KR102146570B1 - Composition for preventing, improving or treating prostate disease comprising extract of Althaea rosea as effective component - Google Patents

Abstract

The present invention relates to a composition for preventing, ameliorating, or treating prostate diseases comprising the extract of the extract as an active ingredient, and the extract of the extract of the present invention has excellent relaxation effect of the smooth muscle of the urethra and the prostate, and thus contains the extract of the extract. The composition of the present invention can be usefully used as a health functional food or pharmaceutical material for the prevention, improvement or treatment of prostate disease.

Description

Composition for preventing, improving or treating prostate disease comprising extract of Althaea rosea as effective component}

The present invention relates to a composition for the prevention, improvement or treatment of prostate disease, comprising an extract of Chok Gyu-geun as an active ingredient.

The prostate is an organ that exists only in men, and it is a kind of hormonal organ the size of a hormonal organ that is located just below the bladder and surrounds the urethra. The urethra obliquely penetrates near the front of the prostate gland. The ejaculatory canals on both sides of the prostate pass through the parenchyma from the back of the urethra, and the prostate parenchyma is divided into three glandular lobes. The upper part is the middle lobe based on the ejaculatory tube penetration part, and the lower part is the left and right side lobes centering on the urethra. It is a vascular structure, roughly divided into glandular tissue and epilepsy. In this stroma, it is separated into 30-50 small glandular lobes, from which excretory ducts are opened on both sides of the posterior urethra. The prostate is one of the sexual appendages responsible for reproductive function along with the testes and seminal vesicles. The prostate makes about 1/3 of the liquid components of male semen, and the prostate fluid not only supplies nutrition to sperm made in the testicles, but also prevents solidification of ejaculated semen, thereby increasing sperm motility, thereby enhancing sperm fertility. Help. In addition, since prostate fluid is alkaline, it acts as an important mediator for sperm activity, such as helping sperm that reaches the fallopian tube to fertilize with an egg safely by neutralizing the strong acidity of the female fallopian tube.

In addition, the prostate is an organ that produces various secretions to prevent dryness of the urethra, and is closely related to androgens, a male hormone. As the secretion increases, it gets bigger and bigger, and the prostate in the 20s and 30s is maintained until the 50s, and then becomes enlarged. 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 it because it will return to its original state soon after stopping hormone treatment. Benign prostatic hyperplasia (BPH) is a disease in which urinary symptoms appear by compressing the urethra due to enlargement of the prostate gland tissue around the urethra due to the effects of aging and sex hormone imbalance. It is a male disease that occurs.

Recently, in Korea, the increase rate of patients with prostatic hyperplasia exceeds 20% every year.It is caused by excessive proliferation of smooth cells and epithelial cells in the prostate transition zone, and enlarged prostate is a lower urinary tract symptom. It is known to be due to anatomical obstruction by the enlarged prostate and functional obstruction by the α1-receptor that contracts the prostate smooth muscle. The main symptoms caused by obstruction include washing or weak urine in which the urine stem becomes thin and weak, delayed urine that has to wait for a long time when starting to urinate, cessation of urination that is stopped regardless of the will during urination, dropping in the end of urination that falls like a drop after urine, and a feeling of residual urine. This is representative. Among the various mechanisms of prostate enlargement, representative mechanisms are known to be related to the male hormones testosterone (T) and dihydrotestosterone (DHT).

Meanwhile, Gyu-geun Chok is a hollyhock ( Althaea rosea ), and the hollyhock is called chokgyuhwa, deokduhwa, junjunghwa, chokgyu, chokgyehwa, danogeum, etc. The root of the hollyhock is known to contain pentosan, methyl pentosan, etc., and is effective in blue fever, blood, diuresis, and drainage. It is known to be used for treatment.

As a prior art related to psyllium, Korean Patent No. 1693220 discloses a composition for enhancing immunity or a composition for the prevention or treatment of viral diseases containing extracts of psyllium, and Korean Laid-Open Patent No. 2016-0074719 Or a composition for preventing, treating, or improving pain containing the extract as an active ingredient is disclosed, but there is no disclosed composition for the prevention, improvement or treatment of prostate disease comprising the extract of the present invention as an active ingredient. .

The present invention is derived from the above requirements, the present invention provides a composition for preventing, ameliorating or treating prostate disease comprising the extract as an active ingredient, and that the extract has the effect of relaxing prostate smooth muscle. By confirming, the present invention was completed.

In order to achieve the above object, the present invention provides a pharmaceutical composition for the prevention or treatment of prostate disease containing the extract as an active ingredient.

In addition, the present invention provides a health functional food composition for the prevention or improvement of prostate disease, comprising the extract of Chok Gyu-geun as an active ingredient.

