KR20200129498A - Composition for preventing or treating prostate-related disease comprising a complex extract of Black ginseng and Platycodon grandiflorum - Google Patents

Abstract

The present invention relates to a composition for preventing, treating or alleviating prostate-related diseases containing a complex extract of black ginseng and Platycodon grandiflorus as an active component. The complex extract of black ginseng and Platycodon grandiflorus of the present invention inhibits prostate cancer cell proliferation. Since the ability to inhibit cancer cell proliferation increases when the complex extract is treated than when each extract is treated alone, the complex extract can be usefully used as a therapeutic agent for prostate-related diseases or as health functional food.

Description

Composition for preventing or treating prostate-related disease comprising a complex extract of Black ginseng and Platycodon grandiflorum, comprising a complex extract of black ginseng and bellflower as active ingredients

The present invention relates to a composition for preventing or treating prostate-related diseases of a complex extract of black ginseng and bellflower.

The prostate gland is a male appendage gland composed of glandular and fibromyal tissues, and although water lumps or stones may occur, prostatitis, enlarged prostate, and prostate cancer are the most common diseases. Prostate cancer is the most common malignant tumor in men, and is one of the most common male cancers in the West, and is the fastest increasing cancer in men due to recent dietary habits in Korea. It occurs in older people over the age of three. According to the central cancer registration data, in 2001, male cancer was ranked 6th with 2.7% and 3.0% in 2002, and the incidence rate of prostate cancer is predicted to increase further in the future as it is increasing rapidly in recent years. to be. In addition to the genetic predisposition, prostate cancer is known to be caused by hormones, dietary habits, and chemicals.

First, prostatic hyperplasia is characterized by bladder storage symptoms such as urinary frequency, nocturia, and unbearable urgency when urinating while feeling strong and sudden urination in men over 50 years of age and urinary delay (when urinating). It is a collective term for symptoms that indicate impaired bladder excretion, such as the phenomenon of urinating only when moxibustion occurs), interruption of urine (a phenomenon that the flow of urine is cut off), and the need to give strength during urination.Testosterone, a male hormone by 5 alpha-reductase It is known that dihydrotestosterone (DHT), which is converted from (testosterone, T), is involved in prostatic hypertrophy (Urology. 2003 Apr;61(4 Suppl 1):2-7.). Recently, the number of patients with prostatic hyperplasia in Korea is increasing rapidly from 4,58,955 in 2006 to 842,069 in 2011, increasing to 83.5%. In particular, the number of patients with prostatic hyperplasia is 2 out of 5 men over 60 years of age, and over 80 years of age, more than half of them complain of enlarged prostate symptoms. The number of patients with prostatic hyperplasia is expected to continue to increase in the future due to the entry into an ultra-aging society and improvement of medical examination rates, and accordingly, requests for the prevention and treatment of prostatic hyperplasia are expected to increase continuously.

In addition, prostatitis is a disease that accounts for about 3 to 12% of all urology patients, but is the most common disease in urology patients under the age of 50. In particular, chronic pelvic pain, the most prominent symptom of prostatitis, is known to be more severe than pain caused by prostatic hyperplasia or sexual dysfunction, and it is common in active young age groups and adversely affects the quality of life. However, it is difficult to diagnose and treat because the cause is unclear and there are no characteristic findings in symptoms or tests. The effect of dihydrotestosterone (DHT), which is converted from testosterone (T), a male hormone by alpha-reductase, on prostatitis has been reported (The Journal of Urology, Volume 170, Issue 6, Part 1). , December 2003, Pages 2486-2489)

Prostate cancer is a malignant tumor that occurs in the prostate, and prostate cancer is also known to be highly related to the conversion of testosterone to dihydrotestosterone by 5-alpha reductase (J Steroid Biochem Mol Biol. 2002 Nov; 82 (4-5):393-400.). In Western cases, prostate cancer is the most common cancer among men and has a high incidence. However, since gastric prostate cancer does not have any specific symptoms, it is difficult to detect it early.Therefore, many people visit the hospital only after symptoms such as bone pain appear due to the growth of cancerous tissues and difficulty urinating, or prostate cancer has spread to other organs such as bones. . Therefore, the demand for prostate cancer prevention and treatment is increasing.

