KR101492713B1 - Composition for preventing or treating benign prostate hyperplasia using fraction of unripe astringent persimmon - Google Patents

Abstract

A composition for preventing or treating enlargement of the prostate gland, which can be applied as a pharmaceutical composition or a functional food for preventing or treating enlargement of the prostate gland by obtaining a fractional extract from a particular persimmon fruit as a natural product, is disclosed. The present invention provides a composition for preventing or treating enlargement of the prostate gland, which comprises a reduced fraction as an active ingredient.

Description

Technical Field [0001] The present invention relates to a composition for preventing or treating enlargement of the prostate gland using fractions thereof,

The present invention relates to a composition for preventing or treating enlargement of the prostate gland, and more particularly, to a composition for preventing or treating enlargement of the prostate gland containing the reduced fraction extracted from the total divided fraction.

Prostate is a type of genitalia that exists only in males. It produces semen to nourish sperm, protects against germs, provides a moving medium, and so on. However, the prostate wraps the urethra just below the bladder, pushing the urethra beneath the bladder as the prostate gathers. The resulting urethral obstruction causes symptoms such as dysuria, pain, urinary frequency, hematuria, and urinary tract obstructive secondary infection.

Recently, it has been reported that the aging population of the society is increasing, the common diseases are increasing in the elderly, and the benign prostatic hyperplasia (BPH) appears in more than 80% of men over 80 years old. Symptoms of urinary tract obstruction require management because they have a significant impact on quality of life.

One hormone that causes enlargement of the prostate, testosterone, is converted into 5α-dehydrotestosterone (DHT) by the 5α-reductase in the prostate. 5 alpha-reductase is present in the prostate, hypocotyl, external reproductive organs, and is a 5-alpha-reducing enzyme that adds a hydrogen atom to the double bond between the 4th carbon and the 5th carbon of steroids. Source. 5 alpha - dihydrotestosterone converted by 5 alpha - reductase affects the development and hypertrophy of the prostate. Thus, the 5 alpha -reductase inhibitor inhibits the conversion of testosterone into 5 alpha-dihydrotestosterone, thereby reducing the size of the prostate gland and thus exhibiting a favorable effect on lower urinary tract symptoms (Nehra A., BJU International 2005 96: 237-243, Miner. M, Clinical Therapeutics 2006 28: 13-25). However, 5 alpha-reductase inhibitors have been shown to reduce prostate size while inducing sexual dysfunction (Gibbons EP, European Urology 2005 47: 824-837).

Prostate enlargement, unlike a disease, has little effect on the severity of the disease. Measuring the size of a simple prostate does not help the diagnosis, but rather the degree of symptoms of the patient plays a major role in the diagnosis. I-PSS (International Prostate Symptom Score) is the most commonly used tool to visualize urinary symptoms, and the severity, moderate severity, and severity of symptoms are classified according to the questionnaire results.

The use of nonselective alpha-blockers (doxazosin, prazosin, and terazosin) in the treatment of benign prostatic hyperplasia leads to improved symptoms of the prostate by reducing the tone of the prostate smooth muscle. However, the symptoms of dizziness and hypotension are less than 10% There are side effects that may cause.

Surgical treatment may be considered as the first treatment in patients with severe symptoms of prostate enlargement. Surgical treatment may be considered if the patient fails the drug treatment, if the infection is repeated, or if hematuria or renal function is impaired. In the case of classic prostatectomy, the effect is certain but is the most invasive treatment method, so it is usually a trend to decrease except when there are other structural problems. In most cases, the prostate is removed through the urethra (Transurethral Resection of the Prostate (TURP) can be effective. However, there is a risk of merging such as sexual dysfunction, urinary incontinence, and bleeding. Side effects reported after treatment include retrograde ejaculation, erectile dysfunction, and urinary incontinence.

On the other hand, it has been claimed that functional foods effective for enlargement of the prostate using natural extracts are mainly used in Europe and have an effect on the prostate. These natural products include Pygeum Africanum, Serenoa Repens, Urtica Dioica, Genistein, Cucurbita Peponic, and the like. In the case of saw palmetto, the oil extracted from the ripe fruit is considered to have an effect, and in vitro experiments showed that it inhibits the 5 alpha - reductase, but it was not clinically confirmed. In addition, it showed almost similar effects as finasteride, but its effects were weaker than other drugs. On the other hand, side effects were less than those of other traditional drugs, while prostate size was reduced, while prostate-specific antigen levels were not reduced.

