WO2021086120A1 - Composition comprenant un extrait de salvia miltiorrhiza bunge comme principe actif pour la prévention ou le traitement de l'hyperplasie bénigne de la prostate ou de l'alopécie - Google Patents

Composition comprenant un extrait de salvia miltiorrhiza bunge comme principe actif pour la prévention ou le traitement de l'hyperplasie bénigne de la prostate ou de l'alopécie Download PDF

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WO2021086120A1
WO2021086120A1 PCT/KR2020/015058 KR2020015058W WO2021086120A1 WO 2021086120 A1 WO2021086120 A1 WO 2021086120A1 KR 2020015058 W KR2020015058 W KR 2020015058W WO 2021086120 A1 WO2021086120 A1 WO 2021086120A1
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extract
alopecia
treatment
dansam
composition
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PCT/KR2020/015058
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English (en)
Korean (ko)
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윤주석
서강식
한정수
김은경
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주식회사 큐롬바이오사이언스
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Priority claimed from KR1020200142540A external-priority patent/KR102462458B1/ko
Application filed by 주식회사 큐롬바이오사이언스 filed Critical 주식회사 큐롬바이오사이언스
Priority to US17/059,984 priority Critical patent/US20210369803A1/en
Priority to EP20810850.6A priority patent/EP3838284A4/fr
Priority to JP2020567509A priority patent/JP7161237B2/ja
Publication of WO2021086120A1 publication Critical patent/WO2021086120A1/fr

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    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/16—Inorganic salts, minerals or trace elements
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
    • A61K31/343—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/24—Heavy metals; Compounds thereof
    • A61K33/30—Zinc; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
    • A61K36/537—Salvia (sage)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/08—Drugs for disorders of the urinary system of the prostate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/14—Drugs for dermatological disorders for baldness or alopecia

