KR20190009717A - Compositions for preventing or treating neuropathy or hearing loss comprising rice bran extract with arabinoxylan - Google Patents
Compositions for preventing or treating neuropathy or hearing loss comprising rice bran extract with arabinoxylan Download PDFInfo
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- KR20190009717A KR20190009717A KR1020180083439A KR20180083439A KR20190009717A KR 20190009717 A KR20190009717 A KR 20190009717A KR 1020180083439 A KR1020180083439 A KR 1020180083439A KR 20180083439 A KR20180083439 A KR 20180083439A KR 20190009717 A KR20190009717 A KR 20190009717A
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- South Korea
- Prior art keywords
- rice bran
- arabinoxylan
- extract
- acid
- present
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Abstract
Description
본 발명은 아라비노자일란 함유 미강 추출물을 포함하는 신경병증 또는 청각손상의 예방 또는 치료용 조성물에 관한 것으로, 구체적으로는 아라비노자일란을 고함량으로 함유하는 미강 추출물의 신경병증 또는 청각손상의 예방 또는 치료 용도에 관한 것이다.The present invention relates to a composition for preventing or treating neuropathy or hearing damage comprising arachinojaylan-containing rice bran extract, and more particularly to a composition for preventing or treating neuropathy or hearing damage of rice bran extract containing a high content of arabinoxylan, Lt; / RTI >
현미, 보리, 밀겨 등에 존재 하는 아라비노자일란(arabinoxylan)은 면역증강, 또는 항암과 같은 생리 활성 효과가 보고되고 있다. 그러나 아라비노자일란(arabinoxylan)은 헤미셀룰로오스(hemicellulose)의 일종으로 아리비노오스와 자일로오스의 중합체로 체내 흡수율이 매우 낮다. 또한 일본과 국내에서 면역 증강 소재로 아라비노자일란 고함량 미강 소재가 개발되어 판매 중이나 일본의 경우 kg당 백만원이 넘는 고가에 수입되고 있다. Arabinoxylan, which is present in brown rice, barley, wheat and the like, has been reported to have physiological activity effects such as immunity enhancement or anti-cancer. However, arabinoxylan is a kind of hemicellulose, which is a polymer of arabinose and xylose, and has a very low absorption rate in the body. In addition, in Japan and the United States, arabinose jilin has been developed and sold as an immunopotentiating material, and in Japan, it is imported at a high price of over one million won per kg.
아라비노자일란은 1986년 여러 식물에서 유래되는 polysaccharide의 한 종류로 식물 세포벽의 주요한 물질 중의 하나로 밝혀졌다. 이후 in vivo와 in vitro 실험을 통해서 면역기능 개선 (Cao, Li, et al., International journal of biological macromolecules 48.1 (2011): 160-164.), 항종양 (Bang, Mai Hong, et al., Anticancer research 30.12 (2010): 5145-5151.), 장내환경 개선 (Mendis, Mihiri, Estelle Leclerc, and Senay Simsek., Carbohydrate polymers 139 (2016): 159-166.), 소화기관 보호효과 (Kamiya, Takeshi, et al., Evidence-Based Complementary and Alternative Medicine 2014), 항비만 (Neyrinck, Audrey M., et al., PloS one 6.6 (2011): e20944.) 등에 효과가 있음을 여러 선행 연구들을 통해 밝혀졌다. Arabidopsis Ilan is a polysaccharide derived from several plants in 1986 and has been identified as one of the major components of plant cell walls. In vivo and in vitro experiments have shown that immune function is improved (Cao, Li, et al., International journal of biological macromolecules 48.1 (2011): 160-164.), Antitumor (Bang, Mai Hong, et al., Anticancer (Mendis, Mihiri, Estelle Leclerc, and Senay Simsek, Carbohydrate polymers 139 (2016): 159-166.), the protective effect of digestive organs (Kamiya, Takeshi, (Neyrinck, Audrey M., et al., PloS one 6.6 (2011): e20944.) were found to be effective in the treatment of hypertension.
그렇기 때문에 아라비노자일란은 항산화제, 면역기능 개선, 항암효과 증진을 위한 건강보조식품으로 사용되고 있다. Therefore, arabinoxylan is used as an antioxidant, a health supplement for improving immune function and anti-cancer effect.
그러나 기존에 신경병증이나 청각 기능 개선을 위한 효능 보고가 되지 않아 본 발명자들은 아라비노자일란 고함량 미강 추출물을 이용하여 신경병증 및 청각 기능 개선을 위한 치료제 및 식품 소재를 개발하고자 예의 노력한 결과, 신경병증 제브라피시 모델에서 뉴로마스트 보호능을 확인하였으며, 이독성 제브라피시 모델에서 청각 유모세포 보호능을 확인하여 본 발명을 완성시켰다.However, the present inventors have tried to develop a therapeutic agent and a food material for improving neuropathy and auditory function using arabinoxylan high-content rice bran extract, and as a result, The neuromast protection ability was confirmed in the zebrafish model, and the ability of protecting the auditory hair cell in the toxic zebrafish model was confirmed, thereby completing the present invention.
본 발명의 하나의 목적은, 아라비노자일란 함유 미강 추출물을 유효성분으로 포함하는, 신경병증 또는 청각 손상의 예방 또는 치료용 약학 조성물을 제공하는 것이다.It is an object of the present invention to provide a pharmaceutical composition for preventing or treating neuropathy or hearing damage comprising an extract of rice bran containing arabinoxylan as an active ingredient.
본 발명의 다른 하나의 목적은 아라비노자일란 함유 미강 추출물을 유효성분으로 포함하는, 신경병증 또는 청각 손상의 예방 또는 개선용 식품 조성물을 제공하는 것이다.It is another object of the present invention to provide a food composition for preventing or ameliorating neuropathy or hearing damage comprising an extract of rice bran containing arabinoxylan as an active ingredient.
상기의 과제를 해결하기 위한 하나의 양태로서, 본 발명은 아라비노자일란 함유 미강 추출물을 유효성분으로 포함하는, 신경병증 또는 청각 손상의 예방 또는 치료용 약학 조성물을 제공한다. As one aspect for solving the above problems, the present invention provides a pharmaceutical composition for preventing or treating neuropathy or hearing damage comprising an extract of rice bran containing arabinoxylan as an active ingredient.
본 발명은, 아라비노자일란 함유 미강 추출물의 신규한 용도를 밝힌 것이다. 구체적으로 본 발명에서는 상기 아라비노자일란 함유 미강 추출물이 신경병증 또는 청각 손상의 예방, 개선 또는 치료 용도를 가짐을 확인하였다.The present invention discloses a novel use of rice bran extract containing arabinoxylan. Specifically, in the present invention, it was confirmed that the extract of rice bran containing arabinoxylan was used for the prevention, amelioration or treatment of neuropathy or hearing damage.
본 발명에서 사용하는 용어, '신경병증'은 말초신경계의 기능적 장애 및 병적 변화를 의미하며, 병리해부적 변화가 확인되는 기질성 질환에 반해, 그와 같은 변화가 확인되지 않는 가능성 질환에 있어서, 특히 심인(心因)의 관여가 확실하다고 생각되는 것에 신경병증을 나타낸다. 예를 들면, 신경성 설사, 신경성 식욕부진 등이 있다.The term " neuropathy " used in the present invention means a functional disorder and a pathological change of the peripheral nervous system. In the case of a potential disease in which such a change is not confirmed, In particular, the involvement of psychosis (psychosis) is thought to be certain to indicate neuropathy. For example, neurogenic diarrhea, anorexia nervosa, and the like.
본 발명의 일실시예에서는 인슐린 과잉으로 인한 인슐린 저항성을 유도하여 말초신경의 기능부진을 통해 신경병증 제브라피시 동물모델을 제조한 후, 신경병증의 증상 중 하나인 뉴로마스트의 감소를 확인하였다. 신경병증 제브라피시 동물모델에 아라비노자일란 함유 미강 추출물을 처리하여 정상군과 비교하여 현저히 감소했던 대조군의 뉴로마스트 수가 미강 추출물 처리군에서는 정상군 수준으로 유의적으로 증가한 것을 확인하여 신경병증에서 아라비노자일란 함유 미강 추출물의 뉴로마스트 보호 효과를 확인하였다 (도 2).In one embodiment of the present invention, a neuropathic zebrafish animal model was produced by inducing insulin resistance due to insulin overload and dysfunction of the peripheral nerves, and then the decrease of neuromast, one of the symptoms of neuropathy, was confirmed. The neuropathic zebrafish animal model treated with rice bran extract containing arabinoxylan significantly increased the number of neuromast in the control group, which was significantly decreased compared with the normal group, to that of the normal group. The neuromast protection effect of the rice bran-containing rice bran extract was confirmed (Fig. 2).