As the elderly population increases, it is clear that the number of patients complaining of benign prostatic hyperplasia will increase. There are several options for the treatment of benign prostatic hyperplasia, each of which has its unique advantages and disadvantages, and its effects, side effects, and price are very widely distributed. Basically, the degree of symptom is the basic choice of treatment method, and patient preference will be an important factor. As described above, many functional foods related to enlargement of the prostate have been traditionally used mainly in Europe, and the effect thereof can be recognized to some extent. In addition, fewer side effects and fewer adverse effects than drug therapy have been reported, and may be helpful for patients who complain of mild symptoms or who have a reluctance to take medication.

On the other hand, a sense (Diospyros kaki ) fruit, there has been reported a composition exhibiting a pharmaceutical efficacy for various uses. In particular, a composition containing as an active ingredient a fraction extracted from an immature chewing gum is effective for the prevention and treatment of benign prostatic hyperplasia Not known.

Accordingly, the present invention provides a composition for preventing or treating enlargement of the prostate gland, which can be applied as a pharmaceutical composition or a functional food for preventing or treating enlargement of the prostate gland by obtaining a fractional extract from a specific persimmon fruit as a natural product.

In addition, it has been found that the fraction extract obtained from a specific persimmon fruit has a direct influence on the specific functional group associated with enlargement of the prostate gland and contains a specific fraction extract before the functional group as an active ingredient, thereby providing a composition having an excellent effect of preventing or treating enlargement of the prostate gland do.

In order to solve the above-mentioned technical problems, the present invention provides a composition for preventing or treating enlargement of the prostate gland comprising the reduced fraction as an active ingredient.

Also, the reduced fraction is obtained by concentrating the filtered solid matter under reduced pressure by alcohol freezing in an alcoholic solution, and extracting the resulting powder from the total of the separated reduced fraction liquid to the fraction layer with an extraction solvent. There is provided a composition for preventing or treating prostatic hyperplasia.

Also, the extracting solvent is at least one selected from the group consisting of hexane, ether, ethyl acetate, and butanol. The present invention also provides a composition for preventing or treating enlargement of the prostate gland.

Also, the present invention provides a composition for preventing or treating enlargement of the prostate gland, comprising the reduced fraction as an active ingredient, characterized in that the treatment for benign prostatic hyperplasia is implemented by inhibiting 5 alpha-reductase activity.

According to the present invention, it is possible to prevent or treat enlargement of the prostate while minimizing side effects when the reduced fraction extracted from the total amount of the fraction is excellent in the inhibitory effect of 5-alpha-reductase activity and contains the reduced fraction as an active ingredient A composition having excellent efficacy can be provided.

BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a graph showing the conversion and inhibition rate of a sample according to an embodiment of the present invention. FIG.

Hereinafter, preferred embodiments of the present invention will be described in detail with reference to the accompanying drawings. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS Hereinafter, the present invention will be described in detail with reference to the accompanying drawings.

DISCLOSURE OF THE INVENTION The present inventors have conducted intensive studies on the separation of persimmon extract having efficacy for prostatic hyperplasia and its use as a pharmaceutical composition, functional food, etc. As a result, surprisingly, it has been surprisingly found that the solid obtained by freezing the alcohol and concentrating the filtered solid is concentrated under reduced pressure The inventors of the present invention found that the reduced fraction obtained by extracting the total fraction of the reduced fraction in which the powder was dissolved into the fraction layer by the extraction solvent was excellent in 5 alpha-reductase activity inhibitory activity.

Accordingly, the present invention discloses a composition for the prevention or treatment of benign prostatic hyperplasia, which comprises a reduced fraction as an active ingredient, wherein the reduced fraction is obtained by concentrating the filtered solid matter under reduced pressure by alcohol freezing, Which comprises extracting the fractions of the present invention as an active ingredient, and extracting the fractions with a fractionating layer by an extraction solvent.

In the present invention, for example, the ripened persimmon is harvested at about 3 to 6 months after cultivation, and may have an outer appearance green color and a size of about 3 to 10 cm in diameter.

In the present invention, the reduced fraction contained as an active ingredient in the composition for preventing or treating enlargement of the prostate gland is obtained through a process of preparing a total reduced fraction from the total undiluted starch and preparing a fraction layer extract from the total fraction.

The total amount of the sub-fraction can be determined, for example, by extracting juice using an immature powder, separating the solid from the solvent by adding alcohol and cooling with water, preparing a powder by concentrating the alcohol extract under reduced pressure, dissolving the powder in distilled water, And removing the solution to separate the solution.

