KR20150107938A - Composition for Improving Memory and Cognitive Function Comprising Psyllium husk - Google Patents
Composition for Improving Memory and Cognitive Function Comprising Psyllium husk Download PDFInfo
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- KR20150107938A KR20150107938A KR1020140029692A KR20140029692A KR20150107938A KR 20150107938 A KR20150107938 A KR 20150107938A KR 1020140029692 A KR1020140029692 A KR 1020140029692A KR 20140029692 A KR20140029692 A KR 20140029692A KR 20150107938 A KR20150107938 A KR 20150107938A
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Abstract
Description
본 발명은 차전자피(Psyllium husk)를 포함하는 기억력 및 인지기능 증진용 조성물에 관한 것으로, 보다 상세하게는 차전자피를 유효성분으로 포함하는 기억력 개선 또는 인지기능 장애의 예방 또는 치료용 약학 조성물, 및 기억력 개선 또는 인지기능 장애의 예방 또는 개선용 건강기능식품 조성물에 관한 것이다.
The present invention relates to a composition for enhancing memory and cognitive function comprising Psyllium husk, and more particularly, to a composition for improving memory or cognitive dysfunction, Or a functional food composition for preventing or ameliorating cognitive dysfunction.
치매는 일반적으로 인간의 인지기능, 지적능력, 감정 및 행동변화 등에서 뚜렷한 손상을 나타내는 복합 임상 증후군으로서, 기억력, 주의력, 언어기능, 시공간 능력 등의 대뇌피질 기능장애가 발생하여 일상, 사회생활을 영위하는데 큰 어려움을 겪게 되는 상태이다. 치매라고 정의할 때는 기억력을 포함하여 다른 인지기능 중 한 가지 이상의 장애가 있는 경우를 말하며, 단순히 기억력만 떨어진 경우는 치매라고 하지 않는다. Dementia is a complex clinical syndrome characterized by a marked impairment in human cognitive function, intellectual ability, emotional and behavioral changes. It causes cortical dysfunction such as memory, attention, language function, and spatio-temporal ability to lead daily life and social life It is in a state of great difficulty. The term "dementia" refers to a condition in which one or more of the other cognitive functions, including memory, is present.
치매의 원인으로는 퇴행성 뇌질환인 알츠하이머병(Alzheimer's Disease)이나 파킨슨병(Parkinson's Disease)에서부터 뇌출혈, 대사성질환인 간성뇌병증, 윌슨병(Wilson's Disease), 감염성 질환인 신경매독, 후천성면역결핍증, 알코올과 같은 약물중독, 뇌외상 등 다양한 병인이 있으며, 어떤 형태로는 중추신경계에 구조적, 기능적 이상을 초래할 수 있는 질환은 치매를 유발할 수가 있다. 그 중에서도 알츠하이머병에 의한 치매가 50 내지 60 %로 가장 많으며, 뇌혈관 질환에 의한 치매가 그 다음이다. Alzheimer's Disease or Parkinson's Disease is the cause of dementia, which can be caused by cerebral hemorrhage, metabolic diseases such as hepatic encephalopathy, Wilson's Disease, infectious diseases such as neurosyphilis, acquired immunodeficiency, Such as drug addiction, brain trauma, etc. In some forms, diseases that may cause structural and functional abnormalities in the central nervous system may cause dementia. Among them, dementia caused by Alzheimer's disease is the most common with 50 to 60%, followed by dementia caused by cerebrovascular disease.
기억 인지 장애는 알츠하이머 질환자들이 처음으로 겪는 증상이며 또한 가장 흔한 증상이다. 알츠하이머병의 초기에 환자들은 최근의 대화나 일의 내용을 자세하게 기억하지 못하는 최근 기억(recent memory) 장애를 겪게 되는데, 이는 해마의 신경세포가 손상되어 최근 기억을 저장하는 기능이 떨어진 데에서 기인한다. 하지만 이 시기에는 먼 과거에 있었던 사건들에 대한 과거 기억(remote long-term memory)은 상대적으로 잘 유지된다. 그러나 병이 점차 진행됨에 따라 장기기억의 저장과 관련된 대뇌피질이 손상되면서 이러한 과거의 기억도 점차 장애를 보이게 된다. Memory cognitive impairment is the first and most common symptom of Alzheimer's disease. In the early stages of Alzheimer's disease, patients suffer from recent memory disorders that do not remember the details of recent conversations or work, due to the impaired ability of hippocampal neurons to damage recent memory . But at this time, the remote long-term memory of events in the distant past is relatively well preserved. However, as disease progresses, memory of the past gradually becomes disturbed as the cerebral cortex associated with the storage of long - term memory is damaged.
한편, 동맥경화에 이어 발생한 혈전에 의해 뇌동맥이 막혀 조직이 죽게 되는 지역이 해마(hippocampus)와 같은 중요 지역에서 발생하면 치매로 발전하게 되며, 혈관성치매에서 가장 많은 비율을 차지하는 것은 가는 혈관들이 막히거나 또는 혈액공급이 원활하지 못해 발생하는 겉질밑 허혈성 혈관성 치매(subcortical ischemic vascular dementia, SIVD)(전체 혈관성 치매의 35 내지 67 % 차지)이다(Roman et al., Subcortical ischaemic vascular dementia. Lancet Neurol 2002;1:426-436). 겉질밑 허혈성 혈관성치매(SIVD)에서의 손상은 주로 백색질에서 일어나며 이러한 질환을 닮은 동물모델을 만들기 위해 다양한 방법들이 사용되고 있다(Hainsworth & Markus, Do in vivo experimental models reflect human cerebral small vessel disease? A systematic review. J Cerebral Blood Flow & Metabolism 2008;28:1877-1891). 혈관성 치매에 대해서는 백색질을 이루는 희소돌기아교세포(oligodendrocyte)가 혈관성치매가 일어나는 조건에서 세포자살에 의해 죽는다는 것이 밝혀졌으며, 이를 억제하여 치료를 하기 위한 연구가 진행되고 있다. On the other hand, if the area in which the cerebral artery is clogged and the tissue is dying due to thrombosis following arteriosclerosis develops in a major region such as the hippocampus, it develops as dementia. The largest proportion of vascular dementia Or subcortical ischemic vascular dementia (SIVD) (35 to 67% of total vascular dementia) caused by poor blood supply (Roman et al., Subcortical ischaemic vascular dementia. Lancet Neurol 2002; : 426-436). Damage to cortical ischemic vascular dementia (SIVD) occurs primarily in the white matter, and a variety of methods have been used to create animal models that resemble these diseases (Hainsworth & Markus, J Cerebral Blood Flow & Metabolism 2008; 28: 1877-1891). In vascular dementia, it has been shown that oligodendrocyte, which is a whitish material, is killed by apoptosis in the condition of vascular dementia, and studies are under way to suppress it.
현재 우리나라의 알츠하이머병 치료제의 경우 외국계열 회사가 98 %의 점유율을 차지하고 있을 정도로 수입에 의존하는 바가 크다. 더욱이 한 회사가 시장의 80 %를 차지하고 있어 사실상 독점하고 있다고 볼 수 있다(한국과학기술정보연구원. 치매치료제. p.116, 2002). 이는 국가경쟁력 측면에서도 치매 치료분야의 성장이 시급함을 알 수 있다. 따라서 부작용이 적으면서 효과적인 항건망제제 및 기억력 개선제의 개발은 알츠하이머 질환자의 삶의 질 향상과 초기 병증 개선 및 치료에 상당한 도움을 줄 수 있으며, 또한 기억인지력의 장애를 겪는 건망증, 치매환자에게도 도움을 줄 수 있을 것으로 사료된다.At present, in the case of Alzheimer's disease treatment in Korea, foreign affiliated companies are highly dependent on imports so that they occupy a share of 98%. In addition, one company accounts for 80% of the market, which is virtually monopolistic (Korea Institute of Science and Technology Information, dementia treatment p.116, 2002). This shows that the growth of dementia treatment sector is urgent in terms of national competitiveness. Therefore, the development of effective anti-cancer drugs and memory-improving agents with fewer side effects can significantly improve the quality of life of Alzheimer's disease patients and improve and cure early-onset disease, as well as for amenorrhea and dementia patients suffering from memory cognitive impairment. It is thought that it can give.
