KR20230069631A - Pharmaceutical Composition for Preventing or Treating Sarcopenia Comprising Steamed Mature Silkworm Products having Silk Protein - Google Patents
Pharmaceutical Composition for Preventing or Treating Sarcopenia Comprising Steamed Mature Silkworm Products having Silk Protein Download PDFInfo
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- KR20230069631A KR20230069631A KR1020210155823A KR20210155823A KR20230069631A KR 20230069631 A KR20230069631 A KR 20230069631A KR 1020210155823 A KR1020210155823 A KR 1020210155823A KR 20210155823 A KR20210155823 A KR 20210155823A KR 20230069631 A KR20230069631 A KR 20230069631A
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- sarcopenia
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- muscle
- silkworm
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Abstract
Description
본 발명은 견사단백질이 함유된 익힌 누에가공물을 포함하는 근감소증의 예방 또는 치료용 조성물에 관한 것으로, 보다 자세하게는 5령4일부터 숙잠기까지의 누에로부터 선택되는 생누에를 물에 넣어 익히거나 또는 증기의 열로 익힌, 견사단백질이 함유된 익힌 누에가공물을 포함하는 근감소증의 예방 또는 치료용 조성물에 관한 것이다.The present invention relates to a composition for the prevention or treatment of sarcopenia comprising a cooked silkworm product containing silk protein, and more specifically, raw silkworms selected from silkworms from the 5th day of age to 4th day of age to the ripening stage are put in water and cooked. Or, it relates to a composition for preventing or treating sarcopenia, comprising a processed silkworm product containing silk protein, cooked with the heat of steam.
의료기술의 발달과 개인 위생의 증진으로 기대수명이 급격히 증가를 하고 있고, 2020년 65세 이상 노인 인구는 8,134,674명으로 전체 인구의 16.5%에 달한다. 또한, 다수의 노인층(노인층 남성의 27.7% 및 여성의 24.3%)이, 골격근육의 감소 및 체중 감소가 나타나는 노인성 근감소증을 겪고 있다. 이러한 노인성 근감소증이나 근력 저하는 영양섭취와 관련 없이 근육세포의 비정상적인 퇴행 및 사멸로 인해 매우 낮은 근육량이 임상적으로 관찰이 되는 경우와 영양섭취의 불균형과 운동 부족에 기인하여 발병하는 경우, 그리고 퇴행성 질환인 대사 질환과 암, 신경계 질환 등의 진행의 결과 2차 질환으로 발병하는 경우 등이 있다.Due to the development of medical technology and the improvement of personal hygiene, life expectancy is rapidly increasing, and in 2020, the elderly population over 65 years old is 8,134,674, accounting for 16.5% of the total population. In addition, a large number of older people (27.7% of older males and 24.3% of females) suffer from geriatric sarcopenia, characterized by loss of skeletal muscle and weight loss. Such senile sarcopenia or muscle weakness is clinically observed when very low muscle mass is observed due to abnormal degeneration and death of muscle cells regardless of nutrition intake, when it occurs due to imbalance in nutritional intake and lack of exercise, and degenerative There are cases where secondary diseases develop as a result of the progression of diseases such as metabolic diseases, cancers, and neurological diseases.
보다 구체적으로, 근감소증(sarcopenia)은 척수신경, 운동신경 또는 골격근 섬유의 퇴행에 의해 유발되는, 아직까지 발병원인이 규명되지 않은 대표적인 난치성 질환 중 하나로서, 근육량 및 근력이 감소하는 퇴행성 질환으로, 정상적인 노화 과정에서 나타나는 근육 소실과 달리, 비정상적으로 급격히 근육량이 감소하는 질환을 말한다. 근감소증에 걸린 개체는 근육량, 운동력 및 근력이 현저히 감소하여 독립적인 생활이 어렵고, 뇌질환, 심장질환, 당뇨병 등의 다른 질환으로부터 호전되기가 어려워 사망률이 높다. 이러한 근감소증은 노화에 의한 일차성 근감소증(Primary sarcopenia)과 다양한 원인들에 의한 이차성 근감소증(Secondary sarcopenia)으로 나누어지는데, 이차성 근감소증의 원인으로는 영양결핍, 활동 저하, 장기 부전, 약물, 염증, 악성 질환, 또는 내분비 대사질환 등이 있다.More specifically, sarcopenia is one of the representative intractable diseases, the cause of which has not yet been identified, caused by degeneration of spinal nerves, motor nerves, or skeletal muscle fibers, and is a degenerative disease in which muscle mass and strength decrease, Unlike muscle loss that occurs during the normal aging process, it refers to a disease in which muscle mass is abnormally and rapidly reduced. Individuals suffering from sarcopenia have significantly reduced muscle mass, motor power, and muscle strength, making it difficult to live independently, and have high mortality rates because it is difficult to improve from other diseases such as brain disease, heart disease, and diabetes. This sarcopenia is divided into primary sarcopenia due to aging and secondary sarcopenia caused by various causes. Inflammation, malignant disease, or endocrine metabolic disease.
일차성 근감소증은 노인성 근감소증(age related sarcopenia)으로도 불리는데, 나이가 들면서 위성세포로 알려진 성인 근육 줄기 세포의 수 및 분화능이 점차 감소하여 발생하는 것으로 알려져 있다(Gabi Shefer et al., Developmental Biology , 2006). 즉, 노인성 근감소증은 노화 개체에서 근원세포의 분화능이 감소하여 나타나는 질환으로, 자율 근육을 조절하는 신경세포가 손상되어 나타나는 근이영양증(muscle dystrophy), 신경 근육 접합 질환, 운동 신경 질환 등의 신경 근육 질환과는 발병 기전 및 치료 방법에서 차이가 있다.Primary sarcopenia, also called age-related sarcopenia, is known to occur as the number and differentiation capacity of adult muscle stem cells, known as satellite cells, gradually decrease with age (Gabi Shefer et al., Developmental Biology , 2006). In other words, geriatric sarcopenia is a disease that occurs due to a decrease in the differentiation potential of myoblasts in aging individuals, and is a neuromuscular disease that occurs when nerve cells that control autonomic muscles are damaged, such as muscle dystrophy, neuromuscular junction disease, and motor neuron disease. The families differ in pathogenesis and treatment methods.
현대 한국 사회는 평균 수명의 증가로 노인 인구가 급격히 증가하고 있고, 핵가족화 및 출산율 저하로 인해 노인의 독립생활 비중이 매우 높아지고 있어, 노인성 근감소증으로 인한 의료 및 사회 비용이 증가할 것으로 예상된다. 그러나, 근감소증의 복잡한 병인으로 인해 현재까지 유효한 치료 표적이 밝혀지지 않았고, 효과적인 치료제가 없어 적극적인 영양 보충 및 운동 요법으로 치료하고 있다. 따라서, 노인성 근감소증의 기전을 밝히고 유효한 치료 표적을 발굴하여, 이를 활용한 약물 스크리닝으로 효과적인 치료제의 개발이 필요하다.In modern Korean society, the elderly population is rapidly increasing due to the increase in life expectancy, and the proportion of elderly people living independently is very high due to nuclear families and declining birth rates, so medical and social costs due to geriatric sarcopenia are expected to increase. However, due to the complex etiology of sarcopenia, an effective treatment target has not been identified so far, and there is no effective treatment, so it is treated with active nutritional supplementation and exercise therapy. Therefore, it is necessary to develop an effective therapeutic agent by identifying the mechanism of senile sarcopenia, discovering an effective treatment target, and screening a drug using the same.
지금까지 연구된 바에 의하면, 골격근의 수축을 유도하는 운동신경이 퇴행되어 골격근의 수축이 진행되지 않거나 또는 골격근 내에서 근육의 수축에 관여하는 단백질의 발현이 감소되거나 상기 단백질이 변형되어 정상적인 골격근의 수축이 진행되지 않으며, 장기적으로는 상기 운동신경 또는 골격근이 섬유성 조직으로 변형되는 것으로 알려져 있다. 이와 같은 근감소증의 근본적인 발병원인이 아직 규명되지 않았고, 운동신경이나 골격근의 퇴행을 방지하거나 또는 회복시킬 수 있는 방법이 개발되지 않고 있기 때문에, 현재로서는 상기 근감소증의 진행을 둔화시키는 방법을 개발하기 위한 연구가 활발히 진행되고 있다.According to studies so far, skeletal muscle contraction does not progress because motor nerves that induce skeletal muscle contraction are degenerated, or the expression of proteins involved in muscle contraction is reduced in skeletal muscle, or the protein is modified to normal contraction of skeletal muscle. This does not progress, and in the long term, it is known that the motor nerve or skeletal muscle is transformed into fibrous tissue. Since the fundamental cause of sarcopenia has not yet been identified, and a method for preventing or recovering the degeneration of motor neurons or skeletal muscles has not been developed, it is currently difficult to develop a method for slowing the progression of sarcopenia. Research is actively under way.
현재 상기 근감소증의 치료 방법으로는 주로 근감소증의 일종인 근육세포의 퇴행 또는 진행성 변이에 의해 유발되는 근위축증을 억제하는 방법이 사용되고 있다. 예를 들어, WO 2007/088123에는 니트록시 유도체를 유효성분으로 포함하는 근위축증 치료제가 개시되어 있고, WO 2006/081997에는 아트라릭산 또는 그의 유도체를 유효성분으로 포함하는 근위축증 치료제가 개시되어 있다. Currently, as a method of treating sarcopenia, a method of suppressing muscular atrophy caused by degeneration or progressive mutation of muscle cells, which is a type of sarcopenia, is mainly used. For example, WO 2007/088123 discloses a treatment for muscular dystrophy containing a nitroxy derivative as an active ingredient, and WO 2006/081997 discloses a treatment for muscular dystrophy containing atraric acid or a derivative thereof as an active ingredient.
그러나, 화합물을 유효성분으로 포함하는 이들 치료제는 근위축증이 발병된 골격근 뿐만 아니라, 근위축증과 관련되지 않은 내장근 또는 심근에도 작용하기 때문에, 크고 작은 다양한 부작용이 유발될 수 있어, 실질적인 치료에 사용되지 못하고 있다. However, since these therapeutic agents containing the compound as an active ingredient act not only on the skeletal muscle with muscular dystrophy, but also on the visceral muscle or myocardium not related to muscular dystrophy, they can cause various side effects, large and small, and have not been used for practical treatment. .
따라서, 인위적인 방법으로 사용되는 치료제가 아니라, 부작용이 없는 천연물에서 유래한 생약제 등을 보편적인 식품의 형태로 섭취하면서, 근감소증만을 효과적으로 감소시킬 수 있는 새로운 근감소증 치료제의 개발이 필요한 실정이다. Therefore, it is necessary to develop a new sarcopenia treatment that can effectively reduce only sarcopenia while ingesting herbal medicines derived from natural products without side effects in the form of common foods, rather than artificially used treatments.
한편, 누에고치를 생산하는 양잠산업은 고조선시대부터 이어온 우리나라의 전통산업으로써 1970년대에는 연간 100만 상자 이상의 누에를 농가에서 사육하였으나, 경제발전과 고급 화학섬유의 영향으로 현재는 크게 위축된 상황이다. 이에, 현재의 양잠산업은 건조누에, 수번데기, 동충하초 등 건강기능식품원료를 생산하는 산업으로 전환하였는데, 그 중 농가의 주 생산품목은 5령3일 건조누에이다. 5령3일 건조누에를 이용하는 이유는 5령3일이 지나 5령 4일부터는 강도가 강한 견사단백질이 누에의 몸속에서 급속히 비대해져 식용으로 사용하기에 매우 어려워지기 때문이다. 견사단백질은 견사선의 형태로 누에 몸속에 저장되어 있다가 누에가 숙잠(grown-up silkworm; mature silkworm)이 되면 이 견사단백질을 뱉어내면서 실크의 원료인 누에고치를 짓게 된다. On the other hand, the sericulture industry that produces silkworm cocoons is a traditional Korean industry that has been continued since the Gojoseon Dynasty. In the 1970s, more than 1 million boxes of silkworms were raised in farms annually, but it is currently in a state of great decline due to economic development and the influence of high-quality chemical fibers. . Accordingly, the current sericulture industry has shifted to an industry that produces health functional food ingredients such as dried silkworms, male pupae, and cordyceps. The reason why 5 instar 3-day dried silkworms are used is that from the 5th instar 4th day after the 5th instar 3 days, the strong silk protein rapidly enlarges in the body of the silkworm, making it very difficult to use for food. The silk protein is stored in the silkworm's body in the form of a silk thread, and when the silkworm becomes a grown-up silkworm (mature silkworm), it spits out the silk protein and builds a silkworm cocoon, a raw material for silk.
이처럼 식용가능한 시기를 지난 숙잠은 실크의 생산을 위한 용도로서 사용되는 것 이외에는 특별하게 이용되지 못하고 있으며, 누에와 관련된 의약품에 관한 연구에 있어서는 주로 실크펩타이드와 관련된 연구만이 진행되고 있을 뿐, 이러한 견사단백질이 함유된 누에(또는 숙잠)를 활용한 연구는 미비한 편이고, 종래 숙잠을 활용하는 대부분의 방법은 누에에 함유된 모든 유용 활성물질을 함께 이용하는 것이 아닌 실크단백질만으로 이루어진 단순한 누에고치만을 이용하는 것으로서 섭취를 위한 누에고치의 가수분해 시 고가의 비용이 소요되고, 유용성분이 유실되는 문제점이 있었는바, 이를 해결하기 위해서는 실크단백질과 더불어 누에에 함유된 모든 성분을 함께 이용하는 것이 필요하다. In this way, silkworms that have passed the edible period are not used in any special way other than for the production of silk, and in research on silkworm-related medicines, only studies related to silk peptides are being conducted. Studies using silkworms (or silkworms) containing protein are incomplete, and most of the conventional methods of utilizing silkworms are not using all useful active substances contained in silkworms together, but only simple silkworm cocoons made of silk protein. When hydrolyzing silkworm cocoons for silkworms, there is a problem of high cost and loss of useful components. In order to solve this problem, it is necessary to use all the ingredients contained in silkworm together with silk protein.
따라서, 견사단백질이 함유된 익힌 누에는 생체적합하며 안전한 천연 물질이므로, 이를 적용하여 근감소증 및 관련 질환들을 치료할 수 있는 치료제로서 사용될 수 있을 것이다.Therefore, since cooked silkworm containing silk protein is a biocompatible and safe natural material, it can be applied as a therapeutic agent for treating sarcopenia and related diseases.
이러한 상황 하에서, 본 발명자들은 탁월하며 인체에 안전한 근감소증 치료제를 개발하기 위하여 예의 노력하였다. 그 결과, 본 발명자들은 견사단백질이 함유된 익힌 누에가공물(익힌 숙잠; 홍잠)이 근감소증(특히, 노인성)에서 유의한 체중 증가, 근육 무게 증가, 근력 증가, 운동 능력 증진, 자세 조절 능력 증진, 공간기억력 증진 및 사회적 기억력 증대 효과를 달성할 수 있음을 규명함으로써 본 발명을 완성하였다. Under these circumstances, the present inventors have made diligent efforts to develop a therapeutic agent for sarcopenia that is excellent and safe for the human body. As a result, the present inventors found that the cooked silkworm product (cooked sookjam; Hongjam) containing silk protein significantly increased weight, increased muscle weight, increased muscle strength, improved exercise ability, improved postural control ability, The present invention was completed by clarifying that spatial memory enhancement and social memory enhancement effects could be achieved.
