TWI387461B - Use of overground part of hedychium coronarium koenig in reducing blood glucose; extracts and compositions of overground part of hedychium coronarium koenig and their uses - Google Patents

野薑花(HEDYCHIUM CORONARIUM KOENIG)地上部份於降低血糖之用途；野薑花地上部份之萃取物及組合物與其用途The ground part of HEDYCHIUM CORONARIUM KOENIG is used for lowering blood sugar; the extract and composition of the ground part of the wild ginger flower and its use

本發明係關於一種草藥於降低血糖、提高胰島素含量及治療及/或預防糖尿病之用途。特定言之，本發明提供一種野薑花地上部份於降低血糖、提高胰島素含量及治療及/或預防糖尿病之用途，以及野薑花地上部份之萃取物及組合物與其用途。The present invention relates to the use of an herbal medicine for lowering blood sugar, increasing insulin content, and treating and/or preventing diabetes. In particular, the present invention provides a method for lowering blood sugar, increasing insulin content, and treating and/or preventing diabetes, and extracts and compositions of the aboveground parts of the wild ginger flower and their uses.

糖尿病為一種由多種引發因素引起之疾病，且其特徵在於空腹狀態期間或在口服耐糖試驗期間投與葡萄糖後，其血糖含量會提高。持久或不受控制之高血糖會與增加及早發之發病率及死亡率相關。異常的葡萄糖體內恆定常直接及間接與脂質、脂蛋白及脂蛋白元代謝之改變以及其他代謝及血液動力學疾病相關。糖尿病公認具有兩種形式。第1型糖尿病(亦稱為胰島素依賴性糖尿病或幼發型糖尿病)在身體之免疫系統破壞了產生調節血糖含量之胰島素的胰臟細胞時發生。第1型糖尿病佔所有經診斷之糖尿病病例之約5%至10%。第1型糖尿病之危險因素包括自體免疫、遺傳及環境因素。第2型糖尿病(亦稱為非胰島素依賴性糖尿病或成年發作型糖尿病)為由身體不能足夠地產生胰島素或適當使用其所引起之代謝病症。通常第2型糖尿病發作之特徵在於胰島素抗性，細胞不對胰島素產生適當反應之病症。因此，需要增加胰島素之量，且胰臟逐漸喪失其產生胰島素之能力。第2型糖尿病為該疾病之最常見形式，佔糖尿病之90%-95%。由於肥胖症及久坐之生活方式日趨流行，所以第2型糖尿病正變成一種流行病。妊娠性糖尿病係指一種於孕婦中診斷出之葡萄糖不耐形式。在懷孕期間，妊娠性糖尿症需要進行母體血糖含量正常化之治療以避免嬰兒體內之併發症。低百分比(約5-10%)之患妊娠性糖尿病之女性於懷孕後出現第2型糖尿病。已患妊娠性糖尿病之女性亦具有20%-50%之概率在隨後5-10年內出現糖尿病。Diabetes is a disease caused by a variety of triggers and is characterized by an increase in blood glucose levels during the fasting state or after administration of glucose during an oral glucose tolerance test. Prolonged or uncontrolled hyperglycemia can be associated with increased morbidity and mortality from early onset. Abnormal glucose in vivo constants are often directly and indirectly associated with changes in lipid, lipoprotein and lipoprotein metabolism, as well as other metabolic and hemodynamic diseases. Diabetes is recognized in two forms. Type 1 diabetes (also known as insulin-dependent diabetes or juvenile diabetes) occurs when the body's immune system destroys the pancreatic cells that produce insulin that regulates blood sugar levels. Type 1 diabetes accounts for approximately 5% to 10% of all diagnosed cases of diabetes. Risk factors for type 1 diabetes include autoimmune, genetic, and environmental factors. Type 2 diabetes (also known as non-insulin dependent diabetes or adult onset diabetes) is a metabolic disorder caused by insufficient production of insulin by the body or proper use thereof. Usually type 2 diabetes episodes are characterized by insulin resistance, a condition in which the cells do not respond appropriately to insulin. Therefore, it is necessary to increase the amount of insulin, and the pancreas gradually loses its ability to produce insulin. Type 2 diabetes is the most common form of the disease, accounting for 90%-95% of diabetes. Type 2 diabetes is becoming an epidemic as obesity and sedentary lifestyles become more prevalent. Gestational diabetes refers to a form of glucose intolerance diagnosed in pregnant women. During pregnancy, pregnancy-induced diabetes requires treatment to normalize maternal blood glucose levels to avoid complications in the infant. A low percentage (about 5-10%) of women with gestational diabetes develop type 2 diabetes after pregnancy. Women who have developed gestational diabetes also have a 20%-50% chance of developing diabetes within the next 5-10 years.

通常以胰島素或降血糖藥物治療連同膳食及運動來控制糖尿病。在一些病例中，雖以此等藥劑進行治療獲得成功，但死亡指數繼續上升。胰島素治療減輕了症狀而非治癒非胰島素依賴性糖尿病(NIDDM)。降血糖劑，諸如磺醯脲(sulfonylurea)及雙胍(biguanide)(二甲雙胍(metformin))亦可降低血糖，但又僅僅減輕症狀。磺醯脲藉由刺激自胰臟β細胞釋放胰島素來降低血糖含量。此等藥劑藉由封閉三磷酸腺苷(ATP)敏感性鉀通道且消除細胞膜之極性來直接刺激胰島素釋放。磺醯脲之副作用包括低血糖症、腎臟病及肝病、腸胃紊亂、心血管疾病的死亡率增加、皮膚反應、眩暈、嗜睡及頭痛。雙胍藉由減少腸對葡萄糖之吸收及肝葡萄糖來降低血糖含量；然而，其並不刺激胰島素分泌。二胍之主要副作用為乳酸中毒及心血管疾病的死亡率增加。α葡糖苷酶抑制劑抑制腸α葡糖苷酶，因此延遲蔗糖及複雜碳水化合物之消化。α葡糖苷酶抑制劑之副作用包括腸胃副作用及低血糖症。噻唑啶二酮(Thiazolidinedione)藉由直接刺激周邊葡萄糖吸收且抑制肝中葡萄糖產生來直接改良胰島素抗性，增強循環胰島素之作用。然而，噻唑啶二酮僅在胰島素存在下有效，且會導致紅血球異常及頭痛。因此，研究者已長期關注藥用植物作為一種開發抗糖尿病劑之可能來源。Diabetes is usually controlled by insulin or hypoglycemic agents along with diet and exercise. In some cases, although treatment with such agents has been successful, the death index continues to rise. Insulin therapy relieves symptoms rather than cure non-insulin-dependent diabetes mellitus (NIDDM). Hypoglycemic agents, such as sulfonylurea and biguanide (metformin), also lower blood sugar, but only reduce symptoms. Sulfaquine reduces blood sugar levels by stimulating insulin release from pancreatic beta cells. These agents directly stimulate insulin release by blocking adenosine triphosphate (ATP)-sensitive potassium channels and eliminating the polarity of the cell membrane. Side effects of sulfonylurea include hypoglycemia, kidney disease and liver disease, gastrointestinal disorders, increased mortality from cardiovascular disease, skin reactions, dizziness, lethargy, and headache. Double sputum reduces blood sugar levels by reducing intestinal absorption of glucose and hepatic glucose; however, it does not stimulate insulin secretion. The main side effects of diterpene are increased mortality from lactic acidosis and cardiovascular disease. Alpha-glucosidase inhibitors inhibit intestinal alpha glucosidase, thus delaying the digestion of sucrose and complex carbohydrates. Side effects of alpha-glucosidase inhibitors include gastrointestinal side effects and hypoglycemia. Thiazolidinedione directly improves insulin resistance by directly stimulating peripheral glucose absorption and inhibiting glucose production in the liver, and enhances the action of circulating insulin. However, thiazolidinedione is only effective in the presence of insulin and can cause red blood cell abnormalities and headaches. Therefore, researchers have long been concerned about medicinal plants as a possible source of anti-diabetic agents.

