KR102563879B1 - Composition for preventing, improving or treating prostate disease comprising extract of Artemisia annua Linne as effective component - Google Patents

Abstract

The present invention relates to a composition for preventing, improving or treating prostate diseases, comprising an extract of Artemisia annua Linne as an active ingredient.

Description

Composition for preventing, improving or treating prostate disease comprising extract of Artemisia annua Linne as effective component}

The present invention relates to a composition for preventing, improving or treating prostate diseases, comprising a Cheongho extract as an active ingredient.

The prostate is an organ that produces various secretions to prevent the urethra from drying out, and is closely related to androgens, male hormones. As the secretion increases, it gradually enlarges, and the prostate in the 20s and 30s is maintained until the 50s and then enlarges. This is called benign prostatic hyperplasia, and even if the size is returned to normal by hormone treatment, the risk of side effects is high, and it is difficult to cure because it returns to its original state soon after hormone treatment is stopped.

Representative diseases occurring in the prostate include benign prostatic hyperplasia, chronic prostatitis and prostate cancer. Prostatitis has various causes, but it is a disease that occurs mainly as a part of bacterial infection, inflammation of unknown cause, and chronic pain, and prostate cancer is a malignant tumor in the relatively outer part of the prostate. According to a survey in the United States, prostate cancer It accounts for about 35% of all male cancer patients, and is increasing by 2-3% every year. The frequency of occurrence in Korea is three per 100,000 people, which is not yet a level of concern, but the rate is gradually increasing due to the rapidly changing diet and rapidly increasing elderly population.

On the other hand, Benign prostatic hyperplasia (BPH) is a disease in which the prostate 'glandular tissue' around the urethra enlarges under the influence of aging and imbalance of sex hormones and compresses the urethra, resulting in urination symptoms. It occurs rapidly after the age of 50 in men. It is a male disease. Recently, the rate of increase in patients with BPH in Korea is rapidly increasing, exceeding 20% every year, and it is caused by excessive proliferation of smooth cells and epithelial cells in the prostate transition zone. It is known to be caused by anatomical obstruction by an enlarged prostate and functional obstruction by α1-receptors that contract prostatic smooth muscle. The main symptoms due to obstruction are thin urine or weak urine stream, delayed urine that requires a long wait to start urinating, cessation of urination that stops regardless of the will while urinating, dripping at the end of urination that falls like water droplets after urinating, and a feeling of residual urine, etc. This is typical. Among various mechanisms of prostatic hyperplasia, it is known that a representative mechanism is related to male hormones, testosterone (T) and dihydrotestosterone (DHT).

On the other hand, Artemisia annua Linne is a plant belonging to the Asteraceae family and is a plant commonly found on roadsides, clearings, and riversides in China, Korea, Japan, Mongolia, and Siberia. In ancient China, it has been used to treat symptoms caused by infection with Plasmodium falciparum, such as malaria (Kooy and Sullivan, J Ethnophamacol., 150:1-13 (2013)). It has been used for the treatment of , pediatric dyspepsia, indigestion, and dysentery. Recently, as the anti-cancer effect of artemisinin, one of the components contained in Artemisia, is known, interest in Artemisia is increasing. According to the current KFDA standard, only young leaves of Artemisia can be used for food, so currently marketed pills and extracts are all processed and marketed only with young leaves, but the roots, leaves, and stems of Artemisia are also effective for medicinal purposes. As it is known, research on this is actively progressing.

Korean Patent No. 1522273 and Korean Patent No. 1793379 disclose a turmeric extract and a prickly pear extract that exhibit androgen receptor reduction and prostate weight reduction effects through the prevention and effect of prostatic hyperplasia, but the present invention's Cheongho ( Artemisia annua Linne ) composition for preventing, improving or treating prostate diseases comprising an extract as an active ingredient has not been disclosed.

Republic of Korea Patent No. 10-1522273 (registered on May 15, 2015) Republic of Korea Patent No. 10-1793379 (registered on October 27, 2017)

The problem to be solved by the present invention is to provide a composition for preventing, improving or treating prostate disease comprising a Cheongho extract as an active ingredient.

