TWI725317B - Use of composition of neoandrographolide in lowering blood sugar - Google Patents

Use of composition of neoandrographolide in lowering blood sugar Download PDF

Info

Publication number
TWI725317B
TWI725317B TW107121756A TW107121756A TWI725317B TW I725317 B TWI725317 B TW I725317B TW 107121756 A TW107121756 A TW 107121756A TW 107121756 A TW107121756 A TW 107121756A TW I725317 B TWI725317 B TW I725317B
Authority
TW
Taiwan
Prior art keywords
composition
neoandrographolide
patent application
scope
use according
Prior art date
Application number
TW107121756A
Other languages
Chinese (zh)
Other versions
TW202000209A (en
Inventor
林郁進
張靜雯
Original Assignee
馬來西亞商科鼎國際有限公司
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 馬來西亞商科鼎國際有限公司 filed Critical 馬來西亞商科鼎國際有限公司
Priority to TW107121756A priority Critical patent/TWI725317B/en
Priority to US16/449,347 priority patent/US11318153B2/en
Publication of TW202000209A publication Critical patent/TW202000209A/en
Application granted granted Critical
Publication of TWI725317B publication Critical patent/TWI725317B/en

Links

Images

Abstract

The present invention provides the use of Neoandrographolide in preparing a composition for lowering blood sugar. Neoandrographolide is the active component in the composition.

Description

新穿心蓮內酯之組成物用於血糖調降之應用The composition of neoandrographolide is used for the application of blood glucose lowering

本發明是有關於新穿心蓮內酯的用途,且特別是有關於新穿心蓮內酯用於製備可調降血糖組成物的用途。The present invention relates to the use of neoandrographolide, and particularly to the use of neoandrographolide for preparing an adjustable blood sugar lowering composition.

糖尿病(Diabetes mellitus)是一種日益嚴重的問題,在發達的國家以及發展中的國家造成許多國民的財務負擔、生活品質下降等問題。糖尿病的特徵是,患者具有高血糖症,且通常伴隨著脂肪及蛋白質的代謝紊亂。一般來說,若不進行治療,糖尿病會引發許多的併發症,例如,心血管疾病、失明、腎功能衰竭和周圍神經損傷等等,嚴重時甚至會造成患者的死亡。就世界衛生組織(World Health Organization;WHO)的統計來說,目前全世界大約有2.5億人患有糖尿病,且到2030年時,患者的數量估計會達到3.6億人。Diabetes mellitus (Diabetes mellitus) is an increasingly serious problem that has caused many people’s financial burdens and reduced quality of life in developed and developing countries. Diabetes is characterized by hyperglycemia, which is usually accompanied by metabolic disorders of fat and protein. Generally speaking, if not treated, diabetes will cause many complications, such as cardiovascular disease, blindness, renal failure and peripheral nerve damage, etc., and even death of the patient in severe cases. According to statistics from the World Health Organization (WHO), there are currently approximately 250 million people living with diabetes in the world, and by 2030, the number of patients is estimated to reach 360 million.

糖尿病可以分為兩種類型,包括第1型糖尿病(胰島素依賴型糖尿病)以及第2型糖尿病(非胰島素依賴型糖尿病)。兩種類型的糖尿病患者的特徵都是其血糖長期高於標準值。糖尿病的病因除了胰島素的分泌不足或甚至不分泌外,胰島素阻抗亦被認為是常見的原因之一。Diabetes can be divided into two types, including type 1 diabetes (insulin-dependent diabetes) and type 2 diabetes (non-insulin-dependent diabetes). The characteristic of both types of diabetic patients is that their blood glucose is long-term higher than the standard value. In addition to insufficient or even no secretion of insulin, the cause of diabetes, insulin resistance is also considered to be one of the common causes.

穿心蓮(Andrographis paniculata;AP)是一種具有前景的可用於治療高血糖症的爵床科植物,其在印度、中國大陸、馬來西亞及臺灣等地均有廣泛栽培。穿心蓮的主要藥用部位是乾燥莖與葉子,穿心蓮葉含有多種二萜內酯化合物,包括去氧穿心蓮內酯(Deoxyandrographolide)、穿心蓮內酯(Andrographolide)、新穿心蓮內酯(Neoandrographolide)、高穿心蓮內酯(Homoandrographolide)、潘尼內酯 (Panicolide)。還含有穿心蓮烷(Andrographan)、穿心蓮酮(Andrographon)、穿心蓮甾醇(Andrographosterin)、β-谷甾醇-D-葡萄糖甙等。根部除了含有穿心蓮內酯之外,還含有5-羥基-7, 8, 2", 3"-四甲氧基黃酮(Mono-o-methylwithtin)、5-羥基-7, 8, 2"-三甲氧基黃酮 (Andrographin)、5, 2"-二羥基-7, 8-二甲氧基黃酮(Panicolin)、芹菜素-7, 4"-二甲醚(Apigenin-7, 4"-dimethyl ether)、a1-谷甾醇和磷酸二氫鉀(KH2 PO4 )等。另據初步分析,穿心蓮還含有甾醇皂甙、糖類及縮合鞣質等酚類物質。Andrographis paniculata (AP) is a promising Acanthaceae plant that can be used to treat hyperglycemia. It is widely cultivated in India, China, Malaysia, and Taiwan. The main medicinal parts of Andrographis paniculata are dry stems and leaves. Andrographis paniculata leaves contain a variety of diterpene lactone compounds, including Deoxyandrographolide, Andrographolide, Neoandrographolide, and High andrographolide. Ester (Homoandrographolide), Panicolide (Panicolide). It also contains Andrographan, Andrographon, Andrographosterin, β-sitosterol-D-glucoside, etc. In addition to andrographolide, the root also contains 5-hydroxy-7, 8, 2", 3"-tetramethoxy flavonoids (Mono-o-methylwithtin), 5-hydroxy-7, 8, 2"-trimethyl Oxyflavone (Andrographin), 5, 2"-dihydroxy-7, 8-dimethoxyflavone (Panicolin), Apigenin-7, 4"-dimethyl ether (Apigenin-7, 4"-dimethyl ether) , A1-sitosterol and potassium dihydrogen phosphate (KH 2 PO 4 ) and so on. According to preliminary analysis, Andrographis paniculata also contains phenolic substances such as sterol saponins, sugars and condensed tannins.

穿心蓮植物的各種成分,特別是新穿心蓮內酯是否具有特定醫療保健功能是值得再探討及研究的議題。The various components of the Andrographis paniculata plant, especially whether neoandrographolide has specific medical and health care functions is a topic worthy of further discussion and research.

本發明提供新穿心蓮內酯的新用途,特別是,新穿心蓮內酯在製備可調降血糖之組成物的用途。經實驗發現,新穿心蓮內酯至少具備可以調降血糖的能力。此外,新穿心蓮內酯具備同時調降血糖、調降血脂、改善肝功能以及改善腎功能的能力。The present invention provides a new use of the new andrographolide, in particular, the use of the new andrographolide in the preparation of an adjustable blood sugar lowering composition. Experiments have found that new andrographolide at least has the ability to lower blood sugar. In addition, Neoandrographolide has the ability to simultaneously lower blood sugar, lower blood lipids, improve liver function, and improve kidney function.

本發明揭露新穿心蓮內酯在製備可調降血糖之組成物的用途,其中所述組成物包括新穿心蓮內酯做為活性成分,所述組成物係用以降低使用者的空腹血糖值。The present invention discloses the use of neoandrographolide in the preparation of an adjustable blood glucose lowering composition, wherein the composition includes neoandrographolide as an active ingredient, and the composition is used to reduce the fasting blood glucose value of the user.

本發明另揭露新穿心蓮內酯在製備可調降血糖之組成物的用途,其中所述組成物包括新穿心蓮內酯做為活性成分,所述組成物係用以降低使用者的糖化血色素指數。The present invention also discloses the use of neoandrographolide in the preparation of an adjustable blood glucose lowering composition, wherein the composition includes neoandrographolide as an active ingredient, and the composition is used to reduce the user's glycated hemoglobin index.

本發明另揭露新穿心蓮內酯在製備可調降血糖之組成物的用途,其中所述組成物包括新穿心蓮內酯做為活性成分,所述組成物係用以增加使用者的葡萄糖耐受性。The present invention also discloses the use of neoandrographolide in the preparation of an adjustable blood sugar lowering composition, wherein the composition includes neoandrographolide as an active ingredient, and the composition is used to increase the user's glucose tolerance .

在本發明的一實施例中,所述組成物所包括的新穿心蓮內酯為唯一活性成分。In an embodiment of the present invention, the new andrographolide included in the composition is the only active ingredient.

在本發明的一實施例中,所述新穿心蓮內酯的最低有效劑量範圍為0.5mg/kg至20mg/kg。In an embodiment of the present invention, the minimum effective dose of the neoandrographolide ranges from 0.5 mg/kg to 20 mg/kg.

在本發明的一實施例中,所述新穿心蓮內酯適用的最低有效劑量範圍為0.625mg/kg至20mg/kg。In an embodiment of the present invention, the applicable minimum effective dose of the neoandrographolide ranges from 0.625 mg/kg to 20 mg/kg.

在本發明的一實施例中,所述組成物為醫藥組成物。In an embodiment of the present invention, the composition is a pharmaceutical composition.

在本發明的一實施例中,所述組成物為一製劑。In an embodiment of the present invention, the composition is a preparation.

在本發明的一實施例中,所述製劑為錠劑、片劑、液劑、粉劑、顆粒劑、散劑、丸劑、滴丸劑、膠囊、軟膏、乳膏、乳膠、凝膠、貼片、注射劑、吸入劑、噴劑或是塞劑。In an embodiment of the present invention, the preparation is a lozenge, tablet, liquid, powder, granule, powder, pill, drop pill, capsule, ointment, cream, latex, gel, patch, injection , Inhalation, spray or suppository.