본 발명의 일실시예에서는 네오마이신 노출을 통해 유도한 신경병증 제브라피시 동물모델을 제조한 후, 신경병증의 증상 중 하나인 뉴로마스트의 감소를 확인하였다. 정상군과 비교하여 현저히 감소했던 대조군의 뉴로마스트 수가 미강 추출물 처리군에서는 정상군 수준으로 유의적으로 증가한 것을 확인하여 신경병증에서 아라비노자일란 함유 미강 추출물이 뉴로마스트의 보호 효과를 확인하였다 (도 3).In one embodiment of the present invention, neuropathic zebrafish animal models induced by neomycin exposure were prepared and then decreased neuromast, one of the symptoms of neuropathy. The number of neuromas of the control group significantly decreased compared with the normal group, and it was confirmed that the extract of the rice bran extract containing the arabinoxygenase significantly inhibited the neuropathic effect of neuromast (FIG. 3 ).
본 발명에서 사용하는 용어, '청각 손상'은 와우각 내 수용기의 퇴화나 손상, 와우각 내의 다른 이상, 혹은 청신경의 이상에 의해 청각 기능에 문제가 생기는 것을 의미한다. 구체적으로, 본 발명의 청각 손상은 감각수용기인 청각 유모 세포의 손상을 의미하는 것일 수 있다.The term " auditory damage " used in the present invention means that a problem occurs in auditory function due to degeneration or damage of receptors in the cochlea, other abnormalities in the cochlea, or abnormality of the auditory nerve. Specifically, the hearing impairment of the present invention may be indicative of damage to auditory hair cells, which are sensory receptors.
본 발명의 일실시예에서는 요산의 산화물로서 췌장의 랑게르한스 섬을 파괴하여 인슐린 결핍을 유발하며 청각신경을 포함한 말초신경의 기능부전을 유발하는 알록산을 처리하여 유도한 신경병증 제브라피시 동물모델에서 아라비노자일란 함유 미강 추출물을 처리한 결과, 정상군과 비교하여 현저히 감소했던 대조군의 청각 유모 세포 수가 미강 추출물 처리군에서 유의적으로 증가한 것을 확인하여 신경병증에서 아라비노자일란 고함량 미강 추출물의 청각 유모 세포 보호 효과를 확인하였다 (도 4). 따라서, 상기 청각 손상은 당뇨병성 청각 손상일 수 있으나, 그 유발원인이 이에 제한되지는 않는다.In one embodiment of the present invention, an animal model of neuropathic zebrafish induced by treatment of alloxan, which causes insulin deficiency by destroying the islet of Langerhans pancreas as an oxide of uric acid and induces dysfunction of peripheral nerve including auditory nerve, As a result of treatment with rice bran extract containing Noja Ilan, it was confirmed that the number of auditory hair cells in the control group, which was significantly decreased compared to the normal group, was significantly increased in the rice bran extract treated group. And the protective effect was confirmed (Fig. 4). Thus, the hearing impairment may be a diabetic hearing impairment, but the cause of the hearing impairment is not limited thereto.
본 발명의 일실시예에서는 이독성을 가져 달팽이관, 청신경, 전정기관등의 손상을 유발하는 가나마이신으로 유도한 이독성 제브라피시 동물모델에서 아라비노자일란 고함량 미강 추출물을 처리한 결과, 정상군과 비교하여 현저히 감소했던 대조군의 청각 유모 세포 수가 미강 추출물 처리군에서 유의적으로 증가한 것을 확인하여 이독성에 의한 청각 손상에서 아라비노자일란 고함량 미강 추출물의 청각 유모 세포 보호 효과를 확인하였다 (도 5).In one embodiment of the present invention, in the toxic zebrafish animal model induced by kanamycin which causes damage to the cochlea, auditory nerve, and vestibular system due to the toxicity, the arabinoxylan content of rice bran extracts was high, The number of auditory hair cells in the control group, which was significantly decreased compared to the control group, was significantly increased in the group treated with rice bran extract, thus confirming the protective effect on the auditory hair cells of the extract of rice bran with high content of arabinoxylan .
본 발명에서 상기 아라비노자일란 함유 미강 추출물은 미강으로부터 미강 추출물을 제조함에 있어서 아라비노자일란이 함유되도록 추출된 것이라면 이에 제한되지 않으며, 구체적으로는 아라비노자일란을 고함유하도록 추출된 것일 수 있다. 이에, '아라비노자일란이 증가된 미강 추출물', '아라비노자일란 고함량 미강 추출물' 또는 '아라비노자일란 고함유 미강 추출물'이라는 용어와 혼용될 수 있다.In the present invention, the extract of rice bran containing the arabinoxylan may be one extracted with high arabinoxylan as long as it is extracted so as to contain arabinozylan in the preparation of rice bran extract from rice bran. Thus, it can be used in combination with the terms 'an increased amount of rice bran extract', 'an extract of rice bran with high content of arabinose ylang', or a rice bran extract containing 'arabinose ylang rice'.
상기 아라비노자일란 함유 미강 추출물은, 미강을 포함하는 배지에, 페니실리움 로퀘포르티 (Penicillium roqueforti) 균주를 접종하여 배양하는 단계를 포함하는, 아라비노자일란이 증가된 미강 추출물의 제조 방법에 의해 제조될 수 있다.The Arabidopsis thaliana containing rice bran extract may be added to a medium containing rice bran, , And culturing the strain by inoculating a strain of Penicillium roqueforti , wherein the arabinozoyllan is increased.
본 발명에서, '미강'은 쌀의 도정과정에서 쌀겨를 제거하여 생산되는 현미의 외피 부분을 의미한다. 곡류의 외피는 일반적으로 브랜층(bran layer)를 주성분으로 하고, 때론 생산과정에서 씨눈(germ)이 포함되기도 한다.In the present invention, 'rice bran' refers to the outer portion of brown rice produced by removing rice bran during the rice ripening process. Grain clusters are generally based on the bran layer and sometimes contain germs during the production process.
본 발명에서, '아라비노자일란'은 생리활성물질 중 하나로, 헤미셀룰로오스(hemicellulose)를 분해하여 만든 아라비노오스(arabinose)와 자일로오스(xylose)로 구성되어 있다. 자일로오스를 주쇄로하여 측쇄에 아라비노오스를 갖는 아라비노자일란은 자일로스가 알파-(1-4)결합으로 이루어진 중합체에 5탄당인 아라비노오스가 부분적으로 결합되어있는 구조이다.In the present invention, 'arabinozaylan' is one of the physiologically active substances and is composed of arabinose and xylose which are formed by decomposing hemicellulose. Arabinosaylan having arabinose in its side chain with xylose as a main chain is a structure in which arabinose, a pentabody, is partially bound to a polymer composed of xylose with an alpha - (1-4) bond.
본 발명에서, 상기 미강으로부터 미강 추출물을 제조함에 있어서, 아라비노자일란의 함량을 증가시키기 위하여 페니실리움 로퀘포르티 (Penicillium roqueforti) 균주를 이용하였다. 구체적으로, 시료인 미강을 포함하는 배지에, 페니실리움 로퀘포르티 (Penicillium roqueforti) 균주를 접종하여 배양하는 단계를 수행하여 생물전환(bioconversion)시킴으로써, 아라비노자일란이 고함량으로 포함되도록 할 수 있다.In the present invention, in order to increase the content of arabinoxylan in the preparation of rice bran extract from rice bran, ( Penicillium roqueforti ) strains were used. Specifically, in a medium containing a sample of rice bran, ( Penicillium roqueforti ) is inoculated and cultured to perform bioconversion, so that arabinozylan is contained in a high content.
본 발명의 제조방법에 의해 제조된 미강 추출물은, 균주를 접종하지 않고 제조된 미강 추출물에 비해 아라비노자일란의 함량이 증가된 것일 수 있다. 또한, 비교 균주인 플루로터스 오스트레투스(Pleurotus ostreatus) 또는 아스퍼질러스 오리재 (Aspergillus oryzae) 균주를 접종한 경우보다도 아라비노자일란의 함량이 증가된 것일 수 있다.The extract of rice bran produced by the production method of the present invention may have an increase in the content of arabinoxylan compared to the rice bran extract prepared without inoculating the strain. In addition, the content of arabinoxylan may be increased compared with the case of inoculation with the comparative strain Pleurotus ostreatus or Aspergillus oryzae strain.
이 때, 아라비노자일란의 함량은 2% 이상일 수 있으며, 구체적으로는 2.5% 이상, 더욱 구체적으로는 2.9% 이상일 수 있다. 이 때, 아라비노오스의 함량은 1% 이상일 수 있으며, 구체적으로는 1.3% 이상, 더욱 구체적으로는 1.5% 이상일 수 있다. 또한, 자일로오스의 함량은 1% 이상일 수 있으며, 구체적으로는 1.5% 이상, 더욱 구체적으로는 1.8% 이상일 수 있다.At this time, the content of arabinoxylan may be 2% or more, specifically 2.5% or more, more specifically 2.9% or more. At this time, the content of arabinose may be 1% or more, specifically 1.3% or more, more specifically 1.5% or more. The content of xylose may be 1% or more, specifically 1.5% or more, more specifically 1.8% or more.
