TWI326600B - Use of genipin as skin marker pigment - Google Patents

Use of genipin as skin marker pigment Download PDF

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TWI326600B
TWI326600B TW96131566A TW96131566A TWI326600B TW I326600 B TWI326600 B TW I326600B TW 96131566 A TW96131566 A TW 96131566A TW 96131566 A TW96131566 A TW 96131566A TW I326600 B TWI326600 B TW I326600B
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skin
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genipin
dye
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1326600 •· , ·. 九、發明說明: 【發明所屬之技術領域】 本發明係關於檐子素(genipin)使用做為人體或動物皮 膚標記染料之新用途。本發明更進一步提供一種人體或動 物皮膚標記組成物,其包括梔子素為標記染料,及醫藥上 可接受之載劑或稀釋劑。 【先前技術】 梔子素(genipin)為去羥梔子苷(genip〇side)之水解產 物,存在茜草科植物槐子樹(Gardenia jasmin〇ides ELUS) 的果實中。在生物醫學方面, 目前已知梔子素具有:(1)做1326600 •··············································································· The invention still further provides a human or animal skin marking composition comprising scorpionin as a labeling dye, and a pharmaceutically acceptable carrier or diluent. [Prior Art] Genipin is a hydrolyzate of genip〇side, which is present in the fruit of Gardenia jasmin〇ides ELUS. In biomedicine, it is currently known that scorpion has: (1)

研究報告指出 胺基酸反應後會形成藍色色素,因此已有 梔子素由於其顏色持久度及靈敏度較優, 1326600 • I * t 故可用於取代茚三a 三酮(ninhydrin)做為指紋分析(fingerprint)The research report pointed out that the amino acid will form a blue pigment after the reaction. Therefore, due to its color durability and sensitivity, the scorpion has 1326600 • I * t, which can be used as a fingerprint instead of ninhydrin. Analysis (fingerprint)

Acta 2003, 480, 267-274.)Acta 2003, 480, 267-274.)