The present invention provides a pharmaceutical composition for preventing or treating prostate disease comprising an extract of Artemisia annua Linne as an active ingredient.

The extraction solvent of the Cheongho ( Artemisia annua Linne ) extract may be water, C1-C4 lower alcohol, or a mixture thereof.

The prostate disease may be prostatitis, benign prostatic hyperplasia or lower urinary tract disease due to benign prostatic hyperplasia.

The Cheongho ( Artemisia annua Linne ) extract can inhibit the activity of 5-alpha reductase in tissues.

The Cheongho ( Artemisia annua Linne ) extract can relax prostate smooth muscle.

The prostate smooth muscle relaxation may be due to activation of a potassium channel.

In addition, the present invention provides an agent for improving dysuria caused by prostate disease, comprising a pharmaceutical composition as an active ingredient.

In addition, the present invention provides a health functional food composition for preventing or improving prostate disease comprising an extract of Artemisia annua Linne as an active ingredient.

The present invention prevents and treats prostate diseases such as benign prostatic hyperplasia by inhibiting the activity of 5-alpha reductase in the prostate and relaxing prostatic smooth muscle, and symptoms of urination disorders such as lower urinary tract disease, frequent urination, and nocturia accompanied by benign prostatic hyperplasia. can improve

1 is a result of measuring the activity of 5-alpha reductase according to the administration of the Cheongho extract of the present invention.
Figure 2 is the result of confirming the relaxation effect of the smooth muscle of the prostate by the Cheongho extract of the present invention.
Figure 3 is the result of confirming that the relaxation effect of the prostate smooth muscle by the Cheongho extract of the present invention is achieved through hyperpolarization control through the activation of the potassium channel (Potassium channel).

The present invention relates to a pharmaceutical composition for preventing or treating prostate disease comprising an extract of Artemisia annua Linne as an active ingredient.

The prostate disease is preferably, but not limited to, benign prostatic hyperplasia, prostate cancer or prostatitis, more preferably benign prostatic hyperplasia, and may include dysuria caused by benign prostatic hyperplasia, wherein the dysuria is lower urinary tract disease, frequent urination. , nocturia, and the like.

The method for producing the Cheongho ( Artemisia annua Linne ) extract is (1) extracting by adding an extraction solvent to Cheongho ( Artemisia annua Linne ); (2) filtering the extract of step (1) and (3) concentrating the filtered extract of step (2) under reduced pressure and drying to prepare an extract, but is not limited thereto.

In the step (1), the extraction solvent is preferably selected from water, C1-C4 lower alcohols, or mixtures thereof, more preferably C1-C4 lower alcohols, and still more preferably 95% (v/ v) Ethyl alcohol, but is not limited thereto.

In the preparation method, all conventional methods known in the art such as filtration, hot water extraction, immersion extraction, reflux cooling extraction and ultrasonic extraction may be used as the extraction method. The extraction solvent is preferably extracted by adding 1 to 20 times the weight of the dried blue tiger, more preferably 5 to 15 times. The extraction temperature is preferably 4 to 50 ° C, but is not limited thereto. In addition, the extraction time is preferably 0.5 to 10 hours, more preferably 0.5 to 5 hours, but is not limited thereto. In the above method, the vacuum concentration in step (3) is preferably performed using a vacuum vacuum concentrator or a vacuum rotary evaporator, but is not limited thereto. In addition, drying is preferably reduced pressure drying, vacuum drying, boiling drying, spray drying or freeze drying, but is not limited thereto.

The Cheongho ( Artemisia annua Linne ) extract can inhibit the activity of 5-alpha reductase in tissue, and the tissue may be prostate tissue.

The blue tiger ( Artemisia annua Linne ) extract can relax the prostate smooth muscle, and the prostate smooth muscle relaxation may be due to the activation of potassium (K) channels.

The Cheongho ( Artemisia annua Linne ) extract can relax urethral or prostate smooth muscle.