본 발명에서, 상기 배양시 산(acid)을 첨가하여 가수분해시키는 단계를 추가로 포함할 수 있다. 또한, 상기 산의 첨가 후 가수분해를 위하여 가열하는 단계를 추가로 포함할 수 있다. 상기 가열하는 단계에 있어서, 가열 후 반응물을 냉각하는 단계를 추가로 포함할 수 있다.In the present invention, it is possible to further include a step of adding an acid during the culturing to hydrolysis. Further, it may further include a step of heating for hydrolysis after addition of the acid. The step of heating may further include cooling the reaction product after heating.
상기 산은 강산을 사용할 수 있으며, 구체적으로는 염산을 사용할 수 있다. 상기 염산의 농도는 이에 제한되지는 않으나, 구체적으로는 5% 내지 10% 가 바람직하며, 보다 구체적으로는 5% 염산일 수 있다.The acid may be a strong acid, specifically hydrochloric acid. The concentration of the hydrochloric acid is not particularly limited, but is preferably 5% to 10%, more specifically 5% hydrochloric acid.
본 발명에서, 미강 추출물을 제조하는 과정에서 페니실리움 로퀘포르티 균주를 접종하기 위한 배지는, 미강으로부터 아라비노자일란 함량이 증가된 미강 추출물을 제조하기 위한 본 발명의 목적을 달성할 수 있는 한 제한되지 않으며, 당업계에 공지된 모든 배지를 사용할 수 있다. 구체적으로, 본 발명의 미강을 생물전환 시키는 단계에서 배지는 감자 추출 배지(PDB)를 사용하는 것일 수 있으며, 배양은 20℃ 내지 30℃, 구체적으로 22℃ 내지 26℃, 더욱 구체적으로 24℃의 교반 배양기에서 3일 내지 5일, 구체적으로 4일 내지 5일, 더욱 구체적으로 4일간 배양하는 것일 수 있다.In the present invention, the medium for inoculating the strain of Penicillium roqueforti in the process of producing the rice bran extract is as long as it can achieve the object of the present invention for producing the rice bran extract with increased content of arabinoxylan from rice bran Any culture medium known in the art may be used without limitation. Specifically, in the step of biotransformation of rice bran of the present invention, the medium may be a potato extract medium (PDB), and the culture may be carried out at a temperature of 20 ° C to 30 ° C, specifically 22 ° C to 26 ° C, For 3 days to 5 days, more specifically for 4 days to 5 days, more specifically for 4 days in an agitation incubator.
한편, 미강 추출물을 제조하기 위한 최종 단계로서, 산 첨가에 의해 산성화된 배지의 중화를 위하여 알칼리 용액을 첨가하는 단계를 추가로 포함할 수 있다. 상기 알칼리 용액은 수산화나트륨, 수산화칼륨, 탄산나트륨, 탄산칼륨일 수 있고, 구체적으로는 수산화나트륨일 수 있으나 이에 제한되지 않는다.On the other hand, as a final step for preparing the rice bran extract, it may further include adding an alkali solution for neutralization of the acidified medium by adding the acid. The alkali solution may be sodium hydroxide, potassium hydroxide, sodium carbonate or potassium carbonate, and may be sodium hydroxide, but is not limited thereto.
상기 중화 단계에 의해 pH를 6 내지 7, 구체적으로는 6.5 내지 6.8로 맞춰줄 수 있다.By the neutralization step, the pH can be adjusted to 6 to 7, specifically 6.5 to 6.8.
상기와 같은 제조 방법을 통해 아라비노자일란을 고함량으로 함유하는 미강 추출물을 제조하는 경우에, 아라비노자일란의 유용성으로 인해 생체이용성 역시 높아질 수 있으며, 그에 따라 본 발명의 최종 목적인 신경병증 또는 청각 손상 예방 및 치료에 더욱 유용하게 사용할 수 있다.In the case of producing a rice bran extract containing a high content of arabinoxylan by the above-described production method, the bioavailability can be increased due to the availability of arabinoxylan, and accordingly, the end result of the present invention, It can be used more effectively for prevention and treatment.
본 발명에서 사용되는 용어, "예방"이란, 본 발명에 따른 아라비노자일란 고함량 미강 추출물을 개체에 투여하여 신경병증 또는 청각 손상의 발병을 억제하거나 지연시키는 모든 행위를 의미할 수 있다. As used herein, the term " prevention " may refer to any action that inhibits or delays the onset of neuropathic or auditory damage by administering an arabinoxylan-rich rice bran extract of the present invention to an individual.
본 발명에서 사용되는 용어, "치료"란, 본 발명의 상기 조성물을 신경병증 또는 청각 손상 발병 의심 개체에 투여하여 신경병증 또는 청각 손상의 증세가 호전되도록 하거나 이롭게 되도록 하는 모든 행위를 의미할 수 있다.The term " treatment ", as used herein, may refer to any action that causes the symptoms of neuropathy or hearing impairment to be improved or benefited by administering the composition of the invention to a suspected neuropathy or hearing impaired subject .
본 발명의 약학 조성물은 단일제제로도 사용할 수 있고, 공인된 신경병증 또는 청각 손상 치료 효과를 가진다고 알려진 약물을 추가로 포함하여 복합제제로 제조하여 사용할 수 있으며, 약제학적으로 허용되는 담체 또는 부형제를 이용하여 제제화함으로써 단위 용량 형태로 제조되거나 다용량 용기 내에 내입시켜 제조될 수 있다. The pharmaceutical composition of the present invention can be used as a single preparation and can be used as a combined preparation containing a drug known to have an effect of treating a recognized neuropathy or hearing damage and can be prepared using a pharmaceutically acceptable carrier or excipient Or may be manufactured in unit dosage form by injection molding or intruding into a multi-dose container.
본 발명에서 사용되는 용어, "약학적으로 허용 가능한 담체"란 생물체를 자극하지 않으면서, 주입되는 화합물의 생물학적 활성 및 특성을 저해하지 않는 담체 또는 희석제를 의미할 수 있다. 본 발명에 사용 가능한 상기 담체의 종류는 특별히 제한되지 아니하며 당해 기술 분야에서 통상적으로 사용되고 약학적으로 허용되는 담체라면 어느 것이든 사용할 수 있다. 상기 담체의 비제한적인 예로는, 식염수, 멸균수, 링거액, 완충 식염수, 알부민 주사 용액, 덱스트로즈 용액, 말토 덱스트린 용액, 글리세롤, 에탄올 등을 들 수 있다. 이들은 단독으로 사용되거나 2 종 이상을 혼합하여 사용될 수 있다. 상기 담체는 비자연적 담체 (non-naturally occuring carrier)를 포함할 수 있다.As used herein, the term " pharmaceutically acceptable carrier " may mean a carrier or diluent that does not disturb the biological activity and properties of the compound being injected, without irritating the organism. The type of the carrier that can be used in the present invention is not particularly limited, and any carrier conventionally used in the art and pharmaceutically acceptable may be used. Non-limiting examples of the carrier include saline, sterilized water, Ringer's solution, buffered saline, albumin injection solution, dextrose solution, maltodextrin solution, glycerol, ethanol and the like. These may be used alone or in combination of two or more. The carrier may comprise a non-naturally occuring carrier.
또한, 필요한 경우 항산화제, 완충액 및/또는 정균제 등 다른 통상의 첨가제를 첨가하여 사용할 수 있으며, 희석제, 분산제, 계면 활성제, 결합제, 윤활제 등을 부가적으로 첨가하여 수용액, 현탁액, 유탁액 등과 같은 주사용 제형, 환약, 캡슐, 과립 또는 정제 등으로 제제화하여 사용할 수 있다.In addition, if necessary, other conventional additives such as an antioxidant, a buffer and / or a bacteriostatic agent can be added and used. A diluent, a dispersant, a surfactant, a binder, a lubricant, Pills, capsules, granules or tablets, and the like.
