KR101988298B1 - Composition for preventing, improving or treating prostate disease comprising extract of Corydalis ternata tuber as effective component - Google Patents

Abstract

The present invention relates to a composition for preventing, ameliorating or treating a prostate disease comprising an ascorbic acid extract as an active ingredient. Since the ascorbic acid extract of the present invention is excellent in the relaxation effect of the urethra and prostate smooth muscle, Can be usefully used as a health functional food or a pharmaceutical material for preventing, ameliorating or treating a prostate disease.

Description

TECHNICAL FIELD [0001] The present invention relates to a composition for preventing, improving or treating a prostate disease comprising an ascorbic acid extract as an active ingredient,

The present invention relates to a composition for preventing, ameliorating, or treating a prostate disease, which comprises a pale color extract as an active ingredient.

The prostate is an organ that exists only in men. It is a type of hormonal organ that is located just below the bladder and surrounds the urethra. The urethra slopes diagonally to the near side of the prostate front. The appendages of both prostates pass through the parenchyma at the back of the urethra, and the prostate parenchyma is separated by three leaflets. The upper part is the middle part based on the appositional puncture part, and the lower part is the left side and the lateral side around the urethra. The structure of the ductal epithelium is divided into anterior segment and epilepsy. In this epilepsy, 30 to 50 small lobes are separated, from which an excretory tube opens to both sides of the posterior urethra. The prostate gland is one of the sex-attaching organs responsible for reproductive function with the testes and seminal vesicles. The prostate produces about one-third of the liquid component of male semen, which not only nourishes the sperm produced in the testicles but also increases the motility of the sperm by preventing the sperm from becoming solidified, Help. In addition, since the prostate fluid is alkaline, it neutralizes the strong acidity of the female fallopian tubes and helps the sperm reaching the fallopian tube safely and fertilize the egg.

In addition, the prostate gland to produce a variety of secretions to keep the urethra dry, is closely related to the male hormone Androgens. As the secretion increases, the size of the prostate increases in the 20s and 30s. This is called benign prostatic hyperplasia and it is difficult to cure it because the risk of side effects is high even if the size is returned to the normal level by the hormone treatment, and soon after stopping the hormone treatment, it returns to the original state. Benign prostatic hyperplasia (BPH) is a disease in which urethral prostate 'umbellate' is enlarged due to aging and imbalance of sex hormones, resulting in urinary symptoms due to the urethra. It is a male disease that happens.

Recently, the rate of growth of patients with hyperplasia of the prostate in Korea has been steadily increasing to more than 20% every year. It is caused by excessive proliferation of smooth muscle and epithelial part of the prostate transplantation part, , Which is known to be due to anatomical occlusion by the enlarged prostate and functional occlusion by the? 1 -receptor which contracts the prostate smooth muscle. The main symptoms of occlusion include urinary tract weakness or weak urine stem or urine, delayed urination to wait for a long time to start urinating, discontinuation of urination to stop irrespective of urinary incontinence, terminal urination dropping like urine drops, This is representative. It is known that the testosterone (T) and the dihydrotestosterone (DHT) are involved in the typical mechanism of the various mechanisms of prostate hypertrophy.

On the other hand, about 300 species (specie) contained in the genus Corydalis genus of the pale color are known, and it grows in the moisture of the mountain. It grows about 20cm from the stem of 1cm diameter, There is one leaf like a bract, the branches are split, the leaves are alternate, the petiole is long, and the bract is split 1-3 times. The cut pieces are obovate and the upper part is deeply or acutely split, with sawtooth on the edge and white on the back. Flower is bloomed in April, light purplish red, 5 ~ 10 spots in gun flower inflorescence, corolla is about 2.5cm long, honeycomb in back, and front spread widely. In one room, tuber is used as a blood sugar, antispasmodic agent and analgesic. It is distributed to Siberia through Korea and northeastern part of China.

The present invention relates to a composition for the prevention and treatment of dental caries, which comprises a colorless extract disclosed in Korean Patent No. 0999597 or dihydrocoridalin isolated therefrom as an active ingredient, and the composition disclosed in Korean Patent No. 3347443 Prior art for compositions for preventing, ameliorating, or treating a prostate disease, which comprises the present colorectal extract as an active ingredient, is disclosed in Japanese Unexamined Patent Publication There is no way.

