KR101681980B1 - Compositions for prevention or treatment of diabetic complications comprising extract of Colona auricaulata - Google Patents
Compositions for prevention or treatment of diabetic complications comprising extract of Colona auricaulata Download PDFInfo
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- KR101681980B1 KR101681980B1 KR1020130131629A KR20130131629A KR101681980B1 KR 101681980 B1 KR101681980 B1 KR 101681980B1 KR 1020130131629 A KR1020130131629 A KR 1020130131629A KR 20130131629 A KR20130131629 A KR 20130131629A KR 101681980 B1 KR101681980 B1 KR 101681980B1
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- Prior art keywords
- diabetic
- colona
- extract
- auricaulata
- extraction
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- A61K2236/30—Extraction of the material
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Abstract
본 발명은 Colona auricaulata 추출물 또는 이의 분획물을 유효성분으로 포함하는 당뇨합병증 예방 또는 치료용 조성물에 관한 것이다. 구체적으로, 본 발명은 Colona auricaulata 추출물 또는 이의 분획물을 유효 성분으로 함유하는 당뇨합병증의 예방 또는 치료용 약학적 조성물, 또는 당뇨합병증의 예방 또는 개선용 식품 조성물에 관한 것이다. 또한, 본 발명은 상기 조성물을 이용하여 당뇨합병증을 예방 또는 치료하는 방법에 관한 것이다.The present invention relates to a colona auricaulata extract or a fraction thereof as an active ingredient. The present invention also relates to a composition for preventing or treating diabetic complications. More specifically, the present invention Colona auricaulata extract or a fraction thereof as an active ingredient, or a food composition for preventing or ameliorating diabetic complications. The present invention also relates to a method for preventing or treating diabetic complications using the composition.
Description
본 발명은 Colona auricaulata 추출물 또는 이의 분획물을 유효성분으로 포함하는 당뇨합병증 예방 또는 치료용 조성물에 관한 것이다. 구체적으로, 본 발명은 Colona auricaulata 추출물 또는 이의 분획물을 유효 성분으로 함유하는 당뇨합병증의 예방 또는 치료용 약학적 조성물, 또는 당뇨합병증의 예방 또는 개선용 식품 조성물에 관한 것이다. 또한, 본 발명은 상기 조성물을 이용하여 당뇨합병증을 예방 또는 치료하는 방법에 관한 것이다.
The present invention relates to a colona auricaulata extract or a fraction thereof as an active ingredient. The present invention also relates to a composition for preventing or treating diabetic complications. More specifically, the present invention Colona auricaulata extract or a fraction thereof as an active ingredient, or a food composition for preventing or ameliorating diabetic complications. The present invention also relates to a method for preventing or treating diabetic complications using the composition.
당뇨병은 전 세계적으로 중요한 성인병 중의 하나로서, 최근 우리나라에서도 급속한 경제 성장과 더불어 당뇨병 유병률이 10%에 달하며, 현재 전 세계적으로 2억4천만명이 넘었으며, 2025년에는 전 세계적으로 3억8천만명으로 증가할 것이며, 이중 60%가 아시아 지역에서 발병할 것이라고 2009년 미국의사협회(JAMA)에서 발표하였다. 특히 당뇨발병시기가 중장년으로 당겨졌으며, 또한 수명이 연장됨으로 인해서 합병증으로 진전되는 것을 피할 수 없는 상황이 되었다. 즉, 일반적으로 당뇨병에 걸린 후 10 ~ 20년이 지나면 체내 거의 모든 기관이 손상을 받아 당뇨성 망막병증(diabetic retinopathy), 당뇨성 백내장(diabetic cataract), 당뇨성 신증(diabetic nephropathy), 당뇨성 신경병증(diabetic neuropathy), 심장병, 암, 골다공증 등으로 나타난다. 만성 당뇨성 신증은 혈액 투석 치료 및 말기 신부전의 가장 중요한 원인이 되고 있으며, 당뇨성 백내장과 망막증은 실명을 초래하고 결국엔 죽음에 이르게 한다.
Diabetes is one of the most important geriatric diseases in the world. In recent years, with the rapid economic growth, the prevalence of diabetes in Korea has reached 10%, now more than 240 million people worldwide, and 308 million in 2025 And 60% of them will develop in Asia, according to the American Medical Association (JAMA) in 2009. In particular, the onset of diabetes mellitus has been pulled into the elderly, and it has become inevitable to progress to complications due to the extended life span. In general, almost 10 to 20 years after the onset of diabetes, almost all the organs in the body are damaged, causing diabetic retinopathy, diabetic cataract, diabetic nephropathy, diabetic neuropathy, Diabetic neuropathy, heart disease, cancer, and osteoporosis. Chronic diabetic nephropathy is the most important cause of hemodialysis treatment and end-stage renal failure, and diabetic cataract and retinopathy cause blindness and eventually death.
미국의 경우 25세에서 74세 연령대의 실명의 원인이 당뇨병이며, 당뇨 발병 후 15년이나 20년이 지나면 60%가 실명으로 이어진다. 그러므로 당뇨환자에게서 합병증이 발병하는 기간이 5년이나 10년 정도 지연만 되더라도 환자와 그 가족의 삶의 질이 달라질 것이며, 국가재정에도 커다란 영향을 끼칠 것이다.
In the United States, diabetes is the cause of blindness in the 25- to 74-year-old age group, and 60% of blindness after 15 or 20 years of diabetes develops blindness. Therefore, even if the duration of complications in diabetic patients is delayed by 5 or 10 years, the quality of life of patients and their families will be different and will have a big impact on national finances.
이러한 당뇨합병증을 유발하는 대표적인 인자 중의 하나로 크게 단백질의 비효소적 당화반응(nonenzymatic glycation of proein) 및 폴리올 경로(polyol pathway) 등이 설명되고 있다.
Nonenzymatic glycation of proenin and polyol pathway have been described as one of the typical factors causing such diabetic complications.
단백질의 비효소적 당화반응(nonenzymatic glycation of protein)이란, 단백질의 리신 잔기 등의 아미노산 그룹과 환원당이 효소 작용 없이 축합반응, 즉 밀리아드 반응을 수행하는 것으로, 이 반응의 결과로 최종당화산물(advanced glycation endproducts, AGEs)이 생성된다. 단백질의 비효소적 당화반응은 (1) 단백질의 리신 잔기 등의 아미노산 그룹과 환원당의 알데히드 또는 케톤이 효소 작용 없이 친핵성 첨가 반응을 하여 초기 단계 산물인 쉬프염기(schiff base)를 형성하고, 상기 쉬프염기와 인접한 케토아민 어닥트(ketoamine adduct)가 서로 축합하여 가역적인 아마도리(Amadori)형의 조기당화산물이 생성되는 단계와 (2) 고혈당 상태가 지속되어 가역적인 아마도리형의 조기당화산물이 분해되지 않고 재배열(rearrangement)되어 비가역산물인 최종당화산물이 생성되고 이렇게 생성된 최종당화산물이 단백질 또는 지질 등과 결합 또는 교차결합(cross-linking)되어 비가역적인 당화단백질 또는 당화지질 등의 산물이 생성되는 단계로 나눌 수 있다.
The nonenzymatic glycation of protein means that the amino acid group such as the lysine residue of the protein and the reducing sugar are subjected to a condensation reaction, that is, a milliad reaction without enzymatic action. As a result, the final glycation product ( advanced glycation endproducts, AGEs) are generated. The non-enzymatic glycosylation of proteins involves (1) nucleophilic addition reaction of an amino acid group such as a lysine residue of a protein and an aldehyde or ketone of a reducing sugar without enzymatic action to form a schiff base as an initial step product, (2) a step of producing an amadori-type early glycation product due to the condensation between the Schiff base and the adjacent ketoamine adduct, and (2) the reversal of the early glycation end product of the reversible amyloid type The final glycation product, which is a non-reversible product, is produced, and the resulting final glycation product is bound or cross-linked with proteins or lipids, thereby producing irreversible glycated proteins or products such as glycated lipids Can be divided into two stages.