따라서, 본 발명의 일 목적은 견사단백질이 함유된 익힌 누에가공물을 유효성분으로 포함하는 근감소증의 예방 또는 치료용 약학적 조성물을 제공하는 데 있다.Accordingly, one object of the present invention is to provide a pharmaceutical composition for the prevention or treatment of sarcopenia comprising a silk protein-containing processed silkworm product as an active ingredient.
또한, 본 발명의 다른 목적은 견사단백질이 함유된 익힌 누에가공물을 포함하는 근감소증의 예방 또는 개선용 식품 조성물 또는 건강기능식품을 제공하는 데 있다.In addition, another object of the present invention is to provide a food composition or health functional food for preventing or improving sarcopenia, including a cooked silkworm product containing silk protein.
또한, 본 발명의 또 다른 목적은 견사단백질이 함유된 익힌 누에가공물을 포함하는 동물의 근감소증의 예방 또는 개선용 사료 사료 첨가제 또는 사료 조성물을 제공하는 데 있다.In addition, another object of the present invention is to provide a feed feed additive or feed composition for preventing or improving sarcopenia in animals, including a cooked silkworm product containing silk protein.
또한, 본 발명의 또 다른 목적은 견사단백질이 함유된 익힌 누에가공물을 포함하는 조성물을 인간을 제외한 개체에 투여하는 단계를 포함하는 근감소증 치료 방법을 제공하는 데 있다.Another object of the present invention is to provide a method for treating sarcopenia comprising administering a composition comprising a silk protein-containing cooked silkworm product to a non-human subject.
본 명세서에서 사용한 용어는 단지 설명을 목적으로 사용된 것으로, 한정하려는 의도로 해석되어서는 안된다. 단수의 표현은 문맥상 명백하게 다르게 뜻하지 않는 한, 복수의 표현을 포함한다. 본 명세서에서, "포함하다" 또는 "가지다" 등의 용어는 명세서 상에 기재된 특징, 숫자, 단계, 동작, 구성요소, 부품 또는 이들을 조합한 것이 존재함을 지정하려는 것이지, 하나 또는 그 이상의 다른 특징들이나 숫자, 단계, 동작, 구성요소, 부품 또는 이들을 조합한 것들의 존재 또는 부가 가능성을 미리 배제하지 않는 것으로 이해되어야 한다.The terms used herein are used for descriptive purposes only and should not be construed as limiting. Singular expressions include plural expressions unless the context clearly dictates otherwise. In this specification, terms such as "include" or "have" are intended to designate that there is a feature, number, step, operation, component, part, or combination thereof described in the specification, but one or more other features It should be understood that the presence or addition of numbers, steps, operations, components, parts, or combinations thereof is not precluded.
다르게 정의되지 않는 한, 기술적이거나 과학적인 용어를 포함해서 여기서 사용되는 모든 용어들은 실시예가 속하는 기술 분야에서 통상의 지식을 가진 자에 의해 일반적으로 이해되는 것과 동일한 의미를 가지고 있다. 일반적으로 사용되는 사전에 정의되어 있는 것과 같은 용어들은 관련 기술의 문맥 상 가지는 의미와 일치하는 의미를 가지는 것으로 해석되어야 하며, 본 출원에서 명백하게 정의하지 않는 한, 이상적이거나 과도하게 형식적인 의미로 해석되지 않는다.Unless defined otherwise, all terms used herein, including technical or scientific terms, have the same meaning as commonly understood by a person of ordinary skill in the art to which the embodiment belongs. Terms such as those defined in commonly used dictionaries should be interpreted as having a meaning consistent with the meaning in the context of the related art, and unless explicitly defined in the present application, they should not be interpreted in an ideal or excessively formal meaning. don't
이하, 본 발명에 대하여 보다 상세히 설명한다.Hereinafter, the present invention will be described in more detail.
본 발명의 일 양태에 따르면, 본 발명은 견사단백질이 함유된 익힌 누에가공물을 유효성분으로 포함하는 근감소증의 예방 또는 치료용 약학적 조성물을 제공한다.According to one aspect of the present invention, the present invention provides a pharmaceutical composition for preventing or treating sarcopenia, comprising a silk protein-containing processed silkworm product as an active ingredient.
본 발명의 누에가공물은 생누에를 물에 넣어 익히거나 또는 증기의 열로 익혀 제조한 것으로써, 견사단백질이 모두 함유된 상태로 식이용으로 섭취가능한 것이 특징이다.The processed silkworm product of the present invention is prepared by cooking raw silkworms in water or by steaming, and is characterized in that it can be consumed as a food while containing all of the silk protein.
본 명세서에서 유효성분을 언급하면서 사용되는 단어 "익힌 누에"는 명세서 내에서 익힌 숙잠 또는 홍잠과 혼용된다.In this specification, the word "cooked silkworm" used while referring to the active ingredient is used interchangeably with cooked sokjam or hongjam within the specification.
종래 당업계에 누에 또는 실크펩타이드를 이용한 건강기능식품이 다양하게 이용되고 있으나, 실크펩타이드가 갖는 성분과 누에의 성분이 다름은 명백하며, 누에의 각 시기별에 있어서도 생것일 때와 이를 익혔을 때의 함유하고 있는 성분의 함량이 다름이 확인된다. Conventionally, health functional foods using silkworms or silk peptides have been used in various ways in the art, but it is clear that the ingredients of silk peptides and the ingredients of silkworms are different. It is confirmed that the content of the components contained in is different.
따라서, 기존에는 식용하지 못하고 견사 생성용 누에고치를 만들기 위해 사육하는 것 이외에는 별다른 용도가 없었던 견사단백질을 갖는 누에를 견사단백질이 함유된 식이용으로 섭취할 수 있는 상태로 가공하여 근감소증의 예방 또는 치료용 조성물의 소재로 이용할 수 있다는 점에서 본 발명의 의의가 있다.Therefore, silkworms having silk proteins, which were previously inedible and had no use other than breeding to make cocoons for silk production, are processed into a state that can be consumed for dietary use containing silk protein to prevent sarcopenia or The significance of the present invention is that it can be used as a material for a therapeutic composition.
이에, 본 발명은 견사단백질이 함유된 익힌 누에가공물을 유효성분으로 함유하는 근감소증의 예방 또는 치료용 조성물 및 이를 포함하는 건강기능식품을 제공하기 위한 것으로써, 구체적인 실예로 상기 견사단백질이 함유된 익힌 누에가공물에 대해 다양한 효능, 즉, 상기 익힌 누에가공물이 체중 증가, 근육 무게 증가, 근력 증가, 운동 능력 증진, 자세 조절 능력 증진, 공간기억력 증진 및/또는 사회적 기억력 증대 효과도 나타냄을 확인한 결과를 토대로 상기 견사단백질이 함유된 익힌 누에가공물은 근감소증, 특히, 노인성 근감소증을 예방하거나 또는 치료할 수 있는 근감소증의 예방 또는 치료용 조성물 또는 이를 포함하는 식품 조성물의 유효성분으로 적용가능하게 된다.Accordingly, the present invention is to provide a composition for preventing or treating sarcopenia containing cooked silkworm products containing silk protein as an active ingredient and a health functional food containing the same, and as a specific example, the silk protein containing Various effects on cooked silkworm products, that is, the results of confirming that the cooked silkworm products also exhibit effects of increasing body weight, increasing muscle weight, increasing muscle strength, enhancing exercise capacity, improving posture control ability, enhancing spatial memory, and/or increasing social memory Based on this, the cooked silkworm product containing the silk protein can be applied as an active ingredient of a composition for preventing or treating sarcopenia, particularly, a composition for preventing or treating senile sarcopenia, or a food composition containing the same.
본 발명에서 용어 "근감소증(sarcopenia)"은 근육의 부피 및 근력이 점진적으로 쇠퇴하는 질환을 의미하며, 골격 근육량의 감소로 인해, 직접적으로 근력의 저하를 유발하고 그 결과 각종 신체기능의 감소 및 장애를 일으키며, 사망 위험성도 증가시키는 것으로 알려져 있다. 이는 노화와 연관되어 나타나는 점진적인 골격근 감소의 결과로 나타나는 질환이다.In the present invention, the term "sarcopenia" refers to a disease in which muscle volume and muscle strength gradually decline, and due to a decrease in skeletal muscle mass, directly causes a decrease in muscle strength, resulting in a decrease in various physical functions and It is known to cause disability and increase the risk of death. It is a disease that appears as a result of the gradual decline of skeletal muscle associated with aging.
상기 근감소증은 근위축증, 근무력증, 근이영양증, 근경직증, 근긴장저하, 근력약화, 근육퇴행위축, 근위축성 측삭경화증 및 중증 근무력증으로 이루어진 군으로부터 선택된 1종 이상일 수 있다.The sarcopenia may be at least one selected from the group consisting of muscular dystrophy, myasthenia gravis, muscular dystrophy, myasthenia gravis, hypotonia, muscle weakness, muscular dystrophy, amyotrophic lateral sclerosis, and myasthenia gravis.
특히, 본 발명의 견사단백질이 함유된 익힌 누에가공물은 상기 근육량 감소를 특이적으로 저해하여 근감소증에 대한 치료 및 예방 효과를 가진다.In particular, the cooked silkworm product containing the silk protein of the present invention has therapeutic and preventive effects on sarcopenia by specifically inhibiting the decrease in muscle mass.
본 명세서에서, 상기 견사단백질을 포함하고 있는 익힌 누에가공물은, 3면잠, 4면잠 등의 모든 누에를 익힌 과정을 통해 제조한 것을 의미하며, 바람직하게는 누에 중 5령4일의 4면잠 누에부터 숙잠기까지의 누에 중 어느 하나 이상을 선택하여 사용할 수 있으며, 더 바람직하게는 숙잠기의 누에를 사용하는 것이 가장 좋다. 이는, 5령3일의 누에도 사용할 수는 있으나 5령4일 이후의 누에에 비해서 누에가 갖는 견사단백질이 적은 편이기 때문에 본 발명이 목적하는 효능을 충분히 발휘하지 못할 우려가 있기 때문이다. In the present specification, the cooked silkworm product containing the silk protein refers to a product manufactured through the process of cooking all silkworms, such as 3 sleep, 4 sleep, etc. It is possible to select and use any one or more of the silkworms up to the sleeping period, and it is best to use silkworms in the sleeping period more preferably. This is because silkworms can be used for silkworms aged 5 days and 3 days, but silkworms have less silk protein than silkworms aged 5 days and 4 days, so there is a concern that the present invention may not sufficiently exhibit the desired efficacy.
한편, 숙잠기의 누에라 함은 누에 몸속에 견사단백질이 가득 차 있는 누에로서 고치를 짓기 전까지의 누에를 의미하는 것으로써, 숙잠기의 누에는 누에똥이 대부분 배출되어 있기 때문에 약학 조성물 또는 식품조성물(건강기능식품)의 유효성분으로 사용하기에 가장 적합하다. On the other hand, the silkworm in the sleeping period means a silkworm full of silk protein in the body of the silkworm before it builds a cocoon. It is most suitable for use as an active ingredient in health functional foods).
본 발명에서는 상기와 같은 누에에 함유되어 있는 견사단백질까지 모두 식이 섭취 가능하도록 하기 위해 상기 누에를 가공하여 가공물 형태로 제조하여 약학 조성물 또는 식품조성물(건강기능식품)의 유효성분으로 사용한다.In the present invention, in order to make all of the silk protein contained in silkworms edible, the silkworms are processed and prepared in the form of a processed product, and used as an active ingredient in a pharmaceutical composition or food composition (health functional food).
상기 유효성분인 익힌 누에가공물은 5령4일의 4면잠 누에부터 숙잠기까지의 누에 중에서 선택되는 생누에를 55 내지 125℃의 온도에서 30분 내지 24시간 동안 물에 넣어 익히거나 또는 증기의 열로 익혀 제조하며, 바람직하게는 상기 누에를 80 내지 125℃의 증기의 열로 100 내지 150분 동안 익혀 견사단백질이 모두 함유되도록 제조하는 것이 특징이다. 즉, 80℃미만의 증기 열로 150분을 초과하여 제조할 경우에는 제조시간이 너무 길어 오히려 견사단백질이 포함된 누에 자체가 갖고 있는 유효성분들이 파괴될 우려가 있으며, 125℃를 초과하여 100분 미만으로 제조할 경우에는 온도가 너무 높아 이 또한, 견사단백질이 포함된 누에 자체가 갖고 있는 유효성분들에 악영향을 미칠 우려가 있기 때문이다.The cooked silkworm product, which is the active ingredient, is prepared by putting raw silkworms selected from silkworms from 4 days old to 4 days old in water at a temperature of 55 to 125 ° C for 30 minutes to 24 hours, or by steam heat. It is prepared by cooking, and preferably, the silkworm is cooked for 100 to 150 minutes with heat of steam at 80 to 125 ° C., so that all silk proteins are contained. That is, when manufacturing for more than 150 minutes with steam heat of less than 80 ° C, the manufacturing time is too long, and there is a risk of destroying the active ingredients of the silkworm itself, including silk protein, and less than 100 minutes in excess of 125 ° C. In the case of manufacturing, the temperature is too high, and this is also because there is a risk of adversely affecting the active ingredients of the silkworm itself containing silk protein.
이러한, 상기 익힌 과정 후에는 통상의 방법으로 건조하여 분말형태로 제조하여 사용할 수 있으며, 바람직하게는 열풍건조 또는 진공동결건조 중 선택된 어느 하나를 통해 건조시켜 분말화하는 것이 좋으며, 유효성분의 손실을 최소화하기 위해서는 진공동결건조 방법이 가장 적합하다.After the above-cooked process, it can be dried by a conventional method and used in powder form. Preferably, it is good to dry it through any one selected from hot air drying or vacuum freeze drying and pulverize it, and to reduce the loss of active ingredients. In order to minimize it, the vacuum freeze-drying method is most suitable.
따라서, 본 발명의 익힌 누에가공물은 열풍건조 또는 진공동결건조물일 수 있다.Therefore, the cooked silkworm product of the present invention may be hot air dried or vacuum freeze dried.
상기 분말화는 가정용 믹서기, 해머밀, 롤러밀, 에어제트밀(동결분쇄) 등 어떠한 방법을 사용해도 무관하지만, 시료유실의 최소화, 성분 왜곡현상 방지 및 미세분말화를 위해서는 롤러밀에 의한 방법이 좋다. 보통 가정용 믹서기나 해머밀로 분쇄하면 분말입자의 크기가 0.1㎜정도 이하로 분쇄하기가 매우 어려운데 비하여, 롤러밀로 수차례 반복 분쇄하면 분말화된 입자의 크기가 평균 10㎛ 정도까지 미세분말화가 가능하여 섭취와 제품에 유리하게 작용할 것으로 예상된다.The powdering may be performed using any method such as a household mixer, hammer mill, roller mill, air jet mill (freeze grinding), but in order to minimize sample loss, prevent component distortion, and finely powder, a roller mill method is preferred. good night. Normally, it is very difficult to grind powder particles to a size of less than 0.1 mm when pulverized with a household blender or hammer mill. On the other hand, when pulverized repeatedly with a roller mill several times, the powdered particles can be finely pulverized to an average size of 10 μm. and products are expected to have a favorable effect.
