WO2021086120A1 - Composition, comprising salvia miltiorrhiza bunge extract as active ingredient, for prevention or treatment of benign prostatic hyperplasia or alopecia - Google Patents

Abstract

The present invention relates to a composition, comprising a Salvia miltiorrhiza Bunge extract as an active ingredient, for treatment or prevention of benign prostatic hyperplasia or alopecia. The Salvia miltiorrhiza Bunge extract comprises 2-70 % of tanshinones including tanshinone1, tanshinone2a, cryptotanshinone, and dihydrotanshinone and can be used to provide a pharmaceutical composition and a health functional food for treatment and prevention of alopecia and benign prostatic hyperplasia.

Description

Composition for the treatment or prevention of prostatic hyperplasia or alopecia containing extract of Salvia miltiorrhiza Bunge as an active ingredient

The present invention relates to a composition for the treatment or prevention of prostatic hyperplasia or alopecia comprising an extract of Salvia miltiorrhiza Bunge as an active ingredient.

Benign prostatic hyperplasia (BPH) is a common chronic disease of the urinary tract in men over 50 years of age (Berry S.J. et al., 1984). BPH is also associated with decreased urinary tract symptoms (LUTS), including intermittent increase in urinary tract, increased urinary tract frequency, urinary tract emergency, weakened urinary tract flow, and incomplete bladder emptying, resulting in poor quality of life and negative effects on daily life in older adults. Go crazy (Sarma, AV et al., 2012).

Although the underlying cause of BPH is unknown, it is well known that the prostate of aged men is affected by androgens (Kim S.K. et al., 2015). During the progression of BPH, androgens promote the proliferation of epithelial cells or stromal cells in the prostate in an autocrine or paracrine manner, resulting in an imbalance of prostate cell proliferation and apoptosis. This has been considered an important cause of BPH (Choi, H.M. et al., 2016).

In particular, dihydrotestosteron (DHT) is well known to be associated with the development of BPH. As we age, testosteron, the male sex hormone, begins to be converted to dihydrotestosterone (DHT) at a high rate in the prostate, which is the concentration of the enzyme reductase, an enzyme that primarily converts testosterone to DHT. The cause is higher. DHT is a more potent androgen compared to TST because of its high binding capacity to the androgen receptor (AR). 5α-reductase type-2 (5AR2) converts TST into DHT in the prostate, and DHT binds to AR to increase the transcription of androgen-dependent genes, ultimately triggering stimulation of protein synthesis related to prostate proliferation. -Enhance the level of specific antigen (PSA). On the other hand, PSA levels increase during progression of BPH and prostate cancer, and for this reason, PSA is widely used in the diagnosis of BPH (Chen, Y. et al., 1996).

The cell cycle occurs in prostate stromal and epithelial cells leading to their division and replication. G1/S progress is highly regulated by cyclin D1. In addition, proliferative nuclear antigen (PCNA) is an acidic nuclear protein recognized as a histological marker for the G1/S phase in the cell cycle. Therefore, the expression of PCNA and cyclin D1 can reflect the proliferative state of prostate cells during BPH (Wang, W., et al., 2004).

Conversely, apoptosis in the prostate epithelium occurs more frequently in the prostate under normal conditions than in BPH. Bcl-2, which inhibits apoptosis, is also found in the prostate epithelium and leads to proliferation of prostate tissue (Cardillo, M., et al., 1997).

Another symptom of male hormones such as dihydrotestosterone (DHT) is male pattern baldness. The causes of hair loss include poor blood circulation, excessive male hormone action, excessive sebum secretion, scalp function decline due to dandruff and other bacteria, genetic factors, and aging stress, but to date, excessive male hormone secretion. The cause of androgenic alopecia, which is the most common type of hair loss, has been identified.

In the case of androgenetic alopecia, healthy hair gradually becomes thinner and shorter, and the hair becomes weaker and breaks easily. This phenomenon is called miniaturization. Hair follicles that are undergoing shrinkage eventually become thin, invisible, and short downy hairs, leading to hair loss. Accordingly, many studies have recently been reported for the prevention and treatment of hair loss through inhibition of male hormone activity.

Testosterone is converted to dihydrotestosterone (DHT), an active male hormone, by 5α-reductase, and the activated dihydrotestosterone binds to the androgen receptor, thereby controlling the protein synthesis of hair follicle cells. By delaying, the growth period of the hair follicle is shortened, and the hair follicle is contracted, causing hair loss. In addition, excessive sebum is produced during the androgenic alopecia process, and as a result, hair loss accompanied by inflammation may appear in the scalp (Dennis A. Holt, et. al,. 1990).

In the case of the currently developed prostatic hypertrophy treatment, which is used as an alpha-1 adrenergic blocker such as terazosin, doxazosin, tamsulasin, alfuzosin, etc., it relieves the symptoms of urethral obstruction by relaxing smooth prostate muscles, but it has low blood pressure and vasodilation by blocking the sympathetic nerve. Side effects such as headache have been reported.

Finasteride (Fi) and Dutasteride, which are 5α-reductase inhibitors, are known to be effective in reducing prostate size by inhibiting the conversion of testosterone to dihydrotestosterone (DHT), an active metabolite by 5α-reductase, and used for BPH and alopecia. However (Park, ES, et al., 2018), these drugs are known to cause side effects such as erectile dysfunction, decreased libido, and decreased semen volume in ejaculation. As such, although the currently used drug treatment is somewhat effective, its side effects are a problem, and in fact, prostatic hyperplasia is one of the persistent aging phenomena, and there is a problem that fundamental treatment is difficult.

Therefore, researchers looking for effective treatment strategies with less side effects are increasingly interested in alternative medicine, including drugs made from natural ingredients. Currently, only saw palmetto extract among natural ingredients is widely known as a functional food having an effect on BPH (Marks, L.S., et al., 2000).

Salvia (Salvia miltiorrhiza Bunge) is a perennial plant belonging to the Lamiaceae family, and its roots are similar in shape to ginseng and its red color gives it the name Danseng. Danseng is known as a medicinal herb that strengthens blood vessels from ancient times, and the tansinone contained in Danseng helps blood vessels rejuvenate by inhibiting the oxidation of waste products in blood vessels, expands blood vessels, improves blood circulation, and improves blood circulation, hypertension or myocardial infarction It is known to prevent vascular diseases such as. In oriental medicine, Dansam is recorded as a medicinal herb that helps in the formation of new blood by promoting blood flow and removing blood stagnation.