在本發明的一實施例中,所述組成物為一外用製劑。In an embodiment of the present invention, the composition is an external preparation.

在本發明的一實施例中,所述外用製劑包括液劑、粉劑、顆粒劑、噴劑、軟膏、乳膏、乳膠、凝膠或是貼片。In an embodiment of the present invention, the external preparation includes liquid, powder, granule, spray, ointment, cream, latex, gel or patch.

在本發明的一實施例中,所述組成物為一口服製劑。In an embodiment of the present invention, the composition is an oral preparation.

在本發明的一實施例中,所述口服製劑包括錠劑、片劑、液劑、粉劑、顆粒劑、散劑、丸劑、滴丸劑或是膠囊。In an embodiment of the present invention, the oral preparation includes lozenges, tablets, liquids, powders, granules, powders, pills, dropping pills or capsules.

在本發明的一實施例中,所述組成物為一醫藥組成物,且所述組成物更包括醫藥上所使用載劑、稀釋劑或賦形劑做為所述組成物中的非活性成分。In an embodiment of the present invention, the composition is a pharmaceutical composition, and the composition further includes a carrier, diluent or excipient used in medicine as an inactive ingredient in the composition .

在本發明的一實施例中,所述組成物為食品組成物,且所述組成物更包括食品上所使用的增味劑、甜味劑、增稠劑或賦形劑做為所述組成物中的非活性成分。In an embodiment of the present invention, the composition is a food composition, and the composition further includes flavor enhancers, sweeteners, thickeners or excipients used on food as the composition Inactive ingredients in the product.

本發明另提供一種組合物作為血糖調節的功能性食品的應用,所述組合物包括由新穿心蓮內酯所組成的活性成分;以及食品上所使用的增味劑、甜味劑、增稠劑或賦形劑做為所述組成物中的非活性成分。The present invention also provides an application of a composition as a functional food for blood sugar regulation. The composition includes an active ingredient composed of neoandrographolide; and a flavor enhancer, sweetener, and thickener used in food Or excipients are used as inactive ingredients in the composition.

在本發明的一實施例中,所述功能性食品的形式為液體飲料、膠狀品、膠囊、錠劑、片劑或粉末。In an embodiment of the present invention, the functional food is in the form of a liquid beverage, gel, capsule, lozenge, tablet or powder.

基於上述,本發明提供一種新穿心蓮內酯的新用途,其適用於降血糖、降血脂、改善肝功能以及改善腎功能等用途。Based on the above, the present invention provides a new use of new andrographolide, which is suitable for lowering blood sugar, lowering blood lipid, improving liver function, improving kidney function, and the like.

為讓本發明的上述特徵和優點能更明顯易懂,下文特舉實施例,並配合所附圖式作詳細說明如下。In order to make the above-mentioned features and advantages of the present invention more comprehensible, the following specific embodiments are described in detail in conjunction with the accompanying drawings.

本發明實施例中所述的新穿心蓮內酯(Neoandrographolide)可以包括從穿心蓮(Andrographis paniculata)植物中所萃取得到的新穿心蓮內酯或是透過化學合成方式合成的新穿心蓮內酯。新穿心蓮內酯的化學結構式乃是以下列化學式1所示:<img wi="315" he="248" file="IMG-2/Draw/02_image001.jpg" img-format="jpg"> 化學式1。The neoandrographolide described in the embodiment of the present invention may include neoandrographolide extracted from the Andrographis paniculata plant or neoandrographolide synthesized by chemical synthesis. The chemical structure of neoandrographolide is shown in the following chemical formula 1: <img wi="315"he="248"file="IMG-2/Draw/02_image001.jpg"img-format="jpg"> Chemical formula 1.

本發明實施例中所述的新穿心蓮內酯乃涵括其生理學上之功能衍生物,也就是說本發明實施例中所述的新穿心蓮內酯包含其於醫藥學上可接受之鹽、其於醫藥學上可接受之對映異構體、其於醫藥學上可接受之固態形式(結晶、半結晶或非晶)、其於醫藥學上可接受之多晶型物、其於醫藥學上可接受之溶劑合物或其醫藥學上可接受之代謝物或醫藥學上可接受之前藥。The new andrographolide described in the embodiments of the present invention includes its physiologically functional derivatives, that is to say, the new andrographolide described in the embodiments of the present invention includes its pharmaceutically acceptable salt, Its pharmaceutically acceptable enantiomers, its pharmaceutically acceptable solid form (crystalline, semi-crystalline or amorphous), its pharmaceutically acceptable polymorphs, its use in medicine Academically acceptable solvates or pharmaceutically acceptable metabolites or pharmaceutically acceptable prodrugs.

本發明一些實施例提供使用新穿心蓮內酯來製備可調降血糖之組成物的用途,所述組成物包括新穿心蓮內酯做為唯一的藥理活性成分。根據本發明實施例,施用所述組成物可以有效地降低備施用者(亦即使用者)的空腹血糖值。根據本發明實施例,施用所述組成物可以有效地降低使用者的糖化血色素指數。根據本發明實施例,施用所述組成物可以有效地增加使用者的葡萄糖耐受性。透過上述的各種應用,使用所述組成物更可以有效地對使用者達到血糖調節的用途。在一些其它實施例中,新穿心蓮內酯是做為組成物中的主要活性成分,但仍可與其它活性成分一起併用來達到血糖調節的用途。Some embodiments of the present invention provide the use of neoandrographolide to prepare an adjustable blood glucose lowering composition, the composition including neoandrographolide as the sole pharmacologically active ingredient. According to an embodiment of the present invention, the administration of the composition can effectively reduce the fasting blood glucose value of the person preparing for the administration (ie, the user). According to an embodiment of the present invention, the administration of the composition can effectively reduce the glycated hemoglobin index of the user. According to an embodiment of the present invention, the administration of the composition can effectively increase the user's glucose tolerance. Through the above-mentioned various applications, the use of the composition can more effectively achieve the purpose of blood glucose regulation for users. In some other embodiments, neoandrographolide is used as the main active ingredient in the composition, but it can still be used together with other active ingredients to achieve blood glucose regulation.

在一些實施例中,當新穿心蓮內酯是用來降低使用者的空腹血糖值時,其適用劑量為0.5 mg/kg至20mg/kg。也就是說,其最低有效劑量為約0.5mg/kg。在一些實施例中,新穿心蓮內酯適用的有效劑量範圍為0.625mg/kg至20mg/kg。在一些實施例中,新穿心蓮內酯的有效劑量範圍為0.625mg/kg至10 mg/kg。在一些實施例中,新穿心蓮內酯的有效劑量範圍為0.625mg/kg至5 mg/kg。在另一實施例中,當新穿心蓮內酯是用來降低使用者的糖化血色素指數時,其適用劑量為0.5 mg/kg至20mg/kg。也就是說,其最低有效劑量為約0.5 mg/kg。在一些實施例中,新穿心蓮內酯的有效劑量範圍為0.625mg/kg至20mg/kg。在一些實施例中,新穿心蓮內酯的有效劑量範圍為0.625mg/kg至10 mg/kg。在一些實施例中,新穿心蓮內酯的有效劑量範圍為0.625mg/kg至5 mg/kg。在本發明一些實施例中,新穿心蓮內酯為所述組成物中的唯一活性成分。換言之,本發明一些實施例中,本案實施例組成物僅使用新穿心蓮內酯作為本案實施例組成物中的藥理活性成分,而穿心蓮萃取物中所包含的其他成分,例如去氧穿心蓮內酯(Deoxyandrographolide)或是穿心蓮內酯(Andrographolide)並不包括在本案實施例組成物中。In some embodiments, when neoandrographolide is used to lower the user's fasting blood glucose level, the applicable dose is 0.5 mg/kg to 20 mg/kg. That is, the lowest effective dose is about 0.5 mg/kg. In some embodiments, the effective dose range of neoandrographolide is 0.625 mg/kg to 20 mg/kg. In some embodiments, the effective dose of neoandrographolide ranges from 0.625 mg/kg to 10 mg/kg. In some embodiments, the effective dose of neoandrographolide ranges from 0.625 mg/kg to 5 mg/kg. In another embodiment, when neoandrographolide is used to reduce the glycated hemoglobin index of the user, the applicable dose is 0.5 mg/kg to 20 mg/kg. That is, the lowest effective dose is about 0.5 mg/kg. In some embodiments, the effective dose of neoandrographolide ranges from 0.625 mg/kg to 20 mg/kg. In some embodiments, the effective dose of neoandrographolide ranges from 0.625 mg/kg to 10 mg/kg. In some embodiments, the effective dose of neoandrographolide ranges from 0.625 mg/kg to 5 mg/kg. In some embodiments of the present invention, neoandrographolide is the only active ingredient in the composition. In other words, in some embodiments of the present invention, the composition of the example of the present case only uses neoandrographolide as the pharmacologically active ingredient in the composition of the example of the present case, while other components contained in the andrographis extract, such as deoxyandrographolide ( Deoxyandrographolide) or Andrographolide (Andrographolide) are not included in the composition of the examples in this case.

