KR100880876B1 - Pharmaceutical composition for the prevention and treatment of the ischemia-reperfusion injury in the flaps or tissues containing anthocyanin extracted from the Black soybean seed coat - Google Patents
Pharmaceutical composition for the prevention and treatment of the ischemia-reperfusion injury in the flaps or tissues containing anthocyanin extracted from the Black soybean seed coat Download PDFInfo
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Abstract
본 발명은 검정콩, 특히 검정콩 껍질로부터 추출된 안토시아닌(anthocyanin)을 유효성분으로 포함하는 피판이나 조직의 허혈-재관류 손상의 예방 또는 치료용 의약 조성물에 관한 것으로, 더욱 상세하게는 상기 안토시아닌은 시아니딘-3-글루코시드(cyanidin-3-glucoside), 델피니딘-3-글루코시드(delphinidin-3-glucoside) 및 피투니딘-3-글리코시드(petunidin-3-glucoside)으로 구성되어 있는 것을 특징으로 한다.The present invention relates to a pharmaceutical composition for the prevention or treatment of ischemia-reperfusion injury of flaps or tissues, which comprises anthocyanin extracted from black soybeans, in particular, black bean husks, as an active ingredient. More specifically, the anthocyanin is cyanidin- 3-glucoside (cyanidin-3-glucoside), delphinidin-3-glucoside (delphinidin-3-glucoside) and petunidin-3-glycoside (petunidin-3-glucoside) is characterized in that it is composed.
검정콩, 검정콩 껍질 성분, 안토시아닌(anthocyanin), 허혈-재관류 손상, 피판, 조직, 시아니딘-3-글루코시드, 델피니딘-3-글루코시드, 피투니딘-3-글리코시드 Black Bean, Black Bean Peel Components, Anthocyanin, Ischemia-Reperfusion Injury, Flap, Tissue, Cyanidin-3-Glucoside, Delphinidine-3-Glucoside, Petunidine-3-Glycoside
Description
도 1은 쥐의 피판(skin flap)의 허혈-재관류 손상(IRI)에 의한 피판의 생존 면적을 측정한 그림이다.1 is a diagram measuring the survival area of the flap due to ischemia-reperfusion injury (IRI) of the skin flap of the rat.
도 2는 시험예 1에서 허혈-재관류 손상 7일 후의 대조군, 실험군 A 및 실험군 B의 피판의 사진이다.Figure 2 is a photograph of the flap of the control group, experimental group A and experimental group 7 days after ischemia-reperfusion injury in Test Example 1.
도 3은 절단된 손가락의 미세접합수술 장면과 수술 후 사진이다.Figure 3 is a microjunction scene and a postoperative photograph of the cut finger.
도 4는 발의 피부와 조직의 괴사를 재건하기 위한 유리피판술 장면과 수술 후 사진이다.Figure 4 is a glass flap scene and postoperative pictures to reconstruct the necrosis of the skin and tissue of the foot.
본 발명은 검정콩, 특히 검정콩 껍질로부터 추출된 안토시아닌(anthocyanin)을 유효성분으로 포함하는 피판이나 조직의 허혈-재관류 손상의 예방 또는 치료용 의약 조성물에 관한 것으로, 더욱 상세하게는 상기 안토시아닌은 시아니딘-3-글루 코시드(cyanidin-3-glucoside), 델피니딘-3-글루코시드(delphinidin-3-glucoside) 및 피투니딘-3-글리코시드(petunidin-3-glucoside)으로 구성되어 있다.The present invention relates to a pharmaceutical composition for the prevention or treatment of ischemia-reperfusion injury of flaps or tissues, which comprises anthocyanin extracted from black soybeans, in particular, black bean husks, as an active ingredient. More specifically, the anthocyanin is cyanidin- 3-glucoside (cyanidin-3-glucoside), delphinidin-3-glucoside (delphinidin-3-glucoside) and petunidin-3-glycoside (petunidin-3-glucoside).