Korean Patent Laid-Open Publication No. 2012-0020639 discloses a composition for treating prostate cancer comprising a single ginseng, and Korean Patent Publication No. 2001-0076810 discloses a method for preparing a composition for treating prostate disease and hemorrhoids. And the composition according to the manufacturing method, such as Hojanggeun, Machihyeon, Ikjiin, Chajeon, Pogongyeong, Geumeunhwa, Yongdamcho, Rhubarb, Gyenaegum, Somok, Mokgwa, Cheonnyeonja, Oryeongji, Dansam, Myrrh, Pagoji, Wiryeongseon, Frankincense, Pills prepared by mixing 2-5wt% each of Yongnoe, Hyeonhosaek, Baekgulchae, Sohoehyang, Samneung, Bongchul, Casualty, Hyangbuja, Oyak, Jiryong, and water are disclosed, but containing the extract of the sweet ginseng of the present invention as an active ingredient. No composition for prophylaxis and treatment of prostatic hyperplasia is described.

In addition, Korean Patent Publication No. 0259037 discloses that Banha, Clove, Bokbunja, Sancho, Manhyeongja, Dansam and White porcelain powders are immersed in oil and ethanol, respectively, and then aged for a certain period of time, and an external solution is prepared and directly applied. Although the external solution for promoting hair growth is described, it is different from the composition of the present invention.

[Prior technical literature]

[Patent Literature]

Korean Patent Publication No. 2012-0020639, A composition for treating prostate cancer containing Dansam, 2012.03.08. open

Korean Patent Publication No. 2001-0076810, A method for preparing a composition for treating prostate disease and hemorrhoids, and a composition according to the method, 2001.08.16. open.

Korean Registered Publication No. 0259037, External solution for hair growth promotion, 2000.03.16. Enrollment

[Non-patent literature]

Berry, S.J.; Coffey, D.S.; Walsh, P.C.; Ewing, L.L. The development of human benign prostatic hyperplasia with age. J. Urol. 1984, 132, 474-479.

Sarma, A.V.; Wei, J.T. Clinical practice. Benign prostatic hyperplasia and lower urinary tract symptoms. N. Engl. J. Med. 2012, 367, 248-257.

Kim, S.K.; Seok, H.; Park, H.J.; Jeon, H.S.; Kang, S.W.; Lee, B.C.; Yi, J.; Song, S.Y.; Lee, S.H.; Kim, Y.O.; et al. Inhibitory effect of curcumin on testosterone induced benign prostatic hyperplasia rat model. BMC Complement. Altern. Med. 2015, 15, 380-386.

Choi, H.M.; Jung, Y.; Park, J.B.; Kim, H.L.; Youn, D.H.; Kang, J. W.; Jeong, M.Y.; Lee, J.H.; Yang, W.M.; Lee, S.G.; et al. Cinnamomi cortex (Cinnamomum verum) suppresses testosterone-induced benign prostatic hyperplasia by regulating 5α-reductase. Sci. Rep. 2016, 6, 31906-31917.

Chen, Y.; Robles, A.I.; Martinez, L.A.; Liu, F.; Gimenez-Conti, I.B.; Conti, C.J. Expression of G1 cyclins, cyclin-dependent kinases, and cyclin-dependent kinase inhibitors in androgen-induced prostate proliferation in castrated rats. Cell Growth Differ. 1996, 7, 1571-1578.

Wang, W.; Bergh, A.; Damber, J.E. Chronic inflammation in benign prostate hyperplasia is associated with focal upregulation of cyclooxygenase-2, Bcl-2, and cell proliferation in the glandular epithelium. Prostate 2004, 61, 60-72.

Cardillo, M.; Berchem, G.; Tarkington, M.A.; Krajewski, S.; Krajewski, M.; Reed, J.C.; Tehan, T.; Ortega, L.; Lage, J.; Gelmann, E.P. Resistance to apoptosis and up regulation of Bcl-2 in benign prostatic hyperplasia after androgen deprivation. J. Urol. 1997, 158, 212-216.

Dennis A. Holt; Mark A. Levy; Hye Ja Oh; Jill M. Erb; Julie I.; Heaslip; Martin Brandt; Hsuan Yin Lan-Hargest; Brian W. Metcalf, Inhibition of steroid 5.alpha.-reductase by unsaturated 3-carboxy steroids, J. Med. Chem. 1990, 333, 943-950.

Park, E.S.; Lee, M.Y.; Jeon, W.W.; Seo, C.S.; You, S.S.; Shin, H.K. Paljung-San, a traditional herbal medicine, attenuates benign prostatic hyperplasia in vitro and in vivo. J. Ethnopharmacol. 2018, 218, 109-115.

Marks, L.S.; Partin, A.W.; Epstein, J.I.; Tyler, V.E.; Simon, I.; Macairan, M. L.; Chan, T.L.; Dorey, F.J.; Garris, J. B.; Veltri, R. W.; et al. Effects of a saw palmetto herbal blend in men with symptomatic benign prostatic hyperplasia. J. Urol. 2000, 163, 1451-1456.

SHAN GAO, SHIQIN LI, QIN LI, FUYONG ZHANG, MENGQI SUN, ZILIN WAN and SHURONG WANG, Protective effects of salvianolic acid B against hydrogen peroxide-induced apoptosis of human umbilical vein endothelial cells and underlying mechanisms, INTERNATIONAL JOURNAL OF MOlecular medicine 44: 457-468, 2019

An object of the present invention is to provide a composition for the treatment or prevention of prostatic hyperplasia comprising an extract of Salvia miltiorrhiza Bunge as an active ingredient.

In order to solve the above problems, the present invention provides a composition for the treatment or prevention of prostatic hyperplasia or alopecia including the active ingredient of Salvia miltiorrhiza Bunge (Salvia miltiorrhiza Bunge) extract.

The Dansam extract may be distilled water or ethanol extract, and other solvents may be used. Depending on the type of extraction solvent, the extraction temperature, extraction time, amount of solvent, and treatment method of residual components may be designed differently. Various solvents may be used as the extraction solvent. Examples of extractable solvents include water, ethanol, methanol, fatty oil, glycerin, horse oil, ethyl acetate, acetone, butanol, isopropanol, and methylene chloride.

The Dansam extract may be an extract extracted with an alcohol having 1 to 6 carbon atoms or a mixed solvent thereof. The alcohol may be ethanol, and may be 40 to 99% ethanol.

The Salvia miltiorrhiza Bunge extract may be a 40-99% ethanol extract.

The sweet ginseng extract may be concentrated. Moisture can be removed by heating the extract at 40~80℃ using the microwave drying method. Alternatively, the extract may be concentrated and dried by a low-temperature vacuum drying method. Low-temperature vacuum drying is a method of drying by maintaining the pressure inside the dryer in a vacuum and controlling the temperature to about 5 to 15°C. There is no denaturation of the extracted components, and taste and aroma are not lost. Depending on the design conditions, methods such as spray drying, cold air drying, hot air drying, freeze drying, far infrared drying, sound drying, and vacuum drying may be used.

Dansam can also be prepared using a cryogenic micro-grinding process (Cryogenic Micro Grinding Technology, CMGT). More specifically, a powder having improved physical properties can be prepared by freezing the Dansam root in a short time at a cryogenic temperature of -196 to -80°C and pulverizing it into fine powder.

