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TWI362267B
TWI362267B TW95106008A TW95106008A TWI362267B TW I362267 B TWI362267 B TW I362267B TW 95106008 A TW95106008 A TW 95106008A TW 95106008 A TW95106008 A TW 95106008A TW I362267 B TWI362267 B TW I362267B
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Taiwan
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honey
mixture
fruit
rats
type
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TW95106008A
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Chinese (zh)
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TW200731983A (en
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Mei Ling Lin
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Senyuh Farm Science Co Ltd
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1 · 1362267 一 100年12月21¾ 九、發明說明: 【發明所屬之技術領域】 本發明係相關於一種蜜拉聖果混合物用於製造調控血 * 糖以及提高胰島素釋放的醫藥組合物或食品的用途。 【先前技術】 ^ 根據行政院衛生署統計,糖尿病患者的數目逐年已驚 人的速度成長’使得糖尿病高居國人十大死因之列。此外 φ ,糖尿病與十大死亡原因中的腦血管疾病、高血壓、心臟 病常伴隨發生’而造成病情難以控制。此對個人' 家庭、 社會乃至國家都是相當沉重的負擔及損失。因此,針對糖 • 尿病的調控實屬刻不容緩的重要課題。 臨床上,將糖尿病分為兩大類:第一型『騰島素依賴 型』糖尿病及第二型『非騰島素依賴型』糖尿病。形成第 一型糖尿病的主要原因可能是個人的基因遺傳、病毒感染 或毒性物質破壞了胰臟的β細胞’或者是自體免疫形成抗p 參細胞抗體,及細胞免疫作用攻擊β細胞,造成胰臟無法正 常分泌胰島素,因此,需注射胰島素來治療e而第二型糖 ^ 尿病形成的原因,目前則仍不明確;推測可能與家族遺傳 或個人飲食習慣有關。此外,此類病人多伴隨騰島素抗性 (insul in resistance)的出現;主要是因β細胞過度地分 泌胰島素(hyperinsulinamia)形成胰島素抗性,造成骨路 肌、脂肪組織及肝臟等周邊組織對胰島素的敏感性 (insulin sensitivity)降低’減低了組織對葡萄糖的利 用率,而造成高血糖的現象。控制血糖、適量運動及均衡 1362267 ~100年12月2日修 飲食是治療糖尿病的三大原則。目前常用的口服降血糖藥 物為磺基尿素(Sulfonylurea)和雙胍類藥物 • (Biguanides;BG)兩大類型,配合著注射胰島素來控制病 ' 人的血糖。一般認為續基尿素的藥物:如甲苯績丁尿素 (tolbutamide) 、 glipizide(Glibenese) 、 glibenclamide(Euglucon)等,乃藉由刺激體内胰島素分 泌,增強胰島素與作用受體的結合,較適合於非胰島素依 φ賴型糖尿病病人的控制,對於沒法分泌胰島素的糖尿病則 無效。另外,雙胍類藥物則是以改善葡萄糖利用率為主, 但不刺激胰島素的分泌,例如metf〇rmin。近來臨床上 也嘗試使用thiaz〇lininedi〇nes這類可增強胰島素敏感 •度的口服降血糖藥物來治療。然而,^論注射姨島素或口 服降血糖藥,雖能有效的控制血糖,卻無法有效抑制糖尿 病病人所產生的心臟、血管、眼睛、腎臟及神經系統等病 因此,為了讓病患有更多用藥的選擇,&更有效的控 制灰糖來防止併發症的發生,讲鉻 的發生力發不同的藥物或健康食品 來輔助Sa床運用是迫切需要的。 【發明内容】 本發明係相關於一種可調控血糖的食品及醫藥組合物 。”㈣用含有蜜拉聖果混合物’以進行血糖調控的目的 兩運成本發明目的,个 4L, m Θ你提供—裡虽'拉聖果混合 用於製造調控血糖以及提高騰惠 捉同胰島素釋放的醫藥組合物或 6 1362267 • · ~w^12 月 2 日修; 食品的用途,其中蜜拉聖果混合物係包含治療有效量的蜜 拉聖果萃取物以及人蔘粉。 本發明亦相關於一種可調控血糖的醫藥組合物,其係 • 包含治療有效量的蜜拉聖果果實萃取物。 較佳的是,治療有效量的蜜拉聖果果實萃取物為至少 40mg/kg 體重。 更佳的是,治療有效量的蜜拉聖果果實萃取物為 ^ 4〇mg/kg 體重至 I20mg/kg 體重。 較佳的是,該醫藥組合物可維持至少二小時的降糖作 用。 更佳的是,該醫藥組合物進而包含人寨。 較佳的是,該醫藥組合物進而包含一個或多個醫藥上 可接受載劑、稀釋劑或賦形劑。 較佳的是,該醫藥組合物係用於第一型糖尿病。1 · 1362267 DECEMBER 213⁄4 IX. DESCRIPTION OF THE INVENTION: TECHNICAL FIELD OF THE INVENTION The present invention relates to a pharmaceutical composition or food for the manufacture of a pharmaceutical composition or food for regulating blood sugar and improving insulin release. use. [Prior Art] ^ According to the statistics of the Department of Health of the Executive Yuan, the number of people with diabetes has grown at an alarming rate every year, making diabetes the top ten causes of death among Chinese people. In addition, φ, diabetes and cerebrovascular diseases among the top ten causes of death, hypertension, and heart disease often accompany the disease, which makes it difficult to control. This is a very heavy burden and loss for the individual 'family, society and even the country. Therefore, the regulation of sugar and urine disease is an important issue that cannot be delayed. Clinically, diabetes is divided into two categories: the first type of "Tengdaosu-dependent" diabetes and the second type of "non-Tengdao-dependent" diabetes. The main reason for the formation of type 1 diabetes may be that the individual's genetic inheritance, viral infection or toxic substances destroy the beta cells of the pancreas' or autoimmune to form anti-p-cell antibody, and cellular immunity attacks the beta cells, causing pancreas Dirty can not normally secrete insulin, therefore, the reason for the injection of insulin to treat e and the formation of type 2 sugar urinary disease is still unclear; speculation may be related to family heredity or personal eating habits. In addition, such patients are often associated with the emergence of insul in resistance; mainly due to the excessive secretion of insulin (hyperinsulinamia) to form insulin resistance, resulting in bone path muscle, adipose tissue and liver and other peripheral tissue pairs Insulin sensitivity reduction reduces the use of glucose by tissues and causes hyperglycemia. Controlling blood sugar, moderate exercise and balance 1362267 ~ December 2, 2006 Diet is the three principles for the treatment of diabetes. The currently used oral hypoglycemic drugs are two types of sulfourea (Sulfonylurea) and biguanide (Biguanides; BG), which are combined with insulin injection to control the blood sugar of people. Drugs that are considered to be based on urea, such as tolbutamide, glibizide (Glibenese), glibenclamide (Euglucon), etc., are effective in non-inhibition by stimulating insulin secretion in the body and enhancing the binding of insulin to the receptor. Insulin is controlled by patients with diabetes mellitus and is not effective for diabetes that cannot secrete insulin. In addition, biguanide drugs are mainly to improve glucose utilization, but do not stimulate insulin secretion, such as metf〇rmin. Recently, clinical attempts have also been made to use oral hypoglycemic drugs such as thiaz〇lininedi〇nes which enhance insulin sensitivity. However, the injection of yoghurt or oral hypoglycemic agents, although effective in controlling blood sugar, can not effectively inhibit the heart, blood vessels, eyes, kidneys and nervous system caused by diabetes patients, so in order to make patients more The choice of multiple medications, & more effective control of gray sugar to prevent the occurrence of complications, it is urgent to talk about the occurrence of chromium to produce different drugs or healthy foods to assist the use of Sa bed. SUMMARY OF THE INVENTION The present invention relates to a food and pharmaceutical composition for regulating blood sugar. "(4) The purpose of the invention is to use the mixture containing the honey-salted fruit mixture for the purpose of blood sugar regulation, a 4L, m Θ you provide - although the 'la sacred fruit mixture is used to manufacture blood sugar regulation and improve the release of insulin Pharmaceutical composition or 6 1362267 • · ~w^December 2nd; the use of food, wherein the honey fruit mixture comprises a therapeutically effective amount of honey fruit extract and human powder. The invention is also related to A pharmaceutical composition for regulating blood glucose, comprising: a therapeutically effective amount of a fruit extract of honey fruit. Preferably, the therapeutically effective amount of fruit extract of honey fruit is at least 40 mg/kg body weight. The therapeutically effective amount of the honey fruit extract is from 4 mg/kg body weight to 12 mg/kg body weight. Preferably, the pharmaceutical composition maintains a hypoglycemic effect for at least two hours. Preferably, the pharmaceutical composition further comprises a human wall. Preferably, the pharmaceutical composition further comprises one or more pharmaceutically acceptable carriers, diluents or excipients. Preferably, the pharmaceutical composition is For the first type Diabetes.

