KR20130049569A - Food additive comprising poncirin showing an inhibition effect of osteoclastogenesis - Google Patents
Food additive comprising poncirin showing an inhibition effect of osteoclastogenesis Download PDFInfo
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- KR20130049569A KR20130049569A KR1020110114666A KR20110114666A KR20130049569A KR 20130049569 A KR20130049569 A KR 20130049569A KR 1020110114666 A KR1020110114666 A KR 1020110114666A KR 20110114666 A KR20110114666 A KR 20110114666A KR 20130049569 A KR20130049569 A KR 20130049569A
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- poncirin
- disease
- bone
- food
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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
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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
- A23L19/00—Products from fruits or vegetables; Preparation or treatment thereof
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
- A23V2200/306—Foods, ingredients or supplements having a functional effect on health having an effect on bone mass, e.g. osteoporosis prevention
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2300/00—Processes
- A23V2300/14—Extraction
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Abstract
Description
본 발명은 폰시린을 유효성분으로 함유하는 파골세포 활성 억제 효과를 가지는 식품첨가제에 관한 것이다.The present invention relates to a food additive having an osteoclast activity inhibitory effect containing ponsyrin as an active ingredient.
1. Kumamoto H, Ooya K. ExpreASion of parathyroid hormone-related protein (PTHrP), osteoclast differentiation factor (ODF)/receptor activator of nuclear factor-kappaB ligand (RANKL) and osteoclastogenesis inhibitory factor (OCIF)/osteoprotegerin (OPG) in ameloblastomas. J Oral Pathol Med. 2004 ; 33(1): 46-52.Kumamoto H, Ooya K. ExpreASion of parathyroid hormone-related protein (PTHrP), osteoclast differentiation factor (ODF) / receptor activator of nuclear factor-kappaB ligand (RANKL) and osteoclastogenesis inhibitory factor (OCIF) / osteoprotegerin (OPG) in ameloblastomas. J Oral Pathol Med. 2004; 33 (1): 46-52.
2. Reddy SV. Regulatory mechanisms operative in osteoclasts. Crit Rev Eukaryot Gene Expr. 2004; 14(4): 255-70.2. Reddy SV. Regulatory mechanisms operative in osteoclasts. Crit Rev Eukaryot Gene Expr. 2004; 14 (4): 255-70.
3. Pang M, Martinez AF, Fernandez I, Balkan W, Troen BR. AP-1 stimulates the cathepsin K promoter in RAW 264.7 cells. Gene. 2007;403(1-2):151-8.3.Pang M, Martinez AF, Fernandez I, Balkan W, Troen BR. AP-1 stimulates the cathepsin K promoter in RAW 264.7 cells. Gene. 2007; 403 (1-2): 151-8.
4. Boyce BF, Yamashita T, Yao Z, Zhang Q, Li F, Xing L. Roles for NF-kappaB and c-Fos in osteoclasts. J Bone Miner Metab. 2005; 23 Suppl: 11-5. Boyce BF, Yamashita T, Yao Z, Zhang Q, Li F, Xing L. Roles for NF-kappa B and c-Fos in osteoclasts. J Bone Miner Metab. 2005; 23 Suppl: 11-5.
5. Khosla S. Minireview: the OPG/RANKL/RANK system. Endocrinology. 2001; 142(12):5050-5.Khosla S. Minireview: the OPG / RANKL / RANK system. Endocrinology. 2001; 142 (12): 5050-5.
6. Han SY, Lee NK, Kim KH, Jang IW, Yim M, Kim JH, Lee WJ, Lee SY. Transcriptional induction of cyclooxygenase-2 in osteoclast precursors is involved in RANKL-induced osteoclastogenesis. Blood. 2005;106(4):1240-5.6.Han SY, Lee NK, Kim KH, Jang IW, Yim M, Kim JH, Lee WJ, Lee SY. Transcriptional induction of cyclooxygenase-2 in osteoclast precursors is involved in RANKL-induced osteoclastogenesis. Blood. 2005; 106 (4): 1240-5.
7. Zheng H, Yu X, Collin-Osdoby P, Osdoby P. RANKL stimulates inducible nitric-oxide synthase expression and nitric oxide production in developing osteoclasts. An autocrine negative feedback mechanism triggered by RANKL-induced interferon-beta via NF-kappaB that restrains osteoclastogenesis and bone resorption. J Biol Chem. 2006; 281(23): 15809-20.7. Zheng H, Yu X, Collin-Osdoby P, Osdoby P. RANKL stimulates inducible nitric-oxide synthase expression and nitric oxide production in developing osteoclasts. An autocrine negative feedback mechanism triggered by RANKL-induced interferon-beta via NF-kappaB that restrains osteoclastogenesis and bone resorption. J Biol Chem. 2006; 281 (23): 15809-20.
8. Murakami A, Song M, Ohigashi H. Phenethyl isothiocyanate suppresses receptor activator of NF-kappaB ligand (RANKL)-induced osteoclastogenesis by blocking activation of ERK1/2 and p38 MAPK in RAW264.7 macrophages. Biofactors. 2007;30(1):1-11.Murakami A, Song M, Ohigashi H. Phenethyl isothiocyanate suppresses receptor activator of NF-kappaB ligand (RANKL) -induced osteoclastogenesis by blocking activation of ERK1 / 2 and p38 MAPK in RAW264.7 macrophages. Biofactors. 2007; 30 (1): 1-11.
9. Liu XH, Kirschenbaum A, Yao S, Levine AC. Interactive effect of interleukin-6 and prostaglandin E2 on osteoclastogenesis via the OPG/RANKL/RANK system. Ann N Y Acad Sci. 2006; 1068:225-33.9. Liu XH, Kirschenbaum A, Yao S, Levine AC. Interactive effect of interleukin-6 and prostaglandin E2 on osteoclastogenesis via the OPG / RANKL / RANK system. Ann N Y Acad Sci. 2006; 1068: 225-33.