The pharmaceutical composition of the present invention may further include a carrier, excipient or diluent in addition to the Cheongho ( Artemisia annua Linne ) extract.

The pharmaceutical composition of the present invention may be administered orally or parenterally, and in the case of parenteral administration, it is preferable to select an external skin or intraperitoneal, rectal, intravenous, intramuscular, subcutaneous, intrauterine intrathecal or intracerebrovascular injection method.

The pharmaceutical composition of the present invention may be prepared using diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrants, and surfactants. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc., and these solid preparations include at least one excipient in one or more compounds, such as starch, calcium carbonate, sucrose or lactose ( It is prepared by mixing lactose), gelatin, etc. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Liquid formulations for oral administration include suspensions, internal solutions, emulsions, syrups, etc. In addition to water and liquid paraffin, which are commonly used simple diluents, various excipients such as wetting agents, sweeteners, aromatics, and preservatives may be included. there is. Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solvents, suspensions, emulsions, freeze-dried formulations, and suppositories. Propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate may be used as non-aqueous solvents and suspending solvents. As a base for the suppository, Witepsol, Macrogol, Tween) 61, cacao butter, laurin paper, glycerogelatin, and the like can be used.

The composition according to the present invention is administered in a pharmaceutically effective amount. In the present invention, "pharmaceutically effective amount" means an amount sufficient to treat a disease at a reasonable benefit / risk ratio applicable to medical treatment, and the effective dose level is based on the type, severity, and activity of the drug in the patient. , sensitivity to the drug, time of administration, route of administration and excretion rate, duration of treatment, factors including drugs used concurrently, and other factors well known in the medical field. The composition of the present invention may be administered as an individual therapeutic agent or in combination with other therapeutic agents, may be administered sequentially or simultaneously with conventional therapeutic agents, and may be administered single or multiple times. Considering all of the above factors, it is important to administer an amount that can obtain the maximum effect with the minimum amount without side effects, which can be easily determined by those skilled in the art.

The dosage of the composition of the present invention can be used in a variety of ranges depending on the patient's body weight, age, sex, health condition, diet, administration time, administration method, excretion rate, and severity of the disease.

In addition, the present invention relates to an agent for improving dysuria due to prostate disease, comprising the pharmaceutical composition as an active ingredient.

In addition, the present invention relates to a health functional food composition for preventing or improving prostate disease, comprising an extract of Artemisia annua Linne as an active ingredient.

The health functional food composition for preventing or improving prostate disease containing the Cheongho ( Artemisia annua Linne ) extract as an active ingredient is prepared by any one selected from beverages, pills, tablets, capsules, and powders, or food It can be prepared by adding as a component of, and can be suitably prepared according to a conventional method.

Examples of foods to which the extract of Artemisia annua Linne of the present invention can be added include meat, sausages, bread, chocolate, candies, snacks, confectionery, pizza, ramen, other noodles, gum, dairy products including ice cream, It may be in any one form selected from various soups, beverages, tea, drinks, alcoholic beverages, and vitamin complexes, and includes all health functional foods in the conventional sense.

The health functional food includes various nutrients, vitamins, minerals (electrolytes), synthetic and natural flavors, coloring agents and enhancers (cheese, chocolate, etc.), pectic acids and their salts, alkynic acids and their salts, organic acids, protective colloidal thickeners , pH regulators, stabilizers, preservatives, glycerin, alcohol, carbonation agents used in carbonated beverages, and the like. In addition, it may contain fruit flesh for the production of natural fruit juice and vegetable beverages. These components may be used independently or in combination.

The health functional food composition of the present invention may contain various flavoring agents or natural carbohydrates as additional components. The natural carbohydrates include monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, polysaccharides such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. As the sweetener, natural sweeteners such as thaumatin and stevia extract, or synthetic sweeteners such as saccharin and aspartame may be used.

Hereinafter, the present invention will be described in more detail using examples. These examples are only for explaining the present invention in more detail, and it is obvious to those skilled in the art that the scope of the present invention is not limited thereto.