美國專利第6,780,440號提供一種適於體重減輕管理及治療糖尿病的草藥組合物，其包含阿魏草(Ferula hermonis )、其萃取物、或阿魏草與適於體重減輕管理之所選草藥、其萃取物及其混合物之組合。美國專利第6,770,307號提及一種預防或治療第II型糖尿病之草藥藥用組合物，其包含來自吉維紫檀(Pterocarpus marsupium )、桑(Morus alba )、貓鬚草(Orthosiphon aristatus )、沿階草(Opiophogon japonicus )、玫瑰(Rosa rugosa )、竹葉青(Commelina communis )、瓜蔞(Trichosanthis kirilowii )及知母(Anemarrhena asphodeloides )之萃取物。美國專利第6,576,270號提及一種針對糖尿病之草藥組合物，其由以下組成：傘花矢車菊(centaurii umbellatum )，龍膽科(Gentianaceae )(矢車菊植物)；西洋蒲公英(Teraxacum officinale )，菊科(Asteraceae )(蒲公英根)；歐洲刺柏(Juniperi communis L)，柏科(Cupresaceae )(杜松子)；異株蕁麻(urticae dioica L)，蕁麻科(Urticeae )(蕁麻植物)；異株蕁麻，蕁麻科(蕁麻根)；菊苣(Cichorium intybus L)，菊苣科(Cichoriaceae )(菊苣根)；黑桑(Morus nigra L)，桑科(Moraceae )(桑葉)；洋蓍草(Achilleae millefolium L)，菊科(洋舊草花)；歐洲越橘(Vaccinium myrtillus L)，杜鵑花科(Ericaceae )(越橘葉)；菜豆(Phaseolus vulgaris L)，豆科(Fabaceae )(豆莢)；歐洲纈草(Valeriana officinalis L)，纈草科(Valerian )(纈草根(Valerian root ))。美國專利第7,482,030號提及一種包含草藥刺葉提燈蘚(Mulinum spinosum )及羅馬甘菊(Chamaemelum nobile )以治療糖尿病之新穎組合物。U.S. Patent No. 6,780,440 provides a herbal composition suitable for weight loss management and treatment of diabetes comprising Ferula hermonis , its extract, or ferula grass and selected herbs suitable for weight loss management, A combination of extracts and mixtures thereof. U.S. Patent No. 6,770,307 referred to for preventing or treating herbal pharmaceutical composition of Type II diabetes, comprising from Givi Rosewood (Pterocarpus marsupium), mulberry (Morus alba), oxalyl whiskers (Orthosiphon aristatus), Ophiopogon ( Opiophogon japonicus ), Rose ( Rosa rugosa ), Commelina communis , Trichosanthis kirilowii and Anemarrhena asphodeloides extracts. U.S. Patent No. 6,576,270 discloses a herbal composition for diabetes consisting of: centaurii umbellatum , Gentianaceae (cornflower plant), western dandelion ( Teaxacum officinale ), Asteraceae ( Asteraceae) ) (dandelion root); Juniperi communis L, Cupresaceae (juniper); urticae dioica L, Urticeae ( rice plant); ramie, ramie (Nettle root); Cichorium intybus L, Cichoriaceae (chicory root); Morus nigra L, Moraceae (mulberry leaf); Amaranth ( Achilleae millefolium L), chrysanthemum Branch (European old grass flower); European bilberry ( Vaccinium myrtillus L), Rhododendron ( Ericaceae ) (Cowberry leaf); Kidney bean ( Phaseolus vulgaris L), Legumaceae ( Fabaceae ) (pod); European valerian ( Valeriana officinalis) L), valine Caoke (by Valerian) (valerian (Valerian root)). U.S. Patent No. 7,482,030 mentioned herbs comprising Mnium spinosa (Mulinum spinosum) and Roman chamomile (Chamaemelum nobile) novel compositions for the treatment of diabetes.

雖然Dhawan B. N.等人(Indian Journal of Expertmental Biology,Vol. 15,March 1977,pp. 208-219)揭示土良薑(Hedychium spicatum Buch-Ham；其係與野薑花有關之品種)地下莖的油萃取物可降低血糖，且Bhandary M.J.等人(Journal of Ethnopharmacology,47(1995)149-158)亦發現於印度的某些地區中，傳統上使用野薑花地下莖乾燥粉末與牛奶的混合物來治療糖尿病，但誠如Bhandary M.J.等人(1995)於其結論中所述，仍需進一步的物化實驗方可發現此等藥物是否確具潛在療效。故依舊需要一種降低血糖及治療及/或預防糖尿病之新穎草藥藥物。Although Dhawan BN et al. (Indian Journal of Expertmental Biology, Vol. 15, March 1977, pp. 208-219) revealed oil extraction of underground stems of the soil of Hedychium spicatum Buch-Ham, which is related to the wild ginger flower. It can lower blood sugar, and Bhandary MJ et al. (Journal of Ethnopharmacology, 47 (1995) 149-158) have also found that in some areas of India, a mixture of dry powder and milk of wild ginger flower stems has traditionally been used to treat diabetes. However, as Bhandary MJ et al. (1995) stated in their conclusions, further physical and chemical experiments are needed to find out whether these drugs have potential therapeutic effects. Therefore, there is still a need for a novel herbal medicine for lowering blood sugar and treating and/or preventing diabetes.

本發明提供一種藉由向個體投與有效量之野薑花地上部份來降低血糖、提高胰島素含量及/或降低胰島素抗性之方法。The present invention provides a method of lowering blood glucose, increasing insulin content, and/or reducing insulin resistance by administering to an individual an effective amount of the aerial part of the ginger flower.

本發明亦提供一種藉由向個體投與有效量之野薑花地上部份來治療及/或預防糖尿病之方法。糖尿病較佳為第I型或第II型糖尿病。The invention also provides a method of treating and/or preventing diabetes by administering to the individual an effective amount of the aerial parts of the wild ginger flower. Diabetes is preferably Type I or Type II diabetes.

本發明進一步提供一種製造野薑花地上部份萃取物之方法及其所製備之萃取物，該萃取物可用以降低血糖、提高胰島素含量、降低胰島素抗性且預防及/或治療糖尿病。The present invention further provides a method of producing a portion of the extract of the wild ginger flower and an extract thereof, which can be used to lower blood sugar, increase insulin content, reduce insulin resistance, and prevent and/or treat diabetes.

本發明亦提供一種含有薑花(Hedychium coronarium )地上部份或其萃取物與適合醫藥學上可接受之賦形劑混合的醫藥組合物。The invention also provides a pharmaceutical composition comprising an aerial part of Hedychium coronarium or an extract thereof in admixture with a pharmaceutically acceptable excipient.

本發明驚人地發現野薑花地上部份可用以提高胰島素之血漿含量、降低血糖及治療及/或預防糖尿病。然而，由於其作用為葡萄糖依賴型，因此不同於傳統的磺醯脲化合物，其不會導致低血糖症，亦即不會降低空腹個體之血糖。基於此發現，野薑花地上部份之萃取物可用於促進胰島素分泌且降低血糖，且因此可用做抗糖尿病劑。The present inventors have surprisingly found that the aerial parts of the wild ginger flower can be used to increase plasma plasma levels of insulin, lower blood glucose, and treat and/or prevent diabetes. However, since its action is glucose-dependent, unlike conventional sulfonylurea compounds, it does not cause hypoglycemia, that is, does not lower the blood sugar of fasting individuals. Based on this finding, the extract of the ground part of the wild ginger flower can be used to promote insulin secretion and lower blood sugar, and thus can be used as an anti-diabetic agent.

本發明之一目標為提供一種野薑花地上部份於製造供降低血糖、提高胰島素含量及/或降低胰島素抗性之藥物的用途。或者，本發明提供一種降低血糖、提高胰島素含量及/或降低胰島素抗性之方法，其包含向個體投與有效量之野薑花地上部份。It is an object of the present invention to provide a use of a portion of the wild ginger flower to produce a medicament for lowering blood glucose, increasing insulin content and/or reducing insulin resistance. Alternatively, the invention provides a method of lowering blood glucose, increasing insulin content, and/or reducing insulin resistance comprising administering to an individual an effective amount of the aerial part of the ginger flower.

本發明之另一目標為提供一種野薑花地上部份於製造供治療及/或預防糖尿病之藥物的用途。或者，本發明提供一種治療及/或預防糖尿病之方法，其包含向個體投與有效量之野薑花地上部份。Another object of the present invention is to provide a use of a portion of the ground of the ginger flower for the manufacture of a medicament for the treatment and/or prevention of diabetes. Alternatively, the invention provides a method of treating and/or preventing diabetes comprising administering to an individual an effective amount of an aerial part of a ginger flower.

本發明之另一目標為提供一種製造野薑花地上部份萃取物之方法及其所製備之萃取物。該萃取物可用以降低血糖、提高胰島素含量、降低胰島素抗性且預防及/或治療糖尿病。Another object of the present invention is to provide a method for producing a portion of the extract of the ground flower of the wild ginger flower and an extract thereof. The extract can be used to lower blood sugar, increase insulin levels, reduce insulin resistance, and prevent and/or treat diabetes.

本發明之另一目標為提供一種包含薑花地上部份或其萃取物以及適合醫藥學上可接受之賦形劑的醫藥組合物。不同於其他藥物，投與本發明的組合物不會過度降低個體之血糖；亦即，不會降低空腹個體之血糖。Another object of the present invention is to provide a pharmaceutical composition comprising an aerial part of ginger flower or an extract thereof and a pharmaceutically acceptable excipient. Unlike other drugs, administration of the compositions of the present invention does not excessively reduce the blood sugar of the individual; that is, does not reduce the blood glucose of the fasting individual.

如本文中所用，「抗糖尿病」或「降血糖」化合物或組合物係指降低血糖含量之藥劑。降血糖或抗糖尿病作用可藉由各種方法量測，包括(但不限於)量測血糖含量及胰島素之血漿含量。As used herein, an "anti-diabetic" or "hypoglycemic" compound or composition refers to an agent that lowers blood glucose levels. Hypoglycemic or anti-diabetic effects can be measured by a variety of methods including, but not limited to, measuring blood glucose levels and plasma levels of insulin.