가역적인 아마도리형의 조기당화산물과 달리 최종당화산물은 비가역적인 반응 산물이므로, 일단 생성되면 혈당이 정상으로 회복되어도 분해되지 않고, 최종당화산물이 결합한 단백질 또는 지질의 생존기간 동안 조직에 축적되어 조직의 구조와 기능을 비정상적으로 변화시켜 조직 곳곳에서 합병증을 유발시킨다(Vinson, J. A. et al., 1996, J. Nutritinal Biochemistry 7: 559-663; Smith, P. R. et al., 1992, Eur . J. Biochem., 210: 729-739).
Unlike the reversible amaryllis type early glycation products, the final glycation products are irreversible reaction products, and once formed, they are not degraded even when the blood glucose is restored to normal, accumulated during the survival period of the protein or lipid bound to the final glycation products, (Vinson, JA et al., 1996, J. Nutritinal Biochemistry 7: 559-663; Smith, PR et al., 1992, Eur . J. Biochem . , ≪ / RTI > 210: 729-739).
예를 들면, 포도당과 여러 종류의 단백질이 반응하여 생성된 최종당화산물 중 하나인 당화 알부민은 만성 당뇨성 신증을 일으키는 중요한 요인으로 작용한다. 당화 알부민은 당화가 진행되지 않은 정상 알부민에 비해 더 용이하게 신사구체 세포 내로 유입되고, 고농도의 포도당은 메산지움 세포를 자극하여 세포외 기질(extracellular matrix) 합성을 증가시킨다. 과도하게 유입된 당화 알부민과 증가된 세포외 기질로 인하여 신사구체의 섬유화가 야기된다. 이와 같은 기전으로 신사구체가 계속 손상 받게 되어 혈액투석 또는 장기이식 등의 극단적인 치료방법을 쓸 수밖에 없는 단계에 이르게 되는 것이다. 또한, 만성 당뇨로 인하여 동맥벽에서는 콜라겐이, 신사구체에서는 기저막성 단백질이 최종당화산물과 결합되어 조직에 축적됨이 보고된바 있다(Brownlee, M., et al., 1986, Sciences, 232, 1629-1632).
For example, glycated albumin, one of the final glycation products produced by the reaction of glucose with various proteins, is an important factor in causing chronic diabetic nephropathy. Glycated albumin enters the ganglion cell more easily than normal albumin without glycosylation, and high glucose stimulates mesangial cells to increase synthesis of extracellular matrix. Overgrowth of glycosylated albumin and increased extracellular matrix cause fibrosis of the glomerulus. Such a mechanism would continue to damage the shrine sphere, leading to a stage where extreme treatment methods, such as hemodialysis or organ transplantation, are inevitable. In addition, it has been reported that collagen in the arterial wall due to chronic diabetes and basement membrane protein in the ganglion cell are combined with the final glycation products and accumulate in tissues (Brownlee, M., et al., 1986, Sciences , 232, 1629- 1632).
이처럼 비효소적 단백질 당화반응에 의하여 기저막, 혈장 알부민, 수정체 단백질, 피브린, 콜라겐 등의 단백질에서 당화가 일어나며, 생성된 최종당화산물이 조직의 구조와 기능을 비정상적으로 변화시켜 당뇨성 망막병증, 당뇨성 백내장, 당뇨성 신증, 당뇨성 신경병증, 족부궤양, 혈관질환 등의 만성 당뇨합병증을 유발시킨다.
Thus, glycosylation occurs in proteins such as basement membrane, plasma albumin, lens protein, fibrin, and collagen by non-enzymatic protein glycosylation, and the resulting final glycation products abnormally change the structure and function of tissues to cause diabetic retinopathy, Diabetic neuropathy, foot ulceration, and vascular disease.
또한, 최종당화산물이 사람의 미세혈관 내피세포에서 폴리올 경로의 주효소인 알도스 환원효소(AR)를 활성화시키는 것이 보고된바 있다(Nakamura, N., et al., 2000, Free Radic Biol . Med., 29: 17-25). 이때 과당은 포도당에 비하여 단백질의 비효소적 당화반응의 속도가 약 10배 정도 빠르다. 따라서, 고농도의 과당이 단백질과 결합하여 결국은 최종당화산물의 형성을 가속화시킨다.
It has also been reported that the final glycated product activates aldose reductase (AR), the main enzyme of the polyol pathway in human microvascular endothelial cells (Nakamura, N., et al., 2000, Free Radic Biol . Med ., 29: 17-25). At this time, fructose is about 10 times faster in non-enzymatic glycosylation of protein than glucose. Thus, a high concentration of fructose binds to the protein and ultimately accelerates the formation of the final glycation end product.
이와 같이 비효소적 당화반응, 폴리올 경로 및 산화적 스트레스(oxidative stress) 작용 기전들이 서로 연관되어 당뇨합병증을 유발시킨다. 따라서, 모든 당뇨합병증의 발병을 지연시키거나 예방 또는 치료하기 위해서는 최종당화산물의 형성을 억제하는 것이 매우 중요함이 밝혀졌다(Brownlee, M., et al., 1988, N. Engl. Med ., 318, 1315-1321).
Thus, nonenzymatic glycation, polyol pathway, and oxidative stress mechanisms are linked to each other to cause diabetic complications. Thus, it has been found that inhibiting the formation of the final glycation end product is very important for delaying, preventing or treating the onset of all diabetic complications (Brownlee, M., et al., 1988, N. Engl. Med . 318, 1315-1321).
현재, 단백질 당화 억제제로서 합성제제인 아미노구아니딘(aminoguanidine)은 친핵성 히드라진(hydrazine)으로 아마도리 산물과 결합하여 단백질과의 교차결합을 방지함으로써 최종당화산물의 생성을 억제하여 합병증으로 진전되는 것을 지연 또는 방지한다(Brownlee, M., et al., 1986, Sciences, 232, 1629-1632; Edelstein, D. et al., 1992, Diabetes, 41, 26-29). 아미노구아니딘은 당뇨합병증의 예방 및 치료에 가장 유망한 합성 의약품으로 제3상 임상실험까지 진행되었으나, 장기간 투여 시 독성이 유발되는 문제점이 나타나 중단되었다. 그러므로, 안전하고 효능이 우수한 천연약제의 개발이 요망되고 있는 실정이다.
At present, aminoguanidine, a synthetic agent as a protein glycosylation inhibitor, is a nucleophilic hydrazine which binds with a lipid product to prevent cross-linking with proteins, thereby inhibiting the production of final glycation products and delaying progression to complications (Brownlee, M., et al., 1986, Sciences , 232, 1629-1632; Edelstein, D. et al., 1992, Diabetes , 41, 26-29). Aminoguanidine is the most promising synthetic drug for the prevention and treatment of diabetic complications, which has progressed to Phase III clinical trials, but it has been discontinued due to toxic effects caused by long-term administration. Therefore, there is a demand for the development of safe and efficacious natural medicines.
이러한 배경하에, 본 발명자들은 천연 약재를 이용한 당뇨합병증 치료제를 개발하던 중 Colona auricaulata 추출물 또는 이의 분획물이 최종당화산물의 생성을 억제함으로써, 당뇨합병증의 지연, 예방 또는 치료 효능이 있음을 확인하고 본 발명을 완성하였다.
Under such background, the inventors of the Colona who develop complications of diabetes treatment using natural herbs auricaulata extract or its fractions inhibit the production of the final glycosylated product, thereby confirming the delayed, prophylactic or therapeutic effect of diabetic complications and have completed the present invention.
