200938207 九、發明說明： 【發明所屬之技術領域】 本發明係關於一種提高人體血液中高密度脂蛋白的 方法，更進一步地，本發明係關於一種將水溶性聚胺基醣 衍生物用於提高血液中高密度脂蛋白的用途。 【先前技術】 ® 幾丁聚醣（chitosan )為幾丁質（Chitin)之胺基多醣 (aminopolySaCcharide)之衍生物，多以貽貝類、蝦或蟹 類之硬殼為原料或以特定黴菌所產生。目前已有許多研究 皆冒指出幾丁聚醣在體重控制有一定的效用，其作用機制 包括降低腸胃道中脂質的吸收並且影響膽固醇與其他固 醇類之乳化與吸收。另外’幾丁聚醣也會降低腸胃道中膽 酸之再吸收，進而降低血液中膽固醇值，然而，幾丁聚醣 因其特殊之結構導致水溶性較差，限制了相關產品之開發 ❹ 與應用。近年來部分幾丁聚醣之研究致力於改善此問題， 傳統之方法係先將有機或無機酸加入聚胺基醣中，使其溶 解於水中，然而這將導致水溶液形成極酸的狀態，降低了 1生物利用性，而提高溶液之pH值則會使聚胺基醣沈 ，。也f研究係將磺酸基團接枝至聚胺基醣的分子結構 中，但這些方法常造成起始物質的嚴重分解。 曰有研究指出不同黏度之幾丁聚醣對於大鼠血液中 =醇：脂質過氧化狀態會有不同影響。雖然已有文獻指 丁貝或幾丁聚醣具有降低血中膽固醇與調整脂蛋白 之效用，然而皆係針對不可溶或低溶解度之幾丁聚醣。水 200938207 溶性之幾丁聚醣衍生物是否具有降血脂功能則需要進— 步評估。 【發明内容】 有鑑於習知技術的缺失’本發明之目的在嘗試尋找一 種可提高血液中高密度脂蛋白之改質聚胺基醣，藉此期望 可找到預防罹患心血管疾病之方針。 ❹ 為達上述目的’本發明之用於提高血液中高密度脂蛋 白之醫藥組合物，該組合物中包含有效劑量之水溶性聚胺 基醋衍生物’其中該水溶性聚胺基醣衍生物係取未改質之 聚胺基膽經烴基續内酯化物項酸化後製得。 本發明也包含一種將水溶性聚胺基醣衍生物用於提 向血液中高密度脂蛋白之用途’其中該水溶性聚胺基醣衍 生物係取未改質之聚胺基醣經烴基續内酯化物績酸化後 製得。 更進一步地’本發明也包含一種將水溶性聚胺基酷衍 ❹ 生物用於製備可提高血液中高密度脂蛋白之醫藥組合物 的用途’其中該水溶性聚胺基醣衍生物係取未改質之聚胺 基聽經烴基磺内酯化物磺酸化後製得。 【實施方式】 本發明之用於提高血液中高密度脂蛋白之醫藥組合 物’該組合物中包含有效劑量之水溶性聚胺基醣衍生物’ 其中該水溶性聚胺基醣衍生物係取未改質之聚胺基醣經 煙基磺内酯化物磺酸化後製得。 200938207 本發明所稱之『改質』係指將水溶性低之聚胺基醣經 化學反應衍生後形成具水溶性之聚胺基醣衍生物，更詳述 之’其係將帶有胺基官能基團之未改質的聚胺基醣於適當 之有機溶劑中，於適當溫度下與一烴基磺内酯化合物反 應’此時聚胺基醣結構中之胺基官能基將可依照預定之比 例部分或全部地被烴基續内酯化合物績酸化。續酸化反應 後的改質水溶性聚胺基醣不溶於改質前所使用的有機溶 ® 劑中，因而可直接過濾得到水溶性聚胺基醣。 依據上述方法改質的聚胺基醣其分子結構長度將實 質相同於未改質前，因為此一改質化學反應並不會水解聚 胺基醣結構。 本發明所稱之『聚胺基醣』係指分子結構中具有胺基 官能基之醣類聚合物，所謂未改質之聚胺基醣可源自天然 界醣類聚合物或化學合成之分子，例如幾丁聚酶、酿胺聚 多醋（glycosaminoglycans，GAG)等0 一般而言，未改質之聚胺基醣其分子量介於300至 1，500,000之間，其係可進一步依據分子量大小細分為四 種類型：（1)分子量低於10,000之非常低分子量分子；（2) 分子量介於10,000至35,000之間的低分子量分子；（3)具 有35,000至140,000之間的高分子量分子；及(4)具有分 子量介於140,000至1，500,000之間的非常高分子量分子。 其中，幾丁聚醣依其型態又可區分為α-幾丁聚醣、 召-幾丁聚醣、直鏈幾丁聚醣、分支幾丁聚醣等。這些幾 丁聚醣可由天然來源（包含甲殼類外殼、昆蟲外骨骼及真 菌的細胞壁）被純化的幾丁質經去乙醯化後製得。一般而 200938207 言幾丁聚醣之去乙酿化程度在至100%之間。經續酸 化之幾丁聚醣由於磺酸根官能基的作用使幾丁聚醣變得 親水性。 當確酸化之反應在一有機溶劑中進行且控制適當溫 度時，將使烴基續内酯連接至幾丁聚醣的醣單體上的胺基 (-NH2)上而非經甲基(-CH2〇H)上，一般而言，改質反 應（即磺酸化反應）係在有機溶劑的迴流溫度（通常高於 Φ 45°c )下進行，且此時烴基磺内酯化合物（特別是1，3-丙烷磺内酯不會因為有機溶劑内含有少量水就發生水解。 適合於磺酸化反應進行的有機溶劑具有極性的有機 溶劑較適合於聚胺基醣的磺酸化反應，例如醇類、醚類、 醇醚類或其混合物。具體態樣包含甲醇、乙醇、異丙醇、 丁醇、曱氧基丙醇（methoxypropanol)或其混合物。一 般而言，溶劑中可容許10%以下的水的存在。 其中’以甲醇為溶劑可因其極性而提供額外的優點， 特別是甲醇會使不論分子量低或高之幾丁聚醣產生膨潤 ❹ 效果（swollen)，使烴基磺内酯化合物可穿透至其中與尚 未改質的醣單體反應。也由於續酸化反應趨勢的明顯差異 而使續酸化反應幾乎發生在醣單體的胺基上而非羥甲基 上。以曱醇作為溶劑進行幾丁聚醣磺酸化改質的反應溫度 了在25 C至67 C間進行。此外，卜曱氧基-2-丙醇特別適 合分子量非常低的幾丁聚醣的改質反應來使用。 士如同前述曾提及，磺酸化反應較佳地係於有機溶劑之 迴流溫度下進行，更精確地說法，磺酸化反應之迴流溫度 係與有機溶劑之種類，以及其與幾丁聚醣之混合物之沸點 200938207 f目關例如甲醇作為有機溶劑時，迴流溫度約在65〜67 。。正丁醇作為有機溶劑時之迴流溫度約在117〜120 C，異丙醇作為有機溶劑時之迴流溫度約在82〜85。(：， 而丨-甲氧基-2-丙醇作為有機溶劑時之迴流溫度則約在 110〜115°C之間。 、本明所稱之炫基續内酯（aikyi/aikenyi suh〇ne)可 區分為烷基磺内酯（alkyl sultone)及烯基磺内 61 ( alkenyl ❹sultone) ’其係可利用下式化學式⑴所示之結構表示之： Γ丫R2 0 一卜。 Ο ⑴， 其中’ R1係選自_(CH2)X-或_CH=CH-，X係為2，3 或4;及R2係選自Η或（^至^烷基。 烴基磺内酯化合物之具體態樣包含，但不限於1，3- =烷續内酯、丨，3_丙烯橫内酯、1，4-丁烧磺内酯、2,4-丁烷 ~内酯或其混合物。 以1，4-丁烷磺内酯為例’當使用正丁醇或卜甲氧基_2_ 丙醇為溶劑，在11〇。〇至13〇ΐ間迴流6〜8小時候，可得 產率為55%〜92%之水溶性幾丁聚醣。 當可輕易理解的是，烴基磺内酯的選擇與用量係可根 據，欲製得之水溶性幾丁聚醣的續酸化程度以及性質來 決疋，所製得之水溶性幾丁聚醣可利用傳統之純化方法， + J如過;慮或結晶等由有機溶劑中移出，而未被續酸化之胺 9 200938207 基則可使該水溶性幾丁聚醣進一步處理應用於各種領域。 本發明包含將水溶性聚胺基醣衍生物用於提高血液 中高密度脂蛋白之用途，其中該水溶性聚胺基醣衍生物係 取未改質之聚胺基醣經烴基磺内酯化物磺酸化後製得。 其中’水溶性聚胺基醣、其製備方法以及續内酯化物 之定義係如前述。 更進一步地，本發明包含將水溶性聚胺基醣衍生物用 0 於製備可提高血液中高密度脂蛋白之醫藥組合物的用 途，其中該水溶性聚胺基醣衍生物係取未改質之聚胺基糖 經烴基績内醋化物續酸化後製得。 