또한, 상기 분말형태로 제조된 후에는 상기 익힌 누에가공물 분말을 추출물 형태로 제조할 수 있으며, 이때 물, 탄소수 1 내지 4개의 저급 알코올 또는 이들의 혼합용매로 추출하여 제조될 수도 있다. 상기 탄소수 1 내지 4개의 저급 알코올은 메탄올, 에탄올, 프로판올, 이소프로판올, 부탄올 및 이소부탄올로 이루어진 군에서 선택될 수 있다. 상기 물, 탄소수 1 내지 4개의 저급 알코올 또는 이들의 혼합용액은 익힌 숙잠 분말의 중량을 기준 1~40배 부피(1kg 기준 1~40ℓ)를 사용할 수 있으며, 바람직하게는 5~40배 부피를 사용할 수 있다. 상기 추출물의 추출조건은 20~100℃에서 1~48시간일 수 있으며, 상기 과정은 1~4번까지 반복할 수 있다. In addition, after being prepared in the powder form, the cooked silkworm processed product powder may be prepared in the form of an extract, and at this time, it may be prepared by extracting with water, a lower alcohol having 1 to 4 carbon atoms, or a mixed solvent thereof. The lower alcohol having 1 to 4 carbon atoms may be selected from the group consisting of methanol, ethanol, propanol, isopropanol, butanol and isobutanol. The water, lower alcohol having 1 to 4 carbon atoms, or a mixed solution thereof may be used in a volume of 1 to 40 times (1 to 40 liters based on 1 kg) based on the weight of the cooked sleep powder, preferably 5 to 40 times the volume. can The extraction condition of the extract may be 1 to 48 hours at 20 to 100 ° C, and the process may be repeated 1 to 4 times.
또 다른 방법으로는, 상기 익힌 누에가공물 분말을 물, 탄소수 1 내지 4개의 저급 알코올 또는 이들의 혼합용매로 추출 농축하여 얻은 추출물에, 물을 가하여 현탁한 후, 바람직하게는 추출물의 중량의 1~1000배, 더 바람직하게는 1~500배, 가장 바람직하게는 1~50배의 물을 가하여 현탁한 후, 상기 현탁물에 헥산, 클로로포름, 에틸아세테이트, 및, 부탄올로 이루어진 군에서 선택되는 용매를 가하여 얻은 분획물로 제조할 수 있다. Another method is to add water to an extract obtained by extracting and concentrating the cooked silkworm processed powder with water, a lower alcohol having 1 to 4 carbon atoms, or a mixed solvent thereof, and then suspending the powder, preferably by weight of 1 to 4% of the weight of the extract. After suspension by adding 1000 times, more preferably 1 to 500 times, and most preferably 1 to 50 times of water, a solvent selected from the group consisting of hexane, chloroform, ethyl acetate, and butanol is added to the suspension. It can be prepared from the fraction obtained by adding
상기 추출물 또는 이의 분획물의 제조온도는 20 내지 100℃일 수 있으나, 이에 제한되는 것은 아니다. 추출 또는 분획 시간은 특별히 제한되는 것은 아니나, 10분 내지 2일 이내에 추출하는 것이 바람직하며, 추출용 기기로는 통상의 추출기기, 초음파분쇄추출기 또는 분획기를 이용할 수 있다. 이렇게 제조된 추출물 또는 분획물은 열풍건조, 감압건조 또는 동결건조하여 용매를 제거할 수 있다. 또한, 상기 추출물 또는 분획물은 칼럼크로마토그래피를 이용하여 정제하여 사용할 수도 있다. 상기 크로마토그래피는 실리카겔 컬럼 크로마토그래피(silica gel column chromatography), 엘에이취-20 컬럼 크로마토그래피(LH-20 column chromatography), 이온교환수지 크로마토그래피(ion exchange resin chromatography), 중압 액체 크로마토그래피(medium pressure liquid chromatography), 박층 크로마토그래피(TLC; thin layer chromatography), 실리카겔 진공 액체 크로마토그래피(silica gel vacuum liquid chromatography) 및 고성능 액체 크로마토그래피(high performance liquid chromatography) 중에서 선택될 수 있다. The preparation temperature of the extract or its fraction may be 20 to 100 ℃, but is not limited thereto. The extraction or fractionation time is not particularly limited, but it is preferable to extract within 10 minutes to 2 days, and as a device for extraction, a conventional extraction device, an ultrasonic crusher or a fractionator may be used. The solvent may be removed from the extract or fraction thus prepared by hot air drying, vacuum drying or lyophilization. In addition, the extract or fraction may be used after being purified using column chromatography. The chromatography is silica gel column chromatography, LH-20 column chromatography, ion exchange resin chromatography, medium pressure liquid chromatography chromatography), thin layer chromatography (TLC), silica gel vacuum liquid chromatography, and high performance liquid chromatography.
본 발명에서, 상기 익힌 누에가공물의 누에 품종은 백견품종, 황견품종, 녹견품종 및 홍견품종으로 이루어진 군으로부터 선택된 1 종 이상일 수 있으며, 본 발명이 목적하는 항근감소증 효과가 발휘되는 한, 상기 익힌 누에가공물의 누에 품종으로는 당업계에 공지된 어떠한 품종의 누에를 사용하여도 무관하다.In the present invention, the silkworm breed of the cooked silkworm product may be at least one selected from the group consisting of white dog breed, yellow dog breed, green dog breed, and red dog breed, and as long as the antisarcomenia effect desired by the present invention is exerted, the cooked silkworm As the silkworm breed of the processed product, any breed of silkworm known in the art may be used.
항근감소증은 체중 증가, 근육 무게 증가, 근력 증가, 운동 능력 증진, 자세 조절 능력 증진, 공간기억력 증진, 사회적 기억력 증대 및 근육 분해 유전자의 발현 억제로 구성된 군으로부터 선택되는 1 종 이상의 효과를 의미하며, 이로 인해 근감소증, 특히, 노인형 근감소증의 개선 효과를 가질 수 있다. Antisarcopenia refers to one or more effects selected from the group consisting of weight gain, muscle weight increase, muscle strength increase, exercise ability improvement, postural control ability improvement, spatial memory improvement, social memory increase, and muscle degradation gene expression inhibition, This may have an effect of improving sarcopenia, in particular, geriatric sarcopenia.
상기 근육 분해 유전자는 본 발명의 목적을 달성할 수 있는 한, 당업계에 공지된 임의의 유전자도 포함할 수 있으며, 바람직하게는, 마이오스타틴 (Myostatin), 아트로진-1 (Atrogin-1), MuRF1 (Muscle RING-finger protein-1) 및 FoxO3 (Forhead box O3)으로 구성된 군으로부터 선택되는 1 종 이상의 유전자일 수 있으나, 이에 한정되지 않는다.As long as the object of the present invention can be achieved, the muscle degradation gene may also include any gene known in the art, and preferably, myostatin, artrogin-1 ), it may be one or more genes selected from the group consisting of MuRF1 (Muscle RING-finger protein-1) and FoxO3 (Forhead box O3), but is not limited thereto.
즉, 본 발명에서는 인위적으로 근감소증을 유발시킨 동물에 본 발명의 익힌 누에가공물을 투여하고, 병증에 미치는 영향을 분석한 결과, 근감소증에 의해 감소된 체중, 근육 중량, 악력 등의 근육 특성이 회복되고, 근육 단백질을 파괴하는 유전자(근육 분해 유전자)의 발현이 감소됨을 확인하였다.That is, in the present invention, as a result of administering the processed silkworm product of the present invention to an animal artificially induced sarcopenia and analyzing the effect on the disease, muscle characteristics such as weight, muscle weight, grip strength, etc. and it was confirmed that the expression of a gene that destroys muscle protein (muscle degradation gene) was reduced.
이처럼, 본 발명에서는 본 발명의 익힌 누에가공물의 신규한 근감소증 예방 또는 치료 효과를 규명하였으며, 이러한 효과는 지금까지 전혀 공지되지 않았고, 본 발명자에 의하여 최초로 규명되었다.As such, in the present invention, a novel sarcopenia preventive or therapeutic effect of the cooked silkworm product of the present invention was identified, and this effect was not known at all until now, and was identified for the first time by the present inventors.
이러한 상기 본 발명의 약학 조성물에는 상기 익힌 누에가공물이 본 발명의 약학 조성물에 0.001~100 중량%로 하여 첨가될 수 있다. 상기 약학 조성물은, 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. In the pharmaceutical composition of the present invention, the cooked silkworm product may be added in an amount of 0.001 to 100% by weight to the pharmaceutical composition of the present invention. The pharmaceutical composition may be formulated and used in the form of oral formulations such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, external preparations, suppositories and sterile injection solutions according to conventional methods, respectively.
본 발명의 약학 조성물은 약학적으로 허용되는 담체, 부형제 및 희석제로 이루어진 군으로부터 선택된 1 종 이상을 추가로 포함할 수 있다.The pharmaceutical composition of the present invention may further include at least one selected from the group consisting of pharmaceutically acceptable carriers, excipients and diluents.
상기 약학 조성물에 포함될 수 있는 담체, 부형제 및 희석제로는 락토즈, 덱스트로즈, 수크로스, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 사카린, 나한과 추출물(몬그로사이드), 스테비아, 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. 경구투여를 위한 고형제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 이러한 고형제제는 본 발명의 조성물에 적어도 하나 이상의 부형제, 예를 들면, 전분, 탄산칼슘, 수크로스 또는 락토오스, 젤라틴 등을 섞어 조제된다. 또한 단순한 부형제 이외에 마그네슘 스테아레이트, 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 등이 포함될 수 있다. 비경구 투여를 위한 제제에는 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조 제제, 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. Carriers, excipients, and diluents that may be included in the pharmaceutical composition include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, saccharin, Monkroside, stevia, starch, and acacia. rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. can When formulated, it is prepared using diluents or excipients such as commonly used fillers, extenders, binders, wetting agents, disintegrants, and surfactants. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc., and these solid preparations include at least one excipient in the composition of the present invention, for example, starch, calcium carbonate, sucrose or lactose, It is prepared by mixing gelatin, etc. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Liquid preparations for oral use include suspensions, solutions for oral use, emulsions, syrups, etc. In addition to water and liquid paraffin, which are commonly used simple diluents, various excipients such as wetting agents, sweeteners, aromatics, and preservatives may be included. . Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solvents, suspensions, emulsions, freeze-dried formulations, and suppositories. Propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate may be used as non-aqueous solvents and suspensions. As a base for the suppository, witepsol, macrogol,
본 발명의 약학 조성물의 투여량은 치료받을 대상의 연령, 성별, 체중과, 치료할 특정 질환 또는 병리 상태, 질환 또는 병리 상태의 심각도, 투여경로 및 처방자의 판단에 따라 달라질 것이다. 이러한 인자에 기초한 투여량 결정은 당업자의 수준 내에 있으며, 일반적으로 투여량은 0.01㎎/㎏/일 내지 대략 2000㎎/㎏/일의 범위이다. 더 바람직한 투여량은 1㎎/㎏/일 내지 500㎎/㎏/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 pathological condition, the route of administration, and the judgment of the prescriber. Determination of dosage based on these factors is within the level of those skilled in the art, and generally dosages range from 0.01 mg/kg/day to approximately 2000 mg/kg/day. A more preferred dosage is 1 mg/kg/day to 500 mg/kg/day. Administration may be administered once a day, or may be administered in several divided doses. The dosage is not intended to limit the scope of the present invention in any way.
본 발명의 약학 조성물을 투여 받는 대상은 쥐, 가축, 인간 등의 모든 포유동물을 포함하나, 투여 대상에게서 목적하는 효과가 발휘되는 한, 이에 한정되지 않는다.Subjects receiving the pharmaceutical composition of the present invention include all mammals such as rats, livestock, humans, etc., but are not limited thereto as long as the desired effect is exerted in the administered subject.
또한, 본 발명의 약학 조성물은 다양한 경로로 투여될 수 있다. 투여의 모든 방식은 예상될 수 있는데, 예를 들면, 경구, 직장 또는 정맥, 근육, 피하, 자궁내 경막 또는 뇌혈관내 주사에 의해 투여될 수 있다. 본 발명의 조성물은 독성 및 부작용이 거의 없으므로 예방 목적으로 장기간 복용시에도 안심하고 사용할 수 있는 약제이다. In addition, the pharmaceutical composition of the present invention can be administered by various routes. All modes of administration are contemplated, eg oral, rectal or intravenous, intramuscular, subcutaneous, intrauterine intrathecal or intracerebrovascular injection. Since the composition of the present invention has little toxicity and side effects, it is a drug that can be safely used even when taken for a long period of time for preventive purposes.
이때, 상기 익힌 누에가공물은 본 발명이 목적하는 효능을 나타내기 위한 유효한 함량으로, 분말 중량면에서 조성물 총 중량에 대하여 0.01~100 중량%로 함유하는 것이 바람직하고, 더욱 바람직하게는 0.1~90 중량%로 함유하는 것이 좋다. At this time, the cooked silkworm product is an effective amount to exhibit the desired efficacy of the present invention, and preferably contains 0.01 to 100% by weight, more preferably 0.1 to 90% by weight, based on the total weight of the composition in terms of powder weight. It is good to contain %.
또한, 본 발명의 다른 양태에 따르면, 본 발명은 상기 익힌 누에가공물을 유효성분으로 포함하는 근감소증 예방 및 개선 효과를 위한 식품 조성물을 제공한다.In addition, according to another aspect of the present invention, the present invention provides a food composition for preventing and improving sarcopenia, comprising the cooked silkworm product as an active ingredient.
상기 식품 조성물은 건강 기능 식품(health functional food), 영양 보조제(nutritional supplement), 식품 첨가제(food additives), 특수의료용도 식품(Special medicinal food) 및 식이보조제 등의 모든 형태의 식품에 대한 조성물을 포함한다.The food composition includes compositions for all types of food such as health functional food, nutritional supplements, food additives, special medicinal food and dietary supplements do.
본 발명의 견사단백질이 함유된 익힌 누에 가공물은 근육 감소 억제 효과 또는 근력 증강(근기능 향상) 효과를 나타내므로, 예컨대, 노년층의 노화 억제용 건강기능식품 또는 성장층의 성장 촉진용 건강기능식품으로 유용하게 사용될 수 있다. 동시에 근감소증으로 고통받는 환자의 특수의료용 식품(Special medicinal food)로 사용될 수 있다.The cooked silkworm processed product containing the silk protein of the present invention exhibits an effect of inhibiting muscle loss or enhancing muscle strength (improving muscle function), so it is useful, for example, as a health functional food for suppressing aging in the elderly or for promoting growth of growth layers. can be used At the same time, it can be used as a special medicinal food for patients suffering from sarcopenia.