본 발명의 목적은 당뇨합병증 유발 원인 중의 하나인 최종당화산물의 생성을 억제하는 효능이 있는 Colona auricaulata 추출물 또는 이의 분획물을 유효성분으로 포함함으로써 수정체 섬유의 변성, 망막과 신장에서의 병적 이상, 족부궤양, 신경병증, 혈관질환 등의 당뇨합병증 발병을 예방, 개선 또는 치료할 수 있는 조성물을 제공하는 것이다.An object of the present invention is Colona operative to inhibit the production of advanced glycation end products of one of causes causing diabetic complications It is intended to provide a composition capable of preventing, ameliorating, or treating the onset of diabetic complications such as denaturation of lens fibers, pathological abnormality in retina and kidney, foot ulcer, neuropathy, vascular disease and the like by including an auricaulata extract or a fraction thereof as an active ingredient .
본 발명의 다른 목적은 상기 조성물을 이용하여 당뇨합병증을 예방 또는 치료하는 방법을 제공하는 것이다.
Another object of the present invention is to provide a method for preventing or treating diabetic complications using the composition.
상기 과제를 해결하기 위하여, 본 발명은 Colona auricaulata 추출물 또는 이의 분획물을 유효성분으로 포함하는 당뇨합병증 예방 또는 치료용 약학적 조성물을 제공한다.
In order to achieve the foregoing object, the present invention Colona The present invention provides a pharmaceutical composition for preventing or treating diabetic complications comprising an auricaulata extract or a fraction thereof as an active ingredient.
본 발명의 Colona auricaulata는 재배한 것, 시판되는 것 등 다양한 방법으로 입수한 것을 사용할 수 있다.
The Colona of the present invention Auricaulata can be cultivated, marketed, and used in a variety of ways.
본 발명에서 사용되는 용어 "추출물"은, Colona auricaulata의 추출 처리에 의하여 얻어지는 추출액, 상기 추출액의 희석액이나 농축액, 상기 추출액을 건조하여 얻어지는 건조물, 상기 추출액의 조정제물이나 정제물, 또는 이들의 혼합물 등, 추출액 자체 및 추출액을 이용하여 형성 가능한 모든 제형의 추출물을 포함한다. 본 발명의 상기 추출물 또는 분획물은 바람직하게는 추출 후 건조 분말 형태로 제조되어 사용될 수 있다.The term "extract" as used in the present invention, Colona all formulations which can be formed using the extract itself and extracts such as an extract obtained by extracting auricaulata , a diluted solution or a concentrate of the extract, a dried product obtained by drying the extract, a controlled preparation or a purified product of the extracted solution, ≪ / RTI > The extract or fraction of the present invention can be prepared and used in the form of a dry powder after extraction.
본 발명의 상기 Colona auricaulata 추출물은, 상기 Colona auricaulata의 천연, 잡종 또는 변종 식물의 다양한 기관으로부터 추출될 수 있고, 예를 들어 Colona auricaulata의 가지, 잎, 뿌리, 꽃 및 열매 뿐만 아니라 식물 조직 배양물로부터도 추출이 가능하다.The Colona of the present invention auricaulata extract, the Colona can be extracted from various agencies of the natural, hybrids or varieties of plants auricaulata, for example, it can be also extracted, as well as branches, leaves, roots, flowers and fruits of Colona auricaulata from plant tissue culture.
본 발명의 상기 Colona auricaulata 추출물은 바람직하게는 Colona auricaulata의 가지, 잎 또는 이의 혼합물의 추출물일 수 있다.
The Colona of the present invention The auricaulata extract may preferably be an extract of a branch, a leaf or a mixture thereof of Colona auricaulata .
본 발명의 상기 Colona auricaulata 추출물은 하기와 같은 방법으로 제조될 수 있으나, 이에 제한되지 않는다.The Colona of the present invention The auricaulata extract can be manufactured by the following method, but is not limited thereto.
Colona auricaulata에 추출 용매를 가하여 추출하는 단계; Colona extracting auricaulata with an extraction solvent;
상기 추출 단계에서 수득한 추출물을 식힌 후 여과하는 단계; 및Cooling the extract obtained in the extracting step and then filtering; And
상기 여과 단계에서 여과한 추출물을 감압 농축하고 건조하는 단계.
The step of concentrating the extract filtered at the filtration step and drying the extract.
본 발명의 상기 Colona auricaulata 추출물에 있어서, 상기 Colona auricaulata를 추출하는 방법은 특별히 제한되지 아니하며, 당해 기술 분야에서 통상적으로 사용하는 방법에 따라 추출할 수 있다. 상기 추출 방법의 비제한적인 예로는, 열수 추출법, 초음파 추출법, 여과법, 환류 추출법 등을 들 수 있으며, 이들은 단독으로 수행되거나 2 종 이상의 방법을 병용하여 수행될 수 있다.The Colona of the present invention In the auricaulata extract, the method for extracting Colona auricaulata is not particularly limited, and may be extracted according to a method commonly used in the art. Non-limiting examples of the extraction method include hydrothermal extraction, ultrasonic extraction, filtration, and reflux extraction. These may be performed alone or in combination with two or more methods.
본 발명에서 상기 Colona auricaulata를 추출하는 데에 사용되는 추출 용매의 종류는 특별히 제한되지 아니하며, 당해 기술 분야에서 공지된 임의의 용매를 사용할 수 있다. 상기 추출 용매의 비제한적인 예로는 물, 알코올 또는 이들의 혼합 용매 등을 들 수 있으며, 알코올을 용매로 사용하는 경우에는 바람직하게는 C1 내지 C4의 알코올, 보다 바람직하게는 C1 내지 C2의 저급 알코올, 더욱 바람직하게는 80% 에탄올 수용액을 사용할 수 있으나 이에 제한되지 않는다. 본 발명의 Colona auricaulata 추출물은 바람직하게는 물 또는 에탄올 추출물일 수 있다.In the present invention Colona The kind of extraction solvent used for extracting auricaulata is not particularly limited, and any solvent known in the art can be used. Particular examples of the extraction solvent is water, alcohol, or and the like, mixed solvents of the foregoing, when using an alcohol as a solvent is preferably to more preferably an alcohol, a C 1 to C 4 C 1 to C 2 lower alcohol, more preferably 80% ethanol aqueous solution, may be used, but not limited thereto. The Colona auricaulata extract of the present invention may preferably be water or an ethanol extract.
본 발명에서 상기 Colona auricaulata를 열수 추출 방법으로 추출하는 경우에는, 1회 내지 5회 반복 추출하는 것이 바람직하며, 3회 반복 추출하는 것이 더욱 바람직하나 이에 한정하지 않는다. 상기 추출 용매는 건조된 Colona auricaulata의 중량 대비 0.1배 내지 10배 첨가할 수 있으며, 0.3배 내지 5배 첨가하는 것이 바람직하다. 추출 온도는 20℃ 내지 70℃인 것이 바람직하나 이에 한정하지 않는다. 또한, 추출 시간은 12시간 내지 48시간인 것이 바람직하나 이에 한정하지 않는다.In the present invention Colona In the case of extracting auricaulata by the hot water extraction method, it is preferable to repeat the extraction once to five times, and it is more preferable to repeat the extraction three times, but it is not limited thereto. The extraction solvent is a dried Colona auricaulata may be added in an amount of 0.1 to 10 times by weight, preferably 0.3 to 5 times by weight. The extraction temperature is preferably 20 占 폚 to 70 占 폚, but is not limited thereto. The extraction time is preferably from 12 hours to 48 hours, but is not limited thereto.
