KR102382638B1 - Composition comprising Protaetia brevitarsis seulensis larva extracts for improving sleep - Google Patents
Composition comprising Protaetia brevitarsis seulensis larva extracts for improving sleep Download PDFInfo
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- KR102382638B1 KR102382638B1 KR1020200077714A KR20200077714A KR102382638B1 KR 102382638 B1 KR102382638 B1 KR 102382638B1 KR 1020200077714 A KR1020200077714 A KR 1020200077714A KR 20200077714 A KR20200077714 A KR 20200077714A KR 102382638 B1 KR102382638 B1 KR 102382638B1
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- sleep
- extract
- larvae
- improving
- active ingredient
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
본 발명은 흰점박이꽃무지 유충 추출물을 함유하는 수면개선용 조성물에 관한 것으로, 보다 상세하게는 흰점박이꽃무지 유충 추출물이 수면 개시시간을 단축시키고 수면시간을 연장시킴으로써 수면을 개선시키는 것을 확인함으로써, 부작용 없이 장기간 안전하게 사용할 수 있는 수면개선 조성물의 개발에 기여할 수 있다.The present invention relates to a composition for improving sleep containing a larvae extract, and more particularly, by confirming that the larvae extract of Platypus larvae shortens the sleep initiation time and extends the sleep time, thereby improving sleep. It can contribute to the development of a sleep improvement composition that can be safely used for a long time without side effects.
Description
본 발명은 흰점박이꽃무지 유충 추출물을 함유하는 수면개선용 조성물에 관한 것으로, 보다 상세하게는 흰점박이꽃무지 유충 추출물을 함유하는 수면 개시시간 단축 및 수면시간 연장용 조성물에 관한 것이다.The present invention relates to a composition for improving sleep containing a larvae extract of White-spotted flower larvae, and more particularly, to a composition for shortening sleep initiation time and extending sleep time, comprising an extract
스트레스가 급증한 사회적 분위기나 환경에 의해 수면장애로 고민하는 사람이 증가하고 있다. 현대인의 수면시간이 크게 줄어든 이유는 장래에 대한 불안, 우울증, 불안장애, 스트레스와 같은 심리적 이유에 의한 정신질환 증가, 직업과 사회적 다변화에 따른 주야간 교대 근무, 그리고 바르지 못한 생활습관 등 다양한 원인에 기인한다. 즉, 사회가 복잡해짐에 따라 할 일이 많아지고 스트레스도 늘어나면서 만성적 수면부족이 생겨난 것이다. 또한 커피 등 카페인이 함유된 음료를 더 많이 섭취하는 것도 이유 중 하나로 꼽히고 있다.The number of people suffering from sleep disorders is increasing due to the social atmosphere or environment in which stress has increased rapidly. The reason why modern people's sleep time has significantly decreased is due to various causes such as anxiety about the future, depression, anxiety disorder, and mental illness due to psychological reasons such as stress, day and night shift work due to occupational and social diversification, and poor lifestyle. do. In other words, as society becomes more complex, there is more work to do and more stress, resulting in chronic sleep deprivation. Consuming more caffeine-containing beverages, such as coffee, is also cited as one of the reasons.
일시적인 스트레스, 수면습관의 변화로 인한 불규칙한 수면습관 등으로 인하여 일시적인 급성불면증이 쉽게 발생하게 되며, 이러한 급성불면증은 규칙적인 수면습관을 유지하고, 불면증을 유발한 스트레스나 원인 인자를 제거하게 되면 정상적인 수면습관으로 돌아오게 된다. 하지만, 잘못된 수면습관을 유지하거나 왜곡된 불면증에 대한 대처는 매일 잠을 못자는 만성불면증을 일으키게 된다.Temporary acute insomnia easily occurs due to temporary stress or irregular sleeping habits due to changes in sleeping habits. return to habit. However, maintaining the wrong sleeping habits or coping with distorted insomnia can cause chronic insomnia.
만성불면증상은 삶의 질을 떨어뜨리고, 우울증의 발생을 10배 이상 증가시키며, 또한 불면증으로 인한 수면장애는 고혈압이나 혈당 조절 문제, 비만 등의 문제를 야기시켜 각종 질병의 유병률을 높일 뿐만 아니라, 의료비 지출의 증가, 주간의 사고 위험성 증가, 직장에서의 업무수행능력 저하 등 환자의 사회적인 부분에서도 영향을 미치고 있다.Chronic insomnia reduces the quality of life and increases the incidence of depression by more than 10 times. In addition, sleep disturbance due to insomnia causes problems such as high blood pressure, blood sugar control problems, obesity, etc., thereby increasing the prevalence of various diseases and medical expenses. It is also affecting the social aspects of patients, such as increased spending, increased risk of accidents during the day, and decreased ability to perform work at work.
이러한 수면장애는 수면각성장애라고도 하며, 불면증, 과면증, 수면각성시간(circadian rhythm, 일간리듬)장애, 수면시 이상행동 등으로 분류한다. 불면증은 수면경향이 감퇴하는 양적 이상을 말하는데, 좀처럼 잠들기가 어려운 취면장애(就眠障碍), 일단 잠이 들었어도 숙면이 되지 않는 숙면장애(熟眠障碍), 아침 일찍 깨는 조조각성(早朝覺醒) 등이 있다. 우리나라는 남성의 경우, 2008년 9만명이었던 수면장애 환자가 2014년에는 17만으로, 여성의 경우는 2008년에 14만명이었던 것이 2014년에는 25만으로 6년새에 2배 가까이 치솟았으며, 이에 따른 수면장애 관련 진료비 또한 약 2.3배 증가하여 사회적 비용 또한 증가하고 있다.These sleep disorders, also called sleep arousal disorders, are classified into insomnia, hypersomnia, circadian rhythm (circadian rhythm) disorders, and abnormal behavior during sleep. Insomnia refers to a quantitative abnormality in which the tendency to sleep is diminished. there is. In Korea, the number of sleep disorder patients in Korea, from 90,000 in 2008 to 170,000 in 2014 and 140,000 in 2008 for women, nearly doubled in 2014 to 250,000 in 6 years. The related medical expenses also increased by about 2.3 times, so the social cost is also increasing.
수면에 관계된 신경전달물질인 세로토닌은 행복을 느끼는 데에 기여한다고 알려져 있다. 세로토닌은 쾌락, 긍정적인 마음, 흥분성 각성을 담당하는 도파민과 불안, 부정적 마음, 스트레스 반응 등을 담당하는 노르아드레날린의 수준을 적정 상태로 유지해주는 역할을 하며 숙면을 취하도록 돕는 멜라토닌 생성에 반드시 필요하다. 이러한 세로토닌의 전구체인 L-트립토판은 오직 섭취만으로 얻을 수 있는 필수 아미노산으로, 세로토닌의 수치를 높여주는 영양제로 시판되고 있으나, 졸림, 설사, 두통의 부작용이 있으며, 파킨슨병 환자나 특이질환 환자는 섭취전 전문가와 상담후 복용해야 한다.Serotonin, a neurotransmitter related to sleep, is known to contribute to feelings of happiness. Serotonin is essential for the production of melatonin, which helps you get a good night's sleep, and plays a role in maintaining proper levels of dopamine, which is responsible for pleasure, positive mind, and excitatory arousal, and noradrenaline, which is responsible for anxiety, negative mind, and stress responses. . L-tryptophan, a precursor of serotonin, is an essential amino acid that can be obtained only by ingestion. It is marketed as a nutritional supplement that increases the level of serotonin, but it has side effects such as drowsiness, diarrhea, and headache. It should be taken after consulting with a specialist.
수면개선제로 시판되고 있는 항히스타민제에는 디펜히드라민(diphenhydramine), 독시라민(doxylamine) 등이 있다. 디펜히드라민은 항히스타민제 중 최면진정작용이 강한 편이며, 잠드는데 걸리는 시간(sleep latency)을 감소시키고 수면의 깊이와 질을 향상시켜 일시적 불면증 완하에 사용한다. 독시라민은 디펜히드라민과 같은 H1 수용체 길항제로, 잠드는 데 걸리는 시간을 감소시킨다. 그러나 상기와 같은 항히스타민제는 시력장애, 변비, 구갈, 배뇨곤란, 빈맥 등의 항콜린 이상반응을 유발할 가능성이 있어, 녹내장, 전립선 비대증 환자에게는 투여가 금지되고 있으며, 모유를 통하여 영유아에게 전달되며, 영유아에게 소량으로도 호흡저하, 의식저하 등의 이상반응을 유발할 수 있다. 또한 고령자의 경우, 노화에 따른 전반적인 기능 저하, 면역력 약화 등에 의한 다양한 약물을 함께 복용하는 경우가 많기 때문에 항콜린제가 과도하게 사용되어 치매 위험성을 높일 수 있다는 연구결과가 있다.Antihistamines marketed as sleep-improving drugs include diphenhydramine and doxylamine. Diphenhydramine has a strong hypnotic and sedative action among antihistamines, and is used to relieve temporary insomnia by reducing sleep latency and improving the depth and quality of sleep. Doxyramine is an H1 receptor antagonist, such as diphenhydramine, that reduces the time it takes to fall asleep. However, antihistamines as described above have the potential to cause adverse anticholinergic reactions such as visual disturbances, constipation, dry mouth, difficulty urinating, and tachycardia, so administration is prohibited for patients with glaucoma and prostatic hyperplasia. Even a small amount may cause adverse reactions such as respiratory depression and loss of consciousness. In addition, in the case of the elderly, there is a study result that anticholinergic drugs are used excessively, which can increase the risk of dementia, because they often take various drugs together due to deterioration of overall function due to aging and weakening of immunity.