On the other hand, ginseng ( Panax ginseng ) is a perennial herb belonging to the Araceae family. The root of ginseng has been known as a tonic or panacea from ancient times, and various pharmacological effects are recognized by recent studies. Ginseng is divided into various types depending on the processing method. First, unprocessed ginseng is called fresh ginseng or fresh ginseng, and ginseng steamed and dried with steam is called red ginseng. Black ginseng is manufactured in a similar way to the red ginseng manufacturing method, but it is manufactured by repeating the process of steaming and drying fresh ginseng. Black ginseng is ginseng with an increased ginsenoside content compared to fresh ginseng or red ginseng, and it was confirmed that ginsenosides that did not exist in ginseng exist in black ginseng.

In addition, Platycodon grandiflorum is a perennial plant that grows wild in Korea, northeastern China, and Japan, and grows in the grasslands of the mountains where sunlight is well lit. The roots of bellflower have been used for edible vegetables or medicinal purposes, and the roots are washed with water and dried or peeled and dried and dried. The main efficacy of bellflower in oriental medicine is known to be good for symptoms such as sore throat, loss of breath, difficulty urinating, diarrhea and aftereffects, which are close to lung disorders such as cough, phlegm, etc. Toxicol. 40: 517 (2002), Han, SB et al., Int. Immunopharmacol. 1: 1969 (2001), Choi, CY et al., Cancer Lett. 166: 17 (2001)].

Recently, the number of patients with prostate-related diseases including enlarged prostate, prostatitis, and prostate cancer has steadily increased with the entry of an ultra-aging society, and consumers' interest in prevention and treatment is increasing.

Accordingly, the present inventors have found that a specific compound ratio extract of black ginseng and bellflower has a preventive or therapeutic effect on prostate-related diseases, and have come to complete a composition for preventing or treating prostate-related diseases using the same.

It is an object of the present invention to provide a pharmaceutical composition for the prevention or treatment of prostate-related diseases comprising a complex extract of black ginseng and bellflower as an active ingredient.

It is an object of the present invention to provide a health functional food for preventing or improving prostate-related diseases, including a complex extract of black ginseng and bellflower as an active ingredient.

Accordingly, the present invention provides a pharmaceutical composition for preventing or treating prostate-related diseases comprising a complex extract of black ginseng and bellflower as an active ingredient.

In addition, the present invention provides a health functional food for the prevention or treatment of prostate-related diseases comprising the complex extract of black ginseng and bellflower as an active ingredient.

In the present invention, the term "prostate-related disease" refers to a disease occurring in the prostate, which is the reproductive and urinary organs of men, for example, one selected from the group consisting of prostatic hyperplasia, prostatitis, prostate cancer, prostate abscess, and prostate calcification Although it may be the above disease, it is not limited thereto, and may include all various diseases caused by a prostate problem. A prostate abscess is a disease in which bacteria penetrate into the prostate through the urethra and rapidly necrosis the surrounding prostate tissue by creating a pus bag following acute inflammation.At the time of an onset, a severe high fever and chills appear suddenly, and urine is discharged even if you want to urinate. You will feel excruciating urinary pain due to the symptoms of urinary lung that cannot be performed. Prostate calcification is a disease caused by the settling of limestones in the prostate. The absent refers to the crystallization of calcium, oxalate, phosphate, etc., which cannot be liquefied when there are too many components in body fluid including urine.

The term "prevention" used in the present invention may mean all actions of inhibiting or delaying the onset of prostate-related diseases by administering the pharmaceutical composition for preventing or treating prostate-related diseases according to the present invention to an individual.

The term "treatment" as used in the present invention may mean any action to improve or benefit the symptoms of a prostate-related disease by administering the composition of the present invention to an individual suspected of developing a prostate-related disease.

As used herein, the term "improvement" may mean any action that at least reduces the severity of a parameter related to the condition being treated, for example, symptoms.

The extract according to the present invention can be used as obtained by extraction and separation from nature using an extraction and separation method known in the art, and "extract" as defined in the present invention is extracted from black ginseng and bellflower using an appropriate solvent. And, for example, a crude extract, a polar solvent-soluble extract, or a non-polar solvent-soluble extract. Any suitable solvent for extracting the extract from the black ginseng and bellflower may be used as long as it is a pharmaceutically acceptable organic solvent, and water or an organic solvent may be used, but is not limited thereto, for example, purified water, Alcohols having 1 to 4 carbon atoms, including methanol, ethanol, propanol, isopropanol, butanol, etc., acetone, ether, benzene, Various solvents, such as chloroform, ethyl acetate, methylene chloride, hexane, and cyclohexane, may be used alone or in combination. As the extraction method, any one of methods such as hot water extraction, cold precipitation extraction, reflux cooling extraction, solvent extraction, steam distillation method, ultrasonic extraction method, elution method, and compression method may be used. In addition, the desired extract may be further subjected to a conventional fractionation process, or may be purified using a conventional purification method.