본 발명의 상기 Colona auricaulata 추출물을 제조하는 방법에 있어서, 상기 감압 농축은 진공 감압 농축기 또는 진공 회전 증발기를 이용하는 것이 바람직하나 이에 한정하지 않는다. 또한, 건조는 감압 건조, 진공 건조, 비등 건조, 분무 건조 또는 동결 건조하는 것이 바람직하나 이에 한정하지 않는다.The Colona of the present invention In the method of producing an auricaulata extract, it is preferable to use a vacuum decompression concentrator or a vacuum rotary evaporator as the decompression concentration, but it is not limited thereto. The drying is preferably performed under reduced pressure, vacuum drying, boiling, spray drying or freeze drying, but not always limited thereto.
본 발명의 구체적인 일 실시예에 따르면, Colona auricaulata의 가지 또는 잎을 물로 세척하고 그늘에서 건조한 다음, 상기 건조된 Colona auricaulata 가지 또는 잎을 분쇄하여 추출 용기에 투입 후, 추출 용매로 상온에서 반복 추출하여 추출물을 수득하였다. 상기 수득한 Colona auricaulata 추출물을 거름종이 등을 이용하여 고형분을 제거하고 여과한 다음, 상기 추출액을 감압 농축하여 Colona auricaulata 추출물을 제조하였다.
According to a specific embodiment of the present invention, Colona The branches or leaves of auricaulata are washed with water and dried in the shade, then the dried Colona auricaulata branches or leaves were pulverized and put into an extraction vessel and repeatedly extracted with an extraction solvent at room temperature to obtain an extract. The obtained Colona The extract of auricaulata was removed by filtration using a filter paper, and then the extract was concentrated under reduced pressure to prepare Colona auricaulata extract.
본 발명에서 사용되는 용어 "분획물"은, 여러 다양한 구성 성분들을 포함하는 혼합물로부터 특정 성분 또는 특정 성분 그룹을 분리하기 위하여 분획을 수행하여 얻어진 결과물을 의미한다.The term "fraction " as used herein means a product obtained by performing fractionation to separate a specific component or a specific component group from a mixture containing various components.
본 발명에서 상기 분획물을 얻는 분획 방법은 특별히 제한되지 아니하며, 당해 기술 분야에서 통상적으로 사용하는 방법에 따라 수행될 수 있다. 상기 분획 방법의 비제한적인 예로는, Colona auricaulata를 추출하여 얻은 추출물에 소정의 용매를 처리하여 상기 추출물로부터 분획물을 얻는 방법을 들 수 있다.The fractionation method for obtaining the fraction in the present invention is not particularly limited and may be carried out according to a method commonly used in the art. Particular examples of the fractionation method, Colona and a method of treating the extract obtained by extracting auricaulata with a predetermined solvent to obtain a fraction from the extract.
본 발명에서 상기 분획물을 얻는 데에 사용되는 분획 용매의 종류는 특별히 제한되지 아니하며, 당해 기술 분야에서 공지된 임의의 용매를 사용할 수 있다. 상기 분획 용매의 비제한적인 예로는 물, 알코올 등의 극성 용매; 헥산, 에틸 아세테이트, 클로로포름, 디클로로메탄 등의 비극성 용매 등을 들 수 있다. 이들은 단독으로 사용되거나 2 종 이상 혼합하여 사용될 수 있다. 상기 분획 용매 중 알코올을 사용하는 경우에는 바람직하게는 C1 내지 C4의 알코올을 사용할 수 있다.
The kind of the fraction solvent used for obtaining the fraction in the present invention is not particularly limited, and any solvent known in the art can be used. Non-limiting examples of the fraction solvent include polar solvents such as water and alcohol; And non-polar solvents such as hexane, ethyl acetate, chloroform and dichloromethane. These may be used alone or in combination of two or more. When alcohols are used in the fraction solvent, C 1 to C 4 alcohols can be preferably used.
본 발명의 상기 Colona auricaulata 추출물 또는 이의 분획물은 최종당화산물의 생성을 억제하는 효능을 나타내며, 이는 본 발명에서 최초로 규명된 것이다.The Colona of the present invention The auricaulata extract or its fractions exhibit an efficacy inhibiting the production of the final glycosylated product, which was first identified in the present invention.
구체적으로 본 발명의 Colona auricaulata 추출물 또는 이의 분획물은 당뇨합병증의 주요 원인 중 하나인, 최종당화산물의 생성을 억제하여 수정체 섬유의 변성, 망막과 신장에서의 병적 이상, 족부궤양, 신경병증, 혈관질환 등의 당뇨합병증 발병을 예방, 개선 또는 치료하는 효과를 나타낸다.Specifically, the Colona auricaulata extract or its fractions inhibits the production of the final glycation end product which is one of the main causes of diabetic complications and causes diabetic complications such as denaturation of lens fiber, pathological abnormality in retina and kidney, foot ulcer, neuropathy and vascular disease Prevention, improvement, or cure.
본 발명의 일 실시예에 따르면, 단백질원으로서 소혈청알부민을 사용하여 상기 소혈청알부민과 과당 또는 글루코스와의 결합 정도를 지표로 이용하여 Colona auricaulata 추출물의 최종당화산물 생성 억제 효능을 평가한 결과, 대표적인 양성대조군인 아미노구아니딘보다 10배나 더 효능이 우수함을 확인할 수 있었다(실험예 1).According to one embodiment of the present invention, the effect of the bovine serum albumin and fructose or glucose on the inhibition of the final glycation endogenesis of Colona auricaulata extract was evaluated by using bovine serum albumin as a protein source as an index, It was confirmed that the efficacy was ten times higher than that of the representative positive control group, aminoguanidine (Experimental Example 1).
또한, 본 발명의 상기 조성물은 당뇨합병증의 예방, 개선 또는 치료 효과를 충분히 나타내는 농도 범위에서 세포 독성을 나타내지 않으며, 천연물로부터 유래된 것이어서 체내에 심각한 자극을 가한다거나 유해한 작용을 유발함이 없이 안정하게 사용될 수 있는 이점이 있다.
In addition, the composition of the present invention does not show cytotoxicity in a concentration range sufficiently exhibiting the prevention, improvement or therapeutic effect of diabetic complication, and is derived from a natural product, so that the composition stably stimulates the body without causing serious irritation or causing harmful action There is an advantage that can be used.
본 발명에서 사용되는 용어 "당뇨합병증"은, 당뇨병이 장기간 지속되는 경우 유발되는 증상을 의미한다. 당뇨합병증은, 당뇨병의 발병 기준 및 판단 기준과 상이하며, 당뇨합병증 치료제는 당뇨병 치료제와는 별개로 사용되고 있다.
The term "diabetic complication" used in the present invention means a symptom caused when the diabetes persists for a long period of time. Diabetic complications are different from the criteria for the onset and judgment of diabetes, and diabetic complications are used separately from diabetic agents.
당뇨합병증 유병의 원인은 최종당화산물(advanced glycation endproducts, AGEs) 및, 알도즈 환원효소(aldose reductase)의 비정상적인 활성과 가속화된 산화성 스트레스에 의해 유발되므로, 당뇨합병증의 치료제로서의 개발시 최종당화산물 및 알도즈 환원효소의 활성과 항산화 효능을 측정하여 치료제의 효능을 판단할 수 있다. 또한, 당뇨합병증으로 당뇨성 망막병증, 당뇨성 백내장, 신증, 신경병증, 심장병 등이 야기되므로, 직접적으로 망막병, 백내장, 신증 및 신경병증 등을 억제하는 것으로 직접적인 치료제의 효능을 나타낸다.
The causes of diabetic complications are caused by the abnormal activity of advanced glycation endproducts (AGEs) and aldose reductase and the accelerated oxidative stress. Therefore, when developing as a therapeutic agent for diabetic complications, The efficacy of the therapeutic agent can be determined by measuring the activity of aldose reductase and antioxidant activity. In addition, since diabetic complications are caused by diabetic retinopathy, diabetic cataract, nephropathy, neuropathy, and heart disease, it directly inhibits retinal diseases, cataracts, nephropathy and neuropathy and thus exhibits a direct therapeutic effect.
