohol in medicament preparation WO2010096987A1 (en)

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