KR20190038037A - Novel use of Polianthes tuberosa - Google Patents

Abstract

The present invention provides a novel use of Polianthes tuberosa. The present invention provides a pharmaceutical composition for treating or preventing benign prostate hyperplasia, comprising Polianthes tuberosa as an effective component. The pharmaceutical composition of the present invention may be used to effectively treat, alleviate, suppress and/or prevent benign prostate hyperplasia.

Description

Novel use of Polianthes tuberosa}

The present invention relates to a monthly downward trend, and more particularly to a new monthly downward trend.

Benign prostate hyperplasia (BPH) is one of the most common menstrual diseases, and refers to a situation in which the urethra around the urethra is abnormally enlarged to prevent the discharge of urine, resulting in a variety of symptoms. Prostate hyperplasia is usually caused by the presence of male hormones in the puberty, because symptoms usually occur when the prostate is over 50 years of age. Therefore, it is known that one of the causes of enlargement of the prostate due to prostatic hyperplasia is the secretion of male hormone.

The main male hormone involved in the growth of prostate tissue is dihydrotestosterone (DHT). DHT is converted by 5AR (5-alpha reductase, 5-alpha reductase) to testosterone. 5AR is a 3-oxo-5α-steroid 4-dehydrogenase that is dependent on NADPH {nicotinamide adenine dinucleotide phosphate (reduced form)} in microsomes and reduces double bond steroids such as testosterone.

Polyanthes tuberosa, also known as bayberry, is mainly used for ornamental purposes. Such a technology for extracting aroma components from a downward direction is known (refer to International Patent Publication No. WO 2006/002249), and related technology development is required.

International Patent Publication No. WO 2006/002249, (2006.01.05), specification

A problem to be solved by the present invention is to provide a new use for a month-down.

The object of the present invention is not limited to the above-mentioned problems, and other matters not mentioned can be clearly understood by those skilled in the art from the following description.

The present inventors have surprisingly found that the menstrual flow has an effect on enlargement of the prostate gland, thereby completing the present invention.

The present invention provides medicinal and / or food uses for the treatment, improvement, inhibition and / or prevention of menstrual hyperplasia. Treatment is meant to include improvement or relief of symptoms associated with enlarged prostate, and prevention is meant to include inhibition of developing into a disease at a pre-disease stage.

In one embodiment, the present invention provides a pharmaceutical composition for the treatment or prevention of hyperplasia of the prostate gland, which comprises a monthly lowering as an active ingredient.

The downward moon ( Polianthes tuberosa L.) is a perennial plant of tropical Mexican origin.

The downward month may be a downward or downward part of the month, for example a flower.

The month downward may be at least one selected from the group consisting of the lower part of the month, the month lower down structure, and the month lower down solvent extract.

The solvent may be polar or polar solvent.

The solvent may be at least one selected from water, alcohol or a mixed solvent thereof.

The alcohol may be a lower alcohol and may be at least one selected from among alcohols having 1 to 5 carbon atoms. More preferably, the alcohol may be methanol.

The treatment or prevention may be based on one or more selected from the group consisting of inhibition of prostate cell survival by inhibiting the decrease of the month, inhibition of prostate cell proliferation, and inhibition of 5-alpha reductase activity in prostate tissue.

The cell proliferation inhibition may be due to inhibition of cell division.

The composition of the present invention may contain the active ingredient in an amount of 0.01 to 95% by weight based on the total weight of the composition.

In addition, the present invention provides a food composition for improving or inhibiting the enlargement of the prostate gland, which comprises the above-mentioned monthly lowering as an active ingredient.

Unless otherwise indicated, the food composition is equally applied to the pharmaceutical composition of the present invention, unless otherwise stated. This " improvement " is included in the " treatment " and means that the condition or symptom is improved. The term " inhibition " means inhibiting the occurrence of a condition or symptom, and may be included in prevention.

The food composition may be variously contained in foods containing beverages, and may be in the form of beverages, gums, tea, health functional foods, etc. The health functional foods may be formulated into tablets, capsules and the like. The term "functional food" as used herein refers to foods prepared (processed) by using raw materials or ingredients having useful functions in accordance with the Korean Health Function Food Act, and the term "functional" To the nutritional control of the structure and function of the body, and to obtain a beneficial effect for health use such as physiological action. The food composition may comprise conventional food additives, and the food additives may be selected from natural compounds such as ketones, chemical compounds such as glycine, sodium citrate, nicotinic acid, cinnamic acid, etc., Additives, L-sodium glutamate preparations, noodle-added alkalies, preservative preparations, tar coloring preparations and the like. In addition, the food composition includes food additives and the like.

