JP7407735B2 - A composition having antitussive and expectorant activity, comprising extracts of Schisandra and Schisandra - Google Patents

Description

TECHNICAL FIELD The present invention relates to a composition for treating or preventing respiratory diseases, which contains as an active ingredient a mixed extract of White Persimmon and Schisandra, or a mixed extract of Cang Perilla and Schisandra. Specifically, the present invention has demonstrated that a mixed extract of Baekhuan and Schisandra or Cangchuan and Schisandra has superior anti-inflammatory and antitussive expectorant properties compared to their single extracts. , provides compositions useful for treating or preventing respiratory diseases.

Coughing occurs when sensory receptors distributed in the throat, larynx, bronchi, pleura, eardrum, sinuses, diaphragm, stomach, esophagus, etc. detect physicochemical stimuli and transmit the stimuli to the brain stem via the vagus nerve. triggered. Coughing is a defense mechanism to prevent foreign objects from being inhaled into the lower respiratory tract, and is an action to clear excess secretions and foreign objects from the airways. Cough itself is important, but coughing can lead to complications such as fatigue, headache, hoarseness, urinary incontinence, and musculoskeletal pain, so it is important to identify the cause of cough and treat or prevent it.

In general, a cough that lasts for three weeks or more is called a chronic cough, which differs from an acute cough caused by a cold and can arise from illnesses caused by various causes. Coughing is an important defense mechanism of the lungs, but if you cough more often than usual, you need to look for the exact cause, as it means there is a disease in the lungs or bronchial tubes.

Also, when dust or irritants enter the body from outside, our bronchi use saliva to push them out of the body through muscle movement, which causes sputum formation. Although we are not usually conscious of it, sputum is continuously produced, passes through the larynx, and is swallowed by the gastrointestinal tract, where it is disposed of. Increased sputum production, changes in viscosity, or decreased ability to process sputum can cause sputum to accumulate in the airways, causing symptoms such as coughing and difficulty breathing.

In recent years, various symptoms have been occurring due to acute or chronic exposure to fine dust, including coughing, difficulty breathing, decreased lung function, and an increase in chronic bronchitis. Therefore, it is very important for modern people to provide safe and effective ways to prevent or treat these respiratory diseases.

Antitussive expectorants are broadly classified into antitussives and expectorants, and antitussives are drugs that suppress coughs regardless of the cause. Drugs that act on the central nervous system and those that act on the peripheral nervous system are classified according to their mechanism of action, and among these, drugs that act on the central nervous system are divided into narcotics, narcotic derivatives, and non-narcotics. Typical narcotic drugs include codeine, hydrocodone, and morphine, which have been proven to have a limited cough suppressing effect, but the results are inconsistent. Additionally, even at optimal doses, there is a risk of drowsiness, constipation, indigestion, and drug abuse or dependence. Among antitussive drugs that act on the peripheral nervous system, the most commonly used drug in Korea is Levodropropizine, which is thought to exert its effect by regulating the levels of sensory neuropeptides in the airways. ing. In addition, theobromine also falls under this category.

The main component of sputum is mucus, and bronchial mucus is secreted from mucous gland cells and serous gland cells that constitute mucus glands and submucosal glands that are normally distributed in the bronchial mucosa. Mucus is made up of 95% water and the remaining 5% is made up of glycoproteins, lipids, minerals, etc. However, because the structure of glycoproteins is a gel-like structure consisting of a double structure of linear polymers, it is sticky. There is sex. Expectorants that remove sputum are divided into agents that increase the water content of sputum and mucolytic agents that reduce viscosity by releasing SS bonds in sputum proteins. Cysteine derivatives such as N-acetylcysteine and carbocysteine are used as such expectorants, but these cysteine derivatives can cause side effects such as bronchospasm when used for a long period of time. There is a risk of causing Therefore, there is a need for the development of an expectorant with fewer side effects and toxicity and with excellent expectorant effects.