The present invention relates to a composition for preventing, ameliorating or treating prostate diseases comprising the extract as an active ingredient, and the extract of the present invention has an excellent relaxing effect of smooth muscle in the prostate, so that the prevention, improvement or treatment of prostate diseases It can be usefully used as a health functional food or pharmaceutical material.

FIG. 1 is a result of confirming the relaxation effect of vascular smooth muscle by adding 1 μM of phenylephrine to the extracted pulmonary artery section to induce contraction, and then treating 200 μg/ml of a sphenoid muscle extract.
Figure 2 is a result of confirming the relaxation effect of the prostate smooth muscle by the extract of the present invention Gyugeun chok. **, *** indicates that the relaxation effect of the smooth muscle treated with the sphenoid muscle extract was statistically significantly increased compared to that of the prostate smooth muscle not treated with the sphenoid muscle extract, ** p<0.01, and *** p<0.001.

The present invention relates to a pharmaceutical composition for the prevention or treatment of prostate disease containing the extract of Chok Gyu-geun as an active ingredient.

The extract can be prepared by a method comprising the following steps, but is not limited thereto:

(1) extracting by adding an extraction solvent to Althaea rosea ;

(2) filtering the extract of step (1); And

(3) preparing an extract by concentrating the filtered extract in step (2) under reduced pressure and drying it.

In the step (1), the extraction solvent is preferably selected from water, a lower alcohol of C ₁ to C ₄ or a mixture thereof, more preferably a lower alcohol of C ₁ to C ₄ , and even more preferably 70% (v/v) ethanol, but is not limited thereto.

In the above manufacturing method, all conventional methods known in the art, such as filtration, hot water extraction, immersion extraction, reflux cooling extraction, and ultrasonic extraction, can be used as the extraction method. The extraction solvent is preferably extracted by adding 1 to 20 times the weight of the dried chopped gyu-geun, more preferably 5 to 15 times. The extraction temperature is preferably 4 to 50 ℃, 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 a vacuum vacuum concentrator or a vacuum rotary evaporator, but is not limited thereto. In addition, the drying is preferably vacuum drying, vacuum drying, boiling drying, spray drying, or freeze drying, but is not limited thereto. Although the chokgyu-geun does not limit a specific part of the chok-gyu-geun, it is preferable that it is a tuber of the chok-gyu-geun.

The prostate disease is preferably an enlarged prostate or lower urinary tract caused by an enlarged prostate, but is not limited thereto, and may include a prostate disease that can be prevented, improved, or treated by relaxing urethral smooth muscle or prostate smooth muscle. The active ingredient of the present invention can relax vascular smooth muscle cells, urethra or prostate smooth muscle, and the relaxation of the vascular smooth muscle cells is characterized by NOS regulation, and the relaxation of prostate smooth muscle activates potassium channels. It is characterized by hyperpolarization control.

The pharmaceutical composition of the present invention may further include a carrier, an excipient, or a diluent in addition to the extract of Chok Gyu-geun.

The pharmaceutical composition of the present invention may be administered orally or parenterally, and when administered parenterally, it is preferable to select an injection method for external use of the skin or intraperitoneal, rectal, intravenous, intramuscular, subcutaneous, intrauterine dural or cerebrovascular injection.

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, and the like, and such solid preparations include at least one excipient in one or more compounds, such as starch, calcium carbonate, sucrose, or lactose ( lactose), gelatin, etc. In addition, in addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Liquid preparations for oral administration include suspensions, liquid solutions, emulsions, syrups, etc.In addition to water and liquid paraffin, which are commonly used simple diluents, various excipients such as wetting agents, sweetening agents, fragrances, and preservatives may be included. have. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized formulations, and suppositories. As the non-aqueous solvent and the suspension solvent, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, and injectable ester such as ethyl oleate may be used. As a base for suppositories, witepsol, macrogol, tween 61, cacao butter, laurin, glycero gelatin, and the like may 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 the type of disease, severity, and drug activity of the patient. , Sensitivity to drugs, time of administration, route of administration and rate of excretion, 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 administered in combination with other therapeutic agents, may be administered sequentially or simultaneously with a conventional therapeutic agent, and may be administered single or multiple. It is important to administer an amount capable of obtaining the maximum effect in a minimum amount without side effects in consideration of all the above factors, and this can be easily determined by a person skilled in the art.

The dosage of the composition of the present invention can be used in various ranges according to the patient's weight, age, sex, health status, diet, administration time, administration method, excretion rate, and severity of disease.

In addition, the present invention relates to a health functional food composition for the prevention or improvement of prostate disease comprising the extract of chokgyu-geun as an active ingredient.