如本文中所用，「萃取物」係指藥用植物之基本成份的濃縮製劑。通常自新鮮植物或經乾燥及/或粉末狀的植物樣本製備萃取物。視情況，該植物及該經乾燥及/或粉末狀的植物樣本可在溶液中加熱。萃取物可以液體形式使用，或與其他液體或固體藥用草藥萃取物混合。或者，本發明之藥用草藥萃取物可藉由進一步沈澱液體形式來獲得固體萃取物。通常藉由乾燥及隨後切割或研磨經乾燥之物質來製備萃取物，或反之亦然。接著可藉助於適當溶劑，藉由浸漬、滲濾、再滲濾、逆流萃取、渦輪萃取，或藉由二氧化碳超臨界(溫度/壓力)萃取來進行萃取製程。溶劑可為(但不限於)水、乙醇、乙醇/水混合物、甲醇、丁醇、異丁醇、丙酮、己烷、石油醚、乙酸乙酯或其他有機溶劑。接著可藉助於噴霧乾燥、真空烘箱乾燥、流體床乾燥或冷凍乾燥進一步蒸發萃取物且因此濃縮，得到軟萃取物(濃縮萃取物)、乾燥萃取物及/或無水萃取物。As used herein, "extract" refers to a concentrated preparation of the essential components of a medicinal plant. Extracts are typically prepared from fresh plants or dried and/or powdered plant samples. Optionally, the plant and the dried and/or powdered plant sample can be heated in solution. The extract can be used in liquid form or mixed with other liquid or solid medicinal herbal extracts. Alternatively, the medicinal herbal extract of the present invention can be obtained by further precipitating a liquid form to obtain a solid extract. The extract is typically prepared by drying and subsequently cutting or grinding the dried material, or vice versa. The extraction process can then be carried out by means of a suitable solvent, by dipping, diafiltration, re-diafiltration, countercurrent extraction, turbine extraction, or by supercritical (temperature/pressure) extraction of carbon dioxide. The solvent can be, but is not limited to, water, ethanol, an ethanol/water mixture, methanol, butanol, isobutanol, acetone, hexane, petroleum ether, ethyl acetate or other organic solvent. The extract can then be further evaporated by means of spray drying, vacuum oven drying, fluid bed drying or freeze drying and thus concentrated to give a soft extract (concentrated extract), a dried extract and/or an anhydrous extract.

如本文中所用，「治療」係指化合物、組合物、治療活性劑或藥物用於診斷、治癒、減輕、治療或預防疾病或其他不良病狀。As used herein, "treatment" refers to a compound, composition, therapeutically active agent or medicament for the diagnosis, cure, alleviation, treatment or prevention of a disease or other undesirable condition.

薑花Ginger Flower

如本文中所用，野薑花、薑花、其同義詞薑蘭(Gandasulium coronarium )、舌狀薑蘭(Gandasulium lingulatum )、薑花最大變種(Hedychium coronarium var.maximum )、舌狀薑花(Hedychium lingulatum )及其常用名稱蝴蝶花(butterfly lily)、花環花(garland flower)、白薑(white ginger)、白薑花(garland lily)及山奈(Sierra Leone Krio lili)係指同一植物絲狀豆蔻(Amomun filiforme)。野薑花為一種誘人之強壯植物，當生長於容器中時會達到6呎。其葉片呈矛狀，尖頭，長8-24 cm及寬2-5 cm且以整齊兩列排列，蔓生於假莖之全部長度上。自仲夏至秋天，莖頂為6-12 cm長簇之看似蝴蝶之芳香白花。最終花被充滿鮮紅色種子之豔麗種莢所代替。該等植物非常強壯，迅速生長超過其容器之容量，且需要每年分割。應在花枯萎之後移除老莖以促進新莖生長。As used herein, wild ginger flower, ginger flower, its synonym Gandasulium coronarium , Gandasulium lingulatum , Hedychium coronarium var. maximum , Hedychium lingulatum Its common names are butterfly lily, garland flower, white ginger, garland lily and Sierra Leone Krio lili. The same plant filamentous soybean meal (Amomun filiforme) ). Wild ginger flower is an attractive and strong plant that reaches 6 inches when grown in a container. Its leaves are spear-shaped, pointed, 8-24 cm long and 2-5 cm wide and arranged in two rows neatly, which are borne on the entire length of the pseudostem. From midsummer to autumn, the stems are 6-12 cm long clusters of fragrant white flowers that look like butterflies. The flower is eventually replaced by a gorgeous seed pod filled with bright red seeds. These plants are very strong and grow rapidly beyond the capacity of their containers and need to be segmented each year. Old stems should be removed after flower wilting to promote new stem growth.

根據本發明，野薑花植物的地上部份可用以降低血糖、提高胰島素含量、降低胰島素抗性且治療及/或預防糖尿病。根據本發明之一實施態樣，該地上部份包括植物的葉及/或假莖。更佳地，本發明係使用薑花之葉及假莖。According to the present invention, the aerial part of the ginger flower plant can be used to lower blood sugar, increase insulin content, reduce insulin resistance, and treat and/or prevent diabetes. According to an embodiment of the invention, the aerial part comprises leaves and/or pseudostems of the plant. More preferably, the present invention uses leaves of ginger flowers and pseudo stems.

薑花地上部份之萃取物Ginger flower extract

根據本發明，藉由以約1:1至約1:100(w/v(g/ml))(較佳為約1:5至約1:50(w/v(g/ml))，更佳為約1:10至約1:20(w/v(g/ml))，且最佳為約1:10(w/v(g/ml)))之比率以溶劑萃取薑花地上部份來製備薑花地上部份之萃取物。較佳使用水、乙醇或水/乙醇混合物萃取薑花地上部份。根據本發明之一實施例，可藉由洗滌植物地上部份，研磨及乾燥植物樣本，混合經研磨-乾燥之植物樣本與溶劑(諸如水、乙醇或其混合物)進行萃取，過濾所得萃取物溶液，濃縮萃取物溶液(較佳在減壓下)且乾燥所得萃取物(較佳經由冷凍乾燥)來製備薑花之萃取物。較佳之情況下，進行萃取的適當溫度係依據用於適合時期之溶劑而定。舉例而言，在約10℃至約45℃(較佳為約20℃至約40℃，且更佳為約25℃)之溫度下以乙醇萃取，且在約50℃至約100℃(較佳為約65℃至約95℃，且更佳為約90℃)之溫度下以水萃取。萃取進行的較佳適當持續時間係視所用溶劑及溫度而定。舉例而言，在25℃下以乙醇萃取10小時以上(較佳為約16小時)，而在100℃下以水萃取約1小時。根據本發明之另一實施態樣，萃取可進行一次以上。According to the present invention, by from about 1:1 to about 1:100 (w/v (g/ml)), preferably from about 1:5 to about 1:50 (w/v (g/ml)), More preferably, the ratio is from about 1:10 to about 1:20 (w/v (g/ml)), and most preferably about 1:10 (w/v (g/ml))). Part to prepare the extract of the ground part of the ginger flower. Preferably, the ground part of the ginger flower is extracted using water, ethanol or a water/ethanol mixture. According to an embodiment of the present invention, the plant extract may be ground and dried, and the ground-dried plant sample may be mixed with a solvent (such as water, ethanol or a mixture thereof) for extraction, and the resulting extract solution may be filtered. The extract of the ginger flower is prepared by concentrating the extract solution (preferably under reduced pressure) and drying the resulting extract (preferably via freeze drying). Preferably, the appropriate temperature for the extraction is based on the solvent used for the appropriate period. For example, it is extracted with ethanol at a temperature of from about 10 ° C to about 45 ° C (preferably from about 20 ° C to about 40 ° C, and more preferably about 25 ° C), and is from about 50 ° C to about 100 ° C (more It is preferably extracted with water at a temperature of from about 65 ° C to about 95 ° C, and more preferably about 90 ° C. The preferred suitable duration for the extraction depends on the solvent and temperature employed. For example, extraction with ethanol at 25 ° C for more than 10 hours (preferably about 16 hours), and extraction with water at 100 ° C for about 1 hour. According to another embodiment of the invention, the extraction can be carried out more than once.

在一實施態樣中，本發明提供一種薑花地上部份之水萃取物。藉由洗滌薑花植物地上部份(較佳為薑花之葉及假莖)，研磨及乾燥(在約60℃下)植物樣本以獲得經研磨-乾燥之植物樣本，在約100℃下以約1:10(w/v(g/ml))之比率以水萃取經研磨-乾燥之植物樣本約1小時以獲得粗產物，過濾及離心粗產物以獲得水萃取物，視情況在約100℃下以約1:10(w/v(g/ml))之比率以水再萃取剩餘植物樣本約1小時以獲得另一粗產物，過濾及離心該另一粗產物以獲得另一水萃取物，視情況合併自先前兩次萃取獲得之水萃取物以獲得合併之水萃取物，且濃縮合併之水萃取物以獲得經濃縮-合併之水萃取物，且視情況製備不同劑量的經濃縮-合併之水萃取物，來製備此類水萃取物。In one embodiment, the invention provides an aqueous extract of the aerial part of the ginger flower. By washing the aerial parts of the ginger flower plant (preferably ginger flower leaves and pseudostems), the plant sample is ground and dried (at about 60 ° C) to obtain a ground-dried plant sample at about 100 ° C. A ratio of about 1:10 (w/v (g/ml)) is extracted with water to extract the milled-dried plant sample for about 1 hour to obtain a crude product, and the crude product is filtered and centrifuged to obtain an aqueous extract, optionally at about 100. The remaining plant sample was re-extracted with water at a ratio of about 1:10 (w/v (g/ml)) at ° C for about 1 hour to obtain another crude product, which was filtered and centrifuged to obtain another water extraction. Extracting the aqueous extract obtained from the previous two extractions as appropriate to obtain a combined aqueous extract, and concentrating the combined aqueous extracts to obtain a concentrated-combined aqueous extract, and optionally preparing different doses of concentrated water. - Combine the water extract to prepare such an aqueous extract.