Furthermore, as antitussive and expectorant agents derived from natural products, ivy leaf extracts and composite agents of ivy leaves and chinensis extracts are widely used. However, in the case of Huanglian, it has been confirmed through animal experiments that it has side effects in terms of safety and toxicity, such as neurotoxicity and inducing renal and intestinal dysfunction. In particular, berberine, which is known as the main component of Huanglian, is a pharmacologically active alkaloid substance that is widely known for its anti-cancer and anti-inflammatory effects, but it is a substance that causes acute toxicity. Therefore, care must be taken when using it. Therefore, there is a need to develop natural product preparations using crude drugs that are safe and can be used for general purposes.

Koidzumi refers to the rhizome of Atractylodes japonica Koidzumi, which belongs to the Compositae family, and Hakushu refers to the rhizome obtained by peeling off the thick root bark at the end of the rhizome and drying it. The properties of Baekju and Cangchu are warm, sweet and bitter in taste, and they mainly act on the spleen and stomach. Therefore, Baekju and Cangchu are known as drugs for treating digestive system dysfunction such as anorexia, lethargy, weakness of the spleen and stomach, and diarrhea. The main pharmacologically active ingredients include atractylone, eudesmol, palmitic acid, and hinesol, which promote intestinal motility, protect the liver, and have choleretic effects. It is known for its antioxidant effects, lowering blood sugar levels, and preventing gastric ulcers.

Schizandra chinensis Baillon is a deciduous tree-climbing plant belonging to the Schizandraceae family, and is one of the main medicinal plants whose red fruits are used as crude drugs and food raw materials. There are two genera and three species of Schisandra in South Korea, and Schisandra is known to be effective in lowering blood pressure and detoxifying alcohol, and has anti-cancer, anti-aging, and anti-aging properties. It has been reported that it has various physiological functions such as immunomodulatory effects and antibacterial activity. The components contained in Schisandra fruit are mainly lignan compounds such as schizandrin, gomisin A, or gomisin N, and various other components such as essential oils and pigments. is also included. In particular, schizandrin is known to exhibit effects such as hypoglycemic action, anti-ulcer action, chronic hepatitis treatment effect, central nervous system stimulating action, and liver protection.

There is a need to overcome the side effects and problems of currently used antitussive expectorants and to develop new therapeutic agents derived from natural products that have excellent antitussive and expectorant effects.

Therefore, it has been newly confirmed through experiments that extracts of Hakushu or Cangzhuang, which have traditionally been used primarily to improve digestive function, also exhibit excellent antitussive and expectorant effects. Furthermore, surprisingly, it was confirmed that the antitussive and expectorant effects were significantly improved when white or blue lily was used in combination with schisandra. In addition, it was confirmed that a mixture of Baekhuan and Schisandra, or a mixture of Cangchuan and Schisandra has an anti-inflammatory effect, and as a result, the present invention relating to a mixed extract of Baekhuan and Schisandra, or Cangchuan and Schisandra was completed.

An object of the present invention is to provide a composition for ameliorating or preventing cough, phlegm, and inflammation-related diseases, which contains a mixed extract of Aspergillus persica and Schisandra or a mixed extract of Aspergillus persica and Schisandra as an active ingredient. Specifically, the present invention provides a method for treating inflammation, in which a mixed extract of Baekshu and Schisandra, or a mixed extract of Cangshu and Schisandra exhibits excellent efficacy even in a much smaller amount than when containing each crude drug extract independently. The object is to provide a composition for improving or preventing cough or sputum production.

TECHNICAL FIELD The present invention relates to a composition for improving or preventing cough or phlegm, which contains as an active ingredient a mixed extract of Aspergillus spp.

The present invention also relates to a composition for ameliorating or preventing inflammatory diseases, which contains as an active ingredient a mixed extract of White Persimmon and Schisandra, or a mixed extract of Cang Persimmon and Schisandra. This may include, but is not limited to, bronchitis catarrh, bronchitis catarrh, and inflammatory bronchitis.