안토시아닌(Anthocyanin)은 흔히 식물체의 꽃, 과실, 줄기, 잎, 뿌리 등에 존재하는 수용성 색소 배당체(glucoside) 물질이다. 흔히 식물체 액포에 존재하며, 세포액의 산성농도, 색소화합물의 화학적 구조, 여러 금속이온들과의 결합 상태에 의해 자색, 적색, 청색 등의 색상을 나타내는 천연 색소이고, 안토시아닌은 어글리콘(aglycone) 및 글리코시드(glycoside)로 구성된다.Anthocyanin is a water soluble pigment glycoside (glucoside) substance that is often found in flowers, fruits, stems, leaves, and roots of plants. Often present in plant vacuoles, it is a natural pigment that shows the color of purple, red, blue, etc. by the acid concentration of cell fluid, chemical structure of pigment compound, and the state of binding to various metal ions. Anthocyanins are aglycone and It consists of glycosides.
현재 안토시아닌 성분은 포도, 딸기, 올리브, 적양배추, 가지, 장미 등의 식물체로부터 추출되어 여러 가지 원료로 이용되고 있으나, 거의 조색소 상태로 추출되어 이용되고 있는 실정으로, 안토시아닌 외에 다른 성분의 화합물이 공존하는 상태로 이용되는 경우가 많다.Currently, anthocyanin is extracted from plants such as grapes, strawberries, olives, red cabbages, eggplants, and roses, and is used as various raw materials. However, the anthocyanin is extracted and used in a roughly pigmented state. It is often used in the state of coexistence.
식물성 천연색소인 안토시아닌은 최근 여러 가지 생리활성이 있는 것으로 알려지고 있다. 예를 들면 노화억제작용, 항균작용, 돌연변이성 억제작용, 콜레스테롤 저하작용, 시력개선 효과, 혈관보호기능, 항궤양기능, 항산화기능 등이 알려져 있다. 이러한 생리활성은 모든 종류의 안토시아닌이 기본적으로 가지는 활성이지만, 최근 각 안토시아닌의 종류에 따라 그 활성의 차이가 있는 것으로 알려지고 있다.Anthocyanin, a plant natural pigment, has recently been known to have various physiological activities. For example, aging inhibitory action, antibacterial action, mutagenicity inhibitory action, cholesterol lowering action, vision improvement effect, vascular protection function, anti-ulcer function, antioxidant function is known. Such physiological activity is basically an activity of all kinds of anthocyanins, but recently, it is known that the activity of each anthocyanin is different depending on the type.
안토시아닌은 장관에서의 흡수도 매우 용이하다고 알려져 있으며 강력한 항산화(antioxidant) 효과를 가지고 있어 간과 심장의 허혈성 경색이나 폐에서 급성 염증 등의 동물 모델에서 세포 및 조직의 보호 효과를 보인 것으로 보고되고 있다 (Takanori Tsuda et al., Archives of biochemistry and biophysics, 1999, 368(2):361-366; Amorini A.M. et al, Free Radic. Res. 2003, 37(4):453-460). 또한 안토시아닌은 한국공개특허 2007-0026284호에서 뇌세포 손상기전의 복잡성 등으로 뇌졸중으로 발생하는 뇌신경 세포의 손상을 보호해 줄 수 있는 치료제용으로 공지되어 있다.Anthocyanins are known to be very easy to absorb in the intestinal tract and have strong antioxidant effects, which have been shown to have protective effects on cells and tissues in animal models such as ischemic infarction of the liver and heart or acute inflammation in the lungs (Takanori Tsuda et al., Archives of biochemistry and biophysics, 1999, 368 (2): 361-366; Amorini AM et al, Free Radic. Res. 2003, 37 (4): 453-460). In addition, anthocyanin is known in Korea Patent Publication No. 2007-0026284 for a therapeutic agent that can protect the damage of brain neurons caused by stroke due to the complexity of the brain cell damage mechanism.