10. Rajkumar S, Jebanesan A. Bioactivity of flavonoid compounds from Poncirus trifoliata L. (Family: Rutaceae) against the dengue vector, Aedes aegypti L. (Diptera: Culicidae). Parasitol Res. 2008;104(1):19-2510. Rajkumar S, Jebanesan A. Bioactivity of flavonoid compounds from Poncirus trifoliata L. (Family: Rutaceae) against the dengue vector, Aedes aegypti L. (Diptera: Culicidae). Parasitol Res. 2008; 104 (1): 19-25
11. Kim JB, Han AR, Park EY, Kim JY, Cho W, Lee J, Seo EK, Lee KT. nhibition of LPS-induced iNOS, COX-2 and cytokines expression by poncirin through the NF-kappaB inactivation in RAW 264.7 macrophage cells. Biol Pharm Bull. 2007; 30(12):2345-51.11.Kim JB, Han AR, Park EY, Kim JY, Cho W, Lee J, Seo EK, Lee KT. nhibition of LPS-induced iNOS, COX-2 and cytokines expression by poncirin through the NF-kappaB inactivation in RAW 264.7 macrophage cells. Biol Pharm Bull. 2007; 30 (12): 2345-51.
12. Lee JH, Lee SH, Kim YS, Jeong CS. Protective effects of neohesperidin and poncirin isolated from the fruits of Poncirus trifoliata on potential gastric disease. Phytother Res. 2009 ; 23(12):1748-53.12.Lee JH, Lee SH, Kim YS, Jeong CS. Protective effects of neohesperidin and poncirin isolated from the fruits of Poncirus trifoliata on potential gastric disease. Phytother Res. 2009; 23 (12): 1748-53.
13. Choi HJ, Park YR, Nepal M, Choi BY, Cho NP, Choi SH, Heo SR, Kim HS, Yang MS, Soh Y. Inhibition of osteoclastogenic differentiation by Ikarisoside A in RAW 264.7 cells via JNK and NF-kappaB signaling pathways. Eur J Pharmacol. 2010;636(1-3):28-35.13.H Choi HJ, Park YR, Nepal M, Choi BY, Cho NP, Choi SH, Heo SR, Kim HS, Yang MS, Soh Y. Inhibition of osteoclastogenic differentiation by Ikarisoside A in RAW 264.7 cells via JNK and NF-kappaB signaling pathways. Eur J Pharmacol. 2010; 636 (1-3): 28-35.
14. 한국 특허등록번호(일자) 1008247040000 (20080417) 14. Korean patent registration number (date) 1008247040000 (20080417)
15. 한국 특허등록번호(일자) 1003228760000 (20020118)15. Korea Patent Registration Number (Date) 1003228760000 (20020118)
골 대사는 골 형성을 담당하는 조골세포와 골 흡수를 담당하는 파골세포의 작용으로 이루어져 있으며, 이들 세포의 기능이 균형을 이루어 항상성을 유지한다. 그러나, 조골세포 활성이 저하되거나 파골세포 활성이 증가되면 골밀도가 감소하여 골다공증이 유발될 수 있다. 골다공증의 유발 요인으로는 여성의 폐경, 갑상선 기능항진, 당뇨병, 스트레스, 흡연 및 운동 부족, 신체적 노화와 glucocorticoid 계열 약물의 복용 등이 알려져 있다(1-3).Bone metabolism is composed of osteoblasts responsible for bone formation and osteoclasts responsible for bone resorption, and the function of these cells is balanced to maintain homeostasis. However, when osteoblast activity decreases or osteoclast activity increases, bone density decreases and osteoporosis may be induced. Factors causing osteoporosis include menopause, hyperthyroidism, diabetes, stress, lack of smoking and exercise, physical aging, and the use of glucocorticoid drugs in women (1-3).
파골세포는 대식세포 계열의 전구세포에서 다양한 분화유발인자들에 의해 분화된다(4-5). 특히, 조골세포로부터 분비되는 RANKL(receptor activator of nuclear factor kappa B ligand)은 파골전구세포 및 파골세포 표면에 존재하는 RANK(receptor activator of nuclear factor kappa B)와 결합하여 파골전구세포가 파골세포로의 분화와 활성화를 유발한다(6). 분화한 파골세포는 NF-B, c-Fos, c-jun, AP-1, NFATc1의 활성화와 MAPK, ERK, JNK, p38 활성화 과정, Src, Akt 활성화등을 통하여 TRAP (tartarate resistant acid phosphatase) cathepsin K, calcitonin receptor 등 파골세포 특이 단백질 발현을 촉진한다(7-9). Osteoclasts are differentiated by various differentiation-causing factors in macrophage progenitor cells (4-5). In particular, RANKL (receptor activator of nuclear factor kappa B ligand) secreted from osteoblasts binds to osteoclast precursor cells and RANK (receptor activator of nuclear factor kappa B) present on the surface of osteoclasts. Causes differentiation and activation (6). Differentiated osteoclasts catarsin TRAP (tartarate resistant acid phosphatase) through activation of NF-B, c-Fos, c-jun, AP-1, NFATc1, MAPK, ERK, JNK, p38 activation process, Src, Akt activation It promotes the expression of osteoclast specific proteins such as K and calcitonin receptor (7-9).
폰시린(Poncirin)은 지실의 주성분으로 알려져 있으며(10), 약리학적으로 항염증 효과(11)와 항위궤양 효과(12) 등이 보고되었다. Poncirin is known as the main component of the chamber (10), and pharmacologically reported anti-inflammatory effects (11) and anti-gastric ulcer effects (12).
이에 본 발명자들은 폰시린(Poncirin) 의 파골세포 분화 억제 효과, 파골세포 분화 및 증식 관련 인자인 TRAP, Cathepsin K, MMP-9 발현억제, NFATc1 등의 유전자 발현 억제 효과를 확인함으로써 본 발명을 완성하게 되었다.
Accordingly, the present inventors have completed the present invention by confirming the effect of inhibiting osteoclast differentiation of poncirin, gene expression inhibitory factors such as TRAP, Cathepsin K, MMP-9 expression, NFATc1, etc. It became.
상기 목적을 달성하기 위하여, 본 발명은 파골세포 억제효능을 나타내는 폰시린(Poncirin)을 유효성분으로 함유하는 골관절질환 예방 및 개선용 식품첨가제을 제공한다.
In order to achieve the above object, the present invention provides a food additive for the prevention and improvement of bone joint disease, which contains a fossil (Poncirin) showing an osteoclast inhibitory effect as an active ingredient.