The present invention also provides a method for the treatment or prevention of benign prostatic hyperplasia comprising the step of administering to a mammal, including a human, in need of monthly administration, a use for the manufacture of a preparation for the treatment or prophylaxis of benign prostatic hyperplasia do. The monthly downward dose to be administered may be a monthly low effective amount.

Unless otherwise indicated, the phrases referred to in the pharmaceutical compositions, food compositions, methods, and uses of the invention are each the same unless otherwise indicated.

The composition may be administered orally or parenterally to mammals including humans, and the active ingredient may be formulated together with a pharmaceutically acceptable carrier to formulate the composition. When formulating, fillers, extenders, binders, wetting agents, disintegrants, surfactants, diluents or excipients usually used may be used. Solid form preparations for oral administration include tablets, pills, powders, granules, capsules and the like, which may contain at least one excipient such as starch, calcium carbonate, sucrose, lactose and And / or gelatin. In addition, lubricants such as magnesium and talc are also used. Liquid preparations for oral administration include suspensions, solutions, emulsions and syrups. Various excipients such as wetting agents, sweetening agents, fragrances and / or preservatives, and the like are used in addition to commonly used simple diluents such as water and liquid paraffin. May be included. Formulations for parenteral administration include injectable solutions, suspensions, emulsions, lyophilisers, nasal cleansers, and suppositories. Injectable solutions, suspensions and emulsions may be prepared by mixing water, non-aqueous or suspensions, and active ingredients. Examples of non-aqueous and suspensions include vegetable oils such as propylene glycol, polyethylene glycol and olive oil, ethyl oleate , And the like. As a base for suppositories, witepsol, macrogol, tween 61, cacao paper, laurin, glycerol and / or gelatin can be used. For parenteral administration, it can be administered by subcutaneous injection, intravenous injection, or intramuscular injection.

The monthly descent contained in the composition of the present invention or used in the use or the method can be used in a dose of 0.01 to 1000 mg / kg, preferably 1 to 500 mg / kg per day on an adult basis. The administration can be administered once or several times a day. However, the scope of the present invention is not limited by the dose and the number of administration.

For example, Remington's Pharmaceutical Science (recent edition), Mack Publishing Company, Easton PA, et al., Which is incorporated herein by reference in its entirety, Reference can be made to the literature.

Accordingly, the composition of the present invention may further comprise a pharmaceutically acceptable additive or a pharmaceutically acceptable additive, and may be composed of the active ingredient and the pharmaceutically acceptable excipient or the pharmaceutically acceptable excipient.

The present invention can effectively treat, ameliorate, inhibit and / or prevent enlargement of the prostate gland.

FIG. 1 is a graph showing the results of analyzing the influence of the downward slope on the 5AR activity.

BRIEF DESCRIPTION OF THE DRAWINGS The advantages and features of the present invention and the manner of achieving them will be more apparent from the following detailed description taken in conjunction with the accompanying drawings. The present invention may, however, be embodied in many different forms and should not be construed as being limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the scope of the invention to those skilled in the art. But is only provided to fully inform the owner of the scope of the invention, and the present invention is only defined by the scope of the claims.

Throughout the specification, "and / or" include each and every combination of one or more of the components mentioned.

The terminology used herein is for the purpose of illustrating embodiments and is not intended to be limiting of the present invention. In the present specification, the singular form includes plural forms unless otherwise specified in the specification. It is noted that the terms " comprises "and / or" comprising ", as used herein, do not exclude the presence or addition of one or more other elements and / or steps.

In this specification, the term 'lowered' refers to a downward or downward part of the month, which is not subjected to a separate drying process after collection, and 'downward drying' refers to drying of the lower part of the month.

Hereinafter, in the examples, it was confirmed that the monthly decrease was effective for the enlargement of the prostate using the enzyme source extracted from the prostate cell line and the prostate tissue.

The reagents and the like used in the examples were the highest available from the market, and those purchased from Sigma Co. were used.

≪ Example 1 >

1-1. Prepare for the month

100 g of 100% -MeOH (HPLC grade) was added to 100 g of monthly dried down material (purchased from Bangladesh, Bangladesh, in 2017, dried and shredded and pulverized and dried at the BRC at the Korea Research Institute of Bioscience and Biotechnology) And sonicated at a temperature of 50 ° C. After 15 minutes of ultrasonic extraction, the mixture was allowed to stand for 2 hours. The same procedure was repeated 10 times a day for 3 days to obtain an extract. Thereafter, the extract was concentrated with a vacuum concentration apparatus (Buchi, R-220) to prepare a monthly solvent extract.