또한, 본 발명의 약학적 조성물은 약제학적으로 유효한 양의 아라비노자일란 고함량 미강 추출물을 포함할 수 있다. 본 발명에서 용어, "약제학적으로 유효한 양"은 의학적 치료에 적용 가능한 합리적인 수혜/위험 비율로 질환을 치료하기에 충분한 양을 의미하며, 일반적으로 0.001 내지 1000 mg/kg의 양, 바람직하게는 0.05 내지 200 mg/kg, 보다 바람직하게는 0.1 내지 100 mg/kg의 양을 일일 1회 내지 수회로 나누어 투여할 수 있다. 그러나 본 발명의 목적상, 특정 환자에 대한 구체적인 치료적 유효량은 달성하고자 하는 반응의 종류와 정도, 경우에 따라 다른 제제가 사용되는지의 여부를 비롯한 구체적 조성물, 환자의 연령, 체중, 일반 건강 상태, 성별 및 식이, 투여 시간, 투여 경로 및 조성물의 분비율, 치료기간, 구체적 조성물과 함께 사용되거나 동시 사용되는 약물을 비롯한 다양한 인자와 의약 분야에 잘 알려진 유사 인자에 따라 다르게 적용하는 것이 바람직하다. In addition, the pharmaceutical composition of the present invention may contain a pharmaceutically effective amount of arabinoxylan high content of rice bran extract. The term " pharmaceutically effective amount " as used herein means an amount sufficient to treat a disease at a reasonable benefit / risk ratio applicable to medical treatment and is generally in the range of 0.001 to 1000 mg / kg, preferably 0.05 To 200 mg / kg, more preferably 0.1 to 100 mg / kg, may be administered once a day to several times per day. For purposes of the present invention, however, the specific therapeutically effective amount for a particular patient will depend upon the nature and extent of the reaction to be achieved, the particular composition, including whether or not other agents are used, the age, weight, Sex and diet of the patient, the time of administration, the route of administration and the rate of administration of the composition, the duration of the treatment, the drugs used or concurrently used with the specific composition, and similar factors well known in the medical arts.
본 발명의 약학적 조성물은 개별 치료제로 투여하거나 다른 치료제와 병용하여 투여될 수 있고 종래의 치료제와는 순차적 또는 동시에 투여할 수 있다. 그리고 단일 또는 다중 투여될 수 있다. 상기 요소를 모두 고려하여 부작용을 유발하지 않으면서 최소한의 양으로 최대 효과를 얻을 수 있는 양을 투여하는 것이 중요하며, 당업자에 의해 용이하게 결정될 수 있다.The pharmaceutical composition of the present invention may be administered as an individual therapeutic agent or in combination with another therapeutic agent, and may be administered sequentially or simultaneously with conventional therapeutic agents. And can be administered singly or multiply. It is important to take into account all of the above factors and to administer an amount that can achieve the maximum effect in a minimal amount without causing side effects, and can be readily determined by those skilled in the art.
본 발명에서 사용된 용어, "투여"는 어떠한 적절한 방법으로 환자에게 본 발명의 약학적 조성물을 도입하는 것을 의미하며, 본 발명의 조성물의 투여 경로는 목적 조직에 도달할 수 있는 한 경구 또는 비경구의 다양한 경로를 통하여 투여될 수 있다.The term " administering " as used herein refers to the introduction of a pharmaceutical composition of the present invention to a patient by any suitable method, and the route of administration of the composition of the present invention may be oral or parenteral May be administered via various routes.
본 발명에 따른 약학 조성물의 투여 방식은 특별히 제한되지 아니하며, 당해 기술 분야에서 통상적으로 사용하는 방식에 따를 수 있다. 상기 투여 방식의 비제한적인 예로, 조성물을 경구 투여 또는 비경구 투여 방식으로 투여할 수 있다. 본 발명에 따른 약학 조성물은 목적하는 투여 방식에 따라 다양한 제형으로 제작될 수 있다. The mode of administration of the pharmaceutical composition according to the present invention is not particularly limited and may be conventionally used in the art. As a non-limiting example of such a mode of administration, the compositions may be administered orally or parenterally. The pharmaceutical composition according to the present invention can be manufactured into various formulations according to the intended administration mode.
본 발명의 조성물의 투여빈도는 특별히 이에 제한되지 않으나, 1일 1회 투여하거나 또는 용량을 분할하여 수회 투여할 수 있다.The frequency of administration of the composition of the present invention is not particularly limited, but it may be administered once a day or divided into several doses.
본 발명에서 사용된 용어, '약학적으로 허용가능한 염'이란 투여되는 아라비노자일란 고함량 미강 추출물의 생물학적 활성과 물성들을 손상시키지 않는 제형을 의미한다. 상기 약학적으로 허용가능한 염은, 약학적으로 허용되는 음이온을 함유하는 무독성 산부가염을 형성하는 산, 예를 들어, 염산, 황산, 질산, 인산, 브롬화수소산, 요드화수소산 등과 같은 무기산, 타타르산, 포름산, 시트르산, 아세트산, 트리클로로아세트산, 트리플로로아세트산, 글루콘산, 벤조산, 락트산, 푸마르산, 말레인산, 살리신산 등과 같은 유기 카본산, 메탄설폰산, 에탄술폰산, 벤젠설폰산, p-톨루엔설폰산 등과 같은 설폰산 등에 의해 형성된 산부가염이 포함된다. 예를 들어, 약학적으로 허용되는 카르복실산 염에는, 리튬, 나트륨, 칼륨, 칼슘, 마그네슘 등에 의해 형성된 금속염 또는 알칼리 토금속 염, 라이신, 아르지닌, 구아니딘 등의 아미노산 염, 디시클로헥실아민, N-메틸-D-글루카민, 트리스(히드록시메틸)메틸아민, 디에탄올아민, 콜린 및 트리에틸아민 등과 같은 유기염 등이 포함된다.The term " pharmaceutically acceptable salt " as used herein means a formulation which does not impair the biological activity and properties of the arabinozoyl high-dose rice bran extract. The pharmaceutically acceptable salts include those acids which form a non-toxic acid addition salt containing a pharmaceutically acceptable anion such as inorganic acids such as hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, hydrobromic acid, hydroiodic acid and the like, Organic carboxylic acids such as formic acid, citric acid, acetic acid, trichloroacetic acid, trifluoroacetic acid, gluconic acid, benzoic acid, lactic acid, fumaric acid, maleic acid and salicinic acid, methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, p- Sulfonic acid such as sulfonic acid, sulfonic acid, sulfonic acid, and the like. For example, pharmaceutically acceptable carboxylic acid salts include metal salts or alkaline earth metal salts formed with lithium, sodium, potassium, calcium, magnesium and the like, amino acid salts such as lysine, arginine and guanidine, dicyclohexylamine, N Organic salts such as methyl-D-glucamine, tris (hydroxymethyl) methylamine, diethanolamine, choline and triethylamine, and the like.
다른 하나의 양태로서, 본 발명은 아라비노자일란 함유 미강 추출물을 유효성분으로 포함하는, 신경병증 또는 청각 손상의 예방 또는 개선용 식품 조성물을 제공한다.In another aspect, the present invention provides a food composition for preventing or ameliorating neuropathy or hearing damage comprising an extract of rice bran containing arabinoxylan as an active ingredient.
상기 "아라비노자일란 함유 미강 추출물", "신경병증"및 "청각 손상"에 관해서는, 전술한 바와 같다.The above-mentioned " arabinose-containing rice bran extracts ", " neuropathy ", and " hearing damage "
본 발명의 상기 식품 조성물을 식품 첨가물로 사용할 경우, 상기 조성물을 그대로 첨가하거나 다른 식품 또는 식품 성분과 함께 사용될 수 있고, 통상적인 방법에 따라 적절하게 사용될 수 있다.When the food composition of the present invention is used as a food additive, the composition can be added as it is, or can be used together with other food or food ingredients, and can be suitably used according to a conventional method.
구체적으로, 상기 식품 조성물은 육류, 소세지, 빵, 쵸코렛, 캔디류, 스넥류, 과자류, 피자, 라면, 껌류, 아이스크림류, 스프, 음료수, 차, 기능수, 드링크제, 알콜 음료 및 비타민 복합제 중 어느 하나의 형태일 수 있다.Specifically, the food composition may be any one of meat, sausage, bread, chocolate, candy, snack, confectionery, pizza, ramen, gum, ice cream, soup, beverage, tea, functional water, Lt; / RTI >
또한, 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 있으며, 그 밖에 천연 과일주스 및 과일주스 음료 및 야채음료의 제조를 위한 과육을 함유할 수 있다. 이들은 단독으로 사용되거나 2종 이상 혼합되어 사용될 수 있다.It is also possible to use a variety of nutrients, vitamins, minerals (electrolytes), flavors such as synthetic flavors and natural flavors, colorants and heavies (cheese, chocolate, etc.), pectic acid and its salts, alginic acid and its salts, The composition may contain a colloidal thickener, a pH adjusting agent, a stabilizer, a preservative, a glycerin, an alcohol, a carbonating agent used in a carbonated beverage, and the like, as well as flesh for the production of natural fruit juice and fruit juice drinks and vegetable drinks . These may be used alone or in combination of two or more.