본원에서 정의되는 상기 골 대사성 질환은 골다공증(osteoprosis), 파제트병(paget disease), 치주질환(periodontal disease), 골전이암(metastatic cancer) 또는 류마티스 관절염(rheumatoid arthiritis), 바람직하게는 골다공증을 포함하는 것을 특징으로 한다.
The bone metabolic disease as defined herein includes osteoprosis, paget disease, periodontal disease, metastatic cancer or rheumatoid arthiritis, preferably osteoporosis. Characterized in that.
이하 본 발명의 화합물은 사용으로 구입가능하나 하기와 같이 식물추출물로부터 분리가능하다.The compounds of the present invention are commercially available but can be separated from plant extracts as follows.
예를 들어, 본 발명의 화합물 및 추출물은 지실을 세척 및 건조시킨 후, 시료 중량의 약 1배 내지 100배, 바람직하게는 약 1배 내지 50배 (w/v) 부피의 물, C1 내지 C4의 저급 알코올 또는 이들의 혼합용매로, 바람직하게는 물 또는 물 및 에탄올을 추출용매로 하여, 약 10 내지 120, 바람직하게는 30 내지 90의 반응온도에서 약 2시간 내지 7일간, 바람직하게는 12 시간 내지 26시간 동안 가열추출법, 초음파 추출법, 환류 추출법, 초고압추출법 등의 통상적인 추출방법, 바람직하게는 환류 추출법으로 1 내지 10회, 바람직하게는 1 내지 5회 반복 추출하는 제 2단계; 상기 단계에서 수득한 추출액을 여과하여 감압 농축하는 제 3단계; 상기 농축된 추출물을 동결 건조하는 제 4단계의 제조방법을 포함하는 단계를 통하여 본 발명의 지실 추출물을 얻고 이를 실리카겔 컬럼크로마토그래피법 또는 세파덱스 컬럼 크로마토그래피법 등의 정제공정을 수회 반복하여 본 발명의 화합물을 수득가능하다. For example, the compounds and extracts of the present invention, after washing and drying the fruiting chamber, have a volume of water of about 1 to 100 times the sample weight, preferably about 1 to 50 times (w / v), C 1 to Lower alcohol of C 4 or a mixed solvent thereof, preferably water or water and ethanol as an extraction solvent, about 2 to 7 days at a reaction temperature of about 10 to 120, preferably 30 to 90, preferably The second step of extracting 1 to 10 times, preferably 1 to 5 times by a conventional extraction method, such as heating extraction, ultrasonic extraction, reflux extraction, ultra-high pressure extraction method for 12 to 26 hours, preferably reflux extraction; A third step of filtering and extracting the extract obtained in the above step under reduced pressure; The fruit extract of the present invention is obtained through a step including a method of preparing the freeze-dried extract of the concentrated extract, and the purification process such as silica gel column chromatography or Sephadex column chromatography is repeated several times. Compounds of
또한 본 발명은 상기 제조방법 및 상기 제조방법으로 제조된 폰시린을 유효성분으로 함유하는 골 대사성 질환의 치료 및 예방을 위한 약학 조성물, 건강기능식품, 또는 식품첨가제를 제공한다. In another aspect, the present invention provides a pharmaceutical composition, health functional food, or food additives for the treatment and prevention of bone metabolic diseases containing the preparation method and the ponsyrin prepared by the production method as an active ingredient.
본 발명에 의한 폰시린은 파골세포 분화 억제 효과, 파골세포 분화 및 증식 관련 인자인 TRAP, Cathepsin K, MMP-9, NFATc1 등의 유전자 발현 억제 효과를 나타내므로, 파골세포 억제용 약학 조성물, 건강기능식품 또는 식품첨가제로서 유용함을 확인하였다.Poncirine according to the present invention shows an inhibitory effect on osteoclast differentiation, osteoclast differentiation and proliferation-related factors such as TRAP, Cathepsin K, MMP-9, NFATc1, etc. It has been found to be useful as a food or food additive.
본 발명의 화합물 및 추출물은, 화합물 및 추출물 총 중량에 대하여 상기 생약 추출물을 0.01 내지 99% 중량으로 포함한다.The compounds and extracts of the present invention comprise 0.01 to 99% by weight of the herbal extracts relative to the total weight of the compounds and extracts.
그러나 상기와 같은 조성은 반드시 이에 한정되는 것은 아니고, 환자의 상태 및 질환의 종류 및 진행 정도에 따라 변할 수 있다.However, the composition is not limited thereto, and may vary depending on the condition of the patient, the type of disease, and the progress of the disease.
본 발명의 화합물 및 추출물을 포함하는 조성물은 약학 조성물의 제조에 통상적으로 사용하는 적절한 담체, 부형제 및 희석제를 더 포함할 수 있다.
Compositions comprising compounds and extracts of the present invention may further comprise suitable carriers, excipients and diluents commonly used in the manufacture of pharmaceutical compositions.