In the present invention, "a (mixed) extract of Hakushu and Schisandra" refers to a mixture of Hakushu and Schisandra extract obtained by extracting Hakushu and Schisandra, respectively, and a mixture of Hakushu and Schisandra. and the resulting extract.

In the present invention, "a (mixed) extract of Cangchuan and Schisandra" refers to a mixture of Cangchuan extract and Schisandra extract obtained by extracting Cangchuan and Schisandra, respectively, and a mixture of Cangchuan and Schisandra. and the resulting extract.

As the extraction method used in the present invention, any commonly used method can be used, such as immersion (cold immersion or hot immersion), hot water extraction, ultrasonic extraction, or reflux cooling extraction. , but not limited to these.

Surprisingly, the mixed extracts of Baekhuang and Schisandra and the mixed extracts of Cangchuan and Schisandra were significantly superior in anti-inflammatory and antitussive expectorant activities compared to single extracts of Baekhuang, Cangchuan, or Schisandra. It was confirmed through experiments that the present invention is effective, and the present invention has been achieved.

In order to maximize the synergistic effects of anti-inflammatory and antitussive and expectorant effects in the mixed extract of Baekhuang and Schisandra and the mixed extract of Cangchuan and Schisandra, the weight ratio of Baekhuang (or Cangchuan) and Schizophrenia to the weight of the herbal medicine should be adjusted. An amount of 0.1:1 to 10:1, more preferably an amount in which the weight ratio of Baekhuang (or Cangchuan) and Schisandra is 0.2:1 to 9:1, even more preferably 0.4:1 to 8. :1, most preferably in an amount of 1:1 to 7:1, it can be confirmed that a significantly superior effect is exhibited. The most excellent effect is shown when Baekju (or Cangchu) and Schisandra are included in a ratio of 5:1.

Extract according to the present invention means a crude extract or a solvent extract fraction of a crude extract, which may be a solution (free extract), a concentrate (soft extract) or a dry powder. , but not limited to these.

In the present invention, white lily (or blue lily) and schisandra may be extracted with water, a lower alcohol having 1 to 4 carbon atoms, or an aqueous solution thereof, but the extraction is not limited thereto.

A mixed extract of Baekhuang (or Cangchuan) and Schisandra japonica consists of the rhizome of Baekhuang (or Canghuang), preferably Baekhuang (or Canghuang), and the fruit part of Schisandra, preferably Schisandra japonica, with water and a lower grade of carbon number 1 to 4. It may be a crude extract (primary extract) obtained by extraction with alcohol or an aqueous solution thereof, or a concentrate thereof. 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, white lily (or blue lily) and schisandra may be extracted with an ethanol aqueous solution, preferably 10 to 90%, more preferably 30 to 70%, and most preferably 50%. It's okay.

The extraction temperature is 40-120°C, preferably 60-90°C, and the extraction time is 2-48 hours, preferably 4-24 hours.

In actual clinical administration, the compositions according to the invention may be administered in a variety of formulations, including oral, rectal, or intravenous, intramuscular, subcutaneous, endometrial, and intracerebrovascular injection. The composition of the present invention can be prepared into oral preparations such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, transdermal preparations, suppositories, and sterile preparations, respectively, according to conventional methods. It may also be formulated into a parenteral preparation in the form of an injection solution.

In other aspects, the composition of the present invention may be used in pharmaceuticals, functional foods, foods, beverages, food additives, and the like.

The mixed extract of Baekhuan and Schisandra and the mixed extract of Cangchuan and Schisandra according to the present invention exhibit excellent anti-inflammatory effect and antitussive expectorant activity, which is better than the single extract of Baekhu, Cangchuan and Schisandra. be effective.

The mixed extract of the present invention is also very useful for improving or treating anti-inflammatory diseases including acute or chronic bronchitis, catarrhal bronchitis, and inflammatory bronchitis.