이때, 상기 익힌 누에가공물은 본 발명의 식품 조성물에 0.01~100 중량%로 하여 사용될 수 있다. 상기 유형의 식품 조성물은 당업계에 공지된 통상적인 방법에 따라 다양한 형태로 제조할 수 있다. 예를 들면, 건강식품으로는 견사단백질이 함유된 익힌 누에 가공물이 함유된 껌, 비타민 복합체, 차, 주스 및 드링크 형태로 제조 할 수 있으며, 견사단백질이 함유된 익힌 누에 가공물을 유효성분으로 하는 식품 조성물을 과립화, 캡슐화 또는 분말화하여 섭취할 수 있다. 본 발명의 기능성 식품 조성물은 식품 제조 시에 통상적으로 첨가되는 성분을 포함할 수 있으며, 예를 들어, 단백질, 탄수화물, 지방, 영양소 및 조미제를 포함할 수 있다. 예컨대, 드링크제로 제조되는 경우에는 본 발명의 견사단백질이 함유된 익힌 누에 가공물 이외에 구연산, 액상과당, 설탕, 포도당, 초산, 사과산, 과즙, 대추 추출액, 감초 추출액 등을 추가로 포함시킬 수 있다.At this time, the cooked silkworm product may be used in an amount of 0.01 to 100% by weight in the food composition of the present invention. Food compositions of this type can be prepared in various forms according to conventional methods known in the art. For example, as a health food, it can be manufactured in the form of chewing gum, vitamin complex, tea, juice, and drink containing cooked silkworm processed products containing silk protein, and foods containing cooked silkworm processed products containing silk protein as an active ingredient. The composition may be ingested by granulating, encapsulating, or powdering. The functional food composition of the present invention may include components commonly added during food preparation, and may include, for example, proteins, carbohydrates, fats, nutrients, and seasonings. For example, when prepared as a drink, citric acid, high fructose corn syrup, sugar, glucose, acetic acid, malic acid, fruit juice, jujube extract, licorice extract, etc. may be further included in addition to the cooked silkworm processed product containing the silk protein of the present invention.
상기 식품 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, 알코올, 탄산 음료에 사용되는 탄산화제 등을 함유할 수 있다. 그밖에 천연 과일쥬스 및 과일 쥬스 음료 및 야채 음료의 제조를 위한 추출물을 함유할 수 있다. 이러한 성분은 독립적으로 또는 조합하여 사용할 수 있다.The food composition includes various nutrients, vitamins, minerals (electrolytes), flavors such as synthetic flavors and natural flavors, colorants and enhancers (cheese, chocolate, etc.), pectic acid and its salts, alginic acid and its salts, organic acids , a protective colloidal thickener, a pH adjusting agent, a stabilizer, a preservative, glycerin, alcohol, a carbonating agent used in carbonated beverages, and the like. In addition, it may contain extracts for the production of natural fruit juice, fruit juice beverages and vegetable beverages. These components may be used independently or in combination.
또한, 본 발명의 또 다른 양태에 따르면, 본 발명은 견사단백질이 함유된 익힌 누에가공물을 포함하는 동물의 근감소증의 예방 또는 개선용 사료 첨가제 또는 이를 포함하는 동물의 근감소증의 예방 또는 개선용 사료 조성물을 제공한다.In addition, according to another aspect of the present invention, the present invention is a feed additive for preventing or improving sarcopenia in animals containing a silk protein-containing cooked silkworm product or a feed for preventing or improving sarcopenia in animals containing the same composition is provided.
상기 견사단백질이 함유된 익힌 누에가공물은 상기 약학 조성물이나 식품 조성물의 경우와 동일하게 준비될 수 있다.The cooked silkworm product containing the silk protein may be prepared in the same way as the pharmaceutical composition or food composition.
본 발명의 견사단백질이 함유된 익힌 누에가공물은 근육 감소 억제 또는 근기능의 향상으로 인하여 전체적인 근력 증가 효과를 나타내므로 동물이나 가축의 성장 촉진제로서 사료 조성물에 포함될 수 있다.The cooked silkworm product containing the silk protein of the present invention exhibits an overall muscle strength increase effect due to inhibition of muscle loss or improvement of muscle function, so it can be included in a feed composition as a growth promoter for animals or livestock.
구체적으로 본 발명에 따른 견사단백질이 함유된 익힌 누에가공물을 유효성분으로 포함하는 사료는 당업계에서 공지된 다양한 형태의 사료로 제조 가능하며, 바람직하게는 농후사료, 조사료 또는 특수사료가 포함될 수 있다.Specifically, the feed containing the silkworm protein-containing cooked silkworm product according to the present invention as an active ingredient can be prepared with various types of feed known in the art, and preferably includes concentrated feed, roughage feed, or special feed. .
농후사료에는 밀, 귀리, 옥수수 등의 곡류를 포함하는 종자 열매류, 곡물을 정제하고 얻는 부산물로서 쌀겨, 밀기울, 보릿겨 등을 포함하는 겨류, 콩, 유체, 깨, 아마인, 코코야자 등을 채유하고 얻는 부산물인 깻묵류와 고구마, 감자 등에서 녹말을 뺀 나머지인 녹말찌꺼기의 주성분인 잔존녹말질류 등의 찌꺼기류, 어분, 물고기찌꺼기, 어류에서 얻은 신선한 액상물을 농축시킨 것인 피시솔루블(fish soluble), 육분, 혈분, 우모분, 탈지분유, 우유에서 치즈, 탈지유에서 카제인을 제조할 때의 잔액인 훼이(whey)를 건조한 건조훼이 등의 동물질사료, 효모, 클로렐라, 해조류 등이 있다.Concentrated feed includes seeds and fruits including grains such as wheat, oats, and corn, bran including rice bran, wheat bran, and barley bran as by-products obtained after refining grains, soybeans, fluids, sesame seeds, linseed, and coco palm oil. Fish soluble, which is a condensed fresh liquid obtained from fish meal, fish meal, fish meal, fish meal, fish meal, fish meal, fish meal, fish meal, fish meal soluble), meat meal, blood meal, feather meal, skim milk powder, animal feed such as dried whey, yeast, chlorella, seaweed, etc.
조사료에는 야초, 목초, 풋베기 등의 생초 사료, 사료용 순무, 사료용 비트, 순무의 일종인 루터베어거 등의 뿌리채소류, 생초, 풋베기작물, 곡실 등을 사일로에 채워 놓고 젖산발효시킨 저장사료인 사일리지(silage), 야초, 목초를 베어 건조시킨 건초, 종축용 작물의 짚, 콩과 식물의 나뭇잎 등이 있다.Forages include raw grass feed such as wild grass, grass, green cutting, turnip for feed, beet for feed, root vegetables such as Lutherbearer, a type of turnip, raw grass, green cut crops, grains, etc. These include silage, grasses, hay from cut and dried grasses, straw from breeding crops, and leaves from leguminous plants.
특수사료에는 패각, 암염 등의 미네랄 사료, 요소나 그 유도체인 디우레이드이소부탄 등의 요소사료, 천연사료 원료만을 배합했을 때 부족하기 쉬운 성분을 보충하거나, 사료의 저장성을 높이기 위해서 배합사료에 미량으로 첨가하는 물질인 사료첨가물, 식이보조제 등이 있다.Special feeds include mineral feeds such as shells and rock salt, urea feeds such as urea or its derivative, diureide isobutane, and ingredients that are likely to be lacking when only natural feed ingredients are mixed, or in trace amounts in formulated feeds to improve the storage life of feeds. There are feed additives, dietary supplements, etc.
본 발명에 따른 사료 조성물은 다양한 사료 첨가제를 포함할 수 있다.The feed composition according to the present invention may include various feed additives.
본 발명에서 용어 "사료 첨가제" 란 영양소 보충 및 체중감소 예방, 사료 내 섬유소의 소화 이용성 증진, 유질개선, 번식장애 예방 및 수태율 향상, 하절기 고온 스트레스 예방 등 다양한 효과를 목적으로 사료에 첨가하는 물질을 말한다. 본 발명의 사료첨가제는 사료관리법상의 보조사료에 해당하며, 탄산수소나트륨(중조), 벤토나이트 (bentonite), 산화마그네슘, 복합광물질 등의 광물질제제, 아연, 구리, 코발트, 셀레늄 등의 미량 광물질인 미네랄제제, 케로틴, 비타민 E, 비타민 A, D, E, 니코틴산, 비타민 B 복합체 등의 비타민제, 메티오닌, 리이산 등의 보호아미노산제, 지방산 칼슘염 등의 보호지방산제, 생균제(유산균제), 효모배양물, 곰팡이 발효물 등의 생균, 효모제 등이 추가로 포함될 수 있다.In the present invention, the term "feed additive" is a substance added to feed for various effects, such as supplementation of nutrients and prevention of weight loss, improvement of digestibility of fiber in feed, improvement of oil quality, prevention of reproductive disorder and improvement of conception rate, and prevention of high temperature stress in summer. say The feed additive of the present invention corresponds to supplementary feed under the Feed Management Act, and is a mineral preparation such as sodium bicarbonate (sodium bicarbonate), bentonite, magnesium oxide, and complex minerals, and minerals such as zinc, copper, cobalt, and selenium, which are trace minerals. preparations, vitamins such as kerotene, vitamin E, vitamins A, D, E, nicotinic acid, and vitamin B complex, protective amino acids such as methionine and lysic acid, protective fatty acids such as calcium salts of fatty acids, probiotics (lactic acid bacteria), yeast culture Water, live bacteria such as fungal fermentation, yeast, and the like may be further included.
본 발명에 따른 사료 조성물은 근육 감소 억제 또는 근기능의 향상으로 인하여 전체적인 근력 증가 효과 및 성장 촉진을 목적으로 하는 개체이면 특별히 한정되지 않고, 어떠한 것이든 적용 가능하다. 상기 개체는 동물, 예를 들어 비-영장류 (예를 들면, 소, 돼지, 말, 고양이, 개, 래트 및 마우스) 및 영장류 (예를 들면, 원숭이, 예를 들어 사이노몰구스 (cynomolgous) 원숭이 및 침팬지)를 비롯한 포유동물을 나타낸다. 상기 개체는 축산용 동물 (예를 들면, 말, 소, 돼지 등) 또는 애완용 동물 (예를 들면, 개 또는 고양이)이다.The feed composition according to the present invention is not particularly limited as long as it is an individual for the purpose of increasing overall muscle strength and promoting growth due to inhibition of muscle loss or improvement of muscle function, and any one can be applied. The subject may include animals such as non-primates (eg cows, pigs, horses, cats, dogs, rats and mice) and primates (eg monkeys such as cynomolgous monkeys and chimpanzees). The subject is a livestock animal (eg, horse, cow, pig, etc.) or a pet animal (eg, dog or cat).
본 발명에 따른 사료 조성물의 복용량은 동물의 종(species), 크기(size), 무게(weight), 나이(age)와 같은 다수의 요인들에 좌우될 것이다. 원칙적으로, 전형적인 복용량은 동물/일 당 0.001 내지 10 g의 범위일 수 있으나, 이에 한정되지 않는다.The dosage of the feed composition according to the present invention will depend on a number of factors such as the species, size, weight and age of the animal. In principle, a typical dosage may range from 0.001 to 10 g per animal/day, but is not limited thereto.
또한, 본 발명의 또 다른 양태에 따르면, 상기 견사단백질이 함유된 익힌 누에가공물을 포함하는 조성물을 인간을 제외한 개체에 투여하는 단계를 포함하는 근감소증 치료 방법을 제공한다.In addition, according to another aspect of the present invention, there is provided a method for treating sarcopenia comprising the step of administering a composition comprising the silk protein-containing cooked silkworm product to a non-human subject.
본 발명의 용어 "개체"란 근감소증이 발병될 가능성이 있거나 또는 발병된 쥐, 가축, 인간 등을 포함하는 포유동물, 양식어류 등을 제한 없이 포함할 수 있다.The term "individual" of the present invention may include, without limitation, mammals, farmed fish, etc., including mice, livestock, humans, etc., which are likely or have developed sarcopenia.
본 발명의 근감소증 치료용 약학 조성물의 투여 경로는 목적 조직에 도달할 수 있는 한 어떠한 일반적인 경로를 통하여도 투여될 수 있다. 본 발명의 약학 조성물은 특별히 이에 제한되지 않으나, 목적하는 바에 따라 복강내 투여, 정맥내 투여, 근육내 투여, 피하 투여, 피내 투여, 경구 투여, 비내 투여, 폐내 투여, 직장내 투여 등의 경로를 통해 투여 될 수 있다. 다만, 경구 투여 시에는 위산에 의하여 상기 견사단백질이 함유된 익힌 누에가공물이 변성될 수 있기 때문에 경구용 조성물은 활성 약제를 코팅하거나 위에서의 분해로부터 보호되도록 제형화 되어야 한다. 또한, 상기 조성물은 활성 물질이 표적 세포로 이동할 수 있는 임의의 장치에 의해 투여될 수 있다.The administration route of the pharmaceutical composition for the treatment of sarcopenia of the present invention may be administered through any general route as long as it can reach the target tissue. The pharmaceutical composition of the present invention is not particularly limited thereto, but depending on the purpose, intraperitoneal administration, intravenous administration, intramuscular administration, subcutaneous administration, intradermal administration, oral administration, intranasal administration, intrapulmonary administration, intrarectal administration, etc. can be administered through However, since the cooked silkworm product containing the silk protein may be denatured by gastric acid during oral administration, the oral composition should be formulated so that the active agent is coated or protected from degradation in the stomach. In addition, the composition may be administered by any device capable of transporting an active substance to a target cell.
본 발명의 방법은 상술한 견사단백질이 함유된 익힌 누에가공물을 유효성분으로 포함하므로, 중복된 내용은 본 명세서의 과도한 복잡성을 피하기 위하여 그 기재를 생략한다.Since the method of the present invention includes the above-described cooked silkworm products containing silk protein as an active ingredient, redundant descriptions are omitted to avoid excessive complexity in the present specification.
종합적으로, 본 발명은, 새로운 형태의 식의약용 원료인 익힌숙잠을 섭취할 경우 근육 감소를 효과적으로 억제시키는 동시에 체중의 증가도 탁월하게 증가시킬 수 있다는 것을 최초로 규명한 것으로서, 본 발명을 이용한 근감소증 억제 건강 보조제 또는 의약품이 개발되어 시판될 것으로 예상되며, 이로 인하여 근감소증에 기인한 각종 질환으로 고통받는 수많은 국민들에게 익힌숙잠의 가치가 크게 부각될 것으로 기대된다. 또한, 익힌숙잠의 활용도 창출 및 고부가가치화로 양잠산업 및 농업 발전에 기여하는 효과 역시 클 것으로 기대된다.Overall, the present invention has been identified for the first time that the intake of cooked sleep, a new type of raw material for food and medicine, can effectively suppress muscle loss and at the same time increase weight gain excellently, It is expected that suppressive health supplements or medicines will be developed and marketed, thereby greatly highlighting the value of a deep sleep to many people suffering from various diseases caused by sarcopenia. In addition, it is expected that the effect of contributing to the development of the sericulture industry and agriculture by creating utilization and high added value of cooked sleep is expected to be great.