Definitions

  • 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 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).
  • LUTS urinary tract symptoms
  • BPH 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).
  • DHT dihydrotestosteron
  • DHT dihydrotestosterone
  • AR androgen receptor
  • PSA specific antigen
  • PCNA proliferative nuclear antigen
  • Bcl-2 which inhibits apoptosis, is also found in the prostate epithelium and leads to proliferation of prostate tissue (Cardillo, M., et al., 1997).
  • DHT dihydrotestosterone
  • Testosterone is converted to dihydrotestosterone (DHT), an active male hormone, by 5 ⁇ -reductase, and the activated dihydrotestosterone binds to the androgen receptor, thereby controlling the protein synthesis of hair follicle cells.
  • DHT dihydrotestosterone
  • the growth period of the hair follicle is shortened, and the hair follicle is contracted, causing hair loss.
  • 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).
  • prostatic hypertrophy treatment which is used as an alpha-1 adrenergic blocker such as terazosin, doxazosin, tamsulasin, alfuzosin, etc.
  • 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 5 ⁇ -reductase inhibitors, are known to be effective in reducing prostate size by inhibiting the conversion of testosterone to dihydrotestosterone (DHT), an active metabolite by 5 ⁇ -reductase, and used for BPH and alopecia.
  • DHT dihydrotestosterone
  • these drugs are known to cause side effects such as erectile dysfunction, decreased libido, and decreased semen volume in ejaculation.
  • side effects such as erectile dysfunction, decreased libido, and decreased semen volume in ejaculation.
  • prostatic hyperplasia is one of the persistent aging phenomena, and there is a problem that fundamental treatment is difficult.
  • Salvia Sudiorrhiza Bunge
  • Danseng 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.
  • 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
  • Korean Patent Publication No. 2001-0076810 discloses a method for preparing a composition for treating prostate disease and hemorrhoids.
  • composition according to the manufacturing method such as Hojanggeun, Machihyeon, Ikjiin, Chajeon, Pogongyeong, Geumeunhwa, Yongdamcho, Rhubarb, Gyenaegum, Somok, Mokgwa, Che choireonja, 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.
  • 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.
  • 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.
  • Cinnamomi cortex (Cinnamomum verum) suppresses testosterone-induced benign prostatic hyperplasia by regulating 5 ⁇ -reductase. Sci. Rep. 2016, 6, 31906-31917.
  • 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.
  • 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°C using the microwave drying method.
  • 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.
  • 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.
  • CMGT cryogenic Micro Grinding Technology
  • 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.
  • methods such as cold air drying, hot air drying, freeze drying, far infrared drying, sound drying, and vacuum drying may be used.
  • Dansam S. miltiorrhza
  • 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 ⁇ g / ml.
  • Danseng S. miltiorrhiza Bunge
  • Danseng (S. miltiorrhiza Bunge) extract may contain tanshinones 2% to 70% of the total weight.
  • 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
  • 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.
  • 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.
  • injectable ester such as ethyl oleate
  • 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 5 ⁇ 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,
  • 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;
  • 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.
  • 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.
  • tanshinones such as tanshinone1, tanshinone2a, cryptotanshinone, dihydrotashinone or tanshinoic acid
  • 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.
  • 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.
  • 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.
  • 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. .
  • 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.
  • 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%)
  • Tanshinone1 (Tan1), Tanshinone2a (Tan2a), Cryptotanshinone (CryT) and Dihydrotanshinone (DihT) 5 ⁇ reductase type 2 (5 ⁇ 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.
  • FIG. 2 is a graph showing quantification of each protein of FIG. 1.
  • FIG. 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.
  • AR androgen receptor
  • PSA prostate specific antigen
  • FIG. 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.
  • FIG. 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.
  • FIG. 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.
  • FIG. 10 is a schematic diagram showing the signaling pathway of Testosterone in BPH and the pharmacological mechanism of sweet ginseng extract.
  • BPH Prostatic hyperplasia
  • DHT Dihydrotestosterone
  • 5AR2 5 ⁇ reductase type 2
  • PSA prostate specific antigen
  • 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.
  • CMGT cryogenic Micro Grinding Technology
  • CMGT cryogenic MicroGrinding Technology
  • CMGT 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.
  • 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.
  • CMGT Cryogenic Micro Grinding Technology
  • Dansam extract T was extracted from the crushed Dansam root with alcohol (EtOH) at 50 ⁇ 80 °C (sweet ginseng extract T).
  • T10 EtOH10%)
  • T40 EtOH40%
  • T70 EtOH70%)
  • T95 EtOH95%)
  • T99 EtOH99%
  • 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.
  • tansinones 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.
  • 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.
  • animal cells were cultured.
  • 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.
  • 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 ⁇ -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).
  • 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 ⁇ g/ml, Tanshinone1, Tanshinone2a, Cryptotanshinone and 15,16-Dihydrotanshinone at a concentration of 5 ⁇ M, respectively, for 24 hours.
  • Harvested LNCaP cells were lysed using cold radiation immunoprecipitation assay (RIPA) buffer containing a protease inhibitor cocktail.
  • RIPA cold radiation immunoprecipitation assay
  • 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 ⁇ g 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.
  • SDS-PAGE sodium dodecyl sulfate-polyacrylamide gel electrophoresis
  • the LNCaP cell line increased the expression level of androgen-related proteins excluding the androgen receptor (AR) by DHT.
  • the expression of SRC-1 increased by DHT was somewhat reduced, and the expression level of androgen receptor (AR) was reduced by 40%.
  • the expression was rather increased.
  • Dansam extract T protein expression of all 5 ⁇ reductase type 2 (5AR2), prostate-specific antigen (PSA), steroid receptor co-activator-1 (SRC-1) and androgen receptor (AR) was significantly reduced. .
  • Dansam extract T suppressed the expression of 5 ⁇ reductase type 2 (5AR2), prostate specific antigen (PSA), and androgen receptor (AR) to a lower level than that of the control group.
  • 15 ⁇ g / ml treatment of Dansam extract T inhibited the expression of androgen-related proteins more effectively than 15,16-Dihydrotanshinone.
  • the content of individual tansinone of 15 ⁇ g/ml of danseng extract T was converted based on the results of Table 1 and shown in Table 2.
  • Tanshinones 1.42 ⁇ g/ml
  • tanshinones are included in the Danseng extract T at 3.33 ⁇ g/ml, and the content of 15,16-Dihydrotanshinone, which has the best inhibitory effect of androgen-related proteins, is only 0.26 ⁇ g/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.
  • AR androgen receptor
  • Prostate PSA prostate specific antigen
  • 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.
  • 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.
  • 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).
  • Sprague-Dawley rats aged 9 weeks 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).
  • 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.
  • FIG. 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.
  • BPH body weight in the animal model for prostatic hyperplasia
  • Con control group
  • BPH+Saw cow palmetto
  • BPH+Fi finasteride
  • Dansam extract S contains at least 15% of salvianolic acid B.
  • 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.
  • 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.
  • the extract S mainly containing salvianolic acid B increases the 5 ⁇ -reductase type 2 (5AR2) and prostate-specific antigen (PSA), which are mainly increased in prostatic hyperplasia.
  • 5AR2 5 ⁇ -reductase type 2
  • PSA prostate-specific antigen
  • FIGS. 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
  • FIG. 8 is a graph showing changes in Prostate index (prostate weight versus body weight) of each sample. As shown in FIGS.
  • 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.
  • 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.
  • 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.
  • Fig. 9 of Dansam extract T40 shows the effect on the expression of prostate hypertrophy-related proteins 5 ⁇ -reductase (5AR2), androgen receptor (AR), and prostate specific antigen (PSA) in an animal model of prostatic hyperplasia. Confirmed.
  • 5AR2 prostate hypertrophy-related proteins 5 ⁇ -reductase
  • AR androgen receptor
  • PSA prostate specific antigen
  • Example 4.2 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 ⁇ g 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 ⁇ -Actin were reacted to the membrane overnight.
  • RIPA cold radiation immunoprecipitation assay
  • FIG. 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-1 ⁇ , which may be to increase the amount and functionality of the mitochondrial cell activation at the same time the energy metabolism.
  • Sirtuin has an anti-aging effect
  • AMPK and PGC-1 ⁇ 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.