同樣地，水溶性聚胺基醋、其製備方法以及續内酯化 物之定義係如前述。 以下實施態樣係用於進一步了解本發明之優點，並非 用於限制本發明之申請專利範圍。 ❹ 實施例1·製備水溶性幾丁聚醣 取161克之高分子量幾丁聚醣（分字量約140,000) 並置放於一燒瓶中，將700毫升的甲醇加入施以攪拌。之 後加熱攪拌燒瓶中之混合物後於65〜67°C之迴流溫度下 下緩慢滴入122克1，3·丙院續内醋。待所有1，3-丙燒橫内 醋被加入後’將混合物迴流四小時，之後將燒瓶冷卻至室 溫後，以過濾方式收集產物並以曱醇潤洗數次，而後置於 真空烘箱中乾燥過夜。經乾燥後秤重得到282克，產率為 99.7%之經烷基磺酸化幾丁聚醣。 200938207 實施例2·改質前後幾丁聚醣對倉鼠之影響 倉鼠飼養輿餵含 四週齡離乳之雄性倉鼠係購自財團法人國家實驗研 究院實驗動物中心’將購得之倉鼠依體重隨機分組飼養於 塑膠飼養籠中，控制12小時晝/夜循環，溫度25±1。(： ’自 由飲水與食用正常飲食（標準組，記為『ND』； AIN-93G ; ❹ iCN Biomedicalsm ’ Costa Mesa，CA ’ USA)，一週後將 標準組以外之倉鼠改餵食高脂肪高膽固醇飲食（high fat and cholesterol diet，記為『HFCD』；AIN-93G modified high-fat diet)，飲食配方可參下表一 表一、飲食配方（g/100g) 内容物 ND HFCD Casein 20 20 Sucrose 10 10 Cornstarch 41.2486 26.2486 Maltodextrin 13.2 13.2 L-Cystein 0.3 0.3 Cellulose 5.0 5.0 So>hcan Oil 5.0 20.() t-butylhydroquinone 0.0014 0.0014 Mineral Mix #210025 3.5 3.5 Vitamin Mix #310025 1.0 1.0 Choline Bitartrate 0.25 0.25 Cholesterol 0.5 0.5200938207 IX. Description of the Invention: [Technical Field] The present invention relates to a method for improving high-density lipoprotein in human blood, and further, the present invention relates to a method for using a water-soluble polyamino sugar derivative for improving blood The use of medium and high density lipoproteins. [Prior Art] ® Chitosan is a derivative of Chitin's aminopolySaCcharide, which is usually made from the hard shell of mussels, shrimps or crabs or produced by specific molds. . Many studies have pointed out that chitosan has a certain effect in weight control, and its mechanism of action includes reducing the absorption of lipids in the gastrointestinal tract and affecting the emulsification and absorption of cholesterol and other sterols. In addition, chitosan can also reduce the reabsorption of bile acids in the gastrointestinal tract, thereby lowering the cholesterol level in the blood. However, chitosan has poor water solubility due to its special structure, which limits the development and application of related products. In recent years, research on some chitosan has been devoted to improving this problem. The traditional method is to add an organic or inorganic acid to the polyurethane to dissolve it in water. However, this will cause the aqueous solution to form a very acidic state and reduce it. 1 bioavailability, and increasing the pH of the solution will cause the polyamino sugar to sink. It has also been studied to graft sulfonic acid groups into the molecular structure of polyamino sugars, but these methods often cause severe decomposition of the starting materials. Studies have shown that chitosan with different viscosities has different effects on the alcohol: lipid peroxidation state in rats. Although the literature has indicated that butyl or chitosan has the effect of lowering blood cholesterol and regulating lipoproteins, it is directed to chitosan which is insoluble or low in solubility. Water 200938207 Whether a soluble chitosan derivative has hypolipidemic function requires further evaluation. SUMMARY OF THE INVENTION In view of the deficiencies of the prior art, the object of the present invention is to seek a modified polyamino sugar which can increase high-density lipoprotein in blood, whereby it is desired to find a policy for preventing cardiovascular diseases.