There is no limitation on the method for preparing the extract of the present invention, and any known method may be used. For example, the extract included in the composition of the present invention may be prepared in a powder state by an additional process such as distillation under reduced pressure and freeze drying or spray drying of the primary extract extracted by the above hot water extraction or solvent extraction method. In addition, the primary extract was further purified using various chromatography such as silica gel column chromatography, thin layer chromatography, high performance liquid chromatography, etc. You can also get it. Therefore, in the present invention, the extract is a concept including all extracts, fractions and purified products obtained in each step of extraction, fractionation, or purification, their dilutions, concentrates, or dried products.

The pharmaceutical composition of the present invention may further contain an adjuvant in addition to the active ingredient. Any of the adjuvants known in the art may be used without limitation, but, for example, Freund's complete adjuvant or incomplete adjuvant may be further included to increase its immunity.

The pharmaceutical composition according to the present invention may be prepared in a form in which an active ingredient is incorporated in a pharmaceutically acceptable carrier. Here, the pharmaceutically acceptable carrier includes carriers, excipients, and diluents commonly used in the pharmaceutical field. Pharmaceutically acceptable carriers that can be used in the pharmaceutical composition of the present invention are not limited thereto, but lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, alginate, gelatin, Calcium phosphate, calcium silicate, cellulose, methyl cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oils.

The pharmaceutical compositions of the present invention can be formulated and used in the form of oral dosage forms such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, etc., external preparations, suppositories, or sterile injectable solutions according to a conventional method. .

In the case of formulation, it can be prepared using diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrants, and surfactants that are commonly used. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc., and such solid preparations include at least one excipient, such as starch, calcium carbonate, sucrose, lactose, gelatin, in the active ingredient. It can be prepared by mixing and the like. Further, in addition to simple excipients, lubricants such as magnesium stearate and talc may also be used. Liquid preparations for oral administration include suspensions, liquid solutions, emulsions, syrups, and other excipients, such as wetting agents, sweeteners, fragrances, and preservatives, in addition to water and liquid paraffin, which are commonly used diluents. I can. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, lyophilized formulations, and suppositories. As the non-aqueous solvent and suspension, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like may be used. As a base for suppositories, witepsol, tween 61, cacao butter, laurin paper, glycerogelatin, and the like may be used.

The pharmaceutical composition according to the present invention can be administered to a subject by various routes. All modes of administration can be expected, for example, by oral, intravenous, intramuscular, subcutaneous, intraperitoneal injection.

The pharmaceutical composition may be formulated in various oral or parenteral dosage forms.

Formulations for oral administration include, for example, tablets, pills, hard, soft capsules, solutions, suspensions, emulsifiers, syrups, and granules. These formulations include diluents (e.g., lactose, dextrose, water) in addition to the active ingredients. Krose, mannitol, sorbitol, cellulose and/or glycine), lubricants (eg, silica, talc, stearic acid and magnesium or calcium salts thereof and/or polyethylene glycol). In addition, the tablet may contain a binder such as magnesium aluminum silicate, starch paste, gelatin, tragacanth, methylcellulose, sodium carboxymethylcellulose and/or polyvinylpyrrolidine, in some cases starch, agar, alginic acid Or disintegrants or boiling mixtures and/or absorbents, colorants, flavors and sweeteners such as sodium salts thereof. The formulation can be prepared by conventional mixing, granulating or coating methods.

In addition, a representative formulation for parenteral administration is a formulation for injection, and as a solvent for the formulation for injection, water, Ringer's solution, isotonic physiological saline or suspension may be mentioned. The sterile fixed oil of the injection preparation can be used as a solvent or suspension medium, and any non-irritating fixed oil including mono- and di-glycerides can be used for this purpose.

In addition, the injectable formulation may use a fatty acid such as oleic acid.

In addition to containing the extract as an active ingredient, the food composition of the present invention may contain various flavoring agents or natural carbohydrates as an additional ingredient, like a conventional food composition.