수면개선을 위한 생약제제로 길초근(Valeriana root)이 이용될 수 있는데, 길초근은 쥐오줌풀(Valeriana officinalis)의 뿌리로, 뇌의 활성을 감소시키는 GABA 또는 GABA 대사체의 분해를 억제하거나 GABA 수용체에 작용하여 신경과민, 심계항진, 초조, 불안, 스트레스 등에 의한 흥분을 억제하고 진정작용을 나타내며, 호프(Hops), 파시플로라(Passiflorora)와 복합제로 사용하기도 한다. 호프(Hops)는 홉(Humulus lupulus)의 암꽃으로, 최면진정작용을 하는 메틸부탄올(methylbutanol)을 생성시키거나 GABA의 활성을 증가시켜 신경과민 혹은 흥분에 의한 불면증에 효과를 나타낸다. 파시플로라(Passiflorora)는 시계꽃(Passiflora incarnata)의 뿌리를 제외한 꽃과 잎, 줄기 등의 추출물로, 뇌에서 GABA의 수치를 증가시켜 경미한 불면증과 불안을 감소시킨다. 그러나 상기의 생약제제들은 유효성분을 추출하는 방법 등에 의하여 임상시험 결과가 일치하지 않거나 서로 상반되는 경우가 있다. 또한 효과가 나타나기까지 며칠에서 몇주간 지속적으로 복용해야 하기 때문에, 급성 불면증에는 효과적이지 않으며, 장기간 복용한 후에는 용량을 서서히 줄여야 한다.Valeriana root can be used as a herbal medicine for improving sleep. Valeriana root is the root of Valeriana officinalis , which inhibits the degradation of GABA or GABA metabolites that reduce brain activity or binds to GABA receptors. By acting, it suppresses excitement caused by nervousness, palpitations, agitation, anxiety, and stress, and exhibits sedation, and is sometimes used as a combination drug with Hops and Passiflorora. Hops are female flowers of hops ( Humulus lupulus ), and they produce methylbutanol, which has a hypnotic and calming action, or increase the activity of GABA, thereby showing an effect on insomnia caused by nervousness or excitement. Passiflorora is an extract of flowers, leaves, stems, etc. excluding the roots of Passiflora incarnata , and increases the level of GABA in the brain to reduce mild insomnia and anxiety. However, there are cases in which the clinical test results of the above herbal preparations do not match or contradict each other due to the method of extracting the active ingredient. In addition, it is not effective for acute insomnia because it has to be taken continuously for several days to several weeks before the effect appears, and the dose should be gradually reduced after taking it for a long time.
이와 같이, 수면제 장기복용자 및 제한자의 경우 이를 대체할 수 있는 수단으로 천연 수면보조제의 필요성이 높아지고 있다. 선진국에서는 수면제를 대체하거나 줄일 수 있는 수면 증진 건강기능식품의 시장이 확대되고 있으며, LOHAS 트렌드의 확산과 수면에 대한 관심 증가에 따라 수면의 질을 높이고자 하는 욕구가 높아지고 있어 불면증 환자뿐만 아니라 일반인의 수면 증진 건강기능식품에 대한 수요도 더욱 확대될 것으로 전망되고 있다.As such, the need for natural sleep aids as a means to replace them is increasing in the case of long-term users of sleeping pills and those who are limited. In developed countries, the market for sleep-promoting health functional foods that can replace or reduce sleeping pills is expanding. The demand for sleep-promoting health functional foods is also expected to expand further.
한편, 흰점박이꽃무지는 민간 및 동의보감 등의 전통 한방의서에서 "제조" 또는 "굼벵이" 라는 속명으로 불리어지고 있는 딱정벌레목, 풍뎅이과, 꽃무지아과에 속하며, 크기는 17 내지 24센티미터의 초식성 곤충으로서, 우리나라를 비롯하여 중국, 일본 및 시베리아 동부 지역에 서식하며, 5월에서 10월에 걸쳐 1 내지 2년에 1회 발생한다고 알려져 있다(고천[古川] 등, 원색곤충백과도감, 집앙사[集英社], 동경[東京], 573-574(1977); 장지이[張芝利], 중국경제곤충지 28책, 초시목, 중국과학원 중국동물지 편찬위원회, 과학출판사(1984)). On the other hand, white-spotted flower radish belongs to the coleoptera family, scarabaceae, which are called "manufacturing" or "slug" in traditional oriental medicine books such as folk and Donguibogam, and are herbivorous insects with a size of 17 to 24 centimeters. It inhabits Korea, China, Japan, and eastern Siberia, and is known to occur once every 1-2 years from May to October (Gocheon et al. ], Tokyo [Tokyo], 573-574(1977);
흰점박이꽃무지는 3령의 성숙유충 상태로 월동하며, 성충은 주간에 활동하고 복숭아, 배 등의 성숙한 과일이나 옥수수, 상수리 나무 등의 즙액을 먹이로 하는 군집성 곤충이다. 이들의 유충은 퇴비나 건초더미 등의 유기물이 풍부한 부식성 토양속에서 서식한다. 흰점박이꽃무지는 오래전부터 간질환 등의 치료를 위한 한방 약재로서 이용되어 왔으며, 최근에 유용한 생체 활성물질의 탐색 및 개발을 위한 곤충자원으로 크게 주목을 받고 있다. 대한민국 특허공개공보 제10-2020-0023576호에는 발효 흰점박이꽃무지 유충 추출물을 유효성분으로 함유하는 간 기능 개선용 조성물이 기재되어 있으며, 대한민국 특허등록공보 제1615551호에는 점박이꽃무지 유충 유래의 항균 펩티드 및 이의 용도가 기재되어 있다. 특히 한국등록특허 제1828294호, 흰점박이꽃무지 유충으로부터 분리된 화합물을 함유하는 항혈전용 조성물이 기재되어 있어 흰점박이꽃무지 유충으로부터 분리된 화합물이 항혈전 활성이 있는 것이 보고되었다. 그러나 본 발명의 흰점박이꽃무지 유충 추출물의 수면개선 효과는 알려지지 않았다.White-spotted flower radish winters as a 3 instar mature larva, and the adults are active during the daytime and feed on mature fruits such as peaches and pears, or the sap of corn and oak trees. Their larvae inhabit humus soils rich in organic matter, such as compost or haystacks. White-spotted flower radish has long been used as a herbal medicine for the treatment of liver diseases, etc., and has recently attracted great attention as an insect resource for the search and development of useful bioactive substances. Korean Patent Laid-Open Publication No. 10-2020-0023576 describes a composition for improving liver function containing a fermented white spot flower radish larva extract as an active ingredient, and Korean Patent Registration No. 1615551 discloses an antibacterial agent derived from spotted flower radish larvae. Peptides and their uses are described. In particular, Korean Patent No. 1828294, which describes an antithrombotic composition containing a compound isolated from White spot larvae, has been reported to have antithrombotic activity of the compound isolated from White spot larvae. However, the sleep improvement effect of the larva extract of the present invention is not known.
본 발명의 목적은 흰점박이꽃무지 유충 추출물을 함유하는 수면개선용 조성물을 제공하는 데 있다.It is an object of the present invention to provide a composition for improving sleep containing an extract of white spot flower radish larvae.
본 발명의 또 다른 목적은 흰점박이꽃무지 유충으로부터 높은 수면개선 활성을 갖는 추출물의 제조방법물을 제공하는 데 있다.Another object of the present invention is to provide a method for preparing an extract having a high sleep improvement activity from larvae of white spot flower larvae.
본 발명은 흰점박이꽃무지(Protaetia brevitarsis seulensis) 유충 추출물을 유효성분으로 포함하는 것을 특징으로 하는 수면개선용 약학 조성물을 제공한다. 상기 흰점박이꽃무지 유충 추출물은, 물(100% H2O)로, 40~80℃에서 2~8시간 추출한 것일 수 있다. 보다 바람직하게는 상기 흰점박이꽃무지 유충 추출물은, 물(100% H2O)로, 50~70℃에서 6~8시간 추출한 것일 수 있다.The present invention provides a sleep improvement pharmaceutical composition comprising an extract of larvae of Protaetia brevitarsis seulensis as an active ingredient. The white spot flower radish larva extract may be extracted with water (100% H 2 O) at 40 to 80° C. for 2 to 8 hours. More preferably, the larvae extract of White-spotted flower radish larvae may be extracted with water (100% H 2 O) at 50 to 70° C. for 6 to 8 hours.
상기 흰점박이꽃무지 유충 추출물은 건조된 것 또는 생물을 그대로 사용할 수 있으며, 1령, 2령, 3령의 유충을 사용할 수 있으나, 바람직하게는 3령의 유충을 사용한다.The larvae extract of White-spotted flower radish larvae can be dried or used as it is, and 1st, 2nd, and 3rd instar larvae can be used, but preferably 3rd instar larvae are used.
상기 흰점박이꽃무지 유충 추출물은 물, 아세트산 수용액, C1 내지 C4의 알코올 또는 이들의 혼합물을 용매로 하여 추출할 수 있으며, 바람직하게는 물 또는 1% 아세트산을 용매로 하며, 더욱 바람직하게는 물(100% H2O)을 용매로 사용한다.The larvae extract of White-spotted flower radish larvae may be extracted using water, an aqueous acetic acid solution, C1 to C4 alcohol, or a mixture thereof as a solvent, preferably water or 1% acetic acid as a solvent, more preferably water ( 100% H 2 O) is used as a solvent.
상기 흰점박이꽃무지 유충 추출물은 흰점박이꽃무지 유충 건조물 또는 생물을 용매에 침지시키고 40~100℃에서 2~8시간 추출할 수 있으며, 바람직하게는 40~80℃에서 4~8시간 추출한 것일 수 있으며, 더욱 바람직하게는 50~70℃에서 6~8시간 추출한다.The larvae extract may be obtained by immersing dried larvae or living organisms in a solvent and extracting it at 40-100° C. for 2-8 hours, preferably at 40-80° C. for 4-8 hours. and more preferably at 50 to 70° C. for 6 to 8 hours.