The present invention provides a composition for preventing, improving or treating a prostate disease comprising an ascorbic acid extract as an active ingredient. The present invention provides a composition for preventing, improving or treating a prostate disease, Confirming that not only the relaxation but also the prostate relaxation effect are excellent, the present invention has been completed.

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

The present invention also provides a health functional food composition for preventing or ameliorating a prostate disease, which comprises a pale yellow extract as an active ingredient.

The present invention relates to a composition for preventing, improving or treating a prostate disease, which comprises a pale color extract as an active ingredient. The present invention relates to a composition for preventing, improving or treating a prostate disease, which comprises a urethral smooth muscle and a prostate smooth muscle , The composition of the present invention containing a pale yellow extract can be effectively used as a health food or medicine for preventing, ameliorating or treating a prostate disease.

Fig. 1 shows the result of confirming the arterial smooth muscle relaxation effect by the ascorbic acid extract.
FIG. 2 is a result of confirming that the effect of the ascorbic acid on the aortic vascular relaxation effect is controlled by NOS in the endothelial cells.
FIG. 3 shows the result of confirming the relaxation effect of the prostate smooth muscle by the pale color extract.
FIG. 4 is a result of confirming that the relaxation effect of prostate smooth muscle by neurocolor extract is controlled through hyperpolarization through activation of potassium channel.
FIG. 5 shows the result of confirming the relaxation effect of the corpus cavernosum tissue by the ascorbic acid extract.

The present invention is based on the Corydalis The present invention relates to a pharmaceutical composition for preventing or treating a prostate disease,

The colorless extract may be prepared by a method including, but not limited to, the following steps:

(1) Corydalis ternata ) with an extraction solvent;

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

(3) The step of extracting the filtered extract of step (2) by concentration under reduced pressure and drying.

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

In the above production method, any conventional method known in the art such as filtration, hot water extraction, immersion extraction, reflux cooling extraction, and ultrasonic extraction may be used. The extraction solvent is preferably added in an amount of 1 to 20 times, more preferably 5 to 15 times, the weight of the dried original color. The extraction temperature is preferably 4 to 50 DEG C, but is not limited thereto. The extraction time is preferably 0.5 to 10 hours, more preferably 0.5 to 5 hours, but not always limited thereto. In the above method, it is preferable to use a vacuum decompression concentrator or a vacuum rotary evaporator for the decompression concentration in the step (3), but it is not limited thereto. The drying is preferably performed under reduced pressure, vacuum drying, boiling, spray drying or freeze drying, but not always limited thereto. The primary color is not limited to a particular part of the primary color but is preferably a primary color.

Preferably, the prostate disease is prostate hyperplasia or lower urinary tract infection caused by enlargement of the prostate gland. However, the present invention is not limited thereto and may include a prostate disease that can be prevented, improved or treated by relaxing the smooth muscle of the urethra or the smooth muscle of the prostate gland. The active ingredient of the present invention, which is the active ingredient, is capable of relaxing vascular smooth muscle cell relaxation, urethra or prostate smooth muscle, and the relaxation of vascular smooth muscle cells is characterized by NOS regulation, and relaxation of prostate smooth muscle activates potassium channel Which is characterized by hyperpolarization control.

The pharmaceutical composition of the present invention may further comprise a carrier, an excipient or a diluent in addition to the above-described precursor extract.

The pharmaceutical composition of the present invention may be administered orally or parenterally, and it is preferable to use an intravenous or intraperitoneal, rectal, intravenous, intramuscular, subcutaneous, intrauterine, or intracerebral injection method during parenteral administration.

