WO2015172614A1 - 五味子总木脂素在制备用于治疗咳嗽的药物或保健品中的应用 - Google Patents

五味子总木脂素在制备用于治疗咳嗽的药物或保健品中的应用 Download PDF

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WO2015172614A1
WO2015172614A1 PCT/CN2015/076068 CN2015076068W WO2015172614A1 WO 2015172614 A1 WO2015172614 A1 WO 2015172614A1 CN 2015076068 W CN2015076068 W CN 2015076068W WO 2015172614 A1 WO2015172614 A1 WO 2015172614A1
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cough
schisandra
lignans
total
group
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French (fr)
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赖克方
钟山
甘振勇
刘晓东
聂怡初
钟南山
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广州医科大学附属第一医院
广州呼吸疾病研究所
呼吸疾病国家重点实验室
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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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/075—Ethers or acetals
    • A61K31/085—Ethers or acetals having an ether linkage to aromatic ring nuclear carbon
    • A61K31/09—Ethers or acetals having an ether linkage to aromatic ring nuclear carbon having two or more such linkages
    • 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)
    • 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)
    • A61K36/79—Schisandraceae (Schisandra family)

Definitions

  • the invention belongs to the field of biomedicine and relates to the use of Schisandra total lignans in preparing medicines or health care products for treating cough, in particular, the medicine or health care for preparing antitussive, relieving cough and eliminating airway inflammation by Schisandra lignans. New use in the product.
  • Cough is the most common symptom in medical clinics and is found in a variety of respiratory and non-respiratory diseases. Cough itself is a defense mechanism that removes excessive secretions from the airways and prevents foreign bodies from inhaling the airways. However, the long-term cough has seriously affected the quality of life of patients and caused a serious psychological burden on patients, and also significantly increased personal and public health expenditures.
  • cough includes acute cough ( ⁇ 3 weeks), subacute cough (3-8 weeks) and chronic cough ( ⁇ 8 weeks).
  • the treatment of cough is generally treated with central antitussives, peripheral antitussives and expectorants, and generally can receive better curative effect.
  • central antitussives such as codeine
  • cough can not be alleviated, so many acute coughs develop into chronic cough, and some patients with chronic cough can even reach several decades.
  • Cough hypersensitivity syndrome Cough hypersensitivity syndrome
  • antitussive drugs such as codeine and dextromethorphan
  • side effects such as constipation, sedation, respiratory depression, etc.
  • Cough drugs cough can not be alleviated, seriously affecting the quality of daily life.
  • Schisandra chinensis The chemical constituents of Schisandra chinensis are mainly volatile oils, lignans, triterpenoids, organic acids and polysaccharides. Among them, biphenyl cyclooctene lignans and triterpene lactones are characteristic of Schisandra. Sexual ingredients. Schisandra has a wide range of pharmacological activities, and there are many reports, especially its protective effect on the liver and the effect of calming the nerves.
  • the lignans are an important component of Schisandra chinensis.
  • the research reports on liver and liver protection are the most widely reported.
  • Schisandra lignans are reported to have anti-tumor, anti-HIV, anti-gastric ulcer and anti-inflammatory. And other effects.
  • total lignans, as an important component of Schisandra chinensis have not been reported in the literature on whether it has a palliative effect on cough.
  • the present invention provides a novel use of Schisandra total lignans for the preparation of a medicament or a health care product for the treatment of acute, subacute or chronic cough.
  • the present invention also provides the use of Schisandra total lignans in the preparation of medicines or health care products for antitussive, relieving cough and eliminating airway inflammation.
  • the Schisandra total lignans are extracted from the Schisandra chinensis, and the lignin content of the extracted Schisandra total lignans is 50% to 100% by mass.
  • the lignans contained in Schisandra total lignans include Schisandrin B, Schisandrin A, Schisandra C, Schizandrol A, Schizandrol B, Schisandrin A and Schisandrin B.
  • the schisandra may be Schisandra chinensis (Turcz.) Baill. (or Schisandra chinensis) and/or Schisandra sphenanthera Rehd.et Wils. (ie, Schisandra chinensis).
  • Schisandra lignans into pharmaceutically acceptable dosage forms by prior art preparation processes in the art, such as, but not limited to, tablets, hard capsules, soft capsules, powders, elixirs. , oral liquid, syrup, granules, pills or injections.
  • the present invention also provides a pharmaceutical or nutraceutical composition for treating cough, the active ingredient of which includes Schisandra total lignans.
  • the pharmaceutical or health care product composition contains 50-100% by mass of a lignan component in Schisandra total lignans;
  • composition may be formulated into a pharmaceutically acceptable dosage form such as, but not limited to, a tablet, a hard capsule, a soft capsule, a powder, an elixir, an oral solution, a syrup, a granule, a pill, or an injection.
  • a pharmaceutically acceptable dosage form such as, but not limited to, a tablet, a hard capsule, a soft capsule, a powder, an elixir, an oral solution, a syrup, a granule, a pill, or an injection.
  • the Schisandra total lignans of the present invention are extracted from Schisandra chinensis by conventional methods known in the art.
  • the total lignans of Schisandra chinensis can be prepared by the method disclosed in the patent application No. CN201110020423: 10 times the amount of 70% ethanol (containing 2% Tween 20), and the schisandra chinensis is refluxed twice, each time 1
  • the extracts were combined and concentrated under reduced pressure.
  • the concentrate was extracted three times with ethyl acetate.
  • the ethyl acetate layer was collected, concentrated under reduced pressure, and diluted with water, and then applied to XAD-4 resin, eluted with distilled water, and then used After elution with 70% ethanol, the 70% ethanol fraction was collected, concentrated under reduced pressure, and then subjected to vacuum spray drying.
  • the present invention is directed to the clinical treatment and difficulty of cough, and the experiment is carried out by using cigarette smoke to stimulate the guinea pig model with increased cough sensitivity and citric acid smoke stimulation.
  • the results show that Schisandra total lignan can significantly prolong cigarette smoke stimulation.
  • Schisandrin A The use of Schisandrin A, Schisandrin B and Schisandrin A had no significant effect, and the effect of Schisandra lignans was significantly better than that of Schisandra chinensis, and it showed a dose-effect relationship, showing antitussive, relieving cough and eliminating gas. The application prospects of tract inflammation.