본 발명의 흰점박이꽃무지 유충 추출물을 유효성분으로 포함하는 것을 특징으로 하는 수면개선용 약학 조성물은 숙면장애, 수면유지장애, 중도각성, 조기각성, 불면증, 일주기 리듬 수면장애, 사건수면으로 이루어진 군에서 선택되는 어느 하나 이상의 수면장애를 개선하는 수면개선용일 수 있다. 숙면장애는 이른바 얕은 잠으로, 수면중 자주 각성을 일으키는 것을 말하며, 중도각성은 잠이 들었으나 중간에 여러번 잠이 깨어 다시 잠이 들기까지 시간이 걸리는 증상을 말한다. 조기각성은 충분한 수면시간을 채우지 못하고 일찍 잠에서 깨어 다시 잠들기 힘든 수면장애이다. 잠이 드는데 어려움을 겪는 입면장애가 길어지고 이러한 수면 장애가 주 3회 이상씩 한 달 이상 반복되는 경우 불면증으로 진단한다.A pharmaceutical composition for improving sleep, characterized in that it contains the extract of the larvae of the present invention as an active ingredient, consisting of sleep disorders, sleep maintenance disorders, moderate awakenings, early awakenings, insomnia, circadian rhythm sleep disorders, and parasomnias. It may be for sleep improvement to improve any one or more sleep disorders selected from the group. Deep sleep disorder is a so-called light sleep, which refers to frequent awakenings during sleep, and moderate awakening refers to a symptom in which a person falls asleep but wakes up several times in the middle and takes a long time to fall asleep again. Early awakening is a sleep disorder in which it is difficult to get back to sleep after not getting enough sleep. Insomnia is diagnosed when sleep disturbances, which are difficult to fall asleep, are prolonged and these sleep disturbances are repeated 3 or more times a week for more than a month.
본 발명의 흰점박이꽃무지 유충 추출물을 유효성분으로 포함하는 것을 특징으로 하는 수면개선용 약학 조성물은 특히 수면 유도시간 감소 또는 수면시간 연장인 것을 특징으로 한다.The pharmaceutical composition for improving sleep, comprising the extract of the white-spotted flower radish larvae of the present invention as an active ingredient, is particularly characterized in that it reduces sleep induction time or prolongs sleep time.
상기 약학적 조성물은, 각각 통상의 방법에 따라 산제, 과립제, 정제, 캡슐제, 현탁액, 에멀젼, 시럽, 액제, 에어로졸 등의 경구형 제형, 외용제, 좌제 및 멸균주사용액의 형태로 제형화하여 사용될 수 있다. 상기 약학적 조성물에 포함될 수 있는 담체, 부형제 및 희석제로는 락토즈, 덱스트로즈, 수크로스, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘포스페이트, 칼슘 실리케이트, 셀룰로즈, 메틸 셀룰로즈, 미정질 셀룰로즈, 폴리비닐 피롤리돈, 물, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 탈크, 마그네슘 스테아레이트 및 광물유를 들 수 있다. 제제화할 경우에는 보통 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제, 감미제, 산미제 등의 희석제 또는 부형제를 사용하여 조제된다. 경구투여를 위한 고형제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 이러한 고형제제는 본 발명의 흰점박이꽃무지 유충 추출물에 적어도 하나 이상의 부형제, 예를 들면, 전분, 탄산칼슘, 수크로스 또는 락토즈, 젤라틴 등을 섞어 조제된다. 또한 단순한 부형제 이외에 스테아린산 마그네슘, 탈크 같은 윤활제들도 사용된다. 경구를 위한 액상 제제로는 현탁제, 내용액제, 유제, 시럽제 등이 해당되는데 흔히 사용되는 단순희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제, 산미제 등이 포함될 수 있다. 비경구 투여를 위한 제제에는 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조제제, 좌제가 포함된다. 비수성용제, 현탁제로는 프로필렌글리콜, 폴리에틸렌글리콜, 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. The pharmaceutical composition may be formulated in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, liquids, aerosols, etc., external preparations, suppositories, and sterile injection solutions according to conventional methods, respectively. can Carriers, excipients and diluents that may be included in the pharmaceutical composition include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. In the case of formulation, it is prepared using commonly used diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrants, surfactants, sweeteners, and acidulants. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc., and these solid preparations include at least one excipient, for example, starch, calcium carbonate, It is prepared by mixing sucrose, lactose, or gelatin. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Liquid formulations for oral use include suspensions, solutions, emulsions, syrups, etc. In addition to water and liquid paraffin, which are commonly used simple diluents, various excipients such as wetting agents, sweetening agents, fragrances, preservatives, and acidulants are used. may be included. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. Non-aqueous solvents and suspending agents include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate. As the base of the suppository, witepsol, macrogol, tween-61, cacao butter, laurin fat, glycerogelatin, and the like can be used.
본 발명의 약학적 조성물의 투여량은 치료받을 대상의 연령, 성별, 체중과, 치료할 특정 질환 또는 병리 상태, 질환 또는 병리 상태의 심각도, 투여 경로 및 처방자의 판단에 따라 달라질 것이다. 이러한 인자에 기초한 투여량 결정은 당업자의 수준 내에 있으며, 일반적으로 투여량은 0.01㎎/㎏/일 내지 대략 500㎎/㎏/일의 범위이다. 바람직한 투여량은 0.1㎎/㎏/일 내지 200㎎/㎏/일이며, 더 바람직한 투여량은 1㎎/㎏/일 내지 200㎎/㎏/일이다. 투여는 하루에 한번 투여할 수도 있고, 수회 나누어 투여할 수도 있다. 상기 투여량은 어떠한 면으로든 본 발명의 범위를 한정하는 것은 아니다. The dosage of the pharmaceutical composition of the present invention will vary depending on the age, sex, and weight of the subject to be treated, the specific disease or pathological condition to be treated, the severity of the disease or pathology, the route of administration, and the judgment of the prescriber. Dosage determination based on these factors is within the level of one of ordinary skill in the art, and dosages generally range from 0.01 mg/kg/day to approximately 500 mg/kg/day. A preferred dosage is 0.1 mg/kg/day to 200 mg/kg/day, and a more preferred dosage is 1 mg/kg/day to 200 mg/kg/day. Administration may be administered once a day, or may be administered in several divided doses. The above dosage does not limit the scope of the present invention in any way.
본 발명의 약학적 조성물은 쥐, 가축, 인간 등의 포유동물에 다양한 경로로 투여될 수 있다. 투여의 모든 방식은 예상될 수 있는데, 예를 들면, 경구, 직장 또는 정맥, 근육, 피하, 자궁 내 경막 또는 뇌혈관 내 주사 및 피부 도포에 의해 투여될 수 있다. 본 발명의 흰점박이꽃무지 유충 추출물은 독성 및 부작용이 거의 없으므로 예방 목적으로 장기간 복용시에도 안심하고 사용할 수 있는 약제이다. The pharmaceutical composition of the present invention may be administered to mammals such as mice, livestock, and humans by various routes. Any mode of administration can be envisaged, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, intrauterine or intracerebrovascular injection and dermal application. Since the larva extract of the present invention has almost no toxicity and side effects, it is a drug that can be safely used even when taken for a long period of time for the purpose of prevention.
본 발명의 다른 일면으로, 본 발명은 흰점박이꽃무지 유충 추출물을 유효성분으로 포함하는 것을 특징으로 하는 수면개선용 건강기능식품을 제공한다.In another aspect of the present invention, the present invention provides a health functional food for improving sleep, characterized in that it contains an extract of white spot flower radish larvae as an active ingredient.
상기 건강기능식품은 흰점박이꽃무지 유충 추출물이 전체 식품 총 중량에 대하여 바람직하게는 0.001~50중량%, 더 바람직하게는 0.001~30중량%, 가장 바람직하게는 0.001~10중량%로 하여 첨가될 수 있다.The health functional food 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 whole food. can
상기 건강기능식품은 정제, 캡슐제, 환제 또는 액제 등의 형태를 포함하며, 본 발명의 추출물을 첨가할 수 있는 식품으로는, 예를 들어, 각종 식품류, 음료, 껌, 차, 비타민 복합제, 건강기능성식품류 등이 있다.The health functional food includes the form of tablets, capsules, pills, or liquids, and the food to which the extract of the present invention can be added, for example, various foods, beverages, gum, tea, vitamin complex, health Functional foods, etc.
상기 수면개선은 숙면장애, 수면유지장애, 중도각성, 조기각성, 불면증, 일주기 리듬 수면장애, 사건수면으로 이루어진 군에서 선택되는 어느 하나 이상의 수면장애를 개선하는 수면개선용일 수 있다. 숙면장애는 이른바 얕은 잠으로 수면중 자주 각성을 일으키는 것을 말하며, 중도각성은 잠이 들었으나 중간에 여러번 잠이 깨어 다시 잠이 들기까지 시간이 걸리는 증상을 말한다. 조기각성은 충분한 수면시간을 채우지 못하고 일찍 잠에서 깨어 다시 잠들기 힘든 수면장애이다. 잠이 드는데 어려움을 겪는 입면장애가 길어지고 이러한 수면 장애가 주 3회 이상씩 한달 이상 반복되는 경우 불면증으로 진단한다.The sleep improvement may be for sleep improvement for improving any one or more sleep disorders selected from the group consisting of deep sleep disorder, sleep maintenance disorder, moderate awakening, early awakening, insomnia, circadian rhythm sleep disorder, and parasomnia. Deep sleep disorder refers to a so-called light sleep, which frequently wakes up during sleep, while moderate awakening refers to a symptom in which a person falls asleep but wakes up several times in the middle and takes a long time to fall asleep again. Early awakening is a sleep disorder in which it is difficult to get back to sleep after not getting enough sleep. Insomnia is diagnosed when sleep disturbances, which are difficult to fall asleep, are prolonged and these sleep disturbances are repeated 3 or more times a week for more than a month.
본 발명의 흰점박이꽃무지 유충 추출물을 유효성분으로 포함하는 것을 특징으로 하는 수면개선용 약학 조성물은 특히 수면 유도시간 감소 또는 수면시간 연장인 것을 특징으로 한다.The pharmaceutical composition for improving sleep, comprising the extract of the white-spotted flower radish larvae of the present invention as an active ingredient, is particularly characterized in that it reduces sleep induction time or prolongs sleep time.