較佳的是,該t藥組合物係用於第二型糖尿病。 較佳的是’該醫藥組合物係能改善騰島素抗性。 本發明另相關於-種提高縢島素釋放的醫藥組合物 其係包含治療有效量的蜜拉聖果果實萃取物。 較佳的是, 4〇mg/kg 體重》 /台療有效a;的蜜拉聖 果果實萃取物為至少 較佳的是,治療有效量的密r m 里的蜜拉聖果果實萃取物為 40mg/kg 體重至 120mg/kg 體重。 本發明另相關於一種可調和△地 巧控血糖的食品,其係含有蜜 拉聖果果實萃取物。 7 1362267Preferably, the t drug composition is for type 2 diabetes. Preferably, the pharmaceutical composition is capable of improving the resistance to temsin. The invention further relates to a pharmaceutical composition for enhancing the release of muslin which comprises a therapeutically effective amount of a fruit extract of melissa fruit. Preferably, 4 〇mg/kg body weight / therapeutic effective a; the honey fruit extract is at least preferably, the therapeutically effective amount of the honey fruit extract in the rm is 40 mg. /kg Weight to 120mg/kg body weight. The invention further relates to a food product which is tunable and dexterously controlled to contain blood sugar, which comprises a fruit extract of honey fruit. 7 1362267

100年12月2日修正替換 【實施方式】 〜 本發明係相關於一種可調控血糖的食品及醫藥組合物 ’其係包含蜜拉聖果的果實萃取物。 贫拉聖果係為山禮科,學名為Correction and Replacement on December 2, 100 [Embodiment] The present invention relates to a food and pharmaceutical composition for regulating blood sugar, which is a fruit extract containing honey fruit. The poor fruit is the mountain ritual, the scientific name

Synsepalum dulcuficum {Schum.)Daniel 1, Sap〇tacfea( 又稱做 miracle fruit,mysterious fruit)。蜜拉聖果是 一種可以使酸性水果轉化成甘之如飴的果實丨原產於西$ 熱帶叢林常綠性灌木植物。聖拉蜜果株高約二至六公尺, 密叢性,蜜拉聖果簇生於枝條末端,呈暗綠色,具短葉柄 ,呈廣披針形或倒披針形,葉面圓形至短尖形,葉脈約八 對,果實為漿果,成熟時呈暗 a紅巴 Z至4年即可開花社 果。蜜拉聖果其果肉含有豐富的糖蛋白、高量的抗氧化物 :維生素C、維生素KI、檸檬酸、蘋果酸 '琥 酸等。種子含有天然固醇等。 单 微量礦物元素。 巧鎮專 ginseng) 力能補虛 「補五臟 心益智」 ^為五加科多年生草本植物的乾燥根 在傳統醫學早就受到重視;中醫―向認為^ 《神農本草經》把它列為「上品」,稱 安精神、定魂魄、止驚悸、除邪氣、明目:門 具有大補元氣、補脾益氣、生 : 功效;臨床應用十分·廣 了抒益曰之 、 也§成治療消渴症的常用t $丨 之-。在當代醫學,也相a去.曰β ^用方劑 進行人蔘的研究。目前 並積極 皂苷(ginsenoside),為人落从 乂上不同的 為人蓁的主要有效成份。人篆皂皆 8 1362267 具有抗衰防老、抗感染 '抑制癌細胞生長、降血脂 脂肪吸收、強身、增強免疫'錢靜 珙靜止痛、降血糖、保護心 肌、改善血凝等多種作用。Synsepalum dulcuficum {Schum.) Daniel 1, Sap〇tacfea (also known as miracle fruit, mysterious fruit). Mela St. Fruit is a kind of fruit that can transform acidic fruit into a succulent fruit. It is native to the western tropical jungle evergreen shrub. The safflower fruit is about two to six meters high, densely clumpy, and the honey sacred fruit is clustered at the end of the branch. It is dark green, with short petiole, broadly lanceolate or oblanceolate, with round to short tips. Shape, about eight pairs of veins, the fruit is a berry, when it is mature, it is dark a red Z to 4 years to bloom. Honey fruit is rich in glycoprotein and high in antioxidants: vitamin C, vitamin KI, citric acid, malic acid, 'succinic acid, etc. The seeds contain natural sterols and the like. Single trace mineral element. Qiaozhen specializes in ginseng) to be able to make up for the "small five dirty heart puzzle" ^ The dry root of perennial herbaceous plants of the five-plus family has long been valued in traditional medicine; Chinese medicine - thinks that "Shen Nong's Herbal Classic" lists it as " The top grade, said the spirit of the spirit, the soul of the soul, the convulsions, the evil spirits, the eyesight: the door has a big vitality, spleen and qi, health: efficacy; clinical application is very broad, and the benefits are also Commonly used for thirst is t$丨之-. In contemporary medicine, it is also a. 曰β ^ used prescriptions for human sputum research. At present, it is active and ginsenoside, which is the main active ingredient of human beings. Human oyster soap 8 1362267 Anti-aging anti-aging, anti-infection 'Inhibition of cancer cell growth, blood fat, fat absorption, strengthening, strengthening immunity 'Qian Jing 珙 static pain, lowering blood sugar, protecting the heart muscle, improving blood coagulation and other effects.

蜜拉聖果可藉由改㈣覺,將原本酸性水果轉化成且 有甜味的效果。本發明係利用蜜拉聖果萃取物作為飲食控 制之食品添加物,提供長期f飲食控制的糖尿病病人一優 良食品添加物。㈣,本發明制f㈣果萃取物配合人 养,可益於輔助a糖調冑。更進一#,本發明利用蜜拉聖 果萃取物作為醫藥組合物,以達到血糖調控的目的。 在本發明的較佳具體實施例中,係以蜜拉聖果萃取物 與人篆以蜜拉聖果萃取物:人篆混合比例=1: 9的比例, 製作成為-蜜拉聖果混合物(meila_ginseng mixt⑽), 作為本發明下列各實施例之用。 :實施例一:蜜拉聖果混合物對血糖調控的初步測試 1. 1實驗動物來源 wlstar雄性大鼠取自國立成功大學醫學院動物令心, 週齡皆在8週以上’體重在200 i 25〇克之間。使用的大 鼠皆飼養於該_心,空調維持室溫在25±lt,光照時間與 黑暗時間各為1 2小時《大鼠可自由進食與飲水。 1.2胰島素依賴型(第一型)糖尿病大鼠的誘導 依照常用的方法,將前述品系8週齡的大鼠絕食後, 腹腔注射戊巴比妥30mg/kg麻醉,自股靜脈注射65mg/kg 的streptozotocin (STZ) ; STZ溶於含有檸檬酸鈉 (1 Ommo 1 /L)的ρΗ4. 5生理食鹽水。待注射一星期後,依照 9 1362267 上述方法自麻醉大鼠尾靜脈採血,供測量空腹的金糖^ 當大鼠空腹的血糖值大於3_g/dL,並有糖尿病的消瘦及 三多症狀(多吃、多喝、多尿)出現,即視為第一型或姨島 素依賴型糖尿病(IDDM)大鼠,簡稱「奶誘發糖尿病大鼠 U非胰島素依賴型(第二型)糖尿病大鼠的誘導 將前述品系8週齡的雄性大鼠,餵食含高量果糖Mela Shengguo can transform the original acidic fruit into a sweet taste by changing (4). The present invention utilizes Melaleus Extract as a food additive for diet control, and provides a good food supplement for diabetic patients with long-term f-dose control. (4) The f (four) fruit extract of the present invention is suitable for human nutrition, and may be beneficial to assisting sugar agitation. Further, the present invention utilizes Mela Extract as a pharmaceutical composition for the purpose of blood sugar regulation. In a preferred embodiment of the present invention, the honeydew fruit extract and the human cockroach are extracted with a mixture of mango and fruit extracts: a mixture ratio of human cockroaches = 1:9, and a mixture of melamine and fruit is prepared. Meila_ginseng mixt (10)) is used as the following examples of the invention. : Example 1: Preliminary test of the regulation of blood sugar by the mixture of honey and fruit. 1. Experimental animal source Wlstar male rats were taken from the National University of Success School Medical School, and the ages were all over 8 weeks' weight at 200 i 25 Between the grams. The rats used were kept in the heart, the air conditioner was maintained at room temperature at 25 ± lt, and the light time and dark time were each 12 hours. The rats were free to eat and drink. 1.2 Induction of insulin-dependent (type 1) diabetic rats According to the usual method, the rats of the above-mentioned strains of 8 weeks old were fasted, intraperitoneally injected with pentobarbital 30 mg/kg, and 65 mg/kg from the femoral vein. Streptozotocin (STZ); STZ was dissolved in ρΗ4.5 physiological saline containing sodium citrate (1 Ommo 1 /L). One week after the injection, blood was collected from the tail vein of anesthetized rats according to the above method according to 9 1362267 for measuring fasting glucose. When the fasting blood glucose of rats was greater than 3_g/dL, there was diabetes thinning and more symptoms. , drink more, more urine), that is, the first type or 姨-dependent diabetic (IDDM) rats, referred to as "milk-induced diabetic rats U non-insulin-dependent (type 2) diabetic rats induction Male rats of the above-mentioned strain 8 weeks old were fed with high amounts of fructose