在另一實施態樣中，本發明提供一種薑花地上部份之乙醇萃取物。藉由洗滌薑花植物地上部份(較佳為薑花之葉及假莖)，研磨及乾燥(在約60℃下)植物樣本以獲得經研磨-乾燥之植物樣本，以約1:10(w/v(g/ml))之比率以95%乙醇萃取經研磨-乾燥之植物樣本約16小時以獲得粗產物，過濾及離心粗產物以獲得乙醇萃取物，視情況以約1:10(w/v(g/ml))之比率以乙醇再萃取剩餘植物樣本以獲得另一粗產物，過濾及離心該另一粗產物以獲得另一乙醇萃取物，視情況合併自先前兩次萃取獲得之乙醇萃取物以獲得合併之乙醇萃取物，且在減壓及適當溫度(例如約40℃)下濃縮合併之乙醇萃取物以獲得經濃縮-合併之乙醇萃取物，且視情況製備不同劑量的經濃縮-合併之乙醇萃取物，來製備此類乙醇萃取物。In another embodiment, the invention provides an ethanolic extract of the aerial part of the ginger flower. By washing the aerial parts of the ginger flower plant (preferably ginger flower leaves and pseudostems), the plant sample is ground and dried (at about 60 ° C) to obtain a ground-dried plant sample at about 1:10 ( Ratio of w/v (g/ml)) The milled-dried plant sample was extracted with 95% ethanol for about 16 hours to obtain a crude product, and the crude product was filtered and centrifuged to obtain an ethanol extract, as the case may be about 1:10 ( The ratio of w/v (g/ml)) is re-extracted with ethanol to obtain another crude product, and the other crude product is filtered and centrifuged to obtain another ethanol extract, which is combined with the previous two extractions as appropriate The ethanol extract is obtained to obtain a combined ethanol extract, and the combined ethanol extract is concentrated under reduced pressure and at a suitable temperature (for example, about 40 ° C) to obtain a concentrated-combined ethanol extract, and different doses are prepared as appropriate. The ethanol extract is concentrated to combine to prepare an ethanol extract.

在另一實施例中，本發明提供一種薑花地上部份之水-乙醇萃取物。藉由洗滌薑花植物地上部份(較佳為薑花之葉及假莖)，研磨及乾燥(在約60℃下)植物樣本以獲得經研磨-乾燥之植物樣本，以約1:10(w/v(g/ml))之比率以約100℃水萃取經研磨-乾燥之植物樣本約1小時以獲得粗產物，過濾及離心粗產物以獲得水萃取物，視情況在約100℃下以1:10(w/v(g/ml))之比率以水再萃取剩餘植物樣本約1小時以獲得另一粗產物，過濾及離心該另一粗產物以獲得另一水萃取物，視情況合併自先前兩次萃取獲得之水萃取物以獲得合併之水萃取物，稀釋合併之水萃取物使得經稀釋水萃取物與經研磨-乾燥之植物樣本的v/w(ml/g)比為約1:1，添加乙醇至經稀釋水萃取物中以使乙醇濃度變成約70%，使乙醇溶液靜置約20小時且接著離心及濃縮所得溶液層，來製備此類水-乙醇萃取物。In another embodiment, the invention provides a water-ethanol extract of the aerial part of the ginger flower. By washing the aerial parts of the ginger flower plant (preferably ginger flower leaves and pseudostems), the plant sample is ground and dried (at about 60 ° C) to obtain a ground-dried plant sample at about 1:10 ( Ratio of w/v (g/ml)) The milled-dried plant sample is extracted with water at about 100 ° C for about 1 hour to obtain a crude product, and the crude product is filtered and centrifuged to obtain an aqueous extract, optionally at about 100 ° C. The remaining plant sample was re-extracted with water at a ratio of 1:10 (w/v (g/ml)) for about 1 hour to obtain another crude product, which was filtered and centrifuged to obtain another aqueous extract, The situation is obtained by combining the water extract obtained from the previous two extractions to obtain a combined water extract, and diluting the combined water extract to obtain a v/w (ml/g) ratio of the diluted water extract to the milled-dried plant sample. For about 1:1, ethanol is added to the diluted water extract to bring the ethanol concentration to about 70%, the ethanol solution is allowed to stand for about 20 hours, and then the resulting solution layer is centrifuged and concentrated to prepare such a water-ethanol extract. .

包含薑花地上部份或其萃取物之醫藥組合物a pharmaceutical composition comprising an aerial part of ginger flower or an extract thereof

根據一態樣，本發明係關於一種包含薑花地上部份或其萃取物以及一或多種適合醫藥學上可接受之賦形劑的醫藥組合物。視投藥模式而定，醫藥組合物較佳含有約0.1重量%至約100重量%之活性成份，所有重量百分比均以總組合物計。According to one aspect, the invention relates to a pharmaceutical composition comprising an aerial part of ginger flower or an extract thereof and one or more pharmaceutically acceptable excipients. Depending on the mode of administration, the pharmaceutical compositions preferably contain from about 0.1% to about 100% by weight of active ingredient, all by weight based on the total composition.

在本發明之一實施例中，薑花地上部份或其萃取物可與一或多種其他抗糖尿病化合物及/或植物萃取物組合。薑花地上部份或其萃取物較佳可與一或多種吉維紫檀、桑、貓鬚草、沿階草、知母、瓜蔞、玫瑰、竹葉青及/或其萃取物組合使用以形成抗糖尿病組合物。可使用此等草藥之任何組合，只要組合物在向患者投與時降低血糖含量即可。In one embodiment of the invention, the aerial part of the ginger flower or an extract thereof may be combined with one or more other anti-diabetic compounds and/or plant extracts. The aerial part of the ginger flower or the extract thereof is preferably used in combination with one or more of the geisha rosewood, mulberry, catgrass, along the grass, the mother, the melon, the rose, the bamboo leaf and/or the extract thereof to form an anti- Diabetes composition. Any combination of such herbs can be used as long as the composition lowers blood glucose levels when administered to a patient.

視疾病之特定臨床狀態而定，組合物可經由任何經接受之全身傳遞系統，包括(但不限於)經口及非經腸途徑，諸如靜脈內、肌肉內、皮下或經皮途徑、經陰道、眼睛或經鼻途徑，以固體、半固體或液體劑型，諸如錠劑、栓劑、丸劑、膠囊、散劑、溶液、懸浮液、乳膏、凝膠、植入物、貼片、子宮托、氣霧劑、洗眼劑及乳液或其類似物，較佳以適於容易地投與固定劑量之單位劑型來投與。醫藥組合物可包括習知載劑或媒劑且亦可包括其他藥用試劑、藥劑、載劑、佐劑等。在本發明中，草藥組合物之載劑較佳包括漿果或水果之基劑、菜湯或肉汁之基劑、豆奶飲料或營養補充劑。Depending on the particular clinical condition of the disease, the composition may be via any accepted systemic delivery system including, but not limited to, oral and parenteral routes such as intravenous, intramuscular, subcutaneous or transdermal routes, transvaginal. , eye or nasal route, in solid, semi-solid or liquid dosage forms, such as tablets, suppositories, pills, capsules, powders, solutions, suspensions, creams, gels, implants, patches, pessaries, gas Aerosols, eye washes and lotions or the like are preferably administered in unit dosage forms suitable for easy administration of a fixed dose. The pharmaceutical compositions may include conventional carriers or vehicles and may also include other pharmaceutical agents, agents, carriers, adjuvants and the like. In the present invention, the carrier of the herbal composition preferably comprises a base of berries or fruits, a base of broth or gravy, a soy milk drink or a nutritional supplement.

薑花地上部份、其萃取物及含其之醫藥組合物的效用或治療方法The effect or treatment of the aerial part of ginger flower, its extract and the pharmaceutical composition containing the same

發明人發現薑花地上部份、其萃取物及包含薑花地上部份及/或其萃取物之醫藥組合物具有提高個體胰島素分泌及降低個體血糖之功能。另外，發明人發現薑花地上部份、其萃取物及含其之醫藥組合物不會過度降低個體之血糖，亦即，不會降低空腹個體之血糖。此外，薑花地上部份、其萃取物及含其之醫藥組合物可降低胰島素抗性。鑒於上文，薑花地上部份、其萃取物及含其之醫藥組合物具有抗糖尿病功能且因此可用於治療或預防糖尿病(包括第I型及第II型糖尿病)。本發明提供一種對患者為高度耐受性且顯示極少有害副作用之抗糖尿病藥劑。The inventors have found that the aboveground part of ginger flower, its extract, and a pharmaceutical composition comprising the aboveground part of ginger flower and/or its extract have the functions of increasing insulin secretion and lowering blood sugar of the individual. Further, the inventors have found that the aerial part of the ginger flower, the extract thereof, and the pharmaceutical composition containing the same do not excessively lower the blood sugar of the individual, that is, do not lower the blood sugar of the fasting individual. In addition, the aerial part of the ginger flower, its extract and the pharmaceutical composition containing the same can reduce insulin resistance. In view of the above, the aboveground part of the ginger flower, its extract and the pharmaceutical composition containing the same have anti-diabetic function and are therefore useful for treating or preventing diabetes (including Type I and Type II diabetes). The present invention provides an anti-diabetic agent that is highly tolerant to a patient and exhibits few deleterious side effects.