한편, 차전자피는 산업적으로 건강기능식품 기능성 원료로서, 식이섬유를 79 % 이상 함유하고 있어 최근 콜레스테롤 개선 및 배변활동 원활의 건강기능식품으로 주목을 받고 있지만 신경계에 미치는 영향에 대해서는 알려진 바 없다.
On the other hand, it is industrially used as a health functional food functional raw material and contains more than 79% of dietary fiber. Recently, it has been noted as a health functional food for improvement of cholesterol and smoothness of bowel movement, but its effect on the nervous system is not known.
이러한 배경 하에서, 상기 차전자피의 기억력 증진 및 인지기능 장애의 예방 및 치료 효능을 밝히기 위하여 예의 노력한 결과, 차전자피가 기억력 손상을 회복시키고 혈관성 치매와 같은 인지기능 장애의 치료에 탁월한 효과가 있음을 확인하여, 본 발명을 완성하였다.
Under these circumstances, the inventors of the present invention have found that the herbal composition of the present invention has excellent effects in the treatment of cognitive dysfunction such as vascular dementia, Thus completing the present invention.
본 발명의 하나의 목적은 차전자피를 유효성분으로 포함하는 기억력 개선 또는 인지기능 장애의 예방 또는 치료용 약학 조성물을 제공하는 것이다.It is an object of the present invention to provide a pharmaceutical composition for preventing or treating memory improvement or cognitive dysfunction, which comprises a heart muscle as an active ingredient.
본 발명의 다른 하나의 목적은 차전자피를 유효성분으로 포함하는 기억력 개선 또는 인지기능 장애의 예방 또는 개선용 건강기능식품 조성물을 제공하는 것이다.
It is another object of the present invention to provide a health functional food composition for preventing or ameliorating a memory effect or a cognitive dysfunction, which comprises a tea extract as an active ingredient.
상기 과제를 달성하기 위한 하나의 양태로서, 본 발명은 차전자피를 유효성분으로 포함하는 기억력 개선 또는 인지기능 장애의 예방 또는 치료용 약학 조성물을 제공한다.
As one aspect for achieving the above object, the present invention provides a pharmaceutical composition for preventing or treating memory improvement or cognitive dysfunction, comprising a cardiotonic extract as an active ingredient.
본 발명에서 용어 "차전자피(Psyllium husk)"는, 질경이과(Plantaginaceae)에 속하는 다년생 초본 질경이(Plantago asiatica)의 성숙한 종자인 차전자의 껍질을 당해 업계에 널리 공지된 추출, 분리, 정제방법에 의해 수득되거나, 시판되는 분말형태의 시약을 말한다. In the present invention, the term " Psyllium husk "is used to refer to a shell of a secondary electron which is a mature seed of a perennial plantago asiatica belonging to Plantaginaceae, obtained by an extraction, separation and purification method well known in the art Or a commercial powdered reagent.
구체적으로 차전자(Psyllium)는 전세계 생산량의 약 80 %를 차지하는 인도가 주산지이며, 1,000 개 차전자의 무게가 2 g 보다 작은 차전자 씨앗의 껍질을 차전자피라고 한다. 보다 구체적으로 차전차피 식이섬유(fiber)는 차전차피의 분말이며, 상기 분말은 차전자의 씨앗을 분쇄하여 전체 씨앗의 약 25 %를 차지하는 껍질을 분리한 다음 제분하여, 가는 입자로 만든 후 체로 걸러 얻을 수 있다. 상기 분말의 섭취방법은 상기 분말 3.5 g을 250 ml 물에 녹여 섭취하거나, 캡슐형태로 섭취되기도 한다.Specifically, Psyllium is the primary source of India, which accounts for about 80% of the world's production, and the shell of tea seeds with a weight of less than 2 g of 1,000 electrons is called a charcoal. More specifically, the fiber of the tea tank is pulverized powder, and the powder is obtained by pulverizing the seeds of the tea leaves to separate the skin which occupies about 25% of the whole seeds, You can get it filtered. The powder may be ingested by dissolving 3.5 g of the powder in 250 ml of water or in the form of a capsule.
한방에서 차전자는 강력한 이뇨제로 신장염, 방광염 및 요도염 등에 널리 사용되어 왔으며, 무기질, 단백질, 비타민류 및 다당류 등이 많이 함유되어 있어, 상기 차전자 성분들은 항염증 작용에 관여하는 것으로 알려져 있다.
In the oriental medicine, tea is a powerful diuretic and has been widely used for nephritis, cystitis and urethritis. It contains minerals, proteins, vitamins and polysaccharides, and these secondary components are known to be involved in anti-inflammatory actions.
본 발명의 차전자피를 유효성분으로 하는 조성물은 기억력 개선 및 인지기능 장애의 예방, 치료 또는 개선 효과가 있다.The composition containing the present invention as an active ingredient has an effect of improving memory and preventing, treating or improving cognitive dysfunction.
본 발명에서 용어 "기억" 또는 "기억력"은 주위 환경으로부터 얻은 새로운 정보나 학습된 경험, 지식을 습득하여 뇌의 특정부위에 부호화하여 저장하고 이를 다시 회상할 수 있는 능력을 의미한다. 본 발명의 조성물은 상기와 같은 기억력을 개선시킬 수 있는 효과가 있으며, 이러한 효과에는 정상인의 기억력을 증진시키는 효과 뿐만 아니라 손상된 기억력 또는 기억력 장애를 회복시키는 모든 효과를 포함할 수 있다.The term "memory" or "memory capacity" in the present invention means the ability to acquire new information, learned experiences, and knowledge obtained from the surrounding environment, to encode and store it in a specific region of the brain and to recall it. The composition of the present invention has the effect of improving the memory ability as described above. Such effects may include not only the effect of enhancing the normal person's memory but also all the effects of restoring the impaired memory or memory disorder.
상기 기억력 장애는 외상, 주의력 결핍, 노화, 질병 등의 다양한 원인에 의하여 상기 기억력이 정상인에 비해 낮아진 상태를 의미하며, 건망증, 집중력 장애, 공간지각력 손실, 학습능력의 둔화, 인지력 상실 등을 포함하는 개념이다.The memory disorder refers to a state in which the memory is lowered compared to a normal person due to various causes such as trauma, attention deficit, aging, and disease, and includes forgetting, concentration disorder, loss of spatial perception, slowing of learning ability, Concept.
본 발명의 일실시예에서는 차전자피의 기억력에 대한 효과를 확인하기 위하여, 스코폴라민으로 기억력 손상(건망증)을 유도한 랫트에서 수동회피실험을 진행한 결과, 차전자피가 스코폴라민에 의한 인지기억력 손상을 회복시키는 효과가 있음을 확인하였다(도 1).
In an embodiment of the present invention, in order to confirm the effect on the memory capacity of the cell wall, the passive avoidance experiment was conducted in rats inducing memory damage (forgetfulness) as scopolamine, (Fig. 1).
본 발명에서 "인지기능"은 지식과 정보를 효율적으로 조작하는 능력으로서, 본 발명의 목적상 인지기능 장애는 상기와 같은 인지기능이 저하되어 생기는 상태, 그에 따른 질환, 그를 증상으로 하는 모든 질환을 포함할 수 있는 개념으로써, 바람직하게는 뇌 신경세포의 손상으로 발생하는 장애를 의미할 수 있다. 본 발명의 인지기능 장애에는 건망증, 알츠하이머병(Alzheimer's disease), 혈관성 치매, 두부손상에 의한 치매 또는 파킨슨씨병(Parkinson's disease) 등이 포함될 수 있으며, 바람직하게는 혈관성 치매일 수 있다.In the present invention, the term "cognitive function" is the ability to efficiently manipulate knowledge and information. For the purpose of the present invention, cognitive dysfunction refers to a condition in which the cognitive function is deteriorated, a disease caused thereby, As a concept that may be included, it may preferably mean a disorder resulting from damage of the cranial nerve cells. The cognitive dysfunction of the present invention may include forgetfulness, Alzheimer's disease, vascular dementia, dementia caused by head injury or Parkinson's disease, and preferably vascular dementia.