본 발명은 흰점박이꽃무지 유충 추출물을 함유하는 수면개선용 조성물에 관한 것으로, 구체적으로는 흰점박이꽃무지 유충 추출물을 함유하는 수면 개시시간 단축 및 수면시간 연장용 조성물에 관한 것이다. 본 발명의 흰점박이꽃무지 유충 추출물을 함유하는 수면개선용 조성물을 통해, 안전하고 부작용이 없는 수면 개선 조성물의 개발할 수 있다. The present invention relates to a composition for improving sleep containing an extract of larvae of White-spotted larvae, and more particularly, to a composition for shortening sleep initiation time and extending sleep time, comprising an extract Through the composition for improving sleep containing the extract of the larva extract of the present invention, it is possible to develop a sleep improving composition that is safe and has no side effects.
도 1은 본 발명의 용매를 달리한 흰점박이꽃무지 유충 추출물이 ICR 마우스의 수면시간에 미치는 영향을 보여주는 그래프이다.
도 2는 본 발명의 흰점박이꽃무지(Protaetia brevitarsis seulensis) 유충 추출물의 HPLC 분석 결과이다.
도 3은 지표성분 함량평가를 위한 L-트립토판 표준품 0.125 mg/mL와 흰점박이꽃무지 유충 추출물의 HPLC 분석 결과이다.
도 4는 본 발명의 흰점박이꽃무지 유충의 추출 용매에 따른 지표성분의 차이를 보여주는 HPLC 분석 결과이다.
도 5는 본 발명의 흰점박이꽃무지 유충의 추출 온도에 따른 지표성분의 차이를 보여주는 HPLC 분석 결과이다.
도 6은 본 발명의 흰점박이꽃무지 유충의 추출 온도에 따른 지표성분의 차이를 나타낸 그래프이다.
도 7은 본 발명의 흰점박이꽃무지 유충의 추출 시간에 따른 지표성분 검출량의 차이를 보여주는 HPLC 분석 결과이다.
도 8은 본 발명의 흰점박이꽃무지 유충의 추출 시간에 따른 지표성분의 차이를 나타낸 그래프이다.
도 9는 본 발명의 흰점박이꽃무지 유충 추출물(PBSWE)의 수면개선 효과를 확인하기 위한 실험 시간표를 도시한 모식도이다.
도 10은 본 발명의 흰점박이꽃무지 유충 추출물(PBSWE)의 수면 유도시간에 미치는 영향을 보여주는 그래프이다.
도 11은 본 발명의 흰점박이꽃무지 유충 추출물(PBSWE)이 ICR 마우스의 수면시간에 미치는 영향을 보여주는 그래프이다.
도 12는 ICR 마우스의 시상하부 고정 과정을 보여주는 사진이다.
도 13은 본 발명의 실험에 사용한 ICR 마우스의 시교차 상핵(SCN) 위치를 보여주는 그림이다.
도 14는 본 발명의 흰점박이꽃무지 유충 추출물(PBSWE)의 ICR 마우스의 아데노신 수용체 A1에 미치는 영향을 보여주는 그래프이다.1 is a graph showing the effect of a larvae extract of the present invention in which different solvents are used on sleep time of ICR mice.
2 is a HPLC analysis result of a larval extract of Protaetia brevitarsis seulensis of the present invention.
3 is an HPLC analysis result of 0.125 mg/mL of L-tryptophan standard and an extract of larvae extract of L-tryptophan for index component content evaluation.
4 is an HPLC analysis result showing the difference in the indicator components according to the extraction solvent of the larva of the present invention.
5 is an HPLC analysis result showing the difference in indicator components according to the extraction temperature of the larva of the present invention.
6 is a graph showing the difference in index components according to the extraction temperature of the larva of the present invention.
7 is an HPLC analysis result showing the difference in the detection amount of the indicator component according to the extraction time of the larva of the present invention.
8 is a graph showing the difference in the index component according to the extraction time of the larva of the present invention.
9 is a schematic diagram showing an experimental timetable for confirming the sleep improvement effect of the larvae extract (PBSWE) of the present invention.
10 is a graph showing the effect of the larvae extract (PBSWE) of the present invention on sleep induction time.
11 is a graph showing the effect of the larvae extract (PBSWE) of the present invention on the sleep time of ICR mice.
12 is a photograph showing the hypothalamic fixation process in ICR mice.
13 is a diagram showing the position of the suprachiasmatic nucleus (SCN) of the ICR mouse used in the experiment of the present invention.
14 is a graph showing the effect of the larvae extract (PBSWE) of the present invention on adenosine receptor A1 in ICR mice.
흰점박이꽃무지(Protaetia brevitarsis seulensis) 유충은 오래전부터 한방 약재로서 이용되어 왔으며, 단백질 함량이 풍부해 식용으로도 사용하여왔다. 본 발명자들은 흰점박이꽃무지 유충 추출물의 생리학적 특성을 연구하던 중, 흰점박이꽃무지 유충 추출물로부터 L-트립토판 유사 활성을 확인하고 본 발명을 완성하게 되었다.The larvae of Protaetia brevitarsis seulensis have been used as herbal medicines for a long time. The present inventors have completed the present invention by confirming L-tryptophan-like activity from the larvae extract of White-spotted flower radish larvae while studying the physiological characteristics of the extract.
이하 본 발명의 바람직한 실시예를 상세히 설명하기로 한다. 그러나 본 발명은 여기서 설명되는 실시예에 한정되지 않고 다른 형태로 구체화될 수도 있다. 오히려, 여기서 소개되는 내용이 철저하고 완전해지고, 당업자에게 본 발명의 사상을 충분히 전달하기 위해 제공하는 것이다.Hereinafter, preferred embodiments of the present invention will be described in detail. However, the present invention is not limited to the embodiments described herein and may be embodied in other forms. Rather, it is provided so that this disclosure will be thorough and complete, and will fully convey the spirit of the invention to those skilled in the art.
<< 실시예Example 1. One. 흰점박이꽃무지white spot flower plain 유충 추출물의 수면시간 연장효과 확인> Confirmation of sleep time extension effect of larval extract>
본 발명의 발명자들은 선행연구를 통하여 흰점박이꽃무지 유충 추출물로부터 5-히드록시인돌린-2-온(5-hydroxyindolin-2-one), 1-메틸1,2,3,4-테트라히드로-β-카르볼린-3-카르복실산(1-methyl-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid) (KR10-1828294 B1) 등의 많은 생리적 활성 화합물을 확인, 분리하는 과정에서 수면개선과 관련있는 L-트립토판 및 이의 유도체들이 포함되어 있는 것을 확인하고 본 발명을 안출하였다.The inventors of the present invention have obtained 5-hydroxyindolin-2-one, 1-methyl1,2,3,4-tetrahydro- Identification and isolation of many physiologically active compounds such as β-carboline-3-carboxylic acid (1-methyl-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid) (KR10-1828294 B1) In the process, it was confirmed that L-tryptophan and its derivatives related to sleep improvement were included, and the present invention was devised.
먼저 흰점박이꽃무지 유충 추출물의 수면시간 연장효과를 확인하기 위하여 건조 흰점박이꽃무지 유충 10g을 100 mL의 물 또는 70%, 95% 에탄올에서 각각 1시간 동안 가열 추출한 후, 추출물을 감압 농축하여 건고하였다. 건고물은 분쇄후, 물에 현탁하여 소정의 농도로 사용하였다.First, in order to check the sleep time extension effect of the larvae extract, 10 g of dried chrysanthemum larvae were heated and extracted in 100 mL of water or 70% and 95% ethanol for 1 hour, respectively, and the extract was concentrated under reduced pressure to dryness. did After grinding, the dried product was suspended in water and used at a predetermined concentration.
특정병원체 부재 (SPF) ICR 마우스(CrljOri:CD1(ICR); (주) 오리엔트 바이오, 한국) 수컷에 각 추출물의 농도를 300 mg/kg이 되도록 경구투여하고, 투여 30분 후, Pentobarbital sodium 45 mg/10mL/kg을 복강투여한 다음, 라이팅 반사(Righting reflex) 소실 시간부터 깨어나기까지의 시간(수면시간)을 측정하여 도 1에 나타내었다. 대조군으로는 동량의 물을 사용하였으며, 각 마우스는 3반복 실시하여 평균과 표준편차로 나타내었다.Specific pathogen-free (SPF) ICR mice (CrljOri:CD1(ICR); Orient Bio, Korea) were orally administered at a concentration of 300 mg/kg of each extract to males, and 30 minutes after administration, Pentobarbital sodium 45 mg After intraperitoneal administration of /10mL/kg, the time from the disappearance of the lighting reflex to the time to wake up (sleep time) was measured and shown in FIG. 1 . As a control group, the same amount of water was used, and each mouse was repeated 3 times and expressed as the mean and standard deviation.
도 1에서 보는 바와 같이 흰점박이꽃무지 유충 추출물은 대조군과 비교하여 유의한 수준으로 마우스의 수면시간을 연장시키는 것을 확인하였다. 특히 물(100% H2O)을 용매로 사용한 추출물이 70% 또는 95% 에탄올보다 수면시간 연장효과가 뛰어난 것을 확인하였다. 이러한 결과를 토대로 흰점박이꽃무지 유충 추출물에 포함된 수면개선 관련 화합물을 HPLC를 통해 확인하였다.As shown in FIG. 1 , it was confirmed that the larvae extract of White-spotted flower radish larvae significantly extended the sleeping time of mice compared to the control group. In particular, it was confirmed that the extract using water (100% H 2 O) as a solvent was superior to the sleep time extension effect than 70% or 95% ethanol. Based on these results, the sleep improvement-related compounds contained in the larvae extract of White-spotted flower radish larvae were identified through HPLC.
<< 실시예Example 2. 2. 흰점박이꽃무지white spot flower plain 유충 추출물로부터 지표성분 확인> Identification of indicator components from larval extracts>
실시예 1과 동일한 방법으로 흰점박이꽃무지 유충을 열수추출하고, 감압 농축하여 흰점박이꽃무지 유충 추출물을 얻었다. 상기 추출물을 물에 현탁하여 10%(v/v)~30%(v/v)의 메탄올 수용액 농도구배를 갖는 Phenomenex biphenyl 5u, 250×4.6㎜ 컬럼을 이용한 SHIMADZU HPLC system을 통해 추출물을 분석하였다. 이때 온도는 30℃, 유속은 0.5 ml/min이었으며, UV/Vis (280nm)로 확인하였다.In the same manner as in Example 1, the larvae of White-spotted flower radish were extracted with hot water and concentrated under reduced pressure to obtain an extract of White-spotted flower radish larvae. The extract was suspended in water and the extract was analyzed through SHIMADZU HPLC system using a
도 2에서 보는 바와 같이, 흰점박이꽃무지 유충 추출물에서 다수의 화합물을 확인하였으며, 일정 분획에서 L-트립토판이 포함된 것을 확인하였다. As shown in FIG. 2 , a number of compounds were identified in the larvae extract, and it was confirmed that L-tryptophan was included in a certain fraction.