實例Instance

實例1　正常大鼠中薑花葉及假莖之乙醇萃取物之葡萄糖耐性試驗Example 1 Glucose tolerance test of ethanol extract of ginger mosaic and pseudostem in normal rats

將26隻史泊格多利大鼠(Sprague-Dawley rat)分為四組：安慰劑組(7隻投與10% Tween 20之大鼠)、陽性對照組(7隻投與格列本脲(glibenclamide)之大鼠)、250 mg/kg HC組(6隻投與250 mg/kg薑花葉及假莖之乙醇萃取物之大鼠)及750 mg/kg HC組(6隻投與750 mg/kg薑花葉及假莖之乙醇萃取物之大鼠)。將大鼠禁食7小時後接著投與250 mg/kg薑花葉及假莖之乙醇萃取物(250 mg/kg HC組)、750 mg/kg薑花葉及假莖之乙醇萃取物(750 mg/kg HC組)、10 mg/kg格列本脲(陽性對照組)及10% Tween 20(安慰劑組)。30分鐘後，各大鼠接受總共5 g/kg葡萄糖(經口(2.5 g/kg)與皮下(2.5 g/kg)投與葡萄糖)。在0分鐘、30分鐘、60分鐘、90分鐘及120分鐘之時間間隔抽取血液樣本以量測葡萄糖(mg/DL)。結果展示於下表及圖1中。Sixteen Sprague-Dawley rats were divided into four groups: placebo (7 rats dosed with 10% Tween 20), and positive control group (7 rats administered glibenclamide ( Glbenclamide) rats, 250 mg/kg HC group (6 rats given 250 mg/kg ginger mosaic and pseudo-stem ethanol extract) and 750 mg/kg HC group (6 doses of 750 mg) /kg Ginger flower and rat stem extract of ethanol extract). The rats were fasted for 7 hours and then administered with ethanol extract of 250 mg/kg ginger mosaic and pseudostem (250 mg/kg HC group), 750 mg/kg ginger mosaic and pseudo stem ethanol extract (750 Mg/kg HC group), 10 mg/kg glibenclamide (positive control group) and 10% Tween 20 (placebo group). After 30 minutes, each rat received a total of 5 g/kg of glucose (administered with oral (2.5 g/kg) and subcutaneous (2.5 g/kg) glucose). Blood samples were taken at time intervals of 0 minutes, 30 minutes, 60 minutes, 90 minutes, and 120 minutes to measure glucose (mg/DL). The results are shown in the table below and in Figure 1.

以平均值+/-標準誤差(SEM)表示數據。由Sigma統計軟體之t檢驗計算p值，其中p<0.05視為顯著的且標記為*；p<0.01視為高度顯著的且標記為**；且p≦0.001視為極度顯著的且標記為***。Data are expressed as mean +/- standard error (SEM). The p-value was calculated from the t test of the Sigma statistical software, where p < 0.05 was considered significant and marked as *; p < 0.01 was considered highly significant and marked as **; and p 0.001 was considered extremely significant and marked as ***.

結果展示，相較於對照組，750 mg/kg HC組在投與葡萄糖後之30、60及90分鐘時間間隔即可顯著降低血糖含量。750 mg/kg HC組在投與葡萄糖後之120分鐘即可高度顯著降低血糖含量。The results showed that the 750 mg/kg HC group significantly reduced blood glucose levels at 30, 60, and 90 minutes after administration of glucose compared to the control group. The 750 mg/kg HC group significantly reduced blood glucose levels 120 minutes after administration of glucose.

實例2　患第II型糖尿病之小鼠中薑花葉及假莖之乙醇萃取物的葡萄糖耐性試驗(短期餐後血糖)Example 2 Glucose tolerance test of ethanol extract of ginger mosaic and pseudostem in mice with type 2 diabetes (short-term postprandial blood glucose)

對12隻患第II型糖尿病之小鼠(db⁺ /db⁺ 小鼠)禁食12小時後接著允許其自由進食2小時。隨後，向6隻對照組小鼠經口投與10% Tween 20且向6隻1.5 g/kg HC組小鼠經口投與1.5 g/kg薑花葉及假莖之乙醇萃取物。在投與該等成份後之0分鐘、10分鐘、30分鐘及60分鐘時間間隔抽取血液以量測葡萄糖(mg/DL)。結果展示於下表及圖2中。Twelve mice with type 2 diabetes (db ⁺ /db ⁺ mice) were fasted for 12 hours and then allowed to eat free for 2 hours. Subsequently, 6 control mice were orally administered with 10% Tween 20 and 6 1.5 g/kg HC mice were orally administered with 1.5 g/kg ginger leaf and pseudo stem ethanol extract. Blood was drawn at intervals of 0 minutes, 10 minutes, 30 minutes, and 60 minutes after administration of the components to measure glucose (mg/DL). The results are shown in the table below and in Figure 2.

以平均值+/-標準誤差(SEM)表示數據。由Sigma統計軟體之t檢驗計算p值，其中p<0.05視為顯著的且標記為*；p<0.01視為高度顯著的且標記為**；且p≦0.001視為極度顯著的且標記為***。Data are expressed as mean +/- standard error (SEM). The p-value was calculated from the t test of the Sigma statistical software, where p < 0.05 was considered significant and marked as *; p < 0.01 was considered highly significant and marked as **; and p 0.001 was considered extremely significant and marked as ***.

結果展示，相較於對照組，1.5 g/kg HC組在投與葡萄糖後之30及60分鐘即可分別高度顯著降低及顯著降低血糖含量。The results showed that compared with the control group, the 1.5 g/kg HC group had a significant and significant reduction in blood glucose levels at 30 and 60 minutes after administration of glucose, respectively.

實例3　正常小鼠中薑花葉及假莖之乙醇萃取物的腹膜內葡萄糖耐性試驗Example 3 Intraperitoneal glucose tolerance test of ethanol extract of ginger mosaic and pseudostem in normal mice

將8隻小鼠(db^- /db^- 小鼠)分為兩組：對照組(4隻投與10%Tween 20之小鼠)及1.5 g/kg HC組(4隻投與1.5 g/kg薑花葉及假莖之乙醇萃取物之小鼠)。對小鼠禁食14小時後接著允許其自由進食2小時。隨後，對於對照組，經口投與10% Tween 20，且對於1.5 g/Kg HC組，經口投與1.5 g/Kg薑花葉及假莖之乙醇萃取物。30分鐘後，向各小鼠腹膜內投與1.5 g/kg葡萄糖。在0分鐘、10分鐘、30分鐘及60分鐘之時間間隔抽取血液以量測葡萄糖(mg/DL)。結果展示於下表及圖3中。Eight mice (db ^- /db ^- mice) were divided into two groups: control group (4 mice administered with 10% Tween 20) and 1.5 g/kg HC group (4 doses of 1.5 g/kg) Ginger leaves and mice with ethanol extract of pseudostem). The mice were fasted for 14 hours and then allowed to eat free for 2 hours. Subsequently, for the control group, 10% Tween 20 was orally administered, and for the 1.5 g/Kg HC group, an ethanol extract of 1.5 g/Kg ginger mosaic and pseudostem was orally administered. After 30 minutes, 1.5 g/kg of glucose was administered intraperitoneally to each mouse. Blood was drawn at intervals of 0 minutes, 10 minutes, 30 minutes, and 60 minutes to measure glucose (mg/DL). The results are shown in the table below and in Figure 3.

以平均值+/-標準誤差(SEM)表示數據。由Sigma統計軟體之t檢驗計算p值，其中p<0.05視為顯著的且標記為*；p<0.01視為高度顯著的且標記為**；且p≦0.001視為極度顯著的且標記為***。Data are expressed as mean +/- standard error (SEM). The p-value was calculated from the t test of the Sigma statistical software, where p < 0.05 was considered significant and marked as *; p < 0.01 was considered highly significant and marked as **; and p 0.001 was considered extremely significant and marked as ***.

結果展示，相較於對照組，1.5g/kg HC組在投與葡萄糖後之30分鐘及60分鐘即可顯著降低血糖含量。此顯示可顯著降低正常小鼠之血糖。The results showed that the 1.5 g/kg HC group significantly reduced blood glucose levels 30 minutes and 60 minutes after administration of glucose compared to the control group. This display can significantly reduce blood sugar in normal mice.

實例4　正常小鼠中薑花葉及假莖之乙醇萃取物的胰島素提高測試Example 4 Insulin boost test of ethanol extract of ginger mosaic and pseudostem in normal mice

測試小鼠及程序與實例3中相同。在0分鐘、10分鐘、30分鐘及60分鐘時間間隔抽取血液以量測胰島素(u g/L)。結果展示於下表及圖4中：Test mice and procedures were the same as in Example 3. Blood was drawn at 0 minute, 10 minute, 30 minute, and 60 minute intervals to measure insulin ( u g/L). The results are shown in the table below and in Figure 4:

以平均值+/-標準誤差(SEM)表示數據。由Sigma統計軟體之t檢驗計算p值，其中p<0.05視為顯著的且標記為*；p<0.01視為高度顯著的且標記為**；且p≦0.001視為極度顯著的且標記為***。Data are expressed as mean +/- standard error (SEM). The p-value was calculated from the t test of the Sigma statistical software, where p < 0.05 was considered significant and marked as *; p < 0.01 was considered highly significant and marked as **; and p 0.001 was considered extremely significant and marked as ***.