The mixed extract of Hakushu and Schisandra and the mixed extract of Cangshu and Schisandra are highly safe active ingredients with no known side effects, and can be widely used in functional foods, food additives, beverages, pharmaceuticals, etc. .

FIG. 2 is a diagram showing the antitussive activity of a mixed extract of Baekhuang and Schisandra, and shows the results of a cough suppression test using guinea pigs. It is a figure which shows the expectorant activity of the mixed extract of Hakushu and Schisandra, and shows the results measured by the phenol red method using mice. FIG. 3 is a diagram showing the results of expectorant activity tests of Erdostein, Example 1, and Example 12.

Hereinafter, the present invention will be explained in more detail with reference to Examples. However, these examples are merely examples for explaining the present invention, and are not intended to limit the scope of the present invention.

[Example 1] Preparation of 50% Ethanol Extract of Schisandra and Schisandra (5:1) 50 g of Schisandra and 10 g of Schisandra were mixed and extracted with 360 ml of 50% (v/v) ethanol for 24 hours at room temperature. Then, the extract was filtered to collect the filtrate, and the residue was re-extracted for 24 hours by adding 6 times the amount of 50% (v/v) ethanol, and the resulting filtrate was combined with the previously collected filtrate. By mixing and concentrating under reduced pressure, 17 g of a mixed extract of Hakushu and Schisandra was obtained.

[Example 2] Preparation of 50% ethanol extract of Schisandra japonica 60 g of Schisandra was prepared in the same manner as in Example 1 with 360 ml of 50% (v/v) ethanol to obtain 22 g of extract.

[Example 3] Preparation of 50% Ethanol Extract of White Persimmon 60 g of White Persimmon was prepared in the same manner as in Example 1 with 360 ml of 50% (v/v) ethanol to obtain 12 g of extract.

[Example 4] Preparation of 50% ethanol extract of white perilla and schisandra (0.2:1) 10 g of white perilla and 50 g of schisandra were mixed and prepared in the same manner as in Example 1 with 360 ml of 50% (v/v) ethanol. , 23 g of extract was obtained.

[Example 5] Preparation of 50% ethanol extract of Schisandra japonica and Schisandra japonica (0.4:1) 20 g of Schisandra japonica and 50 g of Schisandra were mixed and prepared in the same manner as in Example 1 with 420 ml of 50% (v/v) ethanol. , 23 g of extract was obtained.

[Example 6] Preparation of 50% ethanol extract of white perilla and schisandra (1:1) 30 g of white perilla and 30 g of schisandra were mixed, prepared in the same manner as in Example 1 with 360 ml of 50% (v/v) ethanol, and extracted. 18g of material was obtained.

[Example 7] Preparation of 50% ethanol extract of white perilla and schisandra (2.5:1) 50 g of white perilla and 20 g of schisandra were mixed and prepared in the same manner as in Example 1 with 420 ml of 50% (v/v) ethanol. , 23 g of extract was obtained.

[Example 8] Preparation of aqueous extract of Schisandra perilla and Schisandra japonica (5:1) 50 g of Schisandra pericarp and 10 g of Schisandra were mixed and prepared in the same manner as in Example 1 using 360 ml of an aqueous solution to obtain 23 g of extract.

[Example 9] Preparation of 10% ethanol extract of white perilla and schisandra (5:1) 50 g of white perilla and 10 g of schisandra were mixed, prepared in the same manner as in Example 1 with 360 ml of 10% (v/v) ethanol, and extracted. 20g of material was obtained.

[Example 10] Preparation of 30% ethanol extract of white perilla and schisandra (5:1) 50 g of white perilla and 10 g of schisandra were mixed, prepared in the same manner as in Example 1 with 360 ml of 30% (v/v) ethanol, and extracted. 21 g of the product was obtained.

[Example 11] Preparation of 100% ethanol extract of white perilla and schisandra (5:1) 50 g of white perilla and 10 g of schisandra were mixed, prepared in the same manner as in Example 1 with 360 ml of 100% (v/v) ethanol, and extracted. 6g of material was obtained.