The pharmaceutical composition of the present invention can be prepared using a diluent such as a filler, an extender, a binder, a wetting agent, a disintegrant, a surfactant, or an excipient. Solid formulations for oral administration include tablets, pills, powders, granules, capsules, and the like, which may contain one or more excipients such as starch, calcium carbonate, sucrose or lactose lactose, gelatin and the like. In addition to simple excipients, lubricants such as magnesium stearate, talc, and the like may also be used. Liquid preparations for oral administration include suspensions, solutions, emulsions, syrups and the like. Various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like may be included in addition to water and liquid paraffin, which are simple diluents commonly used. have. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, freeze-dried preparations, and suppositories. Examples of non-aqueous solvents and suspensions include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, injectable esters such as ethyl oleate, and the like. Examples of suppositories include witepsol, macrogol, tween 61, cacao butter, laurin, glycerogelatin and the like.

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 will depend on the type of disease, severity, , Sensitivity to the drug, time of administration, route of administration and rate of release, duration of treatment, factors including co-administered drugs, and other factors well known in the medical arts. The composition of the present invention can be administered as an individual therapeutic agent or in combination with other therapeutic agents, and can be administered sequentially or simultaneously with conventional therapeutic agents, and can be administered singly or in multiple doses. It is important to take into account all of the above factors and to administer the amount in which the maximum effect can be obtained in a minimal amount without side effects, which can be easily determined by those skilled in the art.

The dosage of the composition of the present invention may be varied depending on the patient's body weight, age, sex, health condition, diet, administration time, administration method, excretion rate, and severity of disease.

The present invention also relates to a health functional food composition for preventing or ameliorating a prostate disease, which comprises a pale color extract as an active ingredient.

The health functional food composition for preventing or ameliorating a prostate disease, which comprises the above-described color extract as an active ingredient, can be prepared by any one of beverage, ring, tablet, capsule and acid, And can be suitably prepared according to a conventional method.

Examples of the food to which the present color extract can be added include dairy products including meat, sausage, bread, chocolate, candy, snack, confectionery, pizza, ramen and other noodles, gums, ice cream, A tea, a drink, an alcoholic beverage, and a vitamin complex, all of which include health functional foods in a conventional sense.

The health functional foods include various nutrients, vitamins, minerals (electrolytes), synthetic and natural flavors, colorants and enhancers (cheese, chocolate etc.), pectic acid and its salts, alkynic acid and its salts, , pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonating agents used in carbonated drinks, and the like. It may also contain flesh for the production of natural fruit juices and vegetable drinks. These components may be used independently or in combination.

The health functional food composition of the present invention may contain various flavors or natural carbohydrates as an additional ingredient. The natural carbohydrates are sugar saccharides such as monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, polysaccharides such as dextrin and cyclodextrin, xylitol, sorbitol and erythritol. Examples of sweeteners include natural sweeteners such as tau martin and stevia extract, synthetic sweeteners such as saccharin and aspartame, and the like.

Hereinafter, the present invention will be described in more detail with reference to Examples. It is to be understood by those skilled in the art that these embodiments are merely illustrative of the present invention and that the scope of the present invention is not limited thereto.

Example  1. Preparation of pale color extract

The commercially available bullion stem ( Corydalis ternata tuber) was pulverized and 50 l of 70% (v / v) ethanol was added thereto, followed by reflux extraction at 80 ± 2 ° C for 3 hours. The extract was filtered under reduced pressure through Advantec No. 2 (Advantec No. 2, 110 mm) filter paper to remove insoluble matters, and then concentrated under reduced pressure at 40 ° C using a condenser equipped with a cooling condenser. In order to completely remove the solvent of the concentrated extract, the extract was suspended in 3 L of purified water, and then 453.6 g of a 70% (v / v) ethanol extract (yield: 9.1%) was obtained using a freeze dryer.

[Statistical Analysis]

*** P <0.001, ** P <0.01, * P <0.05 were statistically significant compared to normal control (control), and statistical analysis of the results obtained in the examples of the present invention was performed by t- There is a difference.

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

Experimental animals were anesthetized with an 8-week-old male or female SD (Sprague Dawley) rats weighing 300-350 gm in a desiccator containing CO ₂ gas for 1-2 minutes and after a cervical dislocation, After the incision, the descending aorta was cut to remove the blood and the thoracic artery was removed to remove the intravascular coagulation in the modified Kreb's solution shown in Table 1 below. The insect pin was coated with silicone-coated Petri dish (silicon coated petri dish).

