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보안과제 ( ), 일반과제 ( ) 과제번호 : 8100073

제출문 농림축산식품부장관귀하 이보고서를 발효미생물을이용한기능성식품산업화연구사업단 과제의보고서로제 출합니다. 2014 년 02 월 06 일 주관연구기관명 : 명지대학교산학협력단주관연구책임자 : 서주원핵심연구기관명 : 명지대학교산학협력단핵심연구책임자 : 서주원세부연구책임자 : 서주원세부연구기관명 : 경기과학기술진흥원세부연구책임자 : 안은경핵심연구기관명 : ( 주 ) 비엔씨바이오팜핵심연구책임자 : 김종우세부연구책임자 : 김종우세부연구기관명 : 연세대학교산학협력단세부연구책임자 : 김택중핵심연구기관명 : 인제대학교산학협력단핵심연구책임자 : 강재헌 - 1 -

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(billion $) 세계건강식품시장규모 각국의건강식품시장의국가별비중 '97년 '98년 '99년 '00년 '01년 '02년 '07년 ( 추정 ) 자료원 : Nutrition Business Journal(2003) - 15 -

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60 55 50 NC HC BIJI MA B3MG Body weight (g) 45 40 35 30 25 0 7 14 21 28 35 42 49 Feeding days - 26 -

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홍국발효검정콩 MJLH2012005 MJLH2012006 MJLH2012007 식약처규격 ( 홍국기준 ) 성상 적갈색의분말, 특이취 적갈색의분말, 특이취 적갈색의분말, 특이취 연갈색 ~ 적갈색 분말, 특이취 총모나콜린 K (mg/g) 1.27 1.26 1.22 - 시트리닌 (mg/kg 0.028 0.024 0.005 0.05이하 수분 (%) 5.21 5.42 5.34 10% 이하 활성형모나콜린 K 확인됨 확인됨 확인됨 확인됨 대두이소플라본 ( 비배당체, mg/g) 2.79 - - 확인됨 대장균군 음성 - - 음성 잔류농약 불검출 - - 불검출 납 (mg/kg) 0.0197 총비소 (mg/kg) 0.0172 카드뮴 (mg/kg) 0.0501 총수은 (mg/kg) 0.001-38 -

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성분명회사순도 (%) 주성분표준품 monacolin K lactone form (lovastatin/mevinolin MK) monacolin K acid form (mevinolinic acid, MKA) Chromadex 98% 97% - 41 -

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그림 13. H-NMR 1 4 spectrum of compound 그림 15. 그림 14. C-NMR 13 4의 Compound 구조 (4) Identification of compound 5 (mevinolinic acid methyl ester) - White powder; ESI-MS m/ z 437 [M + H]+; H-NMR (CDCl /CD OD, 1 J = 9 8 Hz (1H, dd,., 9.8 Hz, H-5), 5.79 9.1 Hz H-4), 5.41 (1H, dd, H-2 OCH3), ' m, ), 3.72 (3H, s, H-7), 2.8, 7.7 m, 2.35 (1H, m, Hz, H-2), H-9), 172.9 ' 2.8, 6.0 2.49 (2H, d, H-2"), H-10), H-8), J= 6.3 J= J= ' (1H, m, H-4 H-3"), Hz, H-8a), H-3), 2.37 (1H, J= ' H-3 ), 1.53 (2H, 1.07 (3H, d, 7.7 176.9 (C-1"), (C-6 ), 133.3 (C-6), 131.7 (C-4a), 129.5 (C-4), 128.3 (C-5), 72.3 (C-2 ), 69.1 ' (C-4 ), 67.9 (C-1), 51.8 (C-OCH3), 13 42.3 ' (C-3 ), 41.5 ' 175 MHz) J= δ 3) C-NMR (CDCl3/CD3OD, J= ), 3.80 (1H, m, 1.96 (2H, dd, 1.56 (2H, m, Hz, OCH3), δ 5.99 (1H, d, ' ), 2.45 (1H, m, 2.8, 12.2 2.1, 7.0 700 MHz) 3 9.8 Hz, H-6), 5.52 6.3, Hz, H-5 1.67 (2H, m, 1.11 (3H, dd, OCH ; (6H, m, 2 3 Hz H-1), 4.26 2.25 (1H, dd, 1.67 (1H, m, 1.18 (2H, m, Hz, OCH3), 0.89 J= J= (1H, dd, 4 spectrum of compound (C-5 ), 41.5 ' (C-2"), 37.5 (C-8a), 36.3 (C-8), 34.8 (C-10), 32.8 (C-2), 30.6 (C-7), 27.5 (C-3), 26.8 (C-3"), 24.2 (C-9), 22.9 (C-12), 16.2 (C-13), 13.9 (C-11), 11.7 (C-4"). The 1H- - 51 - and 13 C-NMR spectral data were

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O HO O HO 1 linoleic acid 2 -linolenic acid O O HO H O H O O O HO COOCH 3 OH H 4 monacolin K 5 mevinolinic acid methyl ester H OH RO O RO O HOOC HO HO H O O H OR HO 2 1 12 R = Gal Glc 2 1 13 R = Gal Rha 2 1 14 R = Ara deoxy-man O 8 daidzein, R=H 10 daidzin, R=Glucose OH OH O OH 9 genistein, R=H 11 genistin, R=Glucose OH COOH 15 4-hydroxybenzeneacetic acid NH 2 COOH 17 phenylalanine NH 2 N N N N HOH 2 C O OH OH 18 adenosine H 2 N COOH N H 19 tryptophan O O O O HO HO OH O O HO O O O O O HO HO OH O O O 22 6"-acetyldaidzin OH HO OH OH O 23 OH OH O 24 6"-acetylgenistin OH O O O HO HO OH O O OH O 25 OH OH OH OH 26 O OH CH 3 H 3 C COOH H 3 C C C OH OH CH 2 COOH 27-71 -

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α γ α γ Target Primer sequences Accession No. GAPDH 5 -GTATGACTCCACTCACGGCAAA-3 (sense) BC083080 5 -GGTCTCGCTCCTGGAAGATG-3 (antisense) PPARγ 5 -CGCTGATGCACTGCCTATGA-3 (sense) NM_011146 5 -AGAGGTCCACAGAGCTGATTCC-3 (antisense) C/EBPα 5 -AGGTGCTGGAGTTGACCAGT-3 (sense) BC058161 5 -CAGCCTAGAGATCCAGCGAC-3 (antisense) Adiponectin 5 -AGCCTGGAGAAGCCGCTTAT-3 (sense) NM_009605 5 -TTGCAGTAGAACTTGCCAGTGC-3 (antisense) ap2 5 -CATGGCCAAGCCCAACAT-3 (sense) NM_024406 5 -CGCCCAGTTTGAAGGAAATC-3 (antisense) Resistin 5 -TCAACTCCCTGTTTCCAAATGC-3 (sense) NM_022984 5 -TCTTCACGAATGTCCCACGA-3 (antisense) Fas 5 -CTGAGATCCCAGCACTTCTTGA-3 (sense) NM_007988 5 -GCCTCCGAAGCCAAATGAG-3 (antisense) - 73 -

γ α γ α β Name 에탄올추출 % Name 에탄올추출 % Name 에탄올추출 % M2 M3 M4 3-1 25% 에탄올추출물 3-5 25% 에탄올추출물 3-9 25% 에탄올추출물 3-2 50% 에탄올추출물 3-6 50% 에탄올추출물 3-10 50% 에탄올추출물 3-3 75% 에탄올추출물 3-7 75% 에탄올추출물 3-11 75% 에탄올추출물 3-4 100% 에탄올추출물 3-8 100% 에탄올추출물 3-12 100% 에탄올추출물 - 74 -

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γ α γ α γ α γ α - 78 -

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Relative fat accumulation (% of control) Differentiated control 100 Compounds 50 μm 100 μm 200 μm 22 (6''-O-crotonylgenistin) 69.3 ± 9.0 a 22.8 ± 8.7 21.2 ± 6.8 23 (genistein-7-o-α-d-ribofuranoside) 91.7 ± 15.5 54.7 ± 11.5 15.0 ± 6.6 24 (6''-O-acetyldaidzin) 81.3 ± 7.2 83.9 ± 20.6 80.5 ± 18.3 25 (6''-O-acetylgenistin) 89.1 ± 6.0 80.1 ± 4.5 62.9 ± 6.3 γ α γ α γ - 84 -