L-트립토판은 단백질 생합성에 이용되는 α-아미노산의 일종으로, 비타민 B3의 전구체이면서 신경 전달 물질 세로토닌, 호르몬 멜라토닌의 전구체로, 우울, 불안, 수면장애, 체중증가를 개선하고 특히 수면패턴을 안정화시켜주는 것으로 알려져 있다.L-tryptophan is a kind of α-amino acid used in protein biosynthesis. It is a precursor of vitamin B3 and a precursor of the neurotransmitter serotonin and the hormone melatonin. known to give
L-트립토판의 흰점박이꽃무지 유충 추출물 내의 함량을 평가하기 위하여 L-트립토판 표준품 0.125 mg/mL 농도로 상기 조건으로 HPLC 분석하고 이를 도 3에 나타내었다. 이때 L-트립토판 표준품 0.125 mg/mL는 HPLC 분석에서 peak area 1077162를 나타내었다. 실시예 1과 동일한 방법으로 제조한 흰점박이꽃무지 유충 추출물을 10 mg/mL 농도로 HPLC 분석 시 L-트립토판의 peak area는 1124942로 나타났다. 따라서 흰점박이꽃무지유충 추출물 내의 L-트립토판의 함량비는 아래와 같이 계산하여 약 1.3% (13 mg/g) 함유하는 것으로 확인하였다.In order to evaluate the content of L-tryptophan in the L-Tryptophan larvae extract, HPLC analysis was performed under the above conditions at a concentration of 0.125 mg/mL of the L-tryptophan standard, and this is shown in FIG. 3 . At this time, 0.125 mg/mL of L-tryptophan standard showed a peak area of 1077162 in HPLC analysis. The peak area of L-tryptophan was 1124942 by HPLC analysis of the larvae extract prepared in the same manner as in Example 1 at a concentration of 10 mg/mL. Therefore, it was confirmed that the content ratio of L-tryptophan in the White Spotted flower larvae extract was calculated as follows and contained about 1.3% (13 mg/g).
이를 토대로 실시예 1에서 300 mg/kg 의 흰점박이꽃무지 유충 추출물을 ICR 마우스에 경구투여하여 수면시간 연장효과를 나타낸 결과를 분석하여 보면, ICR 마우스에 적용된 흰점박이꽃무지 유충 추출물 내의 L-트립토판의 농도는 약 3.9 mg/kg 인 것을 알 수 있다. 그러나 이러한 용량은 일반적인 L-트립토판의 복용량인 1000 ~ 2000 mg/day 에 비하여 현저히 낮은 용량으로, 이로부터 흰점박이꽃무지 유충 추출물 내에 L-트립토판 이외의 다른 수면개선 활성성분이 포함되어 수면시간 연장에 작용했을 가능성을 확인하였다. 이후 실험에서 흰점박이꽃무지 유충 추출물 내의 활성 화합물을 확인한 결과, L-트립토판 및 L-트립토판 유도체인 (3S)-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid, (1R,3S)-1-methyl-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid, (1S,3S)-1-methyl-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid, methyl 9H-pyrido[3,4-β]indole-1-carboxylate가 포함되는 것을 확인하였으며, 이들 L-트립토판 유도체의 구조적 특징이 L-트립토판과 유사함에 따라 L-트립토판의 수득조건에서 L-트립토판 유도체의 수득도 함께 증가할 것으로 예상되었다.Based on this, an analysis of the results showing the effect of extending sleep time by oral administration of 300 mg/kg of white spot flower radish larva extract in Example 1 to ICR mice shows that L-tryptophan in the extract It can be seen that the concentration of about 3.9 mg / kg. However, this dose is significantly lower than the general L-tryptophan dose of 1000 ~ 2000 mg/day. Possibility of working was confirmed. As a result of confirming the active compounds in the larva extract of P. oleraceae in a later experiment, L-tryptophan and L-tryptophan derivatives, (3S)-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid, (1R ,3S)-1-methyl-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid, (1S,3S)-1-methyl-1,2,3,4-tetrahydro-β-carboline It was confirmed that -3-carboxylic acid, methyl 9H-pyrido[3,4-β]indole-1-carboxylate was included, and as the structural characteristics of these L-tryptophan derivatives were similar to those of L-tryptophan, L-tryptophan was obtained It was expected that the yield of L-tryptophan derivatives also increased under the conditions.
이러한 흰점박이꽃무지 유충 추출물의 L-트립토판 및 L-트립토판 유도체들이 함께 수면 개선에 효과가 있을 것으로 예상하고 L-트립토판을 지표성분으로 선정하여, 상기 지표성분의 수득률을 높일 수 있는 최적화된 추출조건을 확립하였다.Optimized extraction conditions that can increase the yield of L-tryptophan and L-tryptophan derivatives of the L-tryptophan and L-tryptophan derivatives of the larvae extract, and select L-tryptophan as an index component has been established.
<< 실시예Example 3. 3. 흰점박이꽃무지white spot flower plain 유충 추출물의 추출조건 최적화> Optimization of extraction conditions for larval extract>
상기 실시예 2에서 확인한 흰점박이꽃무지 유충 추출물의 L-트립토판 및 L-트립토판 유사 성분의 수득률을 높일 수 있는 최적화 추출조건을 확립하기 위하여 L-트립토판을 지표성분으로 사용하여 이하 실험을 실시하였다.In order to establish optimized extraction conditions that can increase the yield of L-tryptophan and L-tryptophan-like components of the larvae extract confirmed in Example 2, the following experiment was performed using L-tryptophan as an index component.
3.1 3.1 추출용매extraction solvent 설정 Set
건조된 흰점박이꽃무지 유충 10.0 g 씩을 100% H2O 100 mL, 1%(v/v) 아세트산 수용액(1% acetic acid in 100% H2O) 100 mL 및 1%(v/v) 아세트산 94% 에탄올 (in 94% EtOH) 100 mL로 각각 80℃에서 1시간 추출하였다. 흰점박이꽃무지 유충 추출물은 100% H2O를 용매로 한 추출물(PBSWE), 1% 아세트산 수용액을 용매로 한 추출물(PBSAWE) 및 1% 아세트산 94% 에탄올을 용매로 한 추출물(PBSAEE)이 각각 4.2 g 씩이 수득되어 42%의 수율로 동일하였다.10.0 g of dried white spot larvae were mixed with 100 mL of 100% H 2 O, 100 mL of 1% (v/v) aqueous acetic acid (1% acetic acid in 100% H 2 O) and 1% (v/v) acetic acid. Each was extracted with 100 mL of 94% ethanol (in 94% EtOH) at 80 °C for 1 hour. The larvae extract of White Spotted flower radish larvae were 100% H 2 O as a solvent (PBSWE), an extract with 1% aqueous acetic acid as a solvent (PBSAWE), and an extract with 1% acetic acid and 94% ethanol as a solvent (PBSAEE), respectively. 4.2 g each was obtained, which was the same in a yield of 42%.
이를 상기 실시예 2와 같은 방법으로 HPLC 분석한 결과 중 지표성분의 수득률이 높은 100% H2O(PBSWE) 및 1% 아세트산 수용액을 용매로 한 추출물(PBSAWE)의 HPLC 결과를 도 4에 나타내었다. 도 4에서 보는 바와 같이 100% H2O를 용매로 한 조건에서 무게대비 지표성분의 함량이 1% 아세트산 수용액을 용매로 한 추출물(PBSAWE)보다 2배 가량 높게 나타났다. 따라서 이후 실험에서 흰점박이꽃무지 유충의 추출용매를 100% H2O로 사용하였다.As a result of HPLC analysis in the same manner as in Example 2, HPLC results of extracts (PBSAWE) using 100% H 2 O (PBSWE) and 1% acetic acid aqueous solution as solvents with a high yield of indicator components are shown in FIG. . As shown in FIG. 4 , the content of the indicator component by weight was approximately twice higher than that of the extract (PBSAWE) using 1% acetic acid aqueous solution as a solvent under the conditions of 100% H 2 O as a solvent. Therefore, in subsequent experiments, 100% H 2 O was used as the extraction solvent for the larvae of the larvae.
3.2 추출온도 설정3.2 Setting the extraction temperature
건조된 흰점박이꽃무지 유충 1.0 g 씩을 100% H2O 10 mL을 용매로 하여 각각 실온(25℃), 40℃, 50℃, 60℃, 70℃, 80℃, 90℃ 및 100℃에서 1시간 추출하였다. 이후, 흰점박이꽃무지 유충 추출물은 실온(PBSWE25), 40℃(PBSWE40), 50℃(PBSWE50), 60℃(PBSWE60), 70℃(PBSWE70), 80℃(PBSWE80), 90℃(PBSWE90) 및 100℃(PBSWE100)에서 각각 0.3g을 100% H2O를 용매로 한 추출물(PBSWE)은 각각 약 3 g 씩이 수득되어 30%의 수율로 동일하였다.1.0 g of dried white spot larvae were extracted for 1 hour at room temperature (25°C), 40°C, 50°C, 60°C, 70°C, 80°C, 90°C and 100°C, respectively, using 10 mL of 100% H2O as a solvent. did Thereafter, the white spot larva extract was prepared at room temperature (PBSWE25), 40 °C (PBSWE40), 50 °C (PBSWE50), 60 °C (PBSWE60), 70 °C (PBSWE70), 80 °C (PBSWE80), 90 °C (PBSWE90) and At 100° C. (PBSWE100), 0.3 g of each extract (PBSWE) using 100% H 2 O as a solvent was obtained in an amount of about 3 g each, which was the same in a yield of 30%.
