201216975 六、發明說明： 【發明所屬之技術領域】 本發明是有關於一種組合物，特別是有關於一種調 整血脂及保護心血管之組合物。 【先前技術】 所謂心血管疾病包含中風、心臟疾病、高血壓及高 血月曰症等。近年來，這些疾病已成為各先進國家的頭號 殺手。在台灣地區，因心血管疾病而死亡之死亡人數高 居國人十大死因的第二、三及十位’也因而造成無數家 庭之遺憾。 高脂血症與血管功能的老化係為引發心臟血管疾病 ，重要危險因子。當平日飲食中攝取太多的油脂或攝取 高$量之食物，於體内代謝後，血液中脂肪濃度增加， 使得脂肪容易堵塞於血管内，造成血管壁增厚、孔徑變 小等。心臟必須要額外增加力量來輸送血液，才能使血 液輸送至周邊組織，以滿足血液循環對於身體的營養供 應、廢物排出及氣體交換的目的。這些動脈變厚、變僵 硬的生理改變，會使血壓加大、心臟收縮壓增加，使得 :邊的血管壓力增加’導致左心室的肥大，血壓異常增 高，甚至還會造成動脈粥狀硬化的危險。 θ 對於治療心血管疾病上，皆是先透過飲食及運動的 方式改善，若無法改善時，才透過藥物進行治療。除了 可改變飲食習慣（其包含採用低膽固醇、低鹽分、低熱 201216975 高：，水果等)、維持標準體 可“=充== 適口大眾所錢受之營養補充品係為重要之課題。發 【發明内容】 之問題，本發明之目的就是在 心血管之組合物，以達到降低201216975 VI. Description of the Invention: [Technical Field of the Invention] The present invention relates to a composition, and more particularly to a composition for regulating blood lipids and protecting cardiovascular. [Prior Art] The cardiovascular disease includes stroke, heart disease, hypertension, and hyperemia. In recent years, these diseases have become the number one killer in advanced countries. In Taiwan, the number of deaths due to cardiovascular disease is high, and the second, third and tenth deaths of the top ten causes of death in the country have caused regrets for countless families. Hyperlipidemia and aging of vascular function are important risk factors for cardiovascular disease. When you eat too much fat or eat a high amount of food in your diet, the fat concentration in the blood increases after the metabolism in the body, which makes the fat easily clog in the blood vessels, causing the blood vessel wall to thicken and the pore diameter to become smaller. The heart must add extra strength to deliver blood in order to deliver blood to surrounding tissues for the purpose of blood circulation for nutrient supply, waste discharge, and gas exchange. These arterial thickening and stiffening physiological changes will increase blood pressure and increase systolic blood pressure, resulting in: increased vascular pressure on the side - leading to hypertrophy of the left ventricle, abnormally elevated blood pressure, and even the risk of atherosclerosis . θ For the treatment of cardiovascular disease, it is first improved through diet and exercise. If it cannot be improved, it will be treated through drugs. In addition to changing dietary habits (which include low cholesterol, low salt, low heat 201216975 high: fruit, etc.), maintaining the standard body can be "=charge == suitable for the public to receive the nutritional supplements as an important issue. SUMMARY OF THE INVENTION The problem of the present invention is to achieve a reduction in cardiovascular compositions.
有鑑於上述習知技藝 k供一種調整血脂及保護 血脂之功效。 —根據本發明之目的，提出一種調整血脂及保護心血 官之組合物’其包含紅景天複方粉、紅麴、植物固醇、 納豆及維生素B群。1中，旦工相士丨、y , 八τ 、·工厅、天複方粉、紅麴、植物 固醇、納豆及維生素㈣細—預定比例混合。 其中，紅景天複方粉：紅麴及植物固醇：納豆及維 生素B群之預定比例為54〜79 : 14〜39 : 7〜32重量百分 比。 其中，紅景天複方粉可包含洛神、紅景天、丹蔘、 桑葉、決明子、荷葉、仙楂、甘草或其組合。 其中，紅麴可包含莫那可林K(m0nacoHnK)，而納 豆則包含納豆激酶（Nattokinase) 〇 其中’本發明之組合物係可為粉末狀、顆粒狀或液 體狀，或可呈錠劑、膠囊、片劑、粉劑、軟膏劑或喷劑 等之型式。 201216975 ,八中’本發明之組合物係可更包括醫藥與食品可接 =-賦形劑或-添加劑。賦形劑或添加劑可選自由調 味劑、增甜劑、防腐劑、抗氧化劑1合劑、等渗 潤滑:卜錠劑佐劑、著色劑、保濕劑、結合劑以及醫藥 可相谷載劑所組成之群組中。 其中，本發明之組合物可以口服之方式給予。 承上所述，依本發明之調整血脂及保護心血管之組 合物，其可具有一或多個下述優點： (1)因本發明之組合物含有紅景天複方粉其可降 低“肌耗氧里及耗氧指數，具有一定降低血壓和減慢心 跳速率的作用。 (2) 本發明之組合物中的紅麴含有其本身的代謝物 (活性成分）：莫那可林K (m〇nac〇Hn κ)，其可抑制膽固 醇合成步驟中的HMG_c〇a還原酵素 (3 hydroxy-3-methyl-glutaryl-CoA reductase)。而植物固 醇之結構則與人體膽固醇相似，其可於腸道中與動物性 膽固醇競爭吸收。因此，持續實用本發明之組合物，可 使服用者有效降低血脂濃度。 (3) 本發明之組合物中的納豆（含有納豆激酶）不僅 可抑制血栓之形成，更具有溶解血栓之作用。而維生素 B群於體内係擔任輔酶之角色，其可與酵素接合使其活 化，進而使身體中各種代謝得以進行。因此，持續食用 本發明之組合物’可使服用者有效增加代謝能力及保護 心金管功能。 201216975 【實施方式】 實施例1:本發明之調整血脂及保護心血管 物之組成 σ 本發明之調整血脂及保護心、血管之組合物包含红景 天複方粉、紅麴、植物固醇、納豆及維生素Β群。其中二 紅景天複方粉、紅麴、植物固醇、納豆及維生素Β群係 以=預定比例混合，即紅景天複方粉：紅麴及植物固醇 納豆及維生素Β群之預定比例為54〜79 : 14〜39 : 7〜μ 重量百分比。 上述之紅景天複方粉可包含洛神、紅景天、丹蔘、 桑葉:決明子、荷葉、仙楂、甘草或其組合。而紅麴可 包含莫那可林K (monacolin Κ)，而納豆則可包含納豆激 酶（Nattokinase)。 此外，本發明之組合物更可包括醫藥與食品可接受 之一賦形劑或一添加劑，將本發明之組合物製作為粉末 狀、顆粒狀、液體狀或乳膠狀等。又，本發明之組=物 可經過加工處理，進而將其製作呈錠劑、膠囊、片二、 粉劑、軟膏劑或喷劑等之型式，以供各種年齡之使用者 食用（口服）。例如年紀較小或年紀較長之使用者，無法 以錠劑之形式吞食時，可以開水沖泡粉劑形式之本發明 之組合物食用、或以液體形式食用。 