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시험군 투여용량 (g/kg) 투여액량 (ml/kg) 투여물질 대조군 (Control) 0 20 증류수 실험군 I 0.5 20 홍국발효검정콩분말 실험군 II 1 20 홍국발효검정콩분말 실험군 III 2 20 홍국발효검정콩분말 - 159 -

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대조군 (n = 6) 시험군 Ⅰ (n = 7 ) 시험군 Ⅱ (n = 2) p-value 연령 ( 세 ) 44.17 ± 14.22 55.00 ± 3.42 49.67 ± 6.03 0.157 신장 (cm) 163.25 ± 11.51 158.67 ± 10.17 156.30 ±5.22 0.580-177 -

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항목 대조군 (n = 6) 시험군 Ⅰ (n = 7) 시험군 Ⅱ (n = 3) p-value 1) 0 wk 74.58 ± 13.07 68.64 ± 8.94 67.27 ± 6.88 0.511 체중 (kg) 6 wk 74.50 ± 13.05 67.49 ± 8.64 65.13 ± 4.60 0.371 12 wk 72.25 ± 11.93 66.96 ± 8.10 64.44 ± 8.06 0.473 12wk-0wk -2.33 ± 2.32-1.69 ± 1.65-2.83 ± 2.41 0.698 p-value 2) 0.057 0.035 0.179 0 wk 27.80 ± 1.80 27.19 ± 1.51 27.48 ± 1.10 0.791 BMI (kg/ m2 ) 6 wk 27.77 ± 1.72 26.74 ± 1.64 26.58 ± 1.45 0.466 12 wk 26.94 ± 1.03 26.55 ± 1.50 26.29 ± 1.48 0.766 12wk-0wk -0.86 ± 0.91-0.64 ± 0.62-1.18 ± 1.06 0.632 p-value 2) 0.070 0.033 0.193 0 wk 28.28 ± 6.38 30.46 ± 5.85 32.37 ± 6.95 0.640 Total Fat(%) /DEXA 12 wk 26.75 ± 8.75 30.16 ± 6.36 32.17 ± 5.23 0.535 12wk-0wk -1.53 ± 3.04-0.30 ± 1.14-0.20 ± 1.15 0.549 p-value 2) 0.272 0.511 0.878 0 wk 19812.17 ± 4428.15 19771.43 ± 3683.91 20399.33 ± 2972.00 0.971 Total Fat(g) /DEXA 12 wk 17869.50 ± 4772.93 19073.57 ± 3869.77 19436.33 ± 818.90 0.810 12wk-0wk -1942.67 ± 2437.88-697.86 ± 981.13-963.00 ± 2236.73 0.492 p-value 2) 0.108 0.109 0.534 0 wk 51200.50 ± 11584.90 45847.57 ± 8795.99 43439.33 ± 8868.18 0.489 Total Lean(g) /DEXA 12 wk 51033.67 ± 13467.67 44891.57 ± 8381.44 41897.33 ± 8774.11 0.431 12wk-0wk -166.83 ± 2463.84-956.00 ± 1259.92-1542.00 ± 311.02 0.525 p-value 2) 0.875 0.091 0.038-179 -

l < 그림 1> DEXA Arms, Legs, Trunk 부위 Qing He, Xiaojing Zhang, Suyuan He, Luxia Gong, Yungao Sun, Stanley Heshka, Richard J. Deckelbaumand Dympna Gallagher. Higher Insulin, Triglycerides, and Blood Pressure With Greater Trunk Fat in Tanner 1 Chinese. Obesity (2007) 15, 1004 1011. < 그림 2> DEXA 의 Android, Gynoid 부위 Rachel Novotny, Scott Going, Dorothy Teegarden, Marta Van Loan, George McCabe, Linda McCabe, Yihe G. Daida and Carol J. Boushey and the ACT Research Team. Hispanic and Asian Pubertal Girls Have Higher Android/Gynoid Fat Ratio Than Whites. Obesity (2007) 15, 1565 1570. - 180 -

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항목 Arms Legs Trunk Android Gynoid Fat (%) Fat (g) Fat (%) Fat (g) Fat (%) Fat (g) Fat (%) Fat (g) Fat (%) Fat (g) 대조군 (n = 6) 시험군 Ⅰ (n = 7) 시험군 Ⅱ (n = 3) p-value 1) 0 wk 23.52 ± 12.44 25.86 ±10.76 25.80 ± 11.08 0.926 12 wk 21.83 ± 13.15 24.44 ±10.39 23.63 ± 8.70 0.917 12wk-0wk -1.68 ± 2.41-1.41 ±1.72-2.22 ± 3.23 0.892 p-value 2) 0.147 0.073 0.366 0 wk 1786.33 ± 859.81 1801.00 ±806.11 1744.00 ± 733.17 0.995 12 wk 1634.50 ± 913.78 1676.43 ±800.12 1462.00 ± 510.11 0.928 12wk-0wk -151.83 ± 256.33-124.57 ±217.42-282.00 ± 334.75 0.668 p-value 2) 0.207 0.180 0.282 0 wk 23.68 ± 9.01 25.99 ±6.56 30.20 ± 12.28 0.578 12 wk 22.70 ± 10.51 25.14 ±6.82 30.50 ± 11.58 0.505 12wk-0wk -0.98 ± 1.71-0.84 ±1.13 0.30 ± 0.89 0.399 p-value 2) 0.218 0.095 0.618 0 wk 5946.50 ± 2542.06 5785.00 ±1251.18 7132.33 ± 3050.10 0.657 12 wk 5501.17 ± 2650.745 5399.14 ±1301.39 6963.33 ± 2553.45 0.549 12wk-0wk -445.33 ± 369.52-385.86 ±232.37-169.00 ± 502.36 0.526 p-value 2) 0.032 0.005 0.619 0 wk 34.58 ± 4.17 36.63 ±5.13 37.27 ± 2.55 0.621 12 wk 32.60 ± 8.01 36.93 ±5.64 37.03 ± 1.86 0.433 12wk-0wk -1.98 ± 4.62 0.30 ±1.89-0.23 ± 3.14 0.483 p-value 2) 0.341 0.688 0.909 0 wk 11406.83 ± 1800.16 11503.57 ±1941.41 10841.33 ± 925.07 0.859 12 wk 10104.00 ± 1693.45 11321.00 ±1865.14 10335.33 ± 1933.68 0.472 12wk-0wk -1302.83 ± 2024.36-182.57 ±848.24-506.00 ± 1421.72 0.418 p-value 2) 0.176 0.590 0.600 0 wk 38.83 ± 5.03 41.80 ±5.24 42.83 ± 2.46 0.426 12 wk 37.12 ± 8.72 42.29 ±5.99 42.00 ± 2.18 0.380 12wk-0wk -1.72 ± 3.86 0.49 ±1.52-0.83 ± 2.22 0.376 p-value 2) 0.325 0.428 0.583 0 wk 2101.33 ± 167.76 2232.14 ±425.10 2160.00 ± 202.68 0.763 12 wk 1889.17 ± 308.56 2174.86 ±430.33 1926.67 ± 332.83 0.373 12wk-0wk -212.17 ± 307.45-57.29 ±174.53-233.33 ± 294.92 0.464 p-value 2) 0.152 0.419 0.304 0 wk 29.28 ± 8.25 32.54 ±6.98 36.93 ± 11.55 0.446 12 wk 28.22 ± 10.09 31.77 ±7.10 37.27 ± 9.53 0.368 12wk-0wk -1.07 ± 2.48-0.77 ±1.49 0.33 ± 2.29 0.630 p-value 2) 0.341 0.221 0.825 0 wk 3159.33 ± 940.59 3230.86 ±636.37 3859.67 ± 1226.42 0.508 12 wk 2941.17 ± 922.07 3082.14 ±670.75 3718.67 ± 842.45 0.401 12wk-0wk -218.17 ± 259.13-148.71 ±142.15-141.00 ± 387.40 0.848 p-value 2) 0.094 0.033 0.593-182 -