본 발명의 일실시예에서는 차전자피의 혈관성 치매에 대한 효과를 확인하기 위하여, 만성 관류저하 모델을 이용하여 혈관성 치매에 의한 동공대광반사(pupillary light reflex, PLR) 손실 및 백색질 손상에 대한 효과를 확인한 결과, 백색질 중 시각로의 손상으로 인한 PLR 손실이 억제되는 효과를 확인하였으며(표 1), 또한 시각로 부위에서 차전자피에 의해 백색질 손상이 억제되는 효과를 확인하였다(도 2). 따라서, 본 발명의 차전자피가 혈관성 치매를 포함한 인지기능 장애를 개선할 수 있는 효과를 나타냄을 확인하였다.
In an embodiment of the present invention, in order to confirm the effect on the vascular dementia of the cardiomyocyte, the effect of the vascular dementia on the pupillary light reflex (PLR) , PLR loss due to visual damage during the whitening was inhibited (Table 1), and the whitening damage was inhibited by the zona pellucida at the visual area (Fig. 2). Accordingly, it has been confirmed that the present invention has the effect of improving cognitive dysfunction including vascular dementia.
본 발명에서, 용어 "예방"이란 본 발명에 따른 약학 조성물의 투여에 의해 인지기능 장애의 발생, 확산 및 재발을 억제 또는 지연시키는 모든 행위를 의미하고, "치료"란 상기 약학 조성물의 투여에 의해 인지기능 장애의 의심 및 발병 개체의 증상이 호전되거나 이롭게 변경하는 모든 행위를 의미한다.
In the present invention, the term "prevention" means any action that inhibits or delays the occurrence, spread and recurrence of cognitive dysfunction by the administration of the pharmaceutical composition according to the present invention, and "treatment" Suspicion of cognitive dysfunction, and any behavior that alters or alleviates symptoms of an onset individual.
상기 본 발명의 약학조성물은 약학적으로 허용가능한 담체를 추가로 포함할 수 있다. 본 발명의 용어 "약학적으로 허용가능한"이란 상기 조성물에 노출되는 세포나 인간에게 독성이 없는 특성을 나타내는 것을 의미한다. 상기 담체는 완충제, 보존제, 무통화제, 가용화제, 등장제, 안정화제, 기제, 부형제, 윤활제 등 당업계에 공지된 것이라면 제한없이 사용할 수 있다.The pharmaceutical composition of the present invention may further comprise a pharmaceutically acceptable carrier. The term "pharmaceutically acceptable" of the present invention means that it exhibits properties that are not toxic to the cells or humans exposed to the composition. Such carriers may be used without limitation as long as they are known in the art such as buffers, preservatives, wetting agents, solubilizers, isotonic agents, stabilizers, bases, excipients and lubricants.
또한 본 발명의 약학조성물은 각각 통상의 방법에 따라 산제, 과립제, 정제, 캡슐제, 현탁액, 에멀젼, 시럽, 에어로졸 등의 경구형 제형, 외용제, 좌제 및 멸균 주사용액의 형태로 제형화하여 사용될 수 있다. 나아가, 연고제, 로션제, 스프레이제, 패취제, 크림제, 산제, 현탁제, 겔제 또는 젤의 형태의 피부 외용제의 형태로 사용될 수 있다. 본 발명의 조성물에 포함될 수 있는 담체, 부형제 및 희석제로는 락토즈, 덱스트로즈, 수크로스, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로즈, 메틸 셀룰로즈, 미정질 셀룰로스, 폴리비닐 피롤리돈, 물, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 탈크, 마그네슘 스테아레이트 및 광물유를 들 수 있다. 제제화할 경우에는 보통 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 조제된다.In addition, the pharmaceutical composition of the present invention may be formulated in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols and the like, oral preparations, suppositories and sterilized injection solutions according to a conventional method have. Furthermore, it can be used in the form of an external preparation for skin in the form of ointments, lotions, spray agents, patches, creams, powders, suspensions, gels or gels. Examples of carriers, excipients and diluents that can be included in the composition of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, Cellulose, methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. In the case of formulation, a diluent or excipient such as a filler, an extender, a binder, a wetting agent, a disintegrant, or a surfactant is usually used.
경구투여를 위한 고형제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 이러한 고형제제는 상기 트레쿨리아 아프리카나 추출물에 적어도 하나 이상의 부형제 예를 들면, 전분, 칼슘카보네이트 (calcium carbonate), 수크로스(sucrose) 또는 락토오스(lactose), 젤라틴 등을 섞어 조제된다. 또한 단순한 부형제 이외에 마그네슘 스티레이트, 탈크 같은 윤활제들도 사용된다. 경구를 위한 액상 제제로는 현탁제, 내용액제, 유제, 시럽제 등이 해당되는 데 흔히 사용되는 단순희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다. Solid formulations for oral administration include tablets, pills, powders, granules, capsules and the like, which may contain at least one excipient such as starch, calcium carbonate, Sucrose, lactose, gelatin and the like. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Liquid preparations for oral use may include various excipients such as wetting agents, sweetening agents, fragrances, preservatives, etc. in addition to water and liquid paraffin, which are simple diluents commonly used in suspension, liquid solutions, emulsions and syrups have.
비경구 투여를 위한 제제에는 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조 제제, 좌제가 포함된다. 비수성용제, 현탁제로는 프로필렌글리콜 (propylene glycol), 폴리에틸렌 글리콜, 올리브오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다. 좌제의 기제로는 위텝솔(witepsol), 마크로골, 트윈 61(tween 61), 카카오지, 라우린지, 글리세로제라틴 등이 사용될 수 있다.
Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. Examples of the suspending agent include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like. Examples of the suppository base include witepsol, macrogol, tween 61, cacao butter, laurin, glycerogelatin and the like.
본 발명의 약학조성물은 약학적으로 유효한 양으로 투여한다. 본 발명의 용어 "약학적으로 유효한 양"은 의학적 치료에 적용 가능한 합리적인 수혜/위험 비율로 질환을 치료하기에 충분하며 부작용을 일으키지 않을 정도의 양을 의미하며, 유효용량 수준은 환자의 건강상태, 질환의 종류, 중증도, 약물의 활성, 약물에 대한 민감도, 투여 방법, 투여 시간, 투여 경로 및 배출 비율, 치료기간, 배합 또는 동시 사용되는 약물을 포함한 요소 및 기타 의학 분야에 잘 알려진 요소에 따라 결정될 수 있다. 본 발명의 조성물은 개별 치료제로 투여하거나 다른 치료제와 병용하여 투여될 수 있고, 종래의 치료제와 순차적으로 또는 동시에 투여될 수 있으며, 단일 또는 다중 투여될 수 있다. 상기한 요소들을 모두 고려하여 부작용 없이 최소한의 양으로 최대 효과를 얻을 수 있는 양을 투여하는 것이 중요하며, 이는 당업자에 의해 용이하게 결정될 수 있다.The pharmaceutical composition of the present invention is administered in a pharmaceutically effective amount. The term "pharmaceutically effective amount " of the present invention means an amount sufficient to treat a disease at a reasonable benefit / risk ratio applicable to medical treatment and not causing side effects, The type of disease, the severity, the activity of the drug, the sensitivity to the drug, the method of administration, the time of administration, the route of administration and the rate of release, the duration of the treatment, the factors including the drugs used concurrently or concurrently and other factors well known in the medical arts . The composition of the present invention may be administered as an individual therapeutic agent or in combination with other therapeutic agents, and may be administered sequentially or simultaneously with conventional therapeutic agents, and may be administered singly or multiply. It is important to take into account all of the above factors and to administer the amount in which the maximum effect can be obtained in a minimal amount without side effects, which can be easily determined by those skilled in the art.