상기 식품 조성물은 식품첨가물을 추가로 포함할 수 있으며, "식품첨가물"로서의 적합 여부는 다른 규정이 없는 한 식품의약품안정처에 승인된 식품첨가물공전의 총칙 및 일반시험법 등에 따라 해당 품목에 관한 규격 및 기준에 의해 판정한다.The above food composition may further contain food additives, and whether or not the food additive is suitable as a "food additive" includes, unless otherwise specified, the standard for the relevant item in accordance with the general provisions of the Food Additives Ordinance approved by the Food and Drug Administration, And criteria.
상기 "식품첨가물공전"에 수재된 품목으로 예를 들어, 케톤류, 글리신, 구연산칼륨, 니코틴산, 계피산 등의 화학적 합성품, 감색소, 감초추출물, 결정셀롤로오스, 고랭색소, 구아검 등의 천연첨가물, L-글루타민산나트륨제제, 면류첨가알칼리제, 보존료제제, 타르색소제제 등의 혼합 제제류들을 들 수 있다.Examples of the products listed in the above-mentioned "food additives" include natural products such as ketones, chemical products such as glycine, potassium citrate, nicotinic acid and cinnamic acid, coloring matter, licorice extract, crystalline cellulosic, high- , A sodium L-glutamate preparation, a noodle-added alkaline agent, a preservative preparation, a tar coloring agent, and the like.
이때, 상기 식품 조성물을 제조하는 과정에서 음료를 포함한 식품에 첨가되는 본 발명에 따른 혼합 추출물 또는 그의 분획물은 필요에 따라 그 함량을 적절히 가감할 수 있으며, 구체적으로 식품 100 중량%에 0.01 내지 10 중량% 포함되도록 첨가할 수 있지만, 이에 제한되는 것은 아니다.At this time, the content of the mixed extract or the fraction thereof according to the present invention, which is added to the food including the beverage in the course of preparing the food composition, can be appropriately increased or decreased, and specifically 0.01 to 10 wt% %, But the present invention is not limited thereto.
본 발명의 식품 조성물은 건강기능식품으로서 사용될 수 있다. 상기 "건강기능식품"이라 함은 건강기능식품에 관한 법률 제6727호에 따른 인체에 유용한 기능성을 가진 원료나 성분을 사용하여 제조 및 가공한 식품을 의미하며, "기능성"이라 함은 인체의 구조 및 기능에 대하여 영양소를 조절하거나 생리학적 작용 등과 같은 보건 용도에 유용한 효과를 얻을 목적으로 섭취하는 것을 의미한다.The food composition of the present invention can be used as a health functional food. The term "functional food" as used herein means a food prepared and processed using a raw material or ingredient having a useful function in the human body pursuant to Law No. 6727 on Health Functional Foods, and the term "functional" And function of the nutrient for the purpose of obtaining a beneficial effect in health use such as controlling the nutrient or physiological action.
본 발명의 식품 조성물은 통상의 식품 첨가물을 포함할 수 있으며, 상기 "식품 첨가물"로서의 적합 여부는 다른 규정이 없는 한, 식품의약품안정청에 승인된 식품 첨가물 공전의 총칙 및 일반시험법 등에 따라 해당 품목에 관한 규격 및 기준에 의하여 판정한다.The food composition of the present invention may contain conventional food additives. Unless otherwise specified, the suitability of the food additives for the above-mentioned " food additives " Of the present invention.
본 발명의 식품 조성물은 면역 기능 증진을 목적으로, 조성물 총 중량에 대하여 아라비노자일란 고함량 미강 추출물을 0.01 내지 95 중량%, 바람직하게는 1 내지 80 중량% 로 포함할 수 있다. 본 발명의 식품 조성물에 함유되는 아라비노자일란 고함량 미강 추출물은 상기 약학 조성물의 제조에서 언급된 추출방법과 동일한 방법으로 얻어질 수 있다.The food composition of the present invention may contain 0.01 to 95% by weight, preferably 1 to 80% by weight of arabinoxylan high-content rice bran extract, based on the total weight of the composition, for the purpose of improving the immune function. The arabinoxylan high content rice bran extract contained in the food composition of the present invention can be obtained in the same manner as the extraction method mentioned in the production of the above pharmaceutical composition.
또한, 본 발명의 식품 조성물은 면역 기능 증진을 목적으로, 통상 제조 가능한 정제, 캅셀, 분말, 과립, 액상, 환 등의 형태로 제조 및 가공할 수 있다.In addition, the food composition of the present invention can be manufactured and processed in the form of tablets, capsules, powders, granules, liquids, and circles which can be usually prepared for the purpose of enhancing the immune function.
상기 부형제, 희석제, 결합제, 붕해제 등에 대한 용어 정의는 당업계에 공지된 문헌에 기재된 것으로 그 기능 등이 동일 내지 유사한 것들을 포함한다 (대한약전 해설편, 문성사, 한국약학대학협의회, 제 5 개정판, p33-48, 1989).The definitions of the above excipients, diluents, binders, disintegrators, etc. are described in documents known in the art and include the same or similar functions (refer to Korean Pharmacopoeia, Moon Sung, Korean Pharmacological Association, , p. 33-48, 1989).
본 발명에 따른 조성물은 신경병증의 증상들을 개선할 수 있다. 또한, 본 발명에 따른 이독성 약물에 의한 청각 손상의 증상들을 개선할 수 있다. 따라서, 본 발명에 따른 조성물은 신경병증 및 청각 손상의 예방 또는 치료에 유용하게 사용될 수 있다.The composition according to the present invention can improve the symptoms of neuropathy. In addition, the symptoms of hearing damage caused by this toxic drug according to the present invention can be improved. Therefore, the composition according to the present invention can be usefully used for the prevention or treatment of neuropathy and auditory damage.
도 1은 미강추출물과 아라비노자일란이 증가된 미강 추출물의 함량과 크로마토그램을 나타낸다.
도 2는 인슐린저항성으로 유발한 신경병증 제브라피시 모델에서 아라비노자일란 고함량 미강 추출물의 뉴로마스트 보호 효과를 나타낸다.
도 3은 네오마이신으로 유발한 신경병증 제브라피시 모델에서 아라비노자일란 고함량 미강 추출물의 뉴로마스트 보호 효과를 나타낸다.
도 4는 알록산으로 유발한 이독성 제브라피시 모델에서 아라비노자일란 고함량 미강 추출물의 청각 유모 세포 보호 효과를 나타낸다.
도 5는 가나마이신으로 유발한 이독성 제브라피시 모델에서 아라비노자일란 고함량 미강 추출물의 청각 유모 세포 보호 효과를 나타낸다.Fig. 1 shows the contents and chromatograms of bovine corn extract and arabinofuranosyl increased bovine extract.
FIG. 2 shows the neuromost protection effect of the extract of rice bran with high content of arabinofoiane in a neuropathic zebrafish model induced by insulin resistance.
Fig. 3 shows the neuromast protection effect of arabinoxylan high-content rice bran extract in neomycin-induced neuropathic zebrafish model.
Fig. 4 shows the protective effect of arabinoxylan high-content rice bran extracts on auditory hair cells in this toxic zebrafish model induced by alloxan.
FIG. 5 shows the protective effect of arabinoxylan high-content rice bran extracts on auditory hair cells in this toxic zebrafish model induced by kanamycin.
이하, 본 발명을 실시예를 통하여 더욱 상세히 설명한다. 그러나 이들 실시예는 본 발명을 예시하기 위한 것으로, 본 발명의 범위가 이들 실시예에 한정되는 것은 아니다.Hereinafter, the present invention will be described in more detail with reference to examples. However, these examples are for illustrating the present invention, and the scope of the present invention is not limited to these examples.
실시예 1. 아라비노자일란 함유 미강 추출물 제조 방법의 확립Example 1 Establishment of a method for producing rice bran extract containing arabinoxylan
1-1. 아라비노자일란 함유 미강 추출물의 제조를 위한 미강 원시료의 산 가수분해 공정1-1. Acid hydrolysis of rice bran samples for the production of rice bran extract containing arabinoxylan
미강을 mash NO.7, 10, 20의 3개의 채로 층을 분리 한 후, mash NO.10에서 분리된 미강을 시료로 사용하였다. 미강 1g씩 코니칼 튜브(conical tube)에 투입 한 후, 표 1에 개시된 것과 같은 구성의 산 가수 용액 (25, 50, 75% 아세트산, 5, 10, 20% 염산)을 50 ml 각각 첨가하고 수조 (Water bath)에서 3시간 동안 아세트산의 경우 98℃, 염산의 경우 90℃로 가열하였다. 가열 후 상온에서 식히고 상층액을 분리하였다. 상층액 여과 후 1.4 N 수산화나트륨을 이용하여 pH를 6.5-6.8로 조절하고, 50℃에서 농축하였다.Rice bran was separated into three layers of mash NO.7, 10 and 20, and then rice bran extracted from mash NO.10 was used as a sample. 50 ml of acetic acid solution (25, 50, 75% acetic acid, 5, 10, 20% hydrochloric acid) having the same composition as that shown in Table 1 was added to each conical tube (Water bath) for 3 hours at 98 占 폚 for acetic acid and 90 占 폚 for hydrochloric acid. After heating, it was cooled at room temperature and the supernatant was separated. The supernatant was filtered, adjusted to pH 6.5-6.8 with 1.4 N sodium hydroxide, and concentrated at 50 < 0 > C.