對於膠囊形式而言，可為動物性膠囊或植物性膠 囊’動物性膠囊可例如由動物膠(gelatin)所製成，而植物 201216975 性膠囊可例如由缓甲基纖維素納（s〇dium carb〇xy酬^ cellulose)所製成。對於純素者而言，可藉由植物性膠囊 包覆本發明之組合物而食用。其中，賦形劑或添加劑可 ^自由調味劑、增甜劑、防腐劑、抗氧化劑、養合劑、 等滲透劑、潤滑劑、鍵劑佐劑、著色劑、保濕劑、於人 劑以及醫藥可相容載劑所組成之群組中。 。α 實施例2 :較佳實施例 本實施例以動物實驗與人體實驗作驗證，以證實 發明之組合物具有調整血脂及保護心血管之功效。 (一）動物實驗 (1)動物飼養 =大動物中心、，購人四週齡的雄性倉鼠（娜 golden Synan hamster) %隻，每四隻放於一個飼養 内;動：房的環境控制在231力’相對濕度在4〇峨。 山’並以自動定時H控制其光照期與黑暗期，其 到晚上六點為光照期(lightperi〇d)，晚上六點到翌 η早六：為黑暗期(dark peri〇d)，光照期與黑暗期各 先；己錄^ B ^ _養方5^用自由攝食法㈣libi她）， 予要使：物’每曰給予足量飼料與蒸顧水的投 If動物不錢乏，並每天更新或添加新鮮飼料前先 :式樣品’其目的為盡量做到空腹狀態服用測試樣 (2)飼料配方 飼料製備程序為，將是以含大豆油7%的半純化飼料 201216975 (AIN-93G)(對照組）、或含7%大豆油、8%耶子油及0.2% 膽固醇的調整飼料（高油脂高膽固醇組）。將購入飼料置 於-20°C冷凍櫃保存，以確保成分的穩定性。 (3)動物分組 先以動物房内一般飼料5001 (脂肪含量10%，膽固 醇為0.2 ppm)餵食倉鼠二週。待其適應後，於六週齡時 依體重隨機分為七組，每組8隻。實驗期共進行八週， 飼養期間每日測量體重並記錄之。分組依據主要是（1)食 • 用正常飼料（AIN-39G)為對照組一組，每日以管餵同體積 過濾水；（2)银食高油脂高膽固醇飼料，並加上每日以管 假食紅麴、納豆萃取物（其無添加紅景天複方粉，簡稱 RN)為一組，而本發明之組合物（簡稱RNH)包括高、中 及低三種劑量共三組，所以相關組別共有四組；及（3)採 血前一週（即第三週）或前二週（即第六週）服用降血脂藥 物依替米貝（ezitimbe)為一組，合計共六組組別，所以加 上對照組後整個實驗將為七組動物。餵食RNH、RN及 • 臨床降血脂藥ezitimbe皆按其體重變化管餵食所設定的 實驗劑量。七組實驗分組如下： 組別 飼料、介入物及劑量 對照組 正常飼料（含大豆油7 %的基礎飼料） 南脂飼料組 高脂飼料（0.2%膽固醇+ 7 %大豆油+ 8 %椰子油） RNH高劑量組 高脂食物+高劑量之本發明之組合物 (333.4毫克/公斤/天） 201216975 RNH中劑量組 高脂食物+中劑量之本發明之組合物 (83.35毫克/公斤/天） RNH低劑量組 高脂食物+低劑量之本發明之組合物 (41.68毫克/公斤/天） RN組 高脂食物+紅麴、納豆萃取物（27.09毫 克/公斤/天） 正對照組 高脂食物+ ezetimibe (3毫克/公斤/天） (4)樣品收集與分析 所有動物於採血前一晚禁食14小時，以避免血清中 的外生性血脂影響到内生性血脂的值，並使得血液能趨 於穩定。整個實驗採血時間分別為0週、第4週以及第 8週共有三次，採血方式主要以眼窩採血方式進行得到1 毫升的血液，置放於含有EDTA的採血管中冰浴。之後， 於離心機以3,000 rpm (1,570 xg)、4°C的條件下離心15 分鐘，待其離心完後取上清液，此上清液即為血聚，可 進行以下分析： (A) 血脂質測定指標： 包括血清（或血聚；以下皆同）三酸甘油酉旨 (triglyceride，TG)和高密度脂蛋白膽固醇（HDL-C)。 (B) 血中肝功能指標GOT、GPT及腎功能指標血中 尿素氮（BUN)和肌酸酐（creatine)的測定。取出血液上清 液，以生化儀（FUJI DRI-CHEM FDC3000 V2.1-P03E)測 得動物之血脂以及GOT、GPT、尿素氮和肌酸酐。 201216975 以上所試驗之結果以SPSS統計軟體進行分析。所 有數據均以平均值±標準差（mean iSD)表示。血液樣本項 目以一因子的變異數分析（two-way ANOVA test)進行統 計分析’並以；7<0.01及0.05表示具有統計上的差異。、 (5)本發明之組合物對倉鼠體重之影響 請參閱第1圖，其係為本實施例之各組飲食對倉鼠 體重之衫響。由圖中結果顯示，隨著餵食週數的增加， 所有貫驗動物體重皆穩定上升。其中，高脂飼料組與 RNH高劑量組之倉鼠的體重增加最多。而對照組的倉鼠 體重約在中間程度，其與RNH低劑量組及RN組之倉鼠 體重接近。RNH中劑量組之體重則又較前述三組稍低 些，體重增加最少的組別則為服用降血脂藥ezitimbe的 正對照組。推測ezitimbe仍具一定程度的毒性，本實施 例所使用ezitimbe之劑量雖屬安全，但仍可能導致該組 體重較輕。以上所述結果可以發現高脂飼料餵食八週 後’造成實驗動物體重上升，利用ANOVA統計分析組 間並無差異，其結果如表1所示。 表1各組倉鼠在〇、4、8週體重變化 __ 組別 第〇週 第4週 第8週 對照組 90.5 ± 8.0 113.9 ± 10.7 130.1 ± 13.0 tfj脂飼料組 93.1 ± 8.4 120.6 ± 11·4 136.4 ± 11.6 RNH高劑量組 96.8 ± 8.9 122.6 ± 12.7 134.6 ± 16.3 RNH中劑量組 92.1 ± 6.6 113.9 ± 7.3 126.8 ± 9.1 11 201216975 RNH低劑量組 93.3 ± 8.0 115.9 ± 8.6 ------- 130.5 + 1〇 〇 RN組 94.1 ± 8.0 113.5 ± 10.4 _128J_± 9.8 正對照組 96.8 ± 8.6 115.1 ± 13.2 125.3 + 15 Q —--- 」 (6)本發明之組合物對血液生化數值之影響 傲食總共八週的動物實驗中共有三個採血點，分別 為餵食前的〇週、餵食4週後、以及8週後。所得的血 漿需測定血液生化數值，包括血脂生化數值及肝、腎臟 指標，各結果如以下所示。 (a)三酸甘油酉旨 清參閱第2圖，其係為本實施例之各組飲食對倉鼠 體内三酸甘油酯濃度之影響。圖中，所有實驗動物血液 中的三酸甘油酯濃度，第四週所測得之結果皆明顯高於 第八週。其中，對照組除了與RNH高劑量組與RN組外， 其與其他組別皆具有顯著差異（P<0.05)。而第八週時， RNH高劑量組之三酸甘油酯濃度顯著低於高脂飼料組 (/?<0.01)。此外’南RNH中劑量組、RNH低劑量組、rn 組及正對照組，在第四週與第八週血中三酸甘油酯皆略 有下降。而服用降血脂藥ezitimbe —或二週，皆可以降 低血中三酸甘油酯量，但只有服用降血脂藥ezidmbe二 週’即在第八週測定三酸甘油酯濃度與高脂飼料組比 較’於統計上才有差異(^<0.05)。由此結果可知，連續服 用本發明之組合物（特別為高劑量333.4 mg/kg/day)八週 後，具有降低血液中三酸甘油酯濃度之功效，詳細統計 差異如表2所示。 201216975 表2各組倉鼠在0、4、8週TG變化 組別 第0週 第4週 第8週 對照組 328_38±68.74a 165.38±12.97a 116.38±20.63a 南脂飼料組 319.25±45.82a 322.75±79.97b* 279.00±67.63b" RNH高劑量組 356.25±106.72a 241.25±77.65a 181.38±49.82a RNH中劑量組 332.63±86.45a 271.75±54.24b* 210.88±45.67b* RNH低劑量組 375.63±119.68a 256.63±64.98a 206.38±59.65b* RN組 360.38±79.88a 211.13±67.20a 199.00±44.43a 正對照組 373.25±105.25a 246.75±29.33b“ 195.00±58.92a * :代表p值< 0.05 ; **代表p值< 0.01 (b)高密度脂蛋白膽固醇 請參閱第3圖，其係為本實施例之各組飲食對倉鼠 體内高密度脂蛋白之影響。圖中，對照組的之高密度脂 蛋白膽固醇顯著低於其他組〇<0.01)。由此可知因攝食高 • 脂食物四週或八週後的實驗動物，係透過提昇高密度脂 蛋白膽固醇濃度，以便能運走血中過多的膽固醇量以達 到自我保護目的。但，此種保護能力無法長時間延續， 最終仍會造成心血管疾病。而正對照組（服用ezitimbe) 係可降低血中總膽固醇濃度，故合理解釋此組的高密度 脂蛋白膽固醇濃度增加較少。 (c)肝功能指標 本實施之肝功能指標係檢測血漿中麩草酸轉氨基酶 13 201216975 (GOT)、及麵氨酸焦葡萄酸轉氨基酶(GPT) 〇通常體重增 加或服用類固醇治療疾病時GOT和GPT值會上昇。GOT 和GPT用於檢測肝細胞損傷程度，具有相當的實用性。 GPT主要來自肝臟，而GOT常見於許多肝外組織，如心 臟、骨骼肌和腎臟等。因此臨床上GPT才是肝細胞受 損較具特異性的指標。急性肝炎初期，血清GOT值高於 GPT值（G0T/GPT>1)。