在一些實施例中,所述組成物為一醫藥組成物或一製劑。在一些實施例中,所述製劑可以為口服製劑或是外用製劑,但並不以此為限制。在一些實施例中,所述製劑為錠劑、片劑、液劑、粉劑、顆粒劑、散劑、丸劑、滴劑、滴丸劑、膠囊、軟膏、乳膏、乳膠、凝膠、貼片、注射劑、吸入劑、噴劑或是塞劑等等。在一些實施例中,所述口服製劑是指以口服形式施用或可適合於經口投與。出於本發明之目的,口服製劑形式包含膠囊、錠劑、丸劑、顆粒劑、散劑、滴劑及滴丸劑。舉例而言,其製劑可為經包覆或未經包覆、起泡、可溶、口內崩散、腸溶或緩釋錠劑;糖衣錠劑;硬膠囊;軟膠囊;顆粒形式;丸劑;片劑形式調配組成物。較佳地,口服製劑形式為錠劑或膠囊。在一些實施例中,所述外用製劑是液劑、粉劑、顆粒劑、噴劑、軟膏、乳膏、乳膠、凝膠或是貼片。In some embodiments, the composition is a pharmaceutical composition or a preparation. In some embodiments, the preparation may be an oral preparation or an external preparation, but it is not limited thereto. In some embodiments, the formulation is a lozenge, tablet, liquid, powder, granule, powder, pill, drop, drop pill, capsule, ointment, cream, latex, gel, patch, injection , Inhalants, sprays or suppositories, etc. In some embodiments, the oral formulation refers to administration in an oral form or may be suitable for oral administration. For the purpose of the present invention, oral preparation forms include capsules, lozenges, pills, granules, powders, drops, and pills. For example, the preparation can be coated or uncoated, foamed, soluble, orally disintegrating, enteric-coated or sustained-release lozenges; sugar-coated lozenges; hard capsules; soft capsules; granular forms; pills; The composition is formulated in the form of a tablet. Preferably, the oral preparation is in the form of tablets or capsules. In some embodiments, the external preparation is a liquid, powder, granule, spray, ointment, cream, latex, gel, or patch.

在一些實施例中,所述組成物為健康食品組成物、功能性食品組成物、機能保健食品組成物,甚或是可用於作為預防生理機能改變的食品組成物或搭配改變外表機能的食品組成物等等,但並不以此為限制。在一些實施例中,所述食品組成物更包括添加劑、載劑、稀釋劑或賦形劑做為所述組成物中的其他非活性成分。所述載劑、稀釋劑或賦形劑並無特別限制,且可以配合不同的組合物型態或劑型來進行調整。舉例來說,添加劑和賦形劑包括但不限於防黏劑、防發泡劑、緩衝劑、聚合物、抗氧化劑、防腐劑、螯合劑、黏性調節劑、張力調節劑、調味劑、著色劑、香味劑、遮光劑、懸浮劑、黏合劑、填充劑、塑化劑、潤滑劑及其混合物。在一些實施例中,所述組成物更包括食品上所使用的增味劑、甜味劑、增稠劑或賦形劑做為所述組成物中的非活性成分。In some embodiments, the composition is a health food composition, a functional food composition, a functional health food composition, or even a food composition that can be used to prevent changes in physiological functions or a food composition that changes appearance functions Wait, but not as a limit. In some embodiments, the food composition further includes additives, carriers, diluents or excipients as other inactive ingredients in the composition. The carrier, diluent or excipient is not particularly limited, and can be adjusted according to different composition forms or dosage forms. For example, additives and excipients include, but are not limited to, anti-sticking agents, anti-foaming agents, buffers, polymers, antioxidants, preservatives, chelating agents, viscosity regulators, tonicity regulators, flavoring agents, and coloring agents. Agents, fragrances, sunscreens, suspending agents, binders, fillers, plasticizers, lubricants and mixtures thereof. In some embodiments, the composition further includes flavor enhancers, sweeteners, thickeners or excipients used in foods as inactive ingredients in the composition.

在一些實施例中,血糖調節的功能性食品可以使用由新穿心蓮內酯所組成的組合物或包含新穿心蓮內酯的組合物作為主要活性成分。在一些實施例中,所述功能性食品可呈現為液體飲料、膠狀品、膠囊、錠劑、片劑或粉末形式,但並不以此為限制。舉例來說,所述功能性食品可以是任何可藉由口服形式服用或食用的功能性食品。In some embodiments, the functional food for blood glucose regulation may use a composition composed of neoandrographolide or a composition containing neoandrographolide as the main active ingredient. In some embodiments, the functional food may be in the form of a liquid beverage, gel, capsule, lozenge, tablet or powder, but it is not limited thereto. For example, the functional food may be any functional food that can be taken or eaten in an oral form.

針對本發明實施例中的新穿心蓮內酯的應用與功效,將以下列實施例來做為舉例說明。然而,下列的實施例僅是輔助說明,而並非用以限定本發明。實施例 Regarding the application and efficacy of the new andrographolide in the examples of the present invention, the following examples will be used as examples. However, the following embodiments are only an auxiliary description, and are not intended to limit the present invention. Example

在本實施例中,將測試各種劑量之新穿心蓮內酯對於誘導組(誘導所致第2型糖尿病小鼠)的血糖調節能力、生理功能、血液生化物質和一些重要器官組織病理所帶來的影響進行評估。In this example, various doses of new andrographolide will be tested for the blood glucose regulation ability, physiological function, blood biochemical substances, and some important organ tissue pathologies in the induced group (type 2 diabetic mice caused by induction). The impact is assessed.

雄性ICR小鼠(19-21 g)是購買自台灣BioLASCO Co., Ltd。小鼠餵養於環球科技大學之動物中心,溫度調控於22 ± 2℃,相對濕度55 ± 5%,且於實驗前一周施予12小時光照/12小時黑暗週期。對於第II型糖尿病鼠之誘導(誘導處理組STZ),是將菸鹼醯胺(Nicotinamide;Sigma, Saint Louis, MO, USA)食鹽水溶液(210 mg/kg b.w.)以腹膜內注射入小鼠,經15分鐘後將於使用前溶解於檸檬酸鹽緩衝液(pH 4.5)之鏈佐黴素(STZ)(Sigma, 180 mg/kg b. w., i.p.注射)投藥給該小鼠。對照組係接受該二種載劑者。於實驗期間,每週一次記錄實驗動物之食物攝取量及體重。另外,本發明的新穿心蓮內酯(Sigma-Aldrich Chemical Co., Missouri, USA)之投藥量為:NeoL(新穿心蓮內酯低劑量組): 新穿心蓮內酯2.5mg/kg;NeoM(新穿心蓮內酯中劑量組):新穿心蓮內酯5.0mg/kg;NeoH(新穿心蓮內酯高劑量組):新穿心蓮內酯10 mg/kg。上述活性成分是經Tween 20溶解後調整成0.5%甲基纖維素(CMC)溶液。空白組(Sham)則為未經誘導處理的正常小鼠。臨床觀察 Male ICR mice (19-21 g) were purchased from Taiwan BioLASCO Co., Ltd. The mice were fed in the Animal Center of the Universal University of Science and Technology, the temperature was regulated at 22 ± 2°C, the relative humidity was 55 ± 5%, and they were given a 12-hour light/12-hour dark cycle one week before the experiment. For the induction of type II diabetic mice (induction treatment group STZ), nicotinamide (Nicotinamide; Sigma, Saint Louis, MO, USA) saline solution (210 mg/kg bw) was injected intraperitoneally into the mice. After 15 minutes, streptozotocin (STZ) (Sigma, 180 mg/kg bw, ip injection) dissolved in citrate buffer (pH 4.5) before use was administered to the mouse. The control group received the two carriers. During the experiment, the food intake and body weight of the experimental animals were recorded once a week. In addition, the dosage of new andrographolide (Sigma-Aldrich Chemical Co., Missouri, USA) of the present invention is: NeoL (new andrographolide low-dose group): new andrographolide 2.5 mg/kg; NeoM (new andrographolide) Medium-dose lactone group): Neoandrographolide 5.0 mg/kg; NeoH (new andrographolide high-dose group): Neoandrographolide 10 mg/kg. The above active ingredients are adjusted to 0.5% methyl cellulose (CMC) solution after being dissolved in Tween 20. The blank group (Sham) were normal mice without induction treatment. Clinical Observation

每天至少進行兩次觀察動物之身體狀況,每次觀察的時間間隔不少於6小時,以確定動物的健康或死亡狀態。每天至少一次觀察試驗動物之臨床病徵,記錄試驗動物所表現出的毒性作用,包括該等毒性作用的開始時間及過程。試驗結束後,將存活的小鼠犧牲;之後進行屍體解剖,採取血液樣本進行血清生化分析。水攝入量檢測 Observe the animal's physical condition at least twice a day, and the interval between each observation is not less than 6 hours to determine the animal's health or death status. Observe the clinical symptoms of the experimental animals at least once a day, and record the toxic effects shown by the experimental animals, including the onset time and course of the toxic effects. After the experiment, the surviving mice were sacrificed; autopsy was performed afterwards, and blood samples were taken for serum biochemical analysis. Water intake testing

一般來說,糖尿病患者通常會有「多喝水」的臨床症狀。在本實驗例中,是在40天的期間內分別記錄空白組Sham、誘導處理組STZ、新穿心蓮內酯低劑量組NeoL(2.5mg/kg)、新穿心蓮內酯中劑量組NeoM(5.0mg/kg)以及新穿心蓮內酯高劑量組NeoH(10mg/kg)小鼠的水攝入量。實驗結果如圖1所示。Generally speaking, diabetic patients usually have clinical symptoms of "drink plenty of water". In this experimental example, the blank group Sham, the induction treatment group STZ, the neoandrographolide low-dose group NeoL (2.5mg/kg), and the neoandrographolide middle-dose group NeoM (5.0mg /kg) and the water intake of NeoH (10mg/kg) mice in the neoandrographolide high-dose group. The experimental results are shown in Figure 1.