이후 농축된 6종류의 추출물에 대해 고성능액체크로마토그래피(HPLC, Shimadzu LC-20A HPLC instrument, Shimadzu, Japan)를 이용하여 아라비노자일란의 함량을 분석하였다. 컬럼은 역상 컬럼 (Shimadzu VP-ODS, 250L x 4.6, 5㎛), 검출기는 UV 디텍터 (245 nm)를 사용하였다. 이동상은 인산나트륨 완충액(40mM) 79% 와 아세토나이트릴 21%를 사용하였고 유속은 0.7 ml/min로 하였다. 실험에 사용한 아라비노스와 자일로스 표준품은 유도체 1-페닐-3-메틸-5-피라졸론(PMP)를 이용하여 분석에 사용하였다. 표준품 1 mg씩 정량하여 물에 용해시켜 100 ul를 취한 후에 0.3 M NaOH와 0.5 M PMP를 각각 100 ul씩 더하였다. 혼합액은 70 ℃에서 30분간 반응시키고, 식힌 후에 0.3 M HCl 100 ul를 넣어 반응을 정지시켰다. 클로로포름 200 ul를 넣고 섞어 원심분리 한 후에 상층액 100 ul만 취하였고 이를 2번 더 반복하였다. 0.22 um 멤브레인으로 여과 후에 표준품 및 10 ul씩 주입하여 분석실험을 실시하였고, 아라비노스 및 자일로스의 함량을 토대로 아라비노자일란의 함량을 분석하였다 (Zheng, X., Li, L., & Wang, X. (2011). Molecules, 16(4), 2743-2753.).Subsequently, the content of arabinoselanamine was analyzed by high performance liquid chromatography (HPLC, Shimadzu LC-20A HPLC instrument, Shimadzu, Japan) for the six concentrated extracts. The column used was a reversed-phase column (Shimadzu VP-ODS, 250 L x 4.6, 5 μm) and a UV detector (245 nm) as the detector. The mobile phase used was 79% sodium phosphate buffer (40 mM) and 21% acetonitrile and the flow rate was 0.7 ml / min. The arabinose and xylose standards used in the experiments were used for the analysis using the derivative 1-phenyl-3-methyl-5-pyrazolone (PMP). 1 mg of each standard product was dissolved in water, and 100 μl of the solution was added. Then, 100 μl each of 0.3 M NaOH and 0.5 M PMP was added. The mixture was reacted at 70 ° C for 30 minutes, cooled, and then 100 μl of 0.3 M HCl was added to stop the reaction. 200 μl of chloroform was added, and the mixture was centrifuged. Then, 100 μl of the supernatant was collected, and this was repeated two more times. After filtration with 0.22 μm membrane, standard products and 10 μl of each sample were injected. The contents of arabinose and yilos were analyzed based on the contents of arabinose and xylose (Zheng, X., Li, L., & Wang, X. (2011) Molecules, 16 (4), 2743-2753.).
그 결과, 표 2에 나타난 바와 같이, 5% 및 10%의 농도를 가지는 염산 조건에서 아라비노스와 자일로스의 함량이 높게 나타난 것을 확인하였으며, 그 중에서도 5%의 염산이 가장 높은 함량을 나타낸바, 이후의 실험에서는 5% 염산을 최적의 산 가수 용액으로 사용하였다.As a result, as shown in Table 2, it was confirmed that the content of arabinose and xylose was high in hydrochloric acid having a concentration of 5% and 10%, and 5% hydrochloric acid showed the highest content, In the subsequent experiments, 5% hydrochloric acid was used as the optimum acidic solution.
atotal arabinoxylan= 0.88*(% arabinose + % xylose) a total arabinoxylan = 0.88 * (% arabinose +% xylose)
1-2. 아라비노자일란이 증가된 미강 추출물의 제조를 위한 미강 생물전환 공정1-2. Rice Biotransformation Process for the Production of Rice Bran Extract with Increased Arabidopsis
미강을 mash NO.7, 10, 20의 3개의 채로 층을 분리 한 후, mash NO.10에서 분리된 미강을 시료로 사용하였다. 미강 10 g을 250ml 삼각 플라스크에 넣고, 감자 추출 배지(PDB) 20 ml를 넣고 고압증기멸균기(autoclave)를 이용해 멸균 하였다. 완성된 미강 배지를 상온에서 충분히 식힌 후에 배양해놓은 100∮ 페트리 접시의 균주 플루로터스 오스트레투스 (Pleurotus ostreatus, 16855), 페니실리움 로퀘포르티 (Penicillium roqueforti, 11269) 및 아스퍼질러스 오리재 (Aspergillus oryzae, 11896) 3종을 각각 분산시켰다 (표 3). 교반 배양기(24℃)에서 4일간 배양하고, 표면이 완전하게 균주로 차면, 염산(5%) 20 ml를 넣고 수조(Water bath) 100℃에 넣고 6시간 가열시킨다. 상온에서 충분하게 식힌 후, 수산화나트륨(1.4N)를 20 ml 넣어 중화하고 pH를 6.5 내지 6.8로 맞춰 준 후, 여과하였다. 고형분을 페트리 접시에 옮긴 후 건조기(55℃)에서 건조하였다. 액상부분은 적절히 농축 후 페트리 접시의 고체 배지에 잘 뿌려서 건조시켰다. 건조된 추출물은 막자 사발을 이용하여 곱게 간 후, 무게를 측정하여 수율을 구하고 -20℃에 보관하였다. 건조된 추출물은 실시예 1에 개시한 HPLC 측정법을 이용해 아라비노자일란을 함량을 분석하였다. Rice bran was separated into three layers of mash NO.7, 10 and 20, and then rice bran extracted from mash NO.10 was used as a sample. 10 g of rice bran was placed in a 250 ml Erlenmeyer flask, and 20 ml of potato extract medium (PDB) was added thereto and sterilized by autoclave using a high pressure steam sterilizer. The finished rice bran culture broth was sufficiently cooled at room temperature and then cultured. The culture of 100 占 페 Petri dish, Pleurotus ostreatus ( 16855), Penicillium roqueforti ( 11269) and Aspergillus oryzae, 11896) were dispersed (Table 3). When the surface is completely strained, add 20 ml of hydrochloric acid (5%), heat it in a water bath at 100 ° C, and heat it for 6 hours. After sufficiently cooling at room temperature, 20 ml of sodium hydroxide (1.4 N) was added to neutralize the mixture, the pH was adjusted to 6.5 to 6.8, and the mixture was filtered. The solid was transferred to a Petri dish and dried in a dryer (55 ° C). The liquid portion was appropriately concentrated and then sprayed onto a solid medium of a Petri dish and dried. The dried extract was finely ground with a mortar and then weighed and the yield was determined and stored at -20 ° C. The dried extract was analyzed for the content of arabinosyllan using the HPLC assay described in Example 1. [
그 결과, 표 4에 나타난 바와 같이, 페니실리움 로퀘포르티(Penicillium roqueforti, 11269) 균주를 이용한 실험군 8에서 아라비노스와 자일로스 함량이 가장 높은 것으로 나타났다. 이러한 결과를 통해, 페니실리움 로퀘포르티 균주에 의한 생물전환 공정을 이용하는 것이 아라비노자일란 함량 증가에 가장 적합한 것을 확인하였다.As a result, as shown in Table 4, the content of arabinose and xylose was the highest in the experimental group 8 using Penicillium roqueforti ( 11269) strain. From these results, it was confirmed that the use of the bioconversion process by the strain of Penicillium roqueforti is most suitable for increasing the arabinoselan content.
atotal arabinoxylan= 0.88*(% arabinose + % xylose) a total arabinoxylan = 0.88 * (% arabinose +% xylose)
1-3. 아라비노자일란이 증가된 미강 추출물과 기존 미강 추출물 간의 아라비노자일란 함량 비교1-3. Comparison of arabinoxylan content between rice bran extract and rice bran extract with increased arabinoxylan content
본 발명의 아라비노자일란의 함량이 증가한 것을 확인하기 위해, 기존의 미강 추출물과 본 발명의 제조방법으로 제조된 미강 추출물의 아라비노자일란 함량을 비교하였다. In order to confirm that the content of arabinoxylan of the present invention was increased, the content of arabinose-ylan was compared with that of the conventional rice bran extract and the rice bran extract prepared by the production method of the present invention.