由於GOT值下降較快，後期GPT 較GOT高（G0T/GPT<1)，故慢性肝炎時，GOT/GPT比 值常小於1。GOT和GPT濃度與肝損傷嚴重程度或預後 · 少有相關性。 由於攝食高脂食物八週，實驗倉鼠其體重皆增加， 為了檢測各組飲食是否會影響其倉鼠之肝功能，因此測 定各組之倉鼠血液中的GOT及GPT作為肝功能之依據。 請參閱第4圖，其係為本實施例之各組飲食對GOT 之影響。由圖中可知，不論是餵食正常飼料亦或高脂食 物所有實驗動物的GOT指數並無明顯變化，且實驗結果 皆不具有統計分析差異上意義。而對GPT而言，各組間 _ 亦無明顯變化（圖未示）。 (d)腎功能指標尿素氮及肌酸酐 尿素氮是蛋白質的代謝產物。蛋白質經腎臟分泌而 經由尿液排出於體外。如果血中尿素氮的濃度升高，就 能反應腎功能異常。但若缺乏水份、吃大量蛋白質食物、 上消化道出血、嚴重肝病、感染、使用類固醇藥物、及 腎血流量不足等因素影響，也會使血中尿素氮濃度暫時 14 201216975 性上升H角度來說’如果因為腎臟病導致尿素氣 上升時，往往腎臟病已進展到相當的程度，喪失早期债 測的功能，也就是說尿錢不能在早期反應出腎臟病。 肌巧是非常穩定的腎功能指標，f用於評估腎功能障 礙的嚴重程度’及腎臟病的病情監控，但不適用於 腎臟疾病的篩檢。 ^In view of the above-mentioned prior art k, it is useful for adjusting blood lipids and protecting blood lipids. - In accordance with the purpose of the present invention, a composition for regulating blood lipids and protecting heart and blood is provided, which comprises Rhodiola compound powder, red peony root, phytosterol, natto and vitamin B group. In the 1st, the work phase of the gentry, y, eight τ, · Gong Hall, Tianfufang powder, red peony, phytosterol, natto and vitamins (four) fine - a predetermined proportion of mixing. Among them, Rhodiola compound powder: red peony and phytosterol: the predetermined ratio of natto and vitamin B group is 54~79: 14~39: 7~32 weight percentage. Among them, the Rhodiola compound powder may include Luoshen, Rhodiola, Tanjung, Mulberry, Cassia, Lotus, Fairy, Licorice or a combination thereof. Wherein, the red peony may comprise monacolin K (m0nacoHnK), and the natto comprises nattokinase (wherein the composition of the invention may be in the form of a powder, a granule or a liquid, or may be in the form of a lozenge, A type of capsule, tablet, powder, ointment or spray. 201216975, 八中' The composition of the present invention may further comprise a medicinal and food contact =-excipient or -additive. Excipients or additives can be selected from flavoring agents, sweeteners, preservatives, antioxidants 1 mixture, isotonic lubrication: tablets adjuvants, colorants, moisturizers, binders and pharmaceutical phase-loading agents In the group. Among them, the composition of the present invention can be administered orally. According to the present invention, the blood lipid-modifying and cardiovascular-protecting composition according to the present invention may have one or more of the following advantages: (1) The composition of the present invention contains Rhodiola Compound Powder, which can reduce "muscle" Oxygen consumption and oxygen consumption index have a certain effect of lowering blood pressure and slowing heart rate. (2) Red cockroach in the composition of the present invention contains its own metabolite (active ingredient): monacolin K (m) 〇nac〇Hn κ), which inhibits 3 hydroxy-3-methyl-glutaryl-CoA reductase in the cholesterol synthesis step, while the structure of phytosterol is similar to human cholesterol, which is available in the intestine The tract is competing for absorption with animal cholesterol. Therefore, the composition of the present invention can be used continuously, so that the user can effectively lower the blood lipid concentration. (3) The natto (containing nattokinase) in the composition of the present invention can inhibit not only thrombus formation, but also It also has the effect of dissolving blood clots, and the vitamin B group acts as a coenzyme in the body, which can be activated by binding with enzymes, thereby allowing various metabolisms in the body to proceed. Therefore, the combination of the present invention is continuously consumed. The object can effectively increase the metabolic capacity and protect the heart tube function. 