본 발명에서, 당뇨합병증의 비제한적인 예로 당뇨성 망막병증, 당뇨성 백내장, 당뇨성 신증, 당뇨성 신경병증, 족부궤양, 당뇨성 심장병, 암, 골다공증 등을 들 수 있다. 본 발명의 상기 당뇨합병증은 특별히 제한되지 아니하나, 본 발명의 목적상, 바람직하게는 당뇨성 망막병증, 당뇨성 백내장, 당뇨성 신증, 당뇨성 신경병증, 족부궤양 또는 당뇨성 심장병을 의미할 수 있다.
In the present invention, non-limiting examples of diabetic complications include diabetic retinopathy, diabetic cataract, diabetic neuropathy, diabetic neuropathy, foot ulcer, diabetic heart disease, cancer, osteoporosis and the like. The diabetic complication of the present invention is not particularly limited, but it may mean diabetic retinopathy, diabetic cataract, diabetic nephropathy, diabetic neuropathy, foot ulcer or diabetic heart disease for the purpose of the present invention have.
본 발명에서 사용되는 용어, "예방"이란, 본 발명의 상기 조성물을 개체에 투여하여 당뇨합병증의 발병을 억제시키거나 지연시키는 모든 행위를 의미한다.As used herein, the term "prevention" means any action that inhibits or delays the onset of diabetic complications by administering the composition of the present invention to a subject.
본 발명에서 사용되는 용어, "치료"란, 본 발명의 상기 조성물을 개체에 투여하여 당뇨합병증의 증세가 호전되도록 하거나 이롭게 되도록 하는 모든 행위를 의미한다.The term "treatment" as used in the present invention means all the actions that cause the symptom of diabetic complication to be improved or benefited by administering the composition of the present invention to an individual.
본 발명에서 사용되는 용어, "개선"은 치료되는 상태와 관련된 파라미터, 예를 들면 증상의 정도를 적어도 감소시키는 모든 행위를 의미한다.
As used herein, the term "improvement" means any action that at least reduces the degree of symptom associated with the condition being treated.
본 발명의 상기 약학적 조성물에 있어서, 상기 Colona auricaulata 추출물 또는 이의 분획물은 상기 약학적 조성물의 전체의 중량을 기준으로 바람직하게는 1 중량% 내지 99.99 중량%로 함유될 수 있고, 보다 바람직하게는 10 중량% 내지 99.99 중량%로 함유될 수 있으며, 더욱 바람직하게는 50 중량% 내지 99.99 중량%로 함유될 수 있다. 상기 범위 내에서, 상기 Colona auricaulata 추출물 또는 이의 분획물에 따른 최종당화산물의 형성 억제 효과를 비롯한 당뇨합병증 치료 효과가 충분히 발휘되어 본 발명의 목적을 달성하기에 더욱 적합해지는 이점이 있다.
In the pharmaceutical composition of the present invention, the Colona The auricaulata extract or fraction thereof may be contained in an amount of preferably 1% by weight to 99.99% by weight, more preferably 10% by weight to 99.99% by weight, based on the total weight of the pharmaceutical composition, More preferably 50% by weight to 99.99% by weight. Within the above range, the therapeutic effect of diabetic complications including the effect of inhibiting the formation of the final glycation products depending on the Colona auricaulata extract or its fractions can be sufficiently exhibited , which is advantageous to achieve the object of the present invention.
본 발명의 상기 약학적 조성물은, 상기 Colona auricaulata 추출물 또는 이의 분획물을 유효 성분으로 함유하는 것에 더하여, 약학적으로 허용 가능한 담체를 추가로 포함할 수 있다.The pharmaceutical composition of the present invention may further comprise a pharmaceutically acceptable carrier in addition to the above-mentioned Colona auricaulata extract or a fraction thereof as an active ingredient.
본 발명에서, 상기 "약학적으로 허용 가능"하다는 것은, 이를 투여 시 생물체를 자극하지 않으면서, 투여되는 화합물의 생물학적 활성 및 특성을 저해하지 않는, 약학 분야에서 통상적으로 사용되는 것을 의미한다.In the present invention, the above-mentioned "pharmaceutically acceptable" means that it is commonly used in the pharmaceutical field, which does not disturb the biological activity and properties of the compound administered, without irritating the organism upon administration thereof.
본 발명의 상기 약학적 조성물은, 상기 담체와 함께 제제화되어, 식품, 의약품, 사료 첨가제, 음용수 첨가제 등으로 활용될 수 있다.The pharmaceutical composition of the present invention may be formulated together with the carrier to be used as food, medicines, feed additives, drinking water additives, and the like.
본 발명에서, 상기 담체의 종류는 특별히 제한되지 아니하며 당해 기술 분야에서 통상적으로 사용되는 담체라면 어느 것이든 사용할 수 있다. 상기 담체의 비제한적인 예로는, 식염수, 멸균수, 링거액, 완충 식염수, 알부민 주사 용액, 락토오스, 덱스트로오스, 수크로오스, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 말토 덱스트린, 글리세롤, 에탄올 등을 들 수 있다. 이들은 단독으로 사용되거나 2 종 이상을 혼합하여 사용될 수 있다.In the present invention, the type of the carrier is not particularly limited and any carrier conventionally used in the art can be used. Examples of the carrier include, but are not limited to, saline, sterilized water, Ringer's solution, buffered saline, albumin injection solution, lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, maltodextrin, glycerol, . These may be used alone or in combination of two or more.
또한, 본 발명의 상기 약학적 조성물은 필요한 경우, 부형제, 희석제, 항산화제, 완충액 또는 정균제 등 기타 약학적으로 허용 가능한 첨가제 들을 첨가하여 사용할 수 있으며, 충진제, 증량제, 습윤제, 붕해제, 분산제, 계면 활성제, 결합제 또는 윤활제 등을 부가적으로 첨가하여 사용할 수 있다.
In addition, the pharmaceutical composition of the present invention may be supplemented with other pharmaceutically acceptable additives such as excipients, diluents, antioxidants, buffers or bacteriostats, if necessary, and may be used as fillers, extenders, wetting agents, disintegrants, An activator, a binder, a lubricant, or the like may be additionally used.
본 발명의 상기 약학적 조성물은 경구 투여 또는 비경구 투여를 위한 적합한 다양한 제형으로 제제화되어 사용될 수 있다.The pharmaceutical composition of the present invention may be formulated into various formulations suitable for oral administration or parenteral administration.
상기 경구 투여용 제제의 비제한적인 예로는, 트로키제(troches), 로젠지(lozenge), 정제, 수용성 현탁액, 유성 현탁액, 조제 분말, 과립, 에멀젼, 하드 캡슐, 소프트 캡슐, 시럽 또는 엘릭시르제 등을 들 수 있다.Non-limiting examples of such oral dosage forms include troches, lozenges, tablets, aqueous suspensions, oily suspensions, prepared powders, granules, emulsions, hard capsules, soft capsules, syrups or elixirs .
본 발명의 상기 약학적 조성물을 경구 투여용으로 제제화하기 위하여, 락토오스, 사카로오스, 솔비톨, 만니톨, 전분, 아밀로펙틴(Amylopectin), 셀룰로오스(Cellulose) 또는 젤라틴(Gelatin) 등과 같은 결합제; 디칼슘 포스페이트(Dicalcium phosphate) 등과 같은 부형제; 옥수수 전분 또는 고구마 전분 등과 같은 붕괴제; 스테아르산 마그네슘(Magnesium stearate), 스테아르산 칼슘(Calcium stearate), 스테아릴 푸마르산 나트륨(Sodium stearyl fumarate) 또는 폴리에틸렌 글리콜 왁스(Polyethylene glycol wax) 등과 같은 윤활유 등을 사용할 수 있으며, 감미제, 방향제, 시럽제 등도 사용할 수 있다.In order to formulate the pharmaceutical composition of the present invention for oral administration, a binder such as lactose, saccharose, sorbitol, mannitol, starch, amylopectin, cellulose, or gelatin; Excipients such as dicalcium phosphate and the like; Disintegrating agents such as corn starch or sweet potato starch; Lubricants such as magnesium stearate, calcium stearate, sodium stearyl fumarate or polyethylene glycol wax may be used, and sweeteners, fragrances, syrups and the like may also be used. .