본 발명의 조성물은 쥐, 랫트, 생쥐, 가축, 인간 등의 포유동물에 다양한 경로로 투여될 수 있다. 투여의 모든 방식은 예상될 수 있는데, 예를 들면, 경구, 직장 또는 정맥, 근육, 피하, 자궁내 경막 또는 뇌혈관 내(intracerebroventricular) 주사에 의해 투여될 수 있다. 또한, 상기 약학적 조성물 중 유효성분의 투여량은 투여경로, 질병의 정도, 환자의 나이, 성별, 체중 등에 따라 달라질 수 있으며, 일일 1회 내지 수회 투여할 수 있다. 그러나 바람직한 효과를 위해서, 1일 0.01 mg/kg 내지 10 g/kg으로, 바람직하게는 1 mg/kg 내지 1 g/kg으로 투여하는 것이 좋다. 투여는 하루에 한번 투여할 수도 있고, 수회 나누어 투여할 수 있다. 따라서, 상기 투여량은 어떠한 면으로든 본 발명의 범위를 한정하는 것은 아니다.
The composition of the present invention can be administered to mammals such as rats, rats, mice, livestock, humans, and the like in various routes. All modes of administration may be expected, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, intra-uterine or intracerebroventricular injections. The dosage of the active ingredient in the pharmaceutical composition may vary depending on the route of administration, the severity of the disease, the age, sex, and weight of the patient, and may be administered once to several times per day. However, in order to obtain the desired effect, it is preferable to administer it at 0.01 mg / kg to 10 g / kg, preferably 1 mg / kg to 1 g / kg per day. The administration may be carried out once a day or divided into several doses. Thus, the dosage amounts are not intended to limit the scope of the invention in any manner.
다른 하나의 양태로서, 본 발명은 차전자피를 필요로 하는 개체에게 투여하는 단계를 포함하는, 기억력 개선 또는 인지기능 장애의 예방 또는 치료방법을 제공한다.In another aspect, the present invention provides a method for preventing or treating memory improvement or cognitive dysfunction, comprising administering to a subject in need thereof.
본 발명의 용어 "개체"란, 상기 기억력 개선이 필요하거나 인지기능 장애가 발병하였거나 발병할 수 있는 인간을 포함한 원숭이, 소, 말, 양, 돼지, 닭, 칠면조, 메추라기, 고양이, 개, 마우스, 쥐, 랫트, 토끼 또는 기니아 피그를 포함한 모든 동물을 의미하고, 본 발명의 약학 조성물을 개체에게 투여함으로써 상기 질환들을 효과적으로 예방 또는 치료할 수 있다. 본 발명의 약학적 조성물은 기존의 치료제와 병행하여 투여될 수 있다.The term "individual" of the present invention means a monkey, a cow, a horse, a sheep, a pig, a chicken, a turkey, a quail, a cat, a dog, a mouse, and a mouse including a human who needs improvement of the memory, , Rat, rabbit or guinea pig, and the diseases can be effectively prevented or treated by administering the pharmaceutical composition of the present invention to a subject. The pharmaceutical composition of the present invention can be administered in parallel with existing therapeutic agents.
본 발명의 용어 "투여"란, 임의의 적절한 방법으로 환자에게 소정의 물질을 제공하는 것을 의미하며, 본 발명의 조성물의 투여 경로는 목적 조직에 도달할 수 있는 한 어떠한 일반적인 경로를 통하여 투여될 수 있다. 복강 내 투여, 정맥 내 투여, 근육 내 투여, 피하 투여, 피 내 투여, 경구 투여, 국소 투여, 비 내 투여, 폐 내 투여, 직장 내 투여될 수 있으나, 이에 제한되지는 않는다. 또한, 본 발명의 약학적 조성물은 활성 물질이 표적 세포로 이동할 수 있는 임의의 장치에 의해 투여될 수도 있다. 바람직한 투여방식 및 제제는 정맥 주사제, 피하 주사제, 피내 주사제, 근육 주사제, 점적 주사제 등이다. 주사제는 생리식염액, 링겔액 등의 수성 용제, 식물유, 고급 지방산 에스테르(예, 올레인산에칠 등), 알코올 류(예, 에탄올, 벤질알코올, 프로필렌글리콜, 글리세린 등) 등의 비수성 용제 등을 이용하여 제조할 수 있고, 변질 방지를 위한 안정화제(예, 아스코르빈산, 아황산수소나트륨, 피로아황산나트륨, BHA, 토코페롤, EDTA 등), 유화제, pH 조절을 위한 완충제, 미생물 발육을 저지하기 위한 보존제(예, 질산페닐수은, 치메로살, 염화벤잘코늄, 페놀, 크레솔, 벤질알코올 등) 등의 약학적 담체를 포함할 수 있다.
The term "administering" of the present invention means providing the patient with the desired substance in any suitable manner, and the administration route of the composition of the present invention may be administered through any conventional route so long as it can reach the target tissue have. But are not limited to, intravenous, intraperitoneal, intravenous, intramuscular, subcutaneous, intradermal, oral, topical, intranasal, intrapulmonary, rectal. In addition, the pharmaceutical composition of the present invention may be administered by any device capable of moving the active substance to the target cell. The preferred modes of administration and formulations are intravenous, subcutaneous, intradermal, intramuscular, and drip injections. The injectable solution may be a non-aqueous solvent such as an aqueous solvent such as a physiological saline solution or a ring gel solution, a vegetable oil, a higher fatty acid ester (e.g., oleic acid), an alcohol (e.g., ethanol, benzyl alcohol, propylene glycol, glycerin, etc.) (For example, ascorbic acid, sodium hydrogen sulfite, sodium pyrophosphate, BHA, tocopherol, EDTA and the like), an emulsifier, a buffer for pH control, a microbial growth inhibitor And a pharmaceutical carrier such as a preservative (e.g., mercury nitrate, thimerosal, benzalkonium chloride, phenol, cresol, benzyl alcohol, etc.).
또 다른 하나의 양태로서, 본 발명은 차전자피를 유효성분으로 포함하는 기억력 개선 또는 인지기능 장애의 예방 또는 개선용 식품 조성물을 제공한다.In yet another aspect, the present invention provides a food composition for preventing or ameliorating memory impairment or cognitive dysfunction, comprising as an active ingredient a heart meal.
상기 차전자피에 관해서는 상기에서 설명한 바와 같으며, 본 발명의 차전자피는 기억력 개선 및 인지기능 장애의 예방 또는 개선 효과를 가짐으로써 그 목적에 맞게 식품 첨가물로 식품 조성물에 포함시킬 수 있다.As described above, the present invention relates to a method for the prevention of the development of a memory effect and a cognitive dysfunction, which can be included in a food composition as a food additive for the purpose of the present invention.
본 발명의 조성물을 식품 조성물로 사용하는 경우, 상기 차전자피를 그대로 첨가하거나 다른 식품 또는 식품 성분과 함께 사용할 수 있고, 통상의 방법에 따라 적절하게 사용할 수 있다. 유효 성분의 혼합양은 사용 목적(예방, 건강 또는 치료적 처치)에 따라 적합하게 결정될 수 있으며, 식품학적으로 허용가능한 식품 보조 첨가제를 추가로 포함할 수 있다. When the composition of the present invention is used as a food composition, it may be added as it is or may be used in combination with other food or food ingredients, and may be suitably used according to ordinary methods. The amount of the active ingredient to be mixed can be suitably determined according to the intended use (prevention, health or therapeutic treatment), and may further include a food-acceptable food-aid additive.
본 발명의 식품 조성물은 통상적인 의미의 식품을 모두 포함할 수 있으며, 기능성 식품, 건강기능식품 등 당업계에 알려진 용어와 혼용 가능하다.The food composition of the present invention may include all foods having a conventional meaning, and may be mixed with terms known in the art such as functional foods, health functional foods, and the like.