The sweet ginseng concentrate can be dried and prepared in various formulations. After the extract is concentrated and dried by a spray drying method, it can be prepared in various formulations. For example, it can be made into a powder. Low-temperature vacuum drying is a method of drying by maintaining the pressure inside the dryer in a vacuum and controlling the temperature to about 5 to 15°C. There is no denaturation of the extracted components, and taste and aroma are not lost. Depending on the design conditions, methods such as cold air drying, hot air drying, freeze drying, far infrared drying, sound drying, and vacuum drying may be used. Preferably, Dansam (S. miltiorrhza) may be eluted with 50 ℓ of ethanol for 24 hours and then concentrated under reduced pressure. Here, 1500 ml of water was added, and the same amount of n-hexane, dichloromethane (CH ₂ Cl ₂ ) and ethyl acetate (EtOAc) were added and extracted twice in sequence to prepare a red ginseng extract in a gel state. can do.

It may be distilled water or ethanol melt of the cryogenic freeze-freezing fine powder of Danseng. However, the present invention is not limited thereto, and Dansam can be extracted by a known extraction method available such as hot water extraction, distillation extraction, ethanol extraction, ultrasonic ethanol extraction, and ultrasonic water extraction. The Dansam extract may be included in an amount of 0.01 to 700 ㎍ / ㎖.

In the same manner as described above, the content of tansinones, which is an active ingredient of Danseng, can be increased. Danseng (S. miltiorrhiza Bunge) extract may contain tanshinones 2% to 70% of the total weight.

In the above, the Dansam extract may be fractionally extracted with an organic solvent containing methylene chloride, and a specific component may be concentrated through a column.

The Salvia miltiorrhiza Bunge extract may be one containing 2% to 70% of the total weight of tanshinones.

The tanshinones are Tanshinone1 (1,6-Dimethylphenanthro[1,2-b]furan-10,11-dione or 1,6-dimethylnaphtho[1,2-g]benzofuran-10,11-dione), Tanshinone2a (1 ,6,6-Trimethyl-6,7,8,9-tetrahydrophenanthro[1,2-b]furan-10,11-dione), Cryptotanshinone ((R)-1,2,6,7,8,9- Hexahydro-1,6,6-trimethyl-phenanthro(1,2-b)furan-10,11-dione), 15,16-Dihydrotanshinone ((1R)-1,6-dimethyl-1,2-dihydronaphtho[1 ,2-g][1]benzofuran-10,11-dione Dihydrotanshinone-I) may contain one or more of the group consisting of as an active ingredient, and may be other tansinone except for the four kinds of tanshinone.

The present invention provides a composition for the treatment or prevention of prostatic hypertrophy or alopecia, characterized in that it comprises one or more of the group consisting of tanshinone1, tanshinone2a, cryptotanshinone, dihydrotanshinone and tanshinoic acid as an active ingredient.

The major tanshinones known to date include tanshinone1, tanshinone2a, cryptotanshinone or dihydrotanshinone, and include tanshinoic acid and other tanshinones with different terminal functional groups. The active ingredient of Danshen may be tanshinone1, tanshinone2a, cryptotanshinone or dihydrotanshinone, preferably tanshinone2a, or other tanshinones containing dihydrotanshinone or tanshinoic acid as the active ingredient, and more preferably dihydrotanshinone or other tanshinones. have.

The present invention provides a pharmaceutical composition for the treatment or prevention of prostatic hyperplasia, comprising the extract of Danseng Ginseng as an active ingredient. The pharmaceutical composition of the present invention may contain an active ingredient of Danshin, including tanshinones such as tanshinone1, tanshinone2a, cryptotanshinone, dihydrotashinone and/or tanshinoic acid.

The pharmaceutical composition may include a carrier or an excipient, each of which is preferably 0.001% by weight to 90% by weight, more preferably 0.001% by weight to 50% by weight, most preferably It may be added in an amount of 0.001% to 30% by weight.

A suitable dosage of the pharmaceutical composition may be variously prescribed depending on factors such as formulation method, administration mode, patient's age, weight, sex, pathological condition, food, administration time, route of administration, excretion rate, and response sensitivity. . The pharmaceutical composition of the present invention contains the tansinone derivatives as active ingredients. The pharmaceutical composition may be administered orally or parenterally during clinical administration, and may be used in the form of a general pharmaceutical formulation. That is, the composition of the present invention can be administered in various oral and parenteral dosage forms at the time of actual clinical administration, but when formulated, diluents or excipients such as commonly used fillers, extenders, binders, wetting agents, disintegrants and surfactants It is prepared using. Solid preparations for oral administration include tablets, pills, powders, granules and capsules, and such solid preparations include at least one or more excipients such as starch, calcium carbonate, sucrose, and lactose in tansinone derivatives. And it is prepared by mixing gelatin or the like. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Liquid preparations for oral administration include suspensions, liquid solutions, emulsions, and syrups. In addition to water and liquid paraffin, which are commonly used simple diluents, various excipients such as humectants, sweeteners, fragrances and preservatives may be included. have. Preparations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, lyophilized preparations, and suppositories. As the non-aqueous solvent and suspension, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, and injectable ester such as ethyl oleate may be used. As a base for suppositories, witepsol, macrogol, tween61, cacao butter, laurin, glycerol, gelatin, and the like may be used.

Dosage units may contain, for example, 1, 2, 3 or 4 times or 1/2, 1/3 or 1/4 times the individual dosage. The individual dosages preferably contain the amount of the effective drug administered at one time, which is usually all, 1/2, 1/3 or 1/4 times the daily dosage. The effective dose of tansinone derivatives is concentration dependent, but preferably 0.1 mg to 1,000 mg/kg, more preferably 0.4 to 500 mg/kg, and may be administered 1 to 6 times a day. Therefore, it can be administered in the range of 0.1 ~ 6,000 mg / day per 1 kg of adult body weight.

The pharmaceutical composition may be administered to mammals such as mice, livestock, and humans by various routes. All modes of administration can be expected and may be administered, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, intrauterine dural or cerebrovascular injection.

The Salvia miltiorrhiza Bunge extract is at least one of the group consisting of 5α reductase type 2 (5AR2), prostate specific antigen (PSA), steroid receptor coactivator-1 (SRC-1), and androgen receptor (AR). It can reduce protein expression. The protein is an androgen-related protein and exhibits an increasing pattern in prostatic hyperplasia or alopecia.

The present invention is the extract of Salvia miltiorrhiza Bunge,

Crushing the Dansam from which impurities have been removed (1);

The step (2) of immersing the crushed Danseng in step (1) in 40-99% ethanol (EtOH) at 50-80°C and leaving for 2 to 24 hours;

Separating the alcohol from which the ginseng was extracted from the step (2), adding new alcohol to the remaining residue, immersing it in 40 to 99% ethanol (EtOH) at 50 to 80°C, and leaving it for 2 to 12 hours (3);

Separating the alcohol from which the ginseng was extracted from the step (3), adding new alcohol to the remaining residue, immersing it in 40 to 99% ethanol (EtOH) at 50 to 80°C, and leaving it for 2 to 5 hours (4);

Collecting the spirits separated in steps (2) to (4), evaporating and drying them at 45 to 75°C (5);

Treatment of prostatic hyperplasia or alopecia, characterized in that prepared by a method for producing a sweet ginseng extract comprising the step (6) of obtaining a sweet ginseng extract by pulverizing the evaporated and dried solid extract in step (4) and filtering at 80 mesh or more Or it provides a composition for prevention.