본 발명에 따른 견사단백질이 함유된 익힌 누에가공물은 근감소증 모델에서 탁월한 체중 증가, 근력 개선, 근육무게 증가 및/또는 기억력 개선에 효과를 발휘하는 바, 근감소증의 예방, 치료 및 개선용 조성물로 활용될 수 있다. 또한, 본 발명의 유효성분을 활용하여 각종 건강보조식품 또는 의약품이 개발되어 시판될 것으로 예상되는 바, 이로 인하여 견사선을 갖는 익힌 누에가공물의 활용도 창출 및 고부가가치화로 양잠 산업 발전에 기여하는 효과가 클 것으로 기대되며, 근감소증 및 이로 인해 야기되는 각종 성인병으로 인해 치솟는 사회적 비용(보건의료 비용 등)의 감소 및 국민들의 삶의 질 개선에 크게 기여할 것으로 예상된다.The cooked silkworm product containing silk protein according to the present invention is effective in weight gain, muscle strength improvement, muscle weight increase and/or memory improvement in a sarcopenia model, and is therefore used as a composition for preventing, treating, and improving sarcopenia. can be utilized In addition, it is expected that various health supplements or medicines will be developed and marketed using the active ingredients of the present invention, which will contribute to the development of the sericulture industry by creating utilization of cooked silkworm products with silk thread and adding high value. It is expected to greatly contribute to reducing soaring social costs (health care costs, etc.) and improving the quality of life of the people due to sarcopenia and various adult diseases caused by it.
도 1은 일반사료섭취 SAMP8 근감소증 모델(Nf)과 골든실크홍잠사료섭취 SAMP8 근감소증 모델(GS-HJf)에서의 체중 변화를 비교한 결과를 보여준다.
도 2는 일반사료섭취 SAMP8 근감소증 모델(Nf)과 골든실크홍잠사료섭취 SAMP8 근감소증 모델(GS-HJf)에서의 공간기억력 변화를 비교한 결과를 보여준다.
도 3은 일반사료섭취 SAMP8 근감소증 모델(Nf)과 골든실크홍잠사료섭취 SAMP8 근감소증 모델(GS-HJf)에서의 운동능력 변화를 비교한 결과를 보여준다.
도 4는 일반사료섭취 SAMP8 근감소증 모델(Nf)과 골든실크홍잠사료섭취 SAMP8 근감소증 모델(GS-HJf)에서의 근력 변화를 비교한 결과를 보여준다.
도 5는 일반사료섭취 SAMP8 근감소증 모델(Nf)과 골든실크홍잠사료섭취 SAMP8 근감소증 모델(GS-HJf)에서의 근육 무게 변화를 비교한 결과를 보여준다.
도 6은 일반사료섭취 SAMP8 근감소증 모델(Nf)과 골든실크홍잠사료섭취 SAMP8 근감소증 모델(GS-HJf)에서의 근육에 발현되는 근육 생성 관련 유전자들과 근육 분해 관련 유전자들의 발현 변화를 근육에서 비교한 결과를 보여준다.
도 7은 일반사료섭취 DEX-유도 근감소증 모델(Nf)과 다양한 홍잠사료섭취 DEX-유도 근감소증 모델(HJf)에서의 체중 변화를 비교한 결과를 보여준다. 양성 대조군으로는 크레아틴을 섭취한 DEX-유도 근감소증 모델을 사용하였다.
도 8은 일반사료섭취 DEX-유도 근감소증 모델(Nf)과 홍잠사료섭취 DEX-유도 근감소증 모델(HJf)에서의 근육 무게 변화를 비교한 결과를 보여준다.
도 9는 일반사료섭취 DEX-유도 근감소증 모델(Nf)과 홍잠사료섭취 DEX-유도 근감소증 모델(HJf)에서의 공간 기억력 변화를 비교한 결과를 보여준다.
도 10은 일반사료섭취 DEX-유도 근감소증 모델(Nf)과 홍잠사료섭취 DEX-유도 근감소증 모델(HJf)에서의 자세조절 능력 변화를 비교한 결과를 보여준다.
도 11은 일반사료섭취 DEX-유도 근감소증 모델(Nf)과 홍잠사료섭취 DEX-유도 근감소증 모델(HJf)에서의 근력 변화를 비교한 결과를 보여준다.
도 12는 일반사료섭취 DEX-유도 근감소증 모델(Nf)과 홍잠사료섭취 DEX-유도 근감소증 모델(HJf)에서의 사회적 기억력 변화를 비교한 결과를 보여준다.Figure 1 shows the results of comparison of body weight changes in the general feed-intake SAMP8 sarcopenia model (Nf) and the golden silk red jam feed-intake SAMP8 sarcopenia model (GS-HJf).
Figure 2 shows the results of comparing spatial memory changes in the normal feed-intake SAMP8 sarcopenia model (Nf) and the golden silk red jam feed-intake SAMP8 sarcopenia model (GS-HJf).
Figure 3 shows the results of comparing the change in exercise capacity in the general feed SAMP8 sarcopenia model (Nf) and the golden silk red jam feed intake SAMP8 sarcopenia model (GS-HJf).
Figure 4 shows the results of comparison of muscle strength changes in the general feed intake SAMP8 sarcopenia model (Nf) and golden silk red jam feed intake SAMP8 sarcopenia model (GS-HJf).
Figure 5 shows the results of comparison of muscle weight changes in the general feed SAMP8 sarcopenia model (Nf) and the golden silk red jam feed SAMP8 sarcopenia model (GS-HJf).
Figure 6 shows changes in the expression of muscle generation-related genes and muscle breakdown-related genes expressed in muscles in the general feed intake SAMP8 sarcopenia model (Nf) and golden silk red jam feed intake SAMP8 sarcopenia model (GS-HJf) in muscle Shows the comparison result.
Figure 7 shows the results of comparison of body weight changes in the general feed intake DEX-induced sarcopenia model (Nf) and various red jam feed intake DEX-induced sarcopenia models (HJf). As a positive control group, a DEX-induced sarcopenia model in which creatine was ingested was used.
Figure 8 shows the results of comparison of muscle weight changes in the normal feed intake DEX-induced sarcopenia model (Nf) and the red jam feed intake DEX-induced sarcopenia model (HJf).
Figure 9 shows the results of comparing spatial memory changes in the normal feed intake DEX-induced sarcopenia model (Nf) and the red jam feed intake DEX-induced sarcopenia model (HJf).
Figure 10 shows the results of comparing the change in postural control ability in the normal feed intake DEX-induced sarcopenia model (Nf) and the red jam feed intake DEX-induced sarcopenia model (HJf).
Figure 11 shows the results of comparison of muscle strength changes in the normal feed intake DEX-induced sarcopenia model (Nf) and the red jam feed intake DEX-induced sarcopenia model (HJf).
Figure 12 shows the results of comparison of changes in social memory in the normal feed intake DEX-induced sarcopenia model (Nf) and the red jam feed intake DEX-induced sarcopenia model (HJf).
이하, 실시예를 통하여 본 발명을 더욱 상세히 설명하고자 한다. 이들 실시예는 오로지 본 발명을 예시하기 위한 것으로서, 본 발명의 범위가 이들 실시예에 의해 제한되는 것으로 해석되지는 않는 것은 당업계에서 통상의 지식을 가진 자에게 있어서 자명할 것이다.Hereinafter, the present invention will be described in more detail through examples. These examples are only for illustrating the present invention, and it will be apparent to those skilled in the art that the scope of the present invention is not to be construed as being limited by these examples.
실시예 1. 견사단백질이 함유된 익힌 숙잠 동결 건조 분말(익힌 누에가공물; 홍잠)의 제조Example 1. Preparation of cooked silkworm freeze-dried powder containing silk protein (cooked silkworm product; Hongjam)
본 발명자들은 누에를 사육하여 5령4일 이후 숙잠을 100℃ 수증기로 2시간 동안 익혀 익힌 누에 가공물을 제조하였고, 상기 익힌 누에 가공물을 급속 냉동 후 동결건조시켜, 익힌숙잠 동결건조 분말(steamed mature silkworm powder; 홍잠)을 제조하였다. The present inventors bred silkworms and cooked mature silkworms for 2 hours in 100 ° C steam after 5th instar 4th day to prepare a cooked silkworm processed product, freeze-dried the cooked silkworm processed product after rapid freezing, and steamed mature silkworm freeze-dried powder (steamed mature silkworm) powder; Hongjam) was prepared.
통상적으로 약용으로 사용되는 누에는 5령 3일 누에이고 5령 4일 이후의 누에부터는 식용할 수 없는 누에로 여겨졌다. 누에는 5령3일을 지나면서 견사선이 비대해지고, 5령 7일 또는 8일 이후에는 내장이 퇴화하면서 몸속에는 거대해진 견사선 만을 포함하고 있는 숙잠이 된다.Silkworms commonly used for medicinal purposes were 5th instar 3rd silkworms, and 5th instar 4th silkworms were considered inedible silkworms. As silkworms pass through the 5th instar and 3rd day, the silk glands become enlarged, and after the 7th or 8th day of the 5th instar, the internal organs degenerate and become a sleeper containing only the enlarged silk glands in the body.
견사단백질이 누에의 몸체에서 생성되는 것인 5령 3일부터이기는 하나, 이 시기의 누에에는 견사단백질이 적은 편이며, 누에가 5령 4일째가 되면서부터 비로소 누에의 몸 속에 저장되어 있던 견사단백질이 급속히 증가하게 되면서, 바로 하루 전의 누에인 5령3일의 누에보다 체조직이 훨씬 비대해지고 단단해지게 되며, 숙잠기에 이르게 되면 견사단백질의 양이 더욱 증가하게 된다.Although silk protein is produced in the body of the silkworm from the 3rd day of the 5th instar, the silkworm at this time has little silk protein, and the silk protein was stored in the body of the silkworm for the first time when the silkworm reached the 4th day of the 5th instar. As this rapidly increases, body tissue becomes much larger and harder than silkworms of 5 instars and 3 days of the previous day.
따라서, 본 발명에서 이용한 누에는, 누에의 몸체와 함께 5령4일 4면잠 누에부터 숙잠기까지의 누에의 몸체에 급증하는 견사가 더 포함된 것이다.Therefore, the silkworm used in the present invention further includes rapidly growing silk threads in the body of the silkworm from the 5
한편, 성분 분석 결과, 익히기 전의 숙잠 내에 있던 각종 구성성분의 함량이 익힌 숙잠이 되면서 다양하게 변화된 것을 확인하였다. On the other hand, as a result of the component analysis, it was confirmed that the content of various components in the ripe sleep was changed in various ways as the cooked sleep became.
특히, 조단백질의 함량에서 세린, 글리신, 알라닌의 함량이 현저하게 증가한 것을 알 수 있으며 이러한 익힌 숙잠의 성분 변화로 인해 상기 익힌 숙잠이 갖는 약리학적 효과에도 변화가 있을 것임을 확인할 수 있다. In particular, it can be seen that the content of serine, glycine, and alanine significantly increased in the content of crude protein, and it can be confirmed that the pharmacological effect of the cooked sleep will also change due to the change in the components of the cooked sleep.
실시예 2. SAMP8 근감소증 모델에서의 홍잠섭취에 따른 항 근감소증 효과 입증Example 2. Demonstration of anti-sarcoma effect according to hongjam intake in SAMP8 sarcopenia model
본 발명자들은 상기 실시예 1에서 제조된 홍잠의 항 근감소증 효과를 입증하기 위하여, 근감소증을 포함한 다양한 노인성 질환의 연구에 사용되는 대표적인 포유류 모델인 SAMP8 (Senescence-accelerated mouse P-8) 근감소증 모델을 이용하여, 체중, 근력, 공간기억력 및 운동능력 변화를 확인하였다.In order to demonstrate the anti-sarcoma effect of Hongjam prepared in Example 1, the present inventors used the SAMP8 (Senescence-accelerated mouse P-8) sarcopenia model, which is a representative mammalian model used in the study of various geriatric diseases including sarcopenia. Using , changes in weight, muscle strength, spatial memory, and motor skills were confirmed.
간략하게는, 다음과 같다:Briefly, it is as follows:
홍잠을 섭취한 SAMP8 쥐 20마리를 두 개의 군으로 나누어서 각각 생후 4주 후부터 56주 까지 일반사료 (Normal food, Nf)나 홍잠사료 (0.5 g/Kg 체중 HongJam food, HJf)를 먹이면서, 체중, 근력, 공간기억력 및 운동능력의 변화를 확인하였다. Twenty SAMP8 rats that consumed Hongjam were divided into two groups, and fed normal food (Nf) or HongJam food (0.5 g/Kg body weight HongJam food, HJf) from 4 weeks to 56 weeks, respectively, and their body weight, Changes in muscle strength, spatial memory and motor skills were confirmed.
체중은 매주 1회씩 정밀저울을 이용하여 측정하였다. Body weight was measured using a precision balance once a week.
공간기억력은 Y-maze를 이용하여 측정하였다. Spatial memory was measured using Y-maze.
운동 능력은 activity wheel(Jeung Do Bio & Plant Co. LTD)을 이용하는 wheel running test로 측정하였다. Exercise capacity was measured by a wheel running test using an activity wheel (Jeung Do Bio & Plant Co. LTD).
근력은 grip strength tester를 이용하여 34주부터 4주 간격으로 57주까지 측정하였다. Muscle strength was measured from 34 weeks to 57 weeks at 4-week intervals using a grip strength tester.
2-1. 홍잠섭취 SAMP8 근감소증 모델에서의 체중 증량 확인2-1. Confirmation of weight gain in red jam intake SAMP8 sarcopenia model
홍잠섭취 SAMP8 근감소증 모델에서의 체중 수준을 확인한 결과, 도 1에 나타낸 바와 같이, 홍잠섭취 SAMP8 근감소증 모델 쥐의 체중은 일반사료섭취 SAMP8에 비하여 체중이 무거웠다.As a result of confirming the body weight level in the red jam intake SAMP8 sarcopenia model, as shown in Figure 1, the body weight of the red jam intake SAMP8 sarcopenia model rat was heavier than that of the normal feed intake SAMP8.
4주 까지 차이가 없었던 SAMP8 근감소증모델 쥐의 체중이 18주 후부터 홍잠사료 섭취 SAMP8 근감소증 쥐의 무게가 일반사료섭취 SAMP8 근감소증 쥐의 체중에 비하여 유의하게 무거움을 확인할 수 있었다. SAMP8 근감소증 쥐의 체중의 차이는 사료의 차이에 의한 것임을 확인할 수 있었다. 나이에 따라서는 홍잠섭취 SAMP8 모델 쥐는 30주까지는 증가하다가 이후에는 체중이 유지되는 경향을 보여주었다. 이에 반하여 일반사료섭취 SAMP8 모델 쥐는 17주까지 체중이 증가를 하다가 유지되거나 50주 후부터 감소하는 경향을 보여주었다. 가장 체중의 차이가 많이 나는 시점은 생후 56주로서 홍잠사료 섭취 SAMP8 근감소증 모델 쥐의 체중은 일반사료섭취 SAMP8 근감소증 모델 쥐의 체중에 비하여 4.976g이나 더 무거웠다.It was confirmed that the weight of the SAMP8 sarcopenia model rats, which had no difference until 4 weeks, was significantly heavier than the weight of the SAMP8 sarcopenia rats fed the normal diet from 18 weeks later. It was confirmed that the difference in body weight of SAMP8 sarcopenia mice was due to the difference in feed. Depending on the age, the SAMP8 model rats ingesting hongjam showed a tendency to increase their weight up to 30 weeks and then maintain their body weight. On the other hand, the SAMP8 model rats fed the normal diet showed a tendency to increase their body weight up to 17 weeks and then maintain it or decrease it after 50 weeks. The greatest difference in body weight was at 56 weeks after birth, and the body weight of SAMP8 sarcopenia model rats consuming red jam food was 4.976 g heavier than that of normal diet fed SAMP8 sarcopenia model rats.