  • Figure 1 is a representative image of lung tissue and airway pathological section of guinea pig in Example 1 (HE ⁇ 200),
  • Figure 2 shows the effect of schisandra total lignans on the frequency of citric acid smoke stimulation in guinea pigs at different time points.
  • mice used in the specific examples pure white Hartly guinea pig, normal grade, male, weighing 300 ⁇ 50 g, provided by Guangdong Experimental Animal Center (SCXK (Yue) 2008-0002).
  • Guinea pigs are housed in a relatively clean, quiet, constant temperature (23 ⁇ 3 ° C), constant humidity (55 ⁇ 15%) environment, day and night cycle of 12: 12 hours / day, caged, 5 / cage, free access to food And water.
  • the schisandra chinensis was pulverized, and the extract was refluxed twice with 1:10 of 70% ethanol (containing 2% Tween 20) for 1 hour each time.
  • the extracts were combined, concentrated under reduced pressure, and the concentrate was extracted with ethyl acetate three times.
  • the ethyl acetate layer was collected, concentrated under reduced pressure, diluted with an appropriate amount of water, and then applied to the XAD-4 resin, eluted with distilled water, and then eluted with 70% ethanol, and the fraction eluted with 70% ethanol, concentrated under reduced pressure, and then concentrated.
  • Vacuum spray drying was carried out to obtain a lignan content of 83%.
  • Schisandra medicinal material smashed ⁇ 8 times water decoction for 2h, decoction 3 times ⁇ decoction liquid concentration, drying ⁇ Schisandra water extract;
  • PM type single-cavity non-restricted small animal body scanner (1.0L): American Buxco company; digital photography integration system: Japan Nikon company; 0.6m ⁇ 0.6m ⁇ 1m cigarette smoke poisoning box: this Laboratory-made; A1003 electronic balance: Germany Satorius company; MDF-U53V-80 °C low temperature refrigerator: Japan Sanyo company; 3-18K SIGMA high-speed refrigerated centrifuge: Beckman, USA; 22G intravenous indwelling needle: Suzhou Medical Devices Co., Ltd.; Anke TGL-16B ordinary high speed centrifuge: Shanghai Anshang Scientific Instrument Factory; 400 type desktop cryogenic centrifuge: Germany Heraeus Company; XW80A type vortex oscillator: Shanghai Precision Instrument and Meter Co., Ltd.; DK8A constant temperature water bath: Shanghai Jinghong Test Equipment Limited.
  • Example 1 Pharmacological effects of Schisandra lignans on cough sensitivity caused by cigarette smoke stimulation in guinea pigs
  • 1.1 Smoke method After a week of adaptive quiet feeding, the guinea pigs were placed in a self-made cigarette poisoning box, and 10 cigarettes were ignited in the smoker tank each time (baked tobacco type, tar content 12 mg, smoke nicotine content 1.1 Mg, smoke carbon monoxide content 15mg), the cigarette smoke into the poison box through the three-way valve, starting from the burning of the cigarette. Each time the smoke is smoked for 20 minutes, the smoke is smoked twice a day, the interval between each two smokes is more than 6 hours, and the smoke is continuously smoked for 14 days.
  • Guinea pigs were completely randomized into normal group, model group, solvent control group (0.5% PEG400), codeine group, water extract high dose group (dose 500 mg/kg guinea pig/day, drug concentration 50 mg/mL), total lignan High-dose group (dose 500mg/kg guinea pig/day, drug concentration 50mg/mL), total lignan middle dose group (dose 250mg/kg guinea pig/day, drug concentration 25mg/mL), total lignan low dose group (dose 125mg/kg guinea pig/day, drug concentration 12.5mg/mL), Schisandra A high dose group (dose 500mg/kg guinea pig/day, drug concentration 50mg/mL), Schisandra B high dose group (dose 500mg/kg) Guinea pig/day, drug concentration 50 mg/mL) and Schisandra ester A high dose group (dose 500 mg/kg guinea pig/day, drug concentration 50 mg/m
  • the other groups of animals were stimulated by the smoking method in 1.1 above. Except for the normal group and the codeine group, the other groups of guinea pigs were orally administered with the corresponding drugs or solvents for 2 days from the first day of smoking, 2 hours before the second smoke every day.
  • the codeine group was orally administered 1 hour before the citrate cough sensitivity test (30 mg/kg guinea pig, codeine concentration 3 mg/mL). The normal group was raised normally without any treatment.
  • the guinea pigs were placed in the body drawing box. After 2 minutes of adaptation, 0.4 mol/L citric acid was atomized for cough stimulation. After 10 minutes, the atomization was finished, and the observation was continued for 10 minutes. The total number of guinea pig coughs was recorded within 20 minutes from the start of atomization. And cough latency.
  • anesthetized animals were intraperitoneally injected with 3% sodium pentobarbital solution (1 mL/kg), and 10 mL of blood was taken from the heart. 6 mL of 0.1 mol/L pre-cooled PBS buffer was taken, and alveolar lavage was performed in 3 times. The left lung was uniformly irrigated and irrigated 3 times each time to obtain Bronchoalveolar Lavage Fluid (BALF).
  • BALF Bronchoalveolar Lavage Fluid
  • the number of coughs stimulated by citric acid in each experimental group was shown in Table 1.
  • Table 1 The results showed that compared with the model group, total lignans (high, medium and low dose groups) significantly reduced the number of coughs in the model guinea pigs, and showed a dose-related relationship; compared with the model group, the water extract high dose There was no significant difference in the number of coughs in the guinea pigs, the high dose group of Schisandra A, the high dose of Schisandrin B and the high dose of Schisandrin.
  • the cough latency of guinea pig citrate cough challenge test in each experimental group is shown in Table 2.
  • the results showed that compared with the model group, the cough latency of the high, medium and low doses of total lignans was significantly prolonged; the high doses of water extract, schisandrin A, schisandrin and schisandrin had no significant effect on the cough latency of guinea pigs. .
  • the experimental results of the total number of inflammatory cells and classification in BALF of each experimental group are shown in Table 3.
  • the results showed that the total, intermediate and low doses of total lignans significantly reduced the total number of inflammatory cells in BALF compared with the model group; the high and medium doses of total lignans significantly reduced the proportion of neutrophils in BALF.
