WO2019212170A1 - A composition with antitussive and expectoration activities comprising an extract of atractylodis rhizoma alba and schisandrae fructus - Google Patents

A composition with antitussive and expectoration activities comprising an extract of atractylodis rhizoma alba and schisandrae fructus Download PDF

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WO2019212170A1
WO2019212170A1 PCT/KR2019/004598 KR2019004598W WO2019212170A1 WO 2019212170 A1 WO2019212170 A1 WO 2019212170A1 KR 2019004598 W KR2019004598 W KR 2019004598W WO 2019212170 A1 WO2019212170 A1 WO 2019212170A1
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Prior art keywords
atractylodis rhizoma
extract
schisandrae fructus
alba
schisandrae
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PCT/KR2019/004598
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French (fr)
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Jae Hoon You
Min Soo Kim
Jong Lae Lim
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Chong Kun Dang Pharmaceutical Corp.
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Priority to EP19796896.9A priority Critical patent/EP3787658A4/en
Priority to CN201980024280.0A priority patent/CN111971057A/en
Priority to JP2020560326A priority patent/JP7407735B2/en
Publication of WO2019212170A1 publication Critical patent/WO2019212170A1/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/10—Expectorants
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • 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)
    • A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
    • A61K36/284—Atractylodes
    • 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)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/14—Antitussive agents
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2200/00—Function of food ingredients
    • A23V2200/30—Foods, ingredients or supplements having a functional effect on health
    • A23V2200/314—Foods, ingredients or supplements having a functional effect on health having an effect on lung or respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00