나아가 캡슐제의 경우에는 상기 언급한 물질 외에도 지방유와 같은 액체 담체 등을 추가로 사용할 수 있다.
Furthermore, in the case of capsules, in addition to the above-mentioned substances, liquid carriers such as fatty oils can be further used.
상기 비경구용 제제의 비제한적인 예로는, 주사액, 좌제, 호흡기 흡입용 분말, 스프레이용 에어로졸제, 연고, 도포용 파우더, 오일, 크림 등을 들 수 있다.Non-limiting examples of the parenteral preparation include injections, suppositories, respiratory inhalation powders, aerosol preparations for spraying, ointments, powder for application, oils, creams and the like.
본 발명의 상기 약학적 조성물을 비경구 투여용으로 제제화하기 위하여, 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결 건조 제제, 외용제 등을 사용할 수 있으며, 상기 비수성용제, 현탁제로는 프로필렌글리콜, 폴리에틸렌글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다.In order to formulate the pharmaceutical composition of the present invention for parenteral administration, a sterilized aqueous solution, a non-aqueous solvent, a suspending agent, an emulsion, a lyophilized preparation, an external agent and the like can be used. Examples of the non-aqueous solution, the propylene glycol, Polyethylene glycol, vegetable oils such as olive oil, injectable esters such as ethyl oleate, and the like.
또한, 보다 구체적으로 본 발명의 상기 약학적 조성물을 주사액으로 제제화하는 경우, 본 발명의 상기 조성물을 안정제 또는 완충제와 함께 물에서 혼합하여 용액 또는 현탁액으로 제조하고 이를 앰플(ampoule) 또는 바이알(vial)의 단위 투여용으로 제제화할 수 있다. 또한, 본 발명의 상기 약학적 조성물을 에어로졸제로 제제화하는 경우, 수분산된 농축물 또는 습윤 분말이 분산되도록 추진제 등이 첨가제와 함께 배합할 수 있다.More specifically, when the pharmaceutical composition of the present invention is formulated into an injection, the composition of the present invention is mixed with water or a stabilizer or a buffer in water to prepare a solution or suspension, which is then mixed with an ampoule or a vial, And the like. When the pharmaceutical composition of the present invention is formulated into an aerosol formulation, a propellant or the like may be added together with the additive such that the water-dispersed concentrate or the wet powder is dispersed.
또한, 본 발명의 상기 약학적 조성물을 연고, 크림 등으로 제제화하는 경우에는, 동물성 유, 식물성 유, 왁스, 파라핀, 전분, 트라칸트, 셀룰로오스 유도체, 폴리에틸렌 글리콜, 실리콘, 벤토나이트, 실리카, 탈크, 산화 아연 등을 담체로 사용하여 제제화할 수 있다.
When the pharmaceutical composition of the present invention is formulated into an ointment, cream, or the like, it may be an animal oil, a vegetable oil, a wax, a paraffin, a starch, a tracer, a cellulose derivative, a polyethylene glycol, a silicone, a bentonite, Zinc or the like as a carrier.
본 발명의 상기 약학적 조성물의 약학적 유효량, 유효 투여량은 상기 약학적 조성물의 제제화 방법, 투여 방식, 투여 시간 및/또는 투여 경로 등에 의해 다양해질 수 있으며, 상기 약학적 조성물의 투여로 달성하고자 하는 반응의 종류와 정도, 투여 대상이 되는 개체의 종류, 연령, 체중, 일반적인 건강 상태, 질병의 증세나 정도, 성별, 식이, 배설, 해당 개체에 동시 또는 이시에 함께 사용되는 약물 기타 조성물의 성분 등을 비롯한 여러 인자 및 의약 분야에서 잘 알려진 유사 인자에 따라 다양해질 수 있으며, 당해 기술 분야에서 통상의 지식을 가진 자는 목적하는 치료에 효과적인 투여량을 용이하게 결정하고 처방할 수 있다.The pharmaceutically effective amount and the effective dose of the pharmaceutical composition of the present invention may be varied depending on the formulation method, administration method, administration time and / or route of administration of the pharmaceutical composition. The type and severity of the response, the type of subject being treated, the age, body weight, general health status, severity or severity of the disease, sex, diet, excretion, drugs used simultaneously or simultaneously with the subject, , And the like, and those skilled in the art will readily determine and prescribe dosages that are effective for the desired treatment.
본 발명의 상기 약학적 조성물의 보다 바람직한 효과를 위한 투여량은, 바람직하게는 1일 1 mg/kg 내지 1,000 mg/kg, 보다 바람직하게는 10 mg/kg 내지 500 mg/kg일 수 있다. 본 발명의 상기 약학적 조성물의 투여는 하루에 1회 투여될 수 있고, 수회에 나누어 투여될 수 있다. 따라서 상기 투여량은 어떠한 면으로든 본 발명의 범위를 한정하는 것은 아니다.
The dose for the more preferable effect of the pharmaceutical composition of the present invention may be preferably 1 mg / kg to 1,000 mg / kg per day, more preferably 10 mg / kg to 500 mg / kg per day. Administration of the pharmaceutical composition of the present invention can be administered once a day, or divided into several doses. Accordingly, the dosage is not limited in any way to the scope of the present invention.
본 발명의 상기 약학적 조성물의 투여 경로 및 투여 방식은 각각 독립적일 수 있으며, 그 방식에 있어 특별히 제한되지 아니하며, 목적하는 해당 부위에 상기 약학적 조성물이 도달할 수 있는 한 임의의 투여 경로 및 투여 방식에 따를 수 있다. 상기 약학적 조성물은 경구 투여 또는 비경구 투여 방식으로 투여할 수 있다.The route of administration and the mode of administration of the pharmaceutical composition of the present invention may be independent of each other and are not particularly limited in the method and may be arbitrarily administered and administered as long as the pharmaceutical composition can reach the desired site It is possible to follow the method. The pharmaceutical composition may be administered orally or parenterally.
상기 비경구 투여하는 방법으로는, 예를 들어 정맥 내 투여, 복강 내 투여, 근육 내 투여, 경피 투여 또는 피하 투여 등을 이용할 수 있으며, 상기 조성물을 질환 부위에 도포하거나 분무, 흡입하는 방법 또한 이용할 수 있으나 이들에 제한되지 아니한다.The parenteral administration may be, for example, intravenous administration, intraperitoneal administration, intramuscular administration, transdermal administration or subcutaneous administration, and a method of applying, spraying or inhalation the composition to a diseased site may also be used But are not limited to.
본 발명의 상기 약학적 조성물은 바람직하게는 경구 투여 또는 주사 투여될 수 있다.
The pharmaceutical composition of the present invention can preferably be administered orally or by injection.
또한, 본 발명은 Colona auricaulata 추출물 또는 이의 분획물을 유효성분으로 포함하는 당뇨합병증 예방 또는 치료용 약학적 조성물을 개체에 투여하여 당뇨합병증을 예방 또는 치료하는 방법을 제공한다.The invention also Colona The present invention provides a method for preventing or treating diabetic complications by administering to a subject a pharmaceutical composition for preventing or treating diabetic complications comprising an extract of auricaulata or a fraction thereof as an active ingredient.
본 발명에서 사용되는 용어, "개체"는 쥐, 가축, 인간 등을 포함하는 포유 동물을 비롯한 모든 동물을 의미한다.The term "individual" as used herein refers to all animals, including mammals including rats, livestock, humans, and the like.
본 발명의 상기 당뇨합병증의 예방 또는 치료 방법에서, 상기 약학적 조성물에 관한 설명, 및 상기 약학적 조성물의 투여량, 투여 경로, 투여 방식에 관한 설명, 당뇨합병증의 종류, 예방 및 치료의 의미 등은 본 발명의 상기 약학적 조성물과 관련하여 상기에서 설명한 바와 동일하다.
In the method for preventing or treating diabetic complications of the present invention, the description of the pharmaceutical composition, the description of the dose, administration route and administration method of the pharmaceutical composition, the kind of diabetic complication, the meaning of prevention and treatment Are the same as those described above in connection with the pharmaceutical composition of the present invention.
또한, 본 발명은 Colona auricaulata 추출물 또는 이의 분획물을 유효성분으로 포함하는 당뇨합병증 예방 또는 개선용 식품 조성물을 제공한다.The invention also Colona auricaulata extract or a fraction thereof as an active ingredient. The present invention also provides a food composition for preventing or ameliorating diabetic complications.
본 발명의 상기 식품 조성물에서, 상기 Colona auricaulata 추출물 또는 이의 분획물, 및 이의 효능 등은 본 발명의 상기 약학적 조성물과 관련하여 상기에서 설명한 바와 동일하다.In the food composition of the present invention, the Colona auricaulata extract or its fractions, and its efficacy are the same as those described above in connection with the pharmaceutical composition of the present invention.
본 발명의 상기 식품 조성물은 특별히 제한되지 아니하며, 건강 기능 식품 조성물을 포함한다.The food composition of the present invention is not particularly limited and includes a health functional food composition.
본 발명의 상기 건강 기능 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 health functional food composition of the present invention is used as a food additive, the composition may be added as it is or may be used together with other food or food ingredients, and may be appropriately used according to a conventional method.
상기 식품의 종류는 특별히 제한되지 아니하며, 통상적인 의미에서의 식품을 모두 포함한다. 상기 물질을 첨가할 수 있는 식품의 비제한적인 예로는 육류, 소세지, 빵, 초콜릿, 캔디류, 스낵류, 과자류, 피자, 라면, 기타 면류, 껌류, 아이스크림류를 포함한 낙농제품, 각종 스프, 음료수, 차, 드링크제, 알코올 음료 및 비타민 복합제 등을 들 수 있다.The kind of the food is not particularly limited, and includes food in a conventional sense. Non-limiting examples of the food to which the substance can be added include meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gums, dairy products including ice creams, , A drink, an alcoholic beverage, and a vitamin complex.
본 발명의 상기 건강 기능 식품 조성물이 음료 조성물인 경우, 통상의 음료와 같이 여러 가지 향미제 또는 천연 탄수화물 등을 추가 성분으로서 함유할 수 있다. 상기 천연 탄수화물의 비제한적인 예로 포도당, 과당과 같은 모노사카라이드; 말토스, 수크로오스와 같은 디사카라이드; 덱스트린, 사이클로덱스트린과 같은 천연 감미제; 사카린, 아스파르탐과 같은 합성 감미제 등을 들 수 있다. 상기 첨가되는 추가 성분의 비율은 당업자의 선택에 의해 적절하게 결정될 수 있다.When the health functional food composition of the present invention is a beverage composition, various flavoring agents, natural carbohydrates, and the like may be contained as additional components such as ordinary beverages. Non-limiting examples of such natural carbohydrates include monosaccharides such as glucose and fructose; Disaccharides such as maltose and sucrose; Natural sweetening agents such as dextrin, cyclodextrin; Synthetic sweetening agents such as saccharin and aspartame, and the like. The proportion of the additional component added may be appropriately determined by a person skilled in the art.
상기 외에 본 발명의 건강 기능 식품 조성물은 여러 가지 영양제, 비타민, 전해질, 풍미제, 착색제, 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. 그 밖에 본 발명의 건강 기능 식품 조성물은 천연 과일 주스, 과일 음료 또는 야채 음료 등의 제조를 위한 과육을 함유할 수 있다. 이러한 성분은 독립적으로 사용되거나 2 이상을 조합하여 사용할 수 있다. 이러한 첨가물의 비율 또한 당업자에 의해 적절히 선택될 수 있다.
In addition to the above, the health functional food composition of the present invention may contain various nutrients, vitamins, electrolytes, flavors, colorants, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloid thickening agents, pH adjusting agents, stabilizers, , Alcohols, carbonating agents used in carbonated drinks, and the like. In addition, the health functional food composition of the present invention may contain pulp for the production of natural fruit juice, fruit drink or vegetable drink. These components may be used independently or in combination of two or more. The ratios of these additives can also be suitably selected by those skilled in the art.
본 발명의 Colona auricaulata 추출물 또는 이의 분획물을 함유하는 조성물은 당뇨합병증 유발 원인 중의 하나인 최종당화산물의 생성을 억제하는 효능이 있어 수정체 섬유의 변성, 망막과 신장에서의 병적 이상, 족부궤양, 신경병증, 혈관질환 등의 당뇨합병증에 매우 효과적이므로 당뇨합병증의 예방, 개선 또는 치료용 약학적 조성물 및 식품 조성물로서 유용하게 이용할 수 있다. 또한, 본 발명의 Colona auricaulata 추출물 또는 이의 분획물은 독성이 없고 천연물로부터 유래된 물질이어서 인체에 적용하여도 부작용없이 활용할 수 있는 이점이 있다.
The Colona of the present invention The composition containing auricaulata extract or its fractions has an effect of inhibiting the production of a final glycation product, which is one of the causes of diabetic complications. Therefore, the composition of the present invention can be used for the treatment of diabetic complications such as degeneration of lens fiber, pathological abnormality in retina and kidney, It is useful as a pharmaceutical composition and a food composition for preventing, improving or treating diabetic complications. In addition, the Colona auricaulata extract of the present invention or a fraction thereof is not toxic and is derived from a natural product, so that it can be used without any adverse effect even if it is applied to human body.
이하, 실시예를 통하여 본 발명을 보다 상세히 설명한다. 다만, 이들 실시예는 본 발명을 예시적으로 설명하기 위한 것에 불과하므로 본 발명의 범위가 이들 실시예에 의해 한정되는 것으로 해석되어서는 아니된다.
Hereinafter, the present invention will be described in more detail by way of examples. It should be understood, however, that these examples are for illustrative purposes only and are not to be construed as limiting the scope of the invention.
실시예Example 1: One: ColonaColona auricaulataauricaulata 추출물 제조 Extract preparation
실험에 사용된 Colona auricaulata 가지 및 잎이며 증거표본은 한국한의학연구원 한의융합연구본부, 당뇨합병증연구센터 표본실에 보관중이다.
The Colona used in the experiment auricaulata branches and leaves. The specimens are stored in the Korea Fusion Research Center, Korea Research Institute of Oriental Medicine, and the diabetes complication research center sample room.
1) 추출단계1) Extraction step
음건 및 세절한 Colona auricaulata의 가지 및 잎을 분쇄한 후, 1.0 L 80% 에탄올을 넣고, 추출용기에서 상온상태로 48 시간 동안 3 시간 반복 추출한 후, 40℃에서 감압 하에 농축시켜 에탄올 추출물을 얻었다.
Shade and three- cut Colona auricaulata , and then 1.0 L 80% ethanol was added thereto. The extract was repeatedly extracted for 3 hours at room temperature in an extraction vessel for 48 hours, and then concentrated under reduced pressure at 40 ° C to obtain an ethanol extract.
2) 농축 및 건조단계2) Concentration and drying step
상기 추출액을 여과한 후 감압 상태에서 농축하였다. 이때, 구성성분의 분해 및 가수분해를 방지할 수 있도록 농축시 온도를 40℃ 내지 45℃로 유지하였다.