圖1顯示的是本發明實驗例各種劑量之新穿心蓮內酯對於誘導組第2型糖尿病小鼠的水攝入量檢測結果。如圖1所示,誘導處理組STZ的小鼠的水攝入量在40天的期間內明顯地高於空白組Sham的小鼠。此實驗結果證明經誘導的第2型糖尿病小鼠的水攝入量會比一般正常小鼠來得多。另外,經誘導的第II型糖尿病小鼠在被施用不同劑量的新穿心蓮內酯時,實驗結果發現,不論是在高劑量(10mg/kg)或是低劑量(2.5mg/kg)的情況下,經誘導的第II型糖尿病小鼠的飲水量都會明顯地降低。換言之,新穿心蓮內酯能夠單獨做為活性成分來減輕糖尿病小鼠的臨床病徵。口服葡萄糖耐受性試驗 Figure 1 shows the test results of the water intake of various doses of neoandrographolide in the induced group of type 2 diabetic mice in the experimental example of the present invention. As shown in Figure 1, the water intake of STZ mice in the induction treatment group was significantly higher than that of Sham mice in the blank group during a 40-day period. The results of this experiment prove that the water intake of induced type 2 diabetic mice is much higher than that of normal mice. In addition, when the induced type II diabetic mice were administered with different doses of new andrographolide, the experimental results found that whether it was at a high dose (10mg/kg) or a low dose (2.5mg/kg) , The drinking water of induced type II diabetic mice will be significantly reduced. In other words, neoandrographolide alone can be used as an active ingredient to reduce the clinical symptoms of diabetic mice. Oral glucose tolerance test

在本實驗例中,是進行口服葡萄糖耐受性試驗,來評估周邊葡萄糖利用率。在投藥本發明之新穿心蓮內酯低劑量組NeoL(2.5mg/kg)、新穿心蓮內酯中劑量組NeoM(5.0mg/kg)以及新穿心蓮內酯高劑量組NeoH(10mg/kg)30分鐘後,於給予葡萄糖之前採集血液樣本測定樣本中的血糖濃度,此為0小時的血糖值。給予葡萄糖(2 g/kg) 30、60、90、120、150、180分鐘後,採集血液樣本測定樣本中的血糖濃度。實驗結果如圖2所示。In this experimental example, an oral glucose tolerance test was performed to evaluate the peripheral glucose utilization. In the new andrographolide low-dose group NeoL (2.5mg/kg), neoandrographolide middle-dose group NeoM (5.0mg/kg) and neoandrographolide high-dose group NeoH (10mg/kg) for 30 minutes After that, a blood sample is collected before the glucose is administered to determine the blood glucose concentration in the sample, which is the blood glucose level at 0 hours. 30, 60, 90, 120, 150, 180 minutes after the administration of glucose (2 g/kg), a blood sample was collected to determine the blood glucose concentration in the sample. The experimental results are shown in Figure 2.

圖2顯示的是本發明實驗例各種劑量之新穿心蓮內酯對於誘導組第2型糖尿病小鼠的口服葡萄糖耐受性試驗的結果。在圖2中,各數值以平均値±SEM(平均標準誤差)來表示,其中### P<0.001是相較於空白組Sham;*P<0.05,**P<0.01,***P<0.001是相較於誘導處理組STZ。如圖2的實驗結果所示,誘導處理組STZ小鼠的血糖値明顯高於空白組Sham。此實驗結果證明經誘導的第2型糖尿病小鼠的葡萄糖耐受性較正常小鼠來得差。另外,新穿心蓮內酯的三個劑量組(NeoL、NeoM、NeoH)在0至3小時內的血糖値都明顯低於誘導處理組STZ。本發明的新穿心蓮內酯可用以改善經誘導的第2型糖尿病小鼠的低葡萄糖耐受性。換言之,本發明的新穿心蓮內酯可用以提高經誘導的糖尿病小鼠的葡萄糖耐受性。空腹血糖測定 Figure 2 shows the results of the oral glucose tolerance test of various doses of neoandrographolide in the induced group of type 2 diabetic mice in the experimental example of the present invention. In Figure 2, each value is represented by the mean ±SEM (mean standard error), where ### P<0.001 is compared to the blank group Sham; *P<0.05, **P<0.01, ***P <0.001 is compared to STZ in the induction treatment group. As shown in the experimental results in Figure 2, the blood glucose level of STZ mice in the induction treatment group was significantly higher than that of the blank group Sham. The results of this experiment prove that the glucose tolerance of induced type 2 diabetic mice is worse than that of normal mice. In addition, the blood glucose values of the three dose groups of neoandrographolide (NeoL, NeoM, NeoH) within 0 to 3 hours were significantly lower than the STZ of the induction treatment group. The new andrographolide of the present invention can be used to improve the low glucose tolerance of induced type 2 diabetic mice. In other words, the new andrographolide of the present invention can be used to improve the glucose tolerance of induced diabetic mice. Fasting blood glucose measurement

在本實驗例中,是在42天的期間內分別記錄空白組Sham、誘導處理組STZ、新穿心蓮內酯低劑量組NeoL(2.5mg/kg)、新穿心蓮內酯中劑量組NeoM(5.0mg/kg)以及新穿心蓮內酯高劑量組NeoH小鼠的空腹血糖値。實驗結果如圖3所示。In this experimental example, the blank group Sham, the induction treatment group STZ, the neoandrographolide low-dose group NeoL (2.5mg/kg), and the neoandrographolide middle-dose group NeoM (5.0mg /kg) and the fasting blood glucose values of NeoH mice in the neoandrographolide high-dose group. The experimental results are shown in Figure 3.

圖3顯示的是本發明實驗例各種劑量之新穿心蓮內酯對於誘導組第2型糖尿病小鼠的空腹血糖值測定的結果。在圖3中,各數值以平均値±SEM(平均標準誤差)來表示,其中### P<0.001是相較於空白組Sham;*P<0.05,**P<0.01,***P<0.001是相較於誘導處理組STZ。如圖3的實驗結果所示,誘導處理組STZ小鼠的空腹血糖値在0-42天都明顯高於空白組Sham。此實驗結果證明經誘導的第2型糖尿病小鼠的葡萄糖耐受性較正常小鼠來得差。另外,新穿心蓮內酯的三個劑量組(NeoL、NeoM、NeoH)在投藥第七天以後的空腹血糖值皆明顯低於誘導處理組STZ。換言之,本發明的新穿心蓮內酯可用以降低經誘導的糖尿病小鼠的空腹血糖值。從實驗看來,本發明的新穿心蓮內酯可用以降低空腹血糖值而改善經誘導的第2型糖尿病小鼠的血糖升高問題。而且從目前實驗最低有效劑量範圍為2.5mg/kg至10mg/kg的範圍來看,新穿心蓮內酯的三個劑量組(NeoL、NeoM、NeoH)均相當有效。以線性外推法預測其可能可以適用的最低有效劑量可介於0.5 mg/kg至20mg/kg的範圍之間,也可介於0.625 mg/kg至20mg/kg的範圍之間。糖化血色素( HbA1c 測定 Figure 3 shows the results of measuring fasting blood glucose values of various doses of neoandrographolide in the induction group of type 2 diabetic mice in the experimental example of the present invention. In Figure 3, each value is represented by the mean ±SEM (mean standard error), where ### P<0.001 is compared to the blank group Sham; *P<0.05, **P<0.01, ***P <0.001 is compared to STZ in the induction treatment group. As shown in the experimental results in Figure 3, the fasting blood glucose of STZ mice in the induction treatment group was significantly higher than that of the blank group Sham from 0-42 days. The results of this experiment prove that the glucose tolerance of induced type 2 diabetic mice is worse than that of normal mice. In addition, the fasting blood glucose values of the three dose groups of neoandrographolide (NeoL, NeoM, NeoH) after the seventh day of administration were significantly lower than the STZ of the induction treatment group. In other words, the new andrographolide of the present invention can be used to reduce the fasting blood glucose value of induced diabetic mice. From the experimental point of view, the new andrographolide of the present invention can be used to reduce the fasting blood glucose value and improve the problem of increased blood glucose in induced type 2 diabetic mice. Moreover, from the current experimental minimum effective dose range of 2.5mg/kg to 10mg/kg, the three dose groups of neoandrographolide (NeoL, NeoM, NeoH) are all quite effective. The lowest effective dose predicted by linear extrapolation may be between 0.5 mg/kg and 20 mg/kg, or between 0.625 mg/kg and 20 mg/kg. Glycated hemoglobin ( HbA1c ) determination

「糖化血色素」(HbA1c)是指人體血液中的紅血球含有血色素,當血液中的葡萄糖進入紅血球,和血紅素結合後,就形成糖化血色素。一般紅血球平均壽命為120天,葡萄糖附在血色素上不容易脫落,因此檢查血中糖化血色素的濃度,可以反應體內最近2-3個月的血糖控制情況。HbA1C 與血糖的最大差別在於血糖值只代表抽血當時的血糖狀態,而較長時期的血糖控制情形,則須靠 HbA1C 來反映。HbA1C 是偵測早期糖尿病的優良指標,這些患者的病情較輕,原本稍微偏高的血糖在飢餓一段時間後常掉回正常範圍,因此空腹測定血糖時,經常遺漏這類患者,然而 HbA1C 卻無此缺點2009年美國糖尿病學會提出以「糖化血色素」>=6.5%作為糖尿病診斷標準,因此「糖化血色素」除了當作糖尿病的血糖追蹤指標以外,也是新的診斷工具。HbA1C (醣化血色素,glycated hemoglobin) 近幾年已被廣泛應用於需要監控血糖值的糖尿病患者,它可反應採血前一個月左右的血糖控制狀況,並可用來監督血糖控制的情形,還可作為調整藥量的依據。"Glycated hemoglobin" (HbA1c) means that the red blood cells in the human blood contain hemoglobin. When the glucose in the blood enters the red blood cells and combines with hemoglobin, glycated hemoglobin is formed. Generally, the average lifespan of red blood cells is 120 days, and glucose is attached to hemoglobin and it is not easy to fall off. Therefore, checking the concentration of glycated hemoglobin in the blood can reflect the blood sugar control in the body in the past 2-3 months. The biggest difference between HbA1C and blood sugar is that the blood sugar value only represents the blood sugar state at the time of blood draw, and the long-term blood sugar control situation must be reflected by HbA1C. HbA1C is an excellent indicator for detecting early diabetes. These patients have milder conditions. The originally slightly high blood sugar often falls back to the normal range after a period of starvation. Therefore, such patients are often missed when measuring blood sugar on an empty stomach. However, HbA1C does not This shortcoming was proposed by the American Diabetes Association in 2009 to use "glycated hemoglobin">=6.5% as the diagnostic criteria for diabetes. Therefore, "glycated hemoglobin" is a new diagnostic tool in addition to being used as a blood glucose tracking indicator for diabetes. HbA1C (glycated hemoglobin) has been widely used in diabetic patients who need to monitor blood sugar levels in recent years. It can reflect the blood sugar control status about one month before blood sampling, and can be used to monitor blood sugar control and can also be used as an adjustment The basis of the dose.