Definitions

  • the present invention relates to a composition for treating or preventing respiratory diseases, comprising a mixed extract of Atractylodis Rhizoma Alba and Schisandrae Fructus, or of Atractylodis Rhizoma and Schisandrae Fructus as an active ingredient.
  • the present invention provides a composition useful for treating or preventing respiratory diseases by confirming that the mixed extract of Atractylodis Rhizoma Alba and Schisandrae Fructus, or of Atractylodis Rhizoma and Schisandrae Fructus has improved anti-inflammatory, antitussive, and expectoration activities compared to their single extract.
  • Cough is produced when sensory receptors distributed in the throat, larynx, bronchus, pleura, eardrum, sinus, diaphragm, stomach, esophagus, and the like detect physicochemical stimuli to send the same to the brainstem through the vagus nerve.
  • Cough is a defense mechanism to prevent a foreign substance from being inhaled into the lower respiratory tract, so that excessive secretions and foreign substances are cleared from airways. While cough per se is important, it leads to complications such as fatigue, headache, hoarseness, urinary incontinence, and musculoskeletal pain. As such, it is important to identify a cause of the cough and then treat or prevent the same.
  • cough that lasts more than three weeks is called a chronic cough, which is caused by a variety of diseases, unlike an acute cough caused by a cold. While cough is an important defense mechanism of the lung, if more frequent bouts of coughing than usual is observed, it means that lung or bronchial diseases may exist and it is necessary to find the exact cause.
  • Phlegm is persistently produced, passes through the larynx, and is swallowed into the gastrointestinal tract to be finally eliminated, although we are not aware of that process. Due to increased production of phlegm, change in viscosity, or deteriorated elimination activity of phlegm, phlegm is stored in the airway to cause symptoms such as coughing or dyspnea.
  • Antitussives are a medicinal drug for suppressing coughing irrespective of the cause. It can be divided into the two types according to the mechanism of action: an agent acting on the central nervous system (CNS); and that acting on the peripheral nervous system (PNS).
  • the CNS-acting agent can be divided into narcotic opioids, non-narcotic opioids, and nonopioids.
  • the representative narcotic opioids comprise codeine, hydrocodone, and morphine.
  • Their cough suppressant effect has restrictively been proved without showing consistent results. Further, its use in an optimum dose is at risk for drowsiness, constipation, indigestion, or drug abuse or dependence.
  • the most commonly used PNS-acting antitussive in Korea is levodropropizine, which is considered to exert the effect by modulating the levels of sensory neuropeptide within the respiratory tract.
  • Theobromine is also a type of PNS-acting agents.
  • the main ingredient of phlegm is composed of mucus.
  • Bronchial mucus is generally secreted from mucous glandular cells and serous glandular cells which constitute mucous glands and submucosal glands distributed in bronchial mucosa.
  • Mucus consists of 95% of water, and 5% of the rest consisting of glycoproteins, lipids, minerals, etc., where the glycoprotein is in a gel form of double structure of linear polymers, whereby the mucus is sticky.
  • Expectorants for removing phlegm comprise an agent for increasing moisture content in phlegm and mucolytics for reducing the viscosity by breaking down the S-S bond of a phlegm protein.
  • Cysteine derivatives such as N-acetylcysteine and carbocysteine are used as expectorants while they may cause side effects such as bronchospasm with long-term use. Therefore, the development of expectorants with fewer side effects and toxicity as well as superior expectoration effect is required.
  • ivy leaf extract or the extract combination of ivy leaf and Coptidis Rhizoma are widely used as antitussives/expectorants derived from natural products.
  • Coptidis Rhizoma has side effects of safety and toxicity, such as neurotoxicity and renal dysfunction, as confirmed in animal tests.
  • berberine which is known as a main ingredient of Coptidis Rhizoma, is an alkaloid pharmacologically active substance well known to have anti-cancer and anti-inflammatory activity.
  • it since it may cause acute toxicity, it should carefully be used. Accordingly, it is required to develop a natural product formulation using a herb medicine to ensure safety and to be widely used.
  • Atractylodis Rhizoma refers to a rhizome of Atractylodes japonica Koidzumi belonging to the Compositae family while Atractylodis Rhizoma Alba refers to what is produced by peeling off large roots in the end of the rhizome and then drying the same.
  • the nature of Atractylodis Rhizoma Alba and Atractylodis Rhizoma is warm and the taste is sweet and bitter. They act mainly on the spleen and the stomach to exhibit the effect of invigorating spleen, supporting the function of stomach, draining dampness, and allowing a normal function by harmonizing Middle Jiao.
  • Atractylodis Rhizoma Alba and Atractylodis Rhizoma are known as an agent to treat reduced function of digestive system, including anorexia, lethargy, weakness of the spleen and stomach, and diarrhea.
  • Their main pharmacologically active ingredients include atractylone, eudesmol, palmitic acid, hinesol, and the like. It is known that they are effective in promoting intestinal movement, liver protection and bile secretion, anti-oxidation, lowering of blood sugar, and prevention of gastric ulcer.
  • Schisandrae Fructus ( Schisandra chinensis Baillon) is a deciduous woody climbing plant belonging to the Schisandraceae family. It is one of main medicinal plants where the red fruit is used as a herb medicine and food ingredient. There are two genus and three species of Schisandracea in Korea. It is known that Schisandrae Fructus ( Schisandra chinensis Baillon) is effective in lowering blood pressure and detoxifying alcohol and has various physiological functions such as cancer preventive activity, anti-aging activity, immunoregulatory activity, and antibacterial activity. Lignan compounds such as schisandrin, gomisin A, or gomisin N are largely comprised in the fruit of Schisandrae Fructus. Various other ingredients such as essential oils, pigments, etc. are also found. In particular, schisandrin is known to exhibit hypoglycemic activity, anti-ulcer activity, chronic hepatitis treatment, central nervous system stimulation, liver protection, and the like.
  • the present invention related to a mixed extract of Atractylodis Rhizoma Alba and Schisandrae Fructus, or of Atractylodis Rhizoma and Schisandrae Fructus has been accomplished.
  • the present invention is intended to provide a composition for improving or preventing cough, phlegm, or inflammation-related diseases, comprising a mixed extract of Atractylodis Rhizoma Alba and Schisandrae Fructus, or of Atractylodis Rhizoma and Schisandrae Fructus as an active ingredient.
  • the present invention is intended to provide a composition with good efficacy for improving or preventing inflammation, cough, or phlegm, wherein the mixed extract of Atractylodis Rhizoma Alba and Schisandrae Fructus, or of Atractylodis Rhizoma and Schisandrae Fructus is comprised in a significantly smaller amount than when a single herbal extract is independently comprised.
  • the present invention relates to a composition for improving or preventing cough or phlegm, comprising a mixed extract of Atractylodis Rhizoma Alba and Schisandrae Fructus, or of Atractylodis Rhizoma and Schisandrae Fructus as an active ingredient.
  • the present invention relates to a composition for improving or preventing inflammatory diseases, comprising a mixed extract of Atractylodis Rhizoma Alba and Schisandrae Fructus, or of Atractylodis Rhizoma and Schisandrae Fructus as an active ingredient.
  • the inflammatory diseases may include, but are not limited to, acute or chronic bronchitis, catarrhal bronchitis, and inflammatory bronchitis.
  • a (mixed) extract of Atractylodis Rhizoma Alba and Schisandrae Fructus refers to both a mixture of an extract of Atractylodis Rhizoma Alba and an extract of Schisandrae Fructus, which are obtained by extracting Atractylodis Rhizoma Alba and Schisandrae Fructus, respectively, and an extract which is obtained by extracting a mixture of Atractylodis Rhizoma Alba and Schisandrae Fructus.
  • a (mixed) extract of Atractylodis Rhizoma and Schisandrae Fructus refers to both a mixture of an extract of Atractylodis Rhizoma and an extract of Schisandrae Fructus, which are obtained by extracting Atractylodis Rhizoma and Schisandrae Fructus, respectively, and an extract which is obtained by extracting a mixture of Atractylodis Rhizoma and Schisandrae Fructus.
  • the method may be, but is not limited to, (cold or warm) immersion, hot water extraction, ultrasonic extraction, or reflux cooling extraction.
  • Atractylodis Rhizoma Alba and Schisandrae Fructus In order to maximize the synergistic effect on anti-inflammatory, antitussive and expectoration activities from the mixed extract of Atractylodis Rhizoma Alba and Schisandrae Fructus, or of Atractylodis Rhizoma and Schisandrae Fructus, based on the weight of a herb medicine, Atractylodis Rhizoma Alba (or Atractylodis Rhizoma) and Schisandrae Fructus are comprised in a weight ratio from 0.1:1 to 10:1, more preferably, from 0.2:1 to 9:1, even more preferably, from 0.4:1 to 8:1, and most preferably, from 1:1 to 7:1, wherein the remarkably improved efficacy is shown. The most improved effect is when Atractylodis Rhizoma Alba (or Atractylodis Rhizoma) and Schis
  • an extract refers to a crude extract or a solvent extract fraction of the crude extract and may be, but is not limited to, a solution (flow extract), a concentrate (soft extract), or a dry powder.
  • Atractylodis Rhizoma Alba (or Atractylodis Rhizoma) and Schisandrae Fructus may be extracted with water, a lower alcohol having 1 to 4 carbon atoms, or its aqueous solution but is not limited hereto.
  • a mixed extract of Atractylodis Rhizoma Alba (or Atractylodis Rhizoma) and Schisandrae Fructus may be a crude extract (primary extract) or a concentrate thereof obtained by extracting Atractylodis Rhizoma Alba (or Atractylodis Rhizoma), preferably, a rhizome of Atractylodis Rhizoma Alba (or Atractylodis Rhizoma), and Schisandrae Fructus, preferably, a fruit of Schisandrae Fructus, with water, a lower alcohol having 1 to 4 carbon atoms, or its aqueous solution.
  • the lower alcohol having 1 to 4 carbon atoms may be selected from methanol, ethanol, propanol, isopropanol, and sec-butanol.
  • Atractylodis Rhizoma Alba (or Atractylodis Rhizoma) and Schisandrae Fructus may be extracted with an aqueous ethanol solution, preferably 10 to 90%, more preferably 30 to 70%, and most preferably 50% aqueous ethanol solution.
  • the extraction temperature is 40 to 120 °C and, preferably, 60 to 90 °C.
  • the extraction time is 2 to 48 hours and, preferably, 4 to 24 hours.
  • composition according to the present invention may be administered in various formulations for oral, rectal, intravenous, muscular, subcutaneous, endometrium, intracerebroventricular injection, and the like, when actual clinical administration is applied.
  • the composition of the present invention may be formulated in oral formulations comprising as powders, granules, tablets, capsules, suspensions, emulsions, syrups, and aerosols, or parenteral formulations comprising percutaneous formulations, suppositories, and sterile injection solutions in accordance with a conventional formulation method.
  • composition of the present invention may be used in a medicinal drug, a health functional food, a food, a beverage, a food additive, and the like.
  • the mixed extract of Atractylodis Rhizoma Alba and Schisandrae Fructus, or of Atractylodis Rhizoma and Schisandrae Fructus according to the present invention exhibits good anti-inflammatory, antitussive, and expectoration activities, which are superior to the single extract of Atractylodis Rhizoma Alba, Atractylodis Rhizoma, and Schisandrae Fructus.
  • the mixed extract of the present invention is very useful for improving or treating anti-inflammatory diseases including acute or chronic bronchitis, catarrhal bronchitis, and inflammatory bronchitis.
  • the mixed extract of Atractylodis Rhizoma Alba and Schisandrae Fructus or of Atractylodis Rhizoma and Schisandrae Fructus is an active ingredient with high safety and no known side effects. As such, it can widely be used for a health functional food, a food additive, a beverage, a medicinal drug, and the like.
  • Fig. 1 illustrates results of a cough suppression test using guinea pigs, showing the antitussive activity of the mixed extract of Atractylodis Rhizoma Alba and Schisandrae Fructus.
  • Fig. 2 illustrates results of measuring the expectoration activity of the mixed extract of Atractylodis Rhizoma Alba and Schisandrae Fructus in the Phenol Red method using a mouse.
  • Fig. 3 illustrates results of the expectoration activity test of erdosteine, Example 1, and Example 12.
  • nitric oxide which is one of the indicators showing an anti-inflammatory activity
  • DMEM Dulbecco's Modified Eagle Medium
  • FBS fetal bovine serum
  • penicillin 100 U/ml
  • streptomycin 100 ⁇ g/ml
  • a positive control substance L-NMMA, NG-monomethyl-L-arginine
  • an inducer LPS lipopolysaccharide
  • Examples 1 and 4 to 11 the extracts of Examples 1 to 11 according to the present invention were found to have the superior inhibitory effect on the production of nitric oxide in comparison with the positive control group.
  • the activity of the mixed extract of Atractylodis Rhizoma Alba and Schisandrae Fructus Examples 1 and 4 to 11 was remarkably superior to that of the single extract (Examples 2 and 3).
  • the ethanol extract of Atractylodis Rhizoma Alba and Schisandrae Fructus was more effective than the aqueous extract of Atractylodis Rhizoma Alba and Schisandrae Fructus.
  • the 50% ethanol extract of Atractylodis Rhizoma Alba and Schisandrae Fructus showed the most effective effect.
  • the antitussive activity of the mixed extract of Atractylodis Rhizoma Alba and Schisandrae Fructus prepared in Example 1 was measured depending on the dose as follows.
  • the extract of Example 1 at a dose of 300 mg/kg showed a cough suppression rate similar to that of the single extract of Atractylodis Rhizoma Alba.
  • the mixed extract of Atractylodis Rhizoma Alba and Schisandrae Fructus exhibits the similar efficacy in an amount of no more than half of that of the extract of Atractylodis Rhizoma Alba, based on the amount of original Atractylodis Rhizoma Alba.
  • Example 1 showed the similar efficacy to that of the single extract of Schisandrae Fructus.
  • the mixed extract of Atractylodis Rhizoma Alba and Schisandrae Fructus exhibits the similar efficacy in an amount of at least about 20 times less than that of the extract of Schisandrae Fructus, based on the amount of original Schisandrae Fructus.
  • the expectoration activity of the mixed extract prepared in Example 1 was measured depending on the dose as follows.
  • the freeze-stored trachea was then centrifuged at 3000 rpm for 10 minutes. 1N sodium hydroxide (NaOH) was added to the supernatant (0.1 ml of NaOH per ml of the supernatant). Then, the absorbance at 546 nm was measured wherein the expectorant activity was measured with the concentration of phenol red.
  • NaOH sodium hydroxide
  • Atractylodis Rhizoma Alba Schisandrae Fructus Total amount Control Group - 0 ⁇ 34 Extract of Atractylodis Rhizoma Alba 2.20 - 2.20 51 ⁇ 17 Extract of Schisandrae Fructus - 1.27 1.27 98 ⁇ 30
  • Example 1 100 0.29 0.06 0.35 55 ⁇ 25 200 0.58 0.12 0.70 86 ⁇ 18 300 0.88 0.18 1.05 117 ⁇ 22 400 1.17 0.23 1.40 171 ⁇ 32 600 1.46 0.29 1.75 176 ⁇ 26 800 2.33 0.47 2.80 175 ⁇ 34
  • the extract of Example 1 at a dose of 100 mg/kg showed the similar efficacy to that of the extract of Atractylodis Rhizoma Alba.
  • the mixed extract of Atractylodis Rhizoma Alba and Schisandrae Fructus exhibits the similar efficacy in an amount of at least about 7 times less than that of the extract of Atractylodis Rhizoma Alba, based on the amount of original Atractylodis Rhizoma Alba.
  • Example 1 the extract of Example 1 at a dose of 300 mg/kg exhibited the superior efficacy to that of the extract of Schisandrae Fructus.
  • the mixed extract of Atractylodis Rhizoma Alba and Schisandrae Fructus exhibits the similar efficacy in an amount of at least about 7 times less than that of the extract of Schisandrae Fructus, based on the amount of original Schisandrae Fructus.