허혈-재관류 손상(IRI, ischemia-reperfusion injury)이란 신체부위에 대한 혈액의 흐름이 일시적으로 중단(허혈)된 다음, 다시 재개(재관류)되는 경우에 유발된다. 허혈-재관류 손상의 주요 매개인자는 유리라디칼(free radical)과 중성구(neutrophil)로 추측되고 있으며[Askar, I., Oktay, M.F., Gurlek, A., and Bac, B. Protective effects of some antineoplastic agents on ischemia-reperfusion injury in epigastric island skin flaps. Microsurgery. 26: 193, 2006.], 또한 다형핵 중성구(polymorphonuclear neutrophils)는 재관류 동안에 혈관내피세포(vascular endothelial cell)와 상호작용하여 백혈구 부착 및 다양한 염증성 매개인자의 방출을 야기한다[Tosa, Y., Lee, W.P.A., Kollias, N., Randolph, M.A., and May, J.W. Monoclonal antibody to intercellular adhesion molecule 1 protects skin flaps against ischemia-reperfusion injury: An experimental study in rats. Plast. Reconstr. Surg. 101: 1586, 1998.].Ischemia-reperfusion injury (IRI) is caused when the flow of blood to the body is temporarily interrupted (ischemic) and then resumed (reperfusion). The major mediators of ischemia-reperfusion injury are presumed to be free radicals and neutrophils [Askar, I., Oktay, MF, Gurlek, A., and Bac, B. Protective effects of some antineoplastic agents on ischemia-reperfusion injury in epigastric island skin flaps. Microsurgery. 26: 193, 2006.] In addition, polymorphonuclear neutrophils interact with vascular endothelial cells during reperfusion resulting in leukocyte adhesion and release of various inflammatory mediators [Tosa, Y., Lee] , WPA, Kollias, N., Randolph, MA, and May, JW Monoclonal antibody to intercellular adhesion molecule 1 protects skin flaps against ischemia-reperfusion injury: An experimental study in rats. Plast. Reconstr. Surg. 101: 1586, 1998.].
재건수술분야에서의 허혈-재관류 손상은 수부나 기타 신체 조직(귀, 혀, 코 등)이 절단된 환자의 미세접합수술(도 3), 또는 외상이나 암 등 여러 가지 원인에 의해 생긴 조직 결손을 재건하기 위한 피판술(도 4)에서 흔히 발생되어진다. 따라서 피판이나 조직의 허혈-재관류 손상의 기전에 대한 많은 연구가 이루어지고 있다.Ischemia-reperfusion injury in reconstructive surgery may include tissue defects caused by microconjugation surgery (Figure 3) in patients with cuts in the hands or other body tissues (ears, tongues, noses, etc.) or by various causes such as trauma or cancer. It is commonly encountered in flap surgery for reconstruction (FIG. 4). Therefore, much research is being done on the mechanism of ischemia-reperfusion injury of flap or tissue.
또한 많은 약들이 허혈-재관류 손상을 줄이기 위한 피부 피판 모델 실험에 사용되었다. 예를 들면, Trimetazidine(항산화제), 항암제, FK506(면역억제제), Abciximab(혈소판 당단백질 IIb/IIIa 수용체 길항자), ICAM-1에 대한 단클론항체 등이 있다. 그러나 이들 약을 피부 피판의 허혈-재관류 손상에 사용하는 경우, 부작용이 발생하는 문제점이 있고, 이들 약은 상당히 고가라 사용하기에 경제적이지 않다. 따라서 상기 약들은 오로지 연구목적으로만 사용되고 있는 실정이다. 그러므로 주위에서 흔히 구할 수 있고, 값이 싸며, 비교적 안전한 재료를 이용한 약제 개발의 필요성이 대두되고 있다.Many drugs have also been used to test skin flap models to reduce ischemia-reperfusion injury. Examples include Trimetazidine (antioxidant), anticancer agent, FK506 (immunosuppressant), Abciximab (platelet glycoprotein IIb / IIIa receptor antagonist), monoclonal antibody to ICAM-1, and the like. However, when these drugs are used for ischemia-reperfusion injury of skin flaps, there is a problem that side effects occur, and these drugs are quite expensive and are not economical to use. Therefore, the drugs are used only for research purposes. Therefore, there is a need for the development of drugs using materials that are commonly available, inexpensive, and relatively safe.