在本實驗例中,是在連續投藥42天後記錄空白組Sham、誘導處理組STZ、新穿心蓮內酯低劑量組NeoL(2.5mg/kg)、新穿心蓮內酯中劑量組NeoM(5.0mg/kg)以及新穿心蓮內酯高劑量組NeoH小鼠的糖化血色素(HbA1c)的數值。實驗結果如圖4所示。In this experimental example, the blank group Sham, the induction treatment group STZ, the neoandrographolide low-dose group NeoL (2.5mg/kg), and the neoandrographolide middle-dose group NeoM (5.0mg/kg) were recorded after 42 days of continuous administration. kg) and the value of glycated hemoglobin (HbA1c) of NeoH mice in the neoandrographolide high-dose group. The experimental results are shown in Figure 4.

圖4顯示的是本發明實驗例各種劑量之新穿心蓮內酯對於誘導組第2型糖尿病小鼠的糖化血色素(HbA1c)的影響結果。在圖4中,各數值以平均値±SEM(平均標準誤差)來表示,其中### P<0.001是相較於空白組Sham; ***P<0.001是相較於誘導處理組STZ。如圖4的實驗結果所示,誘導處理組STZ小鼠在42天後的HbA1c數值明顯高於空白組Sham。此實驗結果證明經誘導的第2型糖尿病小鼠的血糖控制較正常小鼠來得差。另外,在連續投藥42天後,新穿心蓮內酯的三個劑量組(NeoL、NeoM、NeoH)的HbA1c數值皆明顯低於誘導處理組STZ。換言之,本發明的新穿心蓮內酯可用以改善經誘導的第2型糖尿病小鼠的血糖控制不佳的問題。而且從目前實驗最低有效劑量範圍為2.5mg/kg至10mg/kg的範圍來看,新穿心蓮內酯的三個劑量組(NeoL、NeoM、NeoH)均相當有效。以線性外推法預測其可能可以適用的最低有效劑量可介於0.5mg/kg至20mg/kg的範圍之間,也可介於0.625 mg/kg至20mg/kg的範圍之間。麩胺酸苯醋酸轉氨基酵素( Aspartate Aminotransferase AST )測定 Figure 4 shows the effect of various doses of new andrographolide on the glycated hemoglobin (HbA1c) of the induced group of type 2 diabetic mice in the experimental example of the present invention. In Figure 4, each value is represented by the mean ± SEM (mean standard error), where ### P<0.001 is compared to the blank group Sham; ***P<0.001 is compared to the induction treatment group STZ. As shown in the experimental results in Figure 4, the HbA1c value of STZ mice in the induction treatment group was significantly higher than that of the blank group Sham after 42 days. The results of this experiment prove that the blood glucose control of induced type 2 diabetic mice is worse than that of normal mice. In addition, after 42 days of continuous administration, the HbA1c values of the three dose groups of neoandrographolide (NeoL, NeoM, NeoH) were significantly lower than the STZ of the induction treatment group. In other words, the new andrographolide of the present invention can be used to improve the problem of poor blood glucose control in induced type 2 diabetic mice. Moreover, from the current experimental minimum effective dose range of 2.5mg/kg to 10mg/kg, the three dose groups of neoandrographolide (NeoL, NeoM, NeoH) are all quite effective. The lowest effective dose predicted by linear extrapolation may be between 0.5 mg/kg and 20 mg/kg, or between 0.625 mg/kg and 20 mg/kg. Determination; phenylmercuric acetate glutamate transamination enzymes (AST Aspartate Aminotransferase)

一般來說,第2型糖尿病患者在臨床上常見有非酒精性脂肪肝,進而容易造成肝細胞受損及肝功能的下降。麩胺酸苯醋酸轉氨基酵素(Aspartate Aminotransferase; AST)主要存在於肝臟、心肌,骨骼肌及紅血球中的酵素。當肝臟細胞被破壞或受損時,AST酵素會釋出並進入到血液中。因此,透過血液測試能夠知道肝功能是否有受到影響。Generally speaking, non-alcoholic fatty liver is common in patients with type 2 diabetes, which can easily cause liver cell damage and liver function decline. Aspartate Aminotransferase (AST) is an enzyme mainly found in the liver, myocardium, skeletal muscle and red blood cells. When liver cells are destroyed or damaged, AST enzymes are released and enter the blood. Therefore, it is possible to know whether liver function is affected by blood test.

在本實驗例中,是在連續投藥42天後記錄空白組Sham、誘導處理組STZ、新穿心蓮內酯低劑量組NeoL(2.5mg/kg)、新穿心蓮內酯中劑量組NeoM(5.0mg/kg)以及新穿心蓮內酯高劑量組NeoH小鼠的AST指數。實驗結果如圖5所示。In this experimental example, the blank group Sham, the induction treatment group STZ, the neoandrographolide low-dose group NeoL (2.5mg/kg), and the neoandrographolide middle-dose group NeoM (5.0mg/kg) were recorded after 42 days of continuous administration. kg) and the AST index of NeoH mice in the neoandrographolide high-dose group. The experimental results are shown in Figure 5.

圖5顯示的是本發明實驗例各種劑量之新穿心蓮內酯對於誘導組第2型糖尿病小鼠的麩胺酸苯醋酸轉氨基酵素(AST)指數的影響結果。在圖5中,各數值以平均値±SEM(平均標準誤差)來表示,其中# P<0.05是相較於空白組Sham;*P<0.05是相較於誘導處理組STZ。如圖5的實驗結果所示,誘導處理組STZ小鼠在42天後的AST數值明顯高於空白組Sham。此實驗結果證明經誘導的第2型糖尿病小鼠的肝功能明顯較正常小鼠來得差。另外,在連續投藥42天後,新穿心蓮內酯的三個劑量組(NeoL、NeoM、NeoH)的AST數值都略低於誘導處理組STZ。其中,新穿心蓮內酯低劑量組NeoL(2.5mg/kg)的AST數值降低的最為明顯。此實驗結果表明了本發明的新穿心蓮內酯具備了改善肝功能的作用,而且最低有效劑量判斷為2.5mg/kg,且以線性外推法預測其可能可以適用的最低有效劑量可介於1.25mg/kg至10mg/kg的範圍之間。三酸甘油酯 triglyceride )及總膽固醇( cholesterol )測定 Figure 5 shows the effect of various doses of neoandrographolide on the glutamate phenylacetic acid transaminase (AST) index of the induced group of type 2 diabetic mice in the experimental example of the present invention. In Figure 5, each value is represented by the mean ± SEM (standard error of the mean), where # P<0.05 is compared to the blank group Sham; *P<0.05 is compared to the induction treatment group STZ. As shown in the experimental results in Figure 5, the AST value of STZ mice in the induction treatment group after 42 days was significantly higher than that of the blank group Sham. The results of this experiment proved that the liver function of induced type 2 diabetic mice was significantly worse than that of normal mice. In addition, after 42 days of continuous administration, the AST values of the three dose groups of neoandrographolide (NeoL, NeoM, NeoH) were slightly lower than the STZ of the induction treatment group. Among them, the low-dose neoandrographolide group NeoL (2.5mg/kg) had the most significant decrease in AST value. This experimental result shows that the new andrographolide of the present invention has the effect of improving liver function, and the minimum effective dose is judged to be 2.5 mg/kg, and the minimum effective dose that may be applicable is predicted by linear extrapolation to be between 1.25 Between mg/kg to 10mg/kg. Triglyceride (triglyceride) and total cholesterol (Cholesterol) assay

在臨床上,有高達6至8成比例的糖尿病患會合併出現高血壓與高血脂。糖尿病合併高血脂的機轉較為複雜,最常見的型式包括血中三酸甘油脂上昇,高密度脂蛋白膽固醇(HDL-C)下降與低密度脂蛋白膽固醇(LDL-C)增加。因此,對於糖尿病患者來說,三酸甘油酯及總膽固醇的監控也極為重要。Clinically, up to 6 to 8 percent of diabetic patients will have high blood pressure and hyperlipidemia. The mechanism of diabetes combined with hyperlipidemia is more complicated. The most common types include increased blood triglycerides, decreased high-density lipoprotein cholesterol (HDL-C), and increased low-density lipoprotein cholesterol (LDL-C). Therefore, for diabetic patients, the monitoring of triglycerides and total cholesterol is also extremely important.

在本實驗例中,是在連續投藥42天後記錄空白組Sham、誘導處理組STZ、新穿心蓮內酯低劑量組NeoL(2.5mg/kg)、新穿心蓮內酯中劑量組NeoM(5.0mg/kg)以及新穿心蓮內酯高劑量組NeoH小鼠的三酸甘油酯及血中總膽固醇數值。實驗結果如圖6及圖7所示。In this experimental example, the blank group Sham, the induction treatment group STZ, the neoandrographolide low-dose group NeoL (2.5mg/kg), and the neoandrographolide middle-dose group NeoM (5.0mg/kg) were recorded after 42 days of continuous administration. kg) and the triglyceride and blood total cholesterol values of NeoH mice in the neoandrographolide high-dose group. The experimental results are shown in Figure 6 and Figure 7.

