TW200913898A - Liquid composition for soft capsule filling - Google Patents

Abstract

The present invention provides a liquid composition for soft capsule filling, which disperse the hard oil-soluble ingredient in edible oil, characterized by containing reaction monoglyceride and distill monoglyceride as a dispersion stabilizer for dispersing the hard oil-soluble ingredient.

Description

200913898 ，九、發明說明： 【發明所屬之技術領域】 本毛明係有關軟膠囊充填用液狀組成物。 【先前技術】 八3有油難洛性或粉末狀之有效成分的軟膠囊，一般係 .^ /刀散有效成分於食用油脂中而調製成的分散液予以充填 —Μ明膠作為皮膜之膠囊内，藉此而製造。此時，用以安 定也使該有效成分分散於食用油脂中之分散劑，以往係使 用甘油脂肪酸酯或蜜蠟（參照專利文獻1)。 、八然而’已知若使用蜜蠟作為分散劑，則可能會使有效 成刀^效果無法於生體内充分發揮。因此，不使用蜜壌而 使有效成分安定地分散於食用油脂中的方法，係提案有例 如藉由甘油脂肪酸g旨及氫化加工油脂之組合而 懸浮化，組成物等（參照專利文獻2)。 成刀 但是’以上述技術而言，與使用蜜蠟之以往技術相比， 其有效成分之分散性仍有難處，並非完全令人滿足者。 專利文獻1 :日本特開平7_138151號公報，段落_9] 專利文獻2:日本特開薦]12753號公報，段⑽〇2〇]-【發明内容】 (發明欲解決之課題） /本發明之目的係提供一種不使用蜜蠟且與使用蜜蠟之 以往配方具有同等以上之油難溶性成分之分散安定性的軟 勝囊充填用液散組成物。本發明之另一目的係提供一種令 生體内之油難溶性成分之分散性比使用㈣作為分散劑者 320233 5 200913898 f更良好的軟膠囊充填用液狀組成物。 (解決課題之方案） 本發明人係為了解決上述課題而精心研究，結果得到 下述見解： (i)使用反應單甘油酯及蒸餾單甘油酯作為用以使油難溶 性成分分散之分散安定劑，藉此，即使不使用蜜蠟亦 可使油難溶性成分安定地分散於食用油脂中，· (η)若更進一步使用單酯體含量5〇%以上之二甘油脂肪酸 酉曰’則人工胃液中之油難溶性成分之分散性會明顯地 上升。 本發明係依據上述見解而完成者，提供下述之軟膠囊 充填用液狀組成物。 " 亦即，本發明係有關於下述者： (1) 一種軟膠囊充填用液狀組成物，係使油難‘溶性成分分散 於食用油脂中之組成物，其特徵為：含有反應單甘油酯 及蒸餾單甘油酯作為使該油難溶性成分分散用之分散 安定劑；及 (2) 如上述（1)記載之軟膠囊充填用液狀組成物，復含有單 醋體含量50%以上之二甘油脂肪酸酯。 另外，本發明係有關於下述者： (3) —種使油難溶性成分分散於食用油脂中之分散方法，其 特徵為包含下述步驟：將含有食甩油脂、油難溶性成 分、反應單甘油酯、以及蒸餾單甘油酯之組成物予以混 合及攪拌的步驟；及 320233 6 200913898 (4)如上述（3),己載之分散方法，其中，組成物復含有單酯 體含篁50%以上之二甘油脂肪酸酯。 (發明之效果） (. 本發明之軟膠囊充填用液狀組成物不含有蜜蠟。 本發明之軟膠囊充填用液狀組成物，係與使用蜜蠟作 散劑之以往配方具有同等以上之油難溶性成分之分散 =疋性者。更進—步，本發明之軟膠囊充填用液狀組成物 若含有單酯體含量50%以上之二甘油脂肪酸酯，則與使用 蜜蠟作為分散劑之以往配方相比，在人工胃液中之油難溶 性成分之分散性會明顯地上升。 【實施方式】 本發明之軟膠囊充填用液狀組成物，係使油難溶性成 分分散於食用油脂中之組成物，且含有反應單甘油酯及蒸 顧單甘油酯作為用以使該油難溶性成分分散之分散安定 劑。又以含有單酯體含量50%以上之二甘油脂肪酸酯的組 成物為更佳。藉由含有單酯體含量50%以上之二甘油脂肪 酸酯’可使油難溶性成分之生體内分散性明顯地上升，故 可在生體内充分發揮油難溶性成分（有效成分）之效果。 食用油脂 本發明中所使用之食用油脂’只要是可作為油難溶性 成分之載體使用的食用油脂即可，並無特別限制，可列舉 如撖欖油、芝麻油、米糠油、紅花油、大豆油、玉米油、 菜籽油、棕櫚油、棕櫚油精（palm 〇lein)、棕櫚仁油、向曰 葵油、葡萄籽油、棉籽油、椰子油、花生油等植物油脂， 320233 7 200913898 或中和脂肪酸三甘油酯、t、婦（squalene)、魚油等。本發明 中之食用油脂係以植物油脂為佳，又以植物油脂之沙拉油 為更佳’其中尤以紅花沙拉油為特佳。在本發明巾，可使 用一種食用油脂，亦可任意組合二種以上來使用。 渔難溶性成合 本發明甲所使用之油難溶性成分係由親油性低之物質 所構成，並為構成本發明之軟膠囊充填用液狀組成物之有 效成分者。 ，本發明之油難溶性成分，係指為粉末狀態、且當將該 粉末lg加入食用油脂100g中以2〇t混合時，在3〇 ^ 内不會溶解的物質。 此種油難溶性成分，可縣如：維生素類（尤其是抗壞 血酸、維生素m、維生素B2、維生素B6、維生素βΐ2等 水溶性維生素）、檸樣酸、玻尿酸(.hyato_)、妈粉末等 營養獅成分；蜂王漿萃取物粉末、蜂膠(prQpc)iis)萃取物 ，末、監莓萃取物粉末、巴西蘑料取物粉末、装魚軟骨 萃取物粉末、薑黃粉末、银杏葉萃取物粉末、武机葉 (Gymnema)萃取物粉末、其他動植物粉末、㈣、寡糖、 曱殼素（cMtosan)、食物纖維等健康食品成分；或是生藥 drug)萃取物粉末、中藥、醫藥組成物等藥效成分。 二中以k%萃取物粉末、銀㈣萃取物粉末、維生素類為 佳。油難溶性成分可使用1種或組合2種以上使用。 .反應單甘油酷 本I明中所使用之反應單甘油酯，係甘油與脂肪酸之 320233 8 200913898 產物或由甘油與油脂（二甘油酯）之酯交換反應產物 二盡可能地除去未反應之甘油者，其係含有單甘油酯（甘油 單月曰肪版Sa )、二甘油酯（甘油二脂肪酸酯）及三甘油酯（甘油 一月曰肪駄)之混合物。該反應單甘油酯上中之單甘油 '酯之ί量通常為約4〇至6〇%，較佳為約45至55%。另外， 反應單甘油酉曰1〇〇%中之二甘油醋之含量通常為約^至 4〇% ’較佳為約20至30%。反應單甘油酯100%中之三甘 油酯之含量通常為約1至10%，較佳為約1至5%。 上述反應單甘油酯之組成（亦即反應單甘油酯中之單 、a 甘油、及三甘油酯之含量）係藉由將反應單甘 油酷以HPLC(高速液體層析儀）分析而求得。具體而言，依 據下述所示之分析條件來分析反應單甘油醋，在分析後， 對於以數據處理裝置紀錄於層析圖上之受驗試料 所對應之波峰，使用接八4、Β, —、士& 使用積刀计測疋波峰面積。可依據所測定 之波峰面積，而以面積百分比求得單甘油醋含量、 酯含量、及三甘油酯含量。 HPLC分析條件係如下所述。 (HPLC分析條件） ^高速液體層析儀(型號：LC魏s;島津製作所公司 ?測器mm型號：RID_6A;島津製作所公司雙 吕柱· GPC官柱（型號：sh〇dex kf_8〇2 ;昭 製）2支連結 Λ 〇Ί200913898, IX. Description of the invention: [Technical field to which the invention pertains] The present invention relates to a liquid composition for soft capsule filling. [Prior Art] Eighty-three soft capsules containing oil-soluble or powdery active ingredients are generally filled with a dispersion prepared by dissolving the active ingredient in edible fats and oils - gelatin is used as a capsule in the film. , manufactured by this. In this case, a glycerin fatty acid ester or beeswax is conventionally used as a dispersing agent for dispersing the active ingredient in edible fats and oils (see Patent Document 1). However, it is known that if beeswax is used as a dispersing agent, the effect of effective knife formation may not be fully exerted in the living body. Therefore, a method of dispersing the active ingredient in the edible fat or oil without using the candied fruit, for example, by glycerin fatty acid g and a combination of hydrogenated processed fats and oils, is proposed to be suspended, and the like (see Patent Document 2). However, in terms of the above techniques, the dispersibility of the active ingredient is still difficult compared to the prior art using beeswax, and it is not entirely satisfactory. Patent Document 1: Japanese Laid-Open Patent Publication No. Hei 7-138151, paragraph _9] Patent Document 2: Japanese Patent Application No. 12753, Section (10) 〇 2〇]- [Summary of the Invention] (Problems to be Solved by the Invention) / The present invention It is an object of the invention to provide a liquid dispersion composition for soft capsule filling which does not use beeswax and which has the same dispersion stability as the oil-insoluble component of the conventional formulation using beeswax. Another object of the present invention is to provide a liquid composition for soft capsule filling which is more excellent in dispersibility of the oil-insoluble component in the living body than in the use of (4) as a dispersing agent 320233 5 200913898 f. (Solution to Problem) The inventors of the present invention have intensively studied to solve the above problems, and as a result, have obtained the following findings: (i) using a reaction monoglyceride and a distilled monoglyceride as a dispersion stabilizer for dispersing a poorly soluble component of oil Therefore, even if the beeswax is not used, the hardly soluble component of the oil can be stably dispersed in the edible fat and oil. (η) If the monoglyceride fatty acid 酉曰' of the monoester content of 5% or more is further used, the artificial gastric juice The dispersibility of the poorly soluble components of the oil will increase significantly. The present invention has been completed in accordance with the above findings, and provides the following liquid composition for soft capsule filling. In other words, the present invention relates to the following: (1) A liquid composition for soft capsule filling, which is a composition in which an oil-soluble 'soluble component is dispersed in an edible fat or oil, and is characterized by containing a reaction sheet. The glyceride and the distilled monoglyceride are used as a dispersion stabilizer for dispersing the poorly soluble component of the oil; and (2) The liquid composition for soft capsule filling according to the above (1), which contains a monohydrate content of 50% or more. Diglycerin fatty acid ester. Further, the present invention relates to the following: (3) A method for dispersing a poorly oil-soluble component in edible fats and oils, comprising the steps of: containing chyme oil, poorly soluble oil, and reaction a step of mixing and stirring a composition of a monoglyceride and a distilled monoglyceride; and 320233 6 200913898 (4) A dispersion method according to the above (3), wherein the composition contains a monoester body containing hydrazine 50 More than 2% diglycerin fatty acid ester. (Effect of the Invention) (The liquid composition for soft capsule filling of the present invention does not contain beeswax. The liquid composition for soft capsule filling of the present invention is equivalent to the conventional formulation using beeswax as a powder. Dispersion of poorly soluble components = sputum. Further, if the liquid composition for soft capsule filling of the present invention contains a diglycerin fatty acid ester having a monoester content of 50% or more, and using beeswax as a dispersing agent The dispersibility of the oil-insoluble component in the artificial gastric juice is remarkably increased as compared with the conventional formulation. [Embodiment] The liquid composition for soft capsule filling of the present invention is such that the poorly soluble component of the oil is dispersed in the edible fat or oil. The composition contains a reaction monoglyceride and a vaporized monoglyceride as a dispersion stabilizer for dispersing the poorly soluble component of the oil, and a composition containing a diglycerin fatty acid ester having a monoester content of 50% or more. More preferably, the diglyceride fatty acid ester having a monoester content of 50% or more can significantly increase the dispersibility of the oil-insoluble component in the living body, so that the oil-insoluble component can be sufficiently exhibited in the living body. The edible oil and fat used in the present invention is not particularly limited as long as it is an edible fat or oil which can be used as a carrier for the oil-insoluble component, and examples thereof include eucalyptus oil, sesame oil, and rice bran oil. , safflower oil, soybean oil, corn oil, rapeseed oil, palm oil, palm olein (palm 〇lein), palm kernel oil, hollyhock oil, grape seed oil, cottonseed oil, coconut oil, peanut oil and other vegetable oils, 320233 7 200913898 Or neutralize fatty acid triglycerides, t, squalene, fish oil, etc. The edible oils and fats in the present invention are preferably vegetable oils and oils, and vegetable oils and salad oils are better. The oil of the present invention can be used in combination with two or more kinds of edible fats and oils. The poorly soluble oil-soluble component used in the present invention is composed of a substance having low lipophilicity. And the active ingredient of the liquid composition for filling the soft capsule of the present invention. The oil-insoluble component of the present invention means a powder state, and when the powder lg is added When 100g of edible fats and oils are mixed at 2〇t, they do not dissolve in 3〇^. Such oil-insoluble components can be counted as vitamins (especially ascorbic acid, vitamin m, vitamin B2, vitamin B6, vitamins). ΐ 成分 等 等 水溶性 ΐ ΐ ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; Powder, turmeric cartilage extract powder, turmeric powder, ginkgo biloba extract powder, Gymnema extract powder, other animal and plant powder, (4), oligosaccharide, cMtosan, dietary fiber and other health foods Ingredients; or raw drug drugs) extract powder, traditional Chinese medicine, pharmaceutical composition and other medicinal ingredients. In the second, k% extract powder, silver (four) extract powder, and vitamins are preferred. The oil-insoluble component may be used alone or in combination of two or more. Reaction monoglyceride used in the reaction of monoglycerin, which is a product of glycerol and fatty acid 320233 8 200913898 or a transesterification reaction product 2 of glycerol and fat (diglyceride) to remove unreacted glycerol as much as possible. The present invention comprises a mixture of a monoglyceride (glycerol mono-salt Sa), a diglyceride (diglyceride), and a triglyceride (glycerin January). The amount of the monoglycerol 'ester in the reaction monoglyceride is usually from about 4 to 6 %, preferably from about 45 to 55%. Further, the content of the diglycerin in the reaction monoglycerin 酉曰 1% is usually from about 2 to 4 % by weight, preferably from about 20 to 30%. The content of the triglyceride in 100% of the reaction monoglyceride is usually from about 1 to 10%, preferably from about 1 to 5%. The composition of the above reaction monoglyceride (i.e., the content of a single, a glycerin, and a triglyceride in the reaction monoglyceride) was determined by analyzing the reaction monoglyceride by HPLC (High Speed Liquid Chromatography). Specifically, the reaction monoglyceride was analyzed according to the analysis conditions shown below, and after the analysis, for the peak corresponding to the test sample recorded on the chromatogram by the data processing device, the use of the 8th, 4th, —,士& Use the integrated knife to measure the crest peak area. The monoglycerol content, the ester content, and the triglyceride content can be determined as a percentage of the area based on the measured peak area. The HPLC analysis conditions are as follows. (HPLC analysis conditions) ^High-speed liquid chromatograph (Model: LC Wei s; Shimadzu Corporation) Measurer mm model: RID_6A; Shimadzu Corporation Shuangluzhu·GPC official column (Model: sh〇dex kf_8〇2; Zhao System) 2 links Λ 〇Ί