본 발명에 따른 화합물 및 추출물을 포함하는 조성물은, 각각 통상의 방법에 따라 산제, 과립제, 정제, 캡슐제, 현탁액, 에멀젼, 시럽, 에어로졸 등의 경구형 제형, 외용제, 좌제 및 멸균 주사용액의 형태로 제형화하여 사용될 수 있으며, 이에 포함될 수 있는 담체, 부형제 및 희석제로는 락토즈, 덱스트로즈, 수크로스, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로즈, 메틸 셀룰로즈, 미정질 셀룰로스, 폴리비닐 피롤리돈, 물, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 마그네슘 스테아레이트 및 광물유를 들 수 있다. 제제화할 경우에는 보통 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 조제된다. 경구투여를 위한 고형제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 이러한 고형제제는 상기 화합물에 적어도 하나 이상의 부형제 적어도 면, 전분, 칼슘카보네이트(calcium carbonate), 수크로스(sucrose) 또는 락토오스(lactose), 젤라틴 등을 섞어 조제된다. 또한 단순한 부형제 이외에 마그네슘 스티레이트 탈크 같은 윤활제들도 사용된다. 경구를 위한 액상제제로는 현탁제, 내용액제, 유제, 시럽제 등이 해당되는데 흔히 사용되는 단순희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다. 비경구 투여를 위한 제제에는 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조제제, 좌제가 포함된다. 비수성용제, 현탁제로는 프로필렌글리콜(propylene glycol), 폴리에틸렌 글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다. 좌제의 기제로는 위텝솔(witepsol), 마크로골, 트윈(tween) 61, 카카오지, 라우린지, 글리세로제라틴 등이 사용될 수 있다.Compositions comprising compounds and extracts according to the invention are in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols and the like, oral preparations, suppositories and sterile injectable solutions, respectively, according to conventional methods. Carriers, excipients and diluents that may be included in the formulation include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate , Calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, magnesium stearate and mineral oil. In the case of formulation, a diluent or excipient such as a filler, an extender, a binder, a wetting agent, a disintegrant, or a surfactant is usually used. Solid formulations for oral administration include tablets, pills, powders, granules, capsules and the like, which may contain at least one excipient, such as starch, calcium carbonate, sucrose, Or lactose, gelatin, and the like. In addition to simple excipients, lubricants such as magnesium stearate talc are also used. Examples of the liquid preparation for oral use include suspensions, solutions, emulsions, and syrups. In addition to water and liquid paraffin, simple diluents commonly used, various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like may be included . Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. Examples of the suspending agent include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like. As the base of the suppository, witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used.
본 발명의 추출물의 바람직한 투여량은 환자의 상태 및 체중, 질병의 정도, 약물형태, 투여경로 및 기간에 따라 다르지만, 당업자에 의해 적절하게 선택될 수 있다. 그러나 바람직한 효과를 위해서, 화합물 및 추출물은 1일 0.01 mg/kg 내지 10 g/kg으로, 바람직하게는 1 mg/kg 내지 1 g/kg으로 투여하는 것이 좋다. 투여는 하루에 한번 투여할 수도 있고, 수회 나누어 투여할 수 있다. 그러므로 상기 투여량은 어떠한 면으로든 본 발명의 범위를 한정하는 것은 아니다.Preferred dosages of the extracts of the present invention vary depending on the condition and weight of the patient, the extent of the disease, the form of the drug, the route of administration and the duration, and may be appropriately selected by those skilled in the art. However, for the desired effect, the compound and extract is preferably administered at 0.01 mg / kg to 10 g / kg, preferably 1 mg / kg to 1 g / kg per day. The administration may be carried out once a day or divided into several doses. Therefore, the dose is not intended to limit the scope of the present invention in any aspect.
본 발명의 화합물 및 추출물은 쥐, 생쥐, 가축, 인간 등의 포유동물에 다양한 경로로 투여될 수 있다. 투여의 모든 방식은 예상될 수 있는데, 예를 들면, 경구 및 직장, 또는 정맥등의 방법을 통하여 투여 할 수 있다. The compounds and extracts of the present invention can be administered to mammals such as mice, mice, livestock, humans, etc. by various routes. All modes of administration can be expected, for example by oral and rectal or intravenous methods.
또한 본 발명은 폰시린을 유효성분으로 함유하는 골 대사성 질환의 개선 및 예방을 위한 건강기능식품을 제공한다. In another aspect, the present invention provides a health functional food for the improvement and prevention of bone metabolic diseases containing ponsyrin as an active ingredient.
본 발명의 폰시린을 유효성분으로 포함하는 건강기능식품은 골 대사성 질환의 예방 및 개선을 위한 약제, 식품 및 음료 등에 다양하게 이용될 수 있다. 본 발명의 화합물 및 추출물을 첨가할 수 있는 식품으로는, 예를 들어, 각종 식품류, 음료, 껌, 차, 비타민 복합제, 침출차, 건강보조 식품류 등이 있고, 분말, 과립, 정제, 캡슐 또는 음료인 형태로 사용할 수 있다.Health functional foods containing phonicrin of the present invention as an active ingredient can be used in various ways, such as drugs, foods and beverages for the prevention and improvement of bone metabolic diseases. Foods to which the compounds and extracts of the present invention may be added include, for example, various foods, beverages, gums, teas, vitamin complexes, leach teas, health supplements, and the like, and are powders, granules, tablets, capsules or beverages. Available in form.
따라서 또한, 본 발명은 골 대사성 질환의 예방 및 개선 효과를 갖는 폰시린을 유효성분으로 함유하는 식품 또는 식품첨가제를 제공한다.Therefore, the present invention also provides a food or food additive containing ponsyrin as an active ingredient having an effect of preventing and improving bone metabolic diseases.
본 발명의 화합물 및 추출물을 첨가 가능한 식품형태는 캔디류의 각종 식품류, 음료, 껌, 차, 비타민 복합제, 또는 건강보조 식품류인 식품 등을 포함한다.Food forms to which the compounds and extracts of the present invention can be added include various foods, beverages, gums, teas, vitamin complexes, or health supplements of candy.
본 발명의 화합물 및 추출물은 골 대사성 질환의 예방 및 개선을 목적으로 식품 또는 음료에 첨가될 수 있다. 이 때, 식품 또는 음료 중의 상기 화합물 및 추출물의 양은 일반적으로 본 발명의 건강식품 조성물은 전체 식품 중량의 0.01 내지 15 중량%로 가할 수 있으며, 건강 음료 조성물은 100 ml를 기준으로 0.02 내지 10 g, 바람직하게는 0.3 내지 1 g의 비율로 가할 수 있다. The compounds and extracts of the present invention may be added to foods or beverages for the purpose of preventing and ameliorating bone metabolic diseases. At this time, the amount of the compound and extract in the food or beverage is generally added to the health food composition of the present invention 0.01 to 15% by weight of the total food weight, the health beverage composition is 0.02 to 10 g based on 100 ml, Preferably it can be added in the ratio of 0.3-1 g.