한편, 검정콩은 1998년 미국의 FDA에서 콩단백질에 대하여 관상심장질환 예방효과를 인정한 이래 많은 연구가 되어 왔으며, 필수 지방산, 레시틴, 섬유질, 사포닌 등을 함유하고 있어 고혈압, 당뇨병, 동맥경화, 비만증과 같은 성인병의 예방 및 치료에 효과가 있다고 알려져 있다. 검정콩에 함유된 식물성 섬유는 변비는 물론 대장암 예방효과도 있다고 알려져 있으며, 동의보감에서는 검정콩에 대하여 ‘이는 약으로 쓰며 오장을 보하고 12경을 도와 장을 따스하게 하며 종기를 없애고 절임증을 치료하는 효과가 있다’고 언급하고 있다.On the other hand, black soybeans have been studied since 1998 in the United States FDA recognized the effect of preventing coronary heart disease against soy protein, and contains essential fatty acids, lecithin, fiber, saponin and so on, and hypertension, diabetes, arteriosclerosis, obesity It is known to be effective in the prevention and treatment of the same adult diseases. The vegetable fiber contained in black beans is known to prevent constipation and colorectal cancer. In Dong-bogam, it is effective for black beans to be used as a medicine, to protect the intestines, to protect the intestines, to warm the intestines, to remove boils, and to treat pickles. Is there. '
또한, 검정콩에 포함되어 있는 색소성분인 안토시아닌은 항산화제로서 장복하는 경우에 노화를 방지하는 효과가 있으며, 콩 단백질인 이소플라본은 강력한 항암활성을 가지는 제니스틴을 비롯한 사포닌, 화이토스테롤을 포함하고 있으며 칼슘이 뼈에 흡수되도록 하는 역할도 한다. 특히, 검정콩의 껍질에는 글리시테인이라는 항암물질이 포함되어 있다.In addition, anthocyanin, a pigment component contained in black soybeans, has an effect of preventing aging when worn as an antioxidant, and soy protein, isoflavone, contains saponins and phytosterols including genistin, which have strong anticancer activity. It also helps the calcium get absorbed into the bone. In particular, the black soybeans contain an anticancer substance called glycidine.
안토시아닌은 수용성 색소 배당체로서, 하이드록실기의 개수와 특정 하이드록실기의 메칠화에 의해 크게 6종의 안토시아니딘으로 구분되고, 안토시아니딘과 결합된 당의 종류와 아실기의 종류 및 결합 위치에 따라 수백종으로 구분되어진다.Anthocyanins are water-soluble pigment glycosides, which are largely divided into six types of anthocyanidins by the number of hydroxyl groups and the methylation of specific hydroxyl groups, and the types and bonds of sugars and acyl groups bonded to anthocyanidins. There are several hundred species depending on their location.
현재 안토시아닌의 다양한 건강증진 이익, 즉 잠재적인 항산화 효과, 항염증 효과 및 만성질병의 억제 등으로 인하여 안토시아닌은 주목을 받고 있다.At present, anthocyanins are attracting attention due to the various health-promoting benefits of anthocyanins, namely potential antioxidant effects, anti-inflammatory effects, and suppression of chronic diseases.
이에 본 발명자들은 피판과 조직에서의 허혈-재관류 손상의 예방 및 치료에 관한 연구를 진행하던 중, 놀랍게도 검정콩, 특히 검정콩 껍질로부터 추출된 안토시아닌이 피판에서 허혈-재관류 손상의 예방 및 치료에 효과적임을 발견하고 본 발명을 완성하였다.The inventors of the present invention, while studying the prevention and treatment of ischemia-reperfusion injury in flaps and tissues, surprisingly found that anthocyanins extracted from black soybeans, especially black soybean skin, are effective in preventing and treating ischemia-reperfusion injury in flaps. This invention was completed.