(60%)之飼料(購自Teklad,Medis〇n,们),讓大鼠自由進 食。餵食三週後,A鼠會產生類似第二型糖尿病的現象, 利用刺激胰臟釋放胰島素的藥物甲苯磺丁尿素 ('t〇lbUtamide)來確定大鼠已經產生胰島素阻抗性現象 (resistance)。若甲苯磺丁尿素(t〇lbutamide)在大鼠降 低血糖效果顯著減弱或消失’即視為非胰島素依類型 (NIDDM)糖尿病大鼠,即第二型糖尿病大鼠。 1 · 4給藥方法 係以蜜拉聖果混合物,經口灌食 分鐘後,即可使大鼠血糖下降,故將 ’亦即低劑量。依照健康食品安全及 經初期評估, 40mg/kg的劑量9〇 40mg/kg視為常用量 功效評估方法,為證明劑量與作用的關係,較3個劑量 組,即4〇mg/kg(低劑量)、_g/kg(中劑量)及8〇_以 高劑量)。 初期評估方面,在斷食一夜的大鼠,經灌食蜜拉聖果 混合物後,於30mg/kg戊巴比妥(pent〇barbital)腹腔注 射麻醉’並分別於Q分鐘、6G分鐘、9Q分鐘及12〇分鐘 年12月2曰每正替換 的h間點,抽取尾經脈血,進行血中葡萄糖濃度或姨島素 含量的測量。對照組(8隻動物)則—相同方 量的生理食鹽水。 長期作用的評估方面,動物則每天灌食蜜拉聖果混合 物二次’連續投予兩個錢後,以灌食前—天的血糖值作 為基準(第〇天),接著分別於門 者刀另J於開始灌食後的第2天、第5 =第10天及第15天’以同—時間點(及當天第三次灌 艮^的9G分鐘)來採血,測量該時間點的血糖值,評估蜜 拉聖果混合物的長期作用效果。 以每天三次連續投予十四天,觀察長期給予蜜拉聖果 ::物對正常大鼠血糖的影響 '结果發現,長期投 聖果混合物仍出現相同的降糖作用。以給予高劑量 (80mg/kg)組為例,請參閱第 第®及表一所示,其降糖百 为比由原來第一天的24 2(60%) of the feed (purchased from Teklad, Medis〇n, we), let the rats eat freely. After three weeks of feeding, A mice developed a phenomenon similar to type 2 diabetes. The insulin-resisting drug, tolbutamide ('t〇lbUtamide), which stimulated the pancreas, was used to determine that the rats had developed insulin resistance. If toluene butyrate (t〇lbutamide) is significantly attenuated or disappeared in rats, it is considered to be a non-insulin-dependent type (NIDDM) diabetic rat, that is, a type 2 diabetic rat. 1 · 4 administration method is a mixture of honey and fruit, after oral administration for a few minutes, the blood sugar of the rats can be lowered, so it will be low dose. According to the health food safety and initial evaluation, the dose of 40 mg/kg 9〇40 mg/kg is regarded as the commonly used dose evaluation method, in order to prove the relationship between dose and action, compared with 3 dose groups, ie 4〇mg/kg (low dose) ), _g/kg (medium dose) and 8〇_ at high dose). In the initial assessment, rats who were fasting for one night were given anesthesia by intraperitoneal injection of 30 mg/kg pentobarbital after ingestion of honeydew fruit mixture and were in Q minutes, 6G minutes, 9Q minutes respectively. And 12 minutes of December, every 2 points of the positive replacement, the tail vein blood was taken, and the blood glucose concentration or the sulphate content was measured. The control group (8 animals) was the same amount of physiological saline. In the assessment of long-term effects, the animals were fed a mixture of honey and fruit for two times a day. After two consecutive doses of blood, the blood sugar level before the feeding was used as a reference (the third day), and then the knife was separately J collected blood on the 2nd day, 5th day, the 10th day and the 15th day after the start of feeding, and measured the blood sugar level at the same time point (and 9G minutes of the third irrigation day). Evaluate the long-term effects of the Miragrass mixture. Four consecutive days of daily administration for fourteen days, observing the long-term effect of the administration of honey salad on the blood sugar of normal rats. The results showed that the same hypoglycemic effect still appeared in the long-term mixture of fruit. For example, given the high dose (80mg/kg) group, please refer to the first and the first table, the hypoglycemic ratio is 24 2 from the original first day.

心土1· 6/0,到第十五天的21. 5U 2.1%,兩者並無顯著差里, °~Heart soil 1·6/0, 21. 5U 2.1% on the fifteenth day, there is no significant difference between the two, °~

-·.&quot;員不長期給予蜜拉聖果混合物 對正常大鼠而言身體不I 生變化,而出現無法繼續降糖 的現象。其中,圖中所示「料 p&lt;0.001〇 」為具有顯者差異,即 表一、長期灌食「蜜把4。里.3入&amp; 糖的作用。 [果、一物」對正常大白鼠也 11 1362267-··&quot;The staff does not give a mixture of honey and fruit for a long time. For normal rats, the body does not change, and there is a phenomenon that it is impossible to continue hypoglycemia. Among them, the figure "p<lt;0.001" is shown to have a significant difference, that is, in Table 1, long-term feeding of "Honey 4, Li. 3 into &amp; sugar. [Fruit, one thing" is normal White rat also 11 1362267

溶媒(生理 食鹽水) 0·6±2·1 -0·7±2.2 2.8±3.4 100年9月14日修正替換 Date 5 Date 10 DatP 15 蜜拉聖果混 合物(meila-ginseng mixture) 40 mg/kg 60 mg/kg 80 12.3±2.1*** 10.3±1.8*** 10.7±3.6*** 11.7±3.0*** 11 9±3 7*** 18.1 土 2.1*** 16.7±1.8*** 17.3±1.5*** 17.8±0·9*** 16 1±2 4*** 24.2±1.6*** 21Λ±2Λ*** 19.0±1.9*** 19.0±2.7*** 21.5±2.1 *** 1 · 5血糖及血中胰島素的檢測方法及影響 將靜脈取得的血液,離心得到血清,利用葡萄糖反應 试劑偵測其血糖變化。葡萄糖反應試劑原理乃利用葡萄糖 氧化酵素法:葡萄糖經葡萄糖氧化酵素催化後,被氧化成 葡萄醛酸和過氧化氳,藉著葡萄糖的色素機來氧化呈現深 淺不同的紅色。血糖值乃由血漿和葡萄糖反應試劑反應所 呈現紅色的顏色變化,經吸光度差異與標準品對照換算出 血糖值。血中胰島素含量的檢測則藉由市售試劑(購自美 國Penisula Lab.,Inc.),以ELISA原理,測量血中胰島 素濃度變化。 1. 6大鼠體重、攝食量及飲水紀錄 每天均定時紀錄大鼠體重(g) '攝食量(g/day)及飲水 里(g/day);攝食量及飲水量乃是比較飼料重量或飲水重 里在别後—天的差異’體重則是紀錄每隻大鼠叢實驗前一 天到實驗結束的測量當天體重。 U 葡萄糖挑戰試驗(gluc〇se challenge test) 取斷食一晚的正常Wi star大鼠,以前述方法將大鼠 12 1362267 100年9月14曰修正替換 分為對照組及三組實驗組,每組八隻動物。對照組灌食相 同量的生理食鹽水,實驗組則以胃管給藥方式,分別給予 蜜拉聖果混合物40、60及80mg/kg劑量。60分鐘後,經 腹腔注射0. 5g/kg的葡萄糖給測試大鼠,以此為零點(0) 。然後依照常用方法,收集5 ' 10、20、30、60、90及 1 2 0分鐘後的血液,測量血糖值變化。Solvent (physiological saline) 0·6±2·1 -0·7±2.2 2.8±3.4 September 14, revised replacement Date 5 Date 10 DatP 15 meila-ginseng mixture 40 mg/ Kg 60 mg/kg 80 12.3±2.1*** 10.3±1.8*** 10.7±3.6*** 11.7±3.0*** 11 9±3 7*** 18.1 Soil 2.1*** 16.7±1.8*** 17.3±1.5*** 17.8±0·9*** 16 1±2 4*** 24.2±1.6*** 21Λ±2Λ*** 19.0±1.9*** 19.0±2.7*** 21.5±2.1 * ** 1 · 5 blood glucose and blood insulin detection methods and effects of blood obtained from the vein, centrifuged to obtain serum, using glucose reaction reagent to detect changes in blood sugar. The principle of the glucose reaction reagent is the glucose oxidase method: after being catalyzed by glucose oxidase, glucose is oxidized to glucuronic acid and cerium peroxide, and is oxidized by a glucose dyeing machine to exhibit a deep red color. The blood glucose level is a red color change in response to the reaction of plasma and glucose reagents, and the blood glucose level is converted from the difference in absorbance to the standard. The blood insulin content was measured by a commercial reagent (purchased from Penisula Lab., Inc., USA), and the change in blood insulin concentration was measured by the ELISA principle. 1. 6 Rat body weight, food intake and drinking water record daily weight of rats (g) 'food intake (g / day) and drinking water (g / day); food intake and drinking water is the comparison of feed weight or The difference in drinking water is different - the difference in days is the weight of the day before the end of the experiment from the day before the end of the experiment. U glucose challenge test (gluc〇se challenge test) Take normal overnight Wi star rats, and the rats were divided into the control group and the three groups of experimental groups by the above method. Group of eight animals. The control group was fed the same amount of physiological saline, and the experimental group was given a dose of 40, 60 and 80 mg/kg of the honeydew fruit mixture by gastric tube administration. After 60 minutes, the rats were tested by intraperitoneal injection of 0.5 g/kg of glucose, which was zero (0). The blood after 5 '10, 20, 30, 60, 90, and 120 minutes was collected according to the usual method, and the change in blood glucose level was measured.