南亞已廣泛使用於食物染色。 患者(尤其指癌症患者)在進行定期檢驗及/或放射治 療期間,必需使用塗料標記出欲進行檢驗及/或放射治療之 區域或部位,目前各醫療院所普遍使用一般市售之油性標 記筆’例如習知的馬克筆或奇異筆來進行標定。 然而,習知的油性標記筆在身體上所做的記號,容易 在患者洗澡或擦拭時被去除或淡化,而造成辨識上的困 難,因此常為使標記能較長時間保留在身體上,往往必需 忍受無法清潔身體的不便,在夏曰炎熱的氣溫下尤其是一 項困擾。於是,本案發明人遂創先提出將梔子素應用於人 體或動物皮膚標記上。經本發明之實驗證明,以振子素作 為染料調配成的標§己組成物’能在身體皮膚上保留一段較 長的時間,且不因清洗或擦拭而被除掉,極具有產業利用 132,6600. 性’遂而完成本發明 【發明内容】 本七月目的及優點將部分描述於下,或可由描述中顯 而易見。 本發明目的為提供—種梔子素(genipin)使用做為人體 f動物皮膚標記染料之新用途。於本文令所記載之“皮膚 標記” ’並不限定於醫瘆太而,f ~r w 蜃方面亦可指為使染料能較長期 滯留在皮膚上之用途。例如, 應用於形妝、動物標記及 其他人體或動物辨識方面。 本發明另一目的為,提 捉供種用於人體或動物皮膚之 標記組成物’其包含梔 qG朵科,及醫藥上可接 之載劑或稀釋劑。其他於具體能 H ^ . 、心樣,本發明之標記組成物 可進-步包含額外的染料,以 體態樣,用於本發明標^ ^ 爲不。於-項項具 另一項且體1 ’、且勿之稀釋劑為油性溶劑。於 另項具體態樣,用於本發 性溶劑。 組成物之稀釋劑為酒精 本發明的其他特性 亏注將在下面詳細揭 例觀察後變得顯而易見。 苟丁 ”體貫% 7 1326600 【實施方式】 本發明將詳細描述特殊的具體實施例。這些具體實施 例經由發明解釋提供,並非意欲用以限制本發明。在發明 的範圍及精神内,本發明存在傾向於包括這些及其他變更 及變動。 %實施例1·振子素溶液於皮膚上之至色及掉色試驗 以lOinl酒精溶解l.Ug梔子素成為1〇%栀子素溶 液。取10%梔子素溶液稀釋成終濃度為7%、5%、2%及, 各自200ul ;亦取市售雄獅墨水200U1做為控制組。以tip 沾取各濃度並塗抹在手背上。於指定時間拍攝梔子素於: 膚上之呈色情形,並且以及比對梔子素溶液及市售墨水於 皮膚上之存在情形。結果示於圖1。 • 由第一圖之拍照記錄顯示,梔子素溶液塗抹於皮膚上 後12小時,即逐漸顯現出藍色,並且經過長達實驗期之第 十一天,仍然在皮膚上保留其可辨識之色度。反之市售 雄獅墨水雖然本身即具有顏色,但是在塗抹於皮膚上後第3 天,其原本的顏色已消退至幾乎無法辨識其標記位置並 且在第4天便已完全消逝。 132660.0 * · < » 1 $ 實施例2. 振子素配製成油性與酒精性標記組成物 ! 之體表著色性試驗 首先利用60%酒精配置成10%槐子素溶液。秤取1克梔 子素(\Vako’產品編號:078 — 03021)加入9ml之60%酒精, 至於37°C值溫水槽中反應約1 〇分鐘,待梔子素粉末溶解即 可’配好之溶液需避光冷藏。將所得之1 〇%梔子素溶液,以 酒精性墨水(雄獅,《分一染料、樹脂、溶齊",或油性墨 •水(雄獅,成分—染料、樹脂、溶劑)依下表所示稀釋, 而配製成不同濃度之標記組成物,所得標記組成物之最終 很度分別為〇% 、、2% 、5%及。 梔子~~~South Asia has been widely used for food dyeing. Patients (especially cancer patients) must use paint to mark the area or site to be tested and/or radiotherapy during regular testing and/or radiation therapy. Currently, commercially available oil-based markers are commonly used in hospitals. 'For example, a conventional marker or a singular pen is used for calibration. However, the mark made by the conventional oil-based marker pen on the body is easy to be removed or faded when the patient takes a bath or wipe, which causes difficulty in identification, and therefore often makes the mark remain on the body for a long time, often It is necessary to endure the inconvenience of being unable to clean the body, especially in the hot summer temperatures. Therefore, the inventor of the present invention proposed to apply scorpion scorpion to human or animal skin markers. The experiment of the invention proves that the standard composition prepared by using vibrin as a dye can be kept on the skin for a long period of time, and is not removed by washing or wiping, and has industrial utilization 132, 6600. The present invention will be described in part below, or may be apparent from the description. The object of the present invention is to provide a new use of genidin as a human skin f animal skin marking dye. The "skin mark" described in this document is not limited to the doctor's advice, and f ~r w 亦可 may also be used for the purpose of allowing the dye to remain on the skin for a longer period of time. For example, it is applied to makeup, animal marking and other human or animal identification. Another object of the present invention is to provide a marker composition for use in human or animal skin which comprises 栀qG, and a pharmaceutically acceptable carrier or diluent. Other than the specific energy H ^ . , the heart-shaped, the labeling composition of the present invention may further comprise an additional dye, in the form of a body, for use in the present invention. The other item has a body 1 ' and the diluent is an oily solvent. In another specific aspect, it is used in the present solvent. The diluent of the composition is alcohol. Other characteristics of the present invention The disadvantages will become apparent after the detailed disclosure below. The present invention will be described in detail with reference to the particular embodiments of the present invention, which are not intended to limit the scope of the invention. There are aptitudes to include these and other changes and variations. %Example 1 · The color and color fading of the vibrin solution on the skin is dissolved in lOinl alcohol to form a solution of 1% scorpionin. The hazelnut solution was diluted to a final concentration of 7%, 5%, 2%, and 200 ul each; and the commercially available lion ink 200U1 was also used as the control group. The concentrations were taken at the tip and applied to the back of the hand. The scorpion is photographed on the skin, and the presence of the scorpion solution and the commercially available ink on the skin. The results are shown in Figure 1. • The photo record of the first figure shows the scorpion 12 hours after the solution was applied to the skin, it gradually appeared blue, and after the eleventh day of the experimental period, it still retained its recognizable chromaticity on the skin. Otherwise, the commercially available lion ink itself With color However, on the third day after application to the skin, its original color has faded to almost no recognition of its marked position and has completely disappeared on the fourth day. 132660.0 * · < » 1 $ Example 2. Osmanthus preparation Oil-forming and alcohol-based marker composition! The body surface coloration test is firstly configured with 10% scorpion solution using 60% alcohol. 1 gram of scorpion (+Vako' product number: 078 — 03021) is added to 9ml. 60% alcohol, as for the reaction in a 37 °C warm water tank for about 1 , minutes, when the scorpion powder is dissolved, the solution should be kept in the dark. The resulting 〇% scorpion solution is alcoholic. Ink (Lion, "Dividing a dye, resin, melting", or oily ink • water (lion, ingredient - dye, resin, solvent) is diluted as shown in the table below, and is formulated into different concentrations of the mark The final degree of the resulting marker composition is 〇%, 2%, 5% and 栀~~~