본 발명의 용어 "기능성 식품"은 건강기능식품에 관한 법률 제6727호에 따른 인체에 유용한 기능성을 가진 원료나 성분을 사용하여 제조 및 가공한 식품을 의미하며, "기능성"이라 함은 인체의 구조 및 기능에 대하여 영양소를 조절하거나 생리학적 작용 등과 같은 보건 용도에 유용한 효과를 얻을 목적으로 섭취하는 것을 의미한다.The term "functional food" in the present invention means a food prepared and processed by using a raw material or ingredient having functionality useful to the human body according to Law No. 6727 on health functional foods, and " And function of the nutrient for the purpose of obtaining a beneficial effect in health use such as controlling the nutrient or physiological action.
또한, 본 발명의 용어 "건강기능식품"은 건강보조의 목적으로 특정성분을 원료로 하거나 식품 원료에 들어있는 특정성분을 추출, 농축, 정제, 혼합 등의 방법으로 제조, 가공한 식품을 말하며, 상기 성분에 의해 생체방어, 생체리듬의 조절, 질병의 방지와 회복 등 생체조절기능을 생체에 대하여 충분히 발휘할 수 있도록 설계되고 가공된 식품을 말하는 것으로서, 상기 건강식품용 조성물은 질병의 예방 및 질병의 회복 등과 관련된 기능을 수행할 수 있다.The term "health functional food" of the present invention refers to a food prepared by processing a specific ingredient as a raw material for the purpose of health assisting or by extracting, concentrating, refining, mixing, or the like a specific ingredient contained in a food raw material, Refers to a food which is designed and processed so that the body control function such as bio-defense, regulation of biorhythm, prevention and recovery of disease and the like can be sufficiently exhibited to the living body by the above components. Recovery, and so on.
본 발명의 조성물이 사용될 수 있는 식품의 종류에는 제한이 없다. 아울러 본 발명의 차전자피를 활성성분으로 포함하는 조성물은 당업자의 선택에 따라 식품에 함유될 수 있는 적절한 기타 보조 성분과 공지의 첨가제를 혼합하여 제조할 수 있다. 첨가할 수 있는 식품의 예로는 육류, 소세지, 빵, 쵸코렛, 캔디류, 스낵류, 과자류, 피자, 라면, 기타 면류, 껌류, 아이스크림 류를 포함한 낙농제품, 각종 스프, 음료수, 차, 드링크제, 알콜 음료 및 비타민 복합제 등이 있으며, 본 발명에 따른 화합물을 주성분으로 하여 제조한 즙, 차, 젤리 및 주스 등에 첨가하여 제조할 수 있다. 또한, 환제, 분말, 과립, 침제, 정제, 캡슐 또는 음료의 형태로 사용할 수 있다.There is no limitation on the kind of food in which the composition of the present invention can be used. The composition containing the present invention as an active ingredient may be prepared by mixing a suitable auxiliary ingredient with a known additive which may be contained in the food according to the selection of a person skilled in the art. Examples of foods that can be added include dairy products, such as meat, sausage, bread, chocolates, candies, snacks, confectionery, pizza, ramen, other noodles, gums, ice cream, various soups, drinks, tea, Vitamin complex, and the like, and can be prepared by adding to juice, tea, jelly, juice and the like prepared using the compound according to the present invention as a main component. It can also be used in the form of pills, powders, granules, infusions, tablets, capsules or drinks.
본 발명의 건강 음료 조성물은 지시된 비율로 필수 성분으로서 상기 화합물을 함유하는 외에는 액체성분에는 특별한 제한 점은 없으며 통상의 음료와 같이 여러 가지 향미제 또는 천연 탄수화물 등을 추가 성분으로서 함유할 수 있다. 상술한 천연 탄수화물의 예로는 모노사카라이드, 예를 들어, 포도당, 과당 등; 디사카라이드, 예를 들어 말토스, 슈크로스 등; 폴리사카라이드, 예를 들어 덱스트린, 시클로덱스트린; 등과 같은 통상적인 당 및 자일리톨, 소르비톨, 에리트리톨 등의 당알콜이다. 상술한 것 이외의 향미제로서 천연 향미제 (타우마틴, 스테비아 추출물(예를 들어 레바우디오시드 A, 글리시르히진 등)) 및 합성 향미제(사카린, 아스파르탐 등)를 유리하게 사용할 수 있다. 상기 천연 탄수화물의 비율은 본 발명의 조성물 100 ml 당 일반적으로 약 1 내지 20 g, 바람직하게는 약 5 내지 12 g이다.The health beverage composition of the present invention has no particular limitations on the liquid ingredients other than those containing the above-mentioned compounds as essential ingredients in the indicated ratios, and may contain various flavors or natural carbohydrates as additional ingredients such as ordinary beverages. Examples of the above-mentioned natural carbohydrates include monosaccharides such as glucose, fructose and the like; Disaccharides such as maltose, sucrose and the like; Polysaccharides such as dextrin, cyclodextrins; And sugar alcohols such as xylitol, sorbitol, and erythritol. As natural flavors other than those described above, natural flavors (such as tau martin, stevia extract (e.g., rebaudioside A, glycyrrhizin)) and synthetic flavors (saccharin, aspartame, etc.) have. The ratio of the natural carbohydrate is generally about 1 to 20 g, preferably about 5 to 12 g per 100 ml of the composition of the present invention.
상기 외에 본 발명의 조성물은 여러 가지 영양제, 비타민, 광물(전해질), 합성 풍미제 및 천연 풍미제 등의 풍미제, 착색제 및 중진제(치즈, 초콜릿 등), 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알콜, 탄산 음료에 사용되는 탄산화제 등을 함유할 수 있다. 그밖에 본 발명의 조성물들은 천연 과일 쥬스 및 과일 쥬스 음료 및 야채 음료의 제조를 위한 과육을 함유할 수 있다. 이러한 성분은 독립적으로 또는 조합하여 사용할 수 있다. 이러한 첨가제의 비율은 그렇게 중요하진 않지만 본 발명의 조성물 100 중량부 당 0 내지 약 20 중량부의 범위에서 선택되는 것이 일반적이다.
In addition to the above-mentioned composition, the composition of the present invention can be used as a flavoring agent such as various nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavors, coloring agents and intermediates (cheese, chocolate etc.), pectic acid and its salts, Salts, organic acids, protective colloid thickening agents, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonating agents used in carbonated beverages and the like. In addition, the compositions of the present invention may contain flesh for the production of natural fruit juices and fruit juice drinks and vegetable drinks. These components may be used independently or in combination. The proportion of such additives is not so critical, but is generally selected in the range of 0 to about 20 parts by weight per 100 parts by weight of the composition of the present invention.
본 발명의 차전자피를 포함하는 조성물은 기억력 개선 및 치매와 같은 인지기능 장애의 예방, 개선 및 치료 효과를 나타내는바, 기억력 개선 또는 인지기능 장애의 치료를 위한 의약품 및 건강기능식품 등에 유용하게 사용할 수 있다.
The composition comprising the bat made of the present invention exhibits the effect of preventing, ameliorating and treating cognitive dysfunction such as memory improvement and dementia, and is useful for drugs for improving memory or cognitive dysfunction and health functional foods .
도 1은 스코폴라민에 의해 기억력 손상이 유도된 랫트에서 차전자피(Psyllium husk)의 투여에 따른 기억력 증진 효과를 나타내는 수동회피실험 결과이다.(왼쪽: 정상군으로 정상 랫트, 가운데: 대조군으로 스코폴라민만 투여한 랫트, 오른쪽: 차전자피를 투여한 랫트)
도 2는 혈관성 치매가 유도된 랫트의 시각로(optic tract) 지역에서 차전자피의 투여에 따른 백색질의 수초 손상 정도를 관찰한 결과이다.Figure 1 shows the result of passive avoidance experiment showing the memory enhancing effect of administration of Psyllium husk in rats induced by memory impairment by scopolamine (Left: normal rat as normal group, middle: scopolar as control group) Ruminant-treated rats, right: rats fed with ketchup)
FIG. 2 shows the results of observing the degree of damage of the white matter of the white chick according to the administration of the Korean hamster bark in the optic tract region of the rats induced by vascular dementia.
이하, 실시예를 통하여 본 발명의 구성 및 효과를 더욱 상세히 설명하고자 한다. 이들 실시예는 오로지 본 발명을 예시하기 위한 것일 뿐, 본 발명의 범위가 이들 실시예에 의해 한정되는 것은 아니다.
Hereinafter, the constitution and effects of the present invention will be described in more detail through examples. These examples are only for illustrating the present invention, and the scope of the present invention is not limited by these examples.
실시예 1: 차전자피(Psyllium husk)의 기억력 손상 억제 효과 확인Example 1: Confirmation of inhibitory effect of Psyllium husk on memory impairment
차전자피를 Pharmagen,(USA)으로부터 구입하였다. Charcoal was purchased from Pharmagen, (USA).
실험동물로는 체중 280 내지 300 g 전후의 랫트(Sprague Dawley 8 주령, ㈜샘타코바이오, 오산)를 일주일 동안 실험환경에 적응시켜 사용하였다. 정상군, 대조군 그리고 실험군, 이렇게 3개의 군으로 나누었다. 적응기간(행동실험 전 7일) 및 행동실험기간 동안 500 mg/kg의 농도로 차전자피를 동물사료와 섞어 랫트들이 자유롭게 먹도록 하였으며, 투여 8 일째에 상기 랫트의 복강으로 0.9 mg/kg의 스코폴라민을 행동실험 실시 30 분 전에 주사하여 기억력 상실 동물모델을 확립하였다.As experimental animals, rats (Sprague Dawley 8 weeks old, Sam Taco Bio, Osan) having a weight of about 280 to 300 g were used for one week to adapt to the experimental environment. Normal group, control group, and experimental group. During the adaptation period (7 days before the behavioral test) and during the behavioral experiment, the rats were allowed to mix with the animal feed at a concentration of 500 mg / kg to allow the rats to eat freely. On the eighth day, 0.9 mg / kg scopolar Min was injected 30 minutes before the behavioral experiment to establish a memory loss animal model.
실험동물은 대구가톨릭대학교 의과대학 동물사육실 내에서 온도는 21 내지 24 ℃, 습도는 40 내지 60 %로 유지하였고, 낮 12 시간 밤 12 시간 주기로 하였다.
The experimental animals were kept at 21 to 24 ° C and humidity of 40 to 60% in the animal breeding room of Daegu Catholic University Medical School, and 12 hours and 12 hours at night.
차전자피의 기억력에 대한 효과를 확인하기 위하여, 아세틸콜린 수용체의 길항제인 스코폴라민으로 기억력 손상을 유도한 랫트에서 수동회피실험(passive avoidance test)을 응용한 하기와 같은 실험을 수행하였다.In order to confirm the effects on the memory of cardiopulmonary bypass, the following experiments were conducted using passive avoidance test in rats that induced memory impairment by scopolamine, an acetylcholine receptor antagonist.
구체적으로, 동일한 구조의 밝은 구획과 어두운 구획 (가로 26 cm, 세로 28 cm, 높이 15 cm)이 길로틴 문(guillotine door, 가로 9 cm, 세로 10 cm)으로 연결되어 있는 장치에서 수동회피실험을 수행하였다. 밝은 구획은 전구가 설치되어 있으며 어두운 구획은 전기자극을 줄 수 있도록 바닥에 전기 전도성 망(stainless grid)이 깔려져 있다.Specifically, passive avoidance experiments were performed on a device in which bright compartments and dark compartments (26 cm in width, 28 cm in height, 15 cm in height) of the same structure were connected by a guillotine door (9 cm in width, 10 cm in length) Respectively. The light compartment is equipped with a light bulb, and the dark compartment is equipped with a stainless grid on the bottom to provide electrical stimulation.
수동회피실험은 총 2 일 동안 진행되었다. 첫째 날에는 밝은 구획에 랫트를 넣고 1분간 적응시키고 조명을 켠 다음 칸막이 문을 열어주었다. 일반적으로 랫트는 조명이 없는 어두운 구획으로 들어가게 되는데, 이때 자동적으로 칸막이 문이 닫히도록 하였고, 불이 꺼진 상태에서 바닥의 망을 통해 0.5 mA의 전류를 5초 동안 흘려주어 foot shock을 받게 하였다. 이러한 훈련은 랫트가 20 초 안에 조명이 없는 방으로 들어갈 때까지 반복하였다. The passive avoidance experiment was conducted for a total of 2 days. On the first day, the rats were placed in a bright compartment, adapted for 1 minute, turned on, and opened the compartment door. In general, the rats are placed in a dark compartment without lighting, which automatically closes the compartment door, allowing a current of 0.5 mA to flow through the netting of the floor for 5 seconds to receive a foot shock. This training was repeated until the rats entered the room without illumination in 20 seconds.
실험 둘째 날(24 시간 후), 랫트를 밝은 구획에 다시 넣어주면 랫트는 조명이 들어와도 어두운 구획에 들어가기를 꺼려하게 되며, 이때 랫트가 어두운 구획으로 들어갈 때까지의 소요되는 시간 즉 step-through latency를 측정하였다 (retention trial). 한편, 랫트가 어두운 구획으로 들어가지 않는 경우 cut-off 시간을 300 초로 하였다.
On the second day of the experiment (after 24 hours), if the rats are placed back into the light compartment, the rats are reluctant to enter the dark compartment even when lit, and the time required for the rats to enter the dark compartment, ie, step-through latency (Retention trial). On the other hand, when the rat did not enter the dark compartment, the cut-off time was set to 300 seconds.
실험 결과, 도 1에 나타낸 바와 같이, step-through latency time은 정상군의 경우에 300.00 ± 0.0 초를 기록하였으며, 스코폴라민을 투여하여 기억력 손상을 유도한 군(대조군)의 경우에는 62.2 ± 34.6 초를 기록하여 237.8 초의 차이를 나타냄으로써, 기억력 손상이 확실하게 유발된 것을 확인할 수 있었다.As shown in FIG. 1, the step-through latency time was 300.00 ± 0.0 seconds in the normal group, and 62.2 ± 34.6 in the control group in which the memory damage was induced by administration of scopolamine Sec., Indicating a difference of 237.8 seconds. Thus, it was confirmed that the memory damage was certainly induced.
한편, 스코폴라민의 투여와 함께 차전자피 500 mg/kg 을 투여한 실험군에서는 202.4 ± 49.1 초의 step-through latency time을 보임으로써, 차전자피의 투여가 스코폴라민에 의해 유도된 손상된 기억력의 회복에 현저한 효과가 있음을 확인할 수 있었다(도 1).On the other hand, with the administration of scopolamine, the experimental group treated with 500 mg / kg of chitosan showed a step-through latency time of 202.4 ± 49.1 seconds, so that the administration of chitosan showed a remarkable effect on recovery of scopolamine-induced damaged memory (Fig. 1).
이러한 행동실험 결과를 통하여, 차전자피가 기억력을 회복시키고 인지기능을 증진시키는 데 효과적임을 알 수 있었다.
Through these behavioral test results, it was found that Chaeba - zapi is effective in restoring memory and enhancing cognitive function.
실시예 2: 차전자피의 혈관성 치매에 의한 백색질 손상 억제 효과 확인Example 2: Confirmation of inhibition of whitening damage by vascular dementia
실시예 2-1.Example 2-1. 동공반응조사에 의한 백색질 손상 억제 효과 확인Confirmation of inhibition of white matter damage by investigation of pupil reaction
차전자피의 혈관성 치매에 대한 효과를 확인하기 위하여, 혈관성 치매 모델(bileteral common carotid artery occlusion, BCCAO)을 응용하여 흔히 사용되는 만성 관류저하 모델(chronic hypoperfusion model)을 통해 백색질 손상 억제 효과를 확인하였다.In order to confirm the effects on the vascular dementia of Bombyx mori L., the inhibition effect on the white matter damage was confirmed by the chronic hypoperfusion model commonly used by applying the bilateral common carotid artery occlusion (BCCAO).
차전자피를 Pharmagen,(USA)으로부터 구입하여, 이를 100, 500 및 2,000 mg/kg/day의 용량으로 사료와 섞어서 총경동맥 결찰 5 일 전부터 랫트들에게 먹이기 시작하여 30 일 동안 지속적으로 공급하였다.The tea leaves were purchased from Pharmagen, USA, and fed to rats 5 days before total carotid artery ligation with doses of 100, 500 and 2,000 mg / kg / day, and fed continuously for 30 days.
실험동물로는 체중 280 내지 310 g 전후의 랫트(Sprague Dawley 8 주령, ㈜샘타코바이오, 오산)를 일주일 동안 실험환경에 적응시켜 사용하였다. 정상군, 대조군 그리고 실험군, 이렇게 3개의 군으로 나누었다. 적응기간(행동실험 전 5 일) 및 30 일간의 실험기간 동안 100, 500 및 2,000 mg/kg/day 의 농도로 차전자피를 사료와 섞어 랫트들이 자유롭게 먹도록 하였다. As experimental animals, rats (Sprague Dawley 8 weeks old, Sutako Bio, Osan, Co.) weighing 280-310 g were used for one week to adapt to the experimental environment. Normal group, control group, and experimental group. During the adaptation period (5 days before the behavior test) and 30 days of experiment, the rats were allowed to eat freely at a concentration of 100, 500 and 2,000 mg / kg / day.
실험동물은 대구가톨릭대학교 의과대학 동물사육실 내에서 온도는 21 내지 24 ℃, 습도는 40 내지 60 %로 유지하였고, 낮 12 시간 밤 12 시간 주기로 하였다.
The experimental animals were kept at 21 to 24 ° C and humidity of 40 to 60% in the animal breeding room of Daegu Catholic University Medical School, and 12 hours and 12 hours at night.
차전자피의 혈관성 치매에 대한 효과를 확인하기 위하여, 혈관성 치매 모델(bileteral common carotid artery occlusion, BCCAO)을 응용하여 흔히 사용되는 만성 관류저하 모델(chronic hypoperfusion model)을 통해 백색질 손상 억제 효과를 확인하였다.In order to confirm the effects on the vascular dementia of Bombyx mori L., the inhibition effect on the white matter damage was confirmed by the chronic hypoperfusion model commonly used by applying the bilateral common carotid artery occlusion (BCCAO).
혈관성 치매모델은 체중 280 내지 310 g의 랫트를 흡입마취기(multiplus)를 이용하여 이소플루란(isoflurane, 하나제약, 대한민국)으로 흡입 마취시킨 후, 두 총경동맥(common carotid artery)을 수술로 노출시켜 봉합실로 묶는 BCCAO(bilateral common carotid artery occlusion) 방법으로, 전체 뇌에 공급되는 혈류량을 4주 동안 감소시켜 확립하였다. In vascular dementia model, rats weighing 280-310 g were inhaled into an isoflurane (Hana Pharmaceutical, Korea) using an inhalation anesthesia (multiplus), and then the two common carotid arteries were surgically exposed BCCAO (bilateral common carotid artery occlusion) method was used to establish the blood flow to the whole brain for 4 weeks.
혈관성치매가 발생하면 백색질 중 시각로(optic tract)의 손상이 가장 먼저 그리고 가장 심각하게 발생한다. 급성이든 만성이든 혈액의 저관류에 의해 발생하는 망막 손상의 지표로 동공 반응이 관련되어 있다. 따라서 차전자피가 총경동맥을 묶어 발생시킨 혈관성 치매 모델에서 동공 반응에 어떠한 영향을 주는지 확인하기 위하여, 눈에 밝은 빛을 비추었을 때 약 10 초 안에 조리개가 줄어드는지 줄어들지 않는지에 의한 동공대광반사(pupillary light reflex, PLR) 손실을 조사하였다(Graefe's Arch Clin Exp Ophthalmol. 2006;244:199-204).When vascular dementia occurs, damage to the optic tract in the white matter occurs first and most seriously. Whether acute or chronic, it is an index of retinal damage caused by hypoperfusion of the blood. Therefore, in order to investigate the effect of the cardiopulmonary bypass on the pupillary response in the vascular dementia model of the common carotid artery, pupillary light due to reduction of iris in about 10 seconds when illuminating the eye, reflex, PLR) loss was investigated (Graefe's Arch Clin Exp Ophthalmol 2006; 244: 199-204).
표 1에 나타낸 바와 같이, 대조군에서 양쪽 눈 모두 PLR 손실이 온 랫트는 57 %, 한쪽 눈에만 PLR 손실이 온 랫트는 29 %, 양쪽 모두 PLR 손실이 없는 랫트는 14 %로 나타난 반면, 차전자피를 100 mg/kg의 농도로 사료에 섞어 먹인 실험군에서는 양쪽 눈 모두 PLR 손실이 온 랫트는 38 %, 한쪽 눈만 PLR 손실이 온 랫트는 38 %, 양쪽 모두 PLR 손실 없이 정상인 랫트는 24 % 로 나타났다. As shown in Table 1, in the control group, 57% of the rats with PLR loss in both eyes showed a PLR loss of 29% in one eye, and 14% in the rats without PLR loss in both eyes, In the test group fed with diets mixed with feed at the concentration of mg / kg, PLR loss was 38% in both rats, 38% in one rat, and 24% in normal rats without PLR loss.
또한, 차전자피를 500 mg/kg 및 2000 mg/kg의 농도로 사료에 섞어 먹인 실험군에서는 양쪽 눈에서 모두 PLR 손실이 온 랫트는 전혀 없고, 양쪽 모두 PLR 손실 없이 정상인 랫트는 비율이 훨씬 더 증가하였다.In addition, in the experimental group fed diets containing 500 mg / kg and 2000 mg / kg bacterias, there was no PLR loss in both eyes, and both rats were significantly increased in normal rats without loss of PLR.
따라서, 차전자피를 먹인 실험군이 대조군보다 동공반응이 정상군에 가깝게 유지되고 있음을 확인할 수 있었다.
Therefore, it can be confirmed that the experimental group fed with the cardiopulmonary medicine kept the pupil reaction closer to the normal group than the control group.
실시예 2-2.Example 2-2. 룩솔 패스트 블루(Luxol fast blue) 염색법에 의한 백색질 손상 억제 효과 확인Confirmation of inhibition of whitish damage by Luxol fast blue staining
차전자피의 혈관성 치매에 대한 효과를 확인하기 위하여, 룩솔 패스트 블루염색방법을 통해 백색질 손상 억제 효과를 확인하였다.
In order to confirm the effect on the vascular dementia of Bombyx mori L., the inhibition effect on whitening damage was confirmed by the Luxel Fast Blue staining method.
실험동물로는 체중 280 내지 310 g 전후의 랫트(Sprague Dawley 8 주령, ㈜샘타코바이오, 오산)를 일주일 동안 실험환경에 적응시켜 사용하였다. 정상군, 대조군 그리고 실험군, 이렇게 3개의 군으로 나누었다. 적응기간(행동실험 전 5 일) 및 30 일간의 실험기간 동안 10 및 100 mg/kg/day의 농도로 차전자피를 사료와 섞어 랫트들이 자유롭게 먹도록 하였다.
As experimental animals, rats (Sprague Dawley 8 weeks old, Sutako Bio, Osan, Co.) weighing 280-310 g were used for one week to adapt to the experimental environment. Normal group, control group, and experimental group. During the adaptation period (5 days before the behavior test) and 30 days of experiment, the rats were allowed to eat freely at a concentration of 10 and 100 mg / kg / day.