臨床上,常以葡萄糖挑戰試驗來評估組織對糖分的利 用率。在葡萄糖挑戰試驗中,發現蜜拉聖果混合物確能增 加組織對糖分的利用率。以灌食高劑量(80mg/kg)大鼠為 例,其血糖變化在注射糖分後五分鐘内只升至192. 4土 3. 8mg/dL,與對照組(灌食同量生理食鹽水)相較,血糖的 上升(250. 7±3. Omg/dL)顯著較小。此外,請參閱第二圖及 表二所示,灌食蜜拉聖果混合物可以快速消化外來的高血 糖現象,且此降糖作用可維持二小時之久.,顯示蜜拉聖果 混合物具有增加組織糖分利用的功效。圖中所示「***」 為具有顯著差異,為P〈 0.001。 v 表二、灌食蜜拉聖果混合物對正常大白鼠所進行葡萄 糖挑戰試驗的影響。_ 0分鐘 5分鐘10分鐘20分鐘30分鐘60分鐘90分鐘,n 溶媒(生 理食鹽水 99.8±3.0 250.7±3·0 201·7±3·3 149.6±5.8 124.8±4.1 115.4±4.0 106.4±4‘2 95.8±3.9 ) 蜜拉聖果 混合物 40mg/kg 97.5±4.7 98.8±5.6 98.4±4.3 220.1±2.8 180.1±4.5 109.6±5.5 98.6±2.7* %t^ 1 / / · -i- 个♦ 平中中 个 60 mg/kg 97.2±4.4 210.9±1.8 177.3±4.1 104.0±2.1 97.8±2.6* 1 Ο · 1 J 赢 3¾¾ 95.7±3.5 92.7±3.1 13 1362267 年9月14百^正替換 80mg/kg 104.4土 3.4 192.4±3.7 166.7+6.2 122.3±6.3 1〇5.4±4.2 94.7±2.5* 100.0±3.7 102.5±1.8 木 P &lt; 0.05,** Ρ&lt;〇·(Η,木** Ρ&lt;〇.〇〇1 與對照組於同 一時間點所得數據的差異》 1· 8腹腔注射葡萄糖耐量測定法(intraperitQneai glucose tolerance test: IPGTT) • 以葡萄糖—胰島素指數(glucose-insul in index)作為 評估蜜拉聖果混合物對大鼠胰島素抗性的影響。評估過程 #如下:每天分別灌食40mg/kg、60mg/kg或80mg/kg的蜜 拉聖果混合物給第二型糖尿病大鼠,每組8隻動物,每天 二次,連續投予2週。對照組糖尿病大鼠(n=8)依同法灌 食等量的生理食鹽水。在實驗的最後一天,所評估用的糖 尿病大鼠皆自由進食一天。然後,斷食一天,在進行葡萄 糖耐量試驗。葡萄糖耐量試驗過程如下:在大鼠以 3〇mg/kg的戊巴比妥(pent〇barbital)腹腔注射麻醉,以此 為零點(0)。在以腹腔注射lg/KG的葡萄糖到測試老氡, ί而後一常用方法收集3〇、6〇、9〇及12〇分鐘後的血液, 測里不同時間下血糖值(mg/dL)與胰島素濃度變 .化。最後,將葡萄糖耐量試驗所測得的葡萄糖與胰島素濃 度變化,換算為時間-濃度曲線下面積圖(area under curve,AUC)後,可換算呈葡萄糖_胰島素指數。最後,藉 由葡萄糖-騰島素指數變化評估蜜拉聖果混合物對騰島素 抗性的影響。該指標值越小,顯示胰島素作工能力越好( 膜島素敏感性越佳);反之,指標值越大,顯示姨島素作 工能力越差(胰島素敏感性越差)。 14 Γ362267 [100年9月14日修正替換. 1. 9統計分析 實驗所得結果,皆以「平均值±標準誤差(mean±SE)」 • 來表示而降血糖百分比則以給予蜜拉聖果混合物後所得的 ' 大鼠血糖值’扣掉給予同量溶媒(生理食鹽水)後所得血糖 . 值。將兩者差值再除以給予同量溶媒後所得大鼠血糖值, 以百分比(%)表示。同時,使用一般的生物統計方法以 AN0VA分析’用Dunnett’s post-hoc test評估兩者間的 差異;P&lt;〇. 05,即視為有顯著差異。 '貫施例二:對正常及糖尿病大鼠的調控試驗 2 _ 1蜜拉聖果混合物對正常大鼠的調控試驗 將斷食一夜的大鼠,經口給予不同劑量的蜜拉聖果混 合物’分別為40、60、80mg/kg,再以戊巴比妥 (pentobarbital)麻醉抽血。請參閱第三圖及表三所示, 經60分鐘後,發現4〇mg/kg劑量的蜜拉聖果混合物在正 常大鼠即可產生降血糖作用,血糖值由原先1〇8 4± _ 2. 0mg/dL 降至 98. 7±2. 9mg/dL,降血糖百分比達 9. 〇±2. 3% - 以劑虿相關的型式(dose-dependent manner)出現血糖 -、下降作用。此外,隨時間增加蜜拉聖果混合物的降糖作用 有4加的現象,在灌食9 〇分鐘後,其作用會達到最大 〇 表三、灌食蜜拉聖果混合物對正常大白鼠所產生的降 叔糖作用。 15 1362267 100年12月2日修正替換 0分鐘 60分鐘 90分鐘 120分鐘 溶媒(生理食鹽水 ) 108.5±2.6 107.6±3.6 107.0+2.4 108.0±3.5 蜜拉聖果混合物 40 mg/kg 60 mg/kg 80 mg/kg 108.4+2.0 106.0±2.8 104.1±3.9 95.7+3.0* 87.0+1.31 78.3±2.71 85.1+2.61 81.1+2.51 74.0+251 87.9±1.91 83.0+2.11 75.6±3.51 * P&lt;0. 05,2 P〈0. 01,2 *P〈0. 001 與對照組於同一 時間點所得數據的差異。 此外,為了解蜜拉聖果混合物對正常大鼠的胰島素釋 放作用,進一步以產生最強降血糖作用的同一時間點採血 (即灌食蜜拉聖果混合物後90分鐘),測量其血中胰島素 濃度。請參閱第四圖及表四所示,結果發現,蜜拉聖果混 合物也能以劑量相關性的方式增加血中胰島素濃度,由原 先 172.9±15.5pmol/L 升至 420.9±15.9pmol/L,顯示蜜拉 聖果混合物對正常大鼠具有促進胰島素釋放的作用。其中 ,圖中「2」表示p〈0.01,「1」表示p〈0.001。 表四、灌食蜜拉聖果混合物對正常大鼠血中胰島素的 影響。 灌食90分後 溶媒(生理食鹽水) 172.9115.5 蜜拉聖果混合物 40 mg/kg 258.6±10.9 60 mg/kg 320.4±14.82 80 mg/kg 420.9 ±15.91 16 1 2. 2短期及長期給予蜜拉聖果混合物對第一型糖尿病 大鼠血糖的影響 2 P〈0. 01, 1 P&lt;0. 001與對照組所得數據的差異 1362267 _Jg〇年12月2日修正替換 將斷食-夜的大鼠,經口給予不同劑量的蜜拉聖果混 口物刀別4 40、60、80mg/kg,#以戊巴比妥 (pentobarbitaO麻辭。請第五圖及表五所示經口服⑽ 刀鐘後’即使在普通大鼠能產生血糖下降作用的最高劑量 (80mg/kg) ’在第一型糖尿病大鼠,蜜拉聖果混合物的血 糖下降作用卻不會出現。於是,以每天灌食三次,連續給Clinically, glucose challenge trials are often used to assess tissue utilization of sugar. In the glucose challenge trial, it was found that the Miragrass mixture did increase the tissue's utilization of sugar. Taking high-dose (80mg/kg) rats as an example, the blood glucose changes only rose to 192. 4 soil 3. 8mg/dL within five minutes after the injection of sugar, and the control group (the same amount of physiological saline) In comparison, the rise in blood glucose (250. 7 ± 3. Omg / dL) was significantly smaller. In addition, please refer to the second and second tables. The mixture of honey and fruit extract can quickly digest extraneous hyperglycemia, and the hypoglycemic effect can be maintained for two hours. It shows that the honey salad mixture has increased. The efficacy of tissue sugar utilization. The "***" shown in the figure is significantly different, P < 0.001. v Table 2. Effects of a mixture of honey and fruit extracts on the glucose challenge test in normal rats. _ 0 minutes 5 minutes 10 minutes 20 minutes 30 minutes 60 minutes 90 minutes, n solvent (physiological saline 99.8 ± 3.0 250.7 ± 3. 0 201 · 7 ± 3 · 3 149.6 ± 5.8 124.8 ± 4.1 115.4 ± 4.0 106.4 ± 4' 2 95.8±3.9 ) Mela St. Fruit Mix 40mg/kg 97.5±4.7 98.8±5.6 98.4±4.3 220.1±2.8 180.1±4.5 109.6±5.5 98.6±2.7* %t^ 1 / / · -i- ♦ Pingzhongzhong 60 mg/kg 97.2±4.4 210.9±1.8 177.3±4.1 104.0±2.1 97.8±2.6* 1 Ο · 1 J win 33⁄43⁄4 95.7±3.5 92.7±3.1 13 1362267 September 14 hundred positive replacement 80mg/kg 104.4 soil 3.4 192.4±3.7 166.7+6.2 122.3±6.3 1〇5.4±4.2 94.7±2.5* 100.0±3.7 102.5±1.8 Wood P &lt; 0.05, ** Ρ&lt;〇·(Η,木** Ρ&lt;〇.〇〇1 with Differences in data obtained at the same time point in the control group. 