In addition, the step (1) of crushing the dried ginseng from which the impurities have been removed is to freeze the ginseng at a cryogenic temperature of -196 to -80°C for a short time and pulverize the ginseng to 5 mm or less (Cryogenic Micro Grinding Technology, CMGT). It provides a composition for the treatment or prevention of prostatic hyperplasia or alopecia, characterized in that.

The present invention provides a health functional food for preventing or improving prostatic hyperplasia or alopecia, comprising an extract of Salvia miltiorrhiza Bunge as an active ingredient.

The health functional food provides a health functional food comprising an active ingredient of Danshin including other tanshinones, such as tanshinone1, tanshinone2a, cryptotanshinone, dihydrotashinone or tanshinoic acid, and food supplementary additives that are acceptable in food terms.

The health functional food is preferably 0.001% to 50% by weight, based on the total weight of the health functional food, the active ingredient of the dancinone containing other tanshinones, such as the extract, tanshinone1, tanshinone2a, cryptotanshinone, dihydrotashinone and/or tanshinoic acid, More preferably 0.001% by weight to 30% by weight, most preferably 0.001% by weight to 10% by weight may be added.

Dansam extract of the present invention is preferably added in an amount of 0.001% to 50% by weight, more preferably 0.001% to 30% by weight, and most preferably 0.001% to 10% by weight based on the total weight of the health functional food Can be.

The health functional food includes forms such as tablets, capsules, pills or liquids, and foods to which the extract of the present invention can be added include, for example, meat, sausage, bread, chocolate, candy, snacks, confectionery. , Pizza, ramen, other noodles, gum, powdered milk, sunsik, raw food, fermented lactic acid bacteria, dairy products including ice cream, various soups, beverages, tea, drinks, alcoholic beverages, and vitamin complexes. Specifically, health foods containing Danseng extract include health foods and favorite products such as juice, tea, jelly, and juice made from Dansam extract as a main component, and folk remedies for the purpose of edema, nephritis, urethritis, etc. Can be mentioned.

A composition for treating or preventing prostatic hyperplasia comprising the extract of Danseng as an active ingredient may be prepared as a cosmetic composition. When used as a cosmetic composition, Dansam extract is added as it is or used together with other cosmetic ingredients, and may be appropriately used according to a conventional method. The mixing amount of the active ingredient may be appropriately determined according to the purpose of use thereof, and generally, in an amount of 0.0001 to 10% by weight, preferably 0.1 to 5% by weight, based on the total weight of the raw material in the manufacture of cosmetics using the Dansam extract. Can be added. Cosmetics include skin ointment, cream, softening lotion, nutrient lotion, pack, essence, hair tonic, shampoo, conditioner, hair conditioner, hair treatment, gel, skin lotion, skin softener, skin toner, astringent, lotion, milk lotion , Moisture lotion, nutrition lotion, massage cream, nutrition cream, moisture cream, hand cream, foundation, color cosmetics, nutrition essence, sunscreen, soap, cleansing foam, cleansing lotion, cleansing cream, body lotion and body cleanser It may be a cosmetic composition having any one selected formulation, but is not limited thereto.

When the formulation of the present invention is a surfactant containing cleansing, as a carrier component, aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, isethionate, imidazolinium derivative, methyltaurate, sarcosinate, fatty acid amide Ether sulfates, alkylamidobetaines, fatty alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable oils, linoline derivatives or ethoxylated glycerol fatty acid esters may be used.

The formulation of the present invention may further contain excipients including fluorescent substances, fungicides, hydrophobic substances, moisturizers, fragrances, fragrance carriers, proteins, solubilizers, sugar derivatives, sunscreens, vitamins and plant extracts. .

As described above, according to the present invention, the composition for treating or preventing prostatic hyperplasia comprising the extract of Salvia miltiorrhiza Bunge as an active ingredient provides a safe and powerful composition for the treatment and prevention of prostatic hyperplasia that can replace the conventional treatment with many side effects. can do.

1 is a DHT-derived LNCaP cell line, a sweet ginseng extract S containing salvianolic acid as a main component (about 10-20%), a sweet ginseng extract T containing tanshinone as a main component (about 22%), and its effectiveness. Components Tanshinone1 (Tan1), Tanshinone2a (Tan2a), Cryptotanshinone (CryT) and Dihydrotanshinone (DihT) 5α reductase type 2 (5α reductase type2, 5AR2), androgen receptor (AR), steroid receptor co-activator- 1 (Steroid Receptor Coactivator-1, SRC-1) and Prostate Specific Antigen (PSA) expression changes were confirmed by Western blotting.

2 is a graph showing quantification of each protein of FIG. 1.

3 is a Western blotting result showing the effect on the expression of the androgen receptor (AR) and prostate specific antigen (PSA) by treating the extracts T95, T70, and T40 by concentration in the DHT-treated LNCaP cell line.

4 is a graph showing the quantification of the androgen receptor (AR) (A) and the prostate specific antigen (PSA) (B) of FIG. 3, respectively.

5 is a graph showing changes in the weight of rats according to treatment with Danseng extract T70 to T10 in an animal model for prostatic hyperplasia.

6 is a photograph showing the change in the size of the prostate gland of rats according to treatment with Dansam extract T70 to T10 in an animal model of prostatic hyperplasia.

7 is a graph showing changes in prostate weight of rats according to treatment with Dansam extract T70 to T10 in an animal model of prostatic hyperplasia.

FIG. 8 is a graph showing changes in the Prostate index (prostate weight versus body weight) of rats according to treatment with Dansam extract T70 to T10 in an animal model for prostatic hyperplasia.

9 shows the effect of Dansam extract T40 on the expression of 5α-reductase (5AR2), androgen receptor (AR), and prostate specific antigen (PSA), which are proteins related to prostatic hypertrophy in rats in an animal model of prostatic hyperplasia. Western blotting results showing the effect.

10 is a schematic diagram showing the signaling pathway of Testosterone in BPH and the pharmacological mechanism of sweet ginseng extract.

Prostatic hyperplasia (BPH) is a common chronic disease of the urinary tract among the elderly, and an imbalance of androgen metabolism in the elderly is one of the major causes of BPH. Dihydrotestosterone (DHT) by 5α reductase type 2 (5AR2), which binds to androgen receptor (AR), affects prostate proliferation and growth. In BPH, it has been reported that the expression level of androgen signaling related protein is high, and androgen signaling is related to overexpression of prostate specific antigen (PSA). Another symptom associated with the regulation of dihydrotestosterone (DHT) is alopecia.