따라서 본 발명의 목적은 검정콩 껍질로부터 추출된 안토시아닌을 함유하여 피판이나 조직의 허혈-재관류 손상의 예방 또는 치료에 유용하게 사용되는 의약 조성물을 제공하는 것이다.Accordingly, it is an object of the present invention to provide a pharmaceutical composition containing anthocyanin extracted from black bean husks useful for the prevention or treatment of ischemia-reperfusion injury of flaps or tissues.
본 발명은 검정콩, 특히 검정콩 껍질로부터 추출된 안토시아닌(anthocyanin)을 유효성분으로 포함하는 피판이나 조직의 허혈-재관류 손상의 예방 또는 치료용 의약 조성물에 관한 것으로, 더욱 상세하게는 상기 안토시아닌은 시아니딘-3-글루코시드(cyanidin-3-glucoside), 델피니딘-3-글루코시드(delphinidin-3-glucoside) 및 피투니딘-3-글리코시드(petunidin-3-glucoside)으로 구성되어 있는 것을 특징으로 한다.The present invention relates to a pharmaceutical composition for the prevention or treatment of ischemia-reperfusion injury of flaps or tissues, which comprises anthocyanin extracted from black soybeans, in particular, black bean husks, as an active ingredient. More specifically, the anthocyanin is cyanidin- 3-glucoside (cyanidin-3-glucoside), delphinidin-3-glucoside (delphinidin-3-glucoside) and petunidin-3-glycoside (petunidin-3-glucoside) is characterized in that it is composed.
본 발명의 정제된 안토시아닌은 시아니딘-3-글루코시드(cyanidin-3-glucoside) 65~80중량%, 델피니딘-3-글루코시드(delphinidin-3-glucoside) 15~25중량% 및 피투니딘-3-글리코시드(petunidin-3-glucoside) 5~10중량%로 구성되어 있다.Purified anthocyanin of the present invention is 65 to 80% by weight of cyanidin-3-glucoside, 15 to 25% by weight of delphinidin-3-glucoside and petunidine- 3-glycoside (petunidin-3-glucoside) is composed of 5 to 10% by weight.
본 발명의 활성성분으로서 약제학적으로 유효한 양의 정제된 안토시아닌을 함유한 피판이나 조직의 허혈-재관류 손상의 예방 또는 치료용 의약 조성물은 약제학적으로 허용되는 담체와 함께 여러 가지 다양한 형태로 제형화 될 수 있다. 제형화는 당 분야에 공지된 방법에 따라 수행할 수 있다.Pharmaceutical compositions for the prevention or treatment of ischemia-reperfusion injury of flaps or tissues containing pharmaceutically effective amounts of purified anthocyanins as active ingredients of the present invention may be formulated in a variety of forms with pharmaceutically acceptable carriers. Can be. Formulation can be carried out according to methods known in the art.