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Abstract

The present invention relates to a composition for improving or preventing cough or phlegm, comprising a mixed extract of Atractylodis Rhizoma Alba and Schisandrae Fructus, or of Atractylodis Rhizoma and Schisandrae Fructus as an active ingredient. Specifically, the mixed extract of Atractylodis Rhizoma Alba and Schisandrae Fructus, and of Atractylodis Rhizoma and Schisandrae Fructus of the present invention exhibits improved anti-inflammatory, antitussive, and expectoration activities compared to their single extract.

Description

A COMPOSITION WITH ANTITUSSIVE AND EXPECTORATION ACTIVITIES COMPRISING AN EXTRACT OF ATRACTYLODIS RHIZOMA ALBA AND SCHISANDRAE FRUCTUS
The present invention relates to a composition for treating or preventing respiratory diseases, comprising a mixed extract of Atractylodis Rhizoma Alba and Schisandrae Fructus, or of Atractylodis Rhizoma and Schisandrae Fructus as an active ingredient. Specifically, the present invention provides a composition useful for treating or preventing respiratory diseases by confirming that the mixed extract of Atractylodis Rhizoma Alba and Schisandrae Fructus, or of Atractylodis Rhizoma and Schisandrae Fructus has improved anti-inflammatory, antitussive, and expectoration activities compared to their single extract.
Cough is produced when sensory receptors distributed in the throat, larynx, bronchus, pleura, eardrum, sinus, diaphragm, stomach, esophagus, and the like detect physicochemical stimuli to send the same to the brainstem through the vagus nerve. Cough is a defense mechanism to prevent a foreign substance from being inhaled into the lower respiratory tract, so that excessive secretions and foreign substances are cleared from airways. While cough per se is important, it leads to complications such as fatigue, headache, hoarseness, urinary incontinence, and musculoskeletal pain. As such, it is important to identify a cause of the cough and then treat or prevent the same.
Generally, cough that lasts more than three weeks is called a chronic cough, which is caused by a variety of diseases, unlike an acute cough caused by a cold. While cough is an important defense mechanism of the lung, if more frequent bouts of coughing than usual is observed, it means that lung or bronchial diseases may exist and it is necessary to find the exact cause.
Further, when dust or an irritant comes in the body from the outside, the bronchus of our body expels them together with the saliva to the outside via muscle movement, which results in phlegm production. Phlegm is persistently produced, passes through the larynx, and is swallowed into the gastrointestinal tract to be finally eliminated, although we are not aware of that process. Due to increased production of phlegm, change in viscosity, or deteriorated elimination activity of phlegm, phlegm is stored in the airway to cause symptoms such as coughing or dyspnea.
Recently, various symptoms such as coughing, dyspnea, pulmonary function insufficiency, or increased chronic bronchitis have considerably occurred by acute or chronic exposure to fine dust. Thus, it is very important to provide modern people with a safe and effective way to prevent or treat these respiratory diseases.
An agent for suppressing cough and expectorating phlegm is largely classified into antitussives and expectorants. Antitussives are a medicinal drug for suppressing coughing irrespective of the cause. It can be divided into the two types according to the mechanism of action: an agent acting on the central nervous system (CNS); and that acting on the peripheral nervous system (PNS). The CNS-acting agent can be divided into narcotic opioids, non-narcotic opioids, and nonopioids. The representative narcotic opioids comprise codeine, hydrocodone, and morphine. Their cough suppressant effect has restrictively been proved without showing consistent results. Further, its use in an optimum dose is at risk for drowsiness, constipation, indigestion, or drug abuse or dependence. The most commonly used PNS-acting antitussive in Korea is levodropropizine, which is considered to exert the effect by modulating the levels of sensory neuropeptide within the respiratory tract. Theobromine is also a type of PNS-acting agents.
The main ingredient of phlegm is composed of mucus. Bronchial mucus is generally secreted from mucous glandular cells and serous glandular cells which constitute mucous glands and submucosal glands distributed in bronchial mucosa. Mucus consists of 95% of water, and 5% of the rest consisting of glycoproteins, lipids, minerals, etc., where the glycoprotein is in a gel form of double structure of linear polymers, whereby the mucus is sticky. Expectorants for removing phlegm comprise an agent for increasing moisture content in phlegm and mucolytics for reducing the viscosity by breaking down the S-S bond of a phlegm protein. Cysteine derivatives such as N-acetylcysteine and carbocysteine are used as expectorants while they may cause side effects such as bronchospasm with long-term use. Therefore, the development of expectorants with fewer side effects and toxicity as well as superior expectoration effect is required.
Further, ivy leaf extract, or the extract combination of ivy leaf and Coptidis Rhizoma are widely used as antitussives/expectorants derived from natural products. However, Coptidis Rhizoma has side effects of safety and toxicity, such as neurotoxicity and renal dysfunction, as confirmed in animal tests. In particular, berberine, which is known as a main ingredient of Coptidis Rhizoma, is an alkaloid pharmacologically active substance well known to have anti-cancer and anti-inflammatory activity. However, since it may cause acute toxicity, it should carefully be used. Accordingly, it is required to develop a natural product formulation using a herb medicine to ensure safety and to be widely used.
Atractylodis Rhizoma refers to a rhizome of Atractylodes japonica Koidzumi belonging to the Compositae family while Atractylodis Rhizoma Alba refers to what is produced by peeling off large roots in the end of the rhizome and then drying the same. The nature of Atractylodis Rhizoma Alba and Atractylodis Rhizoma is warm and the taste is sweet and bitter. They act mainly on the spleen and the stomach to exhibit the effect of invigorating spleen, supporting the function of stomach, draining dampness, and allowing a normal function by harmonizing Middle Jiao. Therefore, Atractylodis Rhizoma Alba and Atractylodis Rhizoma are known as an agent to treat reduced function of digestive system, including anorexia, lethargy, weakness of the spleen and stomach, and diarrhea. Their main pharmacologically active ingredients include atractylone, eudesmol, palmitic acid, hinesol, and the like. It is known that they are effective in promoting intestinal movement, liver protection and bile secretion, anti-oxidation, lowering of blood sugar, and prevention of gastric ulcer.
Schisandrae Fructus (Schisandra chinensis Baillon) is a deciduous woody climbing plant belonging to the Schisandraceae family. It is one of main medicinal plants where the red fruit is used as a herb medicine and food ingredient. There are two genus and three species of Schisandracea in Korea. It is known that Schisandrae Fructus (Schisandra chinensis Baillon) is effective in lowering blood pressure and detoxifying alcohol and has various physiological functions such as cancer preventive activity, anti-aging activity, immunoregulatory activity, and antibacterial activity. Lignan compounds such as schisandrin, gomisin A, or gomisin N are largely comprised in the fruit of Schisandrae Fructus. Various other ingredients such as essential oils, pigments, etc. are also found. In particular, schisandrin is known to exhibit hypoglycemic activity, anti-ulcer activity, chronic hepatitis treatment, central nervous system stimulation, liver protection, and the like.
