초록 ▼

본 연구를 통해 백하수오, 구절초 및 측백엽으 수면증진 효과를 처음으로 과학적으로 규명하고 수면증진을 위한 기능성식품을 개발하였다. 펜토바비탈 수면유도 실험과 설치류 수면구조(sleep-wake) 실험에서 백하수오, 구절초 및 측백엽 추출물 모두 농도의존적으로 수면증진효과를 보였다. 반응표면분석법을 이용하여 활성이 가장 우수한 제조조건을 최적화하였다. 기능성분으로는 측백엽과 구절초로부터(-)-$\alpha$-Pinene (+)-3-carene을 동정하였다. (-)-$\alpha$-Pinene

본 연구를 통해 백하수오, 구절초 및 측백엽으 수면증진 효과를 처음으로 과학적으로 규명하고 수면증진을 위한 기능성식품을 개발하였다. 펜토바비탈 수면유도 실험과 설치류 수면구조(sleep-wake) 실험에서 백하수오, 구절초 및 측백엽 추출물 모두 농도의존적으로 수면증진효과를 보였다. 반응표면분석법을 이용하여 활성이 가장 우수한 제조조건을 최적화하였다. 기능성분으로는 측백엽과 구절초로부터(-)-$\alpha$-Pinene (+)-3-carene을 동정하였다. (-)-$\alpha$-Pinene (+)-3-carenedl GABA type A receptor의 agonist로써 세포의 억제성 신경전달을 증대시켜 수면증진 효과가 있다는 것을 brain slice patch 및 in vivo 수면증진 효능 평가를 통해 처음으로 입증하였다. 임상시험 결과, 수면다원검사에 의해 한계는 있었으나 설문지를 통한 주관적 평가에서 유의적으로 불면증상이 호전된것으로 나타났다. 최종 시제품을 국내외 유명제품과 비교한 결과, 수면증진효과가 유사하거나 조금 높은 수준으로 제품화가 가능할 것으로 기대되었다. 이러한 결과를 종합해볼때 백하수오, 구절초 및 측백엽을 이용한 수면증진 기능성식품의 산업화 가능성이 높은 것으로 기대된다.

Abstract ▼

1. Objectives and Background
1.1. Objectives
Development of sleep- enhancing functional foods from Cynanchum wilfordii. Chrysanthemum zawadskii and Thuja oriental is
1.2. Background
In recent years. herbal sleep aids are becoming popular as an alternative to prescription drugs to improve