이를 상기 실시예 1과 같은 방법으로 HPLC 분석한 결과를 도 5에 나타내었다. 건조 흰점박이꽃무지 유충을 40℃에서 한 시간 추출한 경우(PBSWE40), 실온추출보다 지표성분의 함량이 증가하였으며, 50℃에서 한시간 추출한 경우(PBSWE50) 그 함량이 현격히 높아졌다. 또한, 60℃에서 한시간 추출한 경우(PBSWE60) 무게 대비 지표성분의 함량이 가장 높았다. 70℃로 추출한 경우(PBSWE70) 지표성분의 함량은 다소 감소하여 80℃로 추출한 경우(PBSWE80) 60℃에서 한 시간 추출한 경우(PBSWE60)보다 약 33.7% 감소하였으며, 90℃(PBSWE100) 및 100℃(PBSWE100)로 추출한 경우 60℃에서 한 시간 추출한 경우(PBSWE60)보다 지표성분의 함량이 약 40% 감소하였다. 이를 그래프로 나타내면 도 6과 같다. 상기와 같은 결과를 통하여 흰점박이꽃무지 유충 추출물의 지표성분은 50~70℃로 추출하는 경우, 가장 높은 수득률을 얻을 수 있다는 것을 확인하였다. 이후 실험에서 흰점박이꽃무지 유충을 추출용매 100% H2O로, 60℃에서 추출하였다.The results of HPLC analysis in the same manner as in Example 1 are shown in FIG. 5 . The content of indicator components increased when the dried white spot larvae were extracted at 40°C for one hour (PBSWE40), compared to the room temperature extraction, and when extracted at 50°C for one hour (PBSWE50), the content was significantly increased. In addition, in the case of extraction at 60°C for one hour (PBSWE60), the content of the index component was the highest compared to the weight. In the case of extraction at 70 ° C (PBSWE70), the content of the indicator component decreased slightly, and when extracted at 80 ° C (PBSWE80), it was reduced by about 33.7% compared to the case of extraction at 60 ° C for one hour (PBSWE60), and at 90 ° C (PBSWE100) and 100 ° C ( In the case of extraction with PBSWE100), the content of the index component was reduced by about 40% compared to the case of extraction at 60° C. for one hour (PBSWE60). 6 is a graph showing this. Through the above results, it was confirmed that the highest yield can be obtained when the index component of the larvae extract is extracted at 50~70℃. In a subsequent experiment, the larvae of the white-spotted flower radish were extracted with an extraction solvent of 100% H 2 O at 60°C.
3.3 추출시간 설정3.3 Extraction time setting
건조된 흰점박이꽃무지 유충 5.0 g 씩을 100% H2O 10 mL을 용매로 하여 각각 60℃에서 1, 2, 4, 6, 8시간 각각 추출하여 추출 최적화 조건을 확인하였다. 흰점박이꽃무지 유충 추출물은 1시간(PBSWE601), 2시간(PBSWE602), 4시간(PBSWE604), 6시간(PBSWE606) 및 8시간(PBSWE608) 추출물에서 각각 0.3g, 0.4g, 0.2g, 0.25g, 0.5g을 수득하였다.Extraction optimization conditions were confirmed by extracting 5.0 g of dried white spot larvae each using 10 mL of 100% H 2 O as a solvent at 60° C. for 1, 2, 4, 6, and 8 hours, respectively. Platypus larva extract was 0.3 g, 0.4 g, 0.2 g, 0.25 g in 1 h (PBSWE601), 2 h (PBSWE602), 4 h (PBSWE604), 6 h (PBSWE606) and 8 h (PBSWE608) extracts, respectively. , 0.5 g was obtained.
이를 상기 실시예 1과 같은 방법으로 HPLC 분석한 결과를 도 7에 나타내었다. 도 7에서 보는 바와 같이 건조 흰점박이꽃무지 유충을 60℃에서 각 시간별로 추출한 경우, 무게 대비 지표성분의 함량은 6시간 추출이 가장 높았다. 이를 그래프로 나타내면 도 8과 같다. 도 8에서보는 바와 같이 6시간 추출 시, 흰점박이꽃무지 유충 내 지표성분의 함량이 가장 높았으며, 8시간보다 오랜 시간 추출하는 경우, 추출 수율의 증대 효과는 없고 에너지 사용량만 증가하는 것을 예측할 수 있었다.The results of HPLC analysis in the same manner as in Example 1 are shown in FIG. 7 . As shown in FIG. 7 , when the dried white-spotted flower radish larvae were extracted at 60° C. for each hour, the content of the index component relative to the weight was the highest for 6 hours of extraction. 8 is a graph showing this. As shown in FIG. 8, the content of the index component in the larvae of the white spot flower was the highest when extracted for 6 hours, and when extracted for a longer time than 8 hours, it was possible to predict that there is no effect of increasing the extraction yield and only the energy consumption increases. there was.
따라서 흰점박이꽃무지 유충을 추출용매 100% H2O로, 60℃에서 6~8시간 추출한 경우, 무게 대비 지표성분의 함량이 높다는 것을 확인하고, 최적화 추출조건을 확립하였다.Therefore, it was confirmed that the content of the index component was high compared to the weight when extracting the larvae of the White Spotted flower radish with 100% H 2 O as the extraction solvent at 60° C. for 6 to 8 hours, and optimal extraction conditions were established.
<< 실시예Example 4. 4. ICRICR 마우스에서 in the mouse 흰점박이꽃무지white spot flower plain 유충 추출물의 반복투여에 따른 수면시간에 미치는 효과 확인> Confirmation of effect on sleep time according to repeated administration of larval extract>
4.1 4.1 ICRICR 마우스에서 in the mouse 흰점박이꽃무지white spot flower plain 유충 추출물( larvae extract ( PBSWEPBSWE )) 의 수면sleep of 유도시간에 미치는 효과 확인 Confirmation of effect on induction time
본 발명에 따른 흰점박이꽃무지 유충 추출물의 수면개선 효과를 확인하기 위하여 실시예 1과 같이 특정병원체 부재 (SPF) ICR 마우스(CrljOri:CD1(ICR); (주) 오리엔트 바이오, 한국)를 준비하였다. 상기 수컷 ICR 마우스 56마리를 입수 후 5일간 동물실 내에서 순화시켜 사용하였으며, 이 중 무작위 선택한 48마리를 실험에 사용하였다. 실험에 사용한 동물은 ㈜켐온의 실험동물운영위원회에 의해 승인(심의번호 : 2019-09-011)된 실험동물 윤리규정에 적합하게 취급하였다. 동물은 온도 23 ± 3℃, 상대습도 55 ± 15 %, 환기횟수 10-20 회/hr, 조명시간 12 시간 (오전 8 시 점등-오후 8 시 소등) 및 조도 150-300 Lux로 유지되는 경기바이오센터 동물사육구역 1 호실에서 사육하였으며, 온도와 상대습도는 매시간 컴퓨터 시스템을 이용하여 측정하였고, 환기횟수 및 조도는 정기적으로 측정하였다. 실험기간 동안 시험 결과에 영향을 줄만한 이상은 없었다.In order to confirm the sleep improvement effect of the larvae extract according to the present invention, specific pathogen-free (SPF) ICR mice (CrljOri:CD1(ICR); Orient Bio, Korea) were prepared as in Example 1. . The 56 male ICR mice were acclimatized in an animal room for 5 days after acquisition, and 48 randomly selected mice were used in the experiment. Animals used in the experiment were handled in accordance with the ethical regulations for laboratory animals approved by the Experimental Animal Steering Committee of Chemon Co., Ltd. (Review No.: 2019-09-011). Animals are kept at a temperature of 23 ± 3 °C, relative humidity of 55 ± 15 %, ventilation frequency of 10-20 times/hr, illumination time of 12 hours (lights on at 8 am – lights off at 8 pm), and illuminance at 150-300 Lux. They were bred in
ICR 마우스는 하기 6개 그룹으로 군을 분리하고(G1~G6) 표 1과 같이 투여하였다. 투여물질의 투여 시간표는 도 9에 나타내었다.ICR mice were grouped into the following six groups (G1-G6) and administered as shown in Table 1. The administration schedule of the administered material is shown in FIG. 9 .
(mL/kg/day)dose amount
(mL/kg/day)
(mg/kg/day)Dosage
(mg/kg/day)
(PBSWE)test substance
(PBSWE)
(L-tryptophan)control material
(L-tryptophan)
투여물질은 동물의 경배부를 고정하고 1 mL 주사기를 이용하여 10 mL/kg 액량으로 경구로 투여하였으며, 1회/일, 7일간 투여하였다. 투여액량은 최근 측정한 체중을 기준으로 10 mL/kg으로 산출하였다.The administration material was orally administered at an amount of 10 mL/kg using a 1 mL syringe after fixing the animal's cervical region, and was administered once/day for 7 days. The dose was calculated as 10 mL/kg based on the recently measured body weight.
6일째 투여 전 절식을 실시하였으며, 7일 째 시험물질 및 대조물질을 투여하고 30분 후, 펜토바비탈 나트륨(Pentobarbital sodium) 45 mg/10mL/kg을 복강 투여하고 라이팅 반사(Righting reflex) 소실시간(수면 유도시간)을 측정하여 도 10에 나타내었다. 측정결과는 SPSS Statistics 12.0K for Medical Science를 사용하여, 모수적인 다중비교 (parametric multiple comparison procedures)는 ONE-WAY ANOVA 및 Student’s t-test를 실시하여 통하여 군간 비교하고, P<0.05인 경우 통계학적으로 유의하다고 판정하였다.Fasting was performed before administration on the 6th day, and 30 minutes after administration of the test substance and control substance on the 7th day, 45 mg/10mL/kg of Pentobarbital sodium was administered intraperitoneally, and the righting reflex loss time (Sleep induction time) was measured and shown in FIG. Measurement results were performed using SPSS Statistics 12.0K for Medical Science, and parametric multiple comparison procedures were compared between groups through ONE-WAY ANOVA and Student's t-test, and when P<0.05, statistically was judged to be significant.