[Example 12] Preparation of 50% ethanol extract of C. persica and Schisandra (5:1) 50 g of C. persica and 10 g of Schisandra were mixed and extracted with 360 ml of 50% (v/v) ethanol at room temperature for 24 hours. Then, the extract was filtered to collect the filtrate, and the residue was re-extracted for 24 hours by adding 6 times the amount of 50% (v/v) ethanol, and the resulting filtrate was combined with the previously collected filtrate. After mixing, the mixture was concentrated under reduced pressure to obtain 16 g of a mixed extract of C. perilla and Schisandra.

<Experiment example 1. Measurement of nitrogen oxide (NO) production suppression effect>
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 anti-inflammatory effect indicators, an experiment was conducted using the Raw 264.7 macrophage cell line derived from BALB/c mice. went. First, a DMEM (Dulbecco's modified Eagle's 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 for 24 hours. 3×10 ⁵ cells per well were placed in a well plate and cultured for 24 hours under conditions of 5% carbon dioxide and 37°C. After the cells were stabilized, positive control substances (L-NMMA, NG-monomethyl-L-arginine) or the extracts prepared in Examples 1 to 11 were added at a concentration of 200 μg/ml together with the inducer LPS (lipopolysaccharide). The cells were treated and cultured for 24 hours under conditions of 5% carbon dioxide and 37°C.

After the culture was completed, 100 μl of the culture solution was taken and mixed with the same volume of Griess reagent, and the absorbance was measured at 540 nm. A standard curve of various concentrations of sodium nitrite dissolved in the same medium was used to quantify the amount of nitrite in the samples, and the results are shown in Table 1 below.

As shown in Table 1 above, it can be seen that the extracts of Examples 1 to 11 according to the present invention have a superior inhibitory effect on the production of nitrogen oxides compared to the positive control group. In particular, it was confirmed that the activity of the mixed extracts of Schisandra and Schisandra (Examples 1 and 4 to 11) was significantly superior to that of the single extract (Examples 2 and 3).

Particularly, the ethanol extracts of Baekhuo and Schisandra showed better effects than the aqueous extracts of Baekhu and Schisandra, and the 50% ethanol extracts of Baekhu and Schisandra showed the best effects.

Furthermore, it was found that the greater the content of White Perilla and Schisandra in the weight ratio, the more excellent the effect was exhibited.

<Experiment example 2. Evaluation test for antitussive activity>
To evaluate the antitussive activity of the extracts of the present invention, the method of Tanaka et al. (American Journal of Respiratory and Citric Care Medicine, 1998, 158, 42-48) was used.

The antitussive activity of each volume of the mixed extract of White Persimmon and Schisandra prepared in Example 1 was measured as follows.

As experimental animals, 12 male Hartley guinea pigs (Orient Bio, Korea) weighing 350 to 400 g were used in each group. In each experimental group, the extract prepared in Example 1, a 30% ethanol dry extract of Hakushu (11 → 1), and a 10% ethanol dry extract of Schisandra japonica (6.3 → 1) were orally administered, respectively. One hour later, a cough was induced by spraying the guinea pigs with a cough inducer (5% citric acid) for 10 minutes. The number of coughs occurring within 15 minutes from the start of exposure to the cough inducing substance was measured. The 30% ethanol dry extract of Hakushu (11 → 1) and the 10% ethanol dry extract of Schisandra japonica (6.3 → 1) were dried commercially available free extracts. The experimental results are shown in Table 2 and FIG. 1 below.

As shown in Table 2, the extract of Example 1 showed a similar cough suppression rate as the single extract of Hakushu at a dose of 300 mg/kg. Therefore, it was confirmed that the mixed extract of Schisandra japonica and Schisandra japonica exhibits similar efficacy compared to the extract of Schisandra japonica even in a smaller amount, which is less than half of the amount of the original herbal medicine.