1 · 8 intraperitoneal glucose tolerance test (IPGTT) • Glucose-insulin in index as an evaluation of the mixture of honey and fruit Effect of insulin resistance in mice. Evaluation process # as follows: daily feeding of 40 mg/kg, 60 mg/kg or 80 mg/kg of Miragrass mixture to the first Type 2 diabetic rats, 8 animals per group, twice a day for 2 weeks. The diabetic rats in the control group (n=8) were fed the same amount of physiological saline according to the same method. On the last day of the experiment, The diabetic rats used for evaluation were free to eat for one day. Then, one day after fasting, the glucose tolerance test was conducted. The glucose tolerance test procedure was as follows: intraperitoneal injection of pentobarbital at 3 mg/kg in rats. Anesthesia, with zero (0). In the intraperitoneal injection of lg / KG glucose to test the old sputum, ί and then a common method to collect 3 〇, 6 〇, 9 〇 and 12 〇 minutes of blood, measured at different times The lower blood glucose level (mg/dL) and the insulin concentration change. Finally, the glucose and insulin concentration changes measured by the glucose tolerance test are converted into the area under the time-concentration curve (area under curve, AUC). The conversion was glucose-insulin index. Finally, the effect of the honey-salt mixture on the resistance of Tengumycin was evaluated by the change of glucose-Tengdao index. The smaller the value of the indicator, the better the insulin working ability (the better the sensitivity of the membrane); conversely, the larger the index value, the worse the work ability of the insulin (the worse the insulin sensitivity). 14 Γ362267 [Revision and replacement on September 14, 100. 1. 9 results of statistical analysis experiments, all expressed as "mean ± standard error (mean ± SE)" • The percentage of blood glucose lowering is given to the mixture of honey fruit The resulting 'rat blood glucose value' was deducted from the blood glucose obtained after administration of the same amount of vehicle (physiological saline). The difference between the two was divided by the blood glucose level of the rats obtained after the same amount of vehicle was given, expressed as a percentage (%). At the same time, the difference between the two was evaluated by the AN0VA analysis using the general biometric method; P&lt;〇. 05, which was considered to be significantly different. 'Example 2: Regulatory test for normal and diabetic rats 2 _ 1 Mela sacred fruit mixture for normal rat regulation test will be fasted overnight rats, oral administration of different doses of honey salad mixture ' They were 40, 60, and 80 mg/kg, respectively, and then anesthetized with pentobarbital. Please refer to the third and third tables. After 60 minutes, it was found that the 4〇mg/kg dose of the Miragrass mixture can produce hypoglycemic effect in normal rats. The blood glucose level was originally 1〇8 4± _ 2. 0mg / dL decreased to 98. 7 ± 2. 9mg / dL, the percentage of hypoglycemia reached 9. 〇 ± 2. 3% - blood glucose - and decreased in the dose-dependent manner. In addition, the hypoglycemic effect of the Miragrass mixture is increased by 4 times. After 9 minutes of feeding, the effect will reach the maximum. Table 3, the mixture of the honey-salted fruit mixture is produced for normal rats. The effect of lowering the sugar. 15 1362267 December 2, 100 correction replacement 0 minutes 60 minutes 90 minutes 120 minutes solvent (physiological saline) 108.5 ± 2.6 107.6 ± 3.6 107.0 + 2.4 108.0 ± 3.5 Mela fruit mixture 40 mg / kg 60 mg / kg 80 Mg/kg 108.4+2.0 106.0±2.8 104.1±3.9 95.7+3.0* 87.0+1.31 78.3±2.71 85.1+2.61 81.1+2.51 74.0+251 87.9±1.91 83.0+2.11 75.6±3.51 * P&lt;0. 05,2 P< 0. 01, 2 *P<0. 001 The difference between the data obtained at the same time point and the control group. In addition, in order to understand the insulin release effect of the Miragrass mixture on normal rats, the blood insulin concentration was measured at the same time point (ie, 90 minutes after the honey salad mixture). . Referring to the fourth and fourth tables, it was found that the mixture of honey and fruit can also increase the blood insulin concentration in a dose-dependent manner, from the original 172.9±15.5pmol/L to 420.9±15.9pmol/L. It is shown that the honey salad mixture has an effect of promoting insulin release in normal rats. In the figure, "2" indicates p < 0.01, and "1" indicates p < 0.001. Table 4. Effect of the mixture of honey and fruit extract on insulin in normal rats. After 90 minutes of feeding, the vehicle (physiological saline) 172.9115.5 Mela fruit mixture 40 mg/kg 258.6±10.9 60 mg/kg 320.4±14.82 80 mg/kg 420.9 ±15.91 16 1 2. 2 short-term and long-term honey Effect of Lasheng fruit mixture on blood glucose of type 1 diabetic rats 2 P<0.01, 1 P&lt;0. 001 Difference with data obtained from the control group 1362267 _Jg December 2nd revised replacement will be fasting-night Rats, oral administration of different doses of Mola Shengguo mixed mouth knife, 4 40, 60, 80 mg / kg, # pentobarbital (pentobarbitaO 麻 。. Please see the fifth and fifth table oral (10) After the knife knives, the highest dose (80 mg/kg) in the normal rat can produce hypoglycemia. 'In type 1 diabetic rats, the hypoglycemic effect of the honey salad mixture does not occur. So, every day Eat three times, continuously