In the present invention, during the study of the signaling pathways of prostatic hyperplasia (BPH) and alopecia, Salvia miltiorrhiza Bunge extract and its active ingredient are involved in the pathway, thereby providing excellent effects in the treatment and prevention of prostatic hyperplasia (BPH) or alopecia. It was confirmed that there was, and the present invention was completed.

Hereinafter, a preferred embodiment of the present invention will be described in detail. However, the present invention is not limited to the embodiments described herein and may be embodied in other forms. Rather, the content introduced herein becomes thorough and complete, and is provided to sufficiently convey the spirit of the present invention to those skilled in the art.

< Example One. Dansam Component analysis of extract>

1.1. Dansam Extract S Produce

The crushed sweet ginseng roots were extracted in hot water at 50-100°C. After extracting from the hot water for 2 to 24 hours, filtration was performed to remove debris, and the extract was collected, heated, and evaporated to dryness. The evaporated solid was washed with hot water at 100° C. if necessary, dried in a microwave at 55° C. for 25 to 30 minutes, pulverized, and filtered over 60 mesh to prepare. The main component of the extract S of the extract S extracted from the ginseng through the above step was Savianolic acid, which was found to contain about 10 to 20% of the extract.

In order to increase the efficiency of extracting sweet ginseng, the sweet ginseng root can be subjected to a cryogenic micro-grinding process (Cryogenic Micro Grinding Technology, CMGT). CMGT (Cryogenic MicroGrinding Technology) is a processing technology that minimizes changes in natural properties, taste, nutrition, and aroma by rapidly freezing and pulverizing natural products or food materials at an ultra-low temperature of -196 degrees Celsius using liquid nitrogen. It is difficult to crush at room temperature, materials with high fat content, materials with high moisture, etc. can be processed, and in particular, it is possible to improve the dissolving power and dispersing power without impairing the inherent properties of the raw material. In addition, CMGT is an impact-type grinding method that is effective for brittle fracture (remarkably brittle against impact) by cooling raw materials at ultra-low temperatures. The shape of the particles is circular due to pulverization by friction between particles, and when the particle size is the same as that of other pulverization methods, it is less denatured and has low pulverization heat, so it is possible to continuously pulverize a material with a large share, so it is easy to apply it to food materials. The large size of the original was pulverized to less than 5mm in a coarse crusher (Duksan, Korea), and the original product of the size that can use the screw of the one made by Hosokawa (Linrex Mill LX-1, Japan) and one made in Deoksan is used. It is used as it is and crushed.

Dansam CMGT was prepared by using the Cryogenic Micro Grinding Technology (CMGT) of Dansam root. More specifically, it can be used in the preparation of Dansam extract S and the following Dansam extract T by freezing the Dansam root at a cryogenic temperature of -110 to -90°C for a short time and pulverizing at 4500 to 5500 rpm.

1.2. Dansam Extract T Produce

Dansam extract T was extracted from the crushed Dansam root with alcohol (EtOH) at 50 ~ 80 ℃ (sweet ginseng extract T). In addition, in order to check the effect according to the concentration of the extracted alcohol, T10 (EtOH10%), T40 (EtOH40%), T70 (EtOH70%), T95 (EtOH95%), T99 (EtOH99%) were used by varying the concentration of the alcohol. Respectively obtained. The alcohol was extracted for 2 to 24 hours, and if necessary, a new alcohol was extracted for 2 to 12 hours, and then further extracted for 2 to 5 hours in a new alcohol, if necessary, and centrifuged to obtain a supernatant. Thereafter, the obtained supernatant was collected, evaporated and dried at 45 to 75° C., pulverized, and filtered at 80 mesh or more to prepare.

1.3. Dansam Analysis of the components of the extract

The components and contents of the Dansam extract S and Dansam extract T extracted in Examples 1.2 and 1.3 were measured. In particular, among the various compounds identified by existing researchers to establish the four main tanshinone components contained in sweet ginseng, whether components such as Tanshinone1, Tanshinone2a, Cryptotanshinone, Dihydrotanshinone and salvianolic acid B, which are sold as standard products, are present in the sweet ginseng extract. Was confirmed through HPLC analysis. HPLC conditions are as follows. Column; cadeza cd-C18 3.0 μm, 3.0 mm × 250 mm, detector; DAD (254 nm), temperature (Temp.); 40° C., injection volume; 10 μL, flow rate; 0.2 mL/min, Mobile phase; It is 80% MeOH.

In addition to the main tansinone components, the extract of sweet ginseng contains a variety of other tansinones. It is difficult to purchase other standard products of tanshinon. Therefore, in general, tansinones have a common skeleton in terms of molecular structure, have a constant molecular weight (molecular weight around 300kDa), and have similar physicochemical properties. Focusing on this point, Tanshinone2a was set as an index component, and the absorbance standard curve for each concentration was set, and the absorbance was measured in the 270nm wavelength band with a spectrophotometer, and the total tanshinone was quantified using a regression equation. It is shown in Table 1 below.

Compound	Sweet Ginseng Extract S	Sweet Ginseng Extract T
		T10	T40	T70	T95
Total Tanshinones	≪0.1%	1.72%	10.79%	19.34%	22.22%
15,16-Dihydrotanshinone	≪0.1%	≪0.1%	0.64%	1.31%	1.75%
Tanshinone1	≪0.1%	0.20%	1.22%	1.84%	2.03%
Tanshinone2a	≪0.1%	0.28%	1.76%	2.81%	3.11%
Cryptotanshinone	≪0.1%	0.50%	2.62%	5.16%	5.88%
Other Tanshinones	≪0.1%	0.74%	4.55%	8.22%	9.45%
Salvianolic acid B	15.14%	12.98%	2.54%	≪0.1%	≪0.1%

As shown in Table 1, tanshinones were hardly detected in sweet ginseng extract S, which is a hot water extract, and salvianolic acid B was detected at 15.14% in the extract. In addition, it was confirmed that 1.72% of tansinones were extracted from 10% of ethanol and 10.79% of ethanol was extracted from 40%, and it was confirmed that the higher the concentration of ethanol, the higher the extraction efficiency of tansinones. In the ethanol 95% solvent condition, 22.22% of total tansinones were contained in the extract. On the contrary, as the concentration of ethanol increased, the content of salvianolic acid B rapidly decreased.

Among the tanshinones, Cryptotanshinone was the most detected, followed by Tanshinone2a, Tanshinone1, 15,16-Dihydrotanshinone, and the extraction efficiency increased as the ethanol concentration of other tanshinones except the main tanshinones also increased. The sweet ginseng extract T99 was similar to the sweet ginseng extract T95, but the instability in the heating process during the extraction process was high and the efficiency was low in mass production, so the sweet ginseng extract T95 was used as a representative.