1-2. Cell preparation

Three types of prostate cell lines (LNCaP, PC3, DU145) were purchased from Korean Cell Line Bank. Cells were maintained in RPMI-1640 medium supplemented with 10% heat-inactivated FBS (fetal bovine serum), penicillin (P / S) and streptomycin at 5% -CO ₂ , 37 ° C culture conditions.

1-3. Analysis of inhibition of prostate cell viability

(4- {4,5-dimethylthiazol-2-yl) 2,5-diphenyltetrazolium bromide} assay was used to analyze the effect of the monthly downward suppression on prostate cell survival. MTT assay is an experimental method to determine the effect of test substance on cell viability. Using this MTT assay, we investigated the effect of moon - bottoming on the survival of prostate cell lines.

Cells were seeded in a 96-well plate ( ^1.5 × 10 ⁵ cells / ml) prepared in the same manner as in Example 1. 1-2 hrs. After 24 hrs, the solvent extract was dissolved in dimethylsulfoxide (DMSO) mg / ml, and the cells were treated with a final concentration of 100 ug / ml for 24 hours. MTT reagent at a concentration of 2 mg / ml was added to each well in an amount of 10 μl, followed by further incubation for 2 hours. After removing the culture medium, 100 μl of DMSO was added to extract MTT formazan. The amount of MTT formazan was quantified as a multi-well spectroscopic (Tecan, Infinite) at a test wavelength of 540 nm. For each prostate cell line, the control group was treated in the same manner as the month-lower solvent extract treatment group except that the month-down solvent extract was not treated. From the quantitative results, the cell viability (%) as compared with the control group was calculated, and the results are shown in Table 1 below. The cell survival rate of the test substance can be determined from the cell survival rate in comparison with the control group in the following table.

Lower wall solvent extract treatment group LNCaP PC3 DU145 Cell survival rate
(% Compared to the control group) 60 86 66

As shown in Table 1, it can be seen that the downward moon significantly inhibited the survival of all three prostate cell lines.

From these results, it can be seen that the downward moon is effective for the prostatic hyperplasia by inhibiting the survival of prostate cells.

1-4. Analysis of inhibition of prostate cell proliferation

(5-bromo-2'-deoxyuridine) incorporation assay was used for the analysis of the effect of the month-down on prostate cell proliferation inhibition. The BrdU incorporation assay is an experiment to determine whether a test substance inhibits cell division and inhibits cell proliferation. Using this BrdU incorporation assay, we investigated whether the downward mobility affects proliferation of prostate cell lines by cell division inhibition.

Cells were seeded in a 96-well plate (2 × 10 ⁵ cells / ml) prepared in the same manner as in Example 1. 1-2 hours later, 100 μl of each cell was seeded. After 24 hours, And then diluted with the cell culture medium to a final concentration of 100 ug / ml. The degree of BrdU incorporation was measured using a kit (Abcam, ab126556). After 2 hours of extract treatment, 20 μl of BrdU label reagent was added and cultured for 24 hours. After the cell culture solution was completely removed, 200 μl of the fixing solution was added, and the mixture was allowed to stand at room temperature for 30 minutes. Then, the fixing solution was removed and dried. After washing twice with phosphate buffered saline (PBS), 100 μl of anti-BrdU monoclonal Detector Antibody was added and left at room temperature for 1 hour. After removing the fluid, the peroxidase goat anti-mouse IgG was added, and the mixture was allowed to stand for 30 minutes. 100 μl of TMB (3,3 ', 5,5'-tetramethylbenzidine) peroxidase substrate was added and reacted at room temperature for 30 minutes in the shade condition. Then, 100 μl of stop solution was added to terminate the reaction. The degree of BrdU incorportion was measured by multi-well spectroscopy (Tecan, Infinite) at a test wavelength of 450/540 nm. For each prostate cell line, the control group was treated in the same manner as the month-lower solvent extract treatment group except that the month-down solvent extract was not treated. From the quantitative results, the BrdU incorportion ratio (%) of the control group was calculated, and the results are shown in Table 2 below. From the BrdU incorportion ratio as compared to the control group in the following table, the ability to inhibit the cell division of the test substance can be determined.

Lower wall solvent extract treatment group LNCaP PC3 DU145 BrdU incorportion ratio
(% Compared to the control group) 70 82 98

As shown in Table 2, it can be seen that the downward moon inhibited cell division of all three prostate cell lines as compared with the control group. In addition, it can be seen that the downward moon suppressed the proliferation of the prostate by the cell division inhibition. Therefore, it can be understood that the downward moon is effective for the prostatic hyperplasia by inhibiting proliferation of prostate cells.