It is required to overcome side effects and problems of antitussives/expectorants as currently available and to develop a new treatment agent derived from a natural product with improved antitussive and expectoration effect.
Therefore, it has newly been confirmed by the experiments that the extract of Atractylodis Rhizoma Alba or Atractylodis Rhizoma, which has previously been used mainly for improving digestion, have good antitussive and expectoration effect. More surprisingly, when Atractylodis Rhizoma Alba or Atractylodis Rhizoma is used with Schisandrae Fructus, much more improved antitussive and expectoration efficacy was confirmed. It was also confirmed that the mixture of Atractylodis Rhizoma Alba and Schisandrae Fructus, or of Atractylodis Rhizoma and Schisandrae Fructus has anti-inflammatory effect. Based on the above, the present invention related to a mixed extract of Atractylodis Rhizoma Alba and Schisandrae Fructus, or of Atractylodis Rhizoma and Schisandrae Fructus has been accomplished.
The present invention is intended to provide a composition for improving or preventing cough, phlegm, or inflammation-related diseases, comprising a mixed extract of Atractylodis Rhizoma Alba and Schisandrae Fructus, or of Atractylodis Rhizoma and Schisandrae Fructus as an active ingredient. Specifically, the present invention is intended to provide a composition with good efficacy for improving or preventing inflammation, cough, or phlegm, wherein the mixed extract of Atractylodis Rhizoma Alba and Schisandrae Fructus, or of Atractylodis Rhizoma and Schisandrae Fructus is comprised in a significantly smaller amount than when a single herbal extract is independently comprised.
The present invention relates to a composition for improving or preventing cough or phlegm, comprising a mixed extract of Atractylodis Rhizoma Alba and Schisandrae Fructus, or of Atractylodis Rhizoma and Schisandrae Fructus as an active ingredient.
In addition, the present invention relates to a composition for improving or preventing inflammatory diseases, comprising a mixed extract of Atractylodis Rhizoma Alba and Schisandrae Fructus, or of Atractylodis Rhizoma and Schisandrae Fructus as an active ingredient. The inflammatory diseases may include, but are not limited to, acute or chronic bronchitis, catarrhal bronchitis, and inflammatory bronchitis.
In the present invention, the term "a (mixed) extract of Atractylodis Rhizoma Alba and Schisandrae Fructus" refers to both a mixture of an extract of Atractylodis Rhizoma Alba and an extract of Schisandrae Fructus, which are obtained by extracting Atractylodis Rhizoma Alba and Schisandrae Fructus, respectively, and an extract which is obtained by extracting a mixture of Atractylodis Rhizoma Alba and Schisandrae Fructus.
In the present invention, the term "a (mixed) extract of Atractylodis Rhizoma and Schisandrae Fructus" refers to both a mixture of an extract of Atractylodis Rhizoma and an extract of Schisandrae Fructus, which are obtained by extracting Atractylodis Rhizoma and Schisandrae Fructus, respectively, and an extract which is obtained by extracting a mixture of Atractylodis Rhizoma and Schisandrae Fructus.
All methods which are usually used in the art may be available for the extraction process of the present invention. For example, the method may be, but is not limited to, (cold or warm) immersion, hot water extraction, ultrasonic extraction, or reflux cooling extraction.
Surprisingly, it was confirmed through the experiments that a mixed extract of Atractylodis Rhizoma Alba and Schisandrae Fructus, or of Atractylodis Rhizoma and Schisandrae Fructus exhibits remarkably improved effects on the anti-inflammatory, antitussive, and expectoration activities, in comparison to the single extract of Atractylodis Rhizoma Alba, Atractylodis Rhizoma, or Schisandrae Fructus, based on which the present invention is achieved.
In order to maximize the synergistic effect on anti-inflammatory, antitussive and expectoration activities from the mixed extract of Atractylodis Rhizoma Alba and Schisandrae Fructus, or of Atractylodis Rhizoma and Schisandrae Fructus, based on the weight of a herb medicine, Atractylodis Rhizoma Alba (or Atractylodis Rhizoma) and Schisandrae Fructus are comprised in a weight ratio from 0.1:1 to 10:1, more preferably, from 0.2:1 to 9:1, even more preferably, from 0.4:1 to 8:1, and most preferably, from 1:1 to 7:1, wherein the remarkably improved efficacy is shown. The most improved effect is when Atractylodis Rhizoma Alba (or Atractylodis Rhizoma) and Schisandrae Fructus are comprised in a ratio of 5:1.
In the present invention, an extract refers to a crude extract or a solvent extract fraction of the crude extract and may be, but is not limited to, a solution (flow extract), a concentrate (soft extract), or a dry powder.
In the present invention, Atractylodis Rhizoma Alba (or Atractylodis Rhizoma) and Schisandrae Fructus may be extracted with water, a lower alcohol having 1 to 4 carbon atoms, or its aqueous solution but is not limited hereto.
In the present invention, a mixed extract of Atractylodis Rhizoma Alba (or Atractylodis Rhizoma) and Schisandrae Fructus may be a crude extract (primary extract) or a concentrate thereof obtained by extracting Atractylodis Rhizoma Alba (or Atractylodis Rhizoma), preferably, a rhizome of Atractylodis Rhizoma Alba (or Atractylodis Rhizoma), and Schisandrae Fructus, preferably, a fruit of Schisandrae Fructus, with water, a lower alcohol having 1 to 4 carbon atoms, or its aqueous solution. The lower alcohol having 1 to 4 carbon atoms may be selected from methanol, ethanol, propanol, isopropanol, and sec-butanol.
Particularly, in the present invention, Atractylodis Rhizoma Alba (or Atractylodis Rhizoma) and Schisandrae Fructus may be extracted with an aqueous ethanol solution, preferably 10 to 90%, more preferably 30 to 70%, and most preferably 50% aqueous ethanol solution.
The extraction temperature is 40 to 120 ℃ and, preferably, 60 to 90 ℃. The extraction time is 2 to 48 hours and, preferably, 4 to 24 hours.
The composition according to the present invention may be administered in various formulations for oral, rectal, intravenous, muscular, subcutaneous, endometrium, intracerebroventricular injection, and the like, when actual clinical administration is applied. The composition of the present invention may be formulated in oral formulations comprising as powders, granules, tablets, capsules, suspensions, emulsions, syrups, and aerosols, or parenteral formulations comprising percutaneous formulations, suppositories, and sterile injection solutions in accordance with a conventional formulation method.
In another aspect, the composition of the present invention may be used in a medicinal drug, a health functional food, a food, a beverage, a food additive, and the like.
The mixed extract of Atractylodis Rhizoma Alba and Schisandrae Fructus, or of Atractylodis Rhizoma and Schisandrae Fructus according to the present invention exhibits good anti-inflammatory, antitussive, and expectoration activities, which are superior to the single extract of Atractylodis Rhizoma Alba, Atractylodis Rhizoma, and Schisandrae Fructus.
In addition, the mixed extract of the present invention is very useful for improving or treating anti-inflammatory diseases including acute or chronic bronchitis, catarrhal bronchitis, and inflammatory bronchitis.
The mixed extract of Atractylodis Rhizoma Alba and Schisandrae Fructus or of Atractylodis Rhizoma and Schisandrae Fructus is an active ingredient with high safety and no known side effects. As such, it can widely be used for a health functional food, a food additive, a beverage, a medicinal drug, and the like.