< Example 3. Dansam Extract of DHT process LNCaP Identification of androgen pathway-related protein levels in cells>

3.1. Cell culture

Of the extract of the sweet ginseng of the present invention Enlarged prostate And in order to confirm the effect on alopecia, animal cells were cultured. At this time, the animal cells were LNCaP cells, a human prostate adenocarcinoma cell line sensitive to androgen, and were purchased from Korea Cell Line Bank (Seoul, Korea KCLB #:21740). Cells were cultured in RPMI (Roswell Park Memorial Institute) medium added with 100 mg/ml penicillin/stereptomycin and 10% FBS (fetal bovine serum), and cultured in a CO ₂ incubator maintained at 37°C.

3.2 Preparation of the material

Antibodies against goat anti-rabbit immunoglobulin G (IgG, 7074) and anti-mouse IgG (7076) were purchased from Cell Signaling (Danvers, MA). Antibodies against AR (SC-816), SRC1 (SC-32789), PSA (SC-7638) and β-actin (SC-1616) were obtained from Santa Cruz Biotechnology (Dallas, Texas, USA), and antibodies against 5AR2 (ab124877 ) Is Abcam Inc. (Cambridge, Massachusetts, USA). Roswell Park Memorial Institute (RPMI) medium, fetal bovine serum (FBS) and penicillin/streptomycin were purchased from Gibco (Big Cabin, OK, USA). Other reagents containing finasteride, Fi (≥97% purity) and DHT (≥99% purity) are manufactured by Sigma-Aldrich Inc. (St. Louis, Missouri, USA).

3.3 Effect of Dansam extract on DHT-treated LNCaP cells

^{The LNCaP cell line was seeded in 6-well plates (1×10 6} cells/well) in 2 mL of RPMI medium supplemented with 10% FBS, 100 U/mL penicillin and 100 mg/mL streptomycin. One day later, the cells were treated with DHT (10 nmol) and Dansam extract S, Dansam extract T95 at 15 μg/ml, Tanshinone1, Tanshinone2a, Cryptotanshinone and 15,16-Dihydrotanshinone at a concentration of 5 μM, respectively, for 24 hours. Harvested LNCaP cells were lysed using cold radiation immunoprecipitation assay (RIPA) buffer containing a protease inhibitor cocktail. Lysed cells were centrifuged at 13,000 RPM for 20 minutes at 4° C., and protein concentration was measured using BCA analysis. Cell lysates (30 μg protein/sample) were separated by 10% sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) at 120% for 90 minutes and transferred to a nitrocellulose membrane. The membrane was blocked with 5% skim milk for 1 hour at room temperature. Immediately afterwards, primary antibodies such as AR, 5AR2, PSA and SRC-1 (diluted 1:2000) were reacted to the membrane overnight. After washing the membranes they were incubated for 1 hour at room temperature with goat anti-rabbit IgG and anti-mouse IgG horseradish peroxidase (HRP)-conjugated secondary antibodies (diluted to 1:10000). Immunity detection was performed using an enhanced chemiluminescence (ECL) detection reagent and is shown in FIG. 1. Thereafter, the membrane was photographed using a DaVinch-Chemi imaging system (Davinch-K., Seoul). The chemiluminescence intensity of the protein signal was quantified using ImageJ 1.47v software and shown in FIG. 2. Results are presented as mean ± mean standard error (SEM) of data obtained by SPSS version 11.5 for Windows (SPSS Inc., Chicago, Illinois, USA). Means of two consecutive normal distribution variables were compared with Student's t-test for independent samples. Dunnett's multiple range test was used to compare the means of two or three or more groups of variables that did not follow a normal distribution. p <0.05 and p <0.01 were considered as criteria for statistical significance.

1 and 2, the LNCaP cell line increased the expression level of androgen-related proteins excluding the androgen receptor (AR) by DHT. In the case of treatment with Dansam extract S, the expression of SRC-1 increased by DHT was somewhat reduced, and the expression level of androgen receptor (AR) was reduced by 40%. However, in the case of 5α-reductase type 2 (5AR2) and prostate-specific antigen (PSA), which are major increases in prostatic hyperplasia, the expression was rather increased. However, in the case of Dansam extract T, protein expression of all 5α reductase type 2 (5AR2), prostate-specific antigen (PSA), steroid receptor co-activator-1 (SRC-1) and androgen receptor (AR) was significantly reduced. . In particular, Dansam extract T suppressed the expression of 5α reductase type 2 (5AR2), prostate specific antigen (PSA), and androgen receptor (AR) to a lower level than that of the control group.

In addition, when 5 μM of each 5 μM each of Tanshinone1, Tanshinone2a, Cryptotanshinone, and 15,16-Dihydrotanshinone, the major tansinones identified in Danshen, was treated in DHT-induced LNCaP cell line, 15,16-Dihydrotanshinone inhibited androgen-related protein increased by DHT. Showed the most. In particular, 15,16-Dihydrotanshinone inhibited the expression of prostate specific antigen (PSA) and androgen receptor (AR) more than 5 times more than Tanshinone2a at the same concentration. This indicates that a composition effective for the treatment and prevention of androgen-related protein-mediated diseases such as prostatic hyperplasia or alopecia can be provided. 15,16-Dihydrotanshinone also inhibited the expression of 5α reductase type 2 (5AR2) and steroid receptor co-activator-1 (SRC-1) more effectively than Tanshinone2a. On the other hand, 15 ㎍ / ml treatment of Dansam extract T inhibited the expression of androgen-related proteins more effectively than 15,16-Dihydrotanshinone. In order to confirm whether this is the difference in the treatment concentration, the content of individual tansinone of 15 µg/ml of Danseng extract T was converted based on the results of Table 1 and shown in Table 2.

Compound	Sweet Ginseng Extract T95
Total Tanshinones	15 μg/ml	3.33㎍/ml
15,16-Dihydrotanshinone		0.26㎍/ml
Tanshinone1		0.30㎍/ml
Tanshinone2a		0.47㎍/ml
Cryptotanshinone		0.89㎍/ml
Other Tanshinones		1.42㎍/ml

As shown in Table 2, tanshinones are included in the Danseng extract T at 3.33 µg/ml, and the content of 15,16-Dihydrotanshinone, which has the best inhibitory effect of androgen-related proteins, is only 0.26 µg/ml. , It was confirmed that the inhibitory effect of androgen-related proteins was superior to that of other major tansinones. It is possible that a mixture of various types of tansinone contained in Danseng extract T exhibits a synergistic effect, or other tansinones other than the four major tansinones contain compounds having an excellent inhibitory effect on androgen-related proteins.