201216975 [Embodiment] Example 1: Adjusting blood lipid and protecting cardiovascular composition of the present invention σ Adjusting blood lipid and protecting heart and blood vessel combination of the present invention The product includes Rhodiola compound powder, red peony root, phytosterol, natto and vitamin strontium group. Among them, two Rhodiola compound powder, red peony root, plant sterol, natto and vitamin strontium group are mixed in a predetermined ratio, ie red Sedum compound powder: the predetermined ratio of red peony and plant sterol natto and vitamin strontium group is 54~79: 14~39: 7~μ by weight. The above-mentioned Rhodiola compound powder can contain Luoshen, Rhodiola, Dan蔘, mulberry leaves: cassia seed, lotus leaf, immortelle, licorice or a combination thereof, while red peony may contain monacolin K, while natto may contain nattokinase. Furthermore, the composition of the invention The invention may further comprise a pharmaceutical or food acceptable excipient or an additive, and the composition of the present invention is made into a powder, a granule, a liquid or a latex, etc. Further, the group of the present invention may be added. The treatment is carried out in the form of a tablet, a capsule, a tablet, a powder, an ointment or a spray for consumption by a user of various ages (orally), for example, a younger or older user, When it is not possible to swallow in the form of a lozenge, the composition of the present invention in the form of a boiled powder can be eaten or consumed in liquid form. For the capsule form, it can be an animal capsule or a vegetable capsule. Made from animal gelatin, the plant 201216975 capsule can be made, for example, from sodium carbaryl ketone. For vegans, the composition of the invention may be coated by a vegetable capsule. Among them, excipients or additives can be free of flavoring agents, sweeteners, preservatives, antioxidants, nutrients, penetrants, lubricants, key adjuvants, colorants, moisturizers, humans, and pharmaceuticals. In a group consisting of compatible carriers. . α Example 2: Preferred Embodiments This example was verified by animal experiments and human experiments to confirm that the composition of the invention has the effects of regulating blood lipids and protecting cardiovascular. (1) Animal experiment (1) Animal breeding = large animal center, purchase of four-year-old male hamsters (na golden Synan hamster) % only, each of which is placed in one feeding; moving: the environment of the house is controlled at 231 'Relative humidity is 4 〇峨. Mountain 'and control its light period and dark period with automatic timing H, which is light period (lightperi〇d) at 6 pm, 6 pm to 早 早 6: dark peri〇d, light period And the dark period of each first; recorded ^ B ^ _ Yang Fang 5 ^ with free feeding method (four) libi her), to make: the object 'every sputum to give enough feed and steamed water to pay if the animal is not too much, and every day Before updating or adding fresh feed: the purpose of the sample is to try to take the test sample as fast as possible. (2) The feed formula preparation procedure is to use the semi-purified feed containing 7% soybean oil 201216975 (AIN-93G) (Control group), or adjusted feed containing 7% soybean oil, 8% yoghurt oil and 0.2% cholesterol (high fat and high cholesterol group). The purchased feed is stored in a freezer at -20 ° C to ensure the stability of the ingredients. (3) Animal grouping Hamsters were first fed for two weeks in the animal room with a general feed of 5001 (10% fat, 0.2 ppm cholesterol). After being adapted, they were randomly divided into seven groups according to body weight at six weeks of age, with 8 rats in each group. The experiment period was carried out for a total of eight weeks, and the body weight was measured daily during the feeding period and recorded. The grouping is mainly based on (1) food • using normal feed (AIN-39G) as a control group, and feeding the same volume of water every day; (2) silver food high fat and high cholesterol feed, plus daily Tube fake red sorghum, natto extract (with no added Rhodiola compound powder, referred to as RN) as a group, and the composition of the present invention (referred to as RNH) includes three groups of high, medium and low doses, so the relevant group There are four groups; and (3) one week before the blood collection (ie, the third week) or the first two weeks (the sixth week), taking the hypolipidemic drug ezitimbe as a group, a total of six groups, Therefore, after the addition of the control group, the entire experiment will be seven groups of animals. Feeding RNH, RN, and • The clinical hypolipidemic drug ezitimbe was administered at the experimental dose set by the tube of weight change. The seven groups of experiments were grouped as follows: Group feed, intervention and dose control group Normal feed (basic feed containing 7 % soybean oil) High fat diet (0.2% cholesterol + 7 % soybean oil + 8 % coconut oil) RNH high dose group high fat food + high dose of the composition of the invention (333.4 mg / kg / day) 201216975 RNH medium dose group high fat food + medium dose of the composition of the invention (83.35 mg / kg / day) RNH Low-dose group of high-fat food + low-dose composition of the present invention (41.68 mg / kg / day) RN group of high-fat food + red glutinous rice, natto extract (27.09 mg / kg / day) positive control group of high-fat food + Ezetimibe (3 mg/kg/day) (4) Sample collection and analysis All animals were fasted for 14 hours before the blood collection to avoid the exogenous blood lipids in the serum affecting the value of endogenous blood lipids and making the blood tend to stable. The blood collection time of the whole experiment was 0 times, 4 weeks, and 8 weeks, respectively. The blood collection method was mainly to obtain 1 ml of blood by eye socket blood collection, and placed in an ice bath of EDTA-containing blood collection tubes. After that, centrifuge at 3,000 rpm (1,570 xg) and 4 °C for 15 minutes in a centrifuge. After the centrifugation, the supernatant is taken. The supernatant is blood aggregated and can be analyzed as follows: (A) Blood lipid measurement indicators: including serum (or blood agglutination; all of the following) triglyceride (TG) and high density lipoprotein cholesterol (HDL-C). (B) Blood function indicators of liver function GOT, GPT and renal function indicators Determination of blood urea nitrogen (BUN) and creatinine (creatine). The blood supernatant was taken out, and the blood lipids of the animals as well as GOT, GPT, urea nitrogen and creatinine were measured by a biochemical analyzer (FUJI DRI-CHEM FDC3000 V2.1-P03E). 201216975 The results of the above tests were analyzed by SPSS statistical software. All data are expressed as mean ± standard deviation (mean iSD). The blood sample items were statistically analyzed by a two-way ANOVA test and statistically significant at 7 < 0.01 and 0.05. (5) Effect of the composition of the present invention on the body weight of hamsters Referring to Fig. 1, it is the weight of each group of diets for the weight of hamsters of the present embodiment. The results in the figure show that as the number of feeding weeks increases, the body weight of all the tested animals increases steadily. Among them, the hamsters in the high-fat diet group and the RNH high-dose group had the most weight gain. The hamsters in the control group weighed about the middle, which was close to the RNH low dose group and the RN group. The body weight of the RNH middle dose group was slightly lower than the above three groups, and the group with the least weight gain was the positive control group taking the hypolipidemic drug ezitimbe. It is speculated that ezitimbe still has a certain degree of toxicity. Although the dose of ezitimbe used in this example is safe, it may still cause the group to weigh less. The above results showed that after the high-fat diet was fed for eight weeks, the weight of the experimental animals was increased, and there was no difference between the groups by ANOVA statistical analysis. The results are shown in Table 1. Table 1 Changes in body weight of each group of hamsters at 〇, 4, and 8 weeks __ Group Week 4 of the fourth week of the 8th week of the control group 