医药 For the above purpose, the pharmaceutical composition for improving high-density lipoprotein in blood of the present invention, which comprises an effective amount of a water-soluble polyaminoacetic acid derivative, wherein the water-soluble polyamino sugar derivative is The unmodified polyamine bile is obtained by acidification of a hydrocarbyl sultone. The present invention also encompasses the use of a water-soluble polyamino sugar derivative for the delivery of high-density lipoproteins to the blood, wherein the water-soluble polyglycosaccharide derivative is subjected to an unmodified polyamino sugar via a hydrocarbon group. The ester is obtained by acidification. Further, the present invention also encompasses the use of a water-soluble polyamine-based steroidal organism for the preparation of a pharmaceutical composition for improving high-density lipoprotein in blood, wherein the water-soluble polyamino sugar derivative is unchanged. The polyamine-based sulfonate of the hydrocarbon-based sultone is obtained. [Embodiment] The pharmaceutical composition for improving high-density lipoprotein in blood of the present invention comprises an effective amount of a water-soluble polyamino sugar derivative in the composition, wherein the water-soluble polyamino sugar derivative is not taken The modified polyamino sugar is obtained by sulfonating the nicotyl sultone. 200938207 The term "modification" as used in the present invention means that a polyhydric sugar having a low water solubility is chemically reacted to form a water-soluble polyamino sugar derivative, and more specifically, it will have an amine group. The unmodified polyamino sugar of the functional group is reacted with a monoalkyl sultone compound at a suitable temperature in a suitable organic solvent. The amine functional group in the polyamino sugar structure will be as intended. The proportion is partially or wholly acidified by the hydrocarbyl lactone compound. The modified water-soluble polyglycol after the acidification reaction is insoluble in the organic solvent used before the modification, so that the water-soluble polyamino sugar can be directly filtered. The polyamino sugar modified according to the above method will have the same molecular structure length as before the unmodified, since this modified chemical reaction does not hydrolyze the polyamino sugar structure. The term "polyaminoglyco" as used in the present invention refers to a saccharide polymer having an amino functional group in a molecular structure, and the unmodified polyamino saccharide may be derived from a natural saccharide polymer or a chemically synthesized molecule. For example, chitinase, glycosaminoglycans (GAG), etc. 0 Generally, the unmodified polyamino sugar has a molecular weight of between 300 and 1,500,000, which can be further determined by molecular weight. Subdivided into four types: (1) very low molecular weight molecules with a molecular weight below 10,000; (2) low molecular weight