본 발명의 건강 음료 조성물은 지시된 비율로 필수 성분으로서 상기 화합물 및 추출물의 혼합물을 함유하는 것 외에 액체성분에는 특별한 제한점은 없으며 통상의 음료와 같이 여러 가지 향미제 또는 천연 탄수화물 등을 추가 성분으로서 함유할 수 있다. 상술한 천연 탄수화물의 예는 모노사카라이드, 예를 들어, 포도당, 과당 등의 디사카라이드, 예를 들어 말토스, 슈크로스 등의 및 폴리사카라이드, 예를 들어 덱스트린, 시클로덱스트린 등과 같은 통상적인 당 및 자일리톨, 소르비톨, 에리트리톨 등의 당알콜이다. 상술한 것 이외의 향미제로서 천연 향미제(타우마틴, 스테비아 추출물(예를 들어 레바우디오시드 A, 글리시르히진등) 및 합성 향미제(사카린, 아스파르탐 등)를 유리하게 사용할 수 있다. 상기 천연 탄수화물의 비율은 본 발명의 조성물 100 ml당 일반적으로 약 1 내지 20 g, 바람직하게는 약 5 내지 12 g이다.The health beverage composition of the present invention contains a mixture of the compounds and extracts as essential ingredients in the ratios indicated, and there are no particular limitations on the liquid ingredients, and it contains various flavors or natural carbohydrates as additional ingredients, like ordinary drinks. can do. Examples of the above-mentioned natural carbohydrates include monosaccharides such as disaccharides such as glucose and fructose such as maltose, sucrose and the like and polysaccharides such as dextrin, cyclodextrin and the like Sugar, and sugar alcohols such as xylitol, sorbitol, and erythritol. As flavoring agents other than those mentioned above, natural flavoring agents (tauumatin, stevia extract (for example, rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can be advantageously used. The proportion of said natural carbohydrate is generally about 1 to 20 g, preferably about 5 to 12 g per 100 ml of the composition of the present invention.
상기 외에 본 발명의 화합물 및 추출물은 여러 가지 영양제, 비타민, 광물(전해질), 합성 풍미제 및 천연 풍미제 등의 풍미제, 착색제 및 중진제(치즈, 초콜릿 등), 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알콜, 탄산 음료에 사용되는 탄산화제 등을 함유할 수 있다. 그밖에 본 발명의 화합물 및 추출물들은 천연 과일 쥬스 및 과일 쥬스 음료 및 야채 음료의 제조를 위한 과육을 함유할 수 있다. 이러한 성분은 독립적으로 또는 조합하여 사용할 수 있다. 이러한 첨가제의 비율은 그렇게 중요하진 않지만 본 발명의 조성물 100 중량부 당 0 내지 약 20 중량부의 범위에서 선택되는 것이 일반적이다.In addition to the above, the compounds and extracts of the present invention include various nutrients, vitamins, minerals (electrolytes), flavors such as synthetic flavors and natural flavors, coloring and neutralizing agents (such as cheese and chocolate), pectic acid and salts thereof, alginic acid And salts thereof, organic acids, protective colloid thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated beverages, and the like. In addition, the compounds and extracts of the present invention may contain flesh for the production of natural fruit juices and fruit juice beverages and vegetable beverages. These components can be used independently or in combination. The proportion of such additives is not so critical, but is generally selected in the range of 0 to about 20 parts by weight per 100 parts by weight of the composition of the present invention.
본 발명에 의한 폰시린은 파골세포 분화 억제 효과, 파골세포 분화 및 증식 관련 인자인 TRAP, Cathepsin K, MMP-9, NFATc1 등의 유전자 발현 억제 효과를 나타내므로, 파골세포 억제용 약학 조성물, 건강기능식품, 식품첨가제로 유용하게 이용될 수 있다.Poncirine according to the present invention shows an inhibitory effect on osteoclast differentiation, osteoclast differentiation and proliferation-related factors such as TRAP, Cathepsin K, MMP-9, NFATc1, etc. Food, it can be usefully used as a food additive.
도 1은 폰시린(Poncirin) 농도에 따른 RANKL 처리 RAW264.7 세포로부터 TRAP(+) 다핵세포 형성에 미치는 영향을 나타낸 도이며,
도 2는 폰시린(Poncirin) 농도에 따른 TRAP발현에 미치는 영향을 나타낸 도이며,
도 3는 폰시린(Poncirin) 농도에 따른 Cthepsin K 발현에 미치는 영향을 나타낸 도이며,
도 4는 폰시린(Poncirin) 농도에 따른 MMP-9 발현에 미치는 영향을 나타낸 도이며,
도 5는 폰시린(poncirin)의 구조를 나타낸 도이다.1 is a diagram showing the effect on the formation of TRAP (+) multinucleated cells from RANKL treated RAW264.7 cells according to the concentration of poncirin (Poncirin),
2 is a diagram showing the effect on TRAP expression according to the concentration of ponsirin (Poncirin),
3 is a diagram showing the effect on the expression of Cthepsin K according to the concentration of ponsirin (Poncirin),
4 is a diagram showing the effect on the expression of MMP-9 according to the concentration of ponsirin (Poncirin),
5 is a diagram showing the structure of poncirin (poncirin).
이하, 본 발명을 하기 실시예 및 실험예에 의해 상세히 설명한다.Hereinafter, the present invention will be described in detail with reference to the following examples and experimental examples.
단, 하기 실시예 및 실험예는 본 발명을 예시하는 것일 뿐, 본 발명의 내용이 하기 실시예 및 실험예에 의해 한정되는 것은 아니다.
However, the following examples and experimental examples are illustrative of the present invention, and the content of the present invention is not limited by the following examples and experimental examples.
실시예 1. 폰시린의 제조Example 1 Preparation of Fonsirine
폰시린(식품의약품안전청)에서 분양받아 하기 실험예의 시료로 사용하였다.
It was used as a sample of the following experimental example after being sold by ponsulin (Food and Drug Administration).
실험예 1. 세포 배양 및 약물처리Experimental Example 1. Cell Culture and Drug Treatment
실험에 사용한 RAW 264.7 세포는 DMEM(Dulbecco's modified eagle medium)/10% FBS(fetal bovine serum)/PC-SM 배지를 이용하여 CO2 세포배양기에서 배양하였으며, 세포수는 5x103 cells/well 로 96 well plate를 이용하여 배양하였다. 24시간 배양 후 배양액을 버린 후, 10 % FBS, 50 ng/ml RANKL, 1 ng/ml TGFb 가 첨가된 a-MEM 으로 교환하여 세포를 배양했다. 배양액에 여러 농도의 AS를 첨가해 주었다. 2일에 한번씩 동일한 배지로 교환해 주면서 6일간 배양하였다. 실험군은 (1) RANKL 처리하지 않은 대조군(C) (2) RANKL 유도 대조군(C), (2) RANKL 유도군 + 1/의 실시예1의 폰시린(Poncirin)을 투여한 군(PCN1), (3) RANKL 유도군 + 5/의 실시예1의 폰시린(Poncirin)을 투여한 군(PCN5)으로 하였다.