予十四天的方式,評估蜜拉聖果混合物對第一型糖尿病大 鼠降血作用的影響。The effect of the mixture of Mela's fruit mixture on the blood loss of type 1 diabetic rats was evaluated in a fourteen-day manner.

meila-ginseng mixture 80mg/kg 369.7±8. 376.9±7. 366.0±7. 371.6±8. 362.4±8. ___3 8_6__5_i 請參閱第六圖及表六所示’顯示長期給予蜜拉聖果混 合物也有助益於控制第一型糖尿病大鼠的血糖變化。其中 圖中所示「*」為具有顯著差異,即p〈0. 05。 表六、長期灌食「蜜拉聖果混合物」對 s t rep tozo toe in誘發的第一型糖尿病大鼠的血糖所產生之 作用 17 1362267 溶媒(生理食鹽水 Saline) I 100 年 M~TT5^l替換 | _第0天第2天第5天第1〇天第15天 365.6±6.8 365.2±7.8 368.4±4.0 365.9±7.4 366 2±5 8 蜜拉聖果混合物(Meila-ginseng mixture) 80mg/kg 369.7±8.3 366.9±7.8 356.7±7.6 350.6±8 5 342Λ±^Λ _____*** • 表中每組數據得自8隻糖尿病大鼠,以mean ± SE表 示血糖值(單位:mg/dL)。以灌食每曰灌食三次同量溶媒 • (vehicle)的大鼠為對照組;供80 mg/kg產品的糖尿病大 鼠相互比較。 2.3長期給予蜜拉聖果混合物對第二型糖尿病大鼠血 糖的影響 在開始進行實驗前,第二型糖尿病大鼠均先經腹腔注 射10mg/kg曱苯續丁尿素(t〇ibutamide),確認其降糖作 用疋否因騰島素抗性的形成而消失或減弱。然後,以每天 二次 '連續灌食十四天的方式,評估蜜拉聖果混合物對第 •一型糖尿病大鼠降血作用的影響。請參閱第七圖及表七所 示’長期給予蜜拉聖果混合物也能以劑量相關性的方式, .將血糖值下降,圖中所示「*以」為具有顯著差異,為 p&lt;0.001 。 表七、長期灌食蜜拉聖果混合物在高量(60%)果糖飼 料誘發的第二型糖尿病大鼠的血糖所產生之作用 18 1362267 100年9月14日修正替換 第0天~~第2天~~第5天第10天第15天 溶媒(生理食鹽水 Saline) 121.515.6 116.3±4.2 117.9±4.5 121.4+6.1 120.1±3.5 蜜拉聖果混合物 (Meila-ginseng mixture) 40 mg/kg 60 mg/kg 80 mg/kg 118.3±4.4 116.915.4 120.2+6.3 113.8+4.6 innnj_. . 101.8±5.2 101.9±7.2 109.9±6.3 *** *** 99.0+4.9* 99.7±7.8* 94.6±3.5* 100.5±6.7 101·7±6_8 96·8±6.0* 98·4±5·1* 96.0±6.0* 水氺氺 伞幸 氺本 幸本 籲 表中每組數據得自8隻糖尿病大鼠,以mean 土 SE表 示血糠值(單位:mg/dL)。以灌食每日灌食三次同量溶媒 (vehicle)的大鼠為對照組;供同樣灌食40mg/kg、60 mg/kg和80 mg/kg產品的糖尿病大鼠相互比較。* P&lt;0.05 ,木* P&lt;0. 01,*木*P&lt;0. 001與對照組於同一時間點所得數 據的差異。 另外,請參閱第八圖所示,蜜拉聖果混合物可能恢復 甲苯磺丁尿素(tolbutamide)的降糖作用;連續兩週灌食 籲 高劑量蜜拉聖果混合物(80mg/kg)後,其降糖百分率由原 先的4. 0±5. 45恢復至22. 9±4. 35。此項效果的恢復,係因 • 曱苯續丁展素(tolbutamide)誘導胰島素釋放能力是不變 - 的,可是,其降糖作用卻能被恢復,使得胰島素抗性的改 善。因此,當其灌食蜜拉聖果混合物具有改善第二型糖尿 病的胰島素抗性,圖中所示「***」為具有顯著差異,為 ρ〈0.0 0 1 〇 2. 4蜜拉聖果混合物對大鼠胰島素抗性的影響 為確認蜜拉聖果混合物是否可以改善胰島素抗性,在 19 1362267 • » _ 100年9月14曰修正替換 本發明中,進一步取連續兩週灌食蜜拉聖果混合物的第二 型糖尿病大鼠進行葡萄糖耐量試驗,並將所測得血糖及血 中胰島素濃度變化的曲線下面積,以柱狀圖表示,結果請 參閱第九圖及第十圖所示:在血中葡萄糖及胰島素濃度與 蟀康大鼠(108.5±2.6mg/dL; 172.9±15.5pmol/L)相比,以 高量(60%)果糖誘發的第二型糖尿病大鼠確實來的高。圖 中「*料」表示p&lt;0. 001。但是,隨著蜜拉聖果混合物的給 ^ 予’不僅高血糖的狀態會呈現劑量相關性的減少;同時’ 也會降低血中過高的胰島素含量。另外,請參閱第十一圖 及表八所示,常用來評估胰島素抗性的葡萄糖-胰島素指 數也會隨著蜜拉聖果混合物灌食劑量的增加而隨之減少。 顯示灌食蜜拉聖果混合物確能改善胰島素抗性。 表八、長期灌食蜜拉聖果滬合物對由第二型糖尿病大 乳所進行的葡萄糖时量試驗,其血糖(glucose)、胰島素 ^ insulin)變化的濃度—時間曲線下面積(AUC)。 • &quot; 葡萄糖 胰島素 葡萄糖-胰島素指數 _______(mg/dLxmin)_(pmol/Lxmin)_(unitxlO6) 溶媒 45210.2±145.6 348300.5± 2513.8 157466.0±74.3 蜜拉聖果混合物(Meila-ginseng mixture) 40mg/kg 40890.5+100.4*** 265230.61 1543.5*** 108452.0+78.8*** 60 mg/kg 38322.21124.5*** 254220.9±1540.8*** 97422.2±93.5*** 80 mg/kg 37440.6±122.4*** 246960.8+1613.3*** 92461.1+89.6*** 另外,請參閱第十二圖所示,在連續三天給予第一型 糠展病大鼠蜜拉聖果混合物(80 mg/kg)後,再以靜脈注 射方式給予胰島素,發覺胰島素的降糖作用會因而加強, 20 1362267Meila-ginseng mixture 80mg/kg 369.7±8. 376.9±7. 366.0±7. 371.6±8. 362.4±8. ___3 8_6__5_i Please refer to the sixth and sixth tables to show 'long-term administration of honey salad mixture also helps Benefit from controlling blood sugar changes in type 1 diabetic rats. The "*" shown in the figure has a significant difference, that is, p<0.05. Table 6. Effects of long-term feeding of “Mola Fruit Mix” on blood glucose in type 1 diabetic rats induced by st rep tozo toe in 17 1362267 Solvent (physiological saline Saline) I 100 years M~TT5^l Replacement | _ Day 0 Day 2 Day 5 Day 1 Day 15th 365.6±6.8 365.2±7.8 368.4±4.0 365.9±7.4 366 2±5 8 Mela-ginseng mixture 80mg/kg 369.7±8.3 366.9±7.8 356.7±7.6 350.6±8 5 342Λ±^Λ _____*** • Each group of data in the table was obtained from 8 diabetic rats with mean ± SE for blood glucose (unit: mg/dL). Rats fed the same amount of vehicle (vehicle) three times per serving were used as a control group; diabetic rats for 80 mg/kg products were compared with each other. 2.3 The effect of long-term administration of honey salad mixture on blood glucose in type 2 diabetic rats Before the start of the experiment, the second type of diabetic rats were first intraperitoneally injected with 10 mg/kg 〇 续 but urea (t〇ibutamide) to confirm Whether its hypoglycemic effect disappears or weakens due to the formation of resistance to tamsin. Then, the effect of the Miragrass mixture on the blood-reducing effect of the type 1 diabetic rats was evaluated by four consecutive 'four consecutive days' feeding. Please refer to the seventh and seventh tables. 'The long-term administration of the honey fruit mixture can also be dose-dependent. The blood sugar level is lowered. The figure shows "*" as a significant difference, p&lt;0.001 . Table 7. Effect of long-term feeding of honey-salted fruit mixture on blood glucose in type 2 diabetic rats induced by high-volume (60%) fructose feed 18 1362267 Correction of replacement of day 0~~ 2 days ~ ~ 5th day 10th day 15th day solvent (physiological saline Saline) 121.515.6 116.3±4.2 117.9±4.5 121.4+6.1 120.1±3.5 Mela-ginseng mixture 40 mg/kg 60 mg/kg 80 mg/kg 118.3±4.4 116.915.4 120.2+6.3 113.8+4.6 innnj_. . 101.8±5.2 101.9±7.2 109.9±6.3 *** *** 99.0+4.9* 99.7±7.8* 94.6±3.5* 100.5±6.7 101·7±6_8 96·8±6.0* 98·4±5·1* 96.0±6.0* Shuiyu Umbrella Fortunately, each group of data in this table was obtained from 8 diabetic rats. Mean soil SE represents blood stasis value (unit: mg/dL). Rats fed the same amount of vehicle three times a day were used as a control group; diabetic rats for the same feeding of 40 mg/kg, 60 mg/kg and 80 mg/kg products were compared with each other. * P &lt; 0.05, wood * P &lt; 0. 01, * wood * P &lt; 0. 001 The difference between the data obtained at the same time point and the control group. In addition, as shown in Figure 8, the Miragrass mixture may restore the hypoglycemic effect of tolbutamide; after two weeks of feeding high doses of the Miracle mixture (80 mg/kg), The rate of the hypoglycemic was restored from the original 4. 0 ± 5.45 to 22. 9 ± 4. 35. The recovery of this effect is due to the fact that tolbutamide induces insulin release, but its hypoglycemic effect can be restored, resulting in improved insulin resistance. Therefore, when it is used to improve the insulin resistance of type 2 diabetes, the "***" shown in the figure has a significant difference, which is ρ <0.0 0 1 〇 2. 4 honey fruit The effect of the mixture on insulin resistance in rats is to confirm whether the mixture of insulin extracts can improve insulin resistance. In 19 1362267 • » _ September 14 曰 revised replacement of the invention, further take two weeks of feeding honey The area under the curve of the glucose tolerance test in the second type of diabetic rats of the sacred fruit mixture, and the measured changes in blood glucose and blood insulin concentration, is represented by a histogram. The results are shown in the ninth and tenth figures. : In the blood glucose and insulin concentrations compared with Fukang rats (108.5 ± 2.6mg / dL; 172.9 ± 15.5pmol / L), high-quality (60%) fructose-induced type 2 diabetic rats did come high. In the figure, "*" indicates p&lt;0. 001. However, with the addition of the Miragrass mixture, not only does the hyperglycemia state show a dose-related decrease; at the same time, it also reduces the excessive insulin content in the blood. In addition, as shown in Figure 11 and Table 8, the glucose-insulin index commonly used to assess insulin resistance will also decrease as the feeding dose of the Miragrass mixture increases. It is shown that the mixture of honey and fruit extracts can improve insulin resistance. Table 8. The area under the concentration-time curve (AUC) of the glucose-time test conducted by the long-term feeding of the honey-flavored fruit and the blood sugar (glucose) and insulin (insulin) . • &quot; Glucose Insulin Glucose-Insulin Index_______(mg/dLxmin)_(pmol/Lxmin)_(unitxlO6) Solvent 42510.2±145.6 348300.5± 2513.8 157466.0±74.3 Meila-ginseng mixture 40mg/kg 40890.5+100.4*** 265230.61 1543.5*** 108452.0+78.8*** 60 mg/kg 38322.21124.5*** 254220.9±1540.8*** 97422.2±93.5*** 80 mg/kg 37440.6±122.4*** 246960.8 +1613.3*** 92461.1+89.6*** In addition, please refer to the twelfth figure, after giving the first type of agglutination rat honey fruit mixture (80 mg/kg) for three consecutive days, then Insulin is administered intravenously, and the hypoglycemic effect of insulin is enhanced. 20 1362267