Arterial tissues were removed from the adipose tissue and connective tissue using a 50 × magnification microscope (Nikon SMZ-2T) in an ice-cold modified Kreb's solution in a silicon coated petri dish coated with silicone. Depending on the conditions of the experiment, endothelium-derived arterial preparation was prepared by scraping the endothelial cells by inserting a cotton yarn in the arterial blood vessel to prevent the effect of the endothelium-derived relaxing factor (EDRF) Were prepared. The removal of vascular endothelial cells was performed to prevent vascular smooth muscle damage. The presence or absence of vascular endothelial cells was assessed by the presence of 1 μM of carbamylcholine at the time of blood vessel tension test. Respectively. The prepared tissues were cut into small pieces 2-3 mm in length and used for shrinkage experiments.

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

The arterial slice was mounted on two triangular rings made of tungsten wire vertically in a 20-well organ bath filled with modified Kreb's solution, one on the bottom of the organ bath and the other on an isometric transducer (havard bioscience 52- 9503 tension transducer). During the experimental period, vascular tissues were kept at 95% O ₂ and 5% CO ₂ gas mixture to maintain the pH at 7.4, and maintained in a circulating water bath at 37 ° C. Isotonic contraction was stored in a computer via a digital-to-analog converter (Powerlab PL3504 / P, ADI instruments) and then recorded and analyzed using LabChart Pro (ADI insturments).

After securing the arterial section, the tension was increased by 0.5 g at 10 minute intervals to reach the titre storage capacity. The optimal basal tension was determined by the preliminary experiment to be the minimum tension that caused the greatest shrinkage reaction when 20 mM KCl was administered. 2.0 g of tension was applied to make the base tension and stabilized in Kreb's solution modified for 60 minutes. The normal muscle contraction capacity of the tissue was measured by the administration of 60 mM KCl, which was judged to have a complete equilibrium of the thoracic aortic slice and the basal tension was not changed any more. Phenylrefrin, which subsequently treated the degree of contraction by shrinking with 60 mM KCl, (Phenylephrine) shrinkage, and statistically minimized the difference between each tissue. After 60 mM KCl treatment, the cells were washed twice and waited for 30 minutes. When the blood vessel tension reached the storage capacity again, 1 μM of phenylephrine was administered to induce a contraction reaction. At the second Phenylephrine treatment, 1 μM carbamylcholine was administered to confirm the presence or absence of endothelial cells.

After stabilization of the arterial slice, 1 μM of phenylephrine was treated to reach the peak of the shrinkage reaction, and when the condition remained steady, 1, 10, 20, 100, 200, 400, 600 μg / Ml were added to the organ bath to accumulate in the organ bath, and the changes of the contractile force of the blood vessels to each sample were confirmed.

Each vehicle was treated at a concentration not exceeding 0.1% (v / v) in the organ bath, and no changes in the isotropic tension of the vascular smooth muscle at these concentrations were recorded through the experiment.

Phenylephrine was added to the extracted thoracic aorta slices to induce contraction. The pale yellow extracts were added to the organ bath in a volume of 1, 10, 20, 100, 200, 400 and 600 μg / Observation of smooth muscle relaxation revealed that the relaxation of the blood vessels was statistically significantly increased from the concentration of 100 μg / ml (FIG. 1).

L-NAME (NG-nitro-L-arginine methyl ester) (5 μM), which is a nitric oxide synthase (NOS) inhibitor, was pretreated with 1, 10, 20, 100, 200, 400, 600 ㎍ / ㎖ of ascorbic acid was treated to confirm the vasodilatory effect and compared with the case of treatment with the colorless extract without pretreatment. As a result, as shown in FIG. 2, when the L-NAME was pretreated, it was confirmed that the relaxation effect of the thoracic aortic vasculature was reduced compared to the case of not pretreating L-NAME, (nitric oxide synthase) was activated to induce vascular relaxation.