Example 1: Preparation of Cheongho Extract

Cheongho ( Artemisia annua Linne ) was purchased from Kwangmyeongdang Pharmaceutical Co., Ltd., and Cheongho ( Artemisia annua Linne ) extract was prepared by requesting the Korea Plant Extract Bank (KOREA PLANT EXTRACT BANK).

At this time, 95% ethyl alcohol (GR grade) was used as the extraction solvent, and 11.09 g of Cheongho extract prepared with 3.93% extraction yield was distributed and dissolved in DMSO (Dimethyl Sulfoxide) to prepare and use stock did

Example 2: Confirmation of 5-alpha reductase inhibitory effect of Cheongho extract

Male Sprague Dawley (SD) rats aged 13 to 14 weeks were anesthetized for 1 to 2 minutes in a desiccator containing CO ₂ gas, and after cervical dislocation, the bladder and proximal urethra were quickly removed and the area around the prostate was removed. The capsular muscle layer was clearly removed. Prostate tissue was removed and homogenized by adding Phosphate buffer solution (pH 7.4, Life Technologies, USA). The homogenate was centrifuged at 5,000 rpm and 4° C. for 10 minutes, and only the supernatant was taken and used in the experiment. The experiment was conducted based on the amount of protein using the Bradford assay, based on 200 μg, and the activity of 5-Alpha reductase was measured using a commercially available rat 5-Alpha reductase II ELISA kit (Cusabio, USA).

200 μg of the homogenate was reacted with 1, 10, 100 μg/ml of Cheongho extract or 20 μM Finasteride used as a positive control at room temperature, and treated with 1 nM testosterone (Tokyo Chemical Ins. Co., Tokyo, Japan) at 37 ° C. It was reacted for 1 hour and 30 minutes in an incubator. The experiment was conducted according to the manual of Cusabio, and the absorbance was measured at a wavelength of 450 nm, and the concentration of 5-alpha reductase was calculated as Fold for the control group.

Statistical analysis: Statistical analysis was performed by one-way ANOVA, and compared to the Vehicle control group, ** P<0.01, * P<0.05, and compared to the Testosterone group, ## P<0.01, # P<0.05 indicated by

As a result, referring to FIG. 1, when the positive control material Finasteride and 100 μg/ml Cheongho extract were treated, a statistically significant inhibition of 5-alpha reductase activity was observed.

Example 3: Confirmation of prostate relaxation effect of Cheongho extract

Experimental animals are 13-14 weeks old male SD (Sprague Dawley) rats anesthetized for 1-2 minutes in a desiccator containing CO ₂ gas, and after cervical dislocation, the bladder and proximal urethra are quickly removed The capsular muscle layer around the prostate was clearly removed. The physiological solution used in the experiment was Modified Kreb's solution, and its composition is shown in Table 1 below. Hereinafter, the test was performed after removing the adipose tissue and connective tissue surrounding the prostate.

Compoundsrelaxant Content (mM) NaCl 120 CaCl ₂ .H ₂ O 2.5 MgCl ₂ 2 Glucose 11 NaHC0 ₃ 25 NaH ₂ PO ₄ .H ₂ O 1.2 KCl 5.9

Tissue sections were cut into 3-5 mm long sections and used in the experiment. Tissue sections are attached to a loop made of tungsten wire by knotting a single silk fiber. One of the two tungsten rings is connected to the bottom of the organ bath and the other to the isometric transducer (Harvard bioscience 52-9503). Prostate tissue was continuously supplied with a mixed gas of 95% O ₂ and 5% CO ₂ during the experiment period to maintain physiological pH. Isometric contractions were stored in a computer through a digital/analog converter (Powerlab PL3504/P, ADIinstruments), and then recorded and analyzed using LabChart Pro (ADIinstruments). In order to confirm the prostate relaxant effect of Cheongho extract, when the contraction response by 10 μM phenylephrine reaches its peak and becomes continuous, 0.1, 1, 10, 100, 300 and 500 μg/ It was added to the organ bath at a concentration of ㎖ so as to accumulate, and the change in contractile force of the prostate tissue for each sample was observed and the dose-response curve was recorded.