顯示服用蜜拉聖果混》合物有增強騰島素降糖作用的效果 由此可知,室拉聖果混合物具有改善騰島素抗性的能力 2.4大鼠提種、攝食量及飲水的變化 比較大鼠體重’第一型糖尿病大鼠明顯較普通大鼠輕 ,體型也較痩小。 表九、長期灌食蜜拉聖果混合物對第一型糖尿病大鼠 體重之變化_ 天數 _ 〇 2nd 5th 1〇~^ 75^~~ 生理食鹽 228· 6土7. 8 228. 8±8· 5 230. 6±9· 2 235. 6±8. 6±8 9 ^ ' 蜜拉聖果 混合物 40mg/kg 223.5 + 8. 9 225.5 + 5.8 230. 5±5. 8 234.5 + 7.5 240 5±8 5 60mg/kg 2 21.6±8.2 221.6 + 6. 1 228.6 + 7.7 2 34. 6±8. 8 2 38 6 + 9 8 80mg/kg 228.0土8·9 225. 0±8· 6 228.8±6_ 2 230·0±8.4 235: 7Ϊ8: 4 請參閱表十及表十一’在攝食及飲水量方面,第一型 大鼠較健康大鼠吃的多也喝的多,顯出典型的糖尿病症狀 ’長期灌食蜜拉聖果混合物並不影響其體重、飲食量及飲It is shown that taking the honey-salted fruit mixture has the effect of enhancing the hypoglycemic effect of the sinensis. It can be seen that the mixture of the sacred fruit has the ability to improve the resistance of the sinensis. The rats are in need of seed, food intake and drinking water. Comparing rat body weight, type 1 diabetic rats were significantly lighter than normal rats, and their body size was also smaller. Table IX. Changes in body weight of type 1 diabetic rats with long-term feeding of honey-salted fruit mixture _ days _ 〇 2nd 5th 1〇~^ 75^~~ physiological salt 228·6 soil 7. 8 228. 8±8· 5 230. 6±9· 2 235. 6±8. 6±8 9 ^ ' Mela fruit mixture 40mg/kg 223.5 + 8. 9 225.5 + 5.8 230. 5±5. 8 234.5 + 7.5 240 5±8 5 60mg/kg 2 21.6±8.2 221.6 + 6. 1 228.6 + 7.7 2 34. 6±8. 8 2 38 6 + 9 8 80mg/kg 228.0 soil 8·9 225. 0±8· 6 228.8±6_ 2 230 ·0±8.4 235: 7Ϊ8: 4 Please refer to Table 10 and Table XI. In terms of food intake and drinking water, the first type of rats eat more than healthy rats, and they show more typical symptoms of diabetes. Feeding the honey fruit mixture does not affect its weight, diet and drink.