The health functional food composition for the prevention or improvement of prostate disease comprising the extract of Chok Gyu-geun as an active ingredient is prepared in any one selected from beverages, pills, tablets, capsules, and powders, or added as ingredients of food. It can be manufactured by, and can be appropriately manufactured according to a conventional method.

Examples of foods that can be added to the extract of the chop gyu-geun of the present invention include meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gum, dairy products including ice cream, various soups, and beverages. , Tea, beverages, alcoholic beverages and vitamin complexes may be in any one form selected from, and includes all health functional foods in the usual sense.

The health functional food includes various nutrients, vitamins, minerals (electrolytes), synthetic and natural flavors, coloring agents and enhancers (cheese, chocolate, etc.), pectic acid and salts thereof, alkynic acid and salts thereof, organic acids, protective colloid thickeners. , pH adjusters, stabilizers, preservatives, glycerin, alcohol, carbonates used in carbonated beverages, and the like. In addition, it may contain pulp for the manufacture of natural fruit juices 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 ingredients. The natural carbohydrates are monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, and polysaccharides such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. As the sweetener, natural sweeteners such as taumatin and stevia extract, synthetic sweeteners such as saccharin and aspartame can be used.

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

Example One. Gyu-geun Preparation of extract

After pulverizing 500 g of chopped gyu-geun, 5 ℓ of 70% (v/v) ethanol was added, followed by ultrasonic extraction 3 times for 1 hour at room temperature. The extract was filtered under reduced pressure with Advantec No. 2 (110mm) filter paper to remove insoluble substances and then concentrated under reduced pressure at 40°C using a concentrator equipped with a cooling condenser. In order to completely remove the solvent of the extract concentrated under reduced pressure, 0.5 L of purified water was added to suspend the extract, and then an ethanol extract of Chok Gyu-geun was obtained using a freeze dryer.

[Statistical Analysis]

Statistical analysis of the results obtained in the examples of the present invention was performed by t-test, and *** P <0.001, ** P <0.01, * P <0.05 are statistically significant compared to the control group. It means there is a difference.

Example 2. Verification of relaxation effect of pulmonary aorta using vascular section

Experimental animals were anesthetized male SD (Sprague Dawley) rats weighing 300-350 g for 1 to 2 minutes in a desiccator containing CO ₂ gas, followed by cervical dislocation, and rapidly incised along the midline. After that, the descending aorta was cut to give blood and the thoracic aorta was excised, and the intravascular clot was removed from the modified Kreb's solution shown in Table 1 below, and silicone coated petri-dish with a fine insect pin. ).

Arterial tissue was removed from adipose tissue and connective tissue using a stereomicroscope (Nikon SMZ-2T) at 50X magnification in Kreb's solution ice-cold modified in a silicon coated petri-dish. Depending on the conditions of the experiment, to block the effect of the endothelium-derived relaxing factor (EDRF), endothelium-denuded artery preparation is prepared by scraping the endothelial cells by inserting cotton yarn into the arterial blood vessel, or by omitting the above process and endothelium-attached artery preparation. Prepared. Care was taken not to damage the vascular smooth muscle when the vascular endothelial cells were removed, and the presence or absence of endothelial cells was confirmed by administering 1 μM of carbamylcholine during the vascular tension test so that the vascular relaxation reaction did not occur. . The prepared tissue was cut into small sections of 2-3 mm in length and used for the shrinkage test.

Composition of Modified Kreb's Solution Compounds mM NaCl 120 CaCl ₂ H ₂ O 2.5 MgCl ₂ 2 Glucose 11 NaHCO ₃ 25 NaH ₂ PO ₄ H ₂ O 1.2 KCl 5.9

Arterial sections are mounted on two triangular rings made of tungsten wire vertically in a 20-volume organ bath filled with modified Kreb's solution and fixed up and down. One is at the bottom of the organ bath and the other is an isometric transducer (havard bioscience 52- 9503 tension transducer). The vascular tissue was maintained at a pH of 7.4 by continuously supplying a mixed gas of 95% O ₂ and 5% CO ₂ during the experiment, and a constant temperature of 37°C was maintained using a circulation water bath. The isotonic contraction was stored in a computer through a digital/analog converter (Powerlab PL3504/P, ADI instruments), and then recorded and analyzed using LabChart Pro (ADI insturments).