Fig. 1 illustrates results of a cough suppression test using guinea pigs, showing the antitussive activity of the mixed extract of Atractylodis Rhizoma Alba and Schisandrae Fructus.
Fig. 2 illustrates results of measuring the expectoration activity of the mixed extract of Atractylodis Rhizoma Alba and Schisandrae Fructus in the Phenol Red method using a mouse.
Fig. 3 illustrates results of the expectoration activity test of erdosteine, Example 1, and Example 12.
Hereinafter, the present invention will be described in more detail with reference to the following examples. However, these examples are only for illustrating the present invention, but are not to be construed as the limitation of the claimed scope.
[Example 1] Preparation of 50% ethanol extract of Atractylodis Rhizoma Alba and Schisandrae Fructus (5:1)
50 g of Atractylodis Rhizoma Alba and 10 g of Schisandrae Fructus were mixed and extracted with 360 ml of 50% (v/v) ethanol at room temperature for 24 hours. The extract was filtered to obtain and collect the filtrate. The residue was re-extracted for 24 hours by adding 50% (v/v) ethanol in a six times higher amount to obtain the filtrate. The filtrate was mixed with the previously collected filtrate, followed by concentrating under reduced pressure to obtain 17 g of the mixed extract of Atractylodis Rhizoma Alba and Schisandrae Fructus.
[Example 2] Preparation of 50% ethanol extract of Schisandrae Fructus
60 g of Schisandrae Fructus was treated with 360 ml of 50% (v/v) ethanol in the same manner as in Example 1, to obtain 22 g of the extract.
[Example 3] Preparation of 50% ethanol extract of Atractylodis Rhizoma Alba
60 g of Atractylodis Rhizoma Alba was treated with 360 ml of 50% (v/v) ethanol in the same manner as in Example 1, to obtain 12 g of the extract.
[Example 4] Preparation of 50% ethanol extract of Atractylodis Rhizoma Alba and Schisandrae Fructus (0.2:1)
10 g of Atractylodis Rhizoma Alba and 50 g of Schisandrae Fructus were mixed and treated with 360 ml of 50% (v/v) ethanol in the same manner as in Example 1, to obtain 23 g of the extract.
[Example 5] Preparation of 50% ethanol extract of Atractylodis Rhizoma Alba and Schisandrae Fructus (0.4:1)
20 g of Atractylodis Rhizoma Alba and 50 g of Schisandrae Fructus were mixed and treated with 420 ml of 50% (v/v) ethanol in the same manner as in Example 1, to obtain 23 g of the extract.
[Example 6] Preparation of 50% ethanol extract of Atractylodis Rhizoma Alba and Schisandrae Fructus (1:1)
30g of Atractylodis Rhizoma Alba and 30 g of Schisandrae Fructus were mixed and treated with 360 ml of 50% (v/v) ethanol in the same manner as in Example 1, to obtain 18 g of the extract.
[Example 7] Preparation of 50% ethanol extract of Atractylodis Rhizoma Alba and Schisandrae Fructus (2.5:1)
50 g of Atractylodis Rhizoma Alba and 20 g of Schisandrae Fructus were mixed and treated with 420 ml of 50% (v/v) ethanol in the same manner as in Example 1, to obtain 23 g of the extract.
[Example 8] Preparation of aqueous extract of Atractylodis Rhizoma Alba and Schisandrae Fructus (5:1)
50 g of Atractylodis Rhizoma Alba and 10 g of Schisandrae Fructus were mixed and treated with 360 ml of an aqueous solution in the same manner as in Example 1, to obtain 23 g of the extract.
[Example 9] Preparation of 10% ethanol extract of Atractylodis Rhizoma Alba and Schisandrae Fructus (5:1)
50 g of Atractylodis Rhizoma Alba and 10 g of Schisandrae Fructus were mixed and treated with 360 ml of 10% (v/v) ethanol in the same manner as in Example 1, to obtain 20 g of the extract.
[Example 10] Preparation of 30% ethanol extract of Atractylodis Rhizoma Alba and Schisandrae Fructus (5:1)
50 g of Atractylodis Rhizoma Alba and 10 g of Schisandrae Fructus were mixed and treated with 360 ml of 30% (v/v) ethanol in the same manner as in Example 1, to obtain 21 g of the extract.
[Example 11] Preparation of 100% ethanol extract of Atractylodis Rhizoma Alba and Schisandrae Fructus (5:1)
50 g of Atractylodis Rhizoma Alba and 10 g of Schisandrae Fructus were mixed and treated with 360 ml of 100% (v/v) ethanol in the same manner as in Example 1, to obtain 6 g of the extract.
[Example 12] Preparation of 50% ethanol extract of Atractylodis Rhizoma and Schisandrae Fructus (5:1)
50 g of Atractylodis Rhizoma and 10 g of Schisandrae Fructus were mixed and extracted with 360 ml of 50% (v/v) ethanol at room temperature for 24 hours. The extract was filtered to obtain and collect the filtrate. The residue was re-extracted for 24 hours by adding 50% (v/v) ethanol in a six times higher amount to obtain the filtrate. The filtrate was mixed with the previously collected filtrate, followed by concentrating under reduced pressure to obtain 16 g of the mixed extract of Atractylodis Rhizoma and Schisandrae Fructus.
<Experimental Example 1. Measurement of an inhibitory effect on the production of nitric oxide (NO)>
In order to measure the inhibitory effect of the extract of the present invention on the production of nitric oxide (NO), which is one of the indicators showing an anti-inflammatory activity, the experiments on Raw 264.7 macrophage cell line derived from BALB / c mouse were performed. First, DMEM (Dulbecco's Modified Eagle Medium) medium solution supplemented with 10% fetal bovine serum (FBS), penicillin (100 U/ml) and streptomycin (100 μg/ml) was mixed with Raw 264.7 cells and placed in a 24-well plate so that 3 x 105 cells are comprised per well, followed by incubating for 24 hours at 5% carbon dioxide and 37℃. After the cells were stabilized, a positive control substance (L-NMMA, NG-monomethyl-L-arginine) or the extracts prepared in Examples 1 to 11 were treated with an inducer LPS (lipopolysaccharide) at a concentration of 200 μg/ml and incubated for 24 hours at 5% carbon dioxide and 37℃.
After the completion of the incubation, 100 μl of the culture medium was taken and mixed with the same volume of Griess reagent, followed by measuring the absorbance at 540 nm. The nitrite content of the sample was quantified using a standard curve of sodium nitrite in various concentrations dissolved in the same medium. The results are shown in Table 1 below.
Item Treatment Substance Nitric oxide (μM)
Control group Untreated group (vehicle) 1.5
NO induced Group LPS (lipopolysaccharide) 100 g/ml 42.9
Positive control group LPS (lipopolysaccharide) 100 g/ml with L-NMMA 50 nM 30.1
Example 1 Atractylodis Rhizoma Alba and Schisandrae Fructus (5:1) 50% Ethanol 1.1
Example 2 Schisandrae Fructus50% Ethanol 12.9
Example 3 Atractylodis Rhizoma Alba 50% Ethanol 12.0
Example 4 Atractylodis Rhizoma Alba and Schisandrae Fructus (0.2:1) 50% Ethanol 10.0
Example 5 Atractylodis Rhizoma Alba and Schisandrae Fructus (0.4:1) 50% Ethanol 5.2
Example 6 Atractylodis Rhizoma Alba and Schisandrae Fructus (1:1) 50% Ethanol 3.5
Example 7 Atractylodis Rhizoma Alba and Schisandrae Fructus (2.5:1) 50% Ethanol 1.5
Example 8 Atractylodis Rhizoma Alba and Schisandrae Fructus (5:1) Aqueous solution 10.1
Example 9 Atractylodis Rhizoma Alba and Schisandrae Fructus (5:1) 10% Ethanol 7.4
Example 10 Atractylodis Rhizoma Alba and Schisandrae Fructus (5:1) 30% Ethanol 7.7
Example 11 Atractylodis Rhizoma Alba and Schisandrae Fructus (5:1) 100% Ethanol 1.2
As shown in Table 1 above, the extracts of Examples 1 to 11 according to the present invention were found to have the superior inhibitory effect on the production of nitric oxide in comparison with the positive control group. In particular, it was confirmed that the activity of the mixed extract of Atractylodis Rhizoma Alba and Schisandrae Fructus (Examples 1 and 4 to 11) was remarkably superior to that of the single extract (Examples 2 and 3).