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항목 대조군 (n = 6) 시험군 Ⅰ (n = 7) 시험군 Ⅱ (n = 3) p-value 1) 0 wk 265.83 ± 14.50 262.86 ± 11.07 307.33 ± 102.26 0.304 총 콜레스테롤 (mg/dl) 6 wk 235.17 ± 35.27 216.43 ± 17.66 255.33 ± 64.83 0.299 12 wk 248.17 ± 30.47 236.14 ± 28.71 253.67 ± 39.07 0.666 12wk-0wk -17.67 ± 28.32-26.71 ± 26.72-53.67 ± 67.58 0.402 p-value 2) 0.187 0.038 0.303 0 wk 128.17 ± 30.95 132.00 ± 54.71 174.33 ± 64.53 0.394 6 wk 173.83 ± 85.34 155.43 ± 95.45 83.00 ± 12.17 0.329 Triglyceride (mg/dl) 12 wk 127.67 ± 60.88 114.57 ± 33.12 182.33 ± 63.96 0.186 12wk-0wk -0.50 ± 50.09-17.43 ± 49.82 8.00 ± 26.91 0.692 p-value 2) 0.981 0.390 0.658 0 wk 61.50 ± 13.87 57.14 ± 7.88 65.67 ± 17.21 0.587 Cholesterol (mg/dl) 6 wk 56.83 ± 20.49 55.14 ± 12.97 63.00 ± 13.75 0.786 12 wk 58.67 ± 17.94 57.71 ± 10.42 55.33 ± 10.97 0.944 12wk-0wk -2.83 ± 8.23 0.57 ± 3.51-10.33 ± 7.02 0.075 p-value 2) 0.438 0.681 0.126 0 wk 177.17 ± 15.12 170.00 ± 17.07 219.67 ± 68.07 0.092 HDL- LDL- Cholesterol (mg/dl) 6 wk 151.33 ± 31.07 128.00 ± 8.19 172.67 ± 65.39 0.156 12 wk 153.00 ± 18.89 145.71 ± 24.55 154.33 ± 19.86 0.782 12wk-0wk -24.17 ± 23.23-24.29 ± 13.68-65.33 ± 55.01 0.104 p-value 2) 0.051 0.003 0.176-184 -

l l 항목 대조군 (n = 6) 시험군 Ⅰ (n = 7) 시험군 Ⅱ (n = 3) p-value 1) 0 wk 91.23 ± 3.40 90.86 ± 4.96 89.67 ± 5.58 0.887 6 wk 90.83 ± 3.24 89.50 ± 4.65 87.67 ± 6.03 0.607 허리둘레 (cm) 12 wk 88.20 ± 3.35 88.00 ± 4.52 86.67 ± 6.66 0.885 12wk-0wk -3.03 ± 0.45-2.86 ± 1.49-3.00 ± 1.32 0.961 p-value 2) 0.000 0.002 0.059 0 wk 101.97 ± 5.05 100.14 ± 3.38 102.50 ± 2.78 0.617 엉덩이 둘레 (cm) 6 wk 101.75 ± 5.30 98.96 ± 3.52 101.33 ± 1.15 0.454 12 wk 99.58 ± 5.44 98.43 ± 3.36 99.67 ± 2.52 0.856 12wk-0wk -2.38 ± 0.58-1.71 ± 0.70-2.83 ± 2.75 0.395 p-value 2) 0.000 0.001 0.217-185 -

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항목 대조군 (n = 5) 시험군 Ⅰ (n = 7) 시험군 Ⅱ (n = 3) p-value 1) 0 wk 74.50 ± 14.61 68.64 ± 8.94 67.27 ± 6.88 0.582 체중 (kg) 6 wk 74.52 ± 14.60 67.49 ± 8.64 65.13 ± 4.60 0.437 12 wk 72.94 ± 13.21 66.96 ± 8.10 64.44 ± 8.06 0.468 12wk-0wk -1.56 ± 1.49-1.69 ± 1.65-2.83 ± 2.41 0.580 p-value 2) 0.080 0.035 0.179 0 wk 27.29 ± 1.46 27.19 ± 1.51 27.48 ± 1.10 0.959 BMI (kg/ m2 ) 6 wk 27.30 ± 1.45 26.74 ± 1.64 26.58 ± 1.45 0.767 12 wk 26.77 ± 1.05 26.55 ± 1.50 26.29 ± 1.48 0.890 12wk-0wk -0.53 ± 0.47-0.64 ± 0.62-1.18 ± 1.06 0.404 p-value 2) 0.068 0.033 0.193 0 wk 26.34 ± 4.74 30.46 ± 5.85 32.37 ± 6.95 0.324 Total Fat(%) /DEXA 12 wk 24.48 ± 7.56 30.16 ± 6.36 32.17 ± 5.23 0.243 12wk-0wk -1.86 ± 3.28-0.30 ± 1.14-0.20 ± 1.15 0.447 p-value 2) 0.274 0.511 0.878 0 wk 18351.20 ± 2915.90 19771.43 ± 3683.91 20399.33 ± 2972.00 0.663 Total Fat(g) /DEXA 12 wk 16438.60 ± 3622.16 19073.57 ± 3869.77 19436.33 ± 818.90 0.377 12wk-0wk -1912.60 ± 2724.39-697.86 ± 981.13-963.00 ± 2236.73 0.572 p-value 2) 0.192 0.109 0.534 Total Lean(g) /DEXA 0 wk 52595.40 ± 12376.1 6 12 wk 53093.80 ± 13960.3 6 45847.57 ± 8795.99 43439.33 ± 8868.18 0.409 44891.57 ± 8381.44 41897.33 ± 8774.11 0.307 12wk-0wk 498.40 ± 2066.18-956.00 ± 1259.92-1542.00 ± 311.02 0.163 p-value 2) 0.618 0.091 0.038-187 -

l l - 188 -

항목 Arms Legs Trunk Android Gynoid Fat (%) Fat (g) Fat (%) Fat (g) Fat (%) Fat (g) Fat (%) Fat( g) Fat (%) Fa t(g) 대조군 (n = 5) 시험군 Ⅰ (n = 7) 시험군 Ⅱ (n = 3) p-value 1) 0 wk 20.30 ± 10.77 25.86 ± 10.76 25.80 ± 11.08 0.655 12 wk 18.54 ± 11.60 24.44 ± 10.39 23.63 ± 8.70 0.627 12wk-0wk -1.76 ± 2.68-1.41 ± 1.72-2.22 ± 3.23 0.897 p-value 2) 0.216 0.073 0.366 0 wk 1512.60 ± 601.75 1801.00 ± 806.11 1744.00 ± 733.17 0.794 12 wk 1360.00 ± 691.81 1676.43 ± 800.12 1462.00 ± 510.11 0.750 12wk-0wk -152.60 ± 286.58-124.57 ± 217.42-282.00 ± 334.75 0.690 p-value 2) 0.300 0.180 0.282 0 wk 20.72 ± 5.96 25.99 ± 6.56 30.20 ± 12.28 0.255 12 wk 19.20 ± 6.79 25.14 ± 6.82 30.50 ± 11.58 0.171 12wk-0wk -1.52 ± 1.22-0.84 ± 1.13 0.30 ± 0.89 0.128 p-value 2) 0.049 0.095 0.618 0 wk 5095.80 ± 1627.85 5785.00 ± 1251.18 7132.33 ± 3050.10 0.332 12 wk 4593.40 ± 1613.31 5399.14 ± 1301.39 6963.33 ± 2553.45 0.194 12wk-0wk -502.40 ± 382.44-385.86 ± 232.37-169.00 ± 502.36 0.438 p-value 2) 0.042 0.005 0.619 0 wk 33.54 ± 3.68 36.63 ± 5.13 37.27 ± 2.55 0.404 12 wk 31.34 ± 8.26 36.93 ± 5.64 37.03 ± 1.86 0.298 12wk-0wk -2.20 ± 5.13 0.30 ± 1.89-0.23 ± 3.14 0.483 p-value 2) 0.392 0.688 0.909 0 wk 11129.80 ± 1864.16 11503.57 ± 1941.41 10841.33 ± 925.07 0.853 12 wk 9907.20 ± 1815.01 11321.00 ± 1865.14 10335.33 ± 1933.68 0.434 12wk-0wk -1222.60 ± 2252.61-182.57 ± 848.24-506.00 ± 1421.72 0.531 p-value 2) 0.292 0.590 0.600 0 wk 38.12 ± 5.27 41.80 ± 5.24 42.83 ± 2.46 0.348 12 wk 36.04 ± 9.30 42.29 ± 5.99 42.00 ± 2.18 0.300 12wk-0wk -2.08 ± 4.19 0.49 ± 1.52-0.83 ± 2.22 0.325 p-value 2) 0.330 0.428 0.583 0 wk 2108.00 ± 186.68 2232.14 ± 425.10 2160.00 ± 202.68 0.813 12 wk 1898.80 ± 343.97 2174.86 ± 430.33 1926.67 ± 332.83 0.440 12wk-0wk -209.20 ± 343.65-57.29 ± 174.53-233.33 ± 294.92 0.512 p-value 2) 0.245 0.419 0.304 0 wk 26.86 ± 6.41 32.54 ± 6.98 36.93 ± 11.55 0.226 12 wk 25.04 ± 7.18 31.77 ± 7.10 37.27 ± 9.53 0.116 12wk-0wk -1.82 ± 1.86-0.77 ± 1.49 0.33 ± 2.29 0.280 p-value 2) 0.094 0.221 0.825 0 wk 2936.00 ± 855.46 3230.86 ± 636.37 3859.67 ± 1226.42 0.348 12 wk 2681.80 ± 747.15 3082.14 ± 670.75 3718.67 ± 842.45 0.191 12wk-0wk -254.20 ± 272.39-148.71 ± 142.15-141.00 ± 387.40 0.729 p-value 2) 0.105 0.033 0.593-189 -