비교군으로서 기존의 미강 추출물을 제조하기 위해, 미강을 mash NO.7, 10, 20의 3개의 채로 층을 분리 한 후, mash NO.10에서 분리된 미강을 시료로 사용하였다. 미강 1g씩 코니칼 튜브(conical tube)에 투입 한 후 50 ml의 증류수를 넣고 90℃로 가열한 후에 50℃에서 농축한 시료를 미강 추출물로 하였다. As a comparative group, rice bran was separated into three layers of mash NO.7, 10 and 20, and then rice bran extracted from mash NO.10 was used as a sample. One gram of rice bran was put into a conical tube, and 50 ml of distilled water was added thereto. The mixture was heated to 90 ° C and then concentrated at 50 ° C to prepare a rice bran extract.
상기 미강 추출물을 본 발명의 제조 방법으로 제조된 아라비노자일란이 증가된 미강 추출물과 아라비노스 및 자일로스의 함량 비교를 위해 실시예 1에 개시된 HPLC 측증법을 통해 분석하였다. The above extract of rice bran was analyzed for the content of arabinose and arabinose and xylose by the HPLC method described in Example 1.
그 결과, 미강 추출물과 비교했을 때 아라비노자일란이 증가된 미강 추출물의 아라비노스 및 자일로스 함량이 현저히 높음을 확인하여 본 발명의 제조 방법이 아라비노자일란의 함량을 현저하게 증가시키는 것을 확인할 수 있었다 (도 1).As a result, it was confirmed that the content of arabinose and xylose in the rice bran extract, which had increased arabinoxylan compared to rice bran extract, was remarkably high, and it was confirmed that the production method of the present invention significantly increased the content of arabinoselan (Fig. 1).
상기와 같은 결과를 종합하여, 페니실리움 로퀘포르티 균주를 이용한 생물전환 공정을 이용하는 경우, 및 추가로 산 가수분해 공정을 이용하는 경우에 미강 추출물에 아라비노자일란이 고함량으로 함유될 수 있음을 확인하였다.Taken together with the above results, it can be concluded that arabinozylan can be contained in a high content of rice bran extract in the case of using a bioconversion process using a strain of Penicillium roqueforti, and also in the case of using an acid hydrolysis process Respectively.
이에, 실시예 1-2의 방법 중에서 페니실리움 로퀘포르티 균주를 이용한 방법으로 아라비노자일란 고함량 미강 추출물을 제조하여, 이하의 실험에서 이용하였다.Thus, an Arabidopsis rawan high-content rice bran extract was prepared from the method of Example 1-2 using a strain of Penicillium roquefortii and used in the following experiment.
실시예 2. 신경병증 제브라피시에서의 뉴로마스트 보호 효과 확인Example 2 Neuropathic Effect of Neuromast Protective Effect in Zebrafish
2-1. 인슐린 유도 제브라피시 동물모델에서의 뉴로마스트 보호 효과 확인2-1. Identification of neuromast protection in insulin-induced zebrafish animal models
생체 내에서 아라비노자일란 함유 미강 추출물의 신경병증 관련 효과를 확인하기 위해, 수정 후 3일의 제브라피시 유생(zebrafish larvae)를 6웰에 위치시킨 후 10μM 인슐린에서 48시간 동안 노출시켜 인슐린 과잉으로 인한 인슐린 저항성을 유도하였다. 이는 신경세포의 인슐린 수용체의 기능을 저해하여 말초 신경병증을 유발하는 원인이 되며 신경병증의 증상 중 하나로 뉴로마스트의 세포수가 감소하는 것을 확인할 수 있다. 인슐린 유도 신경병증 제브라피시 를 아라비노자일란 함유 미강 추출물 100μg/mL를 48시간 동안 노출시켰다. 직접적인 뉴로마스트의 관찰을 위해 형광현미경(Olympus 1Х70, Olympus, Japan)을 사용하였으며, 형광현미경 관찰 전에 0.1% YO-PRO로 30분동안 뉴로마스트를 염색하였다. 형광현미경을 통해 획득한 이미지는 Focus Lite 소프트웨어를 사용하여 뉴로마스트의 개수를 분석하였다. In order to confirm neuropathy-related effects of arabinoxylan-containing rice bran extracts in vivo, 3 days post-fertilization zebrafish larvae were placed in 6 wells and exposed to 10 μM insulin for 48 hours to induce hyperinsulinemia Insulin resistance was induced. This inhibits insulin receptor function of neurons and causes peripheral neuropathy. Neuropathy is one of the symptoms of neuropathy that can be confirmed that the number of cells in the neuromast is reduced. Insulin-induced neuropathy Zebrafish was exposed to 100 μg / mL of rice bran extract containing arabinoxylan for 48 hours. Fluorescence microscopy (Olympus 1X70, Olympus, Japan) was used for direct neuromast observation and neuromast was stained with 0.1% YO-PRO for 30 min before fluorescence microscopy. Images acquired through fluorescence microscopy were analyzed using Focus Lite software.
그 결과, 도 2에 나타난 바와 같이, 정상군에 비해 미처리 대조군의 뉴로마스트 수가 유의적으로 감소한 것을 확인할 수 있으며, 아라비노자일란 함유 미강 추출물 처리군의 뉴로마스트 개수가 미처리 대조군에 비해 유의적으로 증가한 것을 확인하였다 (도 2). 따라서, 신경병증에서 아라비노자일란 함유 미강 추출물이 뉴로마스트의 보호 효능을 가짐을 확인할 수 있었다.As a result, as shown in FIG. 2, it was confirmed that the neuroma count of the untreated control group was significantly lower than that of the normal control group, and the number of neuromas in the treatment group of arabinofibromycin-containing rice bran extract was significantly higher than that of the untreated control group (Fig. 2). Thus, it was confirmed that the extract of rice bran containing arabinoxylan in the neuropathy has protective effect of neuromast.
2-2. 네오마이신 유도 제브라피시 동물모델에서의 뉴로마스트 보호 효과 확인2-2. Neuromycin-Induced Zebrafish Protective Effect of Neuromast in Animal Model
생체 내에서 아라비노자일란 함유 미강 추출물의 신경병증 관련 효과를 확인하기 위해, 수정 후 5일의 제브라피시 유생(zebrafish larvae)를 24웰에 위치시킨 후 2μM 네오마이신에서 1시간 동안 노출시켜 네오마이신 유도 뉴로마스트 제브라피시 동물모델에 아라비노자일란 함유 미강 추출물 0.1 및 1 μg/mL를 6시간 동안 노출시켰다. 직접적인 뉴로마스트의 관찰을 위해 형광현미경(Olympus 1Х70, Olympus, Japan)을 사용하였으며, 형광현미경 관찰 전에 0.1% YO-PRO로 30분 동안 뉴로마스트를 염색하였다. 형광현미경을 통해 획득한 이미지는 Focus Lite 소프트웨어를 사용하여 뉴로마스트의 개수를 분석하였다. In order to confirm the neuropathic effect of arabinofibromine extract containing arabinoxylan in vivo, zebrafish larvae were placed in 24 wells for 5 days after the modification and exposed for 1 hour in 2 μM neomycin to induce neomycin induction Neuromast zebrafish animal models were exposed to 0.1 and 1 μg / mL bovine corn extract containing arabinoxylan for 6 hours. Fluorescence microscopy (Olympus 1X70, Olympus, Japan) was used for direct neuromast observation and neuromast was stained with 0.1% YO-PRO for 30 min before fluorescence microscopy. Images acquired through fluorescence microscopy were analyzed using Focus Lite software.
그 결과, 도 3에 나타난 바와 같이, 정상군에 비해 미처리 대조군의 뉴로마스트 수가 유의적으로 감소한 것을 확인할 수 있으며, 아라비노자일란 함유 미강 추출물 처리군의 뉴로마스트 개수가 미처리 대조군에 비해 유의적으로 증가한 것을 확인하였다 (도 3). 따라서, 신경병증에서 아라비노자일란 함유 미강 추출물이 뉴로마스트의 보호 효능을 가짐을 확인할 수 있었다.As a result, as shown in FIG. 3, it was confirmed that the number of neuromas of the untreated control group was significantly lower than that of the normal group, and the number of neuromas of the group treated with the extract of rice bran extract containing arabinoxylan was significantly higher than that of the untreated control group (Fig. 3). Thus, it was confirmed that the extract of rice bran containing arabinoxylan in the neuropathy has protective effect of neuromast.