Especially, the ethanol extract of Atractylodis Rhizoma Alba and Schisandrae Fructus was more effective than the aqueous extract of Atractylodis Rhizoma Alba and Schisandrae Fructus. The 50% ethanol extract of Atractylodis Rhizoma Alba and Schisandrae Fructus showed the most effective effect.
Further, it was found that the effect was more remarkable as the content of Atractylodis Rhizoma Alba in the weight ratio of Atractylodis Rhizoma Alba and Schisandrae Fructus increased.
<Experimental Example 2. Evaluation test of antitussive activity >
The method of Tanaka et al. (American Journal of Respiratory and Critical Care Medicine, 1998, 158, 42-48) was used to evaluate the antitussive activity of the extract of the present invention.
The antitussive activity of the mixed extract of Atractylodis Rhizoma Alba and Schisandrae Fructus prepared in Example 1 was measured depending on the dose as follows.
As experimental animals, 12 male Hartely guinea pigs (Orient Bio, Korea) weighing from 350 to 400 g were used in each group. Each of the extract prepared in Example 1, 30% ethanol dried extract (11 → 1) of Atractylodis Rhizoma Alba, and 10% ethanol dried extract (6.3 → 1) of Schisandrae Fructus was orally administered to the respective experimental groups. After 1 hour, a cough inducer (5% citric acid) was sprayed to guinea pigs for 10 minutes to induce cough. The number of coughs that occurred for 15 minutes from the exposure to the cough inducer was measured. The 30% ethanol dried extract (11 → 1) of Atractylodis Rhizoma Alba and the 10% ethanol dried extract (6.3 → 1) of Schisandrae Fructus obtained by drying commercially available fluid extracts were used. The experimental results are shown in Table 2 below and Fig. 1.
Item (mg/kg) Original herb medicine (g/kg) Cough suppression rate (%)
Atractylodis Rhizoma Alba Schisandrae Fructus Total amount
Control group - 0±26
Extract of Atractylodis Rhizoma Alba 2.20 - 2.20 78±7
Extract of Schisandrae Fructus - 1.27 1.27 53±11
Example 1 100 0.29 0.06 0.35 55±12
200 0.58 0.12 0.70 60±16
300 0.88 0.18 1.05 76±10
400 1.17 0.23 1.40 79±12
600 1.46 0.29 1.75 96±3
800 2.33 0.47 2.80 96±4
As shown in Table 2 above, the extract of Example 1 at a dose of 300 mg/kg showed a cough suppression rate similar to that of the single extract of Atractylodis Rhizoma Alba. As such, it was confirmed that when comparing with the extract of Atractylodis Rhizoma Alba, the mixed extract of Atractylodis Rhizoma Alba and Schisandrae Fructus exhibits the similar efficacy in an amount of no more than half of that of the extract of Atractylodis Rhizoma Alba, based on the amount of original Atractylodis Rhizoma Alba.
In addition, the extract of Example 1 at a dose of 100 mg/kg showed the similar efficacy to that of the single extract of Schisandrae Fructus. As such, it was confirmed that when comparing with the extract of Schisandrae Fructus, the mixed extract of Atractylodis Rhizoma Alba and Schisandrae Fructus exhibits the similar efficacy in an amount of at least about 20 times less than that of the extract of Schisandrae Fructus, based on the amount of original Schisandrae Fructus.
As a result, it was found that when comparing with the single use of the extract of Atractylodis Rhizoma Alba or the extract of Schisandrae Fructus, the combination of Atractylodis Rhizoma Alba and Schisandrae Fructus exhibits the significantly superior efficacy in a remarkably small amount of the original herb medicine.
<Experimental Example 3. Evaluation test of expectoration activity of the extract of Atractylodis Rhizoma Alba and Schisandrae Fructus >
The method of Engler et al. (Journal of Ethnopharmacology, 1984, 11, 151-157) was used to evaluate the expectoration activity of the extract of the present invention.
The expectoration activity of the mixed extract prepared in Example 1 was measured depending on the dose as follows.
As experimental animals, 12 male ICR mice (Orient Bio, Korea) weighing from 30 to 33 g were used in each group. Each of the extract prepared in Example 1, 30% ethanol dried extract (11 → 1) of Atractylodis Rhizoma Alba, and 10% ethanol dried extract (6.3 → 1) of Schisandrae Fructus was orally administered to the respective experimental groups. After 30 minutes, 5% phenol red was intraperitoneally injected. After 30 minutes, the cervical dislocation was performed, cutting the abdominal aorta to exsanguinate the animal, followed by dissecting the entire trachea. The isolated trachea was freeze-stored in 1 ml of physiological saline for 24 hours. The freeze-stored trachea was then centrifuged at 3000 rpm for 10 minutes. 1N sodium hydroxide (NaOH) was added to the supernatant (0.1 ml of NaOH per ml of the supernatant). Then, the absorbance at 546 nm was measured wherein the expectorant activity was measured with the concentration of phenol red.
The experimental results are shown in Table 3 below and Fig. 2
Item (mg/kg) Original herb medicine (g/kg) Expectoration ability (%)
Atractylodis Rhizoma Alba Schisandrae Fructus Total amount
Control Group - 0±34
Extract of Atractylodis Rhizoma Alba 2.20 - 2.20 51±17
Extract of Schisandrae Fructus - 1.27 1.27 98±30
Example 1 100 0.29 0.06 0.35 55±25
200 0.58 0.12 0.70 86±18
300 0.88 0.18 1.05 117±22
400 1.17 0.23 1.40 171±32
600 1.46 0.29 1.75 176±26
800 2.33 0.47 2.80 175±34
As shown in Table 3 above, the extract of Example 1 at a dose of 100 mg/kg showed the similar efficacy to that of the extract of Atractylodis Rhizoma Alba. As such, it was confirmed that when comparing with the extract of Atractylodis Rhizoma Alba, the mixed extract of Atractylodis Rhizoma Alba and Schisandrae Fructus exhibits the similar efficacy in an amount of at least about 7 times less than that of the extract of Atractylodis Rhizoma Alba, based on the amount of original Atractylodis Rhizoma Alba.
In addition, the extract of Example 1 at a dose of 300 mg/kg exhibited the superior efficacy to that of the extract of Schisandrae Fructus. As such, it was confirmed that when comparing with the extract of Schisandrae Fructus, the mixed extract of Atractylodis Rhizoma Alba and Schisandrae Fructus exhibits the similar efficacy in an amount of at least about 7 times less than that of the extract of Schisandrae Fructus, based on the amount of original Schisandrae Fructus.
As a result, it was found that when comparing with the single use of the extract of Atractylodis Rhizoma Alba or the extract of Schisandrae Fructus extract, the combination of Atractylodis Rhizoma Alba and Schisandrae Fructus exhibits the significantly superior efficacy in a remarkably small amount of the original herb medicine.
In sum, it was confirmed through the experiments that surprisingly, the combined use of Schisandrae Fructus and Atractylodis Rhizoma Alba increases the cough suppression rate and expectoration ability, compared to the single use of Schisandrae Fructus. Especially, the combination at a dose of at least 300 mg/kg exhibits the excellent cough suppression rate and expectoration ability.
<Experimental Example 4: Evaluation test of expectoration activity of the extract of Atractylodis Rhizoma and Schisandrae Fructus >
In the same manner as in Experimental Example 3, the expectoration activity of Examples 1 and 12 was evaluated by comparing with that of erdosteine as a representative antitussive/expectorant. The results are shown in Table 4 below and Fig. 3.
Expectoration ability (%)
Control group 0.0±18.6
Erdosteine 75.5±83.4
Example 1 88.7±72.7
Example 12 80.6±69.3
As shown in Table 4 above, it was confirmed that the extract of Atractylodis Rhizoma and Schisandrae Fructus exhibits the similar efficacy to that of the mixed extract of Atractylodis Rhizoma Alba and Schisandrae Fructus.