結果展示，相較於對照組，1.5g/kg HC組在投與葡萄糖後之30分鐘及60分鐘即可顯著提高胰島素濃度。此說明薑花葉及假莖之乙醇萃取物顯著促進胰島素分泌。The results showed that the 1.5 g/kg HC group significantly increased insulin concentration 30 minutes and 60 minutes after administration of glucose compared to the control group. This indicates that the ethanol extract of ginger leaves and pseudo stems significantly promotes insulin secretion.

實例5　患第II型糖尿病之小鼠中薑花葉及假莖之乙醇萃取物的胰島素提高測試Example 5 Insulin boost test of ethanol extract of ginger mosaic and pseudostem in mice with type II diabetes

測試小鼠及程序與實例2中相同。在60分鐘時抽取血液以量測胰島素(μg/L)且結果展示於圖5中。1.5 g/kg HC組及對照組中胰島素之濃度為8.51 +/- 0.88 μg/L及5.51 +/- 0.79 μg/L。此等結果展示薑花葉及假莖之乙醇萃取物顯著促進患有第II型糖尿病之小鼠中胰島素分泌。Test mice and procedures were the same as in Example 2. Blood was drawn at 60 minutes to measure insulin (μg/L) and the results are shown in Figure 5. The concentration of insulin in the 1.5 g/kg HC group and the control group was 8.51 +/- 0.88 μg/L and 5.51 +/- 0.79 μg/L. These results show that the ethanol extract of ginger mosaic and pseudostem significantly promotes insulin secretion in mice with type II diabetes.

實例6　患第I型糖尿病之大鼠中薑花葉及假莖之乙醇萃取物的葡萄糖耐性試驗Example 6 Glucose tolerance test of ethanol extract of ginger mosaic and pseudostem in rats with type I diabetes

將12隻患第I型糖尿病之史泊格多利大鼠分為兩組：對照組(6隻投與10% Tween 20之大鼠)及1 g/kg HC組(6隻投與1 g/kg薑花葉及假莖之乙醇萃取物之大鼠)。對大鼠禁食4小時後，接著對於對照組，經口投與10% Tween 20，且對於1 g/kg HC組，經口投與1 g/kg薑花葉及假莖之乙醇萃取物。30分鐘後，向各大鼠投與2.5 g/kg葡萄糖。在0分鐘、30分鐘、60分鐘及90分鐘時間間隔抽取血液樣本以量測葡萄糖(mg/DL)。結果展示於下表及圖6中。Twelve Shigdori rats with type 1 diabetes were divided into two groups: the control group (6 rats administered with 10% Tween 20) and the 1 g/kg HC group (6 rats with 1 g/ Kg ginger leaves and rat stem extracts of ethanol extract). After fasting for 4 hours in the rats, 10% Tween 20 was orally administered to the control group, and ethanol extract of 1 g/kg ginger mosaic and pseudostem was orally administered to the 1 g/kg HC group. . After 30 minutes, each rat was administered 2.5 g/kg glucose. Blood samples were taken at 0 minute, 30 minute, 60 minute, and 90 minute intervals to measure glucose (mg/DL). The results are shown in the table below and in Figure 6.

以平均值+/-標準誤差(SEM)表示數據。由Sigma統計軟體之t檢驗計算p值，其中p<0.05視為顯著的且標記為*；p<0.01視為高度顯著的且標記為**；且p≦0.001視為極度顯著的且標記為***。Data are expressed as mean +/- standard error (SEM). The p-value was calculated from the t test of the Sigma statistical software, where p < 0.05 was considered significant and marked as *; p < 0.01 was considered highly significant and marked as **; and p 0.001 was considered extremely significant and marked as ***.

結果展示，相較於對照組，1 g/kg薑花葉及假莖之乙醇萃取物在投與葡萄糖後之30分鐘及60分鐘即可顯著降低血糖。此顯示薑花葉及假莖之乙醇萃取物具有降低第I型糖尿病大鼠之血糖的有利作用。The results showed that the ethanol extract of 1 g/kg ginger mosaic and pseudostem significantly reduced blood glucose at 30 minutes and 60 minutes after administration of glucose compared to the control group. This shows that the ethanol extract of ginger mosaic and pseudostem has the beneficial effect of lowering blood glucose in type I diabetic rats.

實例7　患第I型糖尿病之大鼠中薑花葉及假莖之乙醇萃取物的胰島素抗性測試Example 7 Insulin Resistance Test of Ethanol Extracts of Ginger Mosaic and Pseudo Stem in Rats with Type I Diabetes

將18隻患第I型糖尿病之史泊格多利大鼠分為三組：對照組(6隻投與10% Tween 20之大鼠)、胰島素組(6隻皮下投與0.3 U/kg胰島素之大鼠)及胰島素+HC組(6隻皮下投與0.3 U/kg胰島素及經口投與1.0 g/kg薑花葉及假莖之乙醇萃取物的大鼠)。對大鼠禁食4小時，且接著對於對照組，投與10% Tween 20，對於胰島素組，投與0.3 U/kg胰島素，且對於胰島素+HC組，投與0.3 U/kg胰島素加1.0 g/kg薑花葉及假莖之乙醇萃取物。在投與2.5 g/kg葡萄糖之後，以30分鐘時間間隔抽取血液以量測葡萄糖(mg/dl)。結果展示於下表及圖7中。Eighteen patients with type I diabetes were divided into three groups: control group (6 rats given 10% Tween 20) and insulin group (6 subcutaneous administration of 0.3 U/kg insulin). Rats and insulin + HC group (6 rats subcutaneously administered with 0.3 U/kg insulin and 1.0 g/kg ginger leaf and ethanol extract of pseudostem). Rats were fasted for 4 hours, and then 10% Tween 20 was administered to the control group, 0.3 U/kg insulin was administered to the insulin group, and 0.3 U/kg insulin plus 1.0 g was administered to the insulin + HC group. /kg Ethanol extract of ginger leaves and pseudo stems. After administration of 2.5 g/kg of glucose, blood was drawn at 30 minute intervals to measure glucose (mg/dl). The results are shown in the table below and in Figure 7.

以平均值+/-標準誤差(SEM)表示數據。由Sigma統計軟體之t檢驗計算p值，其中p<0.05視為顯著的且標記為*或#；p<0.01視為高度顯著的且標記為**或##；且p≦0.001視為極度顯著的且標記為***(*表胰島素組或胰島素+HC組與對照組之比較；#表胰島素組與胰島素+HC組之比較)。Data are expressed as mean +/- standard error (SEM). The p-value was calculated from the t test of the Sigma statistical software, where p < 0.05 was considered significant and marked as * or #; p < 0.01 was considered highly significant and marked as ** or ##; and p 0.001 was considered extreme Significant and marked as *** (*Comparative insulin group or insulin + HC group compared with control group; #表的 insulin group vs. insulin + HC group).

如表中所示，相較於對照組，胰島素組在投與葡萄糖後之30分鐘具有高度顯著降低血糖含量之作用，且在投與葡萄糖後之60分鐘及90分鐘具有顯著降低血糖含量之作用。而相較於胰島素組，胰島素+HC組在投與葡萄糖後之30分鐘及60分鐘後可更顯著降低血糖之含量。As shown in the table, the insulin group had a highly significant effect of lowering blood glucose levels 30 minutes after administration of glucose compared to the control group, and had a significant effect of lowering blood glucose levels at 60 minutes and 90 minutes after administration of glucose. . Compared with the insulin group, the insulin + HC group significantly reduced the blood sugar level 30 minutes and 60 minutes after the administration of glucose.

實例8　正常大鼠中薑花葉及假莖之水萃取物的葡萄糖耐性試驗Example 8 Glucose tolerance test of water extracts of ginger mosaic and pseudostem in normal rats

測試大鼠及程序與實例1中相同。然而，在此情況下，使用24隻史泊格多利大鼠且分為四組：安慰劑組(6隻投與水之大鼠)、0.5 g/kg HC組(6隻投與0.5 g/kg薑花葉及假莖之水萃取物的大鼠)、1 g/kg HC組(6隻投與1 g/kg薑花葉及假莖之水萃取物的大鼠)及1.5 g/kg HC組(6隻投與1.5 g/kg薑花葉及假莖之水萃取物的大鼠)。30分鐘後，各大鼠接受總共5 g/kg葡萄糖(經口(2.5 g/kg)與皮下(2.5 g/kg)投與葡萄糖)。以30分鐘時間間隔抽取血液以量測葡萄糖(mg/dl)。結果展示於下表及圖8中。Test rats and procedures were the same as in Example 1. However, in this case, 24 Spoggard rats were used and divided into four groups: placebo group (6 rats administered with water), 0.5 g/kg HC group (6 doses of 0.5 g/ Kg ginger flower and pseudo-stem water extract of rats), 1 g/kg HC group (6 rats administered with 1 g/kg ginger mosaic and pseudo-stem water extract) and 1.5 g/kg HC group (6 rats administered with 1.5 g/kg ginger leaf and water extract of pseudostem). After 30 minutes, each rat received a total of 5 g/kg of glucose (administered with oral (2.5 g/kg) and subcutaneous (2.5 g/kg) glucose). Blood was drawn at 30 minute intervals to measure glucose (mg/dl). The results are shown in the table below and in Figure 8.