90.5 ± 8.0 113.9 ± 10.7 130.1 ± 13.0 tfj fat feed group 93.1 ± 8.4 120.6 ± 11·4 136.4 ± 11.6 RNH high dose group 96.8 ± 8.9 122.6 ± 12.7 134.6 ± 16.3 RNH medium dose group 92.1 ± 6.6 113.9 ± 7.3 126.8 ± 9.1 11 201216975 RNH low dose group 93.3 ± 8.0 115.9 ± 8.6 ------- 130.5 + 1〇〇RN group 94.1 ± 8.0 113.5 ± 10.4 _128J_± 9.8 Positive control group 96.8 ± 8.6 115.1 ± 13.2 125.3 + 15 Q —--- (6) The effect of the composition of the present invention on blood biochemical values is a total of eight There were three blood collection points in the animal experiment in the week, which were the periorbital weeks before feeding, 4 weeks after feeding, and 8 weeks later. The blood plasma should be measured for blood biochemical values, including biochemical values of blood lipids and liver and kidney indicators. The results are shown below. (a) Triglyceride 参阅 Refer to Fig. 2, which is the effect of the diet of each group of the present example on the concentration of triglyceride in hamsters. In the figure, the concentration of triglyceride in the blood of all experimental animals was significantly higher in the fourth week than in the eighth week. Among them, the control group was significantly different from the other groups except the RNH high-dose group and the RN group (P<0.05). At the eighth week, the concentration of triglyceride in the high-dose RNH group was significantly lower than that in the high-fat diet group (/?<0.01). In addition, the 'South RNH middle dose group, the RNH low dose group, the rn group and the positive control group showed a slight decrease in blood triglyceride at the fourth and eighth weeks. Taking the lipid-lowering drug ezitimbe — or two weeks, can reduce the amount of triglyceride in the blood, but only taking the antihyperlipidemic drug ezidmbe for two weeks', that is, the concentration of triglyceride in the eighth week is compared with the high-fat diet group. There are differences in statistics (^<0.05). From the results, it was found that the composition of the present invention (especially the high dose of 333.4 mg/kg/day) was continuously used for eight weeks, and the effect of lowering the concentration of triglyceride in the blood was obtained. The detailed statistical differences are shown in Table 2. 201216975 Table 2 hamsters in each group at 0, 4, and 8 weeks TG change group 0th week 4th week 8th week control group 328_38±68.74a 165.38±12.97a 116.38±20.63a Nanzhi feed group 319.25±45.82a 322.75± 79.97b* 279.00±67.63b" RNH high dose group 356.25±106.72a 241.25±77.65a 181.38±49.82a RNH medium dose group 332.63±86.45a 271.75±54.24b* 210.88±45.67b* RNH low dose group 375.63±119.68a 256.63±64.98a 206.38±59.65b* RN group 360.38±79.88a 211.13±67.20a 199.00±44.43a Positive control group 373.25±105.25a 246.75±29.33b “195.00±58.92a*: represents p value<0.05; ** Representative p value < 0.01 (b) High density lipoprotein cholesterol Please refer to Fig. 3, which is the effect of the diet of each group on the high density lipoprotein in hamsters of the present example. Lipoprotein cholesterol was significantly lower than that of other groups (<0.01). It can be seen that the experimental animals that were fed four or eight weeks after high-fat foods were able to remove the excess blood by increasing the concentration of high-density lipoprotein cholesterol. The amount of cholesterol is used for self-protection purposes. However, this protection can Can not continue for a long time, will eventually cause cardiovascular disease. The positive control group (take ezitimbe) can reduce the total cholesterol concentration in the blood, so it is reasonable to explain the increase in the concentration of high-density lipoprotein cholesterol in this group. (c) Liver Functional indicators The liver function indicators of this study are used to detect plasma glutamic acid transaminase 13 201216975 (GOT), and the facial acid pyroglutamic acid transaminase (GPT) 〇 usually gain weight or GOT and