The extract was filtered and concentrated under reduced pressure. At this time, the temperature during the concentration was kept at 40 캜 to 45 캜 so as to prevent decomposition and hydrolysis of the constituents.
실험예Experimental Example 1: One: 최종당화산물The final glycation product 생성 억제 효능( Production inhibitory effect ( InIn -- vitrovitro ) 분석) analysis
Colona auricaulata 가지 추출물에 대하여 시험관 내에서 최종당화산물 생성 억제 효능을 분석하였다. Colona auricaulata The inhibitory effect on the final glycation end products was examined in vitro.
단백질은 소혈청알부민(bovine serum albuminl BSA, Sigma, USA)을 이용하여 과당 및 글루코스와의 결합 정도를 지표로 이용하고, 최종당화산물 생성 억제에 우수한 효능을 갖는 아미노구아니딘(aminoguanidine: AG)을 양성대조군으로 사용하였다.Bovine serum albumin (BSA, Sigma, USA) was used as an indicator for the binding of fructose to glucose as an indicator and aminoguanidine (AG) And used as a control.
단백질원인 소혈청알부민(BSA)을 10 ㎎/㎖의 농도로 50 mM 인산완충용액(phosphate buffer; pH 7.4)에 혼합하여 제조하였다. 당원은 0.2 M 과당과 0.2 M 글루코스의 혼합액을 사용하였다. 상기 Colona auricaulata 가지 추출물(25 ㎍/㎖, 50 ㎍/㎖ 및 70 ㎍/㎖) 및 양성대조군인 아미노구아니딘(55.505 ㎍/㎖, 74.75 ㎍/㎖ 및 92.5 ㎍/㎖)을 다양한 농도로 디메틸설폭사이드(DMSO)에 녹인 후 15% 트윈 80을 첨가하였다. 이때 총 디메틸설폭사이드(DMSO)의 함량은 0.2%이었다. 이를 상기 소혈청알부민과 당의 혼합액에 첨가하고 37℃에서 7일 동안 배양하였다. 이때, 0.02% 소듐아자이드(sodium azide)를 항-박테리아제로서 첨가하였다. 소혈청알부민과 당 혼합액을 대조군으로 사용하였다. 각 시험군과 대조군의 공시험군(blank)은 각각 조제한 후 배양하지 않았으며, 모든 배양액은 3개씩 준비하여 최대한 오차를 피하였다. 배양 7일 후, 각각의 배양액에서 생성된 최종당화산물의 함량을 분석하였다. 최종당화산물의 양을 마이크로플레이트 리더(Microplate reader, Excitation; 350 nm, Emission; 450 nm)로 측정하여 생성 억제효능을 하기 수학식 1로 계산하였다. 결과를 하기 표 1에 나타내었다.BSA was added to 50 mM phosphate buffer (pH 7.4) at a concentration of 10 ㎎ / ㎖. The company used a mixture of 0.2 M fructose and 0.2 M glucose. The Colona Amuruanidins (55.505 占 퐂 / ml, 74.75 占 퐂 / ml and 92.5 占 퐂 / ml), which are positive control groups, were dissolved in various concentrations of dimethylsulfoxide (DMSO ) And then 15% Tween 80 was added. At this time, the content of total dimethyl sulfoxide (DMSO) was 0.2%. This was added to the mixture of bovine serum albumin and sugar and incubated at 37 ° C for 7 days. At this time, 0.02% sodium azide was added as an anti-bacterial agent. Bovine serum albumin and sugar mixture were used as controls. Blank of each test group and control group was not cultured after each preparation, and all of the cultures were prepared in triplicate to avoid the maximum error. After 7 days of culture, the content of the final glycation products produced in each culture was analyzed. The amount of the final saccharification product was measured by a microplate reader (Excitation: 350 nm, Emission; 450 nm), and the production inhibitory effect was calculated by the following formula (1). The results are shown in Table 1 below.
[수학식 1][Equation 1]
(㎍/㎖)Conc.
(占 퐂 / ml)
(%)Inhibition
(%)
(㎍/㎖)IC 50
(占 퐂 / ml)
5
102.5
5
10
34.44±1.73
59.23±0.2121.98 ± 1.19
34.44 ± 1.73
59.23 + - 0.21
74
92.555.5
74
92.5
49.69±0.10
52.72±0.2742.76 ± 1.16
49.69 + - 0.10
52.72 ± 0.27
상기 표 1을 통해 알 수 있는 바와 같이, 본 발명에 따른 Colona auricaulata 추출물의 최종당화산물 생성억제효능의 IC50값이 8.14㎍/㎖로 확인되었다. 이는 대표적인 양성대조군인 합성 단일화합물인 아미노구아니딘(IC50 값: 79.98 ㎍/㎖) 보다 9.8 배 효능이 월등히 우수함이 증명되었다.As can be seen from the Table 1, the IC 50 value of the advanced glycation end product Inhibitory potency of Colona auricaulata extract according to the present invention was found to be 8.14㎍ / ㎖. It was proved that the efficacy was 9.8 times better than the representative positive control group, aminoguanidine (IC 50 value: 79.98 / / ml), which is a synthetic single compound.
즉, Colona auricaulata 추출물의 경우 단백질과 당의 결합을 억제하여 최종당화산물의 생성을 강력하게 저해하므로 당뇨합병증로 진행되는 것을 강하게 예방 또는 치료할 수 있음이 확인되었다. That is, Colona auricaulata extract inhibits the binding of protein and sugar to strongly inhibit the production of the final glycation products, and thus it has been confirmed that the progress of diabetic complications can be strongly prevented or treated.
Claims (13)
Claims 1. A pharmaceutical composition for preventing or treating diabetic complications comprising an extract of Colona auricaulata or a fraction thereof as an active ingredient, wherein the diabetic complication includes diabetic retinopathy, diabetic cataract, diabetic neuropathy, diabetic neuropathy, A pharmaceutical composition which is a heart disease.
The method of claim 1, wherein the Colona auricaulata extract is Colona auricaulata , a leaf, or a root thereof.
The pharmaceutical composition according to claim 1, wherein the extract is obtained by extracting with water, a C 1 to C 4 alcohol, or a mixed solvent thereof.
The pharmaceutical composition according to claim 1, wherein the extraction is any one selected from the group consisting of room temperature extraction, hot water extraction, cold extraction, reflux extraction, ultrasonic extraction, and steam extraction.
[Claim 3] The pharmaceutical composition according to claim 1, wherein the Colona auricaulata extract or a fraction thereof inhibits the production of a final glycosylated product, thereby preventing or treating the diabetic complication.
A method of preventing or treating diabetic complications, comprising administering the pharmaceutical composition of any one of claims 1 to 5 to a subject other than a human, wherein the diabetic complication is selected from the group consisting of diabetic retinopathy, diabetic cataract, Diabetic nephropathy, diabetic neuropathy, foot ulcer or diabetic heart disease.
A composition for improving diabetic complications comprising an extract of Colona auricaulata or a fraction thereof as an active ingredient, wherein the diabetic complication includes diabetic retinopathy, diabetic cataract, diabetic neuropathy, diabetic neuropathy, foot ulcer or diabetic heart disease Composition.
9. The method of claim 8, wherein the Colona auricaulata extract is Colona wherein the leaves, roots or the branches of auricaulata are extracted.
The food composition according to claim 8, wherein the extract is obtained by extracting with water, C 1 to C 4 alcohol or a mixed solvent thereof.
9. The food composition according to claim 8, wherein the extraction is any one selected from the group consisting of room temperature extraction, hot water extraction, cold extraction, reflux cooling extraction, ultrasonic extraction and steam extraction.
The food composition according to claim 8, wherein the Colona auricaulata extract or a fraction thereof improves the diabetic complication by inhibiting the production of a final glycosylated product.
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