  • the total number of BALF cells and cell counts in the high-dose group of water extract, schisandrin A, Schisandrin B and Schisandrin A were not significantly different from those in the model group.
  • Example 1 The experimental results of Example 1 showed that the total lignans of Schisandra chinensis increased the cough sensitivity caused by cigarette smoke stimulation, and the guinea pigs had significant effects of reducing the number of coughs, prolonging the cough latency, and alleviating lung and airway inflammation.
  • Embodiment 2 is a diagrammatic representation of Embodiment 1:
  • cough sensitivity screening 0.8mol/L citric acid atomization stimulation for 1min, stop atomization, continue to observe for 5min, record the number of coughs within 6min from the start of nebulization, more than 10 times less than 50 times of guinea pigs Qualified guinea pig.
  • the qualified guinea pigs were completely randomly divided into normal group, solvent control group (0.5% PEG400), codeine group, high-dose water extract group (dose 500 mg/kg guinea pig/day, drug concentration 50 mg/mL), total wood High-dose lipoprotein group (dose 500mg/kg guinea pig/day, drug concentration 50mg/mL), total lignan medium dose group (dose 250mg/kg guinea pig/day, drug concentration 25mg/mL), total lignan low dose Group (dose 125mg/kg guinea pig/day, drug concentration 12.5mg/mL), Schisandra A high dose group (dose 500mg/kg guinea pig/day, drug concentration 50mg/mL), Schisandra B high dose group (dose 500mg/ Kg guinea pig/day, drug concentration 50 mg/mL) and Schisandra ester A high dose group (dose 500 mg/kg guinea pig/day,
  • the other groups of guinea pigs were orally administered with drugs or solvents for 5 days, once a day, 5 days after the fifth day of administration or after 1 h of solvent, citrate cough stimulation: 0.8 mol / L lemon
  • citrate cough stimulation 0.8 mol / L lemon
  • the acid atomization was stimulated for 1 min, the atomization was stopped, and the observation was continued for 5 min, and the number of coughs within 6 minutes from the start of the atomization was recorded.
  • the codeine group was orally administered 1 hour before the citrate cough challenge on the 5th day.
  • the normal group was raised normally, and the citric acid challenge was directly performed on the fifth day.
  • the number of coughs in each experimental group is shown in Table 5. The results showed that compared with the normal group, the number of coughs in the guinea pigs in the high, medium and low doses of total lignans was significantly reduced. The number of coughs in the guinea pigs in the high-dose group of water extract, schisandrin A, Schisandrin B and Schisandrin A was not found. Significant differences.
  • the cough latency of guinea pigs in each experimental group is shown in Table 6. The results showed that compared with the normal group, the cough latency of the guinea pigs in the high, medium and low doses of total lignans was significantly prolonged. The cough latency of guinea pigs in the high doses of water extract, schisandrin A, schisandrin and schisandrin. No significant difference.
  • Example 2 The results of Example 2 indicate that the total lignans of Schisandra chinensis can significantly reduce the cough frequency and prolong the cough latency of guinea pigs caused by citric acid smog stimulation, and show the potential application in the treatment of acute cough.
  • cough sensitivity screening 0.8mol/L citric acid atomization stimulation for 1min, stop atomization, continue to observe for 5min, record the number of coughs within 6min from the start of nebulization, more than 10 times less than 50 times of guinea pigs Qualified guinea pig.
  • the second largest group was randomly divided into 3 groups: normal group, codeine group (30 mg/kg, oral administration), Schisandra total lignan group (250 mg/kg, drug concentration 25 mg/mL, oral administration) 10 in each group, the normal group was directly stimulated by citrate cough, the cough group and the schisandra total lignan group were given cough stimulation 1 hour after the administration, the challenge conditions were the same as the first group; the third group and the fourth group The grouping and challenge conditions of the large group were the same as those of the second group.
  • the administration time of the codeine group and the schisandra total lignan group were 3 h and 5 h before the challenge, respectively. The results are shown in Figure 2.
  • the results of the experiments of Examples 1-3 show that Schisandra lignans can significantly prolong the cough sensitivity caused by cigarette smoke stimulation, increase the cough latency of guinea pigs and citric acid-induced acute cough guinea pigs, reduce the number of coughs, and significantly reduce cough caused by cigarette smoke stimulation.
  • the sensitivity increased the number of inflammatory cells and the proportion of neutrophils in the alveolar lavage fluid of guinea pigs.
  • Pathological sections showed that the infiltration of inflammatory cells in the peripheral bronchioles of guinea pigs was significantly reduced after the intervention of Schisandra lignans, the exudation in the lumen was alleviated, and the alveolar septum was increased.
  • Schisandra chinensis has a significant inhibitory effect on airway inflammation in guinea pigs.
  • the use of Schisandrin A, Schisandrin B and Schisandrin A had no significant effect, and the effect of Schisandra lignans was significantly better than that of Schisandra chinensis, and it showed a dose-effect relationship, showing antitussive, relieving cough and eliminating gas. The application prospects of tract inflammation.
  • the Schisandra total lignans of this example were prepared using the preparation process described above.
  • the syrup prepared in the fourth experiment was clinically tested, including 15 cases of chronic cough and 10 cases of acute cough.
  • the patient consumed syrup 1 to 3 times a day, 10 mL each time, and took 1 to 2 weeks continuously, the total effective rate was 100%.
  • the specific results will be shown in the table below.
  • Case 1 Huang, male, cough for about 1 year, mainly dry cough, all tests are normal, diagnosed as cough hypersensitivity syndrome. Taking 2 bottles of schisandra total lignan syrup, the first day began to work, cough improved by 50%, after adding 2 bottles, the cough improved by 90%, no recurrence.
  • Case 2 Li, female, 24 years old, coughing in January, diagnosed as cough after infection, taking 2 bottles of Schisandra total lignan syrup, taking effect on the next day, the frequency of cough was significantly reduced, after taking 2 bottles, coughing The symptoms are basically eliminated.
  • Case 3 Lai, male, 27 years old, cough for more than 1 year, diagnosed as cough after infection, taking 3 bottles of Schisandra total lignan syrup, the first day of taking the drug started to take effect, the cough frequency decreased, the degree decreased significantly, by the array The cough becomes a single cough, and after the three bottles are taken, the cough is completely eliminated.