도 10에서 보는 바와 같이, 흰점박이꽃무지 유충 추출물(PBSWE) 200 mg/kg/day, 300 mg/kg/day 및 800 mg/kg/day 투여군 (G2-G4) 모두에서 부형제 대조군 (G1)에 비해 통계학적으로 유의하게 수면 유도시간을 감소시키는 효과가 관찰되었다 (P<0.05 or P<0.01). 또한 양성대조물질 투여군 (G6)은 부형제대조군 (G1)에 비해 통계학적으로 유의한 수면 유도시간 감소 효과가 관찰되었다 (P<0.01).As shown in FIG. 10, in all of the 200 mg/kg/day, 300 mg/kg/day, and 800 mg/kg/day administration groups (G2-G4), the excipient control group (G1) A statistically significant decrease in sleep induction time was observed compared to that (P<0.05 or P<0.01). In addition, a statistically significant reduction in sleep induction time was observed in the positive control group (G6) compared to the excipient control group (G1) (P<0.01).
흰점박이꽃무지 유충 추출물(PBSWE)의 수면 유도시간 감소 효과는 흰점박이꽃무지 유충 추출물(PBSWE)의 투여량과 관련있었다. 흰점박이꽃무지 유충 추출물(PBSWE)은 양성 대조군으로 사용한 L-tryptophan(G6, 300 mg/kg/day)보다 낮은 농도(G2, 200 mg/kg/day)에서 L-tryptophan(G6)과 유사한 수면 유도시간을 나타내었으며, L-tryptophan(G6, 300 mg/kg/day)과 같은 농도(G3, 300 mg/kg/day) 및 이보다 높은 농도(G4, 800 mg/kg/day)에서 L-tryptophan(G6, 300 mg/kg/day)보다 큰 수면 유도시간 감소 효과를 갖는 것을 확인하였다.The sleep-inducing time reduction effect of the P. oleifera larva extract (PBSWE) was related to the dose of the P. oleifera larva extract (PBSWE). White spot larva extract (PBSWE) was similar to L-tryptophan (G6) at a lower concentration (G2, 200 mg/kg/day) than L-tryptophan (G6, 300 mg/kg/day) used as a positive control. Induction time was shown, and L-tryptophan at the same concentration (G3, 300 mg/kg/day) and higher concentrations (G4, 800 mg/kg/day) as L-tryptophan (G6, 300 mg/kg/day) (G6, 300 mg/kg/day) was confirmed to have a greater effect of reducing sleep induction time.
G4인 흰점박이꽃무지 유충 추출물(PBSWE) 800 mg/kg/day의 농도는 L-tryptophan이 10.4 mg/kg/day의 농도로 포함되어 있는 것으로 계산할 수 있으며, 이 G4 그룹의 L-tryptophan 농도의 2배 농도인 20 mg/kg/day의 L-tryptophan (G5)에서는 수면 유도시간의 감소가 전혀 나타나지 않은 것을 확인할 수 있었다. 이를 통하여 흰점박이꽃무지 유충 추출물(PBSWE)는 ICR 마우스의 수면 유도시간을 감소시키고, 이러한 효과는 L-tryptophan 단독의 효과가 아님을 확인할 수 있었다.The concentration of 800 mg/kg/day of the G4 larvae extract (PBSWE) can be calculated as containing L-tryptophan at a concentration of 10.4 mg/kg/day, and the concentration of L-tryptophan in this G4 group is It was confirmed that there was no decrease in sleep induction time at the double concentration of 20 mg/kg/day of L-tryptophan (G5). Through this, it was confirmed that the white spot flower radish larva extract (PBSWE) decreased the sleep induction time in ICR mice, and that this effect was not the effect of L-tryptophan alone.
4.2 4.2 ICRICR 마우스에서 in the mouse 흰점박이꽃무지white spot flower plain 유충 추출물( larvae extract ( PBSWEPBSWE )의 수면시간에 미치는 효과 확인) to determine the effect on sleep time
본 발명에 따른 흰점박이꽃무지 유충 추출물이 수면시간에 미치는 효과를 확인하였다. 상기 4.1과 동일한 방법으로 ICR 마우스를 준비하고 6일째 투여 전 절식을 실시하였으며, 7일 째 시험물질 및 대조물질을 투여하고 30분 후, 펜토바비탈 나트륨(Pentobarbital sodium) 45 mg/10mL/kg을 복강 투여하고 라이팅 반사(Righting reflex)가 소실된 후, 소실 시간으로부터 깨어나기까지의 시간(수면시간)을 측정하여 도 11에 나타내었다.The effect of the larvae extract according to the present invention on sleep time was confirmed. ICR mice were prepared in the same manner as in 4.1 above, and fasted before administration on the 6th day, and 30 minutes after administration of the test substance and control substance on the 7th day, 45 mg/10mL/kg of Pentobarbital sodium was administered. After intraperitoneal administration and the loss of the lighting reflex, the time from the disappearance to waking up (sleep time) was measured and shown in FIG. 11 .
측정결과는 SPSS Statistics 12.0K for Medical Science를 사용하여, 모수적인 다중비교 (parametric multiple comparison procedures)는 ONE-WAY ANOVA 및 Student’s t-test를 실시하여 통하여 군간 비교하고, P<0.05인 경우 통계학적으로 유의하다고 판정하였다.Measurement results were performed using SPSS Statistics 12.0K for Medical Science, and parametric multiple comparison procedures were compared between groups through ONE-WAY ANOVA and Student's t-test, and when P<0.05, statistically was judged to be significant.
도 11에서 보는 바와 같이, 흰점박이꽃무지 유충 추출물(PBSWE) 200 mg/kg/day, 300 mg/kg/day 및 800 mg/kg/day 투여군 (G2-G4) 모두에서 부형제 대조군 (G1)에 비해 통계학적으로 유의하게 수면시간 연장 효과가 관찰되었다 (P<0.05 or P<0.01). 또한 양성대조물질 투여군 (G6)은 부형제대조군 (G1)에 비해 통계학적으로 유의한 수면시간 연장 효과가 관찰되었다 (P<0.01).As shown in FIG. 11, in all of 200 mg/kg/day, 300 mg/kg/day, and 800 mg/kg/day administration groups (G2-G4) of the larvae extract (PBSWE), the excipient control group (G1) In comparison, a statistically significant effect of prolonging sleep time was observed (P<0.05 or P<0.01). In addition, in the positive control group (G6), a statistically significant effect of prolonging sleep time was observed compared to the excipient control group (G1) (P<0.01).
흰점박이꽃무지 유충 추출물(PBSWE)은 양성 대조군인 L-트립토판(G6) 보다 낮은 200 mg/kg/day 농도에서 L-트립토판(G6) 300 mg/kg/day 와 유사한 수면시간 연장 효과를 나타내었으며, L-트립토판(G6) 과 같은 농도 (300 mg/kg/day)에서는 L-트립토판(G6)과 유의하게 높은 수면연장 효과를 나타내었다. 이러한 흰점박이꽃무지 유충 추출물(PBSWE)의 수면시간 연장효과는 농도 의존적인 경향을 나타내는 것을 관찰하였다.At a concentration of 200 mg/kg/day lower than that of the positive control, L-tryptophan (G6), the larvae extract (PBSWE) showed a similar sleep time extension effect as that of L-tryptophan (G6) 300 mg/kg/day. , and L-tryptophan (G6) at the same concentration (300 mg/kg/day) showed a significantly higher sleep prolonging effect than L-tryptophan (G6). It was observed that the sleep time prolonging effect of the larvae extract (PBSWE) showed a concentration-dependent trend.
특히 흰점박이꽃무지 유충 추출물(PBSWE)의 가장 높은 투여량 그룹인 G4 (800 mg/kg/day) 내에 1.3% (10.4 mg/kg/day) 보다 약 2배 농도인 20 mg/kg/day의 L-tryptophan (G5)에서는 수면시간의 증가가 나타나지 않은 것을 확인할 수 있었다. 이를 통하여 흰점박이꽃무지 유충 추출물(PBSWE)는 ICR 마우스의 수면시간을 증가시키고, 이러한 효과는 L-tryptophan 단독의 효과가 아님을 확인할 수 있었다. 즉, 흰점박이꽃무지 유충 추출물(PBSWE) 내에 존재하는 L-트립토판 이외의 물질이 상승작용을 통하여 수면연장 효과를 나타내는 것을 알 수 있다.In particular, 20 mg/kg/day, about twice the concentration of 1.3% (10.4 mg/kg/day) in G4 (800 mg/kg/day), which is the highest dose group, of PBSWE larva extract (PBSWE) It was confirmed that there was no increase in sleep time in L-tryptophan (G5). Through this, it was confirmed that the white spot flower radish larva extract (PBSWE) increased the sleep time of ICR mice, and that this effect was not the effect of L-tryptophan alone. In other words, it can be seen that substances other than L-tryptophan present in the white-spotted flower radish larva extract (PBSWE) exhibit a sleep prolonging effect through synergistic action.
4.3 4.3 흰점박이꽃무지white spot flower plain 유충 추출물( larvae extract ( PBSWEPBSWE )이 적용된 ) is applied ICRICR 마우스 뇌의 조직병리학적 검사 Histopathological examination of mouse brain
본 발명에 따른 흰점박이꽃무지 유충 추출물이 적용된 ICR 마우스 뇌의 조직병리학적 검사를 실시하였다.Histopathological examination of the brain of an ICR mouse to which the white-spotted flower radish larva extract according to the present invention was applied was performed.
상기 4.1과 동일한 방법으로 ICR 마우스를 준비하고 상기 4.1 및 4.2의 수면유도시간 및 수면시간 측정을 완료한 후 부검을 실시하여 뇌 조직을 적출하여 10 % 포르말린 완충액에 고정을 실시하였다. 고정된 뇌 조직은 도 12 및 도 13에서 보는 바와 같이 시상하부(hypothalamus)를 중심으로 절한한 후, 도 13과 같이 시교차 상핵 (Suprachiasmatic nucleus, SCN)에서 IHC (adenosine A1 receptor, AA1R)를 실시하여 그 결과를 도 14에 나타내었다.ICR mice were prepared in the same manner as in 4.1, and after measuring the sleep induction time and sleep time in 4.1 and 4.2, an autopsy was performed to extract brain tissue and fix it in 10% formalin buffer. After the fixed brain tissue was cut centered on the hypothalamus as shown in FIGS. 12 and 13, IHC (adenosine A1 receptor, AA1R) was performed in the suprachiasmatic nucleus (SCN) as shown in FIG. 13 Thus, the results are shown in FIG. 14 .