管柱溫度：40°C 320233 9Column temperature: 40 ° C 320233 9

200913898 、 移動相：THF200913898 , Mobile phase : THF

流量：1.0 mL/分鐘 檢液注入量：15/zL 構成本發明所使用之反應單甘油酯的脂肪酸，較佳可 列庫如源自可食用之動植物油脂的碳數6至24的直鏈飽和 脂肪酸（例如己酸、辛酉变、癸酸、月桂酸、肖豆謹酸、標搁 酸、硬脂酸、二十酸、二十二酸、二十 櫚酸、硬脂酸、二十二酸等。 四酸等），更佳為棕 本發明所使用之反應單甘油酯的製法，可列舉如 藉由甘油與油脂之g旨交換反應而製造的方法、⑺藉由甘油 與脂肪酸之醋化反應而製造的方法。此等製法之概略内容 係分別表示於以下之及（2)。 (1)藉由酯交換反應而製造反應單甘油醋的方法Flow rate: 1.0 mL/min Test liquid injection amount: 15/zL The fatty acid constituting the reaction monoglyceride used in the present invention, preferably a linear acid saturation of 6 to 24 carbon atoms derived from edible animal and vegetable oils and fats. Fatty acids (such as hexanoic acid, octanoic acid, citric acid, lauric acid, xiaoji acid, standard acid, stearic acid, icosonic acid, behenic acid, icosanoic acid, stearic acid, behenic acid, etc.) More preferably, the method for producing the reaction monoglyceride used in the present invention is, for example, a method produced by exchanging a reaction of glycerin with a fat or oil, and (7) by acetalization of glycerin with a fatty acid. And the method of manufacturing. The outline contents of these methods are shown in the following (2). (1) A method for producing a reaction monoglycerin by a transesterification reaction