GPT values when taking steroids to treat diseases. GOT and GPT are useful for detecting the degree of hepatocyte injury. GPT is mainly from the liver, and GOT is common in many extrahepatic tissues, such as heart, skeletal muscle and kidney. Therefore, GPT is the liver in clinical practice. The cell damage is more specific. In the early stage of acute hepatitis, the serum GOT value is higher than the GPT value (G0T/GPT>1). Since the GOT value decreases rapidly, the late GPT is higher than the GOT (G0T/GPT<1), so In chronic hepatitis, the GOT/GPT ratio is often less than 1. GOT and GPT concentrations are less correlated with the severity or prognosis of liver injury. Due to the intake of high-fat food for eight weeks, the weight of the experimental hamsters increased. Whether measured in each group diet will affect their liver function hamster, hamsters and therefore measured the blood groups of the GOT and GPT as the basis of liver function. Please refer to Fig. 4, which is the effect of each group of diets on GOT in this example. As can be seen from the figure, there was no significant change in the GOT index of all experimental animals fed either normal or high-fat foods, and the experimental results did not have statistical significance. For GPT, there was no significant change in _ between groups (not shown). (d) Renal function indicators Urea nitrogen and creatinine Urea nitrogen is a metabolite of protein. The protein is secreted by the kidneys and excreted in the urine via the urine. If the concentration of urea nitrogen in the blood increases, it can reflect abnormal renal function. However, if there is lack of water, eating a large amount of protein food, upper gastrointestinal bleeding, severe liver disease, infection, steroid use, and insufficient blood flow to the kidney, it will also cause the blood urea nitrogen concentration to rise temporarily. Say, 'If the urea gas rises due to kidney disease, the kidney disease has often progressed to a considerable extent, losing the function of early debt testing, which means that urine money can not reflect kidney disease at an early stage. Muscle is a very stable indicator of renal function, f is used to assess the severity of renal dysfunction' and condition monitoring of kidney disease, but not for screening for kidney disease. ^
=-併參閱第5及6圖，其分別係為本實施例之各 、、且人B對倉鼠體内尿素氮及肌酸酐之影響。於 照組之尿素氮除了與高脂飼料組具有統計差異 ^組與其他組並無統計上的差異。於第6圖中， Η南劑量組、麵中劑量組、職低劑量組及rn 酸酐並沒明顯上升，故本發明之組合物並不會 對腎功能造成不良影響。 (二）人體實驗 集17位又试者，於試驗前與試驗後各 進仃抽血，以測定血脂質濃度。 試驗期間，每位受試者期為期1個月’於 入太恭aH 續常生活，僅於早晚飯後介 以膠合，本發明之組合物係 以膝囊的方式給予受試者，每日2次 每顆膠囊J£含右睿古♦士找 母-人1粒膠囊’ 吞食。L、3有5G0毫克之本發明組合物，並以溫開水 醇、後，受試者之體重、三酸甘油酯、總膽固 及麵胺酿轉銘 ιΛ 膽固醇(LDL_C) 贱酿轉移每（γ_細myl transf_e，簡稱咖，為 201216975 肝炎指數之指標）皆會測定。體重方面，試驗前後並無差 異（試驗前之平均體重為59.358，試驗後為59.44)。上述 企脂之結果如下表3所示，所有數據皆為平均值，且降 幅、升幅百分比之算式係為（試驗後一試驗前）/試驗前χ 1〇〇。結果顯示，三酸甘油酯、總膽固醇、低密度脂蛋白 膽固醇及麩胺醯轉移酶皆有下降之趨勢，而高密度脂蛋 白則有上升之趨勢。 泰_1__^試者於試驗前後之血脂數據 試驗前 ------ 試驗後 三酸甘 油酉旨 83.35 80.65 口、*m刖攸 總膽固 醇 Jj7.40 179.50 • <肌Λ曰取 高密度 脂蛋白 膽固醇 64.24 69.00 佩 低密度 脂蛋白 膽固醇 116.41 103.41 麵胺醯 轉移酶 --~~~~--- 12.82 平均降 幅、升幅 -3.24 -9.07 7.41 -11.17 -20.27 百分比 此外，企管硬化指數（總膽固醇/高密度脂蛋白膽固 ^方面，試驗前為3.3卜試驗後為2.76，其顯示有下降 =(降幅百分比為_16 7〇)。而冠狀動脈硬化指數（低密 :月曰蛋白膽固醇/高密度脂蛋白膽固醇)方面，試驗前為 驗後為1.64,其亦有下降之趨勢（降幅百分比為 人：合上述結果，經長時間食用本發明之組合物後， &可有效降低血中脂質（三酸甘油醋、膽固醇及低密 201216975 f脂蛋白膽ϋ醇），且並不會影響肝、腎功能。此外 明之組合物中的維生t Β群於體内 色，與酵素接合使其活化，㈣使身體 進行。因此，持續食用本發明之組合物，可使 效增加代謝能力及保護心血管功能。 有 以上所述僅為舉例性，而非為限制性者。任 :本發明之精神與料，㈣其騎之等效修改或變 更，均應包含於後附之申請專利範圍中。 1 【圖式簡單說明】 第1圖係為本實施例之各組飲食對倉鼠體重之影響。 第2圖係、為本實施例之各組飲食對倉鼠體内三酸甘油 酯濃度之影響。 第3圖其係為本實施例之各組飲食對倉鼠體内高密度 脂蛋白膽固醇之影響。 第4圖其係為本實施例之各組飲食對血聚中麵草酸轉 氨基酶（GOT)之影響。 第5圖其係為本實施例之各組飲食對倉鼠體内尿素氮 之影響。 第6圖其係為本實施例之各組飲食對倉鼠體内肌酸針 之影響。 