또한, 일반사료 또는 홍잠사료를 섭취한 SAMP8 근감소증 모델 쥐의 체중을 생후 4주 부터 시작을 해서 56주까지 측정을 한 결과를 보면 홍잠사료 섭취 SAMP8쥐의 체중이 일반사료섭취 SAMP8 쥐의 체중보다 통계적으로 유의하게 증가하였다(F(1, 529) = 228.2058, p = 1.47 x 10-41). 시간 경과에 따라 일반사료 또는 홍잠사료 섭취 SAMP8 근감소증 모델 쥐의 체중은 변화하였다(F(52, 529) = 126.0829, p = 1.72 x 10-52). 시간이 사료의 차이에 따른 체중의 차이에 영향을 미치지는 않았다(F(52, 529) = 11.15529, p = 0.248)In addition, as a result of measuring the body weight of SAMP8 sarcopenia model rats that consumed normal feed or red jam diet starting from 4 weeks after birth to 56 weeks, the body weight of SAMP8 rats fed red jam feed was higher than that of SAMP8 rats fed normal feed. Statistically significant increase (F (1, 529) = 228.2058, p = 1.47 x 10 -41 ). Over time, the body weight of the SAMP8 sarcopenia model rats fed the normal diet or the red jam diet changed (F (52, 529) = 126.0829, p = 1.72 x 10 -52 ). Time did not affect the difference in body weight according to the difference in feed (F (52, 529) = 11.15529, p = 0.248)
즉, 본 발명의 홍잠이 근감소증에서 체중 증량 및 유지에 효과적임을 보여준다.That is, it shows that Hongjam of the present invention is effective for weight gain and maintenance in sarcopenia.
2-2. 홍잠섭취 SAMP8 근감소증 모델에서의 공간기억력 증진 확인2-2. Confirmation of Spatial Memory Enhancement in SAMP8 Sarcopenia Model with Hongjam Intake
노인들의 경우 공간기억력이 감퇴되는 경향이 있으며, SAMP8 근감소증모델 쥐도 기억력에 이상이 있음이 알려져 있다.In the case of the elderly, spatial memory tends to decrease, and it is known that the SAMP8 sarcopenia model rat also has abnormalities in memory.
이러한 홍잠섭취 SAMP8 근감소증 모델에서의 공간기억력 수준을 확인한 결과, 도 2에 나타낸 바와 같이, 일반사료의 섭취 SAMP8 근감소증 모델 쥐와 홍잠사료 섭취 SAMP8 근감소증 모델 쥐의 공간기억력 변화를 Y-maze를 이용하여 확인했을 때, 홍잠사료를 섭취한 경우 36주부터 56주까지 뛰어난 공간 기억력을 보여주었다.As a result of confirming the level of spatial memory in this red jam intake SAMP8 sarcopenia model, as shown in FIG. When confirmed using this method, in the case of consumption of red jam feed, excellent spatial memory was shown from 36 weeks to 56 weeks.
또한, 일반사료섭취 SAMP8 근감소증 모델 쥐에서 관찰되는 공간기억력의 퇴화가 홍잠사료 섭취 SAMP8 근감소증 모델 쥐에서는 관찰되지 않았다. 36주에서 56주까지 4주 간격으로 spontaneous alteration rate의 변화를 측정한 결과, 일반사료섭취 SAMP8 근감소증 모델 쥐에서는 공간기억력의 퇴화가 관찰되었으나, 홍잠사료 섭취 SAMP8 근감소증 모델 쥐에서는 관찰되지 않았다.In addition, the deterioration of spatial memory observed in SAMP8 sarcopenia model rats fed normal feed was not observed in SAMP8 sarcopenia model rats fed red jam diet. As a result of measuring the change in spontaneous alteration rate at 4-week intervals from 36 to 56 weeks, deterioration of spatial memory was observed in SAMP8 sarcopenia model rats fed normal food, but not observed in SAMP8 sarcopenia model rats fed red jam food.
(Two-way ANOVA analysis: Nf vs HJf; F(1, 49) = 14.83315, p = 4.15 x 10-4, Within, weeks; F(4, 49) = 3.887955, p = 9.26 x 10-3, Between-within interaction; F(4, 49) = 0.484623, p= 0.747)(Two-way ANOVA analysis: Nf vs HJf; F (1, 49) = 14.83315, p = 4.15 x 10 -4 , Within, weeks; F (4, 49) = 3.887955, p = 9.26 x 10 -3 , Between -within interaction; F (4, 49) = 0.484623, p = 0.747)
즉, 본 발명의 홍잠이 근감소증에서 공간기억력 증진에 효과적임을 보여준다.That is, it shows that Hongjam of the present invention is effective in enhancing spatial memory in sarcopenia.
2-3. 홍잠섭취 SAMP8 근감소증 모델에서의 운동능력 향상 확인2-3. Confirmation of improvement in exercise capacity in the SAMP8 sarcopenia model with hongjam intake
SAMP8 근감소증 모델 쥐의 운동능력을 확인하기 위하여 wheel running test를 수행한 결과, 도 3에 나타낸 바와 같이, 홍잠사료 섭취 SAMP8 근감소증 모델 쥐의 운동능력이 일반사료섭취 SAMP8 근감소증 모델 쥐에 비하여 뛰어남을 확인하였다. 46주 째와 50주 째의 경우 일반사료섭취 SAMP8 근감소증 모델 쥐의 경우 휠을 분당 13.6회와 19.6회 회전시킬 수 있었는데, 홍잠사료 섭취 SAMP8 근감소증 모델 쥐의 경우는 분당 40.2회와 44.4회를 회전시킬 수 있었다. As a result of performing a wheel running test to confirm the exercise capacity of the SAMP8 sarcopenia model rats, as shown in Figure 3, the exercise capacity of the SAMP8 sarcopenia model rats consuming red jam feed is superior to that of the SAMP8 sarcopenia model rats consuming normal feed. confirmed. At 46 weeks and 50 weeks, the SAMP8 sarcopenia model rats fed the normal diet were able to rotate the wheel at 13.6 and 19.6 times per minute, whereas the SAMP8 sarcopenia model rats fed the red jam diet achieved 40.2 and 44.4 times per minute. could rotate
이에 반하여 근감소증이 발병한 54주 째에는 일반사료섭취 SAMP8 근감소증 모델 마우스는 휠을 분당 4회 회전시킬 수 있었지만, 홍잠섭취 SAMP8 근감소증 모델 쥐의 경우는 20.2회 회전시킬 수 있었다. On the other hand, at 54 weeks after the onset of sarcopenia, the SAMP8 sarcopenia model mice fed the normal diet could rotate the
즉, 일반사료섭취 SAMP8 근감소증 모델 쥐에서 관찰되는 운동능력의 퇴화가 홍잠사료 섭취 SAMP8 근감소증 모델 쥐에서는 나타나진 않음을 확인하였다. 46주부터 54주까지 홍잠섭취 SAMP8 근감소증 모델 쥐의 운동능력이 일반사료섭취 SAMP8 근감소증 모델 쥐에 비하여 통계적으로 유의하게 뛰어났다.That is, it was confirmed that the deterioration of exercise capacity observed in SAMP8 sarcopenia model rats fed a normal diet did not appear in SAMP8 sarcopenia model rats fed a red jam diet. From 46 weeks to 54 weeks, the exercise capacity of SAMP8 sarcopenia model rats fed red jam was statistically significantly superior to that of normal feed fed SAMP8 sarcopenia model rats.
(Two-way ANOVA analysis: Between, Nf vs HJf; F(1, 29) = 20.32269, p = 1.45 x 10-4, within, weeks; F(2, 29) = 5.701859, p = 9.42 x 10-3, between-within interaction; F(4, 49) = 0.412168, p = 0.667) (Two-way ANOVA analysis: Between, Nf vs HJf; F (1, 29) = 20.32269, p = 1.45 x 10 -4 , within, weeks; F (2, 29) = 5.701859, p = 9.42 x 10 -3 , between-within interaction; F (4, 49) = 0.412168, p = 0.667)
상기 결과는 홍잠섭취가 근감소증에 의하여 나타나는 운동능력의 손실을 예방함을 보여준다.The above results show that hongjam intake prevents loss of motor ability caused by sarcopenia.
2-4. 홍잠섭취 SAMP8 근감소증 모델에서의 근력 향상 확인2-4. Confirmation of improvement in muscle strength in the SAMP8 sarcopenia model with Hongjam intake
SAMP8 근감소증 모델 쥐에서의 근력 변화를 확인하기 위하여, 34주째부터 57주째까지 4주 간격으로 grip strength test를 수행한 결과, 도 4에 나타낸 바와 같이, 일반사료섭취 SAMP8 근감소증 모델 쥐와 비교하여 홍잠사료 섭취 SAMP8 근감소증 모델 쥐의 근력이 항상 강함을 확인하였다. 34주에는 홍잠사료 섭취 SAMP8 근감소증 모델 쥐의 근력이 일반사료섭취 쥐보다 32.6% 강하였고, 37주에는 25.4%, 41주에는 6.8%, 45주에는 4.3%, 49주에는 12.7%, 53주에는 9.0%, 57주에는 13.7% 지속적으로 통계적으로 유의하게 강하게 나타났다.In order to confirm the change in muscle strength in the SAMP8 sarcopenia model rat, a grip strength test was performed at 4-week intervals from
(Two-way ANOVA 분석결과: 일반사료 vs 홍잠사료: F(1, 59) = 17.50181, p = 0.000121, weeks: F(5, 59) = 7.429776, p = 3.15 x 10-5, within-between interactioin: F(5, 59) = 0.293668, p = 0.91412)(Two-way ANOVA analysis result: normal diet vs red jam diet: F (1, 59) = 17.50181, p = 0.000121, weeks: F (5, 59) = 7.429776, p = 3.15 x 10 -5 , within-between interactioin : F (5, 59) = 0.293668, p = 0.91412)
2-5. 홍잠섭취 SAMP8 근감소증 모델에서의 근육 무게 증대 확인2-5. Confirmation of muscle weight increase in red jam intake SAMP8 sarcopenia model
57주된 홍잠섭취 SAMP8 근감소증 모델 쥐의 근육의 무게와 일반사료섭취 SAMP8 근감소증 모델 쥐 근육의 무게 변화를 비교한 결과, 도 5에 나타낸 바와 같이, 왼쪽과 오른쪽 뒷다리에서 Quadriceps, Gastrocnemius, Tibialis anterior를 적출한 후 무게를 측정했을 때, 일반사료섭취 SAMP8 근감소증 모델 쥐의 근육들이 홍잠사료 섭취 SAMP8 근감소증 모델 쥐의 근육들에 비하여 무게가 통계적으로 유의하게 적음을 확인하였다. 근육들 간 무게 차이가 통계적으로 유의하게 존재하였다. As a result of comparing the weight change of the muscle weight of the 57-week-old red jam intake SAMP8 sarcopenia model rat and the normal feed intake SAMP8 sarcopenia model rat muscle weight, as shown in Figure 5, Quadriceps, Gastrocnemius, Tibialis anterior in the left and right hind limbs When the weight was measured after extraction, it was confirmed that the muscles of the SAMP8 sarcopenia model rats fed the general diet were statistically significantly less in weight than the muscles of the SAMP8 sarcopenia model rats fed the red jam diet. There was a statistically significant difference in weight between the muscles.
즉, 홍잠을 섭취한 모델 쥐의 근육들의 무게가 통계적으로 유의하게 무거웠다. 오른쪽과 왼쪽 뒷다리 모두 동일하였고, 근육들 간에는 홍잠사료 섭취 군과 일반사료 섭취 군의 무게의 차이가 유의하게 존재하였다. That is, the weight of the muscles of the model rats that consumed Hongjam was statistically significantly heavier. Both the right and left hind limbs were the same, and there was a significant difference in the weight of the muscles between the Red Jam diet group and the general diet group.
(Two-way ANOVA analysis: muscles from the left hind leg: Between, Nf vs HJf; F(1, 39) = 13.708375, p = 6.4 x 10-6, within, muscles; F(3, 39) = 12.358885, p= 1.34 x 10-3, between-within interaction; F(3, 39) = 1.4223519, p = 0.254. the right hind leg: Between, Nf vs HJf; F(1, 39) = 13.42111, p = 7.71 x 10-6, within, muscles; F(3, 39) = 17.013083, p = 2.46 x 10-4, between-within interaction; F(3, 39) = 1.2981033, p = 0.292).(Two-way ANOVA analysis: muscles from the left hind leg: Between, Nf vs HJf ; F (1, 39) = 13.708375, p = 6.4 x 10 -6 , within, muscles ; F (3, 39) = 12.358885, p = 1.34 x 10 -3 , between-within interaction; F (3, 39) = 1.4223519 , p = 0.254. the right hind leg: Between, Nf vs HJf ; 10 -6 , within, muscles ; F (3, 39) = 17.013083, p = 2.46 x 10 -4 , between-within interaction; F (3, 39) = 1.2981033, p = 0.292).
2-6. 홍잠섭취 SAMP8 근감소증 모델에서의 근육 분해 관련 유전자 마커의 발현 감소 확인2-6. Confirmation of decreased expression of muscle degradation-related gene markers in the red jam intake SAMP8 sarcopenia model
57주된 홍잠섭취 SAMP8 근감소증 모델 쥐와 일반사료섭취 SAMP8 근감소증 모델 쥐의 근육에서 발현되는 근육생성 유전자와 근육 분해 유전자의 발현 변화를 비교하고자 하였다.The purpose of this study was to compare the expression changes of myogenic genes and muscle degradation genes expressed in the muscles of 57-week-old red jam-fed SAMP8 sarcopenia model rats and normal feed-fed SAMP8 sarcopenia model rats.
이때, 각 쥐에서 적출된 근육조직에서 총 RNA를 수득하여 cDNA를 합성하고, PCR 방법을 사용하여 상기 합성된 cDNA로부터 상기 각 유전자를 증폭시켜서 이들의 발현수준의 변화를 비교하였다.At this time, total RNA was obtained from the muscle tissues extracted from each mouse to synthesize cDNA, and each gene was amplified from the synthesized cDNA using a PCR method, and the changes in their expression levels were compared.