圖6顯示的是本發明實驗例各種劑量之新穿心蓮內酯對於誘導組第2型糖尿病小鼠的三酸甘油酯(triglyceride)數值的影響結果。在圖6中,各數值以平均値±SEM(平均標準誤差)來表示,其中## P<0.01是相較於空白組Sham;**P<0.01,***P<0.001是相較於誘導處理組STZ。如圖6的實驗結果所示,誘導處理組STZ小鼠在42天後的血中三酸甘油酯數值明顯高於空白組Sham。此實驗結果證明經誘導的第2型糖尿病小鼠具有高血脂、高膽固醇的現象。另外,在連續投藥42天後,新穿心蓮內酯的三個劑量組(NeoL、NeoM、NeoH)的三酸甘油酯(triglyceride)數值皆低於誘導處理組STZ。其中,新穿心蓮內酯中劑量組NeoM(5.0mg/kg)及新穿心蓮內酯高劑量組NeoH(10mg/kg)的三酸甘油酯(triglyceride)的數值最低。此實驗結果表明了本發明的新穿心蓮內酯具有降低三酸甘油酯的作用,且具有劑量依存性(Dose-dependent Effect),而其最低有效劑量為2.5mg/kg。Figure 6 shows the effect of various doses of new andrographolide on the triglyceride value of the induced group of type 2 diabetic mice in the experimental example of the present invention. In Figure 6, each value is represented by the mean ±SEM (mean standard error), where ## P<0.01 is compared with the blank group Sham; **P<0.01, ***P<0.001 is compared with Induction treatment group STZ. As shown in the experimental results of Fig. 6, the blood triglyceride value of STZ mice in the induction treatment group was significantly higher than that of the blank group Sham after 42 days. The results of this experiment prove that the induced type 2 diabetic mice have hyperlipidemia and high cholesterol. In addition, after 42 days of continuous administration, the triglyceride values of the three dose groups of neoandrographolide (NeoL, NeoM, NeoH) were all lower than the STZ of the induction treatment group. Among them, NeoM (5.0mg/kg) in the neoandrographolide middle-dose group and NeoH (10mg/kg) in the neoandrographolide high-dose group had the lowest triglyceride values. This experimental result shows that the new andrographolide of the present invention has the effect of reducing triglycerides, and has a dose-dependent effect, and its minimum effective dose is 2.5 mg/kg.

圖7顯示的是本發明實驗例各種劑量之新穿心蓮內酯對於誘導組第2型糖尿病小鼠的血中總膽固醇(cholesterol)的影響結果。在圖7中,各數值以平均値±SEM(平均標準誤差)來表示,其中### P<0.001是相較於空白組Sham;*P<0.05是相較於誘導處理組STZ。如圖7的實驗結果所示,誘導處理組STZ小鼠在42天後的血中總膽固醇數值明顯高於空白組Sham。此實驗結果證明經誘導的第2型糖尿病小鼠具有高血脂、高膽固醇的現象。另外,在連續投藥42天後,新穿心蓮內酯的三個劑量組(NeoL、NeoM、NeoH)的總膽固醇數值都略低於誘導處理組STZ,顯示新穿心蓮內酯具有改善血中總膽固醇的作用,且其最低有效劑量為2.5mg/kg。血清尿酸( Uric Acid )測定 Figure 7 shows the effect of various doses of new andrographolide on the total cholesterol (cholesterol) in the blood of the induced group of type 2 diabetic mice in the experimental example of the present invention. In Figure 7, each value is represented by the mean ± SEM (mean standard error), where ### P<0.001 is compared to the blank group Sham; *P<0.05 is compared to the induction treatment group STZ. As shown in the experimental results of Figure 7, the total cholesterol value of STZ mice in the induction treatment group after 42 days was significantly higher than that of the blank group Sham. The results of this experiment prove that the induced type 2 diabetic mice have hyperlipidemia and high cholesterol. In addition, after 42 days of continuous administration, the total cholesterol values of the three dose groups of neoandrographolide (NeoL, NeoM, NeoH) are slightly lower than the STZ of the induction treatment group, indicating that neoandrographolide has the ability to improve blood total cholesterol. Effect, and its minimum effective dose is 2.5mg/kg. Serum Uric Acid (Uric Acid) determination

許多研究發現,第二型糖尿病和尿酸過高的高危險因素是相同的,其中,最明顯的是超重及肥胖。第二型糖尿病和尿酸過高不單擁有相同的致病病因,尿酸過多更能增加患上二型糖尿病的風險,因此,降低血液內尿酸的水平能預防第二型糖尿病的發病率。引起人體中尿酸過高的原因有很多,舉凡飲食內容、體重、運動、服用藥物、遺傳等因素都可能造成高尿酸血症。血中尿酸大部分是由腎臟排出,一旦尿酸值升高,在腎臟的濃度也會升高,就容易產生尿酸結晶而沉澱在腎臟,造成腎臟的傷害。因此,高尿酸血症容易造成腎功能的下降。Many studies have found that the high risk factors for type 2 diabetes and high uric acid are the same, of which the most obvious are overweight and obesity. Type 2 diabetes and high uric acid not only have the same cause, but too much uric acid can increase the risk of type 2 diabetes. Therefore, reducing the level of uric acid in the blood can prevent the incidence of type 2 diabetes. There are many reasons for high uric acid in the human body. For example, factors such as diet content, weight, exercise, medication, and genetics may cause hyperuricemia. Most of the uric acid in the blood is excreted by the kidneys. Once the uric acid level rises, the concentration in the kidneys will also increase, and it is easy to produce uric acid crystals and precipitate in the kidneys, causing kidney damage. Therefore, hyperuricemia easily causes a decline in renal function.

在本實驗例中,是在連續投藥42天後記錄空白組Sham、誘導處理組STZ、新穿心蓮內酯低劑量組NeoL(2.5mg/kg)、新穿心蓮內酯中劑量組NeoM(5.0mg/kg)以及新穿心蓮內酯高劑量組NeoH小鼠的血清尿酸(serum uric acid)指數。實驗結果如圖8所示。In this experimental example, the blank group Sham, the induction treatment group STZ, the neoandrographolide low-dose group NeoL (2.5mg/kg), and the neoandrographolide middle-dose group NeoM (5.0mg/kg) were recorded after 42 days of continuous administration. kg) and the serum uric acid index of NeoH mice in the neoandrographolide high-dose group. The experimental results are shown in Figure 8.

圖8顯示的是本發明實驗例各種劑量之新穿心蓮內酯對於誘導組第2型糖尿病小鼠的血清尿酸(serum uric acid)指數的影響結果。在圖8中,各數值以平均値±SEM(平均標準誤差)來表示,其中### P<0.001是相較於空白組Sham;**P <0.01,***P<0.001是相較於誘導處理組STZ。如圖8的實驗結果所示,誘導處理組STZ小鼠在42天後的血清尿酸指數明顯高於空白組Sham。此實驗結果證明經誘導的第2型糖尿病小鼠具有高尿酸血症的現象。另外,在連續投藥42天後,新穿心蓮內酯的三個劑量組(NeoL、NeoM、NeoH)的血清尿酸指數皆明顯低於誘導處理組STZ。此實驗結果表明了本發明的新穿心蓮內酯能夠降低高尿酸血症患者的尿酸指數,達到改善腎功能之效果。此外,從目前實驗最低有效劑量範圍為2.5mg/kg至10mg/kg的範圍來看,新穿心蓮內酯的三個劑量組(NeoL、NeoM、NeoH)均相當有效。以線性外推法預測其可能可以適用的最低有效劑量可介於0.5mg/kg至20mg/kg的範圍之間,也可介於0.625 mg/kg至20mg/kg的範圍之間血清肌酸酐( serum creatinine )測定 Figure 8 shows the effect of various doses of new andrographolide in the experimental example of the present invention on the serum uric acid index of the induced group of type 2 diabetic mice. In Figure 8, each value is represented by the mean ±SEM (mean standard error), where ### P<0.001 is compared with the blank group Sham; **P<0.01, ***P<0.001 is compared In the induction treatment group STZ. As shown in the experimental results in Figure 8, the serum uric acid index of STZ mice in the induction treatment group was significantly higher than that of the blank group Sham after 42 days. The results of this experiment prove that the induced type 2 diabetic mice have hyperuricemia. In addition, after 42 days of continuous administration, the serum uric acid index of the three dose groups of neoandrographolide (NeoL, NeoM, NeoH) were significantly lower than the STZ of the induction treatment group. This experimental result shows that the new andrographolide of the present invention can reduce the uric acid index of patients with hyperuricemia and achieve the effect of improving renal function. In addition, from the current experimental minimum effective dose range of 2.5mg/kg to 10mg/kg, the three dose groups of neoandrographolide (NeoL, NeoM, NeoH) are all quite effective. The lowest effective dose predicted by linear extrapolation may be between 0.5 mg/kg and 20 mg/kg, or between 0.625 mg/kg and 20 mg/kg. Serum creatinine ( serum creatinine ) determination

糖尿病腎病變是糖尿病的重要併發症之一,也常導致病人的死亡。腎臟病變進行至較後期時,其過濾功能會逐漸損害,導致無法清理如肌酸酐類等有害物質,進而造成肌酸酐的上升,最後導致腎臟功能衰竭。檢測病患的血清肌酸酐的濃度可用來判別其腎功能是否受到影響。Diabetic nephropathy is one of the important complications of diabetes and often leads to the death of patients. When kidney disease progresses to a later stage, its filtering function will gradually be impaired, resulting in the inability to clean up harmful substances such as creatinine, which will cause the increase of creatinine, and finally lead to kidney failure. Testing the patient's serum creatinine concentration can be used to determine whether the kidney function is affected.