Hereinafter, as the active fraction, the fraction layer extract can be obtained as a solvent fraction by sequentially sequencing the total fraction of the reduced fraction. For example, when hexane is added and stirred into the total of the fractions to complete the fractionation, the hexane layer and the water layer are separated, and the hexane layer is concentrated under reduced pressure to remove the residual hexane solvent to prepare a hexane fraction layer extract. In order to obtain a fraction layer extract for other solvents.

In vitro studies of the prepared fractionated layer extracts showed that 5 alpha-reductase inhibition was inhibited by using the resected prostate from the experimental animals. As a result, the inhibitory activity of 5 alpha-reductase was inhibited by the prostatic hyperplasia , It is confirmed that the composition according to the present invention is useful for preventing or treating enlargement of the prostate gland.

The composition according to the present invention may contain 0.01 to 99% by weight of the subcutaneous layer extract, based on the total weight, and may be adjusted depending on the condition of the patient and the progress of the disease.

When the composition according to the present invention is applied to a pharmaceutical composition, it can be administered orally, such as powders, granules, tablets, capsules, suspensions, emulsions, syrups and aerosols, or external preparations, suppositories, And may further comprise suitable carriers, excipients or diluents conventionally used in the production of pharmaceutical compositions.

Examples of the carrier, excipient or diluent include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, Microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, magnesium stearate, and mineral oil. In the case of formulation, it can be prepared using diluents or excipients such as fillers, extenders, binders, humectants, disintegrants, surfactants and the like which are usually used.

Solid preparations for oral administration include tablets, pills, powders, granules, capsules and the like, and such solid preparations may be prepared by mixing at least one excipient, at least one starch, calcium carbonate, sucrose or lactose, ≪ / RTI > In addition to simple excipients, lubricants such as magnesium stearate talc may also be used. Examples of the liquid preparation for oral administration include suspensions, solutions, emulsions, and syrups. Various excipients such as wetting agents, sweetening agents, fragrances, preservatives and the like may be included in addition to water and liquid paraffin, which are commonly used simple diluents .

Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, suppositories, and the like. Examples of the suspending agent include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like. Examples of suppository bases include witepsol, Macrogol, tween 61, cacao butter, laurin, glycerogelatin and the like.

The preferred dosage of the composition according to the present invention varies depending on the condition and body weight of the patient, the degree of disease, the type of drug, the administration route and the period of time, but can be appropriately selected by those skilled in the art. However, for the desired effect, the reduced fraction is preferably administered at a dose of 0.01 mg / kg to 10 g / kg per day, preferably 1 mg / kg to 1 g / kg per day. The administration can be carried out once a day or divided into several times, and the administration method is not particularly limited.

The composition according to the present invention can be administered to mammals such as rats, mice, livestock, humans, and the like in various routes. All modes of administration may be expected, for example, by oral, rectal or intravenous administration.

When the composition according to the present invention is applied as a functional food, it can be used variously for medicines, foods, beverages for preventing or improving enlargement of the prostate gland. Examples of the functional food include various foods, beverages, gums, tea, vitamin complex, leavening tea, health supplement foods and the like, and they can be used in the form of powders, granules, tablets, capsules or drinks.

When the fraction layer extract is added to foods for the purpose of preventing or improving enlargement of the prostate gland, the extract may be added in an amount of 0.01 to 15% by weight based on the total weight of the food, May be added in an amount of 0.02 to 10 g, preferably 0.3 to 1 g.

The health drink contains not only the above-mentioned extract as an essential ingredient in the indicated ratio but also the liquid ingredient, and may contain various flavors, natural carbohydrates and the like as an ordinary drink, as an additional ingredient. Examples of the natural carbohydrate include common sugars such as polysaccharides such as disaccharide and dextrin such as monosaccharide, maltose and sucrose such as glucose and fructose, polysaccharides such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol and erythritol have. As the flavor agent, natural flavoring agents (tau martin, stevia extract (rebaudioside A, glycyrrhizin, etc.) and synthetic flavors (saccharin, aspartame, etc.) can be advantageously used. Based on the total weight of the composition, of about 1 to 20 g, preferably 5 to 12 g.

In addition to the above, the functional food may contain flavoring agents such as various nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavors, colorants and heavies (cheese, chocolate, etc.), pectic acid and its salts, Organic acids, protective colloid thickening agents, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonating agents used in carbonated drinks, and the like. In addition, the functional food according to the present invention may contain flesh for the production of natural fruit juice, fruit juice beverage and vegetable beverage. These ingredients may be used independently or in combination, and the added amount may be selected in the range of 0.01 to 20% by weight based on the total weight of the functional food.