As a result, it can be seen that the present invention can provide medicinal and / or food uses for the treatment, amelioration, inhibition and / or prevention of menstrual hyperplasia.

≪ Example 2 >

 5AR is the most important enzyme that mediates the conversion of testosterone into DHT (dihydrotestosterone, dihydrotestosterone). DHT is known to play a major role in the growth of prostate tissue. Therefore, we investigated whether the effect of 5AR on the prostatic hyperplasia was confirmed.

2-1. Prepare for the month

The solvent extract was prepared in the same manner as in Example 1-1.

2-2. Enzyme source preparation

To prepare the 5AR enzyme source, 15-week-old Sprague Dawley rats (COATEC) were anesthetized with CO ₂ and then prostate tissue was extracted. 200 mg of the extracted tissue was washed twice with pH 7.4 PBS and added with 10 ml of lysis buffer (20 mM sodium phsphate, pH 6.5) containing 0.32 M sucrose and 1 mM EDTA (ethylenediaminetetraacetic acid), followed by a glass homogenizer Homogenized. The homogenate was centrifuged at 5,000 rpm for 15 minutes at 4 ° C, and the supernatant was taken. Protein quantification was performed using the Brad Ford reagent and used as the 5AR enzyme source. The remaining homogenate was stored at -70 ° C.

2-3. 5AR activity inhibition assay

(100 μg / ml), testosterone (7.5 mM) and testosterone (100 μg / ml) prepared in the same manner as in Example 2-2, 300 μM of β-NADPH was reacted at 37 ° C. Then, the absorbance of β-NADPH was measured at 350 nm for 30 minutes in total every 5 minutes. Calculation of the measured values was carried out in pg / ml using a standard graph of β-NADPH. The control group was prepared in the same manner as the month-lower solvent extract treatment group, except that methanol was used instead of the downward solvent extract. The positive control group was prepared in the same manner as the month-lower solvent extract treatment group, except that finasteride (100 uM) was treated in place of the downward solvent extract. The results are shown in Fig.

FIG. 1 is a graph showing the effect of the downward moon on 5AR activity, and is a graph showing the degree of inhibition of enzyme activity of 5AR by downward mooning. The x axis represents the control group, the positive control group (the pinasteride treated group) and the month-down solvent extract treated group, and the y axis represents the 5AR enzyme inhibition (5AR inhibition) as a ratio to the control group.

As shown in FIG. 1, the inhibition of 5AR enzyme activity by the finasteride was increased in the positive control group, whereas the inhibitory activity of the 5AR enzyme activity was significantly increased in the group treated with the solvent extract of the lower month .

From these results, it can be seen that the downward direction of the month significantly inhibits the activity of 5AR. Therefore, it can be seen that the downward moon is effective for the enlargement of the prostate by inhibiting 5AR activity.

As a result, it can be seen that the present invention can provide medicinal and / or food uses for the treatment, amelioration, inhibition and / or prevention of menstrual hyperplasia.

≪ Preparation Example 1 > Preparation of pharmaceutical composition

100 mg of corn starch, 100 mg of lactose, and 2 mg of magnesium stearate prepared in the same manner as in Example 1-1, were filled in a gelatin capsule to prepare a capsule.

≪ Preparation Example 2 > Preparation of food composition

(10 wt%), liquid fructose (0.5 wt%), oligosaccharides (2 wt%), sugar (2 wt%) and sodium chloride (0.5 wt%) prepared in the same manner as in Example 1-1 Water was added to adjust the remaining amount, and homogeneously mixed and sterilized instantly to prepare a health drink.

Claims (6)

A method for the treatment or prophylaxis of hypertrophy of the prostate, which comprises administering to a patient in need thereof an effective amount of a monohydrate. [Claim 7] The pharmaceutical composition according to claim 1, wherein the downward moon is at least one selected from the group consisting of a fresh month, a downward month, or a month lower down solvent extract. The pharmaceutical composition according to claim 2, wherein the solvent is at least one selected from water, an alcohol or a mixed solvent thereof. 4. The pharmaceutical composition according to claim 3, wherein the alcohol is at least one selected from among alcohols having 1 to 5 carbon atoms. The pharmaceutical composition according to claim 1, wherein said treatment or prevention is by at least one selected from the group consisting of inhibiting prostate cell survival by said active ingredient, inhibiting prostate cell proliferation, and inhibiting the activity of 5-alpha reductase in prostate tissue. A method for improving or inhibiting the enlargement of the prostate gland comprising administering an effective amount of a month lowering agent.

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