Claims (9)

  1. A composition for improving or preventing cough or phlegm, comprising a mixed extract of Atractylodis Rhizoma Alba and Schisandrae Fructus, or of Atractylodis Rhizoma and Schisandrae Fructus as an active ingredient.
  2. A composition for improving or preventing inflammatory diseases including acute or chronic bronchitis, catarrhal bronchitis, and inflammatory bronchitis, comprising a mixed extract of Atractylodis Rhizoma Alba and Schisandrae Fructus, or of Atractylodis Rhizoma and Schisandrae Fructus as an active ingredient.
  3. The composition according to Claim 1 or 2, characterized in that in the mixed extract of Atractylodis Rhizoma Alba and Schisandrae Fructus, Atractylodis Rhizoma Alba and Schisandrae Fructus have a weight ratio of 0.1:1 to 10:1.
  4. The composition according to Claim 3, characterized in that in the mixed extract of Atractylodis Rhizoma Alba and Schisandrae Fructus, Atractylodis Rhizoma Alba and Schisandrae Fructus have a weight ratio of 1:1 to 7:1.
  5. The composition according to Claim 1 or 2, characterized in that the mixed extract is extracted with an aqueous solution, a lower alcohol having 1 to 4 carbon atoms, or its aqueous alcohol solution.
  6. The composition according to Claim 5, characterized in that the mixed extract is extracted with the aqueous ethanol solution or ethanol.
  7. The composition according to Claim 6, characterized in that the aqueous ethanol solution is a 10 to 90% aqueous ethanol solution.
  8. The composition according to Claim 7, characterized in that the aqueous ethanol solution is a 30 to 70% aqueous ethanol solution.
  9. The composition according to Claim 1, characterized in being used in a medicinal drug, a health functional food, a food, a beverage, or a food additive.
PCT/KR2019/004598 2018-04-30 2019-04-16 A composition with antitussive and expectoration activities comprising an extract of atractylodis rhizoma alba and schisandrae fructus WO2019212170A1 (en)