The RAW 264.7 cells used in the experiment were cultured in a CO2 cell incubator using DMEM (Dulbecco's modified eagle medium) / 10% fetal bovine serum (FBS) / PC-SM medium, and the number of cells was 96 well plate at 5x10 3 cells / well. And cultured using. After culturing for 24 hours, the culture medium was discarded, and the cells were cultured by exchanging with a-MEM to which 10% FBS, 50 ng / ml RANKL, and 1 ng / ml TGFb were added. Different concentrations of AS were added to the culture. It was incubated for 6 days while changing to the same medium every two days. The experimental group (1) RANKL-treated control group (C) (2) RANKL-induced control group (C), (2) RANKL-induced group + 1 / group administered the ponsirin (Poncirin) of Example 1 (PCN1), (3) RANKL induction group + 5 / It was set as the group (PCN5) to which the poncirin of Example 1 was administered.
실험예 2. 파골세포 생성능 측정Experimental Example 2. Measurement of osteoclast generation capacity
RANKL(receptor activator for nuclear factor B ligand)로 RAW 264.7 cell를 파골세포로 유도한 후, 성숙한 파골세포의 발현 marker로 알려진 TRAP를 염색하여 TRAP-positive한 다핵세포(TRAP(+) MNCs)를 확인하였다. 분화시킨 세포를 PBS로 세포를 2회 세척하고, 3.7% formaldehyde -citrate-acetone 용액으로 10분 고정시키고 증류수로 2회 세척하였다. 2% TRAP fast garnet GBC base 용액과 NaNO3 용액을 같은 비율로 섞어 만든 용액과 5% naphtha AS-BI phosphoric acid, 4% acetic acid, 2% tartaric acid를 포함한 용액을 고정시킨 세포에 처리하고 상온에 30분 이상 방치하였다. 광학현미경으로 관찰하여 핵이 3개 이상인 TRAP-positive 한 다핵세포 (TRAP(+) MNCs)를 계수하여 파골세포의 생성지표로 하였다(13).
After inducing RAW 264.7 cells to osteoclasts with RANKL (receptor activator for nuclear factor B ligand), TRAP-positive multinucleated cells (TRAP (+) MNCs) were identified by staining TRAP, a marker for expression of mature osteoclasts. . Differentiated cells were washed twice with PBS, fixed with 3.7% formaldehyde-citrate-acetone solution for 10 minutes and washed twice with distilled water. Treat the cells prepared by mixing 2% TRAP fast garnet GBC base solution with NaNO3 solution in the same ratio and a solution containing 5% naphtha AS-BI phosphoric acid, 4% acetic acid and 2% tartaric acid. It was left for more than a minute. Observed by light microscopy, TRAP-positive multinucleated cells (TRAP (+) MNCs) having three or more nuclei were counted and used as an index for generating osteoclasts (13).
실험예 3. 유전자 발현에 대한 영향Experimental Example 3. Effect on Gene Expression
상기 실시예 1의 폰시린의 파골세포 분화 및 증식 관련 인자인 TRAP, Cathepsin K, MMP-9 발현억제, NFATc1 등의 유전자 발현 등의 유전자 발현에 대한 영향을 알아보기 위해 하기와 같이 실험을 수행하였다.
Experiments were performed as follows to determine the effects on gene expression such as TRAP, Cathepsin K, MMP-9 expression inhibition, NFATc1, etc., which are factors related to osteoclast differentiation and proliferation of ponsyrin. .
3-1. 총 3-1. gun RNARNA 분리 detach
배양하고 있는 B16F10 세포에 1 ml 트리졸 용액 (인비트로젠, USA)를 처리하여 총 RNA를 분리하였다. 분리한 RNA에 100 페놀과 100 클로로포름 : 아이소아밀알코올 (24:1)을 넣고 잘 섞은 후 원심분리하는 과정을 2번 반복하여 상층액을 분리한다. 0.5 ml 아이소프로필 알코올을 이용하여 RNA를 침전시킨 후 70% 에탄올로 세척하고 자연 건조시킨다. 알에네이즈 프리워터 (RNAase free water, 프로메가, 미국)에서 RNA를 녹인 후 알에네이즈-프리-디에네이즈 (RNase-free DNase, 프로메가, 미국)를 첨가하고 -70에서 저장하였다.
Cultures of B16F10 cells were treated with 1 ml Trizol solution (Invitrogen, USA) to isolate total RNA. 100 phenol and 100 chloroform: isoamyl alcohol (24: 1) are added to the isolated RNA, and the mixture is mixed well and centrifuged twice to separate the supernatant. RNA is precipitated using 0.5 ml isopropyl alcohol, washed with 70% ethanol and dried naturally. RNA was thawed in RNAase free water (RNA) free water (Promega, USA), followed by the addition of RNAase-free DNase (RNase-free DNase, Promega, USA) and stored at -70.