l l l l - 190 -

항목 대조군 (n = 5) 시험군 Ⅰ (n = 7) 시험군 Ⅱ (n = 3) p-value 1) 0 wk 267.00 ± 15.89 262.86 ± 11.07 307.33 ± 102.26 0.342 총 콜레스테롤 (mg/dl) 6 wk 246.20 ± 25.34 216.43 ± 17.66 255.33 ± 62.83 0.179 12 wk 249.20 ± 33.95 236.14 ± 28.71 253.67 ± 39.07 0.677 12wk-0wk -17.80 ± 31.67-26.71 ± 26.72-53.67 ± 67.58 0.449 p-value 2) 0.277 0.038 0.303 0 wk 132.80 ± 32.20 132.00 ± 54.71 174.33 ± 64.53 0.394 Triglyceride (mg/dl) 6 wk 152.80 ± 76.06 155.43 ± 95.45 83.00 ± 12.17 0.329 12 wk 134.00 ± 65.81 114.57 ± 33.12 182.33 ± 63.96 0.186 12wk-0wk 1.20 ± 55.81-17.43 ± 49.82 8.00 ± 26.91 0.692 p-value 2) 0.964 0.390 0.658 0 wk 63.00 ± 14.95 57.14 ± 7.88 65.67 ± 17.21 0.587 Cholesterol (mg/dl) 6 wk 61.80 ± 18.43 55.14 ± 12.97 63.00 ± 13.75 0.786 12 wk 62.40 ± 17.26 57.71 ± 10.42 55.33 ± 10.97 0.944 12wk-0wk -0.60 ± 6.88 0.57 ± 3.51-10.33 ± 7.02 0.075 p-value 2) 0.855 0.681 0.126 0 wk 179.20 ± 15.96 170.00 ± 17.07 219.67 ± 68.07 0.092 HDL- LDL- Cholesterol (mg/dl) 6 wk 160.80 ± 23.12 128.00 ± 8.19 172.67 ± 65.39 0.156 12 wk 149.40 ± 18.68 145.71 ± 24.55 154.33 ± 19.86 0.782 12wk-0wk -29.80 ± 20.90-24.29 ± 13.68-65.33 ± 55.01 0.104 p-value 2) 0.033 0.003 0.176-191 -

l l 항목 대조군 (n = 5) 시험군 Ⅰ (n = 7) 시험군 Ⅱ (n = 3) p-value 1) 0 wk 91.28 ± 3.80 90.86 ± 4.96 89.67 ± 5.58 0.895 6 wk 90.80 ± 3.62 89.50 ± 4.65 87.67 ± 6.03 0.657 허리둘레 (cm) 12 wk 88.24 ± 3.74 88.00 ± 4.52 86.67 ± 6.66 0.893 12wk-0wk -3.04 ± 0.50-2.86 ± 1.49-3.00 ± 1.32 0.964 p-value 2) 0.000 0.002 0.059 0 wk 101.66 ± 5.59 100.14 ± 3.38 102.50 ± 2.78 0.680 엉덩이 둘레 (cm) 6 wk 101.40 ± 5.85 98.96 ± 3.52 101.33 ± 1.15 0.558 12 wk 99.40 ± 6.07 98.43 ± 3.36 99.67 ± 2.52 0.891 12wk-0wk -2.26 ± 0.56-1.71 ± 0.70-2.83 ± 2.75 0.447 p-value 2) 0.001 0.001 0.217-192 -

항목 RBC (10^6/ μl ) WBC (10^3/ μl ) Hematocrit (%) Hemoglobin (g/dl) Platelet (10^3/ μl ) 대조군 (n = 6) 시험군 Ⅰ (n = 7) 시험군 Ⅱ (n = 3) p-value 1) 0 wk 4.78 ± 0.36 4.56 ± 0.38 4.64 ± 0.35 0.547 6 wk 4.67 ± 0.42 4.46 ± 0.35 4.69 ± 0.55 0.595 12 wk 4.79 ± 0.39 4.52 ± 0.33 4.76 ± 0.52 0.445 12wk-0wk 0.01 ± 0.31-0.03 ± 0.15 0.11 ± 0.29 0.694 p-value 2) 0.950 0.580 0.565 0 wk 6.82 ± 1.84 7.04 ± 1.73 5.36 ± 0.78 0.357 6 wk 6.48 ± 0.90 6.22 ± 1.85 6.34 ± 1.31 0.953 12 wk 6.85 ± 2.06 6.59 ± 1.68 6.12 ± 1.12 0.845 12wk-0wk 0.03 ± 0.40-0.45 ± 1.46 0.76 ± 0.34 0.268 p-value 2) 0.860 0.448 0.061 0 wk 42.92 ± 2.83 41.63 ± 4.25 41.10 ± 1.15 0.703 6 wk 41.77 ± 3.29 40.70 ± 3.77 41.03 ± 3.20 0.861 12 wk 42.98 ± 2.35 41.30 ± 4.14 41.90 ± 2.60 0.667 12wk-0wk 0.07 ± 2.46-0.33 ± 1.33 0.80 ± 1.61 0.691 p-value 2) 0.950 0.537 0.480 0 wk 14.68 ± 0.98 14.06 ± 1.43 14.13 ± 0.97 0.634 6 wk 14.27 ± 1.11 13.81 ± 1.25 14.00 ± 1.31 0.800 12 wk 14.62 ± 0.87 13.87 ± 1.36 14.27 ± 1.16 0.529 12wk-0wk -0.07 ± 0.75-0.19 ± 0.56 0.13 ± 0.31 0.754 p-value 2) 0.837 0.410 0.529 0 wk 265.67 ± 50.56 231.14 ± 17.06 235.33 ± 48.00 0.276 6 wk 238.83 ± 47.29 243.43 ± 23.12 233.33 ± 74.65 0.945 12 wk 255.17 ± 45.43 239.71 ± 32.88 241.00 ± 90.21 0.847 12wk-0wk -10.50 ± 18.55 8.57 ± 35.12 5.67 ± 57.01 0.604 p-value 2) 0.224 0.542 0.879-193 -