3.4 DHT process LNCaP For cells Dansam Extract of T Effect by concentration

In order to check the inhibitory effect of the androgen-related protein of the sweet ginseng extract according to the ethanol concentration, the sweet ginseng extract 95T, 70T, 40T extracted with ethanol 95%, 70%, and 40%, respectively, was treated in DHT-treated LNCaP cells by concentration and the effect was confirmed. I did. LNCaP cells were treated with DHT in the same manner as in Example 3.3, and the extracts of sweet ginseng T95, T70, and T40 were administered at 5, 10, and 15 µg/ml, respectively, and then androgen receptor (AR) and prostate specific antigen (Prostate PSA). It is shown in Figures 3 and 4 by confirming the expression of.

3 and 4, sweet ginseng extract T95, T70, T40 inhibited the expression of androgen receptor (AR) and prostate specific antigen (Prostate PSA) in a concentration-dependent manner, and sweet ginseng extract T95 was the most effective. In addition, sweet ginseng extract T70 showed no significant difference compared to T40, but sweet ginseng extract T70 tended to have a superior inhibitory effect than T40. Analyzing these results based on the component content in Table 1, it was confirmed that ethanol 40% to 99%, which significantly increases the extraction ratio of tansinones and decreases the content of substances such as salvianolic acid, is the optimum solvent concentration.

< Example 4. In an animal model of prostatic hyperplasia Dansam Extract of T Check the effect>

4.1. Testosterone-induced prostatic hyperplasia animal model construction

Sprague-Dawley rats, 9 weeks old (weight less than 350 g), were used in the experiment after acclimatization for more than a week. After removing the testes to induce prostatic hyperplasia, testosterone (Testosterone, dissolved in corn oil) was injected once/three times at a dose of 3 mg/kg, for a total of 10 times (subcutaneous injection).

4.2. In an animal model of prostatic hyperplasia Dansam Checking the effectiveness of the extract

Sprague-Dawley rats aged 9 weeks (weight less than 350 g) were randomly assigned (1) normal group, (2) prostatic hypertrophy induction and vehicle administration group (negative control group), (3) prostatic hypertrophy induction and dansam extract S administration group, (4) ) Induction of prostatic hypertrophy and administration of sweet ginseng extract T70 group, (5) Induction of prostate hypertrophy and administration of sweet ginseng extract T40, (6) Induction of prostate hypertrophy and administration of sweet ginseng extract T10, (7) Induction of prostate hypertrophy and administration of saw palmetto extract group (positive control group , Notification type raw material), (8) prostatic hypertrophy induction and finasteride administration group (positive control group, therapeutic agent). In the prostatic hyperplasia-inducing group, after removing the testes by the method of Example 4.1, dihydro-testosterone (used by dissolving in corn oil) at a dose of 3 mg/kg once/3 days, a total of 10 subcutaneous injections. (subcutaneous injection), and in the case of the normal group, the same amount of corn oil was injected subcutaneously.

Dansam extract T70~T10 and saw palmetto fruit extract were dissolved in distilled water and administered orally at a dose of 10-25 mg/kg once/day for 14 days. The finasteride administration group (sigma, dissolved in 0.2% tween 80) was orally administered at a dose of 10 mg/kg once/day for 14 days. For the negative control group, only distilled water was orally administered. The body weight was measured at the end of the experiment, and the SD-rat was sacrificed with carbon dioxide gas on the next day after the last administration and treatment, the prostate tissue was removed and the weight was measured, and the results are shown in FIGS. 5 to 7 I got it. All animal procedures were reviewed and approved by Konkuk University's Animal Protection Agency and Use Committee.

5 is a graph showing changes in the weight of rats according to treatment with Danseng extract T70 to T10 in an animal model for prostatic hyperplasia. As shown in FIG. 5, there was no significant difference in body weight in the animal model for prostatic hyperplasia (BPH) compared to the control group (Con), and it was confirmed that an animal model for prostatic hyperplasia treated with testosterone was properly established after the testis removal surgery. Here, when the positive controls, cow palmetto (BPH+Saw) and finasteride (BPH+Fi) were administered, there was no significant difference from the control group (Con). Even in the case, there was no significant change in body weight. However, in the case of Dansam extract S, the weight was decreased compared to the control group. As shown in Table 1, Dansam extract S contains at least 15% of salvianolic acid B. According to SHAN GAO et al. (2019), salvianolic acid B has a powerful antioxidant function in cells to inhibit programmed apoptosis initiated by the oxidation state, and many other anti-inflammatory and anti-cancer functions are known. . However, as reported by SHAN GAO et al. (2019), salvianolic acid B has cytotoxicity at a certain concentration, and other anti-cancer functions also use the cytotoxic effect on cancer cells in many cases. The inventors of the present invention interpreted that the extract S of Danseng Seng contains a high concentration of salvianolic acid B, and thus exhibits a certain cytotoxicity in an animal model of prostatic hyperplasia, and this process appears as a weight loss in SD rats. In particular, as shown in Fig. 1 and Table 1, the extract S mainly containing salvianolic acid B increases the 5α-reductase type 2 (5AR2) and prostate-specific antigen (PSA), which are mainly increased in prostatic hyperplasia. As a result, it is considered that salvianolic acid B needs to be removed in order to use Dansam extract for prostatic hyperplasia.

6 is a photograph showing the change in the size of the prostate gland of rats according to treatment with Dansam extract T70 to T10 in an animal model of prostatic hyperplasia. Rat prostate, whose size was increased by BPH treatment, was reduced by treatment with Dansam extract T70~T10. 7 is a graph showing changes in the prostate weight of rats according to treatment with Dansam extract T70 to T10 in an animal model for prostatic hyperplasia, and FIG. 8 is a graph showing changes in Prostate index (prostate weight versus body weight) of each sample. As shown in FIGS. 6 to 8, the extract S of sweet ginseng decreases the weight of the rat as a whole, and the prostate index (prostate weight versus body weight) increased rather than the prostate hyperplasia model (BPH) because it almost did not reduce the size of the prostate gland.

On the other hand, Danseng extract T70 and T40 showed prostate weight and Prostate index similar to that of the control group (Con), and 40% ethanol extract showed almost the same effect as finasteride, a drug mainly used to treat prostatic hyperplasia or male pattern hair loss. I got it. In the case of sweet ginseng extract T10, there was a certain effect on reducing the prostate weight and Prostate index, but did not show a significant difference as in the sweet ginseng extract T70 and T40. It is understood that the content of tansinones, which increases with extraction by increasing the ethanol concentration, tends to decrease and the amount of salvianolic acid B decreases, and it is understood that the extract of Danseng extract extracted from more than 40% ethanol is effective in the inhibition of androgen-related enzymes. .

4.3. In prostate tissue derived from an animal model of hyperplasia Dansam Checking the effectiveness of the extract

Fig. 9 of Dansam extract T40 shows the effect on the expression of prostate hypertrophy-related proteins 5α-reductase (5AR2), androgen receptor (AR), and prostate specific antigen (PSA) in an animal model of prostatic hyperplasia. Confirmed.