상기 피판이나 조직의 허혈-재관류 손상의 예방 또는 치료용 의약 조성물은 다양한 경구 또는 비경구 투여 형태로 제형화할 수 있다. 경구 투여용 제형으로는 예를 들면 정제, 환제, 경질, 연질 캅셀제, 액제, 현탁제, 유화제, 시럽제, 과립제 등이 있는데, 이들 제형은 유효성분 이외에 희석제(예: 락토즈, 덱스트로즈, 수크로즈, 만니톨, 솔비톨, 셀룰로즈 및/또는 글리신), 활택제(예: 실리카, 탈크, 스테아르산 및 그의 마그네슘 또는 칼슘염 및/ 또는 폴리에틸렌 글리콜)를 함유할 수 있다. 정제는 또한 마그네슘 알루미늄 실리케이트, 전분 페이스트, 젤라틴, 트라가칸스, 메틸셀룰로즈, 나트륨 카복시메틸셀룰로즈 및/또는 폴리비닐피롤리딘과 같은 결합제를 함유할 수 있으며, 경우에 따라 전분, 한천, 알긴산 또는 그의 나트륨 염과 같은 붕해제 또는 비등 혼합물 및/또는 흡수제, 착색제, 향미제, 및 감미제를 함유할 수 있다. 상기 제형은 통상적인 혼합, 과립화 또는 코팅 방법에 의해 제조될 수 있다.The pharmaceutical composition for preventing or treating ischemia-reperfusion injury of the flap or tissue may be formulated in various oral or parenteral dosage forms. Formulations for oral administration include, for example, tablets, pills, hard capsules, soft capsules, solutions, suspensions, emulsifiers, syrups, granules, etc. These formulations may contain diluents (e.g., lactose, dextrose, water, etc.) in addition to the active ingredients. Cross, mannitol, sorbitol, cellulose and / or glycine), glidants such as silica, talc, stearic acid and its magnesium or calcium salts and / or polyethylene glycols. Tablets may also contain binders such as magnesium aluminum silicate, starch paste, gelatin, tragacanth, methylcellulose, sodium carboxymethylcellulose and / or polyvinylpyrrolidine, optionally starch, agar, alginic acid or its Disintegrants or boiling mixtures such as sodium salts and / or absorbents, colorants, flavors, and sweeteners. The formulations may be prepared by conventional mixing, granulating or coating methods.
또한 비경구 투여용 제형의 대표적인 것은 주사용 제제로 용매로서 물, 링거액, 등장성 생리식염수 또는 현탁액을 사용할 수 있으며, 멸균 고정 오일로는 용매 또는 현탁 매질로서 사용할 수 있고, 모노-, 디-글리세라이드를 포함하여 어떠한 무자극성 고정오일도 이러한 목적으로 사용될 수 있으며, 올레산과 같은 지방산은 주사용 제제에 사용할 수 있다. Also typical of parenteral formulations are water, Ringer's solution, isotonic physiological saline or suspension as a solvent for injection, sterile fixed oils can be used as a solvent or suspending medium, mono-, di-glycerol Any non-irritating fixed oil can be used for this purpose, including lides, and fatty acids such as oleic acid can be used in the preparation of injectables.
또한, 수성 또는 유성연고제, 산화방지제, 방부제, 중량제 등을 이용하여 연고제, 크림제, 겔제, 로숀제 등의 외용제로도 제형화될 수 있다.It may also be formulated into external preparations such as ointments, creams, gels, lotions, etc. using aqueous or oily ointments, antioxidants, preservatives, weights and the like.
또한, 지지층 또는 필름형의 기재와 유효성분, 담체 및 피부에 부착하기 위한 특수 점착제를 함유하는 매트릭스와 보호용 호일(=박리 라이너)로 이루어진 경피 패치로도 제형화될 수 있다.It may also be formulated as a transdermal patch consisting of a protective foil (= peeling liner) and a matrix containing a support layer or film-like substrate and a special adhesive for adhering to the active ingredient, carrier and skin.
본 발명의 안토시아닌의 투여량은 환자의 연령, 성별, 체중, 질환의 중증도에 따라 달라지나, 본 발명의 안토시아닌은 환자의 체중 1 kg 당 0.1 mg ~ 1 g을, 1일 1-4회 투여한다.The dose of anthocyanin of the present invention depends on the age, sex, weight, and severity of the disease of the patient, but the anthocyanin of the present invention is administered from 0.1 mg to 1 g per kg of body weight 1-4 times a day. .
이하, 본 발명의 구성을 실시예 및 시험예를 들어, 보다 구체적으로 설명하지만, 본 발명의 권리범위가 이들에 한정되는 것은 아니다.Hereinafter, the structure of the present invention will be described in more detail with reference to Examples and Test Examples, but the scope of the present invention is not limited thereto.