  • Case 4 Zhuo, female, 56 years old, coughing and coughing for more than 10 years, diagnosed as chronic bronchitis, eosinophilic bronchitis, taking 2 bottles of Schisandra total lignan syrup, taking the medicine to take effect the next day, The cough improved by 70%. After taking 2 bottles, the cough was basically eliminated. There was no recurrence after 3 months of follow-up.
  • Case 5 Wu, male, 33 years old, coughing for more than 4 years, a little white sticky sputum, diagnosed as cough hypersensitivity syndrome. Take 2 bottles of schisandra total lignan syrup, take the medicine the next day, the cough is improved by 40%, basically no sputum, after adding 2 bottles, the cough is basically eliminated.
  • the oral administration of Schisandra lignin syrup can effectively alleviate cough and reduce airway inflammation.
  • the total lignans of Schisandra chinensis are extracted from the traditional Chinese medicine Schisandra, and the Schisandra is a Chinese medicine that can be used for health foods announced by the Ministry of Health. There is no toxicity or side effects to the human body.
  • the schisandra lignans can also be made into other pharmaceutically acceptable dosage forms, such as tablets, hard capsules, soft capsules, powders, elixirs, according to the needs of those skilled in the art. Pills, granules, injections or other oral liquid dosage forms and the like.
  • the granules can be prepared by mixing schisandra total lignans with adjuvant starch, sucrose, and disintegrant, and then adding the mixture to a solution of the binder cellulose derivative dissolved in water for extrusion.
  • the granulation method prepares the soft particles into a soft granule, which is dried, sieved, sieved and pulverized, and sieved to obtain uniform granules.
  • the tablet can also be prepared by mixing schisandra total lignans with appropriate amount of starch and talc, moistening with 70% ethanol, preparing granules, and then pressing the tablets with a tableting machine to prepare schisandra total lignans. sheet.
  • Schisandra total lignan capsules can also be prepared by adding appropriate amount of carboxymethyl cellulose and cyclodextrin to Schisandra lignans.

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Abstract

本发明涉及五味子总木脂素在制备治疗咳嗽的药物或保健品中的新用途，具体如在制备治疗镇咳、缓解咳嗽及消除气道炎症的药物或保健品中的新用途。实验表明五味子总木脂素能显著减少香烟烟雾刺激致咳嗽敏感性增高豚鼠及柠檬酸烟雾刺激致急性咳嗽豚鼠的咳嗽次数，延长咳嗽潜伏期，并能显著减轻香烟烟雾刺激致咳嗽敏感性增高豚鼠的气道炎症，提示五味子总木脂素可用于制备镇咳、缓解咳嗽及消除气道炎症的药物。

Description

五味子总木脂素在制备用于治疗咳嗽的药物或保健品中的应用 技术领域