【主要元件符號說明】 201216975=- and also refer to Figures 5 and 6, which are the effects of each of the present examples, and human B on urea nitrogen and creatinine in hamsters. There was no statistical difference between the urea nitrogen in the group and the high fat diet group. There was no statistical difference between the group and the other groups. In Fig. 6, the composition of the present invention does not adversely affect renal function, and the composition of the present invention does not significantly affect the renal function, the mid-dose group, the low-dose group, and the rn-anhydride. (B) Human experiment A set of 17 testers, before and after the test, blood was drawn to determine the blood lipid concentration. During the test period, each subject period lasted for 1 month, and continued to live in Taigong aH. Only after morning and evening meal, the composition of the present invention was administered to the subject as a knee capsule. 2 times per capsule J £ contains right Rui Gu ♦ Shi looking for mother - person 1 capsule ' swallowed. L, 3 has 5G0 mg of the composition of the present invention, and after the warm water alcohol, the weight of the subject, the triglyceride, the total cholesterol and the face amine are transferred to the cholesterol (LDL_C). Γ_fine myl transf_e, referred to as coffee, is an indicator of the 201216975 hepatitis index). In terms of body weight, there was no difference before and after the test (the average body weight before the test was 59.358, and the test was 59.44). The results of the above-mentioned fats are shown in Table 3 below. All the data are average values, and the formulas for the reduction and percentage increase are (before the test) and before the test. The results showed that triglycerides, total cholesterol, low-density lipoprotein cholesterol and glutamine transferase decreased, while high-density lipoproteins showed an upward trend. Thai_1__^ Before the test, the blood lipid data test before the test ------ after the test, triglyceride 酉 83 83.35 80.65 mouth, * m 刖攸 total cholesterol Jj7.40 179.50 • < muscle tendon take high density Lipoprotein cholesterol 64.24 69.00 Peice low density lipoprotein cholesterol 116.41 103.41 Face amine transfer enzyme--~~~~--- 12.82 Average decrease, increase -3.24 -9.07 7.41 -11.17 -20.27 percentage In addition, the firm hardening index (total cholesterol) / High-density lipoprotein cholesterol solids, before the test was 3.3 after the test was 2.76, which showed a decrease = (% reduction of _16 7 〇). And coronary atherosclerosis index (low density: sputum protein cholesterol / high In terms of density lipoprotein cholesterol, the test was 1.64 after the test, which also showed a downward trend (the percentage reduction was human: the above results, after a long time of consumption of the composition of the present invention, & can effectively reduce blood lipids (triglyceride, cholesterol and low-density 201216975 f lipoprotein cholesterol), and does not affect liver and kidney function. In addition, the vitamin T group in the composition of the composition is colored in the body and is bound to the enzyme. Activation, (four) make The body is carried out. Therefore, the continuous consumption of the composition of the present invention can increase the metabolic capacity and protect the cardiovascular function. The above description is merely exemplary and not limiting. Any: the spirit and material of the present invention, (4) The equivalent modification or modification of the ride shall be included in the scope of the patent application attached. 1 [Simple description of the diagram] Figure 1 is the effect of the diet of each group on the weight of hamsters in this example. The effect of the diet of each group in this example on the concentration of triglyceride in hamsters. Fig. 3 is the effect of the diet of each group on the high density lipoprotein cholesterol in hamsters of this example. It is the effect of the diet of each group of this example on the blood glutamate oxalate transaminase (GOT). Fig. 5 is the effect of the diet of each group on the urea nitrogen in the hamster of the present example. It is the effect of the diet of each group in this example on the creatine needle in hamsters. [Main component symbol description] 201216975