例如，在具備攪拌機、加熱用套管、阻擋板等之一东 反應容器中，以2:1之莫耳比置入甘油及油脂，添加例女 虱氧化納作為通f卿並㈣混合，在线環境下，例如 於約180至260°C (較佳為約200至25(rc)、以約〇 5至I :(車又佳為約1至3小時）加熱而進行醋交換反應。反肩 &條件細在常壓下或減壓下純。所得之反應液係令 ^甘油、甘油單脂肪_、甘油二脂肪_、甘油三脂取 酸酯等的混合物。 、y j應二束後’中和反應液中殘存之觸媒，其次將反應 =在減壓下㈣殘存之甘油，若有必要則進行脫鹽、 色、過渡等處理，最後獲得相對於整體而言，含有約4〇 320233 10 200913898 、至60%單甘油酯之反應單甘油酯。 (2)藉由酯化反應而製造反應單甘油酯的方法 例如，在具備攪拌機、加熱用套管、阻擋板等之一般 反應容器中，以1: 1之莫耳比置入甘油及脂肪酸，因應需 '要而添加酸或鹼作為觸媒，在氮氣或二氧化碳等任音惰性 ’氣體環境下，例如於約⑽至赋的範圍（較佳為；· 至严50 C)、加熱約0.5至5小時(較佳為約1至3小時)以 進行酯化反應。所得之；5庙、、右在人1 , 于之反應液係含有甘油、甘油單脂肪酸 酉曰、甘油二脂肪酸酉旨 '甘油三脂肪酸酉旨等的混合物。 反應結束後，中和反應液中殘存之觸媒，其 除殘存之甘油’若有必要則進行脫 -脫色、過慮荨處理，最後獲得相對於整體而言， 約40至60%單甘油酯之反應單甘油酯。 單甘油醋係於商業上製造及販售為例如— 52〇/〇, I素八0Π·Μν_2(Κ)(製品名，單甘㈣含量約5g%，理研維 47。广）、及PGemB_2GG(製品名，單甘油自旨含量約 研維生素公司s)#，在本發明中可使用此 口口作為反應單甘油酯。 e 蓋靡單甘油啤 本發明中所使用之蒸德單甘油醋，係將上述反甘 油酯精製而提高單酯體之含量者， = 之單醋體之含量通常為约90%以上:、館早甘…。咐 蒸館單甘油醋麵中之單甘油醋之含量，係藉由將 320233 11 200913898 —蒸餾單甘油醋以上述分析條件使用hplc分析 =而言，在以上述肌c分析條件分析蒸鶴單甘油^ 了 對於以數據處理裝置紀錄於層析爰 所對應之波峰，使用積分計測：广：枓之各成分 ，之、座痊而并波峰面積，並依據所測定 峰面積’而可以面積百分比求得單甘油醋之含量。 ’將上㈣用之蒸料甘油醋的製造方法，可列舉如 式分:_早:=用分子蒸鶴裝置或離心 于二館裝置專而進仃真空蒸餾之方法。藉由使 醋的獲::對於整體含有約9。%以上單甘油 量之單甘油…一甘-含 ^甘油脂肪酿酷 本發明所使用之二甘油脂肪酸醋，係將油 的二甘:脂肪―方= 為—者，體之含 :甘油脂肪酸醋中之單醋體之含量’藉由將二甘油腊 今，文日以上述分析條件使用HPLC分析而求得。具體 對應之波峰，使圖上之受驗試料之各成分所 波蜂面積，而可以、刀计測定波峰面積’並依據所測定之 、、而了以面積百分比求得單酯體之含量。 作為本發明所用之單酿體含量5〇%以上之二甘油月旨肪 320233 12 200913898 =曰（以下’亦簡稱為二甘油㈣g_之原料而使用的二 j係可列舉如：通常於甘油中添加少量之酸 觸媒，將其在氮氣或二氧化碳等任意惰性氣體環境下乍^ =約刚。^以上之溫度加熱，並進行縮聚反應而獲得的 的z一之千均聚合度為h5至2.4(較佳為平均聚合度約2.0) 、.：油和合物。另外，二甘油係亦可為以環氧丙醇 (心或表氯醇等作為原料而得者。反應 必要亦可進行巾和、脫鹽、脫色等處理。 右有 與知f Γ毛.月中，以將上述二甘油混合物例如使用蒸餾或 5、'斤法等本身為週知之方法進行精製，並使由2分子 甘油所構成之二甘油之含量成為整體之約鄕以上(宜為 約7〇%以上，更宜為約90%以上)的經高漠度化之 二 甘油係較佳。 一 乍為本發明所用之二甘油脂肪酸自旨之原料而使用的脂 t酸，係、可列舉如碳數6至24的直鏈飽和脂肪酸（例如己 二:It癸酸、月桂酸、肉豆囊酸、掠搁酸、硬脂酸、 、 十§久一十四酸等）、不飽和腊肪酸（例如棕 橺冷酉夂（palmitoleic acid)、油酸、反油酸（elaidic acid)、亞 =油酉夂（lin〇leiCaci句、卜次亞麻油酸icacid)、 ，麻油^_ 一十碳四婦酸（arachid〇nic add)、蓖麻油酸 aCid)、縮合蓖麻油酸等），其中以癸酸、月桂酸、 肉f蘿酸、油酸等為較佳。以該脂肪酸而言，可商業性地 取得以70%以上含有癸酸、月桂酸、肉豆蔻酸、或油酸者， 在本發明中以使用該等為佳。該可商業性地取得的脂肪 320233 13 200913898 酸，可列舉如商品名⑴NAA_122(日油公司製）、（2)L刪c L-98(花王公司製）、（3)肉豆蔻酸98(Miy〇shi油脂公司製）、 (4)NAA-142(曰油公司製）、（5)Lunac Μγ_98(花王公司製）、 (6)Extra olein(日油公司製）、⑺Limac 0-V(花王公司製）、 (8)Lunac Ο-P(花王公司製）等。 本發明所使用之二甘油脂肪酸酯之較佳製法的概略内 容係如下所述。例如，在具備攪拌機、加熱用套管、阻擋 板等之一般反應容器中，以莫耳比約j : 〇8至i : 12(^ 佳為約1 . 1)置人二甘油及脂肪酸，添加氫氧化納作為觸 媒並攪拌混合，在氮氣環境下，一邊將酯化反應所產生之 水除去至系統外，一邊以預定溫度加熱。反應溫度通常在 約180至260 C之範圍，較佳為在約200至25〇。〇之範圍。 另外，反應壓力條件為減壓下或常壓下，反應時間為約〇.5 至15小時，又以約1至3小時為佳。就反應之終點而言， 一般以測定反應混合物之酸價為約12以下作為指標。所得 之反應液係含有未反應之脂肪酸、未反應之二甘油、二甘 油單脂肪酸酯、二甘油二脂肪酸酯、二甘油三脂肪酸酯、 二甘油四脂肪酸酯等的混合物。反應結束後，將所得之反 應液冷卻至約120°C以上且未達180它（較佳為約13〇至15〇 °c)，繼而添加酸以中和觸媒，較佳為放置約15分鐘至工 小時，當未反應之一甘油分離為下層時即予以去除，而獲 得二甘油脂肪酸酯。 更進一步，藉由將該二甘油脂肪酸酯例如使用降膜式 分子蒸餾裝置或離心式分子蒸餾裝置等以進行分子蒸鶴、 320233 14 200913898 ^疋使用官柱層析或液—液萃取（liquid-liquid extraction) 本身為週知之方法而進行精製，即可獲得相對於整體含 有約5〇%以上（更佳為約7G%以上）單醋體的二甘油脂肪酸 酯。 單酉日體含置為5〇%以上的二甘油脂肪酸酯，係於商業 上製造及販售為例如p〇em謝_1〇〇(製品名，理研維生素 公司製）、Poem DCM 00v(製品名，理研維生素公句製卜、 及Poem DL 1〇〇(製品名，理研維生素公司製）等，在本發 明中可使用此等市售品作為單醋體含量5〇%以上 脂肪酸酯。 一甘油 其他成分 本發明之軟膠囊充填用液狀組成物，只要是在可 本發明之效果之範圍内，亦可因應需要而含有除了上^食 用油月旨、油難溶性成分、反應單甘㈣、蒸料甘油醋、 以及早醋體含量50%以上之二甘油脂肪酸醋以外的成分。 其他成f可列舉如抗氧化劑（例如萃取生育盼、抗壞血酸棕 櫊酉夂§日等）等。該等其他成分可使用1種或組合2種以上使 用。 #合物之調 本發明之軟朦囊充填用液狀組成物係藉由一邊將上述 食用油月曰、油難溶性成分、反應單甘油醋及蒸鶴單甘油酯 此合授拌’ -邊使此等成分均勻地分散而製造。當本發明 之軟膠囊充填用液狀組成物含有單自旨體含量5G%以上二二 甘油脂肪酸S旨時’可藉由—邊將食用油脂、油難溶性成分二 320233 15 200913898 • 反應單甘油酯、蒸餾單甘油酯及該二甘油脂肪酸酯混合攪 拌’一邊使此等成分均勻地分散而製造。 具體而言，例如將食用油脂、反應單甘油酯及蒸餾單 甘油酯、以及因應需要之二甘油脂肪酸酯加熱到約60至 ' 90°C (較佳為約70至8(TC )並均勻地混合及攪拌後，將其冷 卻至例如約40至60°C，再添加油難溶性成分並均勻地混 合及授拌，藉此而可製造本發明之組成物。又，反應單甘 油Ss、蒸館早甘油醋及二甘油脂肪酸醋，係可使用預先將 此等混合、加熱及熔融者。用以混合及攪拌之裝置係無特 另J限制可使用例如生物混勻機（Bio mixer)、均質機箄古 速攪拌機或高速粉碎機。 成分fch率 本發明之軟膠囊充填用液狀組成物1〇 用油脂之含量係無特職制，例如通常為約2 ^ = /〇，較佳為約25至90質量％，哲貝^ 本發明中之食用油脂之含量若在至8〇質量％， 油難溶性成分充分地分散於食用油二時 之油難溶性成分之分散安定性亦良好。^油脂中 難溶液狀嘯1。。質量%中的油 質…佳為约;限量如响 本發明中之油難溶料10至5〇質量 可使油難溶性成分充分地分散於人=在上述範圍内，則 食用油財之油難溶性成分之分;二：：。另外’由於 刀政女疋性良好，故在軟膠 320233 16 200913898 囊中不會發生油難溶性成分之分離。更進—步，由於使用 軟膠囊充填用液狀組成物而製造的軟膠囊中的 (油難溶性成分）量為充分，故若攝取該軟膠囊，則在生體 内可充分發揮油難溶性成分之效果（例如生理活性等）。 。。本發明之軟膠囊充填用液狀組成物1〇〇 ft%中的反 =甘油酯之含量係無特別限制，例如通常為約0.5至 貝1 /〇，較佳為約0.5至10質量％，更佳為約i至8質量 %。本發明中之該反應單甘油s旨之含量若在上述範圍内， 則由於在食用油脂中之油難溶性成分之分散安定性為良 好，故在軟膠囊中不會發生油難溶性成分之分離。更進一 步，由於軟膠囊中的有效成分（油難溶性成分）量為充分， 故若攝取該軟膠囊，則在生體内可充分發揮油難溶性成分 之效果。 本發明之軟膠囊充填用液狀組成物100質量％中的蒸 餾單甘油酯之含量係無特別限制，例如通常為約〇 5至15 貝畺/〇，車父佳為約〇.5至1〇質量。/〇，更佳為約】至8質量 %。本發明中之該蒸餾單甘油酯之含量若在上述範圍内， 則由於在食用油脂中之油難溶性成分之分散安定性為良 好，故在軟膠囊中不會發生油難溶性成分之分離。更進一 步’由於軟膠囊中的有效成分（油難溶性成分）量為充分， 故若攝取該軟膠囊，則在生體内可充分發揮油難溶性成分 之效果。 當本發明之軟膠囊充填用液狀組成物含有單醋體含量 50%以上的二甘油脂肪酸酯時，該組成物1〇〇質量％中之 320233 17 200913898 該二甘油脂肪酸自旨之含量係無特別限制， 0.05至1.5質量％，較佳為約〇 〇5至i所旦。通常為約 ο·1至/質量％。本發明中之該二甘油^約 上述範圍内，則在實施後述之人工胃液中 、3里右在 時，人工胃液中之油難溶性成分之分二良:分=試驗 體内之油難溶性成分之分散性係成為充分 亦即，生 膠囊中的有效成分（油難溶性成分）量係成為充分， 取該軟膠囊，則在生體内可充分發揮油 故右攝 葱^囊之贺i告 風刀之效果。 依據常法將如此操作而獲得的軟膠囊充填用液狀 ^以明膠作為主成分之皮膜中，即可製造軟膠囊。呈 體而έ，例如可在2片明膠薄片之間，注 八 囊充填用液狀組成物作為内容物，並# 膠 膠囊。 i褚田打錠法而製造軟 之分散方法 藉由將含有食用油脂、油難溶性成分、反應單甘油酉旨 =單甘油醋之組成物予以混合及攪拌，即可使油難溶 成分良好地分散於食用油脂中。如此，本發明之另—態 、’亦為一種使油難溶性成分分散於食用油脂中之分散方 t ί包含將含有食用油脂、油難溶性成分、反應單甘油 酉曰及条館單甘油醋之組成物予以混合及檀拌的步驟。較佳 ，將3有食用油月旨、油難溶性成分、反應單甘油适旨、蒸餾 =甘油酉曰、及單醋體含量50%以上之二甘油脂肪酸醋的組 成物予以混合及攪拌。 320233 18 200913898 本發明之分散方法t 廄罝廿沾姑— )艮用油月曰、油難溶性成分、 應早甘油酯、蒸餾罩廿 吼刀汉 甘曰及翠酉旨體含量·以上之二 甘✓由月日肪酉夂酉旨、以；山你 專之較佳態樣，係盘上述款 填用液狀组成物中所述者 ’、軟膠囊充 予以混合及授拌的方法:3有此等成分之M成物 f迭中將食用t 夥囊充填用液狀組成物之 表仏f將艮用油脂、油難溶八、 單甘油酯、另蓖 刀、反應早甘油酯、蒸餾 混合及攪拌的方法為相目… 甘油月曰肪酸醋予以 ^ . > '同。較佳例如係將食用油脂、反應 早甘油自日、瘵餾皁甘油酯、 阳汉早自日體含量50%以上之二甘 油脂肪酸酯加熱到例如約 C〇k佳為約70至8〇。〇 並均勻地混合及授拌德膝盆 現讦便將其冷部至例如約40至60〇C， 再添加油難溶性成分並均勻地混合及攪拌。 (實施例） 但本發明不受此 以下依據實施例更具體說明本發明 等實施例所限定。 軟膠囊用液狀組成物$事法— 實施例1 时在紅花沙拉油（Cargill Japan公司製）8〇.〇g中添加反應 早甘油脂（商品名：PGemB_2G()，單甘油g|含量約47%，理 研維生素公司製）5.0g及蒸鶴單甘油脂（商品名： s-100’單甘油醋含量約98%’理研維生素公司製)5々， 加熱至80 C並攪拌使其溶解。將此溶液自然冷卻至5〇。〇， 於其中添加核黃素（Rib〇flavin)(理研維生素公司製）〇 3g及 L-抗壞血酸(BASF武田維生素公司製）9 7g，再使用擾摔機 320233 19 200913898 •(型號：uitra-turrax T_25 basic，IKA Japan 公司紫）以 8〇〇〇rPm混合及攪拌10分鐘。將所得之分散液予以真空脫 泡處理後，冷卻至室溫，而獲得約1〇〇g之軟膠囊充填用液 狀組成物（實施品1)。 * 實施例2 使用反應單甘油酯（商品名：p〇emp_2〇〇，單甘油酯含 量約52%，理研維生素公司製）5.〇g替代實施例丨記載之反 應單甘油酯5.〇g，除此之外與實施例1同樣地實施，而獲 得約100g之軟膠囊充填用液狀組成物(實施品2)。 實施例3 使用蒸餾單甘油酯（商品名：p〇emp_1〇〇，單甘油酯含 量=98% ’理研維生素公司製）5 〇g替代實施例丨記載之蒸 餾早甘油酯5.〇g ’除此之外與實施例1同樣地實施，而獲 得約100g之軟膠囊充填用液狀組成物（實施品3)。 比較例1 使用蜜蠟（商品名：脫臭精製蜜蠟高酸，Cerarica野田 公司製）5.0g替代實施例丨記載之反應單甘油酯5 〇g，除此 之外與貫施例1同樣地實施，而獲得約1〇〇g之軟膠囊充填 用液狀組成物（比較品1)。 比較例2 曰使用蒸餾單甘油酯（商品名：P〇em s_100,單甘油酯含 罝約98%，理研維生素公司製）1〇 〇g替代實施例i記載之 反應單甘油酯5.〇g及蒸餾單甘油酯5.〇g，除此之外與實施 例1同樣地實施’而獲得約1〇〇g之軟膠囊充填用液狀組成 320233 20 200913898 * 物（比車父品2) 〇 比較例3 使用反應單甘油酯（商品名：PoemB_2〇〇，單甘油酯含 量約47%，理研維生素公司製）1〇 〇g替代實施例}記載之 *反應單甘油_ 5.〇g及蒸餾單甘油酯5.〇g，除此之外與實施 〃例1同m地實施，而獲得約⑽g之軟膠囊充填用液狀組成 物（比較品3)。 比較例4 使用反應單甘油酯（商品名：p〇em v_2〇〇，單甘油酯含 量約50%，理研維生素公司製）1〇 〇g替代實施例】記載之 反應單甘油酯5.0g&蒸餾單甘油酯5 〇g，除此之外與實施 例1同樣地實施，而獲得約1〇〇g之軟膠囊充填用液狀組成 物（比較品4)。 比較例’5 使用反應單甘油酯（商品名：p〇em ，單甘油酯含 里約52 /〇，理研維生素公司製）1〇 〇g替代實施例】記載之 反應單甘油酯5.〇g及蒸餾單甘油酯5〇g，除此之外與實施 例1同樣地實施，而獲得約1〇〇g之軟膠囊充填用液狀組成 物（比較品5)。 比較例6 使用条餾單甘油酯（商品名：p〇em p_1〇〇，單甘油酯含 量約98%，理研維生素公司製）1〇 〇g替代實施例丄記載之 反應單甘油酯5,0g及蒸餾單甘油酯5〇g，除此之外與實施 例1同樣地實施，而獲得約1〇〇g之軟膠囊充填用液狀組成 320233 21 200913898 Λ物（比較品6)。 軟谬囊充填用液狀組成物之分離之評估 口將以上述方法製作之軟膠囊充填用液狀組成物（實施 m 1至3及比較品】至6)分別各加入吨於離心管（容量 5〇ml ’均附栓塞）中，使用離心機（型號：SL-05，佐久間製 作所公司製）以迴轉數15〇()rpm離心2〇分鐘。然後，從離 、、六取出^官，對於離心管之試料，以目視觀察油難 洛、为（核頁素及L-抗壞血酸）有無分離。結果示於表卜 [表1]For example, in an East reaction vessel equipped with a stirrer, a heating jacket, a barrier plate, etc., glycerin and fat are placed at a molar ratio of 2:1, and a female sulphate is added as a sputum and (4) mixed, online. Under the circumstances, for example, a vinegar exchange reaction is carried out by heating at about 180 to 260 ° C (preferably about 200 to 25 (rc), about 5 to 1 : (the car is preferably about 1 to 3 hours). The conditions are fine under normal pressure or under reduced pressure. The obtained reaction solution is a mixture of glycerin, glycerol mono-fat, glycerol di-fat, and triglyceride-derived acid ester. Neutralize the catalyst remaining in the reaction solution, and then react = glycerol remaining under reduced pressure (4), and if necessary, perform desalting, color, transition, etc., and finally obtain about 4〇320233 10 relative to the whole. 200913898, a reaction to a monoglyceride of 60% monoglyceride. (2) A method for producing a reaction monoglyceride by an esterification reaction, for example, in a general reaction vessel equipped with a stirrer, a heating jacket, a barrier plate, or the like, Put glycerin and fatty acids in a molar ratio of 1:1, add acid or As a catalyst, in an inert inert gas atmosphere such as nitrogen or carbon dioxide, for example, in the range of about (10) to a given range (preferably; to 50 C), heating for about 0.5 to 5 hours (preferably about 1 to 3 hours) to carry out an esterification reaction. The obtained solution is a mixture of glycerin, glycerol mono-fatty acid, glycerol di-fatty acid, and glycerol tri-fatty acid. After the completion of the reaction, the catalyst remaining in the reaction liquid is neutralized, and the remaining glycerin is subjected to de-decoloration and decontamination treatment if necessary, and finally, about 40 to 60% of monoglyceride is obtained relative to the whole. Reaction monoglyceride. Monoglycerin is commercially produced and sold for example - 52〇/〇, I 八八Π·Μν_2(Κ) (product name, single gan (4) content is about 5g%, Liyanwei 47. Wide ), and PGemB_2GG (product name, single glycerin content, about the vitamin company s) #, can be used as the reaction monoglyceride in the present invention. e 靡 靡 甘油 glycerin beer used in the invention Single glycerin, which is refined by the above-mentioned anti-glyceride to increase the content of the monoester Quantity, = the content of single vinegar is usually about 90% or more:, the museum is early .... 