本发明属于生物医药领域，涉及五味子总木脂素在制备用于治疗咳嗽的药物或保健品的用途，特别是五味子总木脂素在制备镇咳、缓解咳嗽及消除气道炎症的药物或保健品中的新用途。
背景技术
咳嗽是内科门诊最常见的症状，见于多种呼吸系统及非呼吸系统疾病。咳嗽本身是一种防御机制，清除气道内过多的分泌物及防止异物误吸入气道。但持续长时间的咳嗽却严重影响了患者的生活质量并造成患者严重的心理负担，同时也显著增加了个人及公共医疗卫生支出。
按照病程来分，咳嗽包括急性咳嗽(<3周)、亚急性咳嗽(3～8周)和慢性咳嗽(≥8周)。目前咳嗽的治疗一般都是采用中枢性镇咳药、周围性镇咳药及祛痰药等进行治疗，一般都能收到较好的疗效。但仍有部分急慢性咳嗽即使采用可待因等中枢性镇咳药物，咳嗽仍旧不能得到缓解，以致许多急性咳嗽发展成为慢性咳嗽，有的慢性咳嗽患者病程甚至达到几十年。
多份国外流行病学研究显示慢性咳嗽在普通人群的发病率约9％～33％，2003年一项英国流行病学调查显示，慢性咳嗽在50～59岁的中年人发病率达12％，慢性咳嗽患者约占呼吸专科门诊患者的20％。近年随着大气环境污染的逐渐加重(如PM2.5、PM10等)，慢性咳嗽的患病率还可能继续上升。目前的研究认为导致慢性咳嗽的主要病因包括：咳嗽变异性哮喘、嗜酸粒细胞性支气管炎、胃食管反流性咳嗽、上气道咳嗽综合征。对于上述病因引起的咳嗽，遵循咳嗽指南进行相应的治疗，大部分患者咳嗽可得到明显缓解。然而，仍有部分慢性咳嗽患者经过系列全面的检查后，未见明显异常，但咳嗽症状持续存在，既往称之为慢性特发性咳嗽(Chronic idiopathic cough,CIC)，其咳嗽症状治疗不佳，且无针对性病因治疗，是目前慢性咳嗽领域的难点及重点所在。有研究发现慢性特发性咳嗽以中年人多见，多以感冒为触发因素，此后咳嗽长期存在，通常对油烟、刺激性气味、冷空气、香烟烟雾等异常敏感，有时甚至大笑或讲话可诱发咳嗽，表现为咳嗽敏感性明显增高。针对此种情况，将咳嗽敏感性增高的慢性咳嗽称之为咳嗽高敏综合征(Cough hypersensitivity syndrome，CHS)。咳嗽敏感性异常增高是慢性咳嗽高敏综合征患者共有的关键特征。
目前对于咳嗽高敏综合征的患者，暂无合适的治疗手段可供选择，大多靠镇咳药物维持治疗。但镇咳药物，如可待因及右美沙芬等，存在着不同程度的副作用，如便秘、镇静、呼吸抑制等，因而限制了其使用，而且部分咳嗽高敏综合征的患者甚至使用中枢性镇咳药物，咳嗽亦不能缓解，严重影响日常生活质量。
五味子味酸、甘，性温。归肺、心、肾经。肺为娇脏，恶燥，五味子甘温而润，润肺止咳；久咳致肾不纳气，五味子味酸收敛，助肾纳气，治疗肺阴亏虚、肾不纳气所致久咳可谓功效极大。《本草会编》记载：“劳嗽，宜用北者；风寒在肺，宜用南者”；《药品化义》记载：“五味子……能收敛肺气，主治虚劳久咳”；《本草求原》记载：“五味子，为咳嗽要药，凡风寒咳嗽、伤暑咳嗽、伤燥咳嗽、劳伤咳嗽、肾水虚咳、肾火虚咳、久咳喘促……皆用之”。张仲景明确指出：凡咳者均可加入五味子。《中华人民共和国药典》载其用于“久咳虚喘，……心悸失眠”。中医临床上五味子广泛用于咳嗽后期的干咳无痰或久咳不已的肺虚咳嗽病症。
五味子的化学成分主要为挥发油类、木脂素类、三萜类、有机酸类及多糖类，其中联苯环辛烯木脂素类和降三萜内酯类成分是五味子属植物的特征性成分。五味子药理活性广泛，相关报道众多，尤其是其对肝脏的保护作用及宁心安神作用方面，研究较多。
木脂素类成分是五味子药材中的一类重要成分，有关其保肝护肝作用的研究报道最多，此外据报道五味子木脂素类成分还具有抗肿瘤、抗HIV、抗胃溃疡、抗炎等功效。但是，总木脂素作为五味子药材中及其重要的一类成分，一直未见关于其对咳嗽是否有缓解功效的文献报道。
发明内容
本发明的目的在于提供五味子总木脂素的新用途，具体在于提供五味子总木脂素在制备治疗咳嗽的药物或保健品中的新用途。
进一步的，本发明提供五味子总木脂素在制备用于治疗急性、亚急性或慢性咳嗽的药物或保健品中的新用途。
进一步的，本发明还提供五味子总木脂素在制备用于镇咳、缓解咳嗽及消除气道炎症的药物或保健品中的应用。
所述五味子总木脂素，是从五味子药材中提取得到的，提取得到的五味子总木脂素中木脂素类成分含量为50％～100％(质量)。
五味子总木脂素中所含的木脂素类成分包括有五味子乙素、五味子甲素、五味子丙素、五味子醇甲、五味子醇乙、五味子酯甲和五味子酯乙等。
所述的五味子药材可以是五味子Schisandra chinensis(Turcz.)Baill.(即北五味子)和/或华中五味子Schisandra sphenanthera Rehd.et Wils.(即南五味子)。
本领域技术人员可以将五味子总木脂素通过本技术领域现有的制剂工艺将其制成药学上可接受的剂型，所述剂型例如但不限于片剂、硬胶囊、软胶囊、散剂、酊剂、口服液、糖浆、颗粒剂、丸剂或注射剂。
本发明还提供一种用于治疗咳嗽的药物或保健品组合物，其活性成分包括五味子总木脂素。
进一步的，所述药物或保健品组合物，其五味子总木脂素中含有50～100％(质量)的木脂素类成分；
进一步的，所述组合物可制成药学上可接收的剂型，剂型例如但不限于片剂、硬胶囊、软胶囊、散剂、酊剂、口服液、糖浆、颗粒剂、丸剂或注射剂。
本发明的五味子总木脂素采用本技术领域现有的常规方法从五味子药材中提取得到。例如，可参照申请号为CN201110020423的专利申请中披露的方法来制备五味子总木脂素：以10倍量的70％乙醇(含2％的Tween 20)回流提取粉碎的五味子2次，每次1小时，合并提取液，减压浓缩，浓缩液用乙酸乙酯萃取3次，收集乙酸乙酯层，减压浓缩后，加适量水稀释，上XAD-4树脂，先用蒸馏水洗脱，然后用70％乙醇洗脱，收集70％乙醇洗脱部分，减压浓缩，之后进行真空喷雾干燥。