It was determined as the minimum tension causing the contraction reaction, and 2.0 g was set as the pre-storage force throughout the entire experiment and applied to the experiment. The basic tension was created by applying a tension of 2.0 g, and it was stabilized in the modified Kreb's solution for about 60 minutes. When it is determined that the underlying tension is no longer changed and the thoracic aortic section is fully equilibrium, Phenyl is administered with 60 mM KCl to confirm the normal muscle contraction capacity of the tissue, and to treat the degree of contraction afterwards by 60 mM KCl. Compared with Phenylephrine contraction, the difference between each tissue was statistically minimized. After treatment with 60mM KCl, after washing twice and waiting for 30 minutes, when the vascular tension reached the pre-storage again, 1 μM phenylephrine was administered to induce a contractile reaction. In order to confirm the presence or absence of endothelial cells during the second phenylephrine treatment, 1 μM carbamylcholine was treated to confirm the presence or absence of vascular smooth muscle relaxation.

After stabilization of the arterial section, when the contraction reaction by 1 μM phenylephrine reaches its peak and is in a continuous state, 200 μg/ml of the prepared sphincter extract is added to accumulate in the organ bath, and 200 μg/ml Changes in the contractile force of blood vessels for the muscle extract were observed. The 200 ㎍ / ㎖ of the extract was diluted with distilled water or DMSO, the vehicle was treated in an organ bath at a concentration of not exceeding 0.1% (v / v), and at these concentrations The change in the isometric tension of the vascular smooth muscle was not recorded.

As a result, as shown in FIG. 1, contraction was induced by adding 1 μM of phenylephrine to the extracted pulmonary artery section, and the effect of relaxing vascular smooth muscle was confirmed by treatment with 200 μg/ml of ductus muscle extract. .

Example 3. Prostate Dorsal lobe Prostate relaxation effect verification using section

An 8-week-old male SD (Sprague Dawley) rat weighing 300-350 g was anesthetized in a desiccator containing CO ₂ gas for 1-2 minutes, and the bladder and proximal urethra were removed quickly after cervical dislocation. The capsular muscle layer around the prostate was removed. The physiological solution used in the experiment was a modified Kreb's solution, and the composition is disclosed in Table 1. The surrounding adipose tissue and connective tissue were removed.

Unlike human tissues, prostate tissues extracted from rats are known to induce smooth muscle contraction by the sympathetic nervous system (Noradrenaline) and the parasympathetic nervous system (Acetylcholine), so the removal of the tissue was noted. In Example 3, the dorsal lobe (Noradrenaline sensitive muscle) was excised and tested.

The tissue was removed from adipose tissue and connective tissue in an ice-cold solution in a silicone-coated Petri dish using a stereo microscope (Nikon SMZ-2T). Afterwards, it was cut into 3~5mm length sections and used for muscle contraction tests. The muscle sections were attached by knotting a single silk fiber to a ring made of tungsten wire. One of the two tungsten rings was connected to the bottom of the organ bath and the other to an isometric transducer (havard bioscience 52-9503). Prostate tissue was continuously supplied with 95% of O ₂ and 5% of CO ₂ mixed gas during the experiment to maintain the physiological pH composition. Isotonic contractions were stored in a computer through a digital/analog converter (Powerlab PL3504/P, ADIinstruments), and then recorded and analyzed using LabChart Pro (ADIinsturments). To verify the effect of the sample, 1, 10, 20, 50, 100, 200, 400, 600 ㎍ of the prepared prickly pear extract, respectively, when the contraction reaction by 1 μM phenylephrine reaches the peak and becomes continuous It was added so as to accumulate in the organ bath at a dose of /ml, and the change in the contractile force of blood vessels for each sample was observed, and the dose-response curve was recorded.

As a result, as disclosed in FIG. 2, it was confirmed that the relaxation of blood vessels increased statistically significantly above the concentration of 10 μg/ml.

Claims (7)

A pharmaceutical composition for the prevention or treatment of lower urinary tract caused by enlarged prostate, containing the extract of chokgyugeun as an active ingredient. The pharmaceutical composition for preventing or treating lower urinary tract due to enlarged prostate according to claim 1, wherein the extraction solvent of the extract of Chok Gyu-geun is water, C ₁ to C ₄ lower alcohol, or a mixture thereof. delete The pharmaceutical composition for preventing or treating lower urinary tract due to prostatic hypertrophy according to claim 1, wherein the chokkyeun extract relaxes urethral smooth muscle or prostate smooth muscle. The pharmaceutical composition for preventing or treating lower urinary tract due to prostatic hypertrophy according to claim 1, further comprising a carrier, an excipient, or a diluent in addition to the extract of Chok Gyu-geun. A health functional food composition for the prevention or improvement of lower urinary tract caused by prostate enlargement, comprising the extract of Chok Gyu-geun as an active ingredient. [7] The method of claim 6, wherein the extract is prepared in any one formulation selected from beverages, pills, tablets, capsules, and powders.Prevention or improvement of lower urinary tract due to prostatic hypertrophy For health functional food composition.

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