度 素 60%酒精 墨水(ml)總體積 (ml)Degree 60% alcohol Ink (ml) total volume (ml)

點在皮膚上,之後 ’將收集到之相片 調配π成之標記組成物以毛細管 母天正常洗澡’並於固定時間地點照相 132660.0 I * · β 進行分析’以評估酒精性或 著程度及掉色現象。 結果: 油性標記組成物於皮膚上之附 如圖2所示,經過試驗後發現,油性標記組成物利用 毛、點於皮膚上會呈現擴散現象,酒精性標記組成物則 無此現象。結果,油性;I® W " 不°己j成物约擴散至原半徑的3倍。 在持久性方面’則是以油性標記組成物為較佳,即便是濃 度低如2%之標記組成物’在經過14天之後,仍然清晰可 見0 而圖係將每天收集到的相片利用影像軟體分析,其中 亦以市售標記筆(奇異筆)染料為比較組。由^ 2所示之 數值圖表發現,不論是本發明之標記組成物,或是一般市 售奇異筆墨水’皆隨著時間增加而顏色會慢慢褪掉,但是 本發明標記組成物之掉色情況較輕微,於第14天時仍有原 來約40%之顏色附著在身體表面上。 實施例3.本發明標記組成物(油性)於塗抹後在不 同時間沖洗之掉色試驗 如實施例1所述’配製得最終濃度為〗0%之(油性) 標記組成物。於受測自願者洗澡前4、6、8、1 〇小時,將 調配元成之標記組成物塗繪於其皮膚上,並於固定時間地 10 4 »Point on the skin, then 'paste the collected photo into a π-forming marker composition to take a normal bath in a capillary mother' and photograph 132660.0 I * · β at a fixed time to analyze 'to assess alcoholicity or degree and color loss . Results: The oily marker composition was attached to the skin. As shown in Fig. 2, it was found that the oily marker composition exhibited a diffusion phenomenon by using hair and spots on the skin, and the alcoholic marker composition did not. As a result, oily; I® W " does not spread about 3 times the original radius. In terms of durability, it is better to use an oil-based marker composition, even if the concentration of the marker composition as low as 2% is clearly visible after 14 days, and the image will be collected every day using the image software. For the analysis, a commercially available marker pen (singular pen) dye was also used as a comparison group. From the numerical graph shown in ^2, it is found that whether the marking composition of the present invention or the commercially available singular pen ink's color gradually fades with time, the coloring of the marking composition of the present invention It is mild, and on the 14th day, about 40% of the original color is attached to the body surface. Example 3. Color drop test of the marking composition (oily) of the present invention after rinsing at different times As described in Example 1, the composition was prepared to have a final concentration of 0% (oily) marking composition. 4, 6, 8 and 1 hour before the bath of the volunteers were tested, the labeled composition of Yuancheng was painted on the skin and fixed at a time of 10 4 »

A 點照相。將於各時間點收集到之相片以影像軟體進行分 折,以評枯染料於皮膚上之附著程度及掉色現象,亦可一 萍觀察與„平估本發明標記組成物對於皮膚之刺激性,及是 會否造成過敏現象。 結果: 如第四圖所示,本發明標記組成物塗抹於皮膚後10小 時’始進行洗澡之掉色情形最輕微,呈色效果亦最佳。即 便疋相同很度之標記組成物,隨著試劑停留於皮膚的時間 越短,也間接影響到後續的呈色時間。 無意受限於任何理論,梔子素已知為一種天然交聯 記:故推測其經塗覆於皮膚上後,會與表皮或真皮中之蛋 白貝產生父聯作用,而有利於其穩定存在皮膚上。故由 ;本發月‘记組成物塗抹於皮膚上後,需時間與皮膚反 ^ w反應效果尚未完成時便經過清潔劑沖洗,會將染料 之色素沖散,而降低存在皮膚表面上之色素含量,遂造成 色效果不佳。因此,本發明標記組成物塗抹後,應至少 半天後才可洗澡,以便維持其標記效果。X,梔子素原本 為無色,t與皮膚之蛋白質組成胺基酸結合後即顯現出藍 色(參見,實施例1所示之結果),因此為使能立即在皮膚 -貝示出‘ 5己位置,可於本發明皮膚標記組成物中,添加 額外的習知染料,再藉由振子素之作用,而使標記能更長A point photo. The photos collected at each time point are divided into image software to evaluate the degree of adhesion and fading of the dye on the skin, and the stimuli of the marking composition of the present invention can be evaluated. And whether it will cