KR20230077692A - Pharmaceutical composition for preventing or treating degenerative brain diseases comprising mixed metabolites driven from cell free supernatants of Bacillus velezensis and Lactobacillus plantarum as an active ingredient - Google Patents
Pharmaceutical composition for preventing or treating degenerative brain diseases comprising mixed metabolites driven from cell free supernatants of Bacillus velezensis and Lactobacillus plantarum as an active ingredient Download PDFInfo
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- KR20230077692A KR20230077692A KR1020220160151A KR20220160151A KR20230077692A KR 20230077692 A KR20230077692 A KR 20230077692A KR 1020220160151 A KR1020220160151 A KR 1020220160151A KR 20220160151 A KR20220160151 A KR 20220160151A KR 20230077692 A KR20230077692 A KR 20230077692A
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- lactobacillus plantarum
- pharmaceutical composition
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Abstract
Description
본 발명은 바실러스 벨레젠시스(Bacillus velezensis) 생산 대사산물 및 락토바실러스 플란타럼(Lactobacillus plantarum) 생산 대사산물을 혼합한 혼합 대사산물을 유효성분으로 포함하는 퇴행성 뇌질환 예방 또는 치료용 약학 조성물에 관한 것이다.The present invention relates to a pharmaceutical composition for the prevention or treatment of degenerative brain diseases comprising, as an active ingredient, a mixed metabolite obtained by mixing a metabolite produced by Bacillus velezensis and a metabolite produced by Lactobacillus plantarum . will be.
현대인들은 지속적인 스트레스, 노화, 과음, 흡연, 약물, 수면부족, 우울 등에 무방비하게 노출되어 있고 이러한 원인으로 인해 노인뿐 아니라 청장년층의 뇌질환에 의해 기억능력이 저하되어 그 정도가 심한 경우 다양한 문제들이 야기될 수 있다. Modern people are defenselessly exposed to constant stress, aging, excessive drinking, smoking, drugs, lack of sleep, depression, etc. Due to these causes, not only the elderly but also the young adults have a decline in memory ability due to brain diseases, causing various problems if the degree is severe. It can be.
기억이란 정보의 저장과 유지, 그리고 회상의 일련의 과정을 의미한다. 기억의 첫 번째 단계는 외부로부터 온 정보를 화학적 또는 물리적 자극의 형태로 감각기관을 통해 받아들이는 저장단계, 두 번째는 정보를 시간이 지남에도 계속 유지할 수 있게 하는 유지단계, 세 번째는 저장되어 있는 정보를 찾아내서 의식수준으로 끌어내는 회상단계이다. 상기 세 단계 중에 어느 하나라도 이상이 생기면 정보 또는 지식을 정확하게 기억할 수 없게 되는 현상 즉, 기억력 저하 내지 감퇴가 일어날 수 있다.Memory refers to a series of processes of storing, maintaining, and recalling information. The first stage of memory is the storage stage in which information from the outside is accepted through the sensory organs in the form of chemical or physical stimuli. It is the recall stage in which information is retrieved and brought to a conscious level. If any one of the above three steps is abnormal, a phenomenon in which information or knowledge cannot be accurately memorized, that is, memory deterioration or decline may occur.
이에 기억능력의 저하 내지 감퇴에 대하여 현재 외과적 방법이나 약물적 방법이 모두 사용되고 있으나, 외과적 방법은 용이하지 아니한 측면이 있어 약물적 방법이 권장되고 있다. 상기 약물적 방법으로서 아세틸콜린을 분해하는 효소인 아세틸콜린에스터라제의 활성억제제(타크린, 아리셉트, 도네페질, 리바스티그린 또는 갈란타민등)가 상업화되어 있으나, 이는 기억능력의 저하 내지 감퇴를 치료하기보다는 신경전달물질을 조절하여 일시적 증상 호전을 나타낼 뿐이다. 더군다나 간 독성, 위장관장애, 심장 서맥 유발, 체중감소, 불면증 등의 부작용과 장기복용에 따른 독성 내지 의존성이 문제점으로 지적되고 있어 이를 보완하기 위한 새로운 치료제들의 개발이 요구되고 있다.Therefore, both surgical and pharmacological methods are currently used for the decline or decline of memory ability, but the surgical method is not easy, so the pharmacological method is recommended. As the above pharmacological method, inhibitors of the activity of acetylcholinesterase, an enzyme that decomposes acetylcholine (tacrine, Aricept, donepezil, rivastigrin or galantamine, etc.) have been commercialized, but these Rather than treating it, it modulates neurotransmitters to show temporary symptom improvement. Furthermore, side effects such as liver toxicity, gastrointestinal disorder, cardiac bradycardia, weight loss, insomnia, and toxicity or dependence due to long-term use have been pointed out as problems, and the development of new treatments to supplement them is required.
더욱이, 식약처 자료에 따르면 지난 2018년 우리나라 건강기능식품 전체 시장에서 기억력 개선 관련 제품은 1조 2135억원으로, 그 점유비는 14.4%이며 면역기능 제품에 이어 두 번째로 높은 점유비를 보였다. 상기에서 언급했듯이 몇 년째 제약업계에서도 기억력 관련 제품을 적지 않게 선보였지만 많은 주목을 받지 못하고 있는 이유는 확실한 개선효과를 보지 못하고 있기 때문인 것으로 생각되며, 이에 따라 청소년층의 기억력 증진에 도움을 주고 20~40대 건망을 호소하는 사람의 건망증을 예방할 수 있고 뇌 기능 저하 및 기억력 감퇴가 급격하게 증가하는 노인들의 치매까지도 예방 및 개선할 수 있는 부작용이 적으며, 효능이 좋고, 새로운 학습과 기억력 증진효과를 갖는 기능성 소재 및 건강기능식품 개발이 요구되고 있다.Moreover, according to data from the Ministry of Food and Drug Safety, in 2018, products related to memory improvement in the entire market for health functional foods in Korea amounted to 1,213.5 billion won, accounting for 14.4%, the second highest share after immune function products. As mentioned above, the pharmaceutical industry has introduced quite a few memory-related products for several years, but it is thought that the reason why they have not received much attention is that they do not have a clear improvement effect. It can prevent forgetfulness of people complaining of forgetfulness and even prevent and improve dementia in the elderly, where brain function decline and memory decline rapidly increase. The development of functional materials and health functional foods is required.
본 발명의 목적은 바실러스 벨레젠시스(Bacillus velezensis) 생산 대사산물 및 락토바실러스 플란타럼(Lactobacillus plantarum) 생산 대사산물을 혼합한 혼합 대사산물을 유효성분으로 포함하는 퇴행성 뇌질환 예방 또는 치료용 약학 조성물을 제공하는 것이다.An object of the present invention is a pharmaceutical composition for preventing or treating degenerative brain disease comprising a mixed metabolite obtained by mixing a metabolite produced by Bacillus velezensis and a metabolite produced by Lactobacillus plantarum as an active ingredient. is to provide
본 발명의 다른 목적은 바실러스 벨레젠시스(Bacillus velezensis ) 생산 대사산물 및 락토바실러스 플란타럼(Lactobacillus plantarum) 생산 대사산물을 혼합한 혼합 대사산물을 유효성분으로 포함하는 퇴행성 뇌질환 예방 또는 개선용 건강기능식품 조성물을 제공하는 것이다. Another object of the present invention is to produce Bacillus velezensis Metabolites and Lactobacillus plantarum ( Lactobacillus plantarum ) To provide a health functional food composition for preventing or improving degenerative brain disease containing a mixed metabolite mixed with metabolites produced as an active ingredient.
본 발명의 또 다른 목적은 바실러스 벨레젠시스(Bacillus velezensis) 생산 대사산물 및 락토바실러스 플란타럼(Lactobacillus plantarum) 생산 대사산물을 혼합한 혼합 대사산물을 유효성분으로 포함하는 기억력 개선용 건강기능식품 조성물을 제공하는 것이다.Another object of the present invention is to produce Bacillus velezensis Metabolites and Lactobacillus plantarum ( Lactobacillus plantarum ) It is to provide a health functional food composition for improving memory comprising a mixed metabolite, which is a mixture of produced metabolites, as an active ingredient.
상기 목적을 달성하기 위해, 본 발명은 바실러스 벨레젠시스(Bacillus velezensis) 생산 대사산물 및 락토바실러스 플란타럼(Lactobacillus plantarum) 생산 대사산물을 혼합한 혼합 대사산물을 유효성분으로 포함하는 퇴행성 뇌질환 예방 또는 치료용 약학 조성물을 제공한다.In order to achieve the above object, the present invention Bacillus velezensis production Metabolites and Lactobacillus plantarum ( Lactobacillus plantarum ) Provided is a pharmaceutical composition for preventing or treating degenerative brain disease comprising a mixed metabolite, which is a mixture of produced metabolites, as an active ingredient.
또한, 본 발명은 바실러스 벨레젠시스(Bacillus velezensis) 생산 대사산물 및 락토바실러스 플란타럼(Lactobacillus plantarum) 생산 대사산물을 혼합한 혼합 대사산물을 유효성분으로 포함하는 퇴행성 뇌질환 예방 또는 개선용 건강기능식품 조성물을 제공한다.In addition, the present invention is Bacillus velezensis ( Bacillus velezensis ) Production metabolites and Lactobacillus plantarum ( Lactobacillus plantarum ) Production metabolites, including mixed metabolites as an active ingredient health function for preventing or improving degenerative brain disease A food composition is provided.
또한, 본 발명은 바실러스 벨레젠시스(Bacillus velezensis) 생산 대사산물 및 락토바실러스 플란타럼(Lactobacillus plantarum) 생산 대사산물을 혼합한 혼합 대사산물을 유효성분으로 포함하는 기억력 개선용 건강기능식품 조성물을 제공한다.In addition, the present invention provides a health functional food composition for improving memory comprising a mixed metabolite obtained by mixing a metabolite produced by Bacillus velezensis and a metabolite produced by Lactobacillus plantarum as an active ingredient. do.
본 발명에 따르면, 바실러스 벨레젠시스(Bacillus velezensis ) 생산 대사산물 및 락토바실러스 플란타럼(Lactobacillus plantarum) 생산 대사산물을 혼합한 혼합 대사산물이 산화 스트레스로 인한 기억력 감소를 억제하는 것을 확인함으로써, 퇴행성 뇌질환 예방, 치료 또는 개선용 조성물이나 기억력 개선용 조성물로서 유용하게 활용될 수 있다.According to the present invention, Bacillus velezensis ( Bacillus velezensis ) Production metabolites and Lactobacillus plantarum ( Lactobacillus plantarum ) By confirming that the mixed metabolites mixed with the production metabolites inhibit memory loss due to oxidative stress, degenerative It can be usefully used as a composition for preventing, treating or improving brain diseases or a composition for improving memory.
도 1은 파킨슨병 유도 초파리 모델(DJ-1βex54)에서 산화 스트레스가 기억력에 미치는 영향을 분석한 결과이다.
도 2는 파킨슨병 유도 초파리 모델(DJ-1βex54)에서 실험예 1에서 제조한 혼합 대사산물의 학습능력 및 맛-연상기억력 개선 효과를 분석한 결과이다. 별표는 통제 대조군과 비교했을 때, 의미있는 변화가 나타난 것을 의미하고, 통계적 의미는 single factor ANOVA with Scheffe’s analysis as a post hoc test로 두 개의 데이터 셋(*P<0.05, **P<0.01)을 분석하여 도출하였으며, 오차 막대는 SEMs를 의미한다.1 is a result of analyzing the effect of oxidative stress on memory in a Parkinson's disease-induced Drosophila model (DJ-1βex54).
Figure 2 shows the results of analyzing the learning ability and taste-associative memory improvement effect of the mixed metabolite prepared in Experimental Example 1 in the Parkinson's disease-induced Drosophila model (DJ-1βex54). An asterisk indicates a significant change compared to the control group, and the statistical significance is single factor ANOVA with Scheffe's analysis as a post hoc test for two data sets (*P<0.05, **P<0.01). It was derived by analysis, and error bars represent SEMs.
이하, 본 발명을 보다 상세하게 설명한다.Hereinafter, the present invention will be described in more detail.
본 발명은 바실러스 벨레젠시스(Bacillus velezensis) 생산 대사산물 및 락토바실러스 플란타럼(Lactobacillus plantarum) 생산 대사산물을 혼합한 혼합 대사산물을 유효성분으로 포함하는 퇴행성 뇌질환 예방 또는 치료용 약학 조성물을 제공한다.The present invention produces Bacillus velezensis Metabolites and Lactobacillus plantarum ( Lactobacillus plantarum ) Provided is a pharmaceutical composition for preventing or treating degenerative brain disease comprising a mixed metabolite, which is a mixture of produced metabolites, as an active ingredient.
상기 혼합 대사산물은 바실러스 벨레젠시스 생산 대사산물 및 락토바실러스 플란타럼 생산 대사산물을 1 : 0.25 내지 4의 중량 비율로 혼합한 것일 수 있다.The mixed metabolite may be a mixture of a metabolite produced by Bacillus bellegensis and a metabolite produced by Lactobacillus plantarum at a weight ratio of 1:0.25 to 4.
또한, 상기 혼합 대사산물은 산화 스트레스(oxidative stress)에 의한 기억력 감소를 억제할 수 있다.In addition, the mixed metabolites can suppress memory loss caused by oxidative stress.
상기 퇴행성 뇌질환은 알츠하이머병(Alzheimer’s disease), 전측두치매(Frontotemporal dementia), 파킨슨병(Parkinson’s disease), 근위축성측색경화증(Amyotrophic lateral sclerosis), 진행성핵상마비(Progressive supranuclear palsy), 피질기저핵변성(Corticobasal degeneration), 피크병(Pick's disease), 경도인지장애(MCI) 및 치매로 이루어진 군에서 선택된 하나 이상일 수 있으나, 이에 한정되는 것은 아니다.The degenerative brain disease is Alzheimer's disease, frontotemporal dementia, Parkinson's disease, amyotrophic lateral sclerosis, progressive supranuclear palsy, corticobasal degeneration ( Corticobasal degeneration), Pick's disease, mild cognitive impairment (MCI), and dementia, but may be one or more selected from, but is not limited thereto.
본 발명에 있어서, 상기 약학 조성물에 포함되는 첨가제의 함량은 특별히 한정되는 것은 아니며 통상의 제제화에 사용되는 함량 범위 내에서 적절하게 조절될 수 있다.In the present invention, the content of the additives included in the pharmaceutical composition is not particularly limited and may be appropriately adjusted within the range of content used in conventional formulations.
상기 약학 조성물은 수용액, 현탁액, 유탁액 등과 같은 주사용 제형, 환약, 캡슐, 과립, 정제, 크림, 젤, 패취, 분무제, 연고제, 경고제, 로션제, 리니멘트제, 파스타제 및 카타플라스마제로 이루어진 군으로부터 선택되는 하나 이상의 외용제 형태로 제형화될 수 있다.The pharmaceutical composition may be formulated into an injectable formulation such as an aqueous solution, suspension, or emulsion, a pill, a capsule, a granule, a tablet, a cream, a gel, a patch, a spray, an ointment, a warning agent, a lotion, a liniment agent, a paste agent, and a cataplasma agent. It may be formulated in the form of one or more external agents selected from the group consisting of
본 발명의 약학 조성물은 제형화를 위해 추가로 있는 약학적으로 허용 가능한 담체 및 희석제를 포함할 수 있다. 상기 약학적으로 허용 가능한 담체 및 희석제는 전분, 당 및 만니톨과 같은 부형제, 칼슘 포스페이트 등과 같은 충전제 및 증량제, 카르복시메틸셀룰로오스, 히드록시프로필셀룰로오스 등과 같은 셀룰로오스 유도체, 젤라틴, 알긴산염, 폴리비닐 피롤리돈 등과 같은 결합제, 활석, 스테아린산 칼슘, 수소화 피마자유 및 폴리에틸렌글리콜과 같은 윤활제, 포비돈 및 크로스포비돈과 같은 붕해제, 폴리소르베이트, 세틸알코올, 글리세롤 등과 같은 계면활성제를 포함하나, 이에 한정되지 않는다. 상기 약학적으로 허용 가능한 담체 및 희석제는 대상체에게 생물학적 및 생리학적으로 친화적인 것일 수 있다. 희석제의 예로는 염수, 수용성 완충액, 용매 및/또는 분산제(dispersion media)를 들 수 있으나, 이에 제한되는 것은 아니다.The pharmaceutical composition of the present invention may additionally contain pharmaceutically acceptable carriers and diluents for formulation. The pharmaceutically acceptable carriers and diluents include excipients such as starch, sugar and mannitol, fillers and extenders such as calcium phosphate, cellulose derivatives such as carboxymethylcellulose and hydroxypropylcellulose, gelatin, alginates, and polyvinyl pyrrolidone. binders such as talc, calcium stearate, lubricants such as hydrogenated castor oil and polyethylene glycol, disintegrants such as povidone and crospovidone, surfactants such as polysorbates, cetyl alcohol, glycerol and the like, but are not limited thereto. The pharmaceutically acceptable carrier and diluent may be biologically and physiologically compatible with the subject. Examples of diluents include, but are not limited to, saline, aqueous buffers, solvents and/or dispersion media.
본 발명의 약학 조성물은 목적하는 방법에 따라 경구 투여하거나 비경구 투여(예를 들어, 정맥 내, 피하, 복강 내 또는 국소에 적용)할 수 있다. 경구 투여일 경우, 정제, 트로키제(troches), 로젠지(lozenge), 수용성 현탁액, 유성 현탁액, 조제 분말, 과립, 에멀젼, 하드 캡슐, 소프트 캡슐, 시럽, 엘릭시르제 등으로 제형화될 수 있다. 비경구 투여일 경우, 주사액, 좌제, 호흡기 흡입용 분말, 스프레이용 에어로졸제, 연고, 도포용 파우더, 오일, 크림 등으로 제형화 될 수 있다.The pharmaceutical composition of the present invention may be administered orally or parenterally (eg, intravenous, subcutaneous, intraperitoneal or topical application) depending on the desired method. For oral administration, it may be formulated into tablets, troches, lozenges, aqueous suspensions, oily suspensions, prepared powders, granules, emulsions, hard capsules, soft capsules, syrups, elixirs, and the like. In the case of parenteral administration, it may be formulated as an injection solution, suppository, powder for respiratory inhalation, aerosol for spray, ointment, powder for application, oil, cream, etc.
본 발명의 약학 조성물의 투여량은 환자의 상태, 체중, 연령, 성별, 건강상태, 식이 체질 특이성, 제제의 성질, 질병의 정도, 조성물의 투여시간, 투여방법, 투여기간 또는 간격, 배설율 및 약물 형태에 따라 그 범위가 다양할 수 있으며, 이 분야 통상의 기술자에 의해 적절하게 선택될 수 있다. 예컨대, 약 0.1 내지 10,000mg/kg의 범위일 수 있으나 이에 제한되지 않으며, 하루 일회 내지 수회에 나누어 투여될 수 있다.The dosage of the pharmaceutical composition of the present invention depends on the patient's condition, weight, age, sex, health condition, dietary constitution specificity, the nature of the preparation, the severity of the disease, the administration time of the composition, the administration method, the administration period or interval, the excretion rate and The range may vary depending on the type of drug, and may be appropriately selected by a person skilled in the art. For example, it may range from about 0.1 to 10,000 mg/kg, but is not limited thereto, and may be divided and administered once or several times a day.
상기 약학 조성물은 목적하는 방법에 따라 경구 투여되거나 비경구 투여(예를 들면, 정맥 내, 피하 내, 복강 내 또는 국소에 적용)될 수 있다. 본 발명의 약학 조성물의 약학적 유효량 및 유효 투여량은 약학 조성물의 제제화 방법, 투여 방식, 투여 시간, 투여 경로 등에 의해 다양해질 수 있으며, 당해 기술 분야에서 통상의 지식을 가진 자는 목적하는 치료에 효과적인 투여량을 용이하게 결정하고 처방할 수 있다. 본 발명의 약학 조성물의 투여는 하루에 1회 투여될 수 있고, 수회에 나누어 투여될 수도 있다.The pharmaceutical composition may be administered orally or parenterally (eg, intravenous, subcutaneous, intraperitoneal or topical application) depending on the desired method. The pharmaceutically effective amount and effective dose of the pharmaceutical composition of the present invention may vary depending on the formulation method, administration method, administration time, administration route, etc. of the pharmaceutical composition, and those skilled in the art can achieve effective treatment for the desired treatment. The dosage can be easily determined and prescribed. Administration of the pharmaceutical composition of the present invention may be administered once a day, or may be divided and administered several times.
또한, 본 발명은 바실러스 벨레젠시스(Bacillus velezensis) 생산 대사산물 및 락토바실러스 플란타럼(Lactobacillus plantarum) 생산 대사산물을 혼합한 혼합 대사산물을 유효성분으로 포함하는 퇴행성 뇌질환 예방 또는 개선용 건강기능식품 조성물을 제공한다.In addition, the present invention is Bacillus velezensis ( Bacillus velezensis ) Production metabolites and Lactobacillus plantarum ( Lactobacillus plantarum ) Production metabolites, including mixed metabolites as an active ingredient health function for preventing or improving degenerative brain disease A food composition is provided.
또한, 본 발명은 바실러스 벨레젠시스(Bacillus velezensis) 생산 대사산물 및 락토바실러스 플란타럼(Lactobacillus plantarum) 생산 대사산물을 혼합한 혼합 대사산물을 유효성분으로 포함하는 기억력 개선용 건강기능식품 조성물을 제공한다.In addition, the present invention Bacillus velezensis ( Bacillus velezensis ) production Metabolites and Lactobacillus plantarum ( Lactobacillus plantarum ) Provides a health functional food composition for improving memory comprising a mixed metabolite, which is a mixture of produced metabolites, as an active ingredient.
본 발명은 통상적으로 이용되는 식품으로써 일반적으로 사용될 수 있다.The present invention can be generally used as a commonly used food.
본 발명의 식품 조성물은 건강기능식품으로서 사용될 수 있다. 상기 "건강기능 식품"이라 함은 건강기능 식품에 관한 법률에 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 보건용도에 유용한 효과를 얻을 목적으로 섭취하는 것을 의미한다.The food composition of the present invention can be used as a health functional food. The term "health functional food" refers to food manufactured and processed using raw materials or ingredients having useful functionalities for the human body in accordance with the Health Functional Food Act, and "functional" refers to food that is not related to the structure and function of the human body. It refers to intake for the purpose of obtaining useful effects for health purposes such as regulating nutrients or physiological functions.
상기 건강기능식품 조성물은 통상의 식품 첨가물을 포함할 수 있으며, 상기 "식품 첨가물"로서의 적합 여부는 다른 규정이 없는 한, 식품의약품안전처에 승인된 식품 첨가물 공전의 총칙 및 일반시험법 등에 따라 해당 품목에 관한 규격 및 기준에 의하여 판정한다.The health functional food composition may include conventional food additives, and the suitability as the "food additive" is determined in accordance with the General Rules and General Test Methods of Food Additives approved by the Ministry of Food and Drug Safety, unless otherwise specified. It is judged according to the specifications and standards for the item.
상기 "식품 첨가물 공전"에 수재된 품목으로는 예를 들어, 케톤류, 글리신, 구연산칼륨, 니코틴산, 계피산 등의 화학적 합성물, 감색소, 감초추출물, 결정셀룰로오스, 고량색소, 구아검 등의 천연첨가물, L-글루타민산나트륨 제제, 면류첨가알칼리제, 보존료제제, 타르색소제제 등의 혼합제제류들을 들 수 있다.Items listed in the "Food Additive Code" include, for example, chemical compounds such as ketones, glycine, potassium citrate, nicotinic acid, and cinnamic acid, natural additives such as dark pigment, licorice extract, crystalline cellulose, goyang pigment, guar gum, and mixed preparations such as sodium L-glutamate preparations, noodle-added alkali preparations, preservative preparations, and tar color preparations.
본 발명의 식품 조성물은 정제, 캡슐, 분말, 과립, 액상, 환 등의 형태로 제조 및 가공할 수 있다. 예를 들어, 캡슐 형태의 건강기능 식품 중 경질 캡슐제는 통상의 경질 캡슐에 본 발명에 따른 조성물을 부형제 등의 첨가제와 혼합 및 충진하여 제조할 수 있으며, 연질 캡슐제는 본 발명에 따른 조성물을 부형제 등의 첨가제와 혼합하고 젤라틴 등 캡슐기제에 충진하여 제조할 수 있다. 상기 연질 캡슐제는 필요에 따라 글리세린 또는 소르비톨 등의 가소제, 착색제, 보존제 등을 함유할 수 있다.The food composition of the present invention can be prepared and processed in the form of tablets, capsules, powders, granules, liquids, pills and the like. For example, among health functional foods in the form of capsules, hard capsules can be prepared by mixing and filling a composition according to the present invention with additives such as excipients in a conventional hard capsule, and soft capsules contain the composition according to the present invention. It can be prepared by mixing with additives such as excipients and filling in a capsule base such as gelatin. The soft capsule may contain a plasticizer such as glycerin or sorbitol, a coloring agent, a preservative, and the like, if necessary.
상기 부형제, 결합제, 붕해제, 활택제, 교미제, 착향제 등에 대한 용어 정의는 당업계에 공지된 문헌에 기재된 것으로 그 기능 등이 동일 내지 유사한 것들을 포함한다. 상기 식품의 종류에는 특별한 제한이 없으며, 통상적인 의미에서의 건강기능식품을 모두 포함한다.Definitions of terms for the excipients, binders, disintegrants, lubricants, corrigents, flavoring agents, etc. are described in literature known in the art, and include those having the same or similar functions. There is no particular limitation on the type of food, and it includes all health functional foods in the usual sense.
본 발명에서 용어 “예방”은 본 발명에 따른 조성물의 투여로 퇴행성 뇌질환의 억제 또는 지연시키는 모든 행위를 말한다. In the present invention, the term "prevention" refers to all activities that inhibit or delay degenerative brain diseases by administering the composition according to the present invention.
본 발명에서 용어 “치료”는 본 발명에 따른 조성물의 투여로 퇴행성 뇌질환의 증세가 호전되거나 이롭게 변경하는 모든 행위를 말한다. In the present invention, the term "treatment" refers to all activities that improve or beneficially change symptoms of degenerative brain diseases by administration of the composition according to the present invention.
본 발명에서 "개선"은 본 발명의 조성물을 개체에 투여하거나 섭취시켜 퇴행성 뇌질환의 나쁜 상태 또는 기억력을 좋게 하는 모든 행위를 의미한다.In the present invention, "improvement" refers to all actions to improve the poor state or memory of degenerative brain disease by administering or ingesting the composition of the present invention to a subject.
이하, 본 발명의 이해를 돕기 위하여 실시예를 들어 상세하게 설명하기로 한다. 다만 하기의 실시예는 본 발명의 내용을 예시하는 것일 뿐 본 발명의 범위가 하기 실시예에 한정되는 것은 아니다. 본 발명의 실시예는 당업계에서 평균적인 지식을 가진 자에게 본 발명을 보다 완전하게 설명하기 위해 제공되는 것이다.Hereinafter, examples will be described in detail to aid understanding of the present invention. However, the following examples are merely illustrative of the contents of the present invention, but the scope of the present invention is not limited to the following examples. The embodiments of the present invention are provided to more completely explain the present invention to those skilled in the art.
[[ 실험예Experimental example 1] 혼합 1] mix 대사산물metabolite 제조 manufacturing
생산식품으로부터 분리한 바실러스 벨레젠시스(Bacillus velezensis) 및 락토바실러스 플란타럼(Lactobacillus plantarum) 균주를 각각 TSB[트립톤(Tryptone) 1.7%, 소이톤(Soytone) 0.3%, 덱스트로스(Dextrose) 0.25%, 염화나트륨(Sodium Chloride) 0.5% 및 디포타슘 포스페이트(Dipotassium Phosphate) 0.25%]와 MRS 액체배지에서 37℃에서 24시간 배양한 후, 10,000 x g 및 4℃ 조건에서 30분 원심분리하여 얻어진 바실러스 벨레젠시스 생산 대사산물 및 락토바실러스 플란타럼 생산 대사산물을 혼합(1:2 중량비)하여 혼합 대사산물을 제조하였다. Bacillus velezensis and Lactobacillus plantarum strains isolated from produced foods were each TSB [Tryptone 1.7%, Soytone 0.3%, Dextrose 0.25 %, sodium chloride (Sodium Chloride) 0.5% and Dipotassium Phosphate (Dipotassium Phosphate) 0.25%] and MRS liquid medium at 37 ° C for 24 hours, followed by centrifugation at 10,000 xg and 4 ° C for 30 minutes. A mixed metabolite was prepared by mixing (1:2 weight ratio) the cis-producing metabolite and the Lactobacillus plantarum-producing metabolite.
[[ 실시예Example 1] 학습능력 및 맛 연상 기억력 개선 효과 분석 1] Analysis of learning ability and taste association memory improvement effect
1-1. 산화 스트레스가 기억력에 미치는 영향 분석1-1. Analysis of the effect of oxidative stress on memory
산화 스트레스(oxidative stress)가 기억력에 미치는 영향을 확인하기 위해, 파킨슨병 유도 초파리 모델 실험을 이용한 실험을 수행하였다. 본 발명에 사용한 초파리는 파킨슨병 유도 모델인 DJ-1βex54로, Bloomington Stock Centor에서 분양 받아 사용하였다. 실험은 안전관리등급 1등급의 실험실에서 수행하였다(허가번호 : 제LML 19-848호). 초파리는 12/12시간의 밤낮 주기, 온도 25℃ 및 습도 60% 조건에서 배양하였다. 실험군은 일반배지 섭식군(5% sucrose)(이하 대조군이라 함) 및 산화 스트레스를 통해 인위적으로 기억력 감소 촉진을 유도한 과산화수소(이하 H2O2라 함) 포함 배지 섭식군(5% 자당 및 1% H2O2)(이하 통제 대조군이라 함)으로 구분하였다.In order to confirm the effect of oxidative stress on memory, an experiment using a Parkinson's disease-induced Drosophila model experiment was performed. Drosophila used in the present invention was DJ-1βex54, an induction model for Parkinson's disease, which was purchased from the Bloomington Stock Center and used. The experiment was conducted in a laboratory with a safety management level of 1 (permit number: LML No. 19-848). Drosophila was cultured under conditions of a 12/12 hour day/night cycle, a temperature of 25° C., and a humidity of 60%. The experimental group consisted of a normal medium feeding group (5% sucrose) (hereinafter referred to as the control group) and a medium feeding group (5% sucrose and 1 % H 2 O 2 ) (hereinafter referred to as control group).
먼저, 초파리를 500mM 자당 수용액(Sucrose, Sigma-Aldrich Company, USA) 및 50mM 카페인(Caffeine, Sigma-Aldrich Company, USA)을 초파리의 앞다리(foreleg)에 반복 노출시켜 학습을 통해 맛을 기억하게 하였다. 그 후, 500mM 자당 수용액을 초파리 다리에 노출시켜 입을 뻗으면, 50mM 카페인 수용액을 초파리 입에 갖다대는 조건반사 훈련을 15회 반복하였다. 조건반사 훈련이 진행되는 동안, 초파리가 갈증으로 자당 수용액 및 카페인 수용액을 구분하지 않고 마시려하는 행동을 취할 수 있으므로, 5, 10 및 15회째 훈련을 마치면 초파리에게 수분을 보충해주었다. 조건반사 훈련이 끝난 후, 본 실험으로 지정된 시간(0, 5, 15, 30, 45 및 60분)마다 500mM 자당 수용액을 다리에 노출하여 입을 뻗는지, 아닌지를 확인하여 맛 연상 기억력을 유지하는지 확인하였다. 초파리가 선호하는 물질(자당 수용액)에 노출시켰을 때, 섭취를 위해 입(proboscis)를 내미는 행동(Proboscis Extension Response; 이하 PER이라 함)을 하고, 선호하지 않는 물질(카페인)에 노출시켰을 때, 입을 다시 집어넣는 행동 원리를 이용하였다. First, Drosophila was repeatedly exposed to 500 mM sucrose aqueous solution (Sucrose, Sigma-Aldrich Company, USA) and 50 mM caffeine (Caffeine, Sigma-Aldrich Company, USA) on the foreleg of Drosophila to remember the taste through learning. After that, conditioned reflex training was repeated 15 times by exposing the 500 mM sucrose aqueous solution to the Drosophila leg and stretching the mouth, and bringing the 50 mM caffeine aqueous solution to the Drosophila mouth. During the conditioned reflex training, since the fruit flies can take the action to drink without distinguishing between the aqueous solution of sucrose and the aqueous solution of caffeine due to thirst, after the 5th, 10th, and 15th training, the fruit flies were supplemented with water. After the conditioned reflex training, the legs were exposed to 500mM sucrose aqueous solution at designated times (0, 5, 15, 30, 45, and 60 minutes) in this experiment to check whether or not the mouth was stretched to check whether the taste association memory was maintained. did When exposed to a substance that Drosophila prefers (sucrose solution), it sticks out its mouth (proboscis) for ingestion (Proboscis Extension Response; hereinafter referred to as PER), and when exposed to a substance it does not prefer (caffeine), it opens its mouth. The action principle of re-entry was used.
그 결과, 도 1에 나타낸 바와 같이, 대조군의 경우, 예비 실험에서 100%의 PER 보이며 자당수용액에 대해 100% 반응하였고, 반복훈련 과정에서 자당수용액에 대한 PER 비율은 점차 감소하여 약 20%까지 감소하는 것을 확인하였다. 이는 반복훈련을 통해 자당 수용액이 아닌 카페인 수용액이 올 것이라는 것을 기억하는 것을 의미한다. 반복훈련 후, 본 실험을 수행한 결과, 자당 수용액에 대한 PER 비율은 점차 증가하는 것을 확인하였다. 이는 반복훈련을 통한 맛연상 기억력이 시간 경과에 따라 감소하는 것을 의미한다.As a result, as shown in Figure 1, in the case of the control group, 100% PER was shown in the preliminary experiment and 100% responded to the sucrose aqueous solution, and the PER ratio to the sucrose aqueous solution gradually decreased to about 20% during the repeated training process. confirmed that. This means remembering that repeated training will come with an aqueous solution of caffeine, not an aqueous solution of sucrose. As a result of this experiment after repeated training, it was confirmed that the PER ratio for the sucrose solution gradually increased. This means that taste association memory through repeated training decreases over time.
또한, 통제 대조군의 경우, 대조군과 유사한 결과를 나타내는 것을 확인하였다. 반복훈련 과정에서 PER 비율이 점차 감소하였고, 반복훈련 후, 본 실험을 수행한 결과, PER 비율이 다시 증가하였다. 그러나 대조군과 비교했을 때, 본 실험의 15분 및 30분에서 PER 비율이 유의적으로 차이가 나는 것을 확인하였다. 이는 산화 스트레스가 기억력 저하를 촉진하는 것을 의미한다.In addition, it was confirmed that the control group showed similar results to the control group. During the repeated training process, the PER ratio gradually decreased, and after repeated training, as a result of conducting this experiment, the PER ratio increased again. However, when compared to the control group, it was confirmed that the PER ratio was significantly different at 15 and 30 minutes of this experiment. This means that oxidative stress promotes memory decline.
1-2. 혼합 1-2. mix 대사산물의metabolite 학습능력 및 learning ability and 맛연상taste association 기억력 개선 효과 분석 Memory improvement effect analysis
상기 혼합 대사산물의 학습능력 및 맛연상 기억력 개선 효과를 확인하기 위해, 통제 대조군(5% 자당 및 1% H2O2) 및 실험군(5% 자당, 1% H2O2 및 5% 혼합 대사산물)을 각각의 배지에서 4일간 배양한 후, 학습능력 및 맛연상 기억력의 차이를 비교 및 분석하였다.In order to confirm the learning ability and taste association memory improvement effect of the mixed metabolite, the control group (5% sucrose and 1% H 2 O 2 ) and the experimental group (5% sucrose, 1% H 2 O 2 and 5% mixed metabolite products) were cultured in each medium for 4 days, and differences in learning ability and taste association memory were compared and analyzed.
그 결과, 도 2에 나타낸 바와 같이, 통제 대조군 및 실험군 모두 예비 실험에서 100%의 PER를 나타내며 자당수용액에 대해 100% 반응하는 것을 확인하였다. 반복훈련 과정에서 통제 대조군 및 실험군 모두 PER 비율은 점차 감소하여 약 10%까지 감소하였다. 반복훈련 후, 본 실험을 수행한 결과, 통제 대조군 및 실험군 모두 PER 비율이 증가하였으나, 실험군이 통제 대조군보다 낮은 PER 비율을 나타내는 것을 확인하였다. 이는 상기 혼합 대사산물이 시간 경과에 따른 기억력 감소를 억제하는 것을 의미한다.As a result, as shown in FIG. 2, it was confirmed that both the control group and the experimental group showed a PER of 100% in the preliminary experiment and responded 100% to the aqueous sucrose solution. During the repeated training process, the PER ratio of both the control group and the experimental group gradually decreased to about 10%. As a result of conducting this experiment after repeated training, the PER ratio increased in both the control group and the experimental group, but it was confirmed that the experimental group showed a lower PER ratio than the control group. This means that the mixed metabolites inhibit memory decline over time.
이상으로 본 발명 내용의 특정한 부분을 상세히 기술하였는 바, 당업계의 통상의 지식을 가진 자에게 있어서, 이러한 구체적 기술은 단지 바람직한 실시양태일 뿐이며, 이에 의해 본 발명의 범위가 제한되는 것이 아닌 점은 명백하다. 즉, 본 발명의 실질적인 범위는 첨부된 청구항들과 그것들의 등가물에 의하여 정의된다.Having described specific parts of the present invention in detail above, it is clear to those skilled in the art that these specific descriptions are only preferred embodiments, and the scope of the present invention is not limited thereby. do. That is, the substantial scope of the present invention is defined by the appended claims and their equivalents.
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