咐 馆 馆 馆 单 单 单 单 单 320 320 320 320 320 320 320 320 320 320 320 320 320 320 320 320 320 320 320 320 320 320 320 320 320 320 320 In the above analysis conditions, using hplc analysis = analysis, in the above-mentioned muscle c analysis conditions analysis of steaming crane monoglycerol ^ for the data processing device recorded in the peak corresponding to the chromatographic enthalpy, using integral measurement: wide: 枓 枓 成分 成分The content of the single glycerin vinegar can be determined by the percentage of the area according to the measured peak area'. The manufacturing method of the glycerin vinegar used in the above (four) can be enumerated as: _ Early: = Method of vacuum distillation using a molecular steaming crane or centrifugation in the second building. By obtaining vinegar:: for the whole contains about 9. % glycerol in a single glycerin amount... glycerol-containing glycerin fat is a diglycerin fatty acid vinegar used in the present invention, which is a diglyceride of oil: fat - square = is, the body contains: glycerin fatty acid vinegar The content of the single vinegar in the 'by glycerol, the present day was determined by HPLC analysis using the above analysis conditions. Specifically, the corresponding peaks can be used to determine the peak area of each component of the test sample on the map, and the peak area can be determined by the knife count, and the content of the monoester body can be determined by the area percentage based on the measured. The di-glycans having a single-breast content of 5% or more as used in the present invention 320233 12 200913898 = 曰 (hereinafter referred to as the raw material of diglycerin (tetra) g_, the two-j series can be exemplified by: usually in glycerin Adding a small amount of acid catalyst, and heating it in an inert gas atmosphere such as nitrogen or carbon dioxide, and heating at a temperature above, and performing a polycondensation reaction, the z-thousacies polymerization degree is h5 to 2.4. (preferably, the average degree of polymerization is about 2.0), and the oil and the compound may be obtained by using glycidol (heart or epichlorohydrin as a raw material). Desalting, decolorization, etc. The right and the f Γ . .. In the middle of the month, the above diglycerin mixture is purified by a method known in itself, such as distillation or 5, 'jin method, etc., and is composed of 2 molecules of glycerin. Preferably, the content of the diglycerin is about 8% or more (preferably about 7% by weight or more, more preferably about 90% or more) of the highly digested diglycerin. The diglycerin used in the present invention is Fat t-acid used in the raw material of fatty acid Listed as a linear saturated fatty acid having a carbon number of 6 to 24 (for example, hexamethylene: It decanoic acid, lauric acid, myristic acid, grazing acid, stearic acid, tens of hexamic acid, etc.), unsaturated Fatty acid (such as palmitoleic acid, oleic acid, elaidic acid, argon oil, lin〇leiCaci, linoleic acid, sesame oil ^_ Preferred is arachidium nic acid (arachid〇nic add), ricinoleic acid aCid), condensed ricinoleic acid, etc., among which citric acid, lauric acid, meat, oleic acid, oleic acid, etc. are preferred. It is preferable to commercially obtain 70% or more of citric acid, lauric acid, myristic acid, or oleic acid, and it is preferable to use the same in the present invention. The commercially available fat 320233 13 200913898 acid, For example, the product name (1) NAA_122 (made by Nippon Oil Co., Ltd.), (2) L-cut c L-98 (made by Kao Corporation), (3) Myristic acid 98 (made by Miy〇shi Oil Co., Ltd.), (4) NAA-142 (Oyster Oil Company), (5) Lunac Μγ_98 (made by Kao Corporation), (6) Extra olein (made by Nippon Oil Co., Ltd.), (7) Limac 0-V (made by Kao Corporation), (8) Luna c Ο-P (manufactured by Kao Corporation). The outline of the preferred method for producing the diglycerin fatty acid ester used in the present invention is as follows. For example, a general reaction including a stirrer, a heating jacket, a barrier plate, and the like is provided. In the container, the molar ratio is about j: 〇8 to i: 12 (^ is preferably about 1.1). The diglycerin and the fatty acid are added, and sodium hydroxide is added as a catalyst and stirred and mixed under a nitrogen atmosphere. The water produced by the esterification reaction is removed to the outside of the system and heated at a predetermined temperature. The reaction temperature is usually in the range of about 180 to 260 C, preferably about 200 to 25 Torr. The scope of 〇. Further, the reaction pressure conditions are under reduced pressure or at normal pressure, and the reaction time is about 0.5 to 15 hours, preferably about 1 to 3 hours. As for the end point of the reaction, the acid value of the reaction mixture is generally determined to be about 12 or less as an index. The resulting reaction solution contains a mixture of unreacted fatty acid, unreacted diglycerin, diglycerin mono-fatty acid ester, diglycerin di-fatty acid ester, diglycerin tri-fatty acid ester, diglycerin tetra-fatty acid ester or the like. After the reaction is completed, the resulting reaction solution is cooled to about 120 ° C or higher and less than 180 (preferably about 13 Torr to 15 ° C), followed by the addition of an acid to neutralize the catalyst, preferably about 15 From minute to hour, when one of the unreacted glycerol is separated into the lower layer, it is removed to obtain a diglycerin fatty acid ester. Further, by using the diglycerin fatty acid ester, for example, using a falling film type molecular distillation apparatus or a centrifugal molecular distillation apparatus, etc., molecular steaming, 320233 14 200913898, using a column chromatography or liquid-liquid extraction (liquid) -liquid extraction) A diglycerin fatty acid ester containing about 5 % by weight or more (more preferably about 7 G % or more) of a single vinegar with respect to the whole can be obtained by purifying it by a known method. A diglyceride fatty acid ester containing 5% or more of a monoterpene body is commercially produced and sold, for example, p〇em Xie 〇〇 (product name, manufactured by Riken Vitamin Co., Ltd.), Poem DCM 00v ( The name of the product, the Riken vitamin formula, and the Poem DL 1〇〇 (product name, manufactured by Riken Vitamin Co., Ltd.), etc., in the present invention, these commercially available products can be used as the fatty acid ester having a single vinegar content of 5% or more. Other components of the glycerin The liquid composition for soft capsule filling of the present invention may contain, in addition to the above-mentioned edible oil, the oil-insoluble component, and the reaction sheet, as long as it is within the range of the effects of the present invention. A component other than the diglycerin fatty acid vinegar having a content of 50% or more of the vinegar and the vinegar, and the other components may be, for example, an antioxidant (for example, extracting fertility expectation, ascorbic acid palm 櫊酉夂 day, etc.). These other components may be used alone or in combination of two or more. The composition of the soft sac filling of the present invention is a liquid composition of the above-mentioned edible oil, which is made of the above-mentioned cooking oil, a poorly soluble oil component, and a reaction sheet. Glycerin and glycerin The mixture is produced by uniformly dispersing the components. When the liquid composition for soft capsule filling of the present invention contains a single-component content of 5 G% or more of diglycerin fatty acid S, it is possible to Edible fats and oils and poorly soluble components are used. 320233 15 200913898 • The reaction monoglyceride, distilled monoglyceride and the diglycerin fatty acid ester are mixed and stirred, and these components are uniformly dispersed and produced. Specifically, for example, The edible fats and oils, the reaction monoglyceride and the distilled monoglyceride, and the diglycerin fatty acid ester as needed are heated to about 60 to '90 ° C (preferably about 70 to 8 (TC ) and uniformly mixed and stirred, The composition of the present invention can be produced by cooling it to, for example, about 40 to 60 ° C, adding a poorly oil-soluble component, and uniformly mixing and mixing. Further, the reaction of monoglycerin Ss, steamed glycerol and glycerin The diglycerin fatty acid vinegar can be mixed, heated and melted in advance. The apparatus for mixing and stirring is not limited to the use of, for example, a biomixer, a homogenizer, an ancient mixer. Or high speed powder The composition of the liquid component of the soft capsule filling of the present invention is not particularly useful, for example, it is usually about 2 ^ = /〇, preferably about 25 to 90% by mass. When the content of the edible fats and oils in the present invention is at most 8% by mass, the oil-insoluble component is sufficiently dispersed in the edible oil 2, and the dispersion stability of the oil-insoluble component is also good. The oil quality in the mass% is preferably about; the amount of the oil insoluble in the present invention is 10 to 5 〇, and the poorly soluble oil component can be sufficiently dispersed in the above-mentioned range, and the edible oil is used. The oil insoluble components are divided into two parts: two:: In addition, because of the good virginity of the knife, the separation of oil-insoluble components does not occur in the soft gel 320233 16 200913898. Further, since the amount of the (oil-insoluble component) in the soft capsule produced by filling the liquid composition with the soft capsule is sufficient, when the soft capsule is ingested, the oil is sufficiently insoluble in the living body. The effect of the component (eg physiological activity, etc.). . . The content of the anti-glyceride in the liquid composition of the soft capsule filling of the present invention is not particularly limited, and is, for example, usually about 0.5 to 10,000 Å, preferably about 0.5 to 10% by mass. More preferably, it is about i to 8 mass%. When the content of the reaction monoglycerin in the present invention is within the above range, since the dispersion stability of the poorly oil-soluble component in the edible fat or oil is good, separation of the poorly soluble component of the oil does not occur in the soft capsule. . Further, since the amount of the active ingredient (oil-insoluble component) in the soft capsule is sufficient, when the soft capsule is ingested, the effect of the oil-insoluble component can be sufficiently exhibited in the living body. The content of the distilled monoglyceride in 100% by mass of the liquid composition for soft capsule filling of the present invention is not particularly limited, and is, for example, usually about 5 to 15 Å / 〇, and the car is preferably about 〇 5 to 1. 