그 결과, 도 6에 나타난 바와 같이 근육 생성 전사인자인 Myogenic differentiation 1 (MyoD)와 Myogenic factor 5 (Myf5), 그리고 근육 생성 조절 인자인 myogenin과 Myogenic factor-6 (Myf-6)의 발현은 두 군간에 차이가 없었다.As a result, as shown in FIG. 6, the expression of myogenic differentiation 1 (MyoD) and myogenic factor 5 (Myf5), which are myogenic transcription factors, and myogenin and myogenic factor-6 (Myf-6), which are myogenic regulators, were significantly different between the two groups. there was no difference in
그러나, 반면, 근육 분해 유전자(마커)로서, muscle specific ubiquitin ligase인 MURF1 (muscle RING finger-1) 및 Astrogin-1; 근육분해유전자의 발현을 증진시키는 FoxO3 (Forhead box O3) 및 Myostatin의 경우, 홍잠섭취 SAMP8 근감소증 쥐의 근육에서 유의하게 감소됨을 확인하였다. However, on the other hand, as muscle degradation genes (markers), muscle specific ubiquitin ligase MURF1 (muscle RING finger-1) and Astrogin-1; In the case of FoxO3 (Forhead box O3) and Myostatin, which enhance the expression of muscle disintegration genes, it was confirmed that the intake of red jam significantly decreased in the muscles of SAMP8 sarcopenia rats.
상기 결과는 홍잠의 섭취가 근육 단백질의 분해를 억제함을 입증한다. The above results prove that intake of Hongjam inhibits muscle protein degradation.
실시예 3. 약물-유도 근감소증 모델에서의 홍잠섭취에 따른 근감소증 발병 예방 입증Example 3. Proof of prevention of sarcopenia by ingestion of hongjam in drug-induced sarcopenia model
본 발명자들은 상기 실시예 1에서 제조된 홍잠이 약물로 유도된 근감소증에 대해서도 항 근감소증 효과를 나타냄을 입증하기 위하여, 근 감소증-유발 약물 모델인 DEX-유도 근감소증 모델을 이용하여, 체중, 근육 무게, 근력, 자세조절 능력, 공간기억력 및 사회적 기억력 수준을 확인하였다.In order to demonstrate that Hongjam prepared in Example 1 exhibits an anti-sarcopenia effect against drug-induced sarcopenia, the present inventors used a DEX-induced sarcopenia model, which is a sarcopenia-induced drug model, to determine weight, Muscle weight, muscle strength, postural control ability, spatial memory and social memory levels were checked.
간략하게는, 다음과 같다:Briefly, it is as follows:
60마리의 C57BL/6J쥐를 6 개의 군으로 나눈 후, 일반사료 (Nf)와 0.5g/Kg 체중 또는 1.0g/Kg 체중 골든실크 홍잠(Golden-Silk HongJam food, GS)와 0.5g/Kg 주황잠 홍잠(Orange-Silk HongJam, OS)사료와 0.5g/Kg 백옥잠 홍잠(White-Jade HongJam, WJ) 사료와 0.6g/Kg 크레아틴(Creatine monohydrate) 사료를 섭취하도록 하였다. 크레아틴은 운동 중 피로감을 줄이고 근육량과 테스터스테론을 증가시켜 준다고 알려진 식품첨가물로서 양성대조군으로 사용되었다. 6주간 사료를 섭취한 쥐들에 근감소증을 유도한다고 알려진 약물인 덱사메타손 (Dexamethasone, DEX)를 PEG400과 혼합한 후, 25mg/Kg 체중의 비율로 C57BL/6J 쥐에 10일간 복강주사 (intraperitoneal injection, IP)를 수행하였다. 60 C57BL/6J rats were divided into 6 groups, and regular feed (Nf) and 0.5 g/Kg body weight or 1.0 g/Kg body weight Golden-Silk HongJam food (GS) and 0.5 g/Kg orange Orange-Silk HongJam (OS) feed, 0.5 g/Kg White-Jade HongJam (WJ) feed, and 0.6 g/Kg creatine (Creatine monohydrate) feed were consumed. Creatine was used as a positive control as a food additive known to reduce fatigue during exercise and increase muscle mass and testosterone. After mixing Dexamethasone (DEX), a drug known to induce sarcopenia in rats that consumed the feed for 6 weeks, with PEG400, intraperitoneal injection (IP) to C57BL/6J rats for 10 days at a rate of 25mg/Kg ) was performed.
체중 변화를 지속적으로 측정하였고 실험이 종료된 후에 근육을 적출한 후 무게를 측정하였다. The weight change was continuously measured, and after the experiment was completed, the muscle was removed and the weight was measured.
근력은 grip strength test를 DEX-IP 전과 후에 수행하여 근력 변화를 측정하였다. As for muscle strength, a grip strength test was performed before and after DEX-IP to measure changes in muscle strength.
Clasping assay를 DEX-IP 전과 후에 수행하여 자제조절능력의 변화를 측정하였다. Clasping assay was performed before and after DEX-IP to measure changes in self-control ability.
Y-maze를 DEX-IP 전과 후에 이용하여 공간기억력의 변화를 측정하였다. Changes in spatial memory were measured using Y-maze before and after DEX-IP.
3-1. 홍잠섭취 DEX-유도 근감소증 모델에서의 체중 증량 확인3-1. Confirmation of weight gain in red jam intake DEX-induced sarcopenia model
DEX-유도 근감소증 모델 쥐의 사료에 따른 체중 변화를 비교한 결과, 도 7에 나타낸 바와 같이, 일반사료와 4개의 홍잠사료 섭취 DEX-유도 근감소증 C57BL/6J 쥐와 크레아틴사료 섭취 DEX-유도 근감소증 C57BL/6J쥐의 몸무게 변화를 측정했을 때, 0.5g/Kg 골든실크홍잠사료 DEX-유도 근감소증 쥐들의 체중이 다른 0.5g/Kg 홍잠사료 섭취군 또는 대조군에 비하여 체중이 무거운 경향을 보임을 알 수 있었다. 이러한 체중 증가 및 DEX-IP 후 체중 유지 효과는 1.0g/Kg 골든실크사료 섭취 DEX-유도 근감소증 모델 쥐에서 더 명확하게 나타남을 확인하였다. As a result of comparing the weight change according to the diet of the DEX-induced sarcopenia model rats, as shown in FIG. 7, DEX-induced sarcopenia C57BL/6J mice and creatine feed intake DEX-induced muscle When the body weight change of sarcopenic C57BL/6J rats was measured, the weight of DEX-induced sarcopenia rats fed with 0.5 g/Kg golden silk hongjam diet tended to be heavier than that of other 0.5g/Kg hongjam diet intake groups or the control group. Could know. It was confirmed that these weight gain and weight maintenance effects after DEX-IP appeared more clearly in DEX-induced sarcopenia model rats consuming 1.0 g/Kg golden silk feed.
{Two-way ANOVA, Between foods [F(5, 840) = 137.1483, p = 2.7 x 10-106], Within Days [F(19, 840) = 35.50741, p = 5.69 x 10-94], Between/Within [F(95, 840) = 0.979774, p = 0.536773]}. {Two-way ANOVA, Between foods [F(5, 840) = 137.1483, p = 2.7 x 10-106], Within Days [F(19, 840) = 35.50741, p = 5.69 x 10-94], Between/ Within [F(95, 840) = 0.979774, p = 0.536773]}.
본 결과는 DEX-유도 근감소증 모델 쥐에서도 SAMP8 유전적 근감소증 모델 쥐에서와 같이 골든실크 홍잠이 가장 뛰어난 체중 유지 효과가 있었고, 0.5g/Kg보다 1.0g/Kg 골든실크 홍잠 섭취가 더 확실한 체중 유지 효과가 있음을 알 수 있다. This result shows that even in DEX-induced sarcopenia model rats, as in the SAMP8 genetic sarcopenia model rats, Golden Silk hongjam had the most excellent weight maintenance effect, and 1.0 g/Kg Golden Silk hongjam intake was more reliable than 0.5 g/Kg. It can be seen that there is a maintenance effect.
3-2. 홍잠섭취 DEX-유도 근감소증 모델에서의 근육 무게 증대 확인3-2. Confirmation of muscle weight increase in red jam intake DEX-induced sarcopenia model
일반사료 또는 다양한 홍잠사료를 섭취한 DEX-유도 근감소증 C57BL/6J 쥐를 생후 91일째에 희생시킨 후, 뒷다리의 quadriceps를 적출하여 무게 변화를 비교한 결과, 도 8에 나타낸 바와 같이, 0.5 g 골든실크홍잠사료(GS 0.5g)과 1.0 g 골든실크홍잠사료(GS 1.0g) 섭취군의 뒷다리 quadriceps의 무게가 일반사료(Nf) 섭취군의 뒷다리 quadriceps에 비하여 각각 8.44%와 12.28%가 증가됨을 확인하였다. 0.5 g 백옥잠홍잠사료(WJ)와 0.5 g 주황잠홍잠사료(OS) 섭취군의 뒷다리 quadriceps 무게는 Nf섭취군의 뒷다리 quadriceps보다 적은 99.08%와 95.85%에 불과하였다. 그리고 creatine 사료 섭취군의 뒷다리 quadriceps 무게는 95.95%에 불과하였다. After sacrificing DEX-induced sarcopenia C57BL/6J mice fed general feed or various red jam feeds at 91 days after birth, the quadriceps of the hind legs were removed and weight changes were compared. As shown in FIG. 8, 0.5 g golden It was confirmed that the weight of the hind leg quadriceps of the group consuming silk red jam feed (GS 0.5 g) and 1.0 g golden silk red jam feed (GS 1.0 g) increased by 8.44% and 12.28%, respectively, compared to the hind quadriceps of the normal feed (Nf) group. did The hind limb quadriceps weights of the 0.5 g white jade japonica diet (WJ) and 0.5 g orange jacaranda red jam diet (OS) were only 99.08% and 95.85% less than those of the Nf group. And the hind limb quadriceps weight of the creatine-fed group was only 95.95%.
이 결과는 골든실크홍잠을 섭취한 쥐들의 근육의 무게가 일반사료섭취군에 비하여 무거움을 보여주고 있다. This result shows that the muscle weight of the rats that consumed Golden Silk Redjam was heavier than that of the normal feed group.
3-3. 홍잠섭취 DEX-유도 근감소증 모델에서의 공간기억력 증대 효과확인3-3. Confirmation of spatial memory enhancement effect in DEX-induced sarcopenia model of hongjam intake
일반사료 또는 다양한 홍잠사료를 섭취한 DEX-유도 근감소증 모델에서의 공간기억력 증대 효과를 Y-maze를 이용하여 확인한 결과, 도 9에 나타낸 바와 같이, 일반사료(Nf) 섭취군의 경우 Dexamethasone intraperitoneal injection (DEX-IP) 후에 공간기억력이 -7.6702% 만큼 감퇴함을 확인 하였다. 이에 반하여 다양한 홍잠섭취군들에서는 일반사료 섭취 군에 비하여 DEX-IP 후에 공간기억력의 감퇴가 일어나지 않음을 확인 하였다. 그 중에서도 특히 0.5g 또는 1.0g의 골든실크홍잠사료 첩취군의(GS 0.5g, GS 1.0g) 경우 각각 11.96761%과 12.93875%의 공간기억력 증가가 확인되었고, 백옥잠홍잠사료 섭취군(WJ)과 주황잠홍잠사료 섭취군(OS)의 경우는 각각 8.670652%와 8.501939%의 공간기억력 증가가 확인되었다. 그리고 양성 대조군인 creatine사료 섭취군도 10.61603%의 공간기억력 증가가 확인되었다.As a result of confirming the spatial memory enhancement effect in the DEX-induced sarcopenia model in which general feed or various red jam feed was consumed using Y-maze, as shown in FIG. 9, Dexamethasone intraperitoneal injection in the case of the general feed (Nf) intake group. After (DEX-IP), it was confirmed that spatial memory decreased by -7.6702%. On the other hand, it was confirmed that spatial memory decline did not occur after DEX-IP in the various red jam intake groups compared to the general feed intake group. Among them, in the case of the 0.5g or 1.0g Golden Silk Redjam feed group (GS 0.5g, GS 1.0g), spatial memory increased by 11.96761% and 12.93875%, respectively. In the case of orange jam red jam feed intake group (OS), spatial memory increased by 8.670652% and 8.501939%, respectively. In addition, the positive control group, the creatine-fed group, also showed an increase in spatial memory of 10.61603%.
이 결과는 골든실크 홍잠 섭취군에서 가장 뛰어난 공간 기억력 증진 효과가 나타냄을 보여주고 있다. This result shows that the golden silk hongjam intake group showed the most excellent spatial memory enhancement effect.
3-4. 홍잠섭취 DEX-유도 근감소증 모델에서의 자세조절능력 증대 효과확인3-4. Confirmation of postural control ability increase effect in DEX-induced sarcopenia model
일반사료 또는 다양한 홍잠사료를 섭취한 DEX-유도 근감소증 모델에서의 자세조절능력 증대효과를 Limb clasping test를 이용하여 확인한 결과, 도 10에 나타낸 바와 같이, 일반사료(Nf) 섭취군의 경우 Dexamethasone intraperitoneal injection (DEX-IP) 후에 자세조절능력 수치가 0.75만큼 악화되었다. 그러나, 0.5g 또는 1.0g 골든실크홍잠사료 섭취군의 경우 DEX-IP후에 각각 0.55와 0.2만큼 악화되어서, 일반사료 대비 27.70%와 73.40% 회복되었음을 확인하였다. 또한, 백옥잠홍잠사료 섭취군(WJ)이나 주황잠홍잠사료(OS) 섭취군의 경우는 DEX-IP 후 악화된 수치가 각각 0.6과 0.05로 각각 일반사료 섭취군과 비교하면 20.00%와 93.40% 회복되었음을 확인하였다. 그리고 크레아틴(creatine) 사료 섭취군의 경우 DEX-IP 후에 악화된 수치가 0.2로서 일반사료 섭취군 대비 73.40% 회복됨을 확인하였다. As a result of confirming the effect of increasing postural control ability in the DEX-induced sarcopenia model ingesting general feed or various red jam feeds using the Limb clasping test, as shown in FIG. 10, in the case of the general feed (Nf) intake group, Dexamethasone intraperitoneal After injection (DEX-IP), the postural control ability value deteriorated by 0.75. However, in the case of the 0.5g or 1.0g golden silk red jam feed intake group, it was confirmed that the values deteriorated by 0.55 and 0.2 after DEX-IP, respectively, and recovered by 27.70% and 73.40% compared to the general feed. In addition, in the case of the white jade and red jam feed intake group (WJ) or the orange japonica red jam feed (OS) intake group, the values deteriorated after DEX-IP were 0.6 and 0.05, respectively, which were 20.00% and 93.40% compared to the general feed intake group, respectively. confirmed to have recovered. And in the case of the creatine feed intake group, it was confirmed that the value deteriorated after DEX-IP was 0.2, which was 73.40% recovery compared to the general feed intake group.
이 결과는 홍잠사료들이 전반적으로 자세조절능력 회복 효과가 있음을 보여주고 있다. This result shows that red jam feed has an overall postural control ability recovery effect.