以平均值+/-標準誤差(SEM)表示數據。由Sigma統計軟體之t檢驗計算p值，其中p<0.05視為顯著的且標記為*；p<0.01視為高度顯著的且標記為**；且p≦0.001視為極度顯著的且標記為***。Data are expressed as mean +/- standard error (SEM). The p-value was calculated from the t test of the Sigma statistical software, where p < 0.05 was considered significant and marked as *; p < 0.01 was considered highly significant and marked as **; and p 0.001 was considered extremely significant and marked as ***.

結果顯示，相較於對照組，1 g/kg薑花葉及假莖之水萃取物在投與葡萄糖後之30分鐘及60分鐘具有高度顯著降低血糖之作用，且在投與葡萄糖後之90分鐘及120分鐘具有極度顯著降低血糖之作用。The results showed that compared with the control group, the water extract of 1 g/kg ginger mosaic and pseudostem had a highly significant effect of lowering blood glucose at 30 minutes and 60 minutes after administration of glucose, and 90 after administration of glucose. Minutes and 120 minutes have an extremely significant effect on lowering blood sugar.

實例9　正常大鼠中薑花葉及假莖之水-乙醇萃取物的葡萄糖耐性試驗Example 9 Glucose tolerance test of water-ethanol extract of ginger mosaic and pseudostem in normal rats

測試大鼠及程序與實例1中相同。然而，在此情況下，使用24隻史泊格多利大鼠且分為四組：安慰劑組(6隻投與水之大鼠)、陽性對照組(6隻投與10 mg/kg格列本脲的大鼠)、0.4 g/kg HC組(6隻投與0.4 g/kg薑花葉及假莖之水-乙醇萃取物的大鼠)及0.8 g/kg HC組(6隻投與0.8 g/kg薑花葉及假莖之水-乙醇萃取物的大鼠)。30分鐘後，各大鼠接受總共5 g/kg葡萄糖(經口(2.5 g/kg)與皮下(2.5 g/kg)投與葡萄糖)。以30分鐘時間間隔抽取血液以量測葡萄糖(mg/dl)。結果展示於下表及圖9中。Test rats and procedures were the same as in Example 1. However, in this case, 24 Spogdog rats were used and divided into four groups: placebo group (6 rats administered with water) and positive control group (6 rats with 10 mg/kg grid) Rats of this urea), 0.4 g/kg HC group (6 rats administered with 0.4 g/kg ginger mosaic and pseudo-stem water-ethanol extract) and 0.8 g/kg HC group (6 donors) 0.8 g/kg ginger mosaic and pseudo-stem water-ethanol extract of rats). After 30 minutes, each rat received a total of 5 g/kg of glucose (administered with oral (2.5 g/kg) and subcutaneous (2.5 g/kg) glucose). Blood was drawn at 30 minute intervals to measure glucose (mg/dl). The results are shown in the table below and in Figure 9.

以平均值+/-標準誤差(SEM)表示數據。由Sigma統計軟體之t檢驗計算p值，其中p<0.05視為顯著的且標記為*；p<0.01視為高度顯著的且標記為**；且p≦0.001視為極度顯著的且標記為***。Data are expressed as mean +/- standard error (SEM). The p-value was calculated from the t test of the Sigma statistical software, where p < 0.05 was considered significant and marked as *; p < 0.01 was considered highly significant and marked as **; and p 0.001 was considered extremely significant and marked as ***.

結果顯示，相較於對照組，0.8 g/kg薑花葉及假莖之水-乙醇萃取物在投與葡萄糖後之30分鐘具有顯著降低血糖之作用，在投與葡萄糖後之60分鐘具有極度顯著降低血糖之作用，且在投與葡萄糖後之90分鐘及120分鐘具有高度顯著降低血糖之作用。The results showed that compared with the control group, the water-ethanol extract of 0.8 g/kg ginger mosaic and pseudostem had a significant blood sugar lowering effect 30 minutes after administration of glucose, and was extremely extreme 60 minutes after administration of glucose. Significantly lowers the effect of blood sugar, and has a highly significant effect of lowering blood glucose at 90 minutes and 120 minutes after administration of glucose.

實例10　正常大鼠中薑花之地下莖(Rhizome)水萃取物的葡萄糖耐性試驗Example 10 Glucose Tolerance Test of Rhizome Water Extract of Ginger Flower in Normal Rats

測試大鼠及程序與實例1中相同。然而，在此情況下，使用24隻史泊格多利大鼠且分為四組：安慰劑組(6隻投與水之大鼠)、0.5 g/kg HC組(6隻投與0.5 g/kg薑花之地下莖水萃取物的大鼠)、1 g/kg HC組(6隻投與1 g/kg薑花之地下莖水萃取物的大鼠)及1.5 g/kg HC組(6隻投與1.5 g/kg薑花之地下莖水萃取物的大鼠)。30分鐘後，各大鼠接受總共5 g/kg葡萄糖(經口(2.5 g/kg)與皮下(2.5 g/kg)投與葡萄糖)。以30分鐘時間間隔抽取血液以量測葡萄糖(mg/dl)。結果展示於下表。Test rats and procedures were the same as in Example 1. However, in this case, 24 Spoggard rats were used and divided into four groups: placebo group (6 rats administered with water), 0.5 g/kg HC group (6 doses of 0.5 g/ Kg ginger flower underground stem water extract of rats), 1 g/kg HC group (6 rats administered with 1 g/kg ginger flower underground water extract) and 1.5 g/kg HC group (6 doses) Rat with 1.5 g/kg ginger flower underground stem water extract). After 30 minutes, each rat received a total of 5 g/kg of glucose (administered with oral (2.5 g/kg) and subcutaneous (2.5 g/kg) glucose). Blood was drawn at 30 minute intervals to measure glucose (mg/dl). The results are shown in the table below.

以平均值+/-標準誤差(SEM)表示數據。由Sigma統計軟體之t檢驗計算p值，其中p<0.05視為顯著的且標記為*；p<0.01視為高度顯著的且標記為**；且p≦0.001視為極度顯著的且標記為***。Data are expressed as mean +/- standard error (SEM). The p-value was calculated from the t test of the Sigma statistical software, where p < 0.05 was considered significant and marked as *; p < 0.01 was considered highly significant and marked as **; and p 0.001 was considered extremely significant and marked as ***.

結果顯示，相較於對照組，各劑量組薑花地下莖之水萃取物在投與葡萄糖後各時間點之血糖濃度都無明顯差異。此顯示薑花地下莖之水萃取物並無降血糖效果。The results showed that compared with the control group, the water extracts of the underground stems of Ginger flower in each dose group had no significant difference in blood glucose concentration at each time point after administration of glucose. This shows that the water extract of the ginger flower underground stem has no hypoglycemic effect.

實例11　正常小鼠中薑花之地下莖(Rhizome)水-乙醇萃取物的葡萄糖耐性試驗Example 11 Glucose Tolerance Test of Rhizome Water-Ethanol Extract in Ginger Flowers in Normal Mice

測試小鼠及程序為禁食14小時後給與自由進食1小時後投藥。使用24隻C57BL/6小鼠且分為四組：安慰劑組(6隻投與10% Tween 20之小鼠)、0.5 g/kg HC組(6隻投與0.5 g/kg薑花地下莖之水-乙醇萃取物的小鼠)、1.0 g/kg HC組(6隻投與1 g/kg薑花地下莖之水-乙醇萃取物的小鼠)及1.5 g/kg HC組(6隻投與1 g/kg薑花地下莖之水-乙醇萃取物的小鼠)。投藥30分鐘後腹腔給葡萄糖(1.5 g/Kg)進行葡萄糖耐受性試驗。以30分鐘時間間隔抽取血液以量測葡萄糖(mg/dl)。結果展示於下表。Test mice and procedures were administered after 14 hours of fasting for 1 hour after free feeding. Twenty-four C57BL/6 mice were used and divided into four groups: placebo group (6 mice dosed with 10% Tween 20), 0.5 g/kg HC group (6 doses of 0.5 g/kg ginger flower underground stems) Water-ethanol extract of mice), 1.0 g/kg HC group (6 mice administered with 1 g/kg ginger flower underground water-ethanol extract) and 1.5 g/kg HC group (6 donors) 1 g/kg ginger flower underground stem water-ethanol extract of mice). Glucose tolerance test was performed on the glucose (1.5 g/Kg) in the abdominal cavity 30 minutes after administration. Blood was drawn at 30 minute intervals to measure glucose (mg/dl). The results are shown in the table below.

以平均值+/-標準誤差(SEM)表示數據。由Sigma統計軟體之t檢驗計算p值，其中p<0.05視為顯著的且標記為*；p<0.01視為高度顯著的且標記為**；且p≦0.001視為極度顯著的且標記為***。Data are expressed as mean +/- standard error (SEM). The p-value was calculated from the t test of the Sigma statistical software, where p < 0.05 was considered significant and marked as *; p < 0.01 was considered highly significant and marked as **; and p 0.001 was considered extremely significant and marked as ***.

結果顯示，相較於對照組，各劑量組薑花地下莖之水-乙醇萃取物在投與葡萄糖後各時間點之血糖濃度都無明顯差異。此顯示薑花地下莖之水-乙醇萃取物並無降血糖效果。The results showed that there was no significant difference in blood glucose concentration at each time point after administration of glucose in the water-ethanol extract of Ginger flower underground stems in each dose group compared with the control group. This shows that the water-ethanol extract of the ginger flower underground stem has no hypoglycemic effect.