〇 Quality. /〇, preferably about 】 to 8 mass%. When the content of the distilled monoglyceride in the present invention is within the above range, since the dispersion stability of the poorly oil-soluble component in the edible fat or oil is good, separation of the poorly oil-soluble component does not occur in the soft capsule. Further, the amount of the active ingredient (oil-insoluble component) in the soft capsule is sufficient. Therefore, when the soft capsule is ingested, the effect of the oil-insoluble component can be sufficiently exhibited in the living body. When the liquid composition for filling a soft capsule of the present invention contains a diglycerin fatty acid ester having a monohydrate content of 50% or more, the composition is in a mass percentage of 320233 17 200913898. There is no particular limitation, and it is 0.05 to 1.5% by mass, preferably about 〇〇5 to i. It is usually about ο·1 to /% by mass. In the above-mentioned range of the diglycerin in the present invention, in the artificial gastric juice to be described later, in the case of 3 right and right, the oil-insoluble component in the artificial gastric juice is divided into two parts: the score = the oil insolubleness in the test body The dispersibility of the component is sufficient, that is, the amount of the active ingredient (oil-insoluble component) in the raw capsule is sufficient, and when the soft capsule is taken, the oil can be fully utilized in the living body, so the right-handed onion capsule is used. The effect of the wind knife. A soft capsule can be produced by filling a soft capsule obtained in such a manner with a liquid film containing gelatin as a main component according to a conventional method. The composition may be, for example, between two sheets of gelatin, and the liquid composition for filling the eight capsules as a content, and #胶胶囊. i. The soft dispersion method by mixing the ingot and the ingot method, by mixing and stirring the composition containing the edible fat, the oil-insoluble component, and the reaction monoglycerin=monoglycerin, the oil-insoluble component can be satisfactorily Dispersed in edible oils and fats. Thus, the other aspect of the present invention is also a dispersion in which the oil-insoluble component is dispersed in the edible fat or oil, and contains the edible fat, the oil-insoluble component, the reaction monoglycerin, and the monoglyceride. The composition is mixed and the steps of sandalwood mixing. Preferably, the composition of the diglycerin fatty acid vinegar having the edible oil, the hardly soluble component, the reaction of the monoglycerin, the distillation = glycerin, and the monohydrate content of 50% or more is mixed and stirred. 320233 18 200913898 Dispersion method of the present invention t 廄罝廿 姑 Gu - ) 艮 油 油 曰 曰 曰 曰 曰 曰 曰 曰 曰 曰 曰 曰 曰 曰 曰 曰 曰 曰 曰 曰 曰 曰 曰 曰 曰 曰 曰 曰 油 油 油 油 油 油 — — — —甘 ✓ From the day of the month, the purpose of the mountain, the best way to do it, the above-mentioned paragraph is filled with the liquid composition, the soft capsule is mixed and mixed: 3 The M-forms with these ingredients will be used to fill the liquid composition of the t-filled capsules, which will be used for oils, oils, insoluble octates, monoglycerides, other knives, early glycerides, and distillation. The method of mixing and stirring is the same as... Glycerin and vinegar are given. ^ > 'The same. Preferably, for example, the edible fats and oils, the reactive early glycerin from the sun, the sulphuric acid glyceride, and the diglycerin fatty acid ester having a body content of 50% or more or more are heated to a temperature of, for example, about 70 to 8 〇. . 〇 Evenly mix and mix the bowls of the sputum. Now cool the parts to a temperature of, for example, about 40 to 60 ° C. Add the oil-insoluble ingredients and mix them evenly and stir. (Embodiment) However, the present invention is not limited by the following examples, and the present invention is more specifically described by way of examples. Liquid composition for soft capsules - Method 1 - In the case of Example 1, a reaction glycerol was added to safflower salad oil (manufactured by Cargill Japan Co., Ltd.) (trade name: PGemB_2G(), monoglycerin g| 47%, made by Riken Vitamin Co., Ltd., 5.0 g and steamed crane monoglyceride (trade name: s-100's monoglycerin content of about 98% 'manufactured by Riken Vitamin Co., Ltd.) 5 々, heated to 80 C and stirred to dissolve. This solution was naturally cooled to 5 Torr. 〇, adding riboflavin (Rib〇flavin) (manufactured by Riken Vitamin Co., Ltd.) 〇3g and L-ascorbic acid (made by BASF Takeda Vitamin Co., Ltd.) 9 7g, and then using the scrambler 320233 19 200913898 • (Model: uitra-turrax T_25 basic, IKA Japan company purple) mixed and stirred for 10 minutes at 8 〇〇〇 rPm. The obtained dispersion liquid was subjected to vacuum defoaming treatment, and then cooled to room temperature to obtain a liquid composition for soft capsule filling of about 1 〇〇g (Example 1). * Example 2 The reaction monoglyceride (trade name: p〇emp_2〇〇, monoglyceride content: about 52%, manufactured by Riken Vitamin Co., Ltd.) was used. 5. 〇g was replaced by the reaction monoglyceride described in Example 5. In the same manner as in Example 1, except that the liquid composition for soft capsule filling (Example 2) was obtained. Example 3 Using distilled monoglyceride (trade name: p〇emp_1〇〇, monoglyceride content = 98% 'manufactured by Riken Vitamin Co., Ltd.) 5 〇g instead of the distilled glyceride described in Example 5 5. 〇g ' In the same manner as in Example 1, a liquid composition for soft capsule filling (Example 3) of about 100 g was obtained. Comparative Example 1 The same procedure as in Example 1 except that 5.0 g of the beeswax (trade name: deodorized purified beeswax high acid, manufactured by Cerarica Noda Co., Ltd.) was used instead of the reaction monoglyceride 5 〇g described in Example 1 This was carried out to obtain a liquid composition for filling a soft capsule of about 1 μg (Comparative Product 1). Comparative Example 2 The distillation monoglyceride (trade name: P〇em s_100, monoglyceride containing about 98%, manufactured by Riken Vitamin Co., Ltd.) was used instead of the reaction monoglyceride described in Example i. In the same manner as in Example 1, except that the monoglyceride was distilled in the same manner as in Example 1, a liquid composition for soft capsule filling of about 1 〇〇g was obtained. 320233 20 200913898 * (Compared to the car parent 2) 〇 Comparative Example 3 The reaction monoglyceride (trade name: PoemB 2 oxime, monoglyceride content: about 47%, manufactured by Riken Vitamin Co., Ltd.) was replaced by 1 gram of * reaction glycerol _ 5. 〇g and distillation A liquid composition (Comparative Product 3) for soft capsule filling of about (10) g was obtained in the same manner as in Example 1 except that the monoglyceride was used in the same manner as in Example 1. Comparative Example 4 A reaction monoglyceride (trade name: p〇em v 2 〇〇, monoglyceride content: about 50%, manufactured by Riken Vitamin Co., Ltd.) was used instead of the reaction described in the example of the monoglyceride 5.0 g & distillation. A liquid composition (Comparative Product 4) for soft capsule filling of about 1 μg was obtained in the same manner as in Example 1 except that the monoglyceride was 5 〇g. Comparative Example '5 Using a reaction monoglyceride (trade name: p〇em, monoglyceride containing about 52 / 〇, manufactured by Riken Vitamin Co., Ltd.) 1 〇〇 g instead of the example] described reaction monoglyceride 5. 〇g A liquid composition for soft capsule filling (Comparative Product 5) of about 1 μg was obtained in the same manner as in Example 1 except that the monoglyceride was distilled in an amount of 5 〇g. Comparative Example 6 A monoglyceride (trade name: p〇em p_1〇〇, a monoglyceride content of about 98%, manufactured by Riken Vitamin Co., Ltd.) was used instead of the reaction monoglyceride 5,0 g described in Example 使用. A liquid composition 320233 21 200913898 (Comparative Product 6) for soft capsule filling of about 1 〇〇g was obtained in the same manner as in Example 1 except that the monoglyceride was distilled in an amount of 5 〇g. The evaluation of the separation of the liquid composition for soft sac filling is carried out by adding the liquid composition of the soft capsule filling method (implementing m 1 to 3 and comparative products) to 6) prepared by the above method, respectively, in a centrifuge tube (capacity) A centrifuge (model: SL-05, manufactured by Sakuma Seisakusho Co., Ltd.) was centrifuged at 15 rpm (rpm) for 2 〇 minutes. Then, from the sample of the centrifuge tube, the sample was centrifuged, and the sample of the centrifuge tube was visually observed for the presence or absence of separation of oil (nuclear and L-ascorbic acid). The results are shown in the table [Table 1]