molecules with a molecular weight between 10,000 and 35,000; (3) high molecular weight molecules with between 35,000 and 140,000; (4) Very high molecular weight molecules having a molecular weight of between 140,000 and 1,500,000. Among them, chitosan can be further classified into α-chitosan, chito-chitosan, linear chitosan, branched chitosan and the like according to its type. These chitosan can be obtained by deacetylating purified chitin from a natural source comprising a crustacean shell, an insect exoskeleton and a cell wall of a fungus. In general, 200938207, the degree of brewing of chitosan is between 100%. The acidified chitosan makes the chitosan hydrophilic due to the action of the sulfonate functional group. When the acidification reaction is carried out in an organic solvent and the appropriate temperature is controlled, the hydrocarbyl lactone will be attached to the amine group (-NH2) on the sugar monomer of the chitosan rather than the methyl group (-CH2). 〇H), in general, the upgrading reaction (ie, the sulfonation reaction) is carried out at the reflux temperature of the organic solvent (usually higher than Φ 45 ° C), and at this time the hydrocarbyl sultone compound (especially 1, 3-propane sultone does not hydrolyze because it contains a small amount of water in the organic solvent. The organic solvent suitable for the sulfonation reaction has a polar organic solvent which is more suitable for the sulfonation reaction of polyamino sugars, such as alcohols and ethers. a class, an alcohol ether or a mixture thereof. The specific aspect comprises methanol, ethanol, isopropanol, butanol, methoxypropanol or a mixture thereof. Generally, 10% or less of water can be tolerated in the solvent. The presence of methanol as a solvent provides additional advantages due to its polarity. In particular, methanol can cause the swelling of the chitosan, which is low or high in molecular weight, to cause the sulfonate to penetrate. To which and not yet changed The reaction of the sugar monomer. The acidification reaction occurs almost on the amine group of the sugar monomer instead of the methylol group due to the obvious difference in the tendency of the acidification reaction. Chitosan sulfonation is carried out using decyl alcohol as a solvent. The modified reaction temperature is carried out between 25 C and 67 C. In addition, the diterpene-2-propanol is particularly suitable for use in the upgrading reaction of a very low molecular weight chitosan. As mentioned above, The sulfonation reaction is preferably carried out at the reflux temperature of the organic solvent, more precisely, the reflux temperature of the sulfonation reaction is the same as the type of the organic solvent, and the boiling point of the mixture with the chitosan 200938207. When methanol is used as the organic solvent, the reflux temperature is about 65 to 67. The reflux temperature of n-butanol as an organic solvent is about 117 to 120 C, and the reflux temperature of isopropanol as an organic solvent is about 82 to 85. And the reflux temperature of 丨-methoxy-2-propanol as an organic solvent is about 110~115 ° C. The succinyl lactone (aikyi/aikenyi suh〇ne) Divided into alkyl sultone and olefin Sulfene 61 (alkenyl ❹sultone) ' can be expressed by the structure shown by the following formula: (1): Γ丫R2 0 卜. Ο (1), where 'R1 is selected from _(CH2)X- or _CH=CH - X is 2, 3 or 4; and R2 is selected from Η or (^ to ^ alkyl. Specific aspects of the hydrocarbyl sultone compound include, but are not limited to, 1,3- = alkanolactone, hydrazine , 3_ propylene translactone, 1,4-butane sultone, 2,4-butane-lactone or a mixture thereof. Taking 1,4-butane sultone as an example 'When n-butanol or The methoxy- 2 -propanol is a solvent, and the water-soluble chitosan can be obtained in a yield of 55% to 92% at a reflux of 6 to 8 hours from 〇 to 13 Torr. It can be easily understood that the choice and amount of the hydrocarbyl sultone can be determined according to the degree of acidification and the nature of the water-soluble chitosan to be prepared, and the water-soluble chitosan can be obtained. By using a conventional purification method, the amine is removed from the organic solvent, and the amine is not subjected to acidification. The 200938207 base can further apply the water-soluble chitosan to various fields. The present invention comprises the use of a water-soluble polyamino sugar derivative for improving high-density lipoprotein in blood, wherein the water-soluble polyamino sugar derivative is an unmodified polyamino sugar via a hydrocarbyl sultone sulphonate. Produced after acidification. The definition of 'water-soluble polyamino sugar, its preparation method and the continuous lactone compound is as described above. Furthermore, the present invention comprises the use of a water-soluble polyamino sugar derivative for the preparation of a pharmaceutical composition for improving high-density lipoprotein in blood, wherein the water-soluble polyamino sugar derivative is unmodified. The polyamino sugar is obtained by successive acidification of the acetate in the hydrocarbon base. Similarly, the water-soluble polyamino vinegar, its preparation method, and the definition of the continued lactone are as described above. The following embodiments are intended to further understand the advantages of the present invention and are not intended to limit the scope of the invention.实施 Example 1 Preparation of Water-Soluble Chitosan 161 g of a high molecular weight chitosan (approximately 14 000 parts by volume) was placed and placed in a flask, and 700 ml of methanol was added thereto for stirring. Thereafter, the mixture in the flask was heated and stirred, and then 122 g of 1,3·propyl vinegar was slowly added dropwise at a reflux temperature of 65 to 67 °C. After all the 1,3-propane burned vinegar was added, the mixture was refluxed for four hours, after which the flask was cooled to room temperature, and the product was collected by filtration and rinsed several times with decyl alcohol, and then placed in a vacuum oven. Dry overnight. After drying, weighed 282 g of a 99.7% yield of alkylsulfonated chitosan. 