실시예 3. 제브라피시 동물모델에서 청각 손상 효과 확인Example 3. Determination of hearing damage effect in an animal model of zebrafish
3-1. 알록산 유도 제브라피시 동물모델에서의 청각 유모 세포 보호 효과 확인3-1. Identification of protective effect of auditory hair cells in alloxan-induced zebrafish animal model
생체 내에서 아라비노자일란 함유 미강 추출물의 청각 손상 관련 효과를 확인하기 위해, 수정 5일 후의 제브라피시 유생을 24웰에 위치시킨 후 600μM 알록산에 72시간 동안 노출시켰다. 알록산은 요산의 산화물로서 췌장의 랑게르한스 섬을 파괴하여 인슐린 결핍을 유발하며 청각신경을 포함한 말초신경의 기능부전을 유발한다. 알록산 유도 제브라피시 동물모델에 아라비노자일란 함유 미강 추출물 100μg/mL를 12시간 동안 노출시킨 후, 직접적인 청각 유모 세포의 관찰을 위해 형광현미경(Olympus 1Х70, Olympus, Japan)을 사용하였으며, 형광현미경 관찰 전에 0.1% YO-PRO로 30분동안 염색하였다. 형광현미경을 통해 획득한 이미지는 Focus Lite 소프트웨어를 사용하여 청각 유모 세포의 개수를 분석하였다. In order to confirm the auditory damage-related effects of arabinoxylan-containing rice bran extracts in vivo, zebrafish larvae after 5 days of fertilization were placed in 24 wells and exposed to 600 μM alloys for 72 hours. Alloxan is an oxide of uric acid that destroys the islets of the pancreas, causing insulin deficiency, and causing peripheral dysfunction, including auditory nerves. After exposure to 100 μg / mL of arachidonic acid-containing rice bran extract for 12 hours, a fluorescence microscope (
그 결과, 도 4에 나타난 바와 같이, 정상군에 비해 미처리 대조군의 청각 유모 세포 수가 유의적으로 감소하였으며, 아라비노자일란 함유 미강 추출물 처리군의 청각 유모 세포 의 수가 미처리 대조군과 비교하여 유의적으로 증가한 것을 확인하였다 (도 4). 따라서, 아라비노자일란 함유 미강 추출물이 청각 유모 세포 보호 효능을 가짐을 확인할 수 있었다.As a result, as shown in FIG. 4, the number of auditory hair cells in the untreated control group was significantly lower than that in the normal group, and the number of auditory hair cells in the group treated with rice bran extract containing arabinoxylan was significantly higher than that of the untreated control group (Fig. 4). Therefore, it was confirmed that the extract of rice bran containing arabinoxylan has auditory hair cell protection effect.
3-2. 가나마이신 유도 이독성 제브라피시 동물모델에서의 청각 유모 세포 보호 효과 확인3-2. Protective effect of ganamycin-induced toxic zebrafish animal model on auditory hair cell protection
수정 5일 후의 제브라피시 유생을 24 웰에 위치시킨 후 25μM 가나마이신에 30분 동안 노출시켰다. 가나마이신은 이독성을 가져 달팽이관, 청신경, 전정기관등의 손상을 유발한다. 가나마이신 유도 이독성 제브라피시 동물모델에 아라비노자일란 함유 미강 추출물 0,1 또는 1 μg/mL를 12시간 동안 노출시킨 후, 직접적인 청각 유모 세포의 관찰을 위해 형광현미경(Olympus 1Х70, Olympus, Japan)을 사용하였으며, 형광현미경 관찰 전에 0.1% YO-PRO로 30분동안 염색하였다. 형광현미경을 통해 획득한 이미지는 Focus Lite 소프트웨어를 사용하여 청각 유모 세포의 개수를 분석하였다. Five days after fertilization, zebrafish larvae were placed in 24 wells and exposed to 25 μM ganamycin for 30 minutes. Kanamycin is toxic and causes damage to the cochlea, auditory nerve, and vestibular system. Kanamycin-induced toxicity Zebrafish animal models were exposed to 0, 1, or 1 μg / mL of arachidonic acid-containing rice bran extracts for 12 hours, and then subjected to fluorescence microscopy (Olympus 1Х70, Olympus, Japan) And stained with 0.1% YO-PRO for 30 min before fluorescence microscopy. Images obtained through fluorescence microscopy were analyzed using Focus Lite software for the number of auditory hair cells.
그 결과, 도 5에 나타난 바와 같이, 정상군에 비해 미처리 대조군의 청각 유모 세포 수가 유의적으로 감소하였으며, 아라비노자일란 함유 미강 추출물 처리군의 청각 유모 세포 의 수가 미처리 대조군과 비교하여 유의적으로 증가한 것을 확인하였다 (도 5). 따라서, 아라비노자일란 함유 미강 추출물이 이독성에 대한 청각 유모 세포 보호 효능을 가짐을 확인할 수 있었다.As a result, as shown in FIG. 5, the number of auditory hair cells in the untreated control group was significantly lower than that in the normal group, and the number of auditory hair cells in the group treated with rice bran extract containing arabinoxylan was significantly higher than that of the untreated control group (Fig. 5). Thus, it was confirmed that the extract of rice bran containing arabinoxylan has an auditory hair cell protection effect against this toxicity.
제제예 1. 정제의 제조Preparation Example 1. Preparation of tablets
아라비노자일란 고함량 미강 추출물 200 ㎎Arabinoxylan high content rice bran extract 200 mg
유당 100 ㎎Lactose 100 mg
전분 100 ㎎Starch 100 mg
스테아린산 마그네슘 적량Magnesium stearate Suitable amount
통상의 정제 제조방법에 따라 상기의 성분을 혼합하고 타정하여 정제를 제조하였다.The above components were mixed and tableted according to a conventional tablet preparation method to prepare tablets.
제제예 2. 액제의 제조Formulation Example 2. Preparation of a liquid preparation
아라비노자일란 고함량 미강 추출물 1000 ㎎Arabinoxylan high content rice bran extract 1000 mg
CMC-Na 20 gCMC-Na 20 g
이성화당 20 gIsomer 20 g
레몬향 적량Lemon incense Suitable amount
정제수를 가하여 전체 1000 ㎖로 맞추었다. 통상의 액제의 제조방법에 따라 상기의 성분을 혼합한 다음, 갈색병에 충전하고 멸균시켜 액제를 제조하였다.Purified water was added to adjust the total volume to 1000 ml. The above components were mixed according to a conventional method for producing a liquid agent, and then filled in a brown bottle and sterilized to prepare a liquid agent.
제제예 3. 캡슐제의 제조Formulation Example 3. Preparation of capsules
아라비노자일란 고함량 미강 추출물 300 ㎎Arabinoxylan high content rice bran extract 300 mg
결정성 셀룰로오스 3 ㎎Crystalline cellulose 3 mg
락토오스 14.8 ㎎Lactose 14.8 mg
마그네슘 스테아레이트 0.2 ㎎Magnesium stearate 0.2 mg
통상의 캡슐제 제조방법에 따라 상기의 성분을 혼합하고 젤라틴 캡슐에 충전하여 캡슐제를 제조하였다.The above components were mixed according to a conventional capsule preparation method and filled in gelatin capsules to prepare capsules.
제제예 4. 주사제의 제조Formulation Example 4. Preparation of injection
아라비노자일란 고함량 미강 추출물 300 ㎎Arabinoxylan high content rice bran extract 300 mg
만니톨 180 ㎎Mannitol 180 mg
주사용 멸균 증류수 2974 ㎎Sterile sterilized water for injection 2974 mg
Na2HPO412H2O 26 ㎎Na 2 HPO 4 12 H 2 O 26 mg
통상의 주사제의 제조방법에 따라 1 앰플당 (2 ㎖) 상기의 성분 함량으로 제조하였다.(2 ml) per ampoule according to the usual injection preparation method.
Claims (7)
A pharmaceutical composition for preventing or treating neuropathy or hearing damage comprising an extract of rice bran containing arabinoxylan as an active ingredient.
2. The pharmaceutical composition according to claim 1, wherein said neuropathy prevention or treatment is achieved by neuromast protection.
The pharmaceutical composition according to claim 1, which is achieved by the prevention of hearing damage or the protection of auditory hair cells.
미강을 포함하는 배지에, 페니실리움 로퀘포르티 (Penicillium roqueforti) 균주를 접종하여 배양하는 단계.
The pharmaceutical composition according to claim 1, wherein the arachinozzan-containing rice bran extract is produced by a manufacturing method comprising the steps of:
Inoculation of Penicillium roqueforti strain into a culture medium containing rice bran.
5. The pharmaceutical composition according to claim 4, wherein the production method further comprises the step of adding an acid during the culture to hydrolyze.
6. The pharmaceutical composition according to claim 5, wherein the acid is hydrochloric acid.
A food composition for preventing or ameliorating neuropathy or hearing damage comprising an extract of rice bran containing arabinoxylan as an active ingredient.
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