實施品1至3之任一者皆完全未發生油難溶性成分之 分離。因此’可知本發明之軟膠囊充填用液狀組成 Γ吏刚：卻，用㈣者(比較品1)具有同等之：雖 命性成》之力散狀性。另_方面，僅使μ鶴單: (比較例—2及6风僅使用反應單甘油醋者（比較例3至^發 生油難溶性成分之分離，相較於實施品為明顯 320233 22 200913898None of the products 1 to 3 was completely separated from the poorly soluble component. Therefore, it can be seen that the liquid composition for soft capsule filling of the present invention is the same as that of (4) (Comparative Product 1), which is equivalent to the force of the life. On the other hand, only the μ cranes are used: (Comparative examples—2 and 6 winds only use the reaction single-glycerin vinegar (comparative example 3 to ^ separation of oil-soluble components, compared with the implementation of the product is obvious 320233 22 200913898

I 貫施例4至9及比較例7至9 )用以製造軟膠囊充填用液狀組成物之原材料 )化紗拉油（Cargill Japan公司製） 2)核黃素（理研維生素公司製） )L-抗壤血酸（basf Japan公司製） 4) 反應單甘油酯（商品名：Poem B-200，單甘油酯含量 約47%，理研維生素公司製） 5) 反應單甘油酯（商品名：p〇em p_2〇〇，單甘油酯含量 約52% ’理研維生素公司製） )热顧單甘油酯（商品名：p〇em S-100，單甘油酯含量 約98% ’理研維生素公司製） 7) 蒸餾單甘油酯（商品名：poem P-ioo，單甘油酯含量 約98%，理研維生素公司製） 8) 二甘油脂肪酸酯（商品名：p〇em DM-100，單酯體含 量約81%，理研維生素公司製） 9) 二甘油脂肪酸酯（商品名：Poem DO-100V，單酯體含 量約88%，理研維生素公司製） 1〇)二甘油脂肪酸酯（商品名：poem DL-100，單酯體含 量約77%，理研維生素公司製） U)二甘油脂肪酸酯（商品名：poem J-2081V，單酯體含 量約38〇/〇，理研維生素公司製） 12)二甘油脂肪醆酯（商品名：poem 0-71-DE，單酯體含 量約38%，理研維生素公司製） 23 320233 200913898 13)蜜蠟（商品名：脫臭精製蜜蠟高酸，Cerarica野田公 司製） (2)原材料之調配組成 在實施例4至9及比較例7至9中，將用以製作軟膠 ‘ 囊充填用液狀組成物（實施品4至9及比較品7至9)的原材 • 料之調配組成顯示於表2。其中，實施品4至9係本發明 實施例4至9所製造之組成物，比較品7至9係相對於該 等實施例而於比較例7至9所製造之組成物。 [表2] 原材料 貫施品 比較品 4 5 6 7 8 9 7 8 9 1)紅花沙拉油 60.0 60.0 60.0 60.0 60.0 60.0 60.0 60.0 60,0 2)核黃素 7.0 7.0 7.0 7.0 7.0 7.0 7.0 7.0 7.0 3)L-抗壞血酸 25.0 25.0 25.0 25.0 25.0 25,0 25.0 25.0 25.0 4)反應單甘油酯 (Poem B-200) 3.6 — 3.6 3.6 3.6 3.6 7.6 一 — 5)反應單甘油酉旨 (Poem P-200) _ 3.6 一 — — — — — — 6)蒸館單.甘油酉旨 (Poem S-100) 4.0 4,0 一 4.0 4.0 4.0 — 7.6 4.0 7)蒸德單甘油酯 (Poem P-100) -'- — 4.0 8)二甘油脂肪酸酯 (Poem DM-100) 0.4 0.4 — — — 一 0.4 — — 9)二甘油脂肪酸酯 (Poem DO-100V) 一 — 0.4 — — 一 — 0.4 — 10)二甘油脂肪酸酯 (Poem DL-100) '一 — — 0.4 — — — — — 11)二甘油脂肪酸酯 (Poem J-2081V) — — — — 0.4 — -— — — 12)二甘油脂肪酸酯 (Poem 0-71-DE) 一 — — — 0.4 — — — 13)蜜蠟 一 —— — — — — — — 4.0 ※表中數值之單位為質量（g)。 24 320233 200913898 (3)製造方法 、依據表2所不之調配組成，製造軟膠囊充填用液狀組 成物。亦即，將反應單甘油醋、蒸館單甘油醋及/或二甘油 月曰肪馱S曰或蛍蠟加入紅花沙拉油中，將其加熱至80。〇並 |檀拌，使此等成分溶解於該沙拉油中。將此溶液於室溫下 ~ :至50C ’於其中添加核黃素（理研維生素公司製）及l_ 抗壞血酸（BASF Janan八=I. Example 4 to 9 and Comparative Examples 7 to 9) A raw material for producing a liquid composition for soft capsule filling, a sauer oil (manufactured by Cargill Japan Co., Ltd.) 2) riboflavin (manufactured by Riken Vitamin Co., Ltd.) L-anti-ascorbic acid (manufactured by basf Japan) 4) Reaction monoglyceride (trade name: Poem B-200, monoglyceride content: about 47%, manufactured by Riken Vitamin Co., Ltd.) 5) Reaction monoglyceride (trade name: P〇em p_2〇〇, the content of monoglyceride is about 52% 'manufactured by Riken Vitamin Co., Ltd.)) Heated monoglyceride (trade name: p〇em S-100, monoglyceride content is about 98%) 7) Distilled monoglyceride (trade name: poem P-ioo, monoglyceride content about 98%, made by Riken Vitamin Co., Ltd.) 8) Diglycerin fatty acid ester (trade name: p〇em DM-100, monoester content) About 81%, made by Riken Vitamin Co., Ltd.) 9) Diglycerin fatty acid ester (trade name: Poem DO-100V, monoester content about 88%, made by Riken Vitamin Co., Ltd.) 1〇) Diglycerin fatty acid ester (trade name: Poem DL-100, the content of monoester is about 77%, made by Riken Vitamin Co., Ltd.) U) Diglycerin fatty acid ester Name: poem J-2081V, monoester body content of about 38 〇 / 〇, made by Riken Vitamin Co., Ltd.) 12) Diglycerin fatty oxime ester (trade name: poem 0-71-DE, monoester body content of about 38%, Riken vitamin Company's) 23 320233 200913898 13) Beeswax (trade name: deodorized refined beeswax high acid, manufactured by Cerarica Noda Co., Ltd.) (2) Preparation of raw materials in Examples 4 to 9 and Comparative Examples 7 to 9 The composition of the raw materials for the preparation of the soft gel-filled liquid composition (Examples 4 to 9 and Comparative Products 7 to 9) is shown in Table 2. Among them, the articles 4 to 9 are the compositions produced in Examples 4 to 9 of the present invention, and the comparative products 7 to 9 are the compositions produced in Comparative Examples 7 to 9 with respect to the examples. [Table 2] Comparative raw materials for raw materials 4 5 6 7 8 9 7 8 9 1) Safflower salad oil 60.0 60.0 60.0 60.0 60.0 60.0 60.0 60.0 60,0 2) Riboflavin 7.0 7.0 7.0 7.0 7.0 7.0 7.0 7.0 7.0 3 L-ascorbic acid 25.0 25.0 25.0 25.0 25.0 25,0 25.0 25.0 25.0 4) Reaction monoglyceride (Poem B-200) 3.6 — 3.6 3.6 3.6 3.6 7.6 I—5) Reaction of monoglycerol (Poem P-200) _ 3.6 I — — — — — — 6) Steaming list. Glycerin (Poem S-100) 4.0 4,0 - 4.0 4.0 4.0 — 7.6 4.0 7) Steamed monoglyceride (Poem P-100) -'- — 4.0 8) Diglycerin fatty acid ester (Poem DM-100) 0.4 0.4 — — — a 0.4 — 9) diglycerin fatty acid ester (Poem DO-100V) one — 0.4 — — one — 0.4 — 10) diglycerol Fatty acid ester (Poem DL-100) 'I-0.4' — — — — 11) Diglycerin fatty acid ester (Poem J-2081V) — — — — 0.4 — — — — — 12) Diglycerin fatty acid ester ( Poem 0-71-DE) One — — — 0.4 — — — 13) Honey wax one — — — — — — — 4.0 ※ The unit of the numerical value in the table is mass (g). 24 320233 200913898 (3) Manufacturing method According to the composition of Table 2, a liquid composition for soft capsule filling is produced. That is, the reaction monoglycerin, steamed monoglycerin, and/or diglycerin, or samarium wax, are added to the safflower salad oil and heated to 80. 〇 | | Tan mix, so that these ingredients are dissolved in the salad oil. This solution was added at room temperature ~: to 50C' to which riboflavin (manufactured by Riken Vitamin Co., Ltd.) and l_ascorbic acid (BASF Janan eight =