Abstract

La présente invention concerne une composition comprenant un extrait de Salvia miltiorrhiza Bunge comme principe actif pour le traitement ou la prévention de l'hyperplasie bénigne de la prostate ou de l'alopécie. L'extrait de Salvia miltiorrhiza Bunge contient 2 à 70 % de tanshinonones comprenant les tanshinone1, tanshinone2a, cryptotanshinone et dihydrotanshinone, et peut être utilisé pour fournir une composition pharmaceutique et un aliment fonctionnel pour la santé pour le traitement et la prévention de l'alopécie et de l'hyperplasie bénigne de la prostate.
PCT/KR2020/015058 2019-10-31 2020-10-30 Composition comprenant un extrait de salvia miltiorrhiza bunge comme principe actif pour la prévention ou le traitement de l'hyperplasie bénigne de la prostate ou de l'alopécie WO2021086120A1 (fr)

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US17/059,984 US20210369803A1 (en) 2019-10-31 2020-10-30 Composition containing salvia miltiorrhiza bunge extract as active ingredient for treatment or prevention of benign prostatic hyperplasia or alopecia
EP20810850.6A EP3838284A4 (fr) 2019-10-31 2020-10-30 Composition comprenant un extrait de salvia miltiorrhiza bunge comme principe actif pour la prévention ou le traitement de l'hyperplasie bénigne de la prostate ou de l'alopécie
JP2020567509A JP7161237B2 (ja) 2019-10-31 2020-10-30 丹参（Ｓａｌｖｉａ ｍｉｌｔｉｏｒｒｈｉｚａ Ｂｕｎｇｅ）抽出物を有効成分として含む前立腺肥大症又は脱毛症の治療又は予防用組成物

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KR10-2020-0049163 2020-04-23
KR1020200142540A KR102462458B1 (ko) 2019-10-31 2020-10-29 단삼(Salvia miltiorrhiza Bunge) 추출물을 유효성분으로 포함하는 전립선비대증 또는 탈모증의 치료 또는 예방용 조성물
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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113350479A (zh) * 2021-06-24 2021-09-07 芭纹连锁管理(深圳)有限公司 一种去除疤痕的药膏及其制备方法

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5234698A (en) * 1988-07-05 1993-08-10 Fahim Mostafa S Intraprostatic injection of zinc ions for treatment of inflammatory conditions and benign and malignant tumors of the prostate
KR100259037B1 (ko) 1998-04-01 2000-07-01 박효석 발모촉진용 외용액제
KR20010076810A (ko) 2000-01-28 2001-08-16 문성수 전립선 질환 및 치질 치료용 조성물의 제조방법 및 그제조방법에 의한 조성물
KR100818586B1 (ko) * 2003-12-30 2008-04-01 주식회사 케이티앤지 대사활성을 촉진시키는 탄시논 유도체를 유효성분으로함유하는 비만 및 대사증후군 치료제
KR20120020639A (ko) 2010-08-30 2012-03-08 주식회사한국전통의학연구소 단삼을 포함하는 전립선암 치료용 조성물
KR20120053248A (ko) * 2010-11-17 2012-05-25 경희대학교 산학협력단 탄시논 ⅱａ의 신규 용도
KR20180055945A (ko) * 2016-11-16 2018-05-28 영진약품 주식회사 간기능 개선용 단삼 추출물을 포함하는 조성물 및 그 제조방법
KR20190049467A (ko) * 2017-10-31 2019-05-09 주식회사 휴엔 단삼 추출물을 함유하는 내장지방형 비만 예방, 개선 또는 치료 조성물