Statistical analysis was performed by T-test, ^** P<0.01, ^* P<0.05 were considered when there was a significant difference compared to the Vehicle control group (Control), ^## P<0.01, ^# P< 0.05 was considered statistically significant compared to the treatment of Inhibitors.

Referring to FIG. 2, after inducing contraction by adding 10 μM phenylephrine to the prostate sections of the excised rats, the Cheongho extract was added to the organ bath at concentrations of 0.1, 1, 10, 100, 300, and 500 μg/ml. As a result of observing the relaxation of smooth muscle by adding it in an accumulative manner, it was possible to observe significant relaxation of prostate smooth muscle from a concentration of 1 μg/ml.

Example 4: Confirmation of prostate relaxation effect of Cheongho extract through potassium channel

The tissue slices excised in Example 3 were pretreated with 10 mM of tetraethylammonium (TEA), and 0.1, 1, 10, 100, 300, and 500 μg/ml of Cheongho extract were added to accumulate in the organ bath, resulting in relaxation of the smooth muscle of the prostate. was confirmed, and compared with the group treated with Cheongho extract without pretreatment.

Referring to Figure 3, compared to the group treated with Cheongho extract without pretreatment, it was observed that the relaxation effect in prostate tissue was partially suppressed in the case of TEA pretreatment. From these results, it can be seen that hyperpolarization through the activation of potassium channels is involved in the relaxation of the prostate by the Cheongho extract of the present invention.

As described above, the composition for preventing or treating prostate diseases comprising the Cheongho extract as an active ingredient according to the present invention inhibits the activity of 5-alpha reductase in the prostate and relaxes the smooth muscle of the prostate, thereby preventing prostate diseases such as benign prostatic hyperplasia. And treatment, can improve the symptoms of dysuria, such as lower urinary tract disease, frequent urination, nocturia, etc. accompanying benign prostatic hyperplasia.

Above, preferred embodiments of the present invention have been described in detail. The description of the present invention is for illustrative purposes, and those skilled in the art will understand that other specific forms can be easily modified without changing the technical spirit or essential features of the present invention.

Therefore, the scope of the present invention is indicated by the following claims rather than the above detailed description, and all changes or modifications derived from the meaning, scope and equivalent concept of the claims are included in the scope of the present invention. should be interpreted

Claims (8)

A pharmaceutical composition for preventing or treating prostate disease comprising an extract of Artemisia annua Linne as an active ingredient,
The Cheongho extract is an ethanol extract,
The prostate disease is characterized in that benign prostatic hyperplasia, dysuria due to prostatic hyperplasia, or both of the above, the pharmaceutical composition. According to claim 1,
Characterized in that the Cheongho extract is a 95% (v / v) ethanol extract, a pharmaceutical composition According to claim 1,
The dysuria is characterized in that the lower urinary tract, frequent urination or nocturia, the pharmaceutical composition. According to claim 1,
The Cheongho ( Artemisia annua Linne ) extract is a pharmaceutical composition, characterized in that for inhibiting the activity of 5-alpha reductase (5-Alpha reductase) in the tissue. According to claim 1,
The Cheongho ( Artemisia annua Linne ) extract is a pharmaceutical composition, characterized in that to relax the prostate smooth muscle. According to claim 5,
The prostate smooth muscle relaxation is a pharmaceutical composition, characterized in that by the activation of potassium channels (Potassium channel). A dysuria improving agent comprising the pharmaceutical composition according to any one of claims 1 to 6 as an active ingredient. A health functional food composition for preventing or improving prostate disease comprising Artemisia annua Linne extract as an active ingredient,
The Cheongho extract is an ethanol extract,
The prostate disease is characterized in that the prostatic hyperplasia, dysuria due to prostatic hyperplasia, or both of the above, health functional food composition.