圖1說明野薑花葉及假莖之乙醇萃取物降低正常大鼠之血糖的作用。對照組表示經口投與10% Tween 20；Gliben 10 mg/kg表示經口投與10 mg/kg格列本脲(glibenclamide)；HC 250 mg/kg表示經口投與250 mg/kg薑花葉及假莖之乙醇萃取物；且HC 750 mg/kg表示經口投與750 mg/kg薑花葉及假莖之乙醇萃取物。X軸表示量測血糖之時間間隔，且Y軸表示血糖濃度。Figure 1 illustrates the effect of ethanol extract of wild ginger leaves and pseudostems on lowering blood glucose in normal rats. The control group indicated oral administration of 10% Tween 20; Gliben 10 mg/kg means oral administration of 10 mg/kg glibenclamide; HC 250 mg/kg means oral administration of 250 mg/kg ginger flower. Ethanol extracts of leaves and pseudostems; and HC 750 mg/kg means ethanol extracts of 750 mg/kg ginger leaves and pseudostems. The X axis represents the time interval at which blood glucose is measured, and the Y axis represents blood glucose concentration.

圖2說明經由葡萄糖耐性試驗，野薑花葉及假莖之乙醇萃取物降低患第II型糖尿病之db⁺ /db⁺ 小鼠之血糖的作用。對照組表示經口投與10% Tween 20；且HC 1.5 g/kg表示經口投與1.5 g/kg薑花葉及假莖之乙醇萃取物。X軸表示採血之時間間隔，且Y軸表示血糖濃度。p值由Sigma統計軟體之t檢驗計算，其中p<0.05視為顯著的且標記*；p<0.01視為高度顯著的且標記**；且p≦0.001視為極度顯著的且標記***。Figure 2 illustrates the effect of ethanol extracts of wild ginger leaves and pseudostems on blood glucose in db ⁺ /db ⁺ mice with type II diabetes via a glucose tolerance test. The control group indicated oral administration of 10% Tween 20; and HC 1.5 g/kg indicated ethanol extract of 1.5 g/kg ginger mosaic and pseudostem by oral administration. The X axis represents the time interval for blood collection and the Y axis represents blood glucose concentration. The p-value was calculated from the t-test of the Sigma statistical software, where p < 0.05 was considered significant and the marker *; p < 0.01 was considered highly significant and labeled **; and p 0.001 was considered extremely significant and marker *** .

圖3說明經由腹膜內葡萄糖耐性試驗，野薑花葉及假莖之乙醇萃取物降低正常db^- /db^- 小鼠之血糖的作用。對照組表示經口投與10% Tween 20；且HC 1.5 g/kg表示經口投與1.5 g/kg薑花葉及假莖之乙醇萃取物。X軸表示採血之時間間隔，且Y軸表示血糖濃度。3 illustrates, via an intraperitoneal glucose tolerance test, and wild ginger mosaic pseudostem ethanol extract of reducing normal db ^- / db ^- mice the blood glucose. The control group indicated oral administration of 10% Tween 20; and HC 1.5 g/kg indicated ethanol extract of 1.5 g/kg ginger mosaic and pseudostem by oral administration. The X axis represents the time interval for blood collection and the Y axis represents blood glucose concentration.

圖4說明經由腹膜內葡萄糖耐性試驗，野薑花葉及假莖之乙醇萃取物促進正常db^- /db^- 小鼠中胰島素分泌的作用。對照組表示經口投與10% Tween 20；且HC 1.5 g/kg表示經口投與1.5 g/kg薑花葉及假莖之乙醇萃取物。X軸表示採血之時間間隔，且Y軸表示血糖濃度。4 illustrates, via an intraperitoneal glucose tolerance test, and the pseudostem mosaic wild ginger extract with ethanol to promote normal db ^- / db ^- mice insulin secretion. The control group indicated oral administration of 10% Tween 20; and HC 1.5 g/kg indicated ethanol extract of 1.5 g/kg ginger mosaic and pseudostem by oral administration. The X axis represents the time interval for blood collection and the Y axis represents blood glucose concentration.

圖5說明經由葡萄糖耐性試驗，野薑花葉及假莖之乙醇萃取物促進患第II型糖尿病之db⁺ /db⁺ 小鼠中胰島素分泌的作用。對照組表示經口投與10% Tween 20；且HC表示經口投與1.5 g/kg薑花葉及假莖之乙醇萃取物。X軸表示採血之時間間隔，且Y軸表示血糖濃度。Figure 5 illustrates the effect of ethanol extract of wild ginger leaves and pseudostems on insulin secretion in db ⁺ /db ⁺ mice with type 2 diabetes via a glucose tolerance test. The control group indicated oral administration of 10% Tween 20; and HC indicated an ethanolic extract of 1.5 g/kg ginger mosaic and pseudostem by oral administration. The X axis represents the time interval for blood collection and the Y axis represents blood glucose concentration.

圖6說明經由葡萄糖耐性試驗，野薑花葉及假莖之乙醇萃取物降低患第I型糖尿病之大鼠之血糖的作用。對照組表示經口投與10% Tween 20及皮下投與生理食鹽水，且HC表示經口投與1 g/kg薑花葉及假莖之乙醇萃取物。X軸表示採血之時間間隔，且Y軸表示血糖濃度。Figure 6 illustrates the effect of ethanol extracts of wild ginger leaves and pseudostems on blood glucose in rats with type 1 diabetes via a glucose tolerance test. The control group indicated oral administration of 10% Tween 20 and subcutaneous administration of physiological saline, and HC indicated ethanol extract of 1 g/kg ginger mosaic and pseudostem by oral administration. The X axis represents the time interval for blood collection and the Y axis represents blood glucose concentration.

圖7說明經由葡萄糖耐性試驗，野薑花葉及假莖之乙醇萃取物降低患第I型糖尿病之大鼠之胰島素抗性的作用。對照組表示經口投與10% Tween 20及皮下投與生理食鹽水；胰島素(0.3 U/kg)表示經口投與10% Tween 20及皮下投與0.3 U/kg胰島素；且胰島素(0.3 U/kg)+HC(1.0 g/kg)表示經口投與1 g/kg薑花葉及假莖之乙醇萃取物及皮下投與0.3 U/kg胰島素。X軸表示採血之時間間隔，且Y軸表示血糖濃度。Figure 7 illustrates the effect of ethanol extracts of wild ginger leaves and pseudostems on insulin resistance in rats with type 1 diabetes via a glucose tolerance test. The control group indicated oral administration of 10% Tween 20 and subcutaneous administration of physiological saline; insulin (0.3 U/kg) means oral administration of 10% Tween 20 and subcutaneous administration of 0.3 U/kg insulin; and insulin (0.3 U) /kg)+HC (1.0 g/kg) means oral administration of ethanol extract of 1 g/kg ginger mosaic and pseudostem and subcutaneous administration of 0.3 U/kg insulin. The X axis represents the time interval for blood collection and the Y axis represents blood glucose concentration.

圖8說明經由葡萄糖耐性試驗，野薑花葉及假莖之水萃取物降低正常大鼠之血糖的作用。ddH₂ O表示經口投與H₂ O；HC 0.5 g/kg表示經口投與0.5 g/kg野薑花葉及假莖之水萃取物；HC 1.0 g/kg表示經口投與1.0 g/kg薑花葉及假莖之水萃取物；且HC 1.5 g/kg表示經口投與1.5 g/kg薑花葉及假莖之水萃取物。X軸表示採血之時間間隔，且Y軸表示血糖濃度。Figure 8 illustrates the effect of water extracts of wild ginger leaves and pseudostems on lowering blood glucose in normal rats via a glucose tolerance test. ddH ₂ O means oral administration of H ₂ O; HC 0.5 g/kg means oral administration of water extract of 0.5 g/kg of wild ginger leaves and pseudostem; HC 1.0 g/kg means oral administration of 1.0 g /kg water extract of ginger mosaic and pseudostem; and HC 1.5 g/kg means oral extract of 1.5 g/kg ginger leaf and pseudostem water extract. The X axis represents the time interval for blood collection and the Y axis represents blood glucose concentration.

圖9說明經由葡萄糖耐性試驗，野薑花葉及假莖之水-乙醇萃取物降低正常大鼠之血糖的作用。ddH₂ O表示經口投與H₂ O；Gliben 10 mg/kg表示經口投與10 mg/kg格列本脲；HC 0.4 g/kg表示經口投與0.4 g/kg薑花葉及假莖之水-乙醇萃取物；且HC 0.8 g/kg表示經口投與0.8 g/kg薑花葉及假莖之水-乙醇萃取物。X軸表示採血之時間間隔，且Y軸表示血糖濃度。Figure 9 illustrates the effect of water-ethanol extract of wild ginger leaves and pseudostems on lowering blood glucose in normal rats via a glucose tolerance test. ddH ₂ O means oral administration of H ₂ O; Gliben 10 mg/kg means oral administration of 10 mg/kg glibenclamide; HC 0.4 g/kg means oral administration of 0.4 g/kg ginger mosaic and false Stem water-ethanol extract; and HC 0.8 g/kg means a water-ethanol extract of 0.8 g/kg ginger mosaic and pseudostem. The X axis represents the time interval for blood collection and the Y axis represents blood glucose concentration.

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