[실시예 1] 안토시아닌 추출 및 정제Example 1 Anthocyanin Extraction and Purification
진주 경상대학교 농경지에서 재배된 검은콩(Glycine max (L) Merr.) 껍질 200g을 이용하여 4℃에서 24시간동안 메탄올로 3회 반복하여 추출하였다. 이 추출액을 감압 농축하여 최종 부피가 200ml이 되게 희석하였다. 상기 안토시아닌이 포함된 용액을 100ml로 농축한 다음, Amberlite XAD-7 컬럼과 Spephadex LH-20을 이용하여 안토시아닌을 정제하였다. 정제된 안토시아닌은 시아니딘-3-글루코시드(cyanidin-3-glucoside) 72%, 델피니딘-3-글루코시드(delphinidin-3-glucoside) 20% 및 피투니딘-3-글루코시드(petunidin-3-glucoside) 6%를 함유하여 구성되었다. Glycine grown in Gyeongsang National University 200 g of max (L) Merr .) shell was extracted three times with methanol at 4 ° C. for 24 hours. The extract was concentrated under reduced pressure and diluted to a final volume of 200 ml. The anthocyanin-containing solution was concentrated to 100 ml, and the anthocyanins were purified using Amberlite XAD-7 column and Spephadex LH-20. Purified anthocyanins were 72% cyanidin-3-glucoside, 20% delphinidin-3-glucoside, and petunidin-3-glucoside. glucoside) 6%.
[시험예 1] 안토시아닌 처리 후 피판의 허혈-재관류 손상(ischemic-reperfusion injury in epigastric flap)의 보호 효과Experimental Example 1 Protective Effect of Ischemic-reperfusion Injury in Epigastric Flap after Flap Anthocyanin Treatment
피부 피판의 허혈-재관류 손상에 대한 안토시아닌의 보호 효과를 알아보기 위하여, 실험용 쥐(Spaugue-Dawley rat, 250g) 30마리를 45㎎/㎏의 소듐 펜토바르 비탈로 복강내 주사하여 마취시켰다. 실험용 쥐는 3개의 군으로 나누어, 실시예 1의 안토시아닌 또는 물을 허혈-재관류 손상 12시간 전에 먹였다.To investigate the protective effect of anthocyanins against ischemia-reperfusion injury of skin flaps, 30 rats of Spaugue-Dawley rats (250 g) were anesthetized by intraperitoneal injection with 45 mg / kg sodium pentobar beta. The experimental rats were divided into three groups and the anthocyanins or water of Example 1 were fed 12 hours before ischemia-reperfusion injury.
대조군 : 물(0.25ml/250g)을 먹임Control: fed water (0.25ml / 250g)
실험군 A : 안토시아닌 50mg/Kg을 먹임Experimental group A: fed anthocyanin 50mg / Kg
실험군 B : 안토시아닌 100mg/Kg을 먹임Experimental group B: fed anthocyanin 100mg / Kg
상기 대조군, 실험군 A 및 실험군 B의 실험용 쥐(각 군별로 10마리)의 흉부와 복부의 털을 제거하고, 오른쪽 부위에 3 X 5 cm의 피판을 디자인하였다. 아래쪽의 하복비동정맥(inferior epigastric vessel)만 남겨두고 피판을 완전히 일으켰다. 그리고 하복비동정맥(inferior epigastric vessel)의 근위부와 원위부의 대퇴 혈관(femoral vessel)도 잘 박리하였다. 원위부의 대퇴 혈관(femoral vessel)은 6-0 나일론(6-0 nylon)으로 결찰하였다. 근위부의 대퇴 혈관(femoral vessel)은 미세혈관 애클란드 2V 클램프(microvascular Acland 2V clamp)로 임시로 결찰하였다. 피판을 다시 배의 원래자리에 옮겨 놓고, 3-0 나일론(3-0 Nylon)으로 고정하였다. 항생제를 근육주사로 주었고, 쥐(rat)가 스스로 피판을 해치는 것을 막기 위해, 투명한 비닐로 피판을 보호하였다. 10시간 뒤 쥐(rat)를 다시 마취하고, 클램프(clamp)를 제거하였다. 그리고 다시 피판을 원래 자리에 철저히 봉합하였다. 수술 후 7일째, 쥐(rat)를 죽인 다음, 피판의 생존 부위와 괴사 부위의 면적을 측정하였다. 