Examples of the above-described natural carbohydrates include monosaccharides such as glucose, fructose, and the like; Disaccharides such as maltose, sucrose, and the like; And polysaccharides, for example, common sugars such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. The above-described flavoring agents can be advantageously used as natural flavoring agents (taumatin), stevia extracts (eg, rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.). The food composition of the present invention can be formulated in the same manner as the pharmaceutical composition and used as a functional food or added to various foods. Foods to which the composition of the present invention can be added include, for example, beverages, meat, chocolate, foods, confectionery, pizza, ramen, other noodles, gums, candy, ice cream, alcoholic beverages, vitamin complexes and health supplements, etc. There is this.

In addition, the food composition includes various nutrients, vitamins, minerals (electrolytes), flavoring agents such as synthetic flavoring and natural flavoring agents, coloring agents and heavy weight agents (cheese, chocolate, etc.), pectic acid and salts thereof, Alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonates used in carbonated beverages, and the like may be contained. In addition, the food composition of the present invention may contain flesh for the production of natural fruit juice and fruit juice beverages and vegetable beverages.

The functional food composition of the present invention can be manufactured and processed in the form of tablets, capsules, powders, granules, liquids, and pills. In the present invention, the term'health functional food composition' refers to a food manufactured and processed using raw materials or ingredients having useful functions for the human body pursuant to Health Functional Food Act No.6727, and with respect to the structure and function of the human body. It means ingestion for the purpose of controlling nutrients or obtaining useful effects for health purposes such as physiological action. The health functional food of the present invention may contain ordinary food additives, and whether it is suitable as a food additive is determined according to the general rules and general test methods for food additives approved by the Food and Drug Administration, unless otherwise specified. It is judged according to standards and standards. Examples of items listed in the'Food Additives Code' include chemical compounds such as ketones, glycine, calcium citrate, nicotinic acid, and cinnamic acid; Natural additives such as reduced pigment, licorice extract, crystalline cellulose, high color pigment, and guar gum; Mixed preparations, such as a sodium L-glutamate preparation, an alkali additive for noodles, a preservative preparation, and a tar color preparation, etc. are mentioned. For example, in the health functional food in the form of a tablet, a mixture obtained by mixing the active ingredient of the present invention with an excipient, a binder, a disintegrant, and other additives is granulated by a conventional method, and then a lubricant, etc. The mixture can be directly compression molded. In addition, the health functional food in the form of a tablet may contain a mating agent or the like, if necessary. Among the health functional foods in the form of capsules, hard capsules can be prepared by filling a mixture of the active ingredient of the present invention with additives such as excipients in a conventional hard capsule, and the soft capsules contain the active ingredient of the present invention with additives such as excipients. The mixture mixed with can be prepared by filling a capsule base such as gelatin. The soft capsules may contain a plasticizer such as glycerin or sorbitol, a colorant, a preservative, and the like, if necessary. Ring-shaped health functional foods can be prepared by molding a mixture of the active ingredient of the present invention, excipients, binders, disintegrants, etc. by conventionally known methods, and can be coated with white sugar or other coating agents if necessary, Alternatively, the surface may be coated with a material such as starch or talc. Health functional foods in the form of granules can be prepared in granular form by a mixture of the excipients, binders, disintegrants, etc. of the active ingredients of the present invention by a known method, and if necessary, may contain flavoring agents, flavoring agents, etc. I can.

Since the black ginseng and bellflower-specific mixture ratio extract according to the present invention has superior prostate cancer cell growth inhibitory ability and apoptosis inducing activity than saw palmetto, a conventional prostate cancer treatment, it effectively treats prostate-related diseases such as prostatic hyperplasia, prostatitis, and prostate cancer. It has a preventive, improved, and curable effect.

1 is a diagram showing the survival rate of human prostate stromal cell lines and cancer cell lines in the extract treatment and in the positive control group.
A: Black ginseng 30% alcohol extract
B: Bellflower 30% alcohol extract
C: black ginseng (2): bellflower (1) complex extract
D: black ginseng (1): bellflower (2) complex extract
E: black ginseng (1): bellflower (1) complex extract
F: saw palmetto

Hereinafter, the present invention will be described in detail according to the embodiments shown in the accompanying drawings, but the present invention is not limited to the illustrated embodiments.

The above and other objects and new features of the present invention will become more apparent from the description of the present specification and the accompanying drawings.

Hereinafter, the present invention will be described in more detail through examples. However, the above embodiments and experimental examples are presented as examples of the present invention, and if it is determined that a detailed description of a technique or configuration well known to those skilled in the art may unnecessarily obscure the subject matter of the present invention, the detailed description thereof will be omitted. Can, and the invention is not limited thereby. The present invention is capable of various modifications and applications within the scope of equivalents interpreted from the description of the claims to be described later and therefrom.