Pan A司製）’再使用攪拌機（型號：Pan A system) 'Re-use mixer (model:

Ultra turrax T-25 basic，IKA Japan 公司製）以 8000rpm 混 、口及授拌1G》知。將所得之分散液予以真空脫泡處理後， 冷卻至室溫，而獲得約1〇〇g之軟膠囊充填用液狀組成物 (實施品4至9及比較品7至9)。 物之評估 對於以上述方法製作之軟膠囊充填用液狀組成物（實 施品4至9及i：卜齡口. 7 、. 一 次比&σ° 7至9)，分別實施下述之試驗。結果 示於表3 〇 (1) 油難溶性成分之分離之評估 〇將以上述方法製作之款膠囊充填用液狀組成物（實施 4至9及比較品7至9)分別各加人％於離心管（容量 制1均附栓塞）中’將其使用離心機（型號：sl_〇5，佐久 以乍所a司製）以迴轉數1500rpm離心20分鐘。然後， =離:機中取出離心f，對於離心管之試料，以目視觀察 、谷生成为（核更素及L-抗壞血酸）有無分離。 (2) 人工月液中之油難溶性成分之分散性評估 將幸人膠囊充填用液狀組成物（實施品4至9及比較品7 25 320233. 200913898 至9)lg及約36°C之人工胃液（以使鹽酸/氣化鈉/離子交換 水之質量比成為7/2/991之方式所調製者）99g放入200ml 容量玻璃製燒杯中，使用攪拌機（製品名：Three-One Moter，型號：BL-600，新東科學公司製，安裝5cm徑4 片葉片型攪拌翼1段）於約36°C之溫水浴中攪拌30分鐘， 使軟膠囊充填用液狀組成物分散於人工胃液中。將所得之 分散液以分析用濾紙No.2(直徑125mm，Advantech公司製） 自然過濾、，使殘留在該滤紙上之殘渔與滤液分離。計量稱 取所得之濾液l〇g於培養皿（直徑70mm，高度50mm)，在 100°C之培養箱（incubator)中熱風乾燥1小時後，測定殘留 於該培養皿上之乾燥物之質量。依據測定之乾燥物之質量 及下式，求得油難溶性成分之溶出率（％)。另外，對於將以 上述攪拌機進行攪拌之時間設為60分鐘者，亦實施同樣之 評估試驗，並求得溶出率（％)。 溶出率（％)= 乾燥物之質量（mg)xlO — 198(mg) : 320(mg) ；~~Ultra turrax T-25 basic, manufactured by IKA Japan, is known for mixing at 8000 rpm, mixing and mixing 1G. The resulting dispersion was subjected to vacuum defoaming treatment, and then cooled to room temperature to obtain a liquid composition for soft capsule filling of about 1 μg (Examples 4 to 9 and Comparative Products 7 to 9). Evaluation of the substance For the liquid composition for soft capsule filling prepared by the above method (Examples 4 to 9 and i: Bu Lingkou. 7 ,. Primary ratio & σ ° 7 to 9), the following tests were carried out, respectively. . The results are shown in Table 3. 〇(1) Evaluation of the separation of the poorly soluble components of the oil. The liquid compositions (Examples 4 to 9 and Comparative Products 7 to 9) of the capsule filling method prepared by the above method were each added in %. In the centrifuge tube (both of which is equipped with a plug), it was centrifuged for 20 minutes at a number of revolutions of 1500 rpm using a centrifuge (model: sl_〇5, Sakuji). Then, the centrifugation f was taken out from the machine, and the sample of the centrifuge tube was visually observed, and the formation of the grain (nuclearin and L-ascorbic acid) was separated. (2) Evaluation of dispersibility of oil-insoluble components in artificial liquids will be for the liquid composition of capsule filling (implementation products 4 to 9 and comparative products 7 25 320233. 200913898 to 9) lg and labor of about 36 ° C 99 g of gastric juice (manufactured in such a manner that the mass ratio of hydrochloric acid/sodium vaporized/ion-exchanged water is 7/2/991) is placed in a 200 ml-capacity glass beaker, and a blender is used (product name: Three-One Moter, model number) :BL-600, manufactured by Shinto Scientific Co., Ltd., equipped with a 5 cm diameter 4 blade type stirring wing 1), stirred in a warm water bath of about 36 ° C for 30 minutes to disperse the soft capsule filling liquid composition in artificial gastric juice. . The obtained dispersion liquid was naturally filtered with Analysis Paper No. 2 (diameter: 125 mm, manufactured by Advantech Co., Ltd.), and the residual fish remaining on the filter paper was separated from the filtrate. The obtained filtrate was weighed and weighed in a petri dish (diameter 70 mm, height 50 mm), and dried by hot air in an incubator at 100 ° C for 1 hour, and then the mass of the dried matter remaining on the petri dish was measured. The dissolution rate (%) of the poorly oil-soluble component was determined based on the measured mass of the dried product and the following formula. Further, the same evaluation test was carried out for setting the time for stirring with the above-mentioned agitator to 60 minutes, and the dissolution rate (%) was determined. Dissolution rate (%) = mass of dry matter (mg) xlO - 198 (mg): 320 (mg); ~~