항목 K (mmol/l) 대조군 (n = 6) 시험군 Ⅰ (n = 7) 시험군 Ⅱ (n = 3) p-value 1) 0 wk 4.30 ± 0.28 4.11 ± 0.24 4.43 ± 0.55 0.341 6 wk 4.28 ± 0.29 4.16 ± 0.22 3.93 ± 0.15 0.166 12 wk 4.17 ± 0.18 1.19 ± 0.26 3.93 ± 0.06 0.227 12wk-0wk -0.13 ± 0.37 0.07 ± 0.36-0.50 ± 0.50 0.139 Cl (mmol/l) p-value 2) 0.414 0.618 0.225 0 wk 102.3 ± 2.25 3 103.0 ± 2.83 101.67 ± 1.53 0.722 6 wk 103.8 ± 1.72 3 103.71 ± 2.06 104.67 ± 1.16 0.743 12 wk 101.8 ± 2.04 3 102.57 ± 2.00 103.67 ± 0.58 0.403 12wk-0wk -0.50 ± 2.43-0.43 ± 2.76 2.00 ± 2.00 0.345 p-value 2) 0.636 0.695 0.225 Creatinine (mg/dl) 0 wk 0.82 ± 0.12 0.83 ± 0.15 0.81 ± 0.15 0.979 6 wk 0.79 ± 0.12 0.79 ± 0.17 0.86 ± 0.20 0.799 12 wk 0.84 ± 0.15 0.78 ± 0.14 0.87 ± 0.21 0.642 12wk-0wk 0.02 ± 0.56-0.04 ± 0.05 0.07 ± 0.06 0.020 p-value 2) 0.421 0.043 0.195 BUN (mg/dl) 0 wk 13.83 ± 3.00 14.57 ± 2.23 11.00 ± 3.00 0.187 6 wk 13.00 ± 4.15 13.29 ± 3.40 11.33 ± 1.53 0.719 12 wk 13.33 ± 3.67 13.14 ± 1.95 12.00 ± 2.65 0.792 12wk-0wk -0.50 ± 3.39-1.43 ± 1.90 1.00 ± 2.00 0.418 p-value 2) 0.733 0.094 0.478-194 -

항목 Uric acid (mg/dl) 대조군 (n = 6) 시험군 Ⅰ (n = 7) 시험군 Ⅱ (n = 3) p-value 1) 0 wk 6.00 ± 0.83 5.31 ± 0.99 5.13 ± 1.12 0.342 6 wk 6.13 ± 1.03 4.86 ± 1.01 5.73 ± 1.45 0.142 12 wk 5.95 ± 1.08 5.24 ± 0.92 5.57 ± 1.66 0.543 12wk-0wk -0.05 ± 0.72-0.07 ± 0.36 0.43 ± 0.64 0.422 p-value 2) 0.872 0.622 0.363 0 wk 9.87 ± 0.69 9.27 ± 0.24 9.13 ± 0.25 0.059 Ca (mg/dl) 6 wk 9.70 ± 0.49 9.03 ± 0.44 9.13 ± 0.23 0.040 12 wk 9.67 ± 0.56 9.06 ± 0.40 9.03 ± 0.06 0.055 12wk-0wk -0.20 ± 0.50-0.21 ± 0.37-0.10 ± 0.26 0.920 p-value 2) 0.374 0.178 0.580 Glucose (mg/dl) 0 wk 93.67 ± 9.71 95.29 ± 7.52 89.33 ±1.53 0.566 6 wk 89.67 ± 10.01 95.71 ± 11.37 83.67 ±2.08 0.229 12 wk 91.17 ± 10.17 91.89 ± 8.24 81.67 ±4.73 0.238 12wk-0wk -2.50 ± 9.85-3.43 ± 9.43-7.67 ±6.11 0.723 p-value 2) 0.562 0.373 0.162 Protein (g/dl) 0 wk 7.65 ± 0.33 7.60 ± 0.42 7.40 ±0.46 0.670 6 wk 7.40 ± 0.30 7.43 ± 0.63 7.40 ±0.30 0.993 12 wk 7.62 ± 0.44 7.33 ± 0.54 7.27 ±0.58 0.446 12wk-0wk -0.03 ± 0.58-0.27 ± 0.22-0.13 ±0.40 0.601 p-value 2) 0.893 0.018 0.625 Albumin (g/dl) 0 wk 4.82 ± 0.26 4.43 ± 0.19 4.30 ± 0.35 0.015 6 wk 4.68 ± 0.15 4.30 ± 0.24 4.37 ± 0.35 0.031 12 wk 4.78 ± 0.31 4.30 ± 0.23 4.30 ± 0.30 0.015 12wk-0wk -0.3 3 ± 0.38-0.13 ± 0.15 0.00 ± 0.17 0.721 p-value 2) 0.837 0.063 1.000 ALP (IU/L) 0 wk 65.67 ± 16.94 66.71 ± 20.21 66.00 ±19.47 0.995 6 wk 65.83 ± 20.31 65.00 ± 19.53 68.67 ±19.86 0.965 12 wk 66.00 ± 22.54 64.86 ± 19.90 60.67 ±21.08 0.937 12wk-0wk 0.33 ± 10.44-1.86 ± 5.67-5.33 ±2.31 0.584 p-value 2) 0.941 0.419 0.057-195 -

항목 CK (IU/L) 대조군 (n = 6) 시험군 Ⅰ (n = 7) 시험군 Ⅱ (n = 3) p-value 1) 0 wk 108.00 ± 42.63 156.14 ± 139.53 126.67 ± 44.50 0.690 6 wk 220.67 ± 140.15 198.86 ± 293.04 174.00 ± 81.56 0.954 12 wk 153.50 ± 91.18 141.14 ± 144.33 128.33 ± 30.53 0.950 12wk-0wk 45.50 ± 76.80-15.00 ± 39.98 1.67 ± 23.71 0.180 p-value 2) 0.206 0.359 0.914 Na (mmol/l) 0 wk 139.83 ± 2.48 139.29 ± 1.89 138.67 ± 2.52 0.758 6 wk 140.00 ± 1.41 139.71 ± 1.25 142.33 ± 2.08 0.059 12 wk 139.33 ± 2.16 139.00 ± 1.73 140.33 ± 0.58 0.574 12wk-0wk -0.50 ± 2.59-0.29 ± 1.50 1.67 ± 2.52 0.351 p-value 2) 0.656 0.631 0.370-196 -

γ 항목 AST (GOT, IU/L) 대조군 (n = 6) 시험군 Ⅰ (n = 7) 시험군 Ⅱ (n = 3) p-value 1) 0 wk 22.00 ± 5.18 27.86 ± 8.07 25.67 ± 1.53 0.289 6 wk 25.17 ± 4.07 28.57 ± 14.51 34.33 ± 17.21 0.582 12 wk 28.83 ± 7.41 25.43 ± 9.43 22.67 ± 1.53 0.531 12wk-0wk 6.83 ± 7.91-2.43 ± 3.31-3.00 ± 3.00 0.019 p-value 2) 0.088 0.100 0.225 0 wk 27.17 ± 9.15 28.00 ± 10.99 27.00 ± 3.00 0.982 ALT (GPT, IU/L) 6 wk 27.67 ± 11.84 28.71 ± 14.60 40.33 ± 30.83 0.561 12 wk 27.50 ± 6.16 24.57 ± 11.03 20.67 ± 6.03 0.552 12wk-0wk 0.33 ± 6.25-3.43 ± 4.86-6.33 ± 4.93 0.229 p-value 2) 0.901 0.111 0.156 0 wk 45.17 ± 39.94 30.43 ± 10.26 41.33 ± 28.54 0.634 γ-gtp (mg/dl) 6 wk 35.50 ± 28.19 29.00 ± 8.56 43.33 ± 29.02 0.630 12 wk 28.33 ± 15.46 27.86 ± 10.51 27.67 ± 19.01 0.997 12wk-0wk -16.83 ± 32.00-2.57 ± 4.83-13.67 ± 9.71 0.452 p-value 2) 0.254 0.208 0.135-197 -

항목 최고혈압 (mmhg) 대조군 (n = 6) 시험군 Ⅰ (n = 7) 시험군 Ⅱ (n = 3) p-value 1) 0 wk 134.00 ± 16.83 130.00 ± 8.00 139.33 ± 17.04 0.411 6 wk 123.83 ± 13.83 127.57 ± 13.29 120.33 ± 24.58 0.296 12 wk 123.67 ± 13.66 118.71 ± 12.47 123.67 ± 13.58 0.989 12wk-0wk -10.33 ± 18.18-11.29 ± 16.52-15.67 ± 13.32 0.745 p-value 2) 0.223 0.121 0.178 0 wk 83.83 ± 11.69 83.43 ± 9.03 87.33 ± 17.24 0.472 최저혈압 (mmhg) 6 wk 76.50 ± 8.46 79.57 ± 8.08 79.33 ± 19.43 0.118 12 wk 78.00 ± 12.30 79.86 ± 9.72 83.33 ± 7.51 0.798 12wk-0wk -5.83 ± 13.82-3.57 ± 12.27-4.00 ± 9.85 0.777 p-value 2) 0.434 0.471 0.555 0 wk 70.17 ± 11.62 72.00 ± 4.55 75.67 ± 1.53 0.022 맥박 ( 회 ) 6 wk 69.50 ± 12.88 68.00 ± 4.97 67.33 ± 8.96 0.019 12 wk 74.33 ± 13.31 68.00 ± 4.28 73.67 ± 12.34 0.033 12wk-0wk 4.17 ± 6.88-4.00 ± 4.04-2.00 ± 13.11 0.052 p-value 2) 0.198 0.480 0.816-198 -