水量。 表十 長期灌食蜜拉聖果混合物對第一型大鼠的攝食 量 天數 0 2nd 5 th 10th 15th 生理時鹽 水 蜜拉聖果 38.6+5.8 38.8+4. 5 40. 6±9. 2 38. 6+3.2 42. 6+5. 0 混合物 40mg/kg 60mg/kg 80mg/kg 43.5+5.9 45.6±6.2 38.0+8.9 45.5+4.8 37.6±6. 5 35.0+5. 6 44.5±8.9 45.6±8.5 40.8+6.2 45. 5±6. 5 44.6+4.8 45. 0±7. 8 45.5+8.3 48. 6+8. 9 7+8. 6 表十 一、長期灌食蜜拉聖果混合物對第一型糖尿病大 21 1362267 100年14日修正替換 白鼠的飲水(water intake)量 天數 0 2nd 5th 10th 15th 溶媒 108.615.8 108.8±10_5 120.6±9.2 118.6±8.2 112.6±11.9 蜜拉聖果混合物 (Meila-ginseng mixture) 40 mg/kg 60 mg/kg 80 mg/kg 113.5±6.9 121.6±8.2 118.0+10.9 115.5±10.8 117.6±7.1 115.0+8.6 114.5+8.9 115.6±8.7 115.8±9.2 111.5+9.5 111.6±10.8 119.0+8.4 115.5±8.5 118.6±8.8 126.7111.4 表中母組數據得自8隻大鼠,以mean 土 SE表示飲水 重量(單位:g/day)。以灌食同量溶媒(vehicle)的大鼠為 對照組;供灌食40mg/kg、60 mg/kg和80 mg/kg產品的 大鼠之比較。 此外’在體重方面,第二型糖尿病顯著較普通大鼠為 胖。可是,灌食蜜拉聖果混合物同樣不影響其體重變化。 同時’動物的攝食量及飲水量也沒有因灌食蜜拉聖果混合 物出現顯著差異。 根據本發明可作之不同修正及變化對於熟悉該項技術 者而言均顯然不會偏離本發明的範圍與精神。雖然本發明 已敛述特定的較佳具體事實’必須瞭解的是本發明不應被 不當地限制於該等特定具體事實上。事實上,在實施本發 明之已述模式方面,對於熟習該項技術者而言顯而易知之 不同修正亦被涵蓋於下列申請專利範圍之内。 【圖式簡單說明】 第一圖係為連續十四天灌食蜜拉聖果混合物對健康大 鼠所產生的降血糖作用。 22 1362267 第二圖 ^ 圖係為灌食蜜拉聖果混合物對 戰試驗的影響。 建康大既葡萄糖挑 弟一圖係為單次給予曰人 糖作用的影響。 犯。對健康大鼠降血 第四圖係為單次給予蜜日人 素釋放作用的影響。 犯。對正常大鼠胰島 第五圖係為單次給予蜜拉聖果混合 大鼠降血糖作用的影響。 尘糖尿病 第六圖係、為連續十四天給予蜜拉聖果混合 糖尿病大鼠體内血糖之影響。 尘 第七圖係為連續給予蜜拉聖果混合物在第二 大鼠所產生的降糖作用。 疾 第八圖係為連續給予蜜拉聖果混合物對甲苯磺丁尿素 tolbutanude)在第二型糖尿病大鼠降也糖作用的影響。’、 第九圖係為連續三天給予蜜拉聖果混合物後,第二型 糖尿病大鼠所進行的葡萄糖耐量試驗之血糖濃度變化。 第十圖係為連續三天給予蜜拉聖果混合物後,第二型 糖尿病大鼠所進行的葡萄糖耐量試驗之胰島素濃度變化。 第十-圖係為連續三天給予f拉聖果混合物後,第二 型糖尿病大鼠所進行的葡萄糖耐量試驗以葡萄糖_騰島素 指數表示之結果。 第十二圖係為連續三天給予蜜拉聖果混合物對騰島素 在第一型糖尿大鼠產生降糖作用的影響。 【主要元件符號說明】 23 1362267 • 100年9月14日修正替換 無The amount of water. Table 10: The number of days of food intake of the first-type rats in the long-term feeding of the honey-salted fruit mixture 0 2nd 5 th 10th 15th physiological saline salt honey fruit 38.6+5.8 38.8+4. 5 40. 6±9. 2 38. 6+3.2 42. 6+5. 0 Mixture 40mg/kg 60mg/kg 80mg/kg 43.5+5.9 45.6±6.2 38.0+8.9 45.5+4.8 37.6±6. 5 35.0+5. 6 44.5±8.9 45.6±8.5 40.8+ 6.2 45. 5±6. 5 44.6+4.8 45. 0±7. 8 45.5+8.3 48. 6+8. 9 7+8. 6 Table XI, long-term feeding of honey fruit mixture for type 1 diabetes Large 21 1362267 Correction of the water intake of the white rats on the 14th of the 100th day of the year 0 2nd 5th 10th 15th Solvent 108.615.8 108.8±10_5 120.6±9.2 118.6±8.2 112.6±11.9 Mela-ginseng mixture 40 mg/kg 60 mg/kg 80 mg/kg 113.5±6.9 121.6±8.2 118.0+10.9 115.5±10.8 117.6±7.1 115.0+8.6 114.5+8.9 115.6±8.7 115.8±9.2 111.5+9.5 111.6±10.8 119.0+8.4 115.5± 8.5 118.6±8.8 126.7111.4 The parent data in the table was obtained from 8 rats, and the drinking water weight (unit: g/day) was expressed by mean soil SE. Rats fed the same amount of vehicle were used as a control group; rats were fed a mixture of 40 mg/kg, 60 mg/kg and 80 mg/kg products. In addition, in terms of weight, type 2 diabetes is significantly fatter than normal rats. However, the filling of the honey fruit mixture does not affect its body weight change. At the same time, there was no significant difference in the amount of food consumed and the amount of water consumed by the animals. It is apparent to those skilled in the art that various modifications and variations can be made without departing from the scope and spirit of the invention. Although the present invention has been described with reference to specific preferred specific embodiments, it should be understood that the invention should not be In fact, the various modifications that are obvious to those skilled in the art are also covered by the following claims. [Simple description of the diagram] The first picture shows the hypoglycemic effect of a mixture of honey and fruit extracts on healthy rats for 14 consecutive days. 22 1362267 Fig. 2 The figure shows the effect of a mixture of honey and fruit mixture on the war test. Jiankang's glucose-picking picture is the effect of a single administration of sugar on the human body. Committed. The lowering of blood in healthy rats The fourth picture is the effect of a single administration of honey. Committed. The fifth panel of normal rat is the effect of hypoglycemic effect in a single dose of honey salad. Dust Diabetes The sixth picture shows the effect of blood glucose on diabetic rats in a mixture of fourteen days. Dust The seventh picture shows the hypoglycemic effect produced by the continuous administration of the honey salad mixture in the second rat. The eighth picture shows the effect of continuous administration of a mixture of honey-salted fruit on tolubutamide (tolbutanude) in hypoglycemic rats in type 2 diabetic rats. The ninth figure shows the change in blood glucose concentration in the glucose tolerance test performed on type 2 diabetic rats after a mixture of honey salads for three consecutive days. The tenth figure shows the change in insulin concentration in the glucose tolerance test performed on type 2 diabetic rats after a mixture of honey salads for three consecutive days. The tenth-graph is the result of the glucose tolerance test performed on the glucose tolerance test in the type 2 diabetic rats after the administration of the f-god mixture for three consecutive days. The twelfth image shows the effect of a mixture of honeysuckle fruit on the hypoglycemic effect of the first type of diabetic rats in three consecutive days. [Explanation of main component symbols] 23 1362267 • Correction replacement on September 14, 100

24twenty four

Claims (1)

.^02267.^02267 ___ 1〇1年2月之^日修正替拖 十、申請專利範圍: 胰丄—種蜜拉聖果混合物用於^11調❻以及提高 治療的醫藥組合物的用途,其中該醫藥組合物包含 ,、有效里的蜜拉聖果混合物 包含蜜拉聖果果實萃取物以及人笑粉 物係 萃&amp;铷办, 八參粉,其中蜜拉聖果果實 卒取物與人蔘粉混合比例為1 : 9。 2 .如申請專利範圍第丄 組合物可雊姓s τ这醫樂 ’夺至〉'二小時的降糖作用。 里中兮醫—申明專利範圍第1至2項任一項所述之用途, 4樂組合物進而包含-個或多個醫華上可接… 、稀釋劑或賦形劑。 醫樂上可接受載劑 其丄::!=圍第1至2項任-項所述之用途, 樂·且5物係用於第一型糖尿病。 1中兮醫荦專利範圍第1至2項任一項所述之用途, ’、°χ醫樂組合物係用於第二型糖尿病。 6 ·如中請專利範圍第—項所 ”中該醫藥組合物係能改善胰島素抗n ' ’ 7.一種可調控血糖的醫藥合 果果實萃取物以及人〃係包含蜜拉聖 篆粉混合比例為=粉’其中蜜拉聖果果實萃取物與人 維持二如:Γ利範圍第7項所述之醫藥組合物,其可 夕一小時的降糖作用。 ^如申請專利範圍第7或8項所述之醫藥植 /、更包含一個或多個 、σ物, 個醫樂上可接受载劑、稀釋劑或賦形劑 25 1362267 101年2月日修正替換 10·如申請專利範圍第7或8項所述之醫藥組合物 ,其係用於第一型糖尿病。 11·如申請專利範圍第7或8項所述之醫藥組合物 ,其係用於第二型糖尿病。 12·如申請專利範圍第7或8項所述之醫藥組合物 ,其係能改善胰島素抗性。 十一、圖式: 如次頁___ 〇 2 2 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 The effective honey salad mixture contains honey fruit extract and human hair powder extract &amp; 铷, 八参粉, in which honey salad fruit is mixed with human powder 1 : 9. 2. If the patent application scope 丄 composition can be surnamed s τ this medical music ‘received> 'two hours of hypoglycemic effect. The use of any of the items 1 to 2 of the invention, wherein the composition further comprises one or more medicinal materials, diluents or excipients. Medically acceptable carrier 丄::! = Uses in items 1 to 2, and Le and 5 are used for type 1 diabetes. The use of any of the above-mentioned items of the first aspect of the invention, wherein the medical composition is used for type 2 diabetes. 6 · The pharmaceutical composition of the patent scope can improve insulin resistance n ' ' 7. A therapeutic fruit extract that can regulate blood sugar and a mixture of human scorpion containing honey sage powder For the = powder' wherein the honey fruit extract and the human maintains the same as: the pharmaceutical composition described in item 7 of the profit range, which can be hypoglycemic for one hour. ^ If the patent application range is 7 or 8 The medical device described in the item, further comprises one or more, sigma, medically acceptable carrier, diluent or excipient. 25 1362267 Modified on February, 2011. Replacement 10 Or the pharmaceutical composition according to the invention, which is for use in the first type of diabetes. 11. The pharmaceutical composition according to claim 7 or 8, which is for use in type 2 diabetes. The pharmaceutical composition according to Item 7 or 8, which is capable of improving insulin resistance. XI. Schema: 2626
TW095106008A 2006-02-23 2006-02-23 Medicinal composition and food capable of adjusting and controlling blood sugar TW200731983A (en)

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