本发明针对咳嗽的临床治疗现状及难点，采用香烟烟雾刺激致咳嗽敏感性增高豚鼠模型及柠檬酸烟雾刺激致急性咳嗽豚鼠模型进行了实验，结果表明，五味子总木脂素能显著延长香烟烟雾刺激致咳嗽敏感性增高豚鼠及柠檬酸刺激致急性咳嗽豚鼠的咳嗽潜伏期、减少咳嗽次数，显著减少香烟烟雾刺激致咳嗽敏感性增高豚鼠肺泡灌洗液中炎症细胞总数及中性粒细胞比例，病理切片观察提示五味子总木脂素干预后豚鼠 细支气管周炎症细胞浸润明显减少，管腔内渗出减轻，肺泡间隔增宽程度减轻，提示五味子总木脂素对豚鼠的气道炎症具有显著的抑制作用。单用五味子甲素、五味子乙素和五味子酯甲无显著作用，并且五味子总木脂素的作用明显好于五味子水提取物，且呈一定量效关系，表现出镇咳、缓解咳嗽及消除气道炎症方面的应用前景。
附图说明
图1，为实施例一豚鼠肺组织和气道病理切片代表图(HE×200)，
图2，为五味子总木脂素不同时间点对柠檬酸烟雾刺激豚鼠咳嗽次数的影响。
具体实施方式
下面结合实施例及附图对本发明作进一步详细的描述，但本发明并不限于此。
具体实施例中所用的实验动物：纯白Hartly豚鼠，普通级，雄性，体重300±50g，广东省实验动物中心提供(SCXK(粤)2008-0002)。豚鼠饲养在相对清洁、安静、恒温(23±3℃)、恒湿(55±15％)环境中，日夜周期为12:12小时/天，分笼饲养，5只/笼，可自由获得食物和水。
具体实施例中所用的药物、试剂、及仪器：
1)五味子总木脂素，其制备过程为：
五味子药材粉碎，用料液比1:10的70％乙醇(含2％的Tween 20)回流提取2次，每次1小时，合并提取液，减压浓缩，浓缩液用乙酸乙酯萃取3次，收集乙酸乙酯层，减压浓缩后，加适量水稀释，上XAD-4树脂，先用蒸馏水洗脱，然后用70％乙醇洗脱，收集70％乙醇洗脱部分，减压浓缩，然后进行真空喷雾干燥，所得产物中木脂素含量为83％。
2)五味子水提取物，其制备过程为：
五味子药材粉碎→8倍量水煎煮2h，共煎煮3次→煎煮液浓缩，干燥→五味子水提取物；
3)五味子甲素、五味子乙素和五味子酯甲：沈阳开笛科技有限公司。0.9％氯化钠注射液：东莞普济药业有限公司。戊巴比妥钠：美国Merck公司。可待因：国药集团工业股份有限公司。“红玫”牌过滤嘴香烟：广州中烟工业有限公司。其它常规试剂：广州化学试剂厂。
4)实验仪器：PM型单腔非限制型小动物体描仪(1.0L)：美国Buxco公司；数码摄影一体化系统：日本Nikon公司；0.6m×0.6m×1m香烟烟雾染毒箱：本实验室自制；A1003电子天平：德国Satorius公司；MDF-U53V-80℃低温冰箱：日本三洋公司；3-18K SIGMA高速冷冻离心机：美国Beckman公司；22G静脉留置针：苏州医疗器械有限公司；Anke TGL-16B型普通高速离心机：上海安停科学仪器厂；400型台式低温离心机：德国Heraeus公司；XW80A型旋涡振荡器：上海精密仪器仪表有限公司；DK8A恒温水浴锅：上海精宏试验仪器有限公司。
具体实施方式中所有数据用“均值±标准差”表示，各组间比较采用spss13.0进行单因素方差分析，方差齐用最小显著差异法(LSD)，方差不齐或非正态的数据采用秩和检验，P＜0.05表示差异有统计学意义。
实施例一：五味子总木脂素对香烟烟雾刺激致咳嗽敏感性增高豚鼠的药理作用
1.1烟熏方法：豚鼠于实验前适应性安静饲养一周后，置于自制香烟染毒箱内，每次点燃10根香烟于烟熏槽内(烤烟型，焦油含量12mg，烟气烟碱含量1.1mg，烟气一氧化碳含量15mg)，通过三通阀将香烟烟雾打入染毒箱内，自香烟燃完开始计时。每次熏烟20分钟，每天熏烟2次，每二次熏烟间隔时间大于6小时，连续熏烟14天。
1.2实验：
豚鼠完全随机分成正常组、模型组、溶剂对照组(0.5％的PEG400)、可待因组、水提取物高剂量组(剂量500mg/kg豚鼠/天，药物浓度50mg/mL)、总木脂素高剂量组(剂量500mg/kg豚鼠/天，药物浓度50mg/mL)、总木脂素中剂量组(剂量250mg/kg豚鼠/天，药物浓度25mg/mL)、总木脂素低剂量组(剂量125mg/kg豚鼠/天，药物浓度12.5mg/mL)、五味子甲素高剂量组(剂量500mg/kg豚鼠/天，药物浓度50mg/mL)、五味子乙素高剂量组(剂量500mg/kg豚鼠/天，药物浓度50mg/mL)和五味子酯甲高剂量组(剂量500mg/kg豚鼠/天，药物浓度50mg/mL)。
除正常组外，其余各组动物均采用上述1.1中的烟熏方法刺激。除正常组及可待因组外，其余各组豚鼠从烟熏第一天开始，于每天的第二次烟熏前2小时经口给予相应的药物或溶剂，连续14天。可待因组于柠檬酸咳嗽敏感性检查前1小时，经口给药(30mg/kg豚鼠，可待因浓度3mg/mL)。正常组正常饲养，不作任何处理。第15天将豚鼠置于体描箱内，适应2min后，雾化0.4mol/L柠檬酸进行咳嗽激发，10min后雾化结束，继续观察10min，记录自雾化开始的20min内豚鼠咳嗽总次数及咳嗽潜伏期。
咳嗽激发实验24h后，3％戊巴比妥钠溶液(1mL/kg)腹腔注射麻醉动物，心脏取血10mL。取6mL 0.1mol/L预冷的PBS缓冲液，分3次进行肺泡灌洗，统一灌洗左肺，每次反复灌洗3次，得肺泡灌洗液(Bronchoalveolar Lavage Fluid，BALF)。将所得BALF震荡混悬，抽取0.5mL，用红细胞裂解液充分裂解，3000转/分钟离心10分钟，取10μL上清液滴入血细胞计数板，光学显微镜下计算BALF炎症细胞总数(细胞总数/mL＝(四大格细胞总数/4)×104/mL)；抽取0.5mL后剩余的BALF于3000rpm离心10min，沉淀用1mLPBS混悬，取100μL制作细胞涂片，自然风干，浸泡于10％中性甲醛中过夜固定，取出后依次进行流水冲洗10min、苏木素染色15sec、流水冲洗1min、1％盐酸酒精脱色2sec、流水冲洗10min、伊红染色5sec、流水冲洗10min、烘干，得中性树胶封片，光学显微镜下连续随机抽取20个400倍视野进行连续计数，每张涂片连续计数400个细胞，计算其中中性粒细胞、嗜酸粒细胞、巨噬细胞、淋巴细胞的比例。