대조군 시험군Ⅰ 시험군Ⅱ 감기 1 2 두드러기 1 복통 1 1 비염 1 설사 1 1 우울감 1 입안건조 1 장염 1 팔저림 1 총건수 4 6 3-199 -

l l l - 200 -

l l l - 201 -

μ μ - 202 -

Total polyphenol (mg/g-dry basis) 400 300 200 100 0 274.78 a 171.08 b 114.77 c DTL RTL PFTL Total flavonoid (mg/g-dry basis) 100 80 60 40 20 0 62.40 a 30.12 b 31.60 b DTL RTL PFTL 120 50 EDA (%). 100 80 60 40 20 0 95.4 a 92.4 ab 85.2 b DTL RTL PFTL 0 25 50 100 200 EDA %/ mg polyphenol. 40 30 20 10 0 25.44 a 21.06 b 12.2 c DTL RTL PFTL Tea leaves mg/ml - 203 -

SOD like activity (munits) 1500 1200 900 600 300 0 DTL RTL PFTL 980 a 820 b 637 c 0 0.5 1 1.5 2 SOD like activity (munits)/mg polyphenol 10,000 8,000 6,000 4,000 2,000 0 7,292.78 a 4,793.06 b 3,566.42 c DTL RTL PFTL Tea leaves mg/ml μ μ μ - 204 -

XO inhibitory activity (%) 50 40 30 20 10 0 DTL RTL PFTL 24.4 a 8.1 b 5.7 b 0 0.5 1 1.5 2 Tea leaves mg/ml XO inhibitory %/mg polyphenol... 120 100 80 60 40 20 0 88.8 a 49.66 b 47.35 b DTL RTL PFTL - 205 -

Nitrite scavenging activity (%). 100 80 60 40 20 0 63.79 a 61.48 a 59.69 a DTL RTL PFTL 38.72 b 32.48 b 19.36 c 1.6 1.1 0.5 Hydrogen peroxide (um) 44.91 a 38.14 b 12.43 c 0 ph 1.2 ph 3.0 ph 6.0 DTL RTL PFTL 60 45 30 15-206 -

- 207 -

360 200 Total polyphenol (mg/g, dry basis). 300 240 180 120 60 0 w ater extracts 286A 70% ethanol extracts 126a 117a 125B 94b 70c 62C 47d 39d 47D 15E 13E 13e 7F FT TM15 TM30 PU FM MM15 MM30 Total flavonoid (mg/g, dry basis). 160 120 80 40 0 w ater extracts 70% ethanol extracts 121A 101a 78b 78B 71b 77b 65C 68c 47D 46D 33d 32d 24E 15F FT TM15 TM30 PU FM MM15 MM30 Theaflavin (%, dry basis). 2 0 1 6 1 2 8 4 0 w ater extract 70% ethanol extract 13.5A 10.8B 3.6C 2.9D 2.5E 1.6b 1.8a 1.0d 0.7e 0.8de 1.2cd 0.4F 0.3 f 0.1G FT TM15 TM30 PU FM MM15 MM30 Thearubigin (%, dry basis). 10 w ater extracts 8 70% ethanol extracts 7.4A 6 4.5B 4.4B 4.0C 4 3.4a 3.4a 2.8b 2.8D 2 1.8E 0.6F 0.6c 0.1e 0.2d 0.1e 0 FT TM15 TM30 PU FM MM15 MM30-208 -

100 0.5 Electon donating ability (%)... 80 60 40 20 0 w ater extracts 70% ethanol extracts 63A 56BC 58B 52a 53C 40b 41b 40b 40D 36c 15d 7E 7e 2F FT TM15 TM30 PU FM MM15 MM30 Reducing power (OD at 700 nm). 0.4 0.3 0.2 0.1 0 w ater extract 0.41a 70% ethanol extract 0.22b 0.23b 0.16c 0.15A 0.12d 0.11B 0.12B 0.10C 0.08D 0.05E 0.05E 0.04e 0.03e FT TM15 TM30 PU FM MM15 MM30 1.5 100 SOD-like activity (units). 1.2 0.9 0.6 0.89a 1.22A 0.77B w ater extract 70% ethanol extract 0.38C 0.3C6 0.32C 0.36C XO inhibitory activity (%). 80 60 40 56b w ater extract 70% ethanol extract 67a 30c 30c 78A 0.3 0 0.22b 0.13c 0.05d 0.08D 0.01e 0.01e 0.01e FT TM15 TM30 PU FM MM15 MM30 20 0 0.6D 6.6C 11.7B 0.7D 11d 0.5e 0.5D 0.6e 0.5D FT TM15 TM30 PU FM MM15 MM30 100 50 w ater extract 85a w ater extract Iron chelating activity (%). 80 60 40 20 70% ethanol extract 48b 45bc 40c 37C 38C 32D 42B 38d 46AB 39BC 35e 48A 43c Hydrogen peroxide (um). 40 30 20 10 70% ethanol extract 36.5a 24.9b 18.7c 16.5A 15.7A 8.4d 8.6B 6.1e 6.7de 4.9C 2.6D 2.2D 8.8d 4.9C 0 0 FT TM15 TM30 PU FM MM15 MM30 FT TM15 TM30 PU FM MM15 MM30-209 -

- 210 -

- 211 -

μ ε - 212 -

ε ε - 213 -

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μ - 215 -

7주간 고지방 식이에서 Fig. 17. 홍국 발효 후-발효차와 녹차식이 섭취에 에 의한 흰쥐 의 간 조직사진 3. M onascus속 미생물을 이용한 홍국 후 후 발효차 시제품 생산 발효차의 비만개선효과를 확인하고, 신속한 제품화와 남 하였다. 녹차(Aspalathus linearis)는 경상 다. 차의 발효는 유념을 5회 채취한 반복하여 37.5%가되게 조정한 1 에서 비한 90분간 음차(CHA)를 조제하였다. 이 후 첫 에서 2 L들이 균하였다. polypropylene 살 씩 혼 40 균한 ml 차는 을 덖 합하여 30 )을 의 음 넣어 착 고 air filter를 부 실 덖 음과 한 후 12 이 되도록 식히고 미리 준 배양하여 에서 최종 수분함량이 2% 내외가 되도록 - 216 - 에서 씩넣 옮겨 온 g 의 incubator에서 15일간 에 사용하였다. 하여 사용하였 음차에 증류수를 가하여 수분함량이 bag에 500 후는 무균상으로 가능한 시제품을 생산 엽 채취 50 덖 솥 물(1지2 녹차 잎을 하루 동안 위조시킨 다음 2 덖 살 액 50 끝난 홍국 배양 하였다. 발효가 가압 군 도 하동 판매가 충분히 발효차를 제조 건조시켜 실험

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NC UMI FMI UM FM HC Fig. 24. 비발효 뽕잎과 발효 뽕잎차의 1% 물 추출물, 2% 분말 8주간 식이에 의한 간조직 사진 후 발효뽕잎차 시제품 생산 b 북 것 크 른 후 40 켰 총 0 00 씩 넣 착 홍 배 액 50 L 0 외 후 5 쳐 려 홍 티백 태 나. M onascus속 미생물을 이용한 시제품 생산용 뽕잎(M. al a leaves)은 경 는 생 뽕잎을 1 leaves: U 2 cm bag에 3 g 균시킨 뽕잎에 미리 준비한 40 을 사용하였다. 뽕잎의 발효 에서 2일간 건조시 으며(unfermented mulberry F), 발효는 건조시킨 뽕잎에 물을 가하여 들이 polypropylene 살 기로 자 경산에서 생산한 에서 수분함량이 2% 내 였다. 사용자의 편이를 고 국 수분 함량이 3 %가 되게 조절한 고 air filter를 부 양 m 를 접종하여 3 가 되도록 건조시킨 하여 하여 121 국발효뽕잎차는 Fig. 25. M onascus속 미생물을 이용한 - 226-1. mm 체로 형 후 에서 90분간 에서 15일간 살 후 2 L 균하였다. 배양한 다음, 서 발효뽕잎차를 제조하 로 제작하여 상품화하였다. 발효뽕잎차 시제품