Example : Sense Fraction  Produce

It is made by using green juice to make juice by measuring the weight of green juice (green persimmon having a diameter of 3 ~ 10 ㎝ which is harvested at 3-6 months after cultivation, A boiled juice was prepared by adding an appropriate amount of ethanol. The ethanol was added so that the final volume was 10 times as much as the weight. Then, it was cooled at 4 캜 for 24 hours and filtered to separate the solids and the solvent. The remaining solids after cooling were again added with 5-fold diluted ethanol and the above filtering process was repeated. After the second cooling, 5-fold ethanol was added to the remaining solid, and the above-mentioned filtering process was repeated. Thereafter, the remaining ethanol extract after filtration was concentrated under reduced pressure to obtain a powder. The extract powder was dissolved in distilled water 10 times by weight, and the extract solution was filtered again to remove the precipitate, and the separated solution was made into the fraction solution.

Then, the total fraction of the fractions was sequentially sequenced as follows to prepare samples of solvent fractions.

First, the same amount of hexane as that of the prepared fraction was added to a separating funnel and stirred. After completion of the fractionation, the hexane layer and the water layer were separated, the hexane layer was concentrated under reduced pressure, and the residual hexane solvent was removed with a nitrogen concentrator to prepare a sample .

Thereafter, the same amount of ether was added to the separating funnel again to the hexane layer and the water layer separated, and the ether layer and the water layer were separated after completion of the fractionation. The ether layer was concentrated under reduced pressure and the remaining ether solvent was removed by a nitrogen concentrator, .

The ethyl acetate layer and the water layer were separated, and the ethyl acetate layer was concentrated under reduced pressure. The residue was dissolved in a residual ethyl acetate solvent Was removed to prepare a sample.

Then, the same amount of butanol was added to the separating funnel again to the ethyl acetate layer and the separated water layer. After the completion of the fractionation, the butanol layer and the water layer were separated. The butanol layer was concentrated under reduced pressure and the residual butanol solvent was removed with a nitrogen concentrator A sample was prepared.

The residue layer was lyophilized to prepare a water layer sample to prepare a final hexane sample, an ether sample, an ethyl acetate sample, a butanol sample and a water layer sample.

Experimental Example : 5 Alpha - Confirmation of reducing enzyme activity inhibitory effect

A homogenous suspension of abdominal prostate of Sprague-Dawley male rats was prepared and the inhibition rate of testosterone 5 alpha-reductase was measured by the following method. Since both the type 1 and type 2 isozymes of the testosterone 5 alpha-reductase are present in the rat prostate, when the enzyme suspension from the rat prostate is used in the neutral pH buffer, the average inhibitory activity is evaluated against the two isozymes .

A 20 w / v% homogenous suspension was prepared using a glass homogenizer in Solution A (0.32 M sucrose, 0.1 mM dithiothreitol, 20 mM sodium phosphate, pH 6.5) at 6 weeks old Sprague-Dawley male rats. The homogenate suspension was then filtered through surgical gauze and centrifuged at 3000 x g for 10 minutes. The precipitated lumps were made to be a 5 w / v% homogenous suspension in Solution A and then homogenized by passing sequentially through 18-gauge and 20-gauge needles. Then, 10 μl of each of the hexane sample, the ether sample, the ethyl acetate sample and the butanol sample (riboflavin was used as a positive control experiment) prepared in the above example was dissolved in 10 μl of ethanol, and the reaction solution (1 mM 0.525 ml of dithiothreitol, 40 mM sodium phosphate, pH 6.5, 5 × 10 ^-5 M NADPH, and 2.2 × 10 ^-9 M [1,2,6,7- ³ H] testosterone) was added to the wells, followed by the addition of 40 μl of the enzyme suspension Respectively. The reaction was then terminated by the addition of 1 ml of ethyl acetate, and 50 μl of the supernatant was separated on TLC with ethyl acetate / cyclohexane (1: 1) developing solvent. The area corresponding to testosterone and 5 alpha-dihydrotestosterone was cut out and each of them was placed in 5 ml of Insta-Gel Plus (PerkinElmer) and ³ H radioactivity was measured with a liquid scintillation counter.

The conversion and inhibition rates for the enzymatic reactions of the respective samples were calculated according to the following equations (1) and (2), and the results are shown in FIG. In FIG. 1, A, B, C and D represent hexane, ether, ethyl acetate and butanol samples, respectively.