도 14에서 보는 바와 같이 AA1R의 측정 결과, 흰점박이꽃무지 유충 추출물(PBSWE) 200 mg/kg/day, 300 mg/kg/day 및 800 mg/kg/day 투여군 (G2-G4) 모두에서 부형제 대조군 (G1)에 비해 통계학적으로 유의한 AA1R의 증가가 관찰되었다 (P<0.05 or P<0.01). 또한 양성대조물질 투여군 (G6)은 부형제대조군 (G1)에 비해 통계학적으로 유의한 AA1R의 증가가 관찰되었다 (P<0.01).As shown in FIG. 14 , as a result of the measurement of AA1R, the excipient control group in all of 200 mg/kg/day, 300 mg/kg/day, and 800 mg/kg/day administration group (G2-G4) A statistically significant increase in AA1R was observed compared to (G1) (P<0.05 or P<0.01). In addition, a statistically significant increase in AA1R was observed in the positive control group (G6) compared to the excipient control group (G1) (P<0.01).
하루 주기를 조절하며 멜라토닌 수용체를 가지고 있어 외부의 멜라토닌 유입시 되먹임 기전을 통해 일주기 시계가 조절된다고 알려진 시교차 상핵 (Suprachiamatic nucleus, SCN)에서, PBSWE 200 mg/kg/day, 400 mg/kg/day 및 800 mg/kg/day 투여군 (G2-G4)은 Neuron의 수의 변화 없이 아데노신 수용체 A1(Adenosine receptor A1; AA1R)의 유의한 증가가 조직병리학적으로 관찰되어, 흰점박이꽃무지 유충 추출물(PBSWE)의 투여가 수면의 항상성에 관여하는 인자인 AA1R 를 증가시키는 효력이 있는 것을 확인하였다. 이러한 흰점박이꽃무지 유충 추출물(PBSWE)의 AA1R 증가는 상기 수면유도시간 및 수면시간에 대한 효과와 같이 L-tryptophan 보다 낮은 농도에서도 뚜렷하게 관찰되었다.
<< 제제예Formulation example 1. 약학적 제제> 1. Pharmaceutical preparations>
본 발명의 흰점박이꽃무지 유충 추출물(PBSWE)을 락토즈 175.9g, 감자전분 180g 및 콜로이드성 규산 32g과 혼합하였다. 이 혼합물에 10% 젤라틴 용액을 첨가시킨 후, 분쇄하여 14 메쉬체를 통과시켰다. 이것을 건조시키고 여기에 감자전분 160g, 활성 50g 및 스테아린산 마그네슘 5g을 첨가해서 얻은 혼합물을 정제로 만들었다. The larva extract (PBSWE) of the present invention was mixed with 175.9 g of lactose, 180 g of potato starch and 32 g of colloidal silicic acid. After adding a 10% gelatin solution to this mixture, it was ground and passed through a 14 mesh sieve. This was dried, and 160 g of potato starch, 50 g of activity and 5 g of magnesium stearate were added thereto, and the resulting mixture was made into tablets.
<< 제제예Formulation example 2. 건강기능식품의 제조> 2. Manufacturing of health functional food>
제제예Formulation example 2-1. 건강기능식품의 제조 2-1. Manufacturing of health functional food
본 발명의 흰점박이꽃무지 유충 추출물(PBSWE) 2g, 비타민 혼합물 적량, 비타민 A 아세테이트 70㎍, 비타민 E 1.0㎎, 비타민 B1 0.13㎎, 비타민 B2 0.15㎎, 비타민 B6 0.5㎎, 비타민 B12 0.2㎍, 비타민 C 10㎎, 비오틴 10㎍, 니코틴산아미드 1.7㎎, 엽산 50㎍, 판토텐산 칼슘 0.5㎎, 무기질 혼합물 적량, 황산제1철 1.75㎎, 산화아연 0.82㎎, 탄산 마그네슘 25.3㎎, 제1인산칼륨 15㎎, 제2인산칼슘 55㎎, 구연산칼륨 90㎎, 탄산칼슘 100㎎, 염화마그네슘 24.8㎎을 섞어 과립으로 제조하였으나, 용도에 따라 다양한 제형으로 변형시켜 제조할 수 있다. 또한, 상기의 비타민 및 미네랄 혼합물의 조성비를 임의로 변형 실시하여도 무방하며, 통상의 건강기능식품 제조방법에 따라 상기의 성분을 혼합하여 제조할 수 있다.2g of white spot flower radish larva extract (PBSWE) of the present invention, vitamin mixture appropriate amount,
제제예Formulation example 2-2. 건강기능성 음료의 제조 2-2. Manufacturing of health functional beverages
본 발명의 흰점박이꽃무지 유충 추출물(PBSWE) 1g, 구연산 0.1g, 프락토올리고당 100g, 정제수 900g을 섞어 통상의 음료 제조방법에 따라 교반, 가열, 여과, 살균, 냉장하여 음료를 제조하였다.A beverage was prepared by mixing 1 g of the white spot flower radish larva extract (PBSWE) of the present invention, 0.1 g of citric acid, 100 g of fructooligosaccharide, and 900 g of purified water, followed by stirring, heating, filtration, sterilization, and refrigeration according to a conventional beverage preparation method.
Claims (10)
상기 흰점박이꽃무지 유충 추출물은 물을 용매로 하여, 50~70℃에서 6~8시간 추출한 것을 특징으로 하는 흰점박이꽃무지 유충 추출물을 유효성분으로 포함하는 것을 특징으로 하는 수면개선용 약학 조성물.In the pharmaceutical composition for improving sleep, it characterized in that it contains the extract of larvae of Protaetia brevitarsis seulensis as an active ingredient,
A pharmaceutical composition for improving sleep, characterized in that the larvae extract is extracted from water as a solvent at 50 to 70° C. for 6 to 8 hours.
상기 수면개선은 숙면장애, 수면유지장애, 중도각성, 조기각성, 불면증, 일주기 리듬 수면장애, 사건수면으로 이루어진 군에서 선택되는 어느 하나 이상의 수면장애의 개선인 것을 특징으로 하는 흰점박이꽃무지 유충 추출물을 유효성분으로 포함하는 것을 특징으로 하는 수면개선용 조성물. The method of claim 1,
The sleep improvement is a sleep disorder, sleep maintenance disorder, moderate awakening, early awakening, insomnia, circadian rhythm sleep disorder, parasomnia, characterized in that the improvement of any one or more sleep disorders selected from the group consisting of A composition for improving sleep, comprising an extract as an active ingredient.
상기 불면증의 개선은 수면 유도시간 감소 또는 수면시간 연장인 것을 특징으로 하는 흰점박이꽃무지 유충 추출물을 유효성분으로 포함하는 것을 특징으로 하는 수면개선용 약학 조성물.4. The method of claim 3,
The improvement of insomnia is a sleep-improving pharmaceutical composition, characterized in that it comprises an extract of white-spotted flower radish larvae as an active ingredient, characterized in that the sleep induction time is reduced or the sleep time is prolonged.
상기 수면개선용 조성물은 아데노신 수용체 A1(Adenosine receptor A1; AA1R)을 증가시키는 것을 특징으로 하는 흰점박이꽃무지 유충 추출물을 유효성분으로 포함하는 것을 특징으로 하는 수면개선용 약학 조성물.The method of claim 1,
The composition for improving sleep is a pharmaceutical composition for improving sleep, characterized in that it comprises an extract of white-spotted flower radish larvae as an active ingredient, characterized in that it increases adenosine receptor A1 (AA1R).
상기 흰점박이꽃무지 유충 추출물은 물을 용매로 하여, 50~70℃에서 6~8시간 추출한 것을 특징으로 하는 흰점박이꽃무지 유충 추출물을 유효성분으로 포함하는 것을 특징으로 하는 수면개선용 건강기능식품.In the health functional food for improving sleep, characterized in that it contains the extract of larvae of Protaetia brevitarsis seulensis as an active ingredient,
Health functional food for improving sleep, characterized in that the larva extract of White-spotted flower radish larvae is extracted using water as a solvent and at 50-70° C. for 6-8 hours, as an active ingredient .
상기 수면개선은 숙면장애, 중도각성, 조기각성, 불면증, 일주기 리듬 수면장애, 사건수면으로 이루어진 군에서 선택되는 어느 하나 이상의 수면장애의 개선인 것을 특징으로 하는 흰점박이꽃무지 유충 추출물을 유효성분으로 포함하는 것을 특징으로 하는 수면개선용 건강기능식품. 7. The method of claim 6,
The sleep improvement is a sleep disorder, intermediate awakening, early awakening, insomnia, circadian rhythm sleep disorder, parasomnia, characterized in that any one or more sleep disorders selected from the group consisting of an active ingredient Health functional food for sleep improvement, characterized in that it comprises a.
상기 불면증의 개선은 수면 유도시간 감소 또는 수면시간 연장인 것을 특징으로 하는 흰점박이꽃무지 유충 추출물을 유효성분으로 포함하는 것을 특징으로 하는 수면개선용 건강기능식품.9. The method of claim 8,
The improvement of insomnia is a health functional food for improving sleep, characterized in that it contains an extract of white spot flower radish larvae as an active ingredient, characterized in that it reduces sleep induction time or extends sleep time.
상기 수면개선용 건강기능식품은 아데노신 수용체 A1(Adenosine receptor A1; AA1R)을 증가시키는 것을 특징으로 하는 흰점박이꽃무지 유충 추출물을 유효성분으로 포함하는 것을 특징으로 하는 수면개선용 건강기능식품.7. The method of claim 6,
The health functional food for improving sleep is a health functional food for improving sleep, characterized in that it comprises an extract of white spot flower radish larvae as an active ingredient, characterized in that it increases adenosine receptor A1 (AA1R).
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