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성별 시험군 대조군 N=50 N=50 남, n(%) 45 (90.00) 44 (88.00) 여, n(%) 5 (10.00) 6 (12.00) p-value 0.7493 $ Mean±SD 49.48±10.58 49.62±10.30 연령 ( 세 ) Min, Max 26.00, 68.00 28.00, 68.00 0.9467 * - 261 -

시험군 대조군 N=35 N=36 p-value* Mean±SD Mean±SD Baseline( 방문 1) 40.14±15.77 35.53±14.82 0.2080 6주 ( 방문3) 36.54±16.03 35.56±14.78 AST Change from baseline -3.60±14.74 0.03±14.93 0.3066 (GOT) p-value** 0.1576 0.9912 (IU/L) 12주 ( 방문4) 36.65±21.10 36.53±13.40 Change from baseline -3.49±23.13 1.00±14.49 0.3331 p-value** 0.3789 0.6813 Baseline( 방문 1) 54.63±23.77 45.22±18.22 0.0650 6주 ( 방문3) 46.91±22.34 47.06±25.11 ALT Change from baseline -7.71±18.60 1.83±18.78 0.0349 (GPT) p-value** 0.0194 0.5618 (IU/L) 12주 ( 방문4) 45.71±25.66 46.42±24.76 Change from baseline -8.91±21.01 1.19±18.53 0.0349 p-value** 0.0170 0.7013 Baseline( 방문 1) 90.34±47.20 79.58±38.82 0.2972 6주 ( 방문3) 82.17±49.20 85.31±51.12 Change from baseline -8.17±25.35 5.72±36.59 0.0670 r-gtp p-value** 0.0650 0.3545 (IU/L) 12주 ( 방문4) 74.69±46.19 89.81±58.51 Change from baseline -15.66±30.23 10.22±43.25 0.0047 p-value** 0.0043 0.1650-262 -

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시험군 대조군 N=50 N=50 p-value* Mean±SD Mean±SD Baseline( 방문 1) 38.82±14.99 34.94±12.94 0.1690 6 주 ( 방문 3) 36.66±15.18 35.32±13.10 AST (GOT) (IU/L) Change from baseline -2.16±12.76 0.38±13.44 0.3348 p-value** 0.2369 0.8424 12 주 ( 방문 4) 36.18±18.81 36.56±13.64 Change from baseline -2.64±19.64 1.62±15.15 0.2274 p-value** 0.3465 0.4531 Baseline( 방문 1) 51.34±24.84 44.74±18.38 0.1344 6주 ( 방문3) 46.12±24.31 47.32±24.88 ALT (GPT) (IU/L) Change from baseline -5.22±16.79 2.58±17.56 0.0254 p-value** 0.0327 0.3040 12 주 ( 방문 4) 45.24±25.87 47.14±24.58 Change from baseline -6.10±19.22 2.40±19.28 0.0296 p-value** 0.0294 0.3831 Baseline( 방문 1) 92.84±43.87 79.92±39.61 0.1254 6주 ( 방문3) 91.76±53.76 85.18±47.97 r-gtp (IU/L) Change from baseline -1.08±31.90 5.26±32.10 0.3243 p-value** 0.8118 0.2522 12 주 ( 방문 4) 87.08±57.88 86.18±54.17 Change from baseline -5.76±42.38 6.26±44.10 0.1678 p-value** 0.3413 0.3204-264 -

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시험군 대조군 평가변수 N=35 N=36 p-value* Mean±SD Mean±SD Baseline( 방문 2) 81.03±20.74 71.50±17.52 6 주 ( 방문 3) 79.26±21.40 72.25±19.32 Change from baseline -1.77±16.18 0.75±14.65 0.4933 TOTAL p-value** 0.5215 0.7606 12주 ( 방문4) 81.23±19.54 69.08±16.10 Change from baseline -0.20±14.54-2.42±17.16 0.4910 p-value** 0.9356 0.4037 Baseline( 방문2) 32.54±10.24 27.69±9.25 6 주 ( 방문 3) 33.37±10.96 28.61±8.92 전반적 피로도 Change from baseline 0.83±7.54 0.92±7.41 0.9605 p-value** 0.5198 0.4630 12주 ( 방문4) 33.20±9.29 27.50±7.80 Change from baseline 0.66±6.79-0.19±8.50 0.6429 p-value** 0.5707 0.8916 Baseline( 방문2) 26.63±6.77 24.08±5.92 6주 ( 방문3) 24.77±7.03 24.03±6.41 Change from baseline -1.86±5.52-0.06±5.17 0.1600 일상생활기능장애 p-value** 0.0544 0.9490 12주 ( 방문4) 25.94±6.69 22.25±5.49 Change from baseline -0.69±5.35-1.83±5.91 0.3945 p-value** 0.4536 0.0712 Baseline( 방문2) 21.86±6.15 19.72±4.71 6주 ( 방문3) 21.11±5.10 19.61±5.66 Change from baseline -0.74±5.40-0.11±5.16 0.6161 상황적피로 p-value** 0.4217 0.8980 12주 ( 방문4) 22.09±4.85 19.33±4.47 Change from baseline 0.23±4.95-0.39±4.97 0.6018 p-value** 0.7865 0.6416-266 -

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시험군 대조군 평가변수 N=50 N=50 p-value* Mean±SD Mean±SD Baseline( 방문 2) 75.48±22.92 72.76±18.51 6 주 ( 방문 3) 75.10±21.68 72.68±19.13 Change from baseline -0.38±14.99-0.08±14.19 0.9183 TOTAL p-value** 0.8585 0.9684 12주 ( 방문4) 76.28±20.57 70.72±16.82 Change from baseline 0.80±13.59-2.04±15.39 0.3303 p-value** 0.6789 0.3531 Baseline( 방문2) 30.34±10.73 28.84±9.43 6주 ( 방문3) 31.12±11.04 28.96±8.66 전반적 피로도 Change from baseline 0.78±6.85 0.12±7.02 0.6354 p-value** 0.4247 0.9043 12 주 ( 방문 4) 31.12±10.03 28.28±7.82 Change from baseline 0.78±6.23-0.56±7.57 0.3362 p-value** 0.3804 0.6033 Baseline( 방문2) 24.86±7.99 24.40±6.40 6주 ( 방문3) 23.84±7.21 24.32±6.89 일상생활 기능장애 Change from baseline -1.02±5.37-0.08±5.60 0.3935 p-value** 0.1851 0.9199 12 주 ( 방문 4) 24.60±6.98 23.02±6.02 Change from baseline -0.26±5.39-1.38±5.42 0.3028 p-value** 0.7343 0.0782 Baseline( 방문2) 20.28±6.49 19.52±4.70 6주 ( 방문3) 20.14±5.34 19.40±5.40 상황적 피로 Change from baseline -0.14±4.97-0.12±4.82 0.9837 p-value** 0.8428 0.8609 12 주 ( 방문 4) 20.56±5.31 19.42±4.45 Change from baseline 0.28±4.44-0.10±4.64 0.6765 p-value** 0.6576 0.8795-268 -