3-2. 3-2. cDNAcDNA 제조 Produce
상기 실험예 3-1에서 분리한 대조군 및 실험군 각각의 전체 RNA액 (13 ug RNA 함유)에 올리고dT 1 을 넣은 후 조심스럽게 혼합한 다음, 70oC에서 5분간 배양하였다. 프라이머가 풀리도록 실온에서 약 10분간 방치한 다음, 사스크립트 버퍼 (cyscript buffer), 0.1 M DTT, dUTP 뉴클레오티드, dUTP 시다이-표지된 뉴클레오티드, 사스크립트 역전사효소 (Cyscript reverse transcriptase)를 첨가한 후, 아주 조심스럽게 혼합하였다. 이 후, 42oC에서 90분간 배양한 후, 얼음 상에 방치하였다. 여기에 2.5 M 수산화나트륨을 가한 후 37oC에서 15분간 배양하였으며, 2 M HEPES 버퍼를 가하여 중화시켜 cDNA를 제조하였다.OligodT 1 was added to the total RNA solution (containing 13 ug RNA) of each of the control and experimental groups isolated in Experimental Example 3-1, mixed carefully, and then incubated at 70 ° C. for 5 minutes. Leave primers at room temperature for about 10 minutes to release the primers, then add cyscript buffer, 0.1 M DTT, dUTP nucleotides, dUTP seeded-labeled nucleotides, Cyscript reverse transcriptase, and then add Mix carefully. Thereafter, the cells were incubated at 42 ° C. for 90 minutes and then left on ice. 2.5 M sodium hydroxide was added thereto, followed by incubation at 37 ° C. for 15 minutes, and neutralized by adding 2 M HEPES buffer to prepare cDNA.
3-3. 3-3. RealReal timetime RTRT -- PCRPCR
우선 시험관에 정량한 RNA 5 ug, 50 ng/의 랜덤 헥사머 (random hexamer) 3 , 10 mM dNTP 1 를 넣고 DEPC-H2O를 가하여 10 의 RNA/프라이머 혼합물을 만들었다. 실험용 sample을 65℃에서 5분간 배양시킨 후 1분 이상 얼음에 방치하였다. 반응 혼합물로 10배의 RT 버퍼 2 , 25 mM 염화마그네슘 4 , 0.1 M DTT 2 , RNAase(프로메가, 미국) 1 을 섞어 준비하였다. 반응 혼합물을 RNA/프라이머 혼합물에 가하여 섞고 실온에 2분간 방치한 후, SuperScript II RT (프로메가, 미국) 1 (50 units)를 가하고 25oC에 10분간 배양 시켰다. 다시 42oC에서 50분간 배양 시킨 다음, 70oC에서 15분간 가열하여 불활성 시키고 얼음 상에서 식혔다. RNase (프로메가, 미국)1 를 가하고 다시 37oC에서 20분간 배양 시킨 다음, 사용 시까지 -20oC에 보관하였다. 각각의 옵티컬 튜브 (optical tube, 깁코, 미국)에 2배의 사이버 그린믹스 (SYBR Green Mix, 다카라, 일본) 12.5 , cDNA 0.2 , 5 pmol/ 프라이머 쌍 혼합 1 , 11.3 H2O를 넣고, 50oC 2 분 1 사이클, 95oC 10분 1 사이클, 95oC 15초, 60oC 30초, 72oC 30초 40 사이클, 72oC 10분 1 사이클로 증폭시켰다. PCR을 마친 후 튜브를 꺼낸 다음, 반응액 5 ul를 사용하여 3% 아가로스 겔에서 PCR 특이성을 측정했다. SDS 7000 소프트웨어를 사용하여 리얼 타임 PCR (real time PCR) 결과를 분석하였다. First, 5 ug of RNA, 50 ng / random hexamer (random hexamer) 3, 10 mM dNTP 1, were added to the test tube, and DEPC-H 2 O was added to make an RNA / primer mixture of 10. The experimental sample was incubated at 65 ° C. for 5 minutes and then left on ice for at least 1 minute. The reaction mixture was prepared by mixing
RAW264.7 세포에 RANKL (receptor activator for nuclear factor B ligand) 처리시 TRAP(+) 다핵세포(MNCs) 발현이 증가하여 파골세포 분화가 촉진되었으며, 상기 실시예에서 폰시린은 1 ug/ml, 5 ug/ml, 농도에서 증 RANKL (receptor activator for nuclear factor B ligand) 유도 파골세포 분화를 억제시키는 것으로 나타났다(도 1) TRAP(tartarate resistance Acid Phosphatase), Cathepsin K, MMP-9, NFATc1는 RANKL 처리시 발현이 증가하였으며, 상기의 폰시린은 1 ug/ml, 5 ug/ml, 농도에서 증가한 유전자 발현을 현저히 억제함을 확인하였다 (도 2, 도 3 및 도 4 참조). 따라서 폰시린은 티로시나아제, TRAP, Cathepsin K, MMP-9, NFATc1 유전자 발현을 억제하는데 탁월한 효과가 있음을 알 수 있었다.
Treatment of receptor activator for nuclear factor B ligand (RANKL) in RAW264.7 cells increased expression of TRAP (+) multinucleated cells (MNCs) to promote osteoclast differentiation. ug / ml, it was shown to inhibit the receptor activator for nuclear factor B ligand (RANKL) -induced osteoclast differentiation at concentrations (FIG. 1) (tartarate resistance Acid Phosphatase), Cathepsin K, MMP-9, NFATc1 when RANKL treatment Expression was increased, and the phonicrin was found to significantly inhibit the gene expression increased at 1 ug / ml, 5 ug / ml, concentration (see Fig. 2, 3 and 4). Thus, it can be seen that ponsyrin has an excellent effect on inhibiting tyrosinase, TRAP, Cathepsin K, MMP-9, and NFATc1 gene expression.
통계처리는 스튜던트의 t-검정을 이용해 개별 비교를 하였으며, p값이 0.05 미만일 때 유의한 차이가 있는 것을 판정하였다.
Statistical treatments were compared individually using Student's t-test and determined that there was a significant difference when the p-value was less than 0.05.
하기에 본 발명의 화합물을 함유하는 조성물의 제제예를 설명하나, 본 발명은 이를 한정하고자 함이 아닌 단지 구체적으로 설명하고자 함이다.
Hereinafter, formulation examples of the composition containing the compound of the present invention will be described, but the present invention is not intended to be limited thereto but is specifically described.
제제예Formulation example 1. One. 산제의Sanje 제조 Produce
폰시린 200 mgPonsiline 200 mg
유당 100 mg
탈크 10 mg
상기의 성분들을 혼합하고 기밀포에 충진하여 산제를 제조한다.
The above components are mixed and filled in airtight bags to prepare powders.
제제예Formulation example 2. 정제의 제조 2. Preparation of tablets
폰시린 200 mgPonsiline 200 mg
옥수수전분 100 mg
유당 100 mg
스테아린산 마그네슘 2 mgMagnesium stearate 2 mg
상기의 성분들을 혼합한 후 통상의 정제의 제조방법에 따라서 타정하여 정제를 제조한다.