In Equation 1, D and T are the ³ H radioactivity quantities measured in the 5 alpha-dihydrotestosterone and testosterone regions, respectively, and R _sample and R _control are the conversion rates of the sample and the control sample, respectively. The IC50 (50% maximal inhibitory concentration) was calculated from inhibition rates at several concentrations using linear regression analysis, and each enzyme reaction was performed in duplicate.

As shown in FIG. 1, the inhibitory effect of the 5-alpha-reductase activity on the reduced fractions according to the present invention was confirmed, and it was confirmed that the inhibitory effect was clear in the layer A (hexane sample) and the layer B (ether sample) . Therefore, it can be seen that the reduced fraction according to the present invention has an effective effect on the enlargement of the prostate from the invitro activity.

Hereinafter, the composition containing the reduced fraction according to the present invention will be described as a pharmaceutical composition and a preparation for application as a functional food, but the present invention is not limited thereto.

Formulation example  One: Powder  Produce

Table 1 below shows the powder composition containing the above-described reduced fraction layer extract according to the present invention as an active ingredient. Powders can be prepared by mixing the following ingredients and filling the airtight container.

Formulation example  2: Preparation of tablets

Table 2 below shows a tablet composition containing the above-described reduced fraction layer extract according to the present invention as an active ingredient. The tablet may be prepared by mixing the following ingredients and then tableting according to a conventional tablet preparation method.

Formulation example  3: Capsule  Produce

In Table 3 below, the capsule composition containing the above-described reduced fraction layer extract according to the present invention as an active ingredient is illustrated. The capsules may be prepared by mixing the following ingredients according to the conventional method for preparing a capsule, and filling the capsules with gelatin.

Formulation example  4: Injection preparation

In the following Table 4, the composition of injections containing the above-described reduced fraction layer extract according to the present invention as an active ingredient is illustrated. The injectable preparation can be prepared in the following ingredient contents per ampoule (2 ml) according to the usual injection preparation method.

Formulation example  5: Liquid  Produce

In Table 5, the composition of the liquid composition containing the above-described reduced fraction layer extract according to the present invention as an active ingredient is illustrated. The liquid preparation is prepared by adding and dissolving each of the following ingredients in purified water according to a conventional liquid preparation method, mixing the following components after adding a proper amount of lemon flavor, adding purified water to adjust the total volume to 100 ml, filling and sterilizing in a brown bottle .

Formulation example  6: Health food manufacturing

Table 6 below shows the functional health food composition containing the above-described reduced fraction layer extract according to the present invention as an active ingredient. In the following composition, the composition ratio of the vitamin and mineral mixture shows that a composition suitable for health food is mixed and formulated as a preferable preparation. However, the blending ratio may be arbitrarily changed, and each ingredient may be mixed The granules can then be prepared and used in the manufacture of a health food composition according to conventional methods.

Formulation example  7: Manufacture of health drinks

Table 7 below shows the functional health beverage composition containing the above-described reduced fraction layer extract according to the present invention as an active ingredient. For example, the following ingredients are mixed in accordance with a conventional health drink manufacturing method, and the mixture is heated at 85 DEG C for about 1 hour under stirring, and the solution thus obtained is filtered to obtain a sterilized 2 liter container. After sealing sterilization, It can be stored and used. Although the following composition ratio is mixed with the ingredients suitable for the preferred beverage as a preferred embodiment, the blending ratio may be arbitrarily varied according to the regional and national preference such as the demand class, the demanding country, and the use purpose.

The preferred embodiments of the present invention have been described in detail with reference to the drawings. It will be understood by those of ordinary skill in the art that various changes in form and details may be made therein without departing from the spirit and scope of the present invention as defined by the appended claims.

Accordingly, the scope of the present invention is defined by the appended claims rather than the foregoing detailed description, and all changes or modifications derived from the meaning, range, and equivalence of the claims are included in the scope of the present invention Should be interpreted.

Claims (4)

A composition for preventing or treating enlargement of the prostate gland comprising a reduced fraction as an active ingredient,
The reduced fraction is obtained by concentrating an alcoholic extract obtained by freezing and filtering with an alcohol to obtain a powder by concentration under reduced pressure, then dissolving the powder in distilled water, adding an extraction solvent to the total of the reduced fraction, stirring the mixture, Wherein the extracting solvent is hexane or ether. The composition for preventing or treating enlargement of the prostate gland according to claim 1, delete delete The method according to claim 1,
Wherein the treatment for hyperplasia of the prostate is performed by inhibiting 5 alpha-reductase activity. The composition for preventing or treating benign prostatic hyperplasia comprising the reduced fraction as an active ingredient.

Images