在本實驗例中,是在連續投藥42天後記錄空白組Sham、誘導處理組STZ、新穿心蓮內酯低劑量組NeoL(2.5mg/kg)、新穿心蓮內酯中劑量組NeoM(5.0mg/kg)以及新穿心蓮內酯高劑量組NeoH小鼠的血清肌酸酐(serum creatinine)指數。實驗結果如圖9所示。In this experimental example, the blank group Sham, the induction treatment group STZ, the neoandrographolide low-dose group NeoL (2.5mg/kg), and the neoandrographolide middle-dose group NeoM (5.0mg/kg) were recorded after 42 days of continuous administration. kg) and the serum creatinine index of NeoH mice in the neoandrographolide high-dose group. The experimental results are shown in Figure 9.

圖9顯示的是本發明實驗例各種劑量之新穿心蓮內酯對於誘導組第2型糖尿病小鼠的血清肌酸酐(serum creatinine)指數的影響結果。在圖9中,各數值以平均値±SEM(平均標準誤差)來表示,其中# P<0.05是相較於空白組Sham;***P<0.001是相較於誘導處理組STZ。如圖9的實驗結果所示,誘導處理組STZ小鼠在42天後的血清肌酸酐指數明顯高於空白組Sham。此實驗結果證明經誘導的第2型糖尿病小鼠的腎臟廓清率受到誘導藥影響而下降。另外,在連續投藥42天後,新穿心蓮內酯的三個劑量組(NeoL、NeoM、NeoH)的血清肌酸酐指數皆明顯低於誘導處理組STZ。此實驗結果表明了本發明的新穿心蓮內酯能夠降低病患的血清肌酸酐的升高作用,進而達到保護腎臟的功能。此外,從目前實驗最低有效劑量範圍為2.5mg/kg至10mg/kg的範圍來看,新穿心蓮內酯的三個劑量組(NeoL、NeoM、NeoH)均相當有效。以線性外推法預測其可能可以適用的最低有效劑量可介於0.5mg/kg至20mg/kg的範圍之間,也可介於0.625 mg/kg至20mg/kg的範圍之間。Figure 9 shows the effect of various doses of neoandrographolide on the serum creatinine (serum creatinine) index of the induced group of type 2 diabetic mice in the experimental example of the present invention. In Figure 9, each value is represented by the mean ± SEM (mean standard error), where # P<0.05 is compared to the blank group Sham; ***P<0.001 is compared to the induction treatment group STZ. As shown in the experimental results in Figure 9, the serum creatinine index of STZ mice in the induction treatment group was significantly higher than that of the blank group Sham after 42 days. The results of this experiment prove that the kidney clearance rate of induced type 2 diabetic mice is reduced by the effect of the inducer. In addition, after 42 days of continuous administration, the serum creatinine index of the three dose groups of neoandrographolide (NeoL, NeoM, NeoH) were significantly lower than the STZ of the induction treatment group. This experimental result shows that the new andrographolide of the present invention can reduce the increase of the patient's serum creatinine, thereby achieving the function of protecting the kidney. In addition, from the current experimental minimum effective dose range of 2.5mg/kg to 10mg/kg, the three dose groups of neoandrographolide (NeoL, NeoM, NeoH) are all quite effective. The lowest effective dose predicted by linear extrapolation may be between 0.5 mg/kg and 20 mg/kg, or between 0.625 mg/kg and 20 mg/kg.

綜上所述,本發明的實驗結果發現,新穿心蓮內酯能夠單獨地改善經誘導的第2型糖尿病小鼠的葡萄糖耐受性、降低空腹血糖及糖化血色素HbA1C,顯示其降血糖的用途。新穿心蓮內酯能夠單獨地降低經誘導的第2型糖尿病小鼠的AST數值,顯示其具備改善肝功能之用途。新穿心蓮內酯能夠單獨地改善經誘導的第2型糖尿病小鼠的三酸甘油酯及血中總膽固醇數值,顯示其降血酯的用途。此外,新穿心蓮內酯能夠單獨地改善經誘導的第2型糖尿病小鼠的血清尿酸指數及血清肌酸酐指數,顯示其具備改善腎功能之用途。In summary, the experimental results of the present invention found that neoandrographolide alone can improve the glucose tolerance of induced type 2 diabetic mice, lower fasting blood glucose and glycosylated hemoglobin HbA1C, showing its use in lowering blood sugar. Neoandrographolide alone can reduce the AST value of induced type 2 diabetic mice, showing that it has the purpose of improving liver function. Neoandrographolide can individually improve the triglycerides and total blood cholesterol values of induced type 2 diabetic mice, showing its use in lowering blood lipids. In addition, neoandrographolide alone can improve the serum uric acid index and serum creatinine index of induced type 2 diabetic mice, showing that it has the purpose of improving renal function.

雖然本發明已以實施例揭露如上,然其並非用以限定本發明,任何所屬技術領域中具有通常知識者,在不脫離本發明的精神和範圍內,當可作些許的更動與潤飾,故本發明的保護範圍當視後附的申請專利範圍所界定者為準。Although the present invention has been disclosed in the above embodiments, it is not intended to limit the present invention. Anyone with ordinary knowledge in the relevant technical field can make some changes and modifications without departing from the spirit and scope of the present invention. The scope of protection of the present invention shall be determined by the scope of the attached patent application.

Sham‧‧‧空白組STZ‧‧‧誘導處理組NeoL‧‧‧新穿心蓮內酯低劑量組NeoM‧‧‧新穿心蓮內酯中劑量組NeoH‧‧‧新穿心蓮內酯高劑量組Sham‧‧‧Blank group STZ‧‧‧Induction treatment group NeoL‧‧‧New andrographolide low-dose group NeoM‧‧‧New andrographolide middle-dose group NeoH‧‧‧New andrographolide high-dose group

圖1顯示的是本發明實驗例各種劑量之新穿心蓮內酯對於誘導組第2型糖尿病小鼠的水攝入量檢測結果。 圖2顯示的是本發明實驗例各種劑量之新穿心蓮內酯對於誘導組第2型糖尿病小鼠的口服葡萄糖耐受性試驗的結果。 圖3顯示的是本發明實驗例各種劑量之新穿心蓮內酯對於誘導組第2型糖尿病小鼠的空腹血糖測定的結果。 圖4顯示的是本發明實驗例各種劑量之新穿心蓮內酯對於誘導組第2型糖尿病小鼠的糖化血色素(HbA1c)的影響結果。 圖5顯示的是本發明實驗例各種劑量之新穿心蓮內酯對於誘導組第2型糖尿病小鼠的麩胺酸苯醋酸轉氨基酵素(AST)指數的影響結果。 圖6顯示的是本發明實驗例各種劑量之新穿心蓮內酯對於誘導組第2型糖尿病小鼠的三酸甘油酯(triglyceride)數值的影響結果。 圖7顯示的是本發明實驗例各種劑量之新穿心蓮內酯對於誘導組第2型糖尿病小鼠的血中總膽固醇(cholesterol)數值的影響結果。 圖8顯示的是本發明實驗例各種劑量之新穿心蓮內酯對於誘導組第2型糖尿病小鼠的血清尿酸(serum uric acid)指數的影響結果。 圖9顯示的是本發明實驗例各種劑量之新穿心蓮內酯對於誘導組第2型糖尿病小鼠的血清肌酸酐(serum creatinine)指數的影響結果。Figure 1 shows the test results of the water intake of various doses of neoandrographolide in the induced group of type 2 diabetic mice in the experimental example of the present invention. Figure 2 shows the results of the oral glucose tolerance test of various doses of neoandrographolide in the induced group of type 2 diabetic mice in the experimental example of the present invention. Figure 3 shows the results of fasting blood glucose measurement of various doses of neoandrographolide in the induction group of type 2 diabetic mice in the experimental example of the present invention. Figure 4 shows the effect of various doses of new andrographolide on the glycated hemoglobin (HbA1c) of the induced group of type 2 diabetic mice in the experimental example of the present invention. Figure 5 shows the effect of various doses of neoandrographolide on the glutamate phenylacetic acid transaminase (AST) index of the induced group of type 2 diabetic mice in the experimental example of the present invention. Figure 6 shows the effect of various doses of new andrographolide on the triglyceride value of the induced group of type 2 diabetic mice in the experimental example of the present invention. Figure 7 shows the effect of various doses of new andrographolide in the experimental example of the present invention on the blood total cholesterol (cholesterol) value of the induced group of type 2 diabetic mice. Figure 8 shows the effect of various doses of new andrographolide in the experimental example of the present invention on the serum uric acid index of the induced group of type 2 diabetic mice. Figure 9 shows the effect of various doses of neoandrographolide on the serum creatinine (serum creatinine) index of type 2 diabetic mice in the induced group of experimental examples of the present invention.