200938207 Example 2: Effect of chitosan on hamsters before and after modification. Hamster feeding 舆 Feeding male hamsters containing four weeks old milk was purchased from the Experimental Animal Center of the National Experimental Research Institute of the consortium. In a plastic cage, the 12-hour day/night cycle is controlled at a temperature of 25 ± 1. (: 'Free drinking water and normal diet (standard group, recorded as "ND"; AIN-93G; ❹ iCN Biomedicalsm ' Costa Mesa, CA 'USA), one week later changed the hamsters outside the standard group to a high-fat, high-cholesterol diet (High fat and cholesterol diet, denoted as "HFCD"; AIN-93G modified high-fat diet), diet formula can be referred to the following table, diet formula (g / 100g) content ND HFCD Casein 20 20 Sucrose 10 10 Cornstarch 41.2486 26.2486 Maltodextrin 13.2 13.2 L-Cystein 0.3 0.3 Cellulose 5.0 5.0 So>hcan Oil 5.0 20.() t-butylhydroquinone 0.0014 0.0014 Mineral Mix #210025 3.5 3.5 Vitamin Mix #310025 1.0 1.0 Choline Bitartrate 0.25 0.25 Cholesterol 0.5 0.5
除一般進食外’並於實驗組每週一、三、五、六固定 灌食5或10mg/kgBW之幾丁質（分別記為LCH及HCH) 11 200938207 或5或25mg/kgBW之水溶性幾丁聚醣（分別記為LMCH 及HMCH)，同時在HFCD組中部分倉鼠合併餵食降血脂 藥物 probucol (記為 HFCD+P)。 飼養期間每日進行體重與進食量之記錄。 含鼠之犧牲、採樣輿分析In addition to general eating, and in the experimental group once a week, three, five, six fixed feeding 5 or 10mg / kg BW of chitin (respectively labeled as LCH and HCH) 11 200938207 or 5 or 25mg / kg BW water soluble Butanose (referred to as LMCH and HMCH, respectively), while in the HFCD group, some hamsters were fed with the lipid-lowering drug probucol (denoted as HFCD+P). Daily weight and food intake were recorded during the feeding period. Rat sacrifice, sampling analysis
實驗動物於七週後於犧牲前先禁食12小時，之後利 用二氧化碳窒息法將其犧牲後，立刻由肝門靜脈採取血液 樣品並搭配使用EDTA作為抗凝血劑，血液樣品於4°c環 境中以300g之離心力離心10分鐘以取得血清樣品，以進 行肝功能（AST、ALT )與血清脂質（Tc、TG、 LDL_cholesterol、HDL-cholesterol)分析。 獲得之數據以SAS電腦統計軟體進行變異數分析 (analysis of variance，簡稱 ANOVA)，同時配合 Tukey，s test進行統計分析’以分析實驗數據間是否達到顯著性差 異（P<〇.〇5)。 ^ ❹ 結果 生長變杷與肝功·％ 利用幾丁質（CH)或水溶性幾丁聚_ (mch)银食 之倉鼠，其體重增加量、肝臟、心臟、脾臟與腎臟相對於 體重之相關重量皆與ND組無差異，顯示餵食幾丁質或水 溶性幾丁聚醣對倉鼠之進食、生長與重要臟器都不會造成 負擔影響。 至於判斷肝功能之A S T與A LT活性亦與N D組無差 12 200938207 異，顯示餵食幾丁質或水溶性幾丁聚醣不影響倉鼠之肝功 月匕 I韆 表 弋把#腊’笔儀 下表二係為倉鼠金液中各血脂成分之數據統計分析 ^成分 組別 三酸甘油脂 膽固醇 高密度脂蛋白-膽 固醇 低密度脂蛋白 -膽固醇 ND 25.7± 5.51b 140.8±22.40c 116.0±19.27c 26.2+4.82° HFCD 43.8± 6.08a 276.4+ 7.40- 176 ()± 9 30 h 76.4±5.02 a HFCD+P 26.6± 5.80b 224.5±19.02b 194.4+18.89ab 60.5±7.42b HFCD + LCH 25.8+ 6.65 b 237.2±17.61 b 188.7±13.84 ab 65.417.83 b HFCD + HCH 27.9±11.19b 236.5+ 6.57 b 193.6±14.46ab 65.5+3.21 b HFCD+LMCH 18.7+ 2.31 b 245.1±31.8〇b 185.6±13.45 ab 64.4+9.48 b HFCD + HMCH Vnrfcrma Hi 29.3+ 3.30b 237.6+ 7.96 b 200 0+28 07 d 61.3+3.30 ❹ LMCH:如* BW ^ ❹ 由上表可知，餵食高膽固醇食物（HFCD)之倉鼠其 各項與血脂相關之數值皆顯著上升，倘配合降血脂藥物^ 者幾丁質使用，可將南密度脂蛋白提升，但是當饒食高膦After seven weeks, the experimental animals were fasted for 12 hours before sacrifice. After sacrificed by carbon dioxide asphyxiation, blood samples were taken from the hepatic portal vein and used together with EDTA as an anticoagulant. Blood samples were taken at 4 ° C. The samples were centrifuged for 10 minutes at 300 g to obtain liver samples (AST, ALT) and serum lipids (Tc, TG, LDL_cholesterol, HDL-cholesterol). The data obtained were analyzed by SAS computer statistical software (analysis of variance, ANOVA), and statistical analysis was performed with Tukey, s test to analyze whether the experimental data reached a significant difference (P<〇.