The prostate tissue harvested in Example 4.2 was lysed using cold radiation immunoprecipitation assay (RIPA) buffer containing a protease inhibitor cocktail. Lysed cells were centrifuged at 4° C. for 20 minutes at 13,000 RPM, and protein concentration was measured using BSA assay. Cell lysates (30 μg protein/sample) were separated by 10% sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) at 120% for 90 min and transferred to a nitrocellulose membrane. The membrane was blocked with 5% skim milk for 1 hour at room temperature. Immediately after, primary antibodies such as AR, 5AR2, PSA and β-Actin were reacted to the membrane overnight. After washing the membranes they were incubated for 1 hour at room temperature with goat anti-rabbit IgG and anti-mouse IgG horseradish peroxidase (HRP)-conjugated secondary antibodies. Immunodetection was performed using an enhanced chemiluminescence (ECL) detection reagent, and the membrane was photographed using a DaVinch-Chemi imaging system (Davinch-K., Seoul) and is shown in FIG. 9.

As shown in FIG. 9, it was confirmed that 5AR2 and PSA were significantly increased in the prostatic hyperplasia-induced animal model, and expression of proteins in both 5AR2, AR, and PSA was significantly suppressed by 40T of Dansam extract.

10 is a schematic diagram showing the signaling pathway of Testosterone in BPH and the pharmacological mechanism of sweet ginseng extract. The cause of prostatic hyperplasia is not yet clear, but aging, male hormone imbalance (especially dihydrotestosterone, DHT), and metabolic disorders are presumed to be the main causes of prostatic hyperplasia. Saw palmetto fruit extract (health functional food notification type material) and finasteride (prostate hypertrophy treatment) currently in use target male hormones only, but to maximize the therapeutic effect, aging, unbalanced male hormones, and metabolic disorders are combined. There is a need for a strategy that can be improved with. The main tansinone component of the extract of Danshen Extract is a NAD ⁺ -promoting agent that targets the'NQO1' enzyme in the cytoplasm, and at the same time converts NADH, a co-substrate, to NAD+, thereby increasing the concentration of ^{NAD + in vivo.} The NQO1 enzyme is a two-electron reductase of the flavo protein family. It reduces NADH or NADPH as a cofactor and reduces the quinone system to hydroquinone. In general, it removes active oxygen and metabolizes vitamin K. NAD ⁺ - promoting agent (main component tanshinone) intracellular NAD ⁺ is increased by the enable Sirtuin and AMPK and PGC-1α, which may be to increase the amount and functionality of the mitochondrial cell activation at the same time the energy metabolism. In particular, Sirtuin has an anti-aging effect, and AMPK and PGC-1α are proteins that play a key role in improving metabolic diseases, and have the potential to effectively ameliorate'prostatic hypertrophy' caused by'aging, metabolic disease, and male hormone imbalance'. This was expected to be large, and through the above results, it was confirmed that the ethanol extract of 40% or more (40-99%) of the Danseng extract has an excellent effect in the prevention or treatment of prostatic hyperplasia or alopecia.

Claims (12)

1. Dansam (Salvia miltiorrhiza Bunge) composition for the treatment or prevention of prostatic hyperplasia or alopecia, comprising an extract as an active ingredient.
2. The method of claim 1,

   The Salvia miltiorrhiza Bunge (Salvia miltiorrhiza Bunge) extract is a composition for the treatment or prevention of prostatic hypertrophy or alopecia, characterized in that it comprises an extract obtained by extracting Salvia miltiorrhiza Bunge with water, alcohol having 1 to 6 carbon atoms, or a mixed solvent thereof.
3. The method of claim 1,

   The Dansam (Salvia miltiorrhiza Bunge) extract is a composition for the treatment or prevention of prostatic hyperplasia or alopecia, characterized in that 40 to 99% ethanol extract.
4. The method of claim 1,

   The Dansam (Salvia miltiorrhiza Bunge) extract is a composition for the treatment or prevention of prostatic hyperplasia or alopecia, characterized in that it contains 2% to 70% of the total weight of tanshinones.
5. The method of claim 4,

   The tanshinones are Tanshinone1, Tanshinone2a, Cryptotanshinone, 15,16-Dihydrotanshinone, Tanshinoic acid composition for the treatment or prevention of prostatic hypertrophy or alopecia, characterized in that it comprises as an active ingredient at least one of the group consisting of.
6. The method of claim 4,

   The tanshinone is a composition for the treatment or prevention of prostatic hypertrophy or alopecia, characterized in that it contains 15,16-Dihydrotanshinone as an active ingredient.
7. The method of claim 1,

   The Salvia miltiorrhiza Bunge extract is at least one of the group consisting of 5α reductase type 2 (5AR2), prostate specific antigen (PSA), steroid receptor coactivator-1 (SRC-1), and androgen receptor (AR). A composition for the treatment or prevention of prostatic hyperplasia or alopecia, characterized in that reducing protein expression.
8. The method according to any one of claims 1 to 7,

   The Dansam (Salvia miltiorrhiza Bunge) extract,

   Crushing the Dansam from which impurities have been removed (1);

   The step (2) of immersing the crushed Danseng in step (1) in 40-99% ethanol (EtOH) at 50-80°C and leaving for 2 to 24 hours;

   Separating the alcohol from which the ginseng was extracted from the step (2), adding new alcohol to the remaining residue, immersing it in 40 to 99% ethanol (EtOH) at 50 to 80°C, and leaving it for 2 to 12 hours (3);

   Separating the alcohol from which the ginseng was extracted from the step (3), adding new alcohol to the remaining residue, immersing it in 40 to 99% ethanol (EtOH) at 50 to 80°C, and leaving it for 2 to 5 hours (4);

   Collecting the spirits separated in steps (2) to (4), evaporating and drying them at 45 to 75°C (5);

   Treatment of prostatic hyperplasia or alopecia, characterized in that prepared by a method for producing a sweet ginseng extract comprising the step (6) of obtaining a sweet ginseng extract by pulverizing the evaporated and dried solid extract in step (4) and filtering at 80 mesh or more Or a preventive composition.
9. The method of claim 8,

   The step (1) of crushing the Dansam from which the impurities have been removed is characterized by pulverizing the Dansam in a short time at a cryogenic temperature of -196 to -80°C and pulverizing it to 5 mm or less (Cryogenic Micro Grinding Technology, CMGT). A composition for the treatment or prevention of prostatic hyperplasia or alopecia.
10. Dansam (Salvia miltiorrhiza Bunge) extract as an active ingredient for preventing or improving prostatic hypertrophy or alopecia health functional food.
11. The method of claim 10,

    The Salvia miltiorrhiza Bunge (Salvia miltiorrhiza Bunge) extract is a health functional food for preventing or improving prostatic hyperplasia or alopecia, characterized in that it comprises an extract obtained by extracting Salvia miltiorrhiza Bunge with water, alcohol having 1 to 6 carbon atoms, or a mixed solvent thereof.
12. The method of claim 10,

    The alcohol is a composition for the treatment or prevention of prostatic hyperplasia or alopecia, characterized in that 40 to 99% ethanol extract.

Images