豚鼠抽取BALF后，从心脏注入50mLPBS进行灌洗，从气管注入2.5mL4％多聚甲醛，然后剪取一块右下肺组织及一段气管，10％中性甲醛固定24h以上。取出已固定好的肺组织，依次进行乙醇梯度脱水、生物透明剂处理、浸蜡、包埋、切片、脱蜡、梯度酒精水化、双蒸水短暂漂洗，最后进行HE染色后，中性树胶封片，进行病理观察。
实验结果：与正常组比较，各实验组豚鼠气道阻力未见明显差异，提示本实验建模方法未造成豚鼠气道阻力增加，有别于慢性阻塞性肺疾病动物模型。
各实验组豚鼠柠檬酸激发咳嗽次数见表1。结果表明，与模型组比较，总木脂素(高、中、低剂量组)均能显著减少模型豚鼠的咳嗽次数，且表现出一定的剂量相关性；与模型组比较，水提取物高剂量组、五味子甲素高剂量组、五味子乙素高剂量组和五味子酯甲高剂量组豚鼠咳嗽次数无显著差异。
表1各实验组对香烟烟雾刺激致咳嗽敏感性增高模型豚鼠的咳嗽次数影响
Figure PCTCN2015076068-appb-000001
(n＝7～10)
Figure PCTCN2015076068-appb-000002
注：与模型组比较：*P<0.05，**P<0.01
各实验组豚鼠柠檬酸咳嗽激发实验咳嗽潜伏期见表2。结果表明，与模型组比较，总木脂素高、中、低剂量干预组咳嗽潜伏期均显著延长；水提取物、五味子甲素、五味子乙素和五味子酯甲高剂量对豚鼠咳嗽潜伏期无显著影响。
表2各实验组对香烟烟雾刺激致咳嗽敏感性增高模型豚鼠的咳嗽潜伏期影响
Figure PCTCN2015076068-appb-000003
(n＝7～10)
Figure PCTCN2015076068-appb-000004
注：与模型组比较：*P<0.05，**P<0.01
各实验组BALF中炎症细胞总数及分类比较实验结果见表3。结果表明，与模型组比较，总木脂素高、中、低剂量均能显著减少BALF中炎症细胞总数；总木脂素的高、中剂量可显著减少BALF中中性粒细胞的比例。与模型组比较，水提取物、五味子甲素、五味子乙素和五味子酯甲高剂量组豚鼠BALF细胞总数及细胞分类计数与模型组无显著差异。
表3各实验组对慢性咳嗽敏感性增高模型豚鼠的支气管肺泡灌洗液炎症细胞总数和分类的作用
Figure PCTCN2015076068-appb-000005
(n＝7～10)
Figure PCTCN2015076068-appb-000006
注：与模型组比较：*P<0.05，**P<0.01
病理切片观察结果表明，与模型组比较，五味子总木脂素各剂量组豚鼠肺组织及气管病理均明显改善：豚鼠细支气管周炎症细胞浸润明显减少，管腔内渗出减轻，肺泡间隔增宽程度减轻，提示五味子总木脂素具有明显的减轻肺及气道炎症的作用。而水提取物、五味子甲素、五味子乙素和五味子酯甲高剂量组豚鼠肺组织及气管病理改善不明显。豚鼠肺组织及气管病理切片代表图见附图1。
实施例一的实验结果表明，五味子总木脂素对香烟烟雾刺激致咳嗽敏感性增高豚鼠具有显著的降低咳嗽次数、延长咳嗽潜伏期、减轻肺及气道炎症的作用。
实施例二：
豚鼠静养一周后，进行咳嗽敏感性筛选：0.8mol/L柠檬酸雾化刺激1min，停止雾化，继续观察5min，记录自雾化开始6min内的咳嗽次数，大于10次小于50次的豚鼠为合格豚鼠。
将筛选合格的豚鼠完全随机分成正常组、溶剂对照组(0.5％的PEG400)、可待因组、水提取物高剂量组(剂量500mg/kg豚鼠/天，药物浓度50mg/mL)、总木脂素高剂量组(剂量500mg/kg豚鼠/天，药物浓度50mg/mL)、总木脂素中剂量组(剂量250mg/kg豚鼠/天，药物浓度25mg/mL)、总木脂素低剂量组(剂量125mg/kg豚鼠/天，药物浓度12.5mg/mL)、五味子甲素高剂量组(剂量500mg/kg豚鼠/天，药物浓度50mg/mL)、五味子乙素高剂量组(剂量500mg/kg豚鼠/天，药物浓度50mg/mL)和五味子酯甲高剂量组(剂量 500mg/kg豚鼠/天，药物浓度50mg/mL)。除正常组及可待因组外，其余各组豚鼠连续5天每天经口给予药物或溶剂，1次/天，第五日给药或溶剂后1h进行柠檬酸咳嗽激发：0.8mol/L柠檬酸雾化刺激1min，停止雾化，继续观察5min，记录自雾化开始6min内的咳嗽次数。可待因组于第5日柠檬酸咳嗽激发前1小时经口给药。正常组正常饲养，第五日直接进行柠檬酸激发。
各实验组的咳嗽次数如表5所示。结果表明，与正常组比较，总木脂素高、中、低剂量干预组的豚鼠咳嗽次数均显著减少，水提取物、五味子甲素、五味子乙素和五味子酯甲高剂量组豚鼠咳嗽次数无显著差异。
表5各实验组柠檬酸致急性咳嗽豚鼠的咳嗽次数
Figure PCTCN2015076068-appb-000007
(n＝8)
Figure PCTCN2015076068-appb-000008
注：与正常组组比较：*P<0.05，**P<0.01
各实验组豚鼠的咳嗽潜伏期如表6所示。结果表明，与正常组比较，总木脂素高、中、低剂量干预组豚鼠的咳嗽潜伏期均显著延长，水提取物、五味子甲素、五味子乙素和五味子酯甲高剂量干预组豚鼠咳嗽潜伏期无显著差异。
表6各实验组柠檬酸致急性咳嗽豚鼠的咳嗽潜伏期
Figure PCTCN2015076068-appb-000009
(n＝8)
Figure PCTCN2015076068-appb-000010
Figure PCTCN2015076068-appb-000011
注：与正常组比较：*P<0.05，**P<0.01
实施例二的结果说明五味子总木脂素能显著降低柠檬酸烟雾刺激致急性咳嗽豚鼠的咳嗽次数、延长咳嗽潜伏期，表现出治疗急性咳嗽方面的应用潜力。
实施例三
豚鼠静养一周后，进行咳嗽敏感性筛选：0.8mol/L柠檬酸雾化刺激1min，停止雾化，继续观察5min，记录自雾化开始6min内的咳嗽次数，大于10次小于50次的豚鼠为合格豚鼠。