〇5). ^ ❹ Result Growth and phlegm and liver function·% Use of chitin (CH) or water-soluble chitosan _ (mch) silver food hamster, its weight gain, liver, heart, spleen and kidney relative to body weight The weights were not different from those of the ND group, indicating that feeding chitin or water-soluble chitosan did not affect the feeding, growth and important organs of hamsters. As for the AST and A LT activity of liver function, it is also different from the ND group. It shows that feeding chitin or water-soluble chitosan does not affect the liver function of hamsters. The following table 2 is the statistical analysis of the blood lipid components in the hamster gold liquid. ^Component group triglyceride cholesterol high density lipoprotein-cholesterol low density lipoprotein-cholesterol ND 25.7± 5.51b 140.8±22.40c 116.0±19.27c 26.2+4.82° HFCD 43.8± 6.08a 276.4+ 7.40- 176 ()± 9 30 h 76.4±5.02 a HFCD+P 26.6± 5.80b 224.5±19.02b 194.4+18.89ab 60.5±7.42b HFCD + LCH 25.8+ 6.65 b 237.2±17.61 b 188.7±13.84 ab 65.417.83 b HFCD + HCH 27.9±11.19b 236.5+ 6.57 b 193.6±14.46ab 65.5+3.21 b HFCD+LMCH 18.7+ 2.31 b 245.1±31.8〇b 185.6±13.45 ab 64.4+9.48 b HFCD + HMCH Vnrfcrma Hi 29.3+ 3.30b 237.6+ 7.96 b 200 0+28 07 d 61.3+3.30 ❹ LMCH: as * BW ^ ❹ As can be seen from the above table, hamsters fed with high cholesterol food (HFCD) and their blood lipids The relevant values have increased significantly. If combined with the hypolipidemic drugs, the chitin will be used. Density lipoprotein improved, but when spare food high phosphine
固醇飲食配合水溶性幾丁㈣食用後，其提升效果較配^ 降血脂藥或幾丁質食用顯著。 Q 综上所述，水溶性幾丁聚酶較固態之幾丁質 酶比較，除了流動録’其水可溶性佳之特性適合添加 流體食物或飲品之巾，且有效提升錢巾高密度脂蛋白: 其他實施觴樣 在本說明書巾賴露的所有特徵都可能與其他方法 13 200938207 結合，本說明書中所揭露的每一個特徵都可能選擇性的以 相同、相等或相似目的特徵所取代，因此，除了特別顯著 的特徵之外，所有的本說明書所揭露的特徵僅是相等或相 似特徵中的一個例子。 雖然本發明已以較佳實施例揭露如上，然其並非用以限定 本發明，任何熟悉此技藝者，在不脫離本發明之精神和範 圍内，當可作各種之更動與潤飾。After the sterol diet combined with the water-soluble diced (four), the lifting effect is significantly higher than that of the hypolipidemic drug or chitin. Q In summary, the water-soluble chitinase is more stable than the solid chitinase, except for the mobile record, which is suitable for adding fluid food or drink towels, and effectively enhances the high-density lipoprotein of the money towel: EMBODIMENT OF THE INVENTION All features of this specification may be combined with other methods 13 200938207. Each feature disclosed in this specification may be selectively replaced with the same, equal or similar purpose characteristics, therefore, except In addition to the salient features, all of the features disclosed in this specification are only one of the equivalent or similar features. While the present invention has been described in its preferred embodiments, it is not intended to limit the invention, and various modifications and changes can be made without departing from the spirit and scope of the invention.
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