1. Objectives and Background
1.1. Objectives
Development of sleep- enhancing functional foods from Cynanchum wilfordii. Chrysanthemum zawadskii and Thuja oriental is
1.2. Background
In recent years. herbal sleep aids are becoming popular as an alternative to prescription drugs to improve sleep quality and avoid side-effects. In western societies. herbal sleep aids such as valerian are readily available. There are many medicinal plants used traditionally for treatment of insomnia in Korea. However, scientific evidence and mechanism for hypnotic activity of Korean medicinal plants have not been fully investigated . Therefore, study on hypnotic effects of traditional medicinal plants is needed.
2. Contents and Scopes of the Research
2.1. 2009
- Subject 1: Isolation of active compounds
- Subject 2: Pharmacological studies of active compounds
- Subject 3: Animal study for evaluation of sleep- enhancing effect
2.2. 2010
- Subject 1: Standardization of active compounds and development of prototype
- Subject 2: Studies on action mechanism of active compounds
- Subject 3: Human tria ls for evaluation of sleep-enhancing effect
3. Research Results
3.1. Subject 1
We demonstrated that extracts of Cynanchum wi lfordii (CW). Chrysanthemum zawadskii (CZ) and Thuja oriental is (TO) had sleep-enhancing effects using pentobarbital-induced sleep test and sleep structure analysis. Their hypnotic effects were fully inhibited by a GABA receptor antagonist, flumazenil, Optimal extraction conditions of CW, CZ and TO were X1 (EtOH concentration) = 95.0%, X2 (extraction time) = 47.0 h, X1 = 25.0%. X2 = 14.7 hand X1 = 95 .0%. X2 = 52.8 h. respectively. (- )-$\alpha$- pinene and (+)-3-carene were identified as a active compound from CZ and TO, and they were major compounds in CZ and TO. In the oral acute toxicity tests for CW. CZ. TO and their combination. no deaths occurred in all the tested groups during 14 day observation period. CW, CZ and TO or their combination preparation might provide a useful means for the treatment of insomnia.
3.2. Subject 2
Extracts and isolated compounds from CZ and TO were tested for an enhancing effect of GABA receptor activities in mouse brain slices using Patch Clamp recording technique. We recorded the miniature IPSCs (mIPSCs) mediated by postsynaptic GABA receptors and measured the amplitude, frequency, and decay time constants of averaged mIPSCs. We tested several iso lated compounds of flavonoid group including rutin, umbelliferone, quercitrin, apigenin, hespertin, amentoflavone but did not observe any effect on the mIPSCs . We tested two essential oi ls including (- )-$\alpha$-pinene, (+)-3-carene and found that these two significantly increased the decay time constant of mIPSCs . These two compounds showed significantly increased the decay time constant of mlPSCs compared to the well known sleep aid, diazepam, indicating that these two compounds promise a good potential for functional food for sleep aid.
3.3 Subject 3
This double blind placebo cont rolled trial was to evaluate the efficacy and to lerability of Sleep Enhancing Material (SEM) for the treatment in subjects with insomnia. Sixty five subjects who were complaining subjective insomnia were random ly assigned to either SEM or placebo for 1 week. Efficacy was assessed with the ISS, PSQI and polysomnography at the baseline and week. Repeated measures analysis of variance on the ISS, PSQI and PSG scores showed no significant decrease over time in the both groups without significant group difference and time by group interaction effect. However, in terms of sleep latency, total sleep time, sleep satisfaction, sleep efficiency, awakening frequency and slow wave sleep, SEM showed some effective tendency in the treatment of subjective insomnia.
4. Applications of Research Results
- Papers: acceptance of 1 paper
- Patents : application of 1 patent
- Technology Transfe r: transferred to the participating company until 2011 . Aug .

목차 Contents

• 1. 겉표지 (앞면) ...1
• 2. 제출문 ...3
• 3. 보고서 요약서 ...4
• 4. 요약문(한글) ...5
• 5. 요약문(영문) ...7
• 6. 연구성과 실적 및 향후 계획 ...9
• 7. 참여연구원 현황표 ...17
• II. 총괄연구과제 연구결과 ...18
• 1. 연구개발과제의 배경 및 필요성 ...19
• 2. 국내외 기술개발 현황 ...26
• 3. 연구개발과제의 추진체계 ...32
• 4. 연구개발 수행 내용 및 결과 ...34
• 5. 목표달성도 및 관련분야 기여도 ...88
• 6. 향후 연구성과 추진 계획 ...89
• 7. 연구개발결과의 파급효과 ...90
• 8. 연구개발결과의 활용계획 ...90
• 9. 연구개발과정에서 수집한 해외과학기술정보 ...91
• III. 제1세부 연구과제 연구결과 ...92
• 1. 연구개발과제의 목표 ...93
• 2. 연구개발과제의 추진체계 ...94
• 3. 연구개발수행 내용 및 결과 ...95
• 4. 참고문헌 ...231
• IV. 제2세부 연구과제 연구결과 ...234
• 1. 연구개발과제의 목표 ...235
• 2. 연구개발과제의 추진체계 ...238
• 3. 연구개발수행 내용 및 결과 ...239
• 4. 참고문헌 ...243
• V. 제3세부 연구과제 연구결과 ...244
• 1. 연구개발과제의 목표 ...245
• 2. 연구개발과제의 추진체계 ...248
• 3. 연구개발수행 내용 및 결과 ...249
• 4. 참고문헌 ...275
• VI. 첨부서류 ...277
• 1. 자체평가의견서 ...278
• 2. 실적 증빙자료 ...282
• 3. 기타 첨부서류 ...287