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5234698A (en) * 1988-07-05 1993-08-10 Fahim Mostafa S Intraprostatic injection of zinc ions for treatment of inflammatory conditions and benign and malignant tumors of the prostate
KR100259037B1 (ko) 1998-04-01 2000-07-01 박효석 발모촉진용 외용액제
KR20010076810A (ko) 2000-01-28 2001-08-16 문성수 전립선 질환 및 치질 치료용 조성물의 제조방법 및 그제조방법에 의한 조성물
KR100818586B1 (ko) * 2003-12-30 2008-04-01 주식회사 케이티앤지 대사활성을 촉진시키는 탄시논 유도체를 유효성분으로함유하는 비만 및 대사증후군 치료제
KR20120020639A (ko) 2010-08-30 2012-03-08 주식회사한국전통의학연구소 단삼을 포함하는 전립선암 치료용 조성물
KR20120053248A (ko) * 2010-11-17 2012-05-25 경희대학교 산학협력단 탄시논 ⅱａ의 신규 용도
KR20180055945A (ko) * 2016-11-16 2018-05-28 영진약품 주식회사 간기능 개선용 단삼 추출물을 포함하는 조성물 및 그 제조방법
KR20190049467A (ko) * 2017-10-31 2019-05-09 주식회사 휴엔 단삼 추출물을 함유하는 내장지방형 비만 예방, 개선 또는 치료 조성물

Non-Patent Citations (12)

* Cited by examiner, † Cited by third party
Title
BERRY, S.J.COFFEY, D.S.WALSH, P.C.EWING, L.L.: "The development of human benign prostatic hyperplasia with age", J. UROL., vol. 132, 1984, pages 474 - 479
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., vol. 158, 1997, pages 212 - 216, XP005568088, DOI: 10.1097/00005392-199707000-00073
CHEN, Y.ROBLES, A.I.MARTINEZ, L.A.LIU, F.GIMENEZ-CONTI, I.B.CONTI, C.J.: "Expression of Gl cyclins, cyclin-dependent kinases, and cyclin-dependent kinase inhibitors in androgen-induced prostate proliferation in castrated rats", CELL GROWTH DIFFER, vol. 7, 1996, pages 1571 - 1578
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 5a-reductase", SCI. REP., vol. 6, 2016, pages 31906 - 31917
DENNIS A. HOLTMARK A. LEVYHYE JA OHJILL M. ERBJULIE I.HEASLIPMARTIN BRANDTHSUAN YIN LAN-HARGESTBRIAN W. METCALF: "Inhibition of steroid 5.alpha.-reductase by unsaturated 3-carboxy steroids", J. MED. CHEM., vol. 333, 1990, pages 943 - 950
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., vol. 15, 2015, pages 380 - 386
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., vol. 163, 2000, pages 1451 - 1456, XP005555426, DOI: 10.1016/S0022-5347(05)67641-0
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., vol. 218, 2018, pages 109 - 115
SARMA, A.V.WEI, J.T.: "Clinical practice. Benign prostatic hyperplasia and lower urinary tract symptoms", N. ENGL. J. MED., vol. 367, 2012, pages 248 - 257
SHAN GAOSHIQIN LIQIN LIFUYONG ZHANGMENGQI SUNZILIN WANSHURONG 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, vol. 44, 2019, pages 457 - 468
WANG CHAO; DU XIAOLING; YANG RUI; LIU JIE; XU DA; SHI JIANDANG; CHEN LINFENG; SHAO RUI; FAN GUANWEI; GAO XIUMEI; TIAN GUO; ZHU YAN: "The prevention and treatment effects of tanshinone IIA on oestrogen/androgen-induced benign prostatic hyperplasia in rats", JOURNAL OF STEROID BIOCHEMISTRY & MOLECULAR BIOLOGY, ELSEVIER SCIENCE LTD., OXFORD., GB, vol. 145, 5 October 2014 (2014-10-05), GB, pages 28 - 37, XP029112266, ISSN: 0960-0760, DOI: 10.1016/j.jsbmb.2014.09.026 *
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, vol. 61, 2004, pages 60 - 72

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113350479A (zh) * 2021-06-24 2021-09-07 芭纹连锁管理(深圳)有限公司 一种去除疤痕的药膏及其制备方法

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