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1050520C (en) * 1997-03-19 2000-03-22 李刚 Chinese drugs for treatment of chronic broncheitis and asthma
KR20050101942A (en) * 2004-04-20 2005-10-25 (주)바이오솔루션 A health food composition for prevention and treatment of allergic rhinitis and influenza and a method for preparation thereof
WO2006114054A1 (en) * 2005-04-27 2006-11-02 Shuhua Zhu Use of amorphophallus rivieri durieu and extract thereof in the manufacture of a medicament for treating acute, chronic bronchitis
KR20140083932A (en) * 2014-02-17 2014-07-04 박윤걸 Manufacturing method of Health food comprising Extracts from Pear, Cudrania tricuspidata leaves, Hovenia dulcis, Lindera obtusiloba, Schizandra chinensis, Smilax china, Citrus aurantium and Luffa cylindrica and Health food manufactured by the same
CN107596093A (en) * 2017-09-30 2018-01-19 四川金堂海纳生物医药技术研究所 A kind of decoction medicine and preparation method for treating chronic bronchitis and pulmonary emphysema

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1165026C (en) * 2002-08-29 2004-09-01 李微 Multifunctional advertizing tower
JP2007161643A (en) 2005-12-14 2007-06-28 Taisho Pharmaceut Co Ltd Prophylactic or ameliorating agent for pms
CN102698233A (en) * 2012-06-14 2012-10-03 何本阳 Traditional Chinese medicine mixture for treating cold-fluid heat type child capillary bronchitis and preparation method of same
CN104721767A (en) * 2013-12-20 2015-06-24 施泽晶 Chinese medicinal composition for treatment of children cough and preparation method thereof
CN103977019B (en) * 2014-05-16 2016-08-24 广州医科大学附属第一医院 Fruit of Chinese magnoliavine total starches is used for treating the application in the medicine of cough or health products in preparation
CN104069227A (en) * 2014-07-23 2014-10-01 河南中医学院 Traditional Chinese medicine for treating coughing, phlegm, and asthma
CA2988131A1 (en) * 2015-06-03 2016-12-08 Op Nano Co., Ltd. Therapeutic methods and compositions for treating non-small cell lung cancer
CN105213751A (en) * 2015-11-16 2016-01-06 周建卿 A kind of Chinese medicine composition for the treatment of cough

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1050520C (en) * 1997-03-19 2000-03-22 李刚 Chinese drugs for treatment of chronic broncheitis and asthma
KR20050101942A (en) * 2004-04-20 2005-10-25 (주)바이오솔루션 A health food composition for prevention and treatment of allergic rhinitis and influenza and a method for preparation thereof
WO2006114054A1 (en) * 2005-04-27 2006-11-02 Shuhua Zhu Use of amorphophallus rivieri durieu and extract thereof in the manufacture of a medicament for treating acute, chronic bronchitis
KR20140083932A (en) * 2014-02-17 2014-07-04 박윤걸 Manufacturing method of Health food comprising Extracts from Pear, Cudrania tricuspidata leaves, Hovenia dulcis, Lindera obtusiloba, Schizandra chinensis, Smilax china, Citrus aurantium and Luffa cylindrica and Health food manufactured by the same
CN107596093A (en) * 2017-09-30 2018-01-19 四川金堂海纳生物医药技术研究所 A kind of decoction medicine and preparation method for treating chronic bronchitis and pulmonary emphysema

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See also references of EP3787658A4 *

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