Moreover, the extract of Example 1 showed similar efficacy as the single extract of Schisandra chinensis at a dose of 100 mg/kg. Therefore, it was confirmed that the mixed extract of Schisandra and Schisandra exhibits similar efficacy compared to the Schisandra extract even in a smaller amount, which is about 20 times or more of the amount of the original medicine of Schisandra.

From these results, it can be seen that the use of a combination of White Persimmon and Schisandra extracts exhibits significantly better efficacy than the use of either the White Persimmon extract or the Schisandra extract alone, even if the amount of the herbal medicine is very small.

<Experiment example 3. Evaluation test of expectorant activity of Hakushu and Schisandra extract>
To assess the expectorant activity of the extracts of the invention, the method of Engler et al. (Journal of Ethnopharmacology, 1984, 11, 151-157) was used.

The expectorant activity of each volume of the mixed extract prepared in Example 1 was measured as follows.

As experimental animals, 12 male ICR mice (Orient Bio, Korea) weighing 30 to 33 g were used in each group. In each experimental group, the extract prepared in Example 1, a 30% ethanol dry extract of Hakushu (11 → 1), and a 10% ethanol dry extract of Schisandra (6.3 → 1) were orally administered for 30 Minutes later, 5% phenol red was injected intraperitoneally. Thirty minutes later, the neck was dislocated, the abdominal aorta was exsanguinated, and the entire trachea was dissected. The separated trachea was placed in 1 ml of physiological saline and stored refrigerated for 24 hours. After 24 hours, the refrigerated trachea was centrifuged at 3000 rpm for 10 minutes, 1N sodium hydroxide (NaOH) was added to the supernatant (0.1 ml of NaOH per 1 ml of supernatant), and the absorbance at 546 nm was measured. Expectorant activity was measured at a concentration of .

The experimental results are shown in Table 3 and FIG. 2 below.

As shown in Table 3 above, the extract of Example 1 exhibited similar efficacy to that of the white perilla extract at a dose of 100 mg/kg. Therefore, it was confirmed that the mixed extract of Schisandra spp. and Schisandra japonica exhibits similar efficacy even in an amount that is about 7 times or more lower than the amount of the original herbal medicine.

Furthermore, the extract of Example 1 showed better efficacy than Schisandra extract at a dose of 300 mg/kg. Therefore, it was confirmed that the mixed extract of Schisandra and Schisandra exhibits similar efficacy even in an amount that is about 7 times or more lower than the amount of the original medicine of Schisandra compared to the Schisandra extract.

From these results, it can be seen that the use of a combination of White Persimmon and Schisandra extracts exhibits significantly better efficacy than the use of either the White Persimmon extract or the Schisandra extract alone, even if the amount of the herbal medicine is very small.

In short, as confirmed in the above experiment, surprisingly, the cough suppression rate and sputum excretion activity were significantly improved when Schisandra was used in combination with Schisandra spp. than when Schisandra was used alone. It was confirmed that doses of 1 kg or more showed excellent cough suppression rate and sputum excretion ability.

<Experimental example 4: Evaluation test of expectorant activity of C. perilla and Schisandra extract>
In the same manner as in Experimental Example 3, the expectorant activity of Erdostein, a typical antitussive expectorant, and Examples 1 and 12 were evaluated. The results are shown in Table 4 and FIG. 3 below.

As shown in Table 4, it can be seen that the mixed extract of Cangzhuang and Schisandra has similar efficacy to the mixed extract of Bacteria and Schisandra.

Claims (2)

The active ingredient is composed of an extract of White Persimmon and Schisandra, or an extract of Blue Persimmon and Schisandra; :1 to 5:1, and the extract is an aqueous solution of 10% or more of a lower alcohol having 1 to 4 carbon atoms, or an extract using a lower alcohol having 1 to 4 carbon atoms. or a composition for prevention. The composition according to claim 1, wherein the composition is used in the form of a pharmaceutical, a food with health claims, a food, a drink, or a food additive.

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