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시험군 대조군 N=50 N=50 p-value* Mean±SD Mean±SD Baseline( 방문 1) 4.87±0.43 4.94±0.40 RBC (106/ml) 12 주 ( 방문 4) 4.85±0.43 4.94±0.42 Change from baseline -0.01±0.18 0.00±0.19 0.6578 p-value** 0.6020 0.9080 Baseline( 방문 1) 15.14±1.13 15.23±1.16 Hb (g/dl) 12 주 ( 방문 4) 15.22±1.13 15.37±1.23 Change from baseline 0.08±0.58 0.14±0.62 0.5736 p-value** 0.3600 0.1081 Baseline( 방문 1) 44.84±2.93 45.17±3.23 Hct (%) 12 주 ( 방문 4) 44.60±3.11 45.07±3.53 Change from baseline -0.25±1.90-0.10±1.67 0.6763 p-value** 0.3604 0.6809 Baseline( 방문 1) 6.31±1.76 6.33±1.72 WBC (103/ml) 12 주 ( 방문 4) 6.62±1.86 6.40±1.64 Change from baseline 0.31±1.66 0.06±1.27 0.4129 p-value** 0.1964 0.7214 Baseline( 방문 1) 235.50±47.55 243.12±66.44 Platelet (103/ml) 12 주 ( 방문 4) 241.24±52.36 243.52±78.22 Change from baseline 5.74±17.39 0.40±26.07 0.2315 p-value** 0.0237 0.9140-270 -

Na (mmol/l) K (mmol/l) Cl (mmol/l) Calcium (mg/dl) CK (IU/L) Protein (g/dl) 시험군 대조군 N=50 N=50 Mean±SD Mean±SD Baseline( 방문 1) 140.32±2.01 140.70±1.80 12 주 ( 방문 4) 140.28±2.03 140.50±2.48 p-value* Change from baseline -0.04±2.32-0.20±1.70 0.6952 p-value** 0.9035 0.4101 Baseline( 방문 1) 4.26±0.33 4.28±0.33 12 주 ( 방문 4) 4.25±0.33 4.25±0.25 Change from baseline -0.01±0.36-0.03±0.29 0.7858 p-value** 0.8772 0.5328 Baseline( 방문 1) 103.16±2.25 103.42±2.16 12 주 ( 방문 4) 103.24±1.92 103.38±2.40 Change from baseline 0.08±2.35-0.04±2.03 0.7855 p-value** 0.8111 0.8898 Baseline( 방문 1) 9.41±0.36 9.34±0.29 12 주 ( 방문 4) 9.27±0.34 9.30±0.27 Change from baseline -0.14±0.30-0.04±0.29 0.1101 p-value** 0.0018 0.2967 Baseline( 방문 1) 141.46±118.44 138.14±74.90 12 주 ( 방문 4) 242.46±580.95 138.96±81.27 Change from baseline 101.00±581.77 0.82±98.60 0.2354 p-value** 0.2255 0.9533 Baseline( 방문 1) 7.56±0.39 7.44±0.38 12 주 ( 방문 4) 7.46±0.37 7.50±0.34 Change from baseline -0.10±0.30 0.06±0.28 0.0082 p-value** 0.0267 0.1390-271 -

Albumin (g/dl) Glucose (mg/dl) T. Bilirubin (g/dl) ALP Creatinine (mg/dl) BUN (mg/dl) Uric acid (mg/dl) LDH 시험군 대조군 N=50 N=50 Mean±SD Mean±SD Baseline( 방문 1) 4.68±0.21 4.63±0.23 12 주 ( 방문 4) 4.65±0.23 4.68±0.24 p-value* Change from baseline -0.04±0.16 0.04±0.19 0.0296 p-value** 0.1267 0.1216 Baseline( 방문 1) 109.14±24.89 101.92±19.99 12 주 ( 방문 4) 105.68±21.03 104.86±22.92 Change from baseline -3.46±18.08 2.94±14.77 0.0554 p-value** 0.1822 0.1655 Baseline( 방문 1) 0.88±0.41 0.80±0.32 12 주 ( 방문 4) 0.88±0.42 0.84±0.32 Change from baseline -0.00±0.26 0.04±0.24 0.3823 p-value** 0.9129 0.2522-272 -

시험군 대조군 N=50 N=50 Mean±SD Mean±SD p-value* Total Chole. (mg/dl) Triglyceride HDL-chole. LDL-chole. PT aptt - 273 -

체중 (kg) 시험군 대조군 N=50 N=50 p-value* Mean±SD Mean±SD Baseline( 방문2) 74.78±9.39 72.74±9.80 6주 ( 방문3) 74.72±9.55 72.78±9.76 Change from baseline -0.06±1.34 0.04±1.12 0.6864 p-value** 0.7535 0.8009 12주 ( 방문4) 74.88±9.67 72.67±9.67 Change from baseline 0.10±1.61-0.07±1.09 0.5339 p-value** 0.6629 0.6429 Baseline( 방문2) 77.92±9.90 75.20±9.09 6주 ( 방문3) 77.32±9.43 72.60±9.12 Change from baseline -0.60±7.06-2.60±10.94 0.2806 맥박 p-value** 0.5505 0.0993 ( 회 /min) 12주 ( 방문4) 77.76±10.82 74.28±8.43 Change from baseline -0.16±7.95-0.92±8.52 0.6457 p-value** 0.8875 0.4487 Baseline( 방문2) 130.80±13.78 128.50±11.97 6주 ( 방문3) 131.98±13.68 129.64±11.48 Change from baseline 1.18±15.35 1.14±11.73 0.9884 수축기압 p-value** 0.5893 0.4953 (mmhg) 12주 ( 방문4) 130.38±13.54 128.68±11.74 Change from baseline -0.42±13.99 0.18±10.94 0.8117 p-value** 0.8328 0.9078 Baseline( 방문2) 82.74±9.77 79.76±8.49 6주 ( 방문3) 84.34±9.52 81.04±7.84 Change from baseline 1.60±8.45 1.28±7.81 0.8446 이완기압 p-value** 0.1870 0.2524 (mmhg) 12주 ( 방문4) 84.38±8.54 81.58±8.03 Change from baseline 1.64±8.93 1.82±6.76 0.9098 p-value** 0.2004 0.0627-274 -

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원료명지표성분표시량 (1일 3,360mg) 비고도라지추출물로써 3g 개별인정서도라지추출물 (Platycodin D 27.9mg) 2013-26호 - 283 -

상온 (25 ) 가속 (40 ) 시험항목제조시 1 개월 2 개월 3 개월 1 개월 2 개월 3 개월 성상적합적합적합적합적합적합적합 대장균군음성음성음성음성음성음성음성 붕해도 ( 장용성 ) 적합적합적합적합적합적합적합 납불검출 - - 불검출 - - 불검출 총비소불검출 - - 불검출 - - 불검출 카드뮴불검출 - - 불검출 - - 불검출 총수은불검출 - - 불검출 - - 불검출 - 284 -

항목 - 285 -

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1 차년도 (2011) 구분 출원 특허신품종 등록 품종명칭등록 품종생산수입판매신고 품종보호 출원 등록 유전자원등록 목표 0 0 0 0 0 0 0 0 0 달성 5 0 0 0 0 0 1 2 논 SCI 문 비 SCI 기타 2차년도 (2012) 3차년도 (2013) 계 목표 4 0 0 0 0 0 0 4 5 달성 4 1 0 0 0 0 0 5 7 목표 5 0 0 0 0 0 0 6 6 달성 2 1 0 0 0 0 0 5 1 목표 9 0 0 0 0 0 0 10 11 달성 11 2 0 0 0 0 0 11 10 구분기술실시 ( 이전 ) 상품화정책자료교육지도언론홍보기타 1) 활용건수목표 4 4 8 달성 - - 6 1-314 -

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β - 316 -

Two New Isoflavone Glycosides from the Extracts of the Fungus Monascus pilosus-fermented Black Soybean Bull. Chem. Soc. Korean Triterpenoid Saponins Isolated from Platycodon grandiflorum Inhibit Hepatitis C Virus Replication H i n d a w i P u b l i s h i n g Corporation - 317 -

지원대상 ( 학위별취득자 ) 성별 계열별 박사 석사 학사 기타 남 여 공학 농림수산학 의약보건학 인력양성자수 3 1 2 3-318 -

Global Market 2004 2005 2007 2008 2009 HCV Therapy 2.72 2.97 3.46 3.7 3.97-319 -

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주 의 이보고서는농림축산식품부에서시행한발효미생물을이용한기능성식품 산업화연구사업단의연구보고서입니다 이보고서내용을발표할때에는반드시농림축산식품부에서시행한발효 미생물을이용한기능성식품산업화연구사업단의연구결과임을밝혀야 합니다 국가과학기술기밀유지에필요한내용은대외적으로발표또는공개하여서는 아니됩니다 - 337 -