Example  3. Prostate Oblique lobe  Prostate relaxation effect

8-week-old male or female Sprague Dawley (SD) rats weighing 300-350 gm were anesthetized for 1 to 2 minutes in a desiccator containing CO ₂ gas, and after a cervical dislocation, the bladder and proximal urethra And the capsular muscle layer around the prostate gland was cleanly removed. The physiological solution used in the experiment was modified Kreb's solution and its composition is shown in Table 1.

Peripheral adipose tissue and connective tissue were removed. Unlike human tissue, the prostate tissue extracted from the rat is known to cause smooth muscle contraction by the sympathetic nervous system (Noradrenaline) and the parasympathetic nervous system (Acetylcholine). Noradrenaline sensitive muscle was extracted and used for the experiment.

The tissue was removed from the adipose tissue and connective tissue using a stereomicroscope (Nikon SMZ-2T) in an ice-cold solution in a silicon coated petri dish. Afterwards, it was cut into 3 ~ 5mm sections and used for muscle contraction experiment. Muscle slices were attached to a ring made of tungsten wire, knotted with single silk fibers. 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 kept at physiological pH by continuously supplying 95% O ₂ and 5% CO ₂ gas during the experiment. Isotonic contraction was stored on a computer via a digital-to-analog converter (Powerlab PL3504 / P, ADI Instruments) and then recorded and analyzed using LabChart Pro (ADI insturments).

When the state of the shrinkage reaction is maintained, the prepared prostate tissue is treated with 1 μM of phenylephrine, and the prepared prostate tissue is treated with 1, 10, 20, 100, 200, 400, 600 μg / ml of pale color extracts were added to each organ bath to determine the shrinking force of each sample.

As a result, it was confirmed that the relaxation of blood vessels was statistically significantly increased above the concentration of 50 / / ml as disclosed in Fig.

Example  4. Dorsal  Using the slice, confirm the prostate relaxation effect through the potassium channel

1, 10, 20, 100, 200, and 400 (mg / ml) were pretreated with 1 mM TEA (tetraethylammonium) after inducing contraction by adding 1 μM of phenylephrine to the left prostate- , 600 μg / ml of pale color extract was added to the organ bath to confirm the relaxation effect of the smooth muscle of the prostate.

As a result, as shown in FIG. 4, when the pretreatment was performed as compared with the case of pretreatment without the pretreatment, the relaxation effect in the incisal side of the prostate was reduced. Therefore, potassium channel) was activated by the activation of hyperpolarization.

Example  5. Confirmation of the prostate relaxation effect using the corpus cavernosal section

1, 10, 20, 100, 200, 400, and 600 μg / ml of Phenylephrine were added to the excised penile corpuscles to accumulate in the organ bath, The relaxation of cavernosal smooth muscle was confirmed. It was confirmed that the relaxation of the smooth muscle of the cavernosal smooth muscle was statistically significantly increased from the concentration of 200 μg / ml (FIG. 5).

Claims (7)

A pharmaceutical composition for preventing or treating prostatic hyperplasia or lower urinary tract infection caused by enlargement of the prostate, which contains Corydalis ternata extract as an active ingredient. The pharmaceutical composition according to claim 1, wherein the extraction solvent of the pale yellow extract is water, a C ₁ -C ₄ lower alcohol, or a mixture thereof, for the prophylaxis or treatment of prostatic hypertrophy or prostatic hyperplasia. delete The pharmaceutical composition according to claim 1, wherein the pale yellow extract relaxes the smooth muscle of the urethra or the smooth muscle of the prostate, or a prophylactic treatment for the prevention or treatment of the lower urinary tract caused by enlargement of the prostate. The pharmaceutical composition according to claim 1, further comprising a carrier, an excipient or a diluent in addition to the pale yellow extract, for the prophylaxis or treatment of prostatic hypertrophy or prostatic hypertrophy. A health functional food composition for preventing or ameliorating prostatic hyperplasia or prostate hyperplasia of lower urinary tract including pale color extract as an active ingredient. 7. The method according to claim 6, wherein the ascitic extract is prepared from any one of a beverage, a ring, a tablet, a capsule, and a powder. Or improving health functional food composition.

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