3-5. 홍잠섭취 DEX-유도 근감소증 모델에서의 근력 증대 효과 확인3-5. Confirmation of muscle strength increase effect in DEX-induced sarcopenia model
일반사료 또는 다양한 홍잠사료를 섭취한 DEX-유도 근감소증 모델에서의 근력 증대효과를 grip strength test를 이용하여 확인한 결과, 도 11에 나타낸 바와 같이, 일반사료(Nf) 섭취군의 경우 Dexamethasone intraperitoneal injection (DEX-IP) 후에 -0.20013 N 만큼 감소하였다. 이에 비하여 0.5g 또는 1.0ㅎ 골든실크홍잠사료 섭취군에서는 각각 -0.05333 N 과 -0.03237 N 만 감소하였다.As a result of confirming the effect of increasing muscle strength in the DEX-induced sarcopenia model ingesting general feed or various red jam feeds using a grip strength test, as shown in FIG. 11, in the case of the general feed (Nf) intake group, Dexamethasone intraperitoneal injection ( After DEX-IP), it decreased by -0.20013 N. In contrast, only -0.05333 N and -0.03237 N were decreased in the group consuming 0.5 g or 1.0 ha of golden silk red jam feed, respectively.
그리고 백옥잠 홍잠 사료섭취군과 주황잠 홍잠 사료섭취군에서도 각각 -0.05007 N과 -0.02287 N 만 감소하였다. 이에 비하여 크레아틴사료섭취군에서는 일반사료섭취군과 비슷하게 -0.1966 N 감소되었다. And only -0.05007 N and -0.02287 N were decreased in the white jade jam red jam feed intake group and the orange jam red jam feed intake group, respectively. In contrast, the creatine feed intake group decreased -0.1966 N similarly to the general feed intake group.
이 결과는 홍잠사료의 섭취가 DEX에 의해 유도되는 근력 감소를 방지할 수 있음을 보여준다. This result shows that intake of red jam feed can prevent muscle strength loss induced by DEX.
3-6. 홍잠섭취 DEX-유도 근감소증 모델에서의 사회적 기억력 증대 효과 확인3-6. Confirmation of social memory enhancement effect in DEX-induced sarcopenia model of hongjam intake
일반사료 또는 다양한 홍잠사료를 섭취한 DEX-유도 근감소증 모델에서의 사회적 기억력 증대 효과를 Social interaction assay를 수행하여 확인한 결과, 도 12에 나타낸 바와 같이, 일반사료(Nf) 섭취군의 경우 Dexamethasone intraperitoneal injection (DEX-IP) 후에 사회적 기억력이 -20.5178% 감소하였지만, 다양한 홍잠사료 섭취군과 크레아틴 섭취군에서는 사회적 기억력의 감소가 나타나지 않았다. 0.5g 또는 1.0g 골든실크홍잠사료 섭취군은 각각 -0.69906%와 -0.83705%의 변화가 있었고, 백옥잠홍잠사료 섭취군과 주황잠홍잠사료 섭취군의 경우는 각각 -0.95935%와 3.314759%의 변화가 있었다. 그리고 크레아틴사료섭취군은 0.770995%의 변화가 있었다. As a result of confirming the effect of increasing social memory in the DEX-induced sarcopenia model in which general feed or various red jam feeds were consumed by performing Social interaction assay, as shown in FIG. 12, in the case of the general feed (Nf) intake group, Dexamethasone intraperitoneal injection After (DEX-IP), social memory decreased by -20.5178%, but there was no decrease in social memory in the various red jam feed and creatine intake groups. The 0.5g or 1.0g golden silk red jam feed intake group had a change of -0.69906% and -0.83705%, respectively, and the white jade red jam feed intake group and orange red jam feed intake group had a change of -0.95935% and 3.314759%, respectively. there was And the creatine feed intake group had a change of 0.770995%.
이 결과는 골든실크홍잠사료를 섭취한 경우, DEX-IP에 의하여 손상되는 사회적 기억력을 막아 줌을 보여준다. This result shows that the social memory damaged by DEX-IP is prevented when golden silk red jam feed is consumed.
종합적으로, 심각한 체중 저하와 근력 이상을 보여주는 근감소증 모델에서 홍잠은 체중 증가, 근력 개선, 근육 무게 증가, 기억력 개선 및 근육 분해 유전자 발현 억제 효과 모두에 탁월한 효과를 나타내었다. 이 결과는 홍잠의 섭취가 근감소증의 발병을 예방하고 치료할 수 있음을 보여준다. Overall, Hongjam showed excellent effects on weight gain, muscle strength improvement, muscle weight increase, memory improvement, and muscle decomposition gene suppression effect in sarcopenia models showing severe weight loss and muscle strength abnormalities. These results show that consumption of hongjam can prevent and treat the onset of sarcopenia.
이상 상기 실험결과를 토대로, 견사단백질이 함유된 익힌 누에가공물을 유효성분으로 포함하는 근감소증의 예방 및 치료용 조성물이 제공됨에 따라, 근감소증에 대한 건강기능식품 또는 의약품의 천연물 소재제공이 가능해짐으로 인해 국민건강증진과 보건의료 비용 감소 등에 큰 기여를 할 것으로 기대된다.Based on the above experimental results, as a composition for preventing and treating sarcopenia containing silk protein-containing processed silkworm as an active ingredient is provided, it is possible to provide natural materials for health functional foods or pharmaceuticals for sarcopenia. As a result, it is expected to make a great contribution to improving public health and reducing health care costs.
상기의 본 발명은 바람직한 실시예를 중심으로 살펴보았으며, 본 발명이 속하는 기술분야에서 통상의 지식을 가진 자는 본 발명의 본질적 기술 범위 내에서 상기 본 발명의 상세한 설명과 다른 형태의 실시예들을 구현할 수 있을 것이다. 여기서 본 발명의 본질적 기술범위는 특허청구범위에 나타나 있으며, 그와 동등한 범위 내에 있는 모든 차이점은 본 발명에 포함된 것으로 해석되어야 할 것이다.The present invention has been examined with a focus on preferred embodiments, and those skilled in the art can implement embodiments of a different form from the detailed description of the present invention within the essential technical scope of the present invention. You will be able to. Here, the essential technical scope of the present invention is shown in the claims, and all differences within the equivalent range should be construed as being included in the present invention.
<제제예 1. 약학적 제제><Formulation Example 1. Pharmaceutical formulation>
실시예 1의 견사단백질이 함유된 익힌 누에가공물 분말(홍잠) 200g을 락토오스 175.9g, 감자전분 180g 및 콜로이드성 규산 32g과 혼합하였다. 이 혼합물에 10% 젤라틴 용액을 첨가시킨 후, 분쇄해서 14 메쉬체를 통과시켰다. 이것을 건조시키고 여기에 감자전분 160g, 활석 50g 및 스테아린산 마그네슘 5g을 첨가해서 얻은 혼합물을 정제로 만들었다. 200 g of cooked silkworm product powder (Hongjam) containing silk protein of Example 1 was mixed with 175.9 g of lactose, 180 g of potato starch, and 32 g of colloidal silicic acid. After adding 10% gelatin solution to this mixture, it was pulverized and passed through a 14 mesh sieve. It was dried and the mixture obtained by adding 160 g of potato starch, 50 g of talc and 5 g of magnesium stearate was made into tablets.
<제제예 2. 식품 제조><Formulation Example 2. Food Manufacturing>
제제예 2-1. 조리용 양념의 제조Formulation Example 2-1. Preparation of seasoning for cooking
실시예 1의 견사단백질이 함유된 익힌 누에가공물 분말을 조리용 양념에 1 중량%로 첨가하여 건강 증진용 조리용 양념을 제조하였다.A cooking seasoning for health promotion was prepared by adding 1% by weight of the cooked silkworm product powder containing the silk protein of Example 1 to the cooking seasoning.
제제예 2-2. 밀가루 식품의 제조Formulation example 2-2. Manufacture of Flour Food
실시예 1의 견사단백질이 함유된 익힌 누에가공물 분말을 밀가루에 0.1 중량%로 첨가하고, 이 혼합물을 이용하여 빵, 케이크, 쿠키, 크래커 및 면류를 제조하여 건강 증진용 식품을 제조하였다.The cooked silkworm product powder containing the silk protein of Example 1 was added to wheat flour at 0.1% by weight, and bread, cakes, cookies, crackers, and noodles were prepared using the mixture to prepare health-promoting foods.
제제예 2-3. 스프 및 육즙(gravies)의 제조Formulation Example 2-3. Preparation of soups and gravies
실시예 1의 견사단백질이 함유된 익힌 누에가공물 분말을 스프 및 육즙에 0.1 중량%로 첨가하여 건강 증진용 수프 및 육즙을 제조하였다.The cooked silkworm product powder containing the silk protein of Example 1 was added to the soup and broth in an amount of 0.1% by weight to prepare soup and broth for health promotion.
제제예 2-4. 유제품(dairy products)의 제조Formulation Example 2-4. Manufacture of dairy products
실시예 1의 견사단백질이 함유된 익힌 누에가공물 분말을 우유에 0.1 중량%로 첨가하고, 상기 우유를 이용하여 버터 및 아이스크림과 같은 다양한 유제품을 제조하였다.The cooked silkworm processed product powder containing the silk protein of Example 1 was added to milk in an amount of 0.1% by weight, and various dairy products such as butter and ice cream were prepared using the milk.
제제예 2-5. 야채주스 제조Formulation Example 2-5. vegetable juice manufacturing
실시예 1의 견사단백질을 갖는 누에가공물 분말을 토마토주스 또는 당근주스에 0.5 중량%로 첨가하여 건강증진용 야채주스를 제조하였다.Vegetable juice for health promotion was prepared by adding 0.5% by weight of silkworm processed product powder having silk protein of Example 1 to tomato juice or carrot juice.
제제예 2-6. 과일주스 제조Formulation Example 2-6. fruit juice manufacturing
실시예 1의 견사단백질을 갖는 누에가공물 분말을 사과주스 또는 포도주스 0.1 중량%로 첨가하여 건강 증진용 과일주스를 제조하였다. Fruit juice for health promotion was prepared by adding 0.1% by weight of apple juice or grape juice to silkworm processed powder having silk protein of Example 1.
Claims (14)
A pharmaceutical composition for the prevention or treatment of sarcopenia comprising a silk protein-containing processed silkworm product as an active ingredient.
상기 근감소증은 노인성 근감소증인 것을 특징으로 하는,
근감소증의 예방 또는 치료용 약학적 조성물.
According to claim 1,
Characterized in that the sarcopenia is senile sarcopenia,
A pharmaceutical composition for preventing or treating sarcopenia.
상기 근감소증은 근위축증, 근무력증, 근이영양증, 근경직증, 근긴장저하, 근력약화, 근육퇴행위축, 근위축성 측삭경화증 및 중증 근무력증으로 이루어진 군으로부터 선택된 1종 이상인 것을 특징으로 하는,
근감소증의 예방 또는 치료용 약학적 조성물.
According to claim 1,
Characterized in that the sarcopenia is at least one selected from the group consisting of muscular dystrophy, myasthenia gravis, muscular dystrophy, myasthenia, hypotonia, muscle weakness, muscular dystrophy, amyotrophic lateral sclerosis and myasthenia gravis,
A pharmaceutical composition for preventing or treating sarcopenia.
상기 조성물은, 체중 증가, 근육 무게 증가, 근력 증가, 운동 능력 증진, 자세 조절 능력 증진, 공간기억력 증진, 사회적 기억력 증대 및 근육 분해 유전자의 발현 억제로 구성된 군으로부터 선택되는 1 종 이상의 효과를 나타내는 것을 특징으로 하는,
근감소증의 예방 또는 치료용 약학적 조성물.
According to claim 1,
The composition exhibits one or more effects selected from the group consisting of weight gain, muscle weight increase, muscle strength increase, exercise capacity enhancement, posture control ability enhancement, spatial memory enhancement, social memory enhancement, and muscle degradation gene expression inhibition. characterized by,
A pharmaceutical composition for preventing or treating sarcopenia.
상기 근육 분해 유전자는 마이오스타틴 (Myostatin), 아트로진-1 (Atrogin-1), MuRF1 (Muscle RING-finger protein-1) 및 FoxO3 (Forhead box O3)으로 구성된 군으로부터 선택되는 1 종 이상의 유전자인 것을 특징으로 하는,
근감소증의 예방 또는 치료용 약학적 조성물.
According to claim 4,
The muscle degradation gene is one or more genes selected from the group consisting of Myostatin, Atrogin-1, MuRF1 (Muscle RING-finger protein-1) and FoxO3 (Forhead box O3) characterized in that,
A pharmaceutical composition for preventing or treating sarcopenia.
상기 익힌 누에가공물은 5령4일의 4면잠 누에부터 숙잠기까지의 누에 중에서 선택되는 견사단백질을 갖는 생누에를 55 내지 125℃의 온도에서 30분 내지 24시간 동안 물에 넣어 익히거나 또는 증기의 열로 익혀 제조한 것을 특징으로 하는,
근감소증의 예방 또는 치료용 약학적 조성물.
According to claim 1,
The cooked silkworm product is cooked by putting raw silkworms having silk protein selected from silkworms from 5 instar 4 day silkworms to sleeping silkworms in water for 30 minutes to 24 hours at a temperature of 55 to 125 ° C. Characterized in that it is prepared by cooking with heat,
A pharmaceutical composition for preventing or treating sarcopenia.
상기 익힌 누에가공물은 열풍건조 또는 진공동결건조물인 것을 특징으로 하는,
근감소증의 예방 또는 치료용 약학적 조성물.
According to claim 6,
Characterized in that the cooked silkworm product is hot air dried or vacuum freeze-dried,
A pharmaceutical composition for preventing or treating sarcopenia.
상기 익힌 누에가공물은 물, 탄소수 1 내지 4개의 알코올 또는 이들의 혼합용매로 추출된 추출물인 것을 특징으로 하는,
근감소증의 예방 또는 치료용 약학적 조성물.
According to claim 1,
Characterized in that the cooked silkworm product is an extract extracted with water, alcohol having 1 to 4 carbon atoms or a mixed solvent thereof,
A pharmaceutical composition for preventing or treating sarcopenia.
상기 조성물은 약학적으로 허용되는 담체, 부형제 및 희석제로 이루어진 군으로부터 선택된 1 종 이상을 추가로 포함하는 것을 특징으로 하는,
근감소증의 예방 또는 치료용 약학적 조성물.
According to claim 1,
Characterized in that the composition further comprises at least one selected from the group consisting of pharmaceutically acceptable carriers, excipients and diluents,
A pharmaceutical composition for preventing or treating sarcopenia.
A food composition for preventing or improving sarcopenia, comprising a processed silkworm protein-containing cooked silkworm product.
A health functional food for preventing or improving sarcopenia, including a processed silkworm product containing silk protein.
A feed additive for preventing or improving sarcopenia in animals, comprising a processed silkworm product containing silk protein.
A feed composition for preventing or improving sarcopenia in animals comprising the feed additive of claim 12.
A method for treating sarcopenia comprising the step of administering to a non-human subject a composition comprising a silkworm protein-containing processed silkworm product.
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KR101546446B1 (en) | 2013-06-24 | 2015-08-24 | 대한민국 | Health functional food and cosmetic composition containing silkworm products having silk protein |
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KR101546446B1 (en) | 2013-06-24 | 2015-08-24 | 대한민국 | Health functional food and cosmetic composition containing silkworm products having silk protein |
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