Example 1: Preparation and Characterization of Complex Extracts of Black Ginseng and Bellflower

1.1 Preparation of complex extract of black ginseng and bellflower

For black ginseng, dry the washed ginseng at 40℃ for 3~10 hours in a hot air dryer, put the first steamed ginseng in the steamed ginseng, and rapidly increase the temperature from room temperature to 60~70℃ and hold for 10 minutes until the target temperature (90~98℃). The temperature was raised and steamed for 2 to 5 hours, dried for 1 day at a temperature of 30-40°C, and the above process was repeated 3-5 times to prepare.

The complex extract of black ginseng and bellflower was immersed in 30% alcoholic solution for 24 hours and extracted twice at room temperature for 24 hours, and the resulting filtrates were combined and concentrated under reduced pressure to obtain an EtOH extract.

The extracts of black ginseng and bellflower were 1:3 to 3:1, preferably 1:2, 2:1, to obtain a complex extract in a mixing ratio of 1:1.

1.2 Confirmation of cytotoxicity of complex extracts of black ginseng and bellflower

Human prostate stromal cells (WPMY-1) and cancer cells (LNCap) used in this experiment were cultured at 37°C and 5% CO2 in RPMI 1640 medium containing 10% FBS and 1% penicillin/streptomycin (100 u/ml). And cultured.

Thereafter, the cytotoxicity of the composite extract to human prostate stromal cells (WPMY-1) and human prostate cancer cell lines (LNCap) was measured using MTT assay. The cultured WPMY-1 and LNCap cells were dispensed into a 96 well plate at a concentration of 2×104 cells/well, pre-incubated for 24 hours, and then the complex extracts were treated at different concentrations (50, 100, 150, 200 μg/ml). Incubated for an additional 24 hours. In order to measure the cell viability, MTT solution was treated and reacted for 4 hours at 37°C. Formazan stained purple was dissolved by adding DMSO, and absorbance was measured at 570 nm. The results are shown in FIG. 1.

As shown in FIG. 1, it was confirmed that the complex extract of black ginseng and bellflower of the present invention was not toxic to human prostate stromal cell lines.

Example 2: Observation of cancer cell proliferation inhibitory effect of complex extract of black ginseng and bellflower

The cytotoxicity of the human prostate cancer cell line (LNCap) cultured in the same manner as in Example 1.2 was measured using the MTT assay. The results are shown in FIG. 1.

As shown in Figure 1, the black ginseng 30% alcohol extract (A) was found to inhibit prostate cancer cell proliferation by 50% at a lower concentration than the bellflower 30% alcohol extract (B). In addition, it was confirmed that all the complex extracts inhibited prostate cancer cell proliferation by 50% at a very low concentration. In particular, the mixed extract (C) in the ratio of black ginseng (2): bellflower (1) inhibited prostate cancer cell proliferation by 50% at 12.74 ug/ml. % Inhibition was confirmed to be about 12 times better than the positive control saw palmetto (F), which inhibited prostate cancer cell proliferation by 50% at 154 ug/ml.

Claims (7)

Black ginseng and bellflower ( Platycodon grandiflorum ) a pharmaceutical composition for preventing or treating prostate-related diseases comprising a complex extract as an active ingredient. The method of claim 1, wherein the solvent used for the extraction is methanol, ethanol, acetone, ethyl acetate, hexane, butanol, methylene chloride, water, or a mixed solvent thereof. Pharmaceutical composition. The pharmaceutical composition for preventing or treating prostate-related diseases according to claim 1, wherein the complex extract is a mixture of extracts of black ginseng and bellflower in a mixing ratio of 1:3 to 3:1. The pharmaceutical composition of claim 1, wherein the prostate-related disease is at least one disease selected from the group consisting of prostatic hyperplasia, prostatitis, prostate cancer, prostate abscess, and prostate calcification. Health functional food for preventing or improving prostate-related diseases, comprising a complex extract of black ginseng and bellflower as an active ingredient. The health functional food for preventing or improving prostate cancer according to claim 5, wherein the complex extract is a mixture of extracts of black ginseng and bellflower in a mixing ratio of 1:3 to 3:1. The health functional food composition of claim 5, wherein the prostate-related disease is at least one disease selected from the group consisting of prostatic hyperplasia, prostatitis, prostate cancer, prostate abscess, and prostate calcification.

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