xlOO 又，在上述式之數值中，「198(mg)」係相當於人工胃 液99g中所含有之氯化納之質量，「320(mg)」係相當於軟 膠囊充填用液狀組成物lg中所含有之油難溶性成分之質 量° 26 320233 200913898 [表3] 油難溶性成分 無分離 人工胃___率(％)XlOO Further, in the numerical value of the above formula, "198 (mg)" corresponds to the mass of sodium chloride contained in 99 g of artificial gastric juice, and "320 (mg)" corresponds to liquid composition for soft capsule filling lg The quality of the poorly soluble oil component contained in the product. 26 320233 200913898 [Table 3] The oil-insoluble component has no separation artificial stomach ___ rate (%)

由表3之結果可知，與 發生油難溶性成分之Λ “ 之任—者皆完全未 者（比較品9)，實施^相較於使用㈣作為分散劑 之溶出率係明顯上成分對於人工胃液 ^早甘料、但使用單自旨體含量並非為观以上之二甘油 :肪酸醋者（實施品8及9)，雖然未發生分離，但溶出率不 ，此外，未使用蒸餾單甘油醋或反應單甘油醋中之任一 =材料者（比較品7及8)皆會發生油難溶性成分之分離。 (產業上之可利用性） 曰本發明之軟膠囊充填用液狀組成物雖然不含有蜜蠟， =/、油難洛性成分之分散安定性亦良好，且在軟膠囊中不 :發生油難〆谷性成分之分離。再者，本發明之軟膠囊充填 液狀!且成物若含有單醋體含量5〇%以上之二甘油月旨肪酸 320233 27 200913898 礞 酯，則在生體内之油難溶性成 此，可在生體内充分發揮上之成因 所以:本發明之軟膠囊充:用液之狀== 衣以以油難溶性成分作為有效成分的軟膠囊。 【圖式簡單說明】 益 μ*、 【主要元件符號說明】 無 320233 28As can be seen from the results of Table 3, the dissolution rate of the oil-insoluble component, which is completely incomplete (Comparative Product 9), is significantly higher than that of the use of (4) as a dispersing agent. ^Immediately, but the use of the single-agent content is not the above two diglycerides: fatty acid vinegar (implementation products 8 and 9), although no separation, but the dissolution rate is not, in addition, the use of distilled monoglycerin Or the reaction of any of the monoglycerin vinegars = materials (Comparatives 7 and 8) may cause separation of the oil-insoluble components. (Industrial Applicability) 液 The liquid composition for soft capsule filling of the present invention is It does not contain beeswax, and the dispersion stability of the oil-soluble ingredients is also good, and it does not occur in soft capsules: separation of oil-soluble glutinous components occurs. Furthermore, the soft capsule of the present invention is filled with liquid! If the product contains a diglyceride having a single vinegar content of 5% or more and a fatty acid 320233 27 200913898 oxime ester, the oil in the living body is poorly soluble, and the cause can be fully utilized in the living body. Invented soft capsule filling: the shape of the liquid == clothing to make the oil difficult to dissolve As an active ingredient a soft capsule. [Brief Description of the drawings] Yi μ *, [REFERENCE SIGNS main components None 32,023,328

Claims (1)

卷 200913898 十、申請專利範園·· 1. 一種軟膠囊夯# 於食用油脂中之=組成物’係使油難溶性成分分散 及蒸顧單甘油3:作=’：特徵為：含有反應單甘油_ 安定劑。 為使該油難溶性成分分散用之分散 2· 2請專利範圍第W之軟膠囊充填㈣狀組成物，復 s有单醋體含量50%以上之二甘油脂肪酸醋。 320233 29 200913898 七、指定代表圖··本案無圖式 (一） 本案指定代表圖為：第（）圖。 (二) 本代表圖之元件符號簡單說明： 八、本案若有化學式時，請揭示最能顯示發明特徵的化學式： 本案無代表化學式 4 320233Volume 200913898 X. Applying for a patent Fan Garden·· 1. A kind of soft capsule 夯# in the edible oils and fats = the composition 'is the oil insoluble components dispersed and steamed into the monoglycerin 3: for = ': characteristic: containing the reaction sheet Glycerin _ stabilizer. In order to disperse the oil-insoluble component, it is used to disperse 2·2. The soft capsule of the patent range W is filled with a (four)-shaped composition, and the di-glycerin fatty acid vinegar having a single vinegar content of 50% or more is used. 320233 29 200913898 VII. Designation of the representative figure · This case has no schema (1) The representative representative of the case is: (). (2) A brief description of the symbol of the representative figure: 8. If there is a chemical formula in this case, please disclose the chemical formula that best shows the characteristics of the invention: This case does not represent the chemical formula 4 320233