筛选合格的豚鼠正常饲养3天后，随机分为4大组，每大组30只。第一大组随机分为3小组，每小组10只，均直接进行柠檬酸咳嗽激发：0.8mol/L柠檬酸雾化刺激1min，停止雾化，继续观察5min，记录自雾化开始6min内的咳嗽次数。第二大组随机分为3小组：正常组、可待因组(30mg/kg，经口给药)、五味子总木脂素组(250mg/kg，药物浓度25mg/mL，经口给药)，每小组10只，正常组直接进行柠檬酸咳嗽激发，可待因组和五味子总木脂素组给药1小时后进行咳嗽激发，激发条件同第一大组；第三大组和第四大组的分组及激发条件均与第二大组相同，可待因组和五味子总木脂素组给药时间分别为激发前3h和5h。结果如图2所示，表明五味子总木脂素(250mg/kg)一次性给药1h后即能显著减少柠檬酸烟雾刺激致豚鼠急性咳嗽次数，并且在给药5h后仍能表现出显著的药效，而可待因在给药5h后咳嗽次数与正常组已无显著差异。
实施例1～3的研究结果表明，五味子总木脂素能显著延长香烟烟雾刺激致咳嗽敏感性增高豚鼠及柠檬酸刺激致急性咳嗽豚鼠的咳嗽潜伏期、减少咳嗽次数，显著减少香烟烟雾刺激致咳嗽敏感性增高豚鼠肺泡灌洗液中炎症细胞总数及中性粒细胞比例，病理切片观察提示五味子总木脂素干预后豚鼠细支气管周炎症细胞浸润明显减少，管腔内渗出减轻，肺泡间隔增宽程度减轻，提示五味子总木脂素对豚鼠的气道炎症具有显著的抑制作用。单用五味子甲素、五味子乙素和五味子酯甲无显著作用，并且五味子总木脂素的作用明显好于五味子水提取物，且呈一定量效关系，表现出镇咳、缓解咳嗽及消除气道炎症方面的应用前景。
实施例四(五味子总木脂素糖浆的制备例)
将2kg五味子总木脂素，用适量水溶解制成五味子总木脂素溶液，备用；另取蔗糖2kg，加水煮沸，加入前面已制备好的五味子总木脂素溶液，及苯甲酸钠4g，混匀，静置，取上清液，加水至2000mL，混匀，制成五味子总木脂素的糖浆，每瓶100mL分装。
服用方法：每天1～3次，每次10mL，病情严重者可酌情加量。
本实施例的五味子总木脂素采用前文所述的制备过程制得。
应用例
实施四制得的糖浆经过临床实验，其中有慢性咳嗽15例和急性咳嗽10例，患者每日饮用糖浆1～3次，每次10mL，连续服用1～2周，总有效率为100％，具体结果将下表所示。
病例 显效 有效 无效
急性咳嗽 8 2 0
慢性咳嗽 10 5 0
下面就其中几个个典型病例进行详细介绍：
病例1：黄某，男，咳嗽1年左右，干咳为主，各项检查均正常，诊断为咳嗽高敏综合征。服用五味子总木脂素糖浆2瓶，第2天开始起效，咳嗽好转5成，加服2瓶后，咳嗽好转9成，无复发。
病例2：李某，女，24岁，咳嗽1月，诊断为感染后咳嗽，服用五味子总木脂素糖浆2瓶，服药第二天起效，咳嗽频率显著减少，加服2瓶后，咳嗽症状基本消除。
病例3：赖某，男，27岁，咳嗽1年余，诊断为感染后咳嗽，服用五味子总木脂素糖浆3瓶，服药第一天开始起效，咳嗽频率减少，程度显著下降，由阵发性咳嗽转为单声咳，3瓶服用完后，咳嗽完全消除。
病例4：卓某，女，56岁，咳嗽、咳痰10年余，诊断为慢性支气管炎、嗜酸性粒细胞性支气管炎，服用五味子总木脂素糖浆2瓶，服药第二天起效，咳嗽好转7成，加服2瓶后，咳嗽基本消除，3月后随访无复发。
病例5：伍某，男，33岁，咳嗽4年余，有少许白粘痰，诊断为咳嗽高敏综合征。服用五味子总木脂素糖浆2瓶，服药第二天起效，咳嗽好转4成，基本无痰，加服2瓶后，咳嗽基本消除。
由上述实施例可见，仅通过口服五味子总木脂素糖浆便能有效缓解咳嗽，减轻气道炎症，而且，五味子总木脂素提取自中药五味子，五味子为卫生部公布的可用于保健食品的中药，对人体无任何毒性及副作用。
五味子总木脂素除了制成糖浆外，本领域技术人员根据需要也可以采用现有制剂工艺将其制成药学上可接受的其他剂型，例如片剂、硬胶囊、软胶囊、散剂、酊剂、丸剂、颗粒剂、注射剂或其他口服液剂型等等。例如可以通过如下方法制成颗粒剂：将五味子总木脂素和辅料淀粉、蔗糖以及崩解剂进行混合，再将混合物加入用水溶解的粘合剂纤维素衍生物溶液中进行混合，采用挤出制粒法将药物制成软粒，经干燥，过筛、筛上物适当粉碎、再过筛，可制成均匀颗粒。也可通过如下方法制成片剂：将五味子总木脂素和适量淀粉、滑石粉混合，用70％乙醇湿润，制成颗粒，然后用压片机压片，从而制成五味子总木脂素片。还可通过向五味子总木脂素中加入适量羧甲基纤维素、环糊精，来制备五味子总木脂素胶囊。这些制剂工艺均为本技术领域现有技术，在此不再一一赘述。
以上所述，仅是本发明的较佳实施例而已，并非对本发明做任何形式上的限制，故凡未脱离本发明技术方案的内容，依据本发明的技术实质对以上实施例所做的任何简单修改、等同变化与修饰，均仍属于本发明技术方案的范围内。

Claims (10)

  1. 五味子总木脂素在制备用于治疗咳嗽的药物或保健品中的应用。
  2. 根据权利要求1所述的应用，其特征在于，所述药物或保健品为用于治疗急性、亚急性或慢性咳嗽的药物或保健品。
  3. 根据权利要求1所述的应用，其特征在于，所述药物或保健品为用于镇咳、缓解咳嗽或消除气道炎症的药物或保健品。
  4. 根据权利要求1～3任意一项所述的应用，其特征在于，所述五味子总木脂素是从五味子中提取得到的。
  5. 根据权利要求4所述的应用，其特征在于，所述五味子总木脂素其中含有50～100％的木脂素类成分。
  6. 根据权利要求4所述的应用，其特征在于，所述的五味子为五味子Schisandra chinensis(Turcz.)Baill.、华中五味子Schisandra sphenanthera Rehd.et Wils.中的至少一种。
  7. 根据权利要求1～3任意一项所述的应用，其特征在于，所述五味子总木脂素制成药学上可接受的剂型。
  8. 根据权利要求7所述的应用，其特征在于，所述剂型为片剂、硬胶囊、软胶囊、散剂、酊剂、口服液、糖浆、颗粒剂、丸剂或注射剂。
  9. 一种用于治疗咳嗽的药物或保健品组合物，其特征在于，其活性成分包括五味子总木脂素。
  10. 根据权利要求9所述药物或保健品组合物，其特征在于，所述五味子总木脂素中含有50～100％的木脂素类成分；和/或，所述药物或保健品组合物制成药学上可接受的剂型。
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