After mixing the above components, tablets are prepared by tableting according to the usual preparation method of tablets.
제제예Formulation example 3. 캅셀제의 제조 3. Preparation of capsules
폰시린 200 mgPonsiline 200 mg
결정성 셀룰로오스 3 mg
락토오스 14.8 mgLactose 14.8 mg
마그네슘 스테아레이트 0.2 mgMagnesium stearate 0.2 mg
통상의 캅셀제 제조방법에 따라 상기의 성분을 혼합하고 젤라틴 캡슐에 충전하여 캅셀제를 제조한다.
The above components are mixed in accordance with a conventional method for producing a capsule, and filled in a gelatin capsule to prepare a capsule.
제제예Formulation example 4. 주사제의 제조 4. Preparation of injections
폰시린 200 mgPonsiline 200 mg
만니톨 180 mgMannitol 180 mg
주사용 멸균 증류수 2974 mgSterile distilled water for injection 2974 mg
Na2HPO4 ,12H2O 26 mgNa 2 HPO 4 , 12H 2 O 26 mg
통상의 주사제의 제조방법에 따라 1 앰플당 (2㎖) 상기의 성분 함량으로 제조한다.
(2 ml) per 1 ampoule according to the usual injection preparation method.
제제예Formulation example 5. 5. 액제의Liquid 제조 Produce
폰시린 200 mgPonsiline 200 mg
이성화당 10 g10 g per isomer
만니톨 5 g5 g mannitol
정제수 적량Purified water
통상의 액제의 제조방법에 따라 정제수에 각각의 성분을 가하여 용해시키고 레몬향을 적량 가한 다음 상기의 성분을 혼합한 다음 정제수를 가하여 전체를 정제수를 가하여 전체 100 ml로 조절한 후 갈색병에 충진하여 멸균시켜 액제를 제조한다.
Each component was added and dissolved in purified water according to the usual liquid preparation method, and the lemon flavor was added in an appropriate amount. Then, the above components were mixed, and purified water was added thereto. The whole was added with purified water to adjust the total volume to 100 ml, And sterilized to prepare a liquid preparation.
제제예Formulation example 6. 건강 식품의 제조 6. Manufacture of health food
폰시린 1000 mgPonsyrine 1000 mg
비타민 혼합물 적량Vitamin mixture quantity
비타민 A 아세테이트 70 Vitamin A Acetate 70
비타민 E 1.0 Vitamin E 1.0
비타민 B1 0.13 Vitamin B1 0.13
비타민 B2 0.15 Vitamin B2 0.15
비타민 B6 0.5 Vitamin B6 0.5
비타민 B12 0.2 Vitamin B12 0.2
비타민 C 10
비오틴 10
니코틴산아미드 1.7 Nicotinamide 1.7
엽산 50 Folic acid 50
판토텐산 칼슘 0.5 Calcium Pantothenate 0.5
무기질 혼합물 적량Mineral mixture quantity
황산제1철 1.75 Ferrous Sulfate 1.75
산화아연 0.82 Zinc Oxide 0.82
탄산마그네슘 25.3 Magnesium Carbonate 25.3
제1인산칼륨 15
제2인산칼슘 55 Dicalcium Phosphate 55
구연산칼륨 90 Potassium Citrate 90
탄산칼슘 100
염화마그네슘 24.8 Magnesium chloride 24.8
상기의 비타민 및 미네랄 혼합물의 조성비는 비교적 건강식품에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만, 그 배합비를 임의로 변형 실시하여도 무방하며, 통상의 건강식품 제조방법에 따라 상기의 성분을 혼합한 다음, 과립을 제조하고, 통상의 방법에 따라 건강식품 조성물 제조에 사용할 수 있다.
Although the composition ratio of the above-mentioned vitamin and mineral mixture is comparatively mixed with a composition suitable for health food as a preferred embodiment, the compounding ratio may be arbitrarily modified, and the above ingredients are mixed according to a conventional method for producing healthy foods , Granules can be prepared and used in the manufacture of health food compositions according to conventional methods.
제제예Formulation example 7. 건강 음료의 제조 7. Manufacture of health drinks
폰시린 1000 mgPonsyrine 1000 mg
구연산 1000 Citric Acid 1000
올리고당 100 g100 g of oligosaccharide
매실농축액 2 gPlum concentrate 2 g
타우린 1 gTaurine 1 g
정제수를 가하여 전체 900 Purified water is added to the total 900
통상의 건강음료 제조방법에 따라 상기의 성분을 혼합한 다음, 약 1시간동안 85에서 교반 가열한 후, 만들어진 용액을 여과하여 멸균된 2l 용기에 취득하여 밀봉 멸균한 뒤 냉장 보관한 다음 본 발명의 건강음료 조성물 제조에 사용한다. The above components were mixed according to a conventional health drink manufacturing method, and the mixture was stirred and heated at 85 for about 1 hour. The resulting solution was filtered and sterilized in a sterilized 2 l vessel. The resulting solution was refrigerated, Used in the manufacture of health beverage compositions.
상기 조성비는 비교적 기호음료에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만, 수요계층, 수요국가, 사용용도 등 지역적, 민족적 기호도에 따라서 그 배합비를 임의로 변형 실시하여도 무방하다.Although the composition ratio is a mixture of the components suitable for the preferred beverage as a preferred embodiment, the blending ratio may be arbitrarily varied according to the regional and national preferences such as the demand level, the demanding country, and the intended use.
Claims (2)
Food or food additives for the prevention and improvement of bone joint disease, which contains poncirin (Poncirin) showing an osteoclast inhibitory effect as an active ingredient.
상기 골 대사성 질환은 골다공증(osteoprosis), 파제트병(paget disease), 치주질환(periodontal disease), 골전이암(metastatic cancer) 또는 류마티스 관절염(rheumatoid arthiritis)인 식품 또는 식품첨가제.The method of claim 1,
The bone metabolic disease is osteoporosis (osteoprosis), paget disease (paget disease), periodontal disease (periodontal disease), metastatic cancer or rheumatoid arthiritis (rheumatoid arthiritis) food or food additives.
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