수술 전에 디자인한 피판을 100으로 하여 생존한 피판의 면적을 백분율로 나타내었다.The hairs of the chest and abdomen of the experimental rats (10 mice in each group) of the control group, the experimental group A and the experimental group B were removed, and a flap of 3 × 5 cm was designed on the right side. The flap was completely developed, leaving only the lower inferior epigastric vessels. The femoral vessels of the proximal and distal portions of the inferior epigastric vessels were also well detached. The distal femoral vessels were ligated with 6-0 nylon. The proximal femoral vessels were temporarily ligated with a microvascular Acland 2V clamp. The flap was returned to its original position and fixed with 3-0 Nylon. Antibiotics were given by intramuscular injection, and the flap was protected with clear vinyl to prevent rats from harming the flap themselves. After 10 hours the rats were anesthetized again and the clamps were removed. The flap was then completely sealed back to its original position. Seven days after the operation, rats were killed, and the areas of survival and necrosis of the flap were measured. The area of the flap that survived was expressed as a percentage by using the flap designed before the operation as 100.
그 결과를 도 1에 도식화하였다. 도 1로부터 안토시아닌을 수술 12시간 전에 먹인 실험군 A 및 B는 대조군(62%)에 비해 피부 피판에서 생존 면적이 74.5% 및 83%로 증가하였으며, 안토시아닌의 농도가 높을수록 피판의 생존 면적이 증가되었음을 알 수 있다.The result is shown in FIG. Experimental groups A and B fed anthocyanin 12 hours before surgery from FIG. 1 increased the survival area of the skin flap to 74.5% and 83% compared to the control group (62%), and the higher anthocyanin concentration increased the survival area of the flap. Able to know.
상기에서 살펴본 바와 같이, 본 발명의 검정콩, 특히 검정콩 껍질로부터 추출된 안토시아닌(anthocyanin) 즉, 시아니딘-3-글루코시드(cyanidin-3-glucoside) 65~80중량%, 델피니딘-3-글루코시드(delphinidin-3-glucoside) 15~25중량% 및 피투니딘-3-글리코시드(petunidin-3-glucoside) 5~10중량%로 구성된 안토시아닌은 항산화 및 항염증 특성을 가지고 있어, 피판이나 조직의 허혈-재관류 손상으로부터 피판이나 조직의 생존을 개선시키는 유용한 효과를 나타내어, 우수한 허혈-재관류 손상의 예방 및 치료제로 유용하게 상용될 수 있다.As described above, 65 to 80% by weight of anthocyanin, that is, cyanidin-3-glucoside extracted from black bean, particularly black bean skin of the present invention, delphinidin-3-glucoside ( Anthocyanin, consisting of 15-25% by weight of delphinidin-3-glucoside and 5-10% by weight of petunidin-3-glucoside, has antioxidant and anti-inflammatory properties and ischemia in flaps and tissues. It has a useful effect of improving the survival of flaps or tissues from reperfusion injury and can be usefully used as a prophylactic and therapeutic agent for superior ischemia-reperfusion injury.
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| PCT/KR2008/000509 WO2008126979A1 (en) | 2007-04-11 | 2008-01-28 | Pharmaceutical composition for the prevention and treatment of the ischemia-reperfusion injury in the flaps or tissues containing anthocyanin extracted from the black soybean seed coat |
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| KR20010084705A (en) * | 2000-02-28 | 2001-09-06 | 김동태 | Method for extracting natural anthocyanin pigments from a seed coat |
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