Figure 107121756-A0101-11-0002-1
Figure 107121756-A0101-11-0002-1

Sham‧‧‧空白組 Sham‧‧‧blank group

STZ‧‧‧誘導處理組 STZ‧‧‧Induction treatment group

NeoL‧‧‧新穿心蓮內酯低劑量組 NeoL‧‧‧New Andrographolide Low Dose Group

NeoM‧‧‧新穿心蓮內酯中劑量組 NeoM‧‧‧New Andrographolide Middle Dose Group

NeoH‧‧‧新穿心蓮內酯高劑量組 NeoH‧‧‧New Andrographolide High Dose Group

Claims (13)

新穿心蓮內酯在製備可調降血糖之組成物的用途,其中所述組成物包括新穿心蓮內酯做為唯一活性成分,所述組成物係用以降低第2型糖尿病患者的空腹血糖值,且所述新穿心蓮內酯適用的最低有效劑量為0.625mg/kg。 The use of neoandrographolide in the preparation of an adjustable blood glucose lowering composition, wherein the composition includes neoandrographolide as the sole active ingredient, and the composition is used to reduce the fasting blood glucose level of patients with type 2 diabetes, And the applicable minimum effective dose of the new andrographolide is 0.625 mg/kg. 新穿心蓮內酯在製備可調降血糖之組成物的用途,其中所述組成物包括新穿心蓮內酯做為唯一活性成分,所述組成物係用以降低第2型糖尿病患者的糖化血色素指數,且所述新穿心蓮內酯適用的最低有效劑量為0.625mg/kg。 The use of neoandrographolide in the preparation of an adjustable blood sugar lowering composition, wherein the composition includes neoandrographolide as the sole active ingredient, and the composition is used to reduce the glycated hemoglobin index of patients with type 2 diabetes, And the applicable minimum effective dose of the new andrographolide is 0.625 mg/kg. 新穿心蓮內酯在製備可調降血糖之組成物的用途,其中所述組成物包括新穿心蓮內酯做為唯一活性成分,所述組成物係用以增加第2型糖尿病患者的葡萄糖耐受性,且所述新穿心蓮內酯適用的最低有效劑量為0.625mg/kg。 The use of neoandrographolide in the preparation of an adjustable blood glucose lowering composition, wherein the composition includes neoandrographolide as the sole active ingredient, and the composition is used to increase the glucose tolerance of patients with type 2 diabetes , And the applicable minimum effective dose of the new andrographolide is 0.625 mg/kg. 如申請專利範圍第1-3項中任一項所述的用途,其中所述組成物為一醫藥組成物。 The use according to any one of items 1 to 3 in the scope of the patent application, wherein the composition is a pharmaceutical composition. 如申請專利範圍第1-3項中任一項所述的用途,其中所述組成物為一製劑。 The use according to any one of items 1 to 3 in the scope of the patent application, wherein the composition is a preparation. 如申請專利範圍第5項所述的用途,其中所述製劑為錠劑、片劑、液劑、粉劑、顆粒劑、散劑、丸劑、滴丸劑、膠囊、軟膏、乳膏、乳膠、凝膠、貼片、注射劑、吸入劑、噴劑或是塞劑。 The use as described in item 5 of the scope of patent application, wherein the preparations are lozenges, tablets, liquids, powders, granules, powders, pills, dropping pills, capsules, ointments, creams, latex, gels, Patches, injections, inhalants, sprays or suppositories. 如申請專利範圍第1-3項中任一項所述的用途,其中所述組成物為一外用製劑。 The use according to any one of items 1 to 3 in the scope of the patent application, wherein the composition is an external preparation. 如申請專利範圍第7項所述的用途,其中所述外用製劑包括液劑、粉劑、顆粒劑、噴劑、軟膏、乳膏、乳膠、凝膠或是貼片。 The use according to item 7 of the scope of patent application, wherein the external preparation includes liquid, powder, granule, spray, ointment, cream, latex, gel or patch. 如申請專利範圍第1-3項中任一項所述的用途,其中所述組成物為一口服製劑。 The use according to any one of items 1 to 3 in the scope of the patent application, wherein the composition is an oral preparation. 如申請專利範圍第9項所述的用途,其中所述口服製劑包括錠劑、片劑、液劑、粉劑、顆粒劑、散劑、丸劑、滴丸劑或是膠囊。 The use according to item 9 of the scope of patent application, wherein the oral preparations include lozenges, tablets, liquids, powders, granules, powders, pills, dropping pills or capsules. 如申請專利範圍第1-3項中任一項所述的用途,其中所述組成物更包括醫藥上所使用載劑、稀釋劑或賦形劑做為所述組成物中的非活性成分。 The use according to any one of items 1 to 3 in the scope of the patent application, wherein the composition further includes a pharmaceutical carrier, diluent or excipient as an inactive ingredient in the composition. 如申請專利範圍第1-3項中任一項所述的用途,其中所述組成物更包括增味劑、甜味劑、增稠劑或賦形劑做為所述組成物中的非活性成分。 The use according to any one of items 1 to 3 in the scope of the patent application, wherein the composition further includes a flavor enhancer, a sweetener, a thickener or an excipient as an inactive agent in the composition ingredient. 如申請專利範圍第12項所述的用途,其中所述組成物的形式為液體飲料、膠狀品、膠囊、錠劑、片劑或粉末。 The use according to item 12 of the scope of the patent application, wherein the composition is in the form of a liquid beverage, a gel, a capsule, a lozenge, a tablet or a powder.
TW107121756A 2018-06-25 2018-06-25 Use of composition of neoandrographolide in lowering blood sugar TWI725317B (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
TW107121756A TWI725317B (en) 2018-06-25 2018-06-25 Use of composition of neoandrographolide in lowering blood sugar
US16/449,347 US11318153B2 (en) 2018-06-25 2019-06-22 Method of using Neoandrographolide for lowering blood sugar, lowering blood lipid, improving liver function and improving renal function

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
TW107121756A TWI725317B (en) 2018-06-25 2018-06-25 Use of composition of neoandrographolide in lowering blood sugar

Publications (2)

Publication Number Publication Date
TW202000209A TW202000209A (en) 2020-01-01
TWI725317B true TWI725317B (en) 2021-04-21

Family

ID=69941932

Family Applications (1)

Application Number Title Priority Date Filing Date
TW107121756A TWI725317B (en) 2018-06-25 2018-06-25 Use of composition of neoandrographolide in lowering blood sugar

Country Status (1)

Country Link
TW (1) TWI725317B (en)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115068491A (en) * 2021-03-15 2022-09-20 中国医学科学院药物研究所 Medical application of andrographolide as LTB4 receptor inhibitor
CN115068467A (en) * 2021-03-15 2022-09-20 中国医学科学院药物研究所 Medical application of andrographolide as LTB4 receptor inhibitor

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103766901A (en) * 2014-01-08 2014-05-07 浙江大学 Application of andrographolide C to preparation of weight-losing food or medicine

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103766901A (en) * 2014-01-08 2014-05-07 浙江大学 Application of andrographolide C to preparation of weight-losing food or medicine

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
Subramanian R et al., "Effect of Andrographolide and Ethanol Extract of Andrographis paniculata on Liver Glycolytic, Gluconeogenic, and Lipogenic Enzymes in a Type 2 Diabetic Rat Model", Pharmaceutical Biology, Vol.46, No.11, P.772–780, 2008, 2009/01/05
Yang T et al., "Hypolipidemic effects of andrographolide and neoandrographolide in mice and rats", Phytotherapy Research, Vol.27, P.618–623, 2012/06/29
Yang T et al., "Hypolipidemic effects of andrographolide and neoandrographolide in mice and rats", Phytotherapy Research, Vol.27, P.618–623, 2012/06/29 Subramanian R et al., "Effect of Andrographolide and Ethanol Extract of Andrographis paniculata on Liver Glycolytic, Gluconeogenic, and Lipogenic Enzymes in a Type 2 Diabetic Rat Model", Pharmaceutical Biology, Vol.46, No.11, P.772–780, 2008, 2009/01/05 *

Also Published As

Publication number Publication date
TW202000209A (en) 2020-01-01

Similar Documents

Publication Publication Date Title
US8404746B2 (en) Anti-diabetes composition containing chicoric acid and/or one of the metabolites thereof
US20070036874A1 (en) Compositions and methods for controlling glucose and lipid uptake from foods
CN101229181A (en) Medicine compounds for curing diabetes and complications thereof
TWI725317B (en) Use of composition of neoandrographolide in lowering blood sugar
JP2006528666A (en) Use of phthalide derivatives for the treatment and prevention of diabetes
US11044930B2 (en) Composition comprising cinnamon extract
JP6977053B2 (en) A composition for the prevention or treatment of obesity or a metabolic syndrome caused by obesity containing formic acid or a pharmaceutically acceptable salt thereof as an active ingredient.
WO2007009392A1 (en) The use of chlorogenic acid in the manufacturing medicaments for treating and/or preventing hepatic injury
JP2010518117A (en) Methods and materials for reducing or eliminating risk factors associated with syndrome X
US11623010B2 (en) Pharmaceutical carrier in the preparation of an anti-diabetic pharmaceutical composition and methods for treatment
WO2012140894A1 (en) Pharmaceutical composition
US20070036872A1 (en) Alpha-glucosidase activity inhibitor
TWI721282B (en) Use of composition of neoandrographolide for improving renal function
TWI722294B (en) Use of composition of neoandrographolide for improving liver function
JP5984328B2 (en) Independent Kakkonto extract combination agent
US11318153B2 (en) Method of using Neoandrographolide for lowering blood sugar, lowering blood lipid, improving liver function and improving renal function
TWI766295B (en) Herbal composition for reducing uric acid and the use in reducing uric acid, body fat, and blood glucose thereof
JP2010512382A (en) PHARMACEUTICAL COMPOSITION FOR PREVENTION AND TREATMENT OF DIABE CONTAINING SICONIN COMPOUND AND USE
KR100773246B1 (en) Composition comprising of trillium kamtschaticum extracts as an effective ingredient for decreasing weight gain and lowering plasma glucose level
CN110404029B (en) Composition with blood sugar reducing effect and preparation method and application thereof
US11744870B2 (en) Traditional Chinese medicine composition for treating metabolic syndrome and preparations thereof
KR101572311B1 (en) A composition for preventing or treating obesity comprising 2-amino-2-norbornanecarboxylic acid
TWI717757B (en) Use of composition containing labisia pumila var. alata extracts in improving acute hemorrhagic anemia
JP2009275026A (en) Composition having pancreatic lipase activity-imhibitory effect
KR100478150B1 (en) Health care food comprising an extract of the crude drug complex as an effective ingredient for preventing diabetes