만성 관류저하 모델에서는 랫트의 양쪽 총경동맥을 묶으면 척추동맥을 통해 공급된 혈액이 윌리스환(circle of Willis)을 거쳐 뇌에 공급된다. 하지만 공급되는 혈액의 양이 적어 백색질 부분이 선택적으로 죽게 되며 이 지역으로는 뇌들보 (corpus callosum), 속섬유막 (internal capsule) 및 시각로 (optic tract)가 있다(Farkas et al., Permanent, bilateral common carotid artery occlusion in the rat: a model for chronic cerebral hypoperfusion-related neurodegenrative diseases. Brain Res Rev 2007;54:162-180). 뇌에는 세포체(cell body)와 축삭(axon) 등으로 구성된 신경세포(neuron) 외에도 신경세포에 영양분을 공급하고 과잉의 신경전달물질을 제거하는 별아교세포(astrocyte)와 신경세포를 구성하는 축삭(axon)을 통해 전기신호전달을 원활하게 하기 위해 필요한 수초(말이집)(myelin)를 생성하는 희소돌기아교세포(oligodendrocyte) 및 신경세포가 죽거나 감염되었을 때 죽은 세포를 제거하는 역할을 하는 미세아교세포(microglia)로 구성되어 있으며(Allen & Barres, Neuroscience:than just brain glue. Nature 2009 Feb 5;457(7230):675-7), 세포외기질로는 주로 다당류인 히알유로난(hyaluronan)으로 구성되어 있다(Rauch, Extracellular matrix components associated with remodeling processes in brain. Cell Mol Life Sci 2004;61:2031-2045). 이 중에서 혈관성 치매에 관여하는 백색질에는 신경세포의 축삭이 주를 이루고 있기 때문에 조직을 백색질 위주로 관찰하며 이들 손상을 확인하기 위하여 룩솔 패스트 블루(Luxol fast blue) 염색법을 실시하였다.In the chronic perfusion-depleted model, when both the carotid arteries of the rats are tied, the blood supplied through the vertebral artery is supplied to the brain through the circle of Willis. However, the amount of blood to be supplied is low and the white matter is selectively killed. There are corpus callosum, internal capsule, and optic tract in this region (Farkas et al., Permanent, bilateral common carotid artery occlusion in the rat: a model for chronic cerebral hypoperfusion-related neurodegenerative diseases. Brain Res Rev 2007; 54: 162-180). In addition to neurons composed of cell bodies and axons, the brain also contains astrocyte that nourishes nerve cells and removes excess neurotransmitters, and axons that make up nerve cells. (Oligodendrocyte), which produces the myelin necessary to facilitate the transmission of electrical signals through the microglial cells (oligodendrocyte) and microglial cells that act to remove dead cells when nerve cells die or become infected microglia) (Nature 2009 Feb 5; 457 (7230): 675-7), and the extracellular matrix consists mainly of the polysaccharide hyaluronan (Allen & Barres, Neuroscience: (Rauch, Extracellular matrix components associated with remodeling processes in brain. Cell Mol Life Sci 2004; 61: 2031-2045). Among them, the white matter involved in vascular dementia was mainly composed of axons of nerve cells. Therefore, the tissues were observed mainly in white color and the luxol fast blue staining was performed to confirm these damages.
구체적으로, 혈관(capillary)에 혈액이 공급되지 않으면 에너지 소모는 많고 활성산소종의 발생이 높은 희소돌기아교세포(oligodendrocyte)가 세포자살 등에 의해 먼저 죽게 될 뿐만 아니라 (McTigue & Tripathi, 2008), 활성화된 기질 금속단백분해효소(matrix metalloproteinase)에 의해 수초를 구성하는 단백질인 MBP (myelin-basic protein) 등이 분해되면서 수초가 손상된다(Arai & Lo, 2009 ; Mctigue & Tripathi, 2008). 이에 따른 수초의 손상은 조직 슬라이드를 백색질이 존재하는 위치인 브레그마(bregma point)로부터 -2.64 내지 -3.12 mm 위치를 획득하여 룩솔 패스트 블루 용액과 탄산 리튬(lithium carbonate) 용액을 이용하여 염색을 실시하고, 수초의 상태에 따라 점수를 매겨 수초의 손상 정도를 판단하였다(Pistorio et al., A modified technique for high-resolution staining of myelin. J Neurosci Methods 2006;153:135-146). 각각의 환산된 점수는 하기 표 2에 나타낸 바와 같으며, 손상이 잘 일어나는 지역 가운데 대표적인 시각로 지역을 중심으로 관찰하였다.Specifically, when blood is not supplied to the capillary, oligodendrocytes, which have high energy consumption and high levels of reactive oxygen species, are first killed by cell suicide (McTigue & Tripathi, 2008) (Arai & Lo, 2009; Mctigue & Tripathi, 2008), which is the result of degradation of myelin-basic protein (MBP), a protein that constitutes a few seconds by matrix metalloproteinase. The damage of a few seconds is obtained by obtaining the position of -2.64 to -3.12 mm from the bregma point where the whitish is present on the tissue slide, and dyeing is carried out using Luxol Fast Blue solution and lithium carbonate solution , And a score of several seconds to determine the degree of damage of a few seconds (Pistorio et al., A modified technique for high-resolution staining of myelin J Neurosci Methods 2006; 153: 135-146). Each converted score was as shown in Table 2 below, and was observed around the area as a representative example of the area where damage is likely to occur.
상기 실험결과, 도 2에 나타낸 바와 같이, 혈관성 치매를 유도하지 않은 정상군에 비하여 혈관성 치매를 유도한 대조군에서 손상점수가 매우 높게 나타나는 것을 확인할 수 있었으며, 반면 차전자피를 100 mg/kg 의 농도로 투여한 군(0.66 ± 0.25, p<0.05)에서는 대조군(1.57 ± 0.28, p<0.05)에 비하여 손상점수가 현저하게 감소하는 것을 확인할 수 있었다. As shown in FIG. 2, in the control group inducing vascular dementia, the score of damage was significantly higher than that of the normal group not inducing vascular dementia. On the other hand, when the control group was administered at a concentration of 100 mg / kg In the group (0.66 ± 0.25, p <0.05), the score of damage was significantly lower than that of the control group (1.57 ± 0.28, p <0.05).
이와 같은 실험결과를 통하여, 차전자피의 투여가 혈관성 치매 발생시 생기는 백색질의 손상을 억제한다는 것을 확인할 수 있었으며, 그에 따라 차전자피가 혈관성 치매의 개선에 효과가 있음을 알 수 있었다.
From these results, it was confirmed that the administration of B. trachomatis inhibited the damage of white matter caused by vascular dementia. Thus, it was found that the B. trachomatis was effective in the improvement of vascular dementia.
이상의 설명으로부터, 본 발명이 속하는 기술분야의 당업자는 본 발명이 그 기술적 사상이나 필수적 특징을 변경하지 않고서 다른 구체적인 형태로 실시될 수 있다는 것을 이해할 수 있을 것이다. 이와 관련하여, 이상에서 기술한 실시 예들은 모든 면에서 예시적인 것이며 한정적인 것이 아닌 것으로서 이해해야만 한다. 본 발명의 범위는 상기 상세한 설명보다는 후술하는 특허 청구범위의 의미 및 범위 그리고 그 등가 개념으로부터 도출되는 모든 변경 또는 변형된 형태가 본 발명의 범위에 포함되는 것으로 해석되어야 한다.
From the above description, it will be understood by those skilled in the art that the present invention may be embodied in other specific forms without departing from the spirit or essential characteristics thereof. In this regard, it should be understood that the above-described embodiments are to be considered in all respects as illustrative and not restrictive. The scope of the present invention should be construed as being included in the scope of the present invention without departing from the scope of the present invention as defined by the appended claims.
Claims (5)
A pharmaceutical composition for preventing or treating memory improvement or cognitive dysfunction, comprising Psyllium husk as an active ingredient.
The composition according to claim 1, wherein the cognitive dysfunction is any one selected from the group consisting of forgetfulness, Alzheimer's disease, vascular dementia, dementia caused by head injury, or Parkinson's disease.
The composition of claim 1, wherein the particulate material is in the form of a powder.
A health functional food composition for preventing or ameliorating memory impairment or cognitive dysfunction, which comprises as an active ingredient a cardiovascular disease.
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20210086806A (en) * | 2019-12-30 | 2021-07-09 | 재단법인 통합의료진흥원 | Composition for preventing, ameliorating or treating side effect of chemotherapeutic regimen comprising Psyllium husk as active ingredient |
| KR20210118492A (en) | 2020-03-23 | 2021-10-01 | 주식회사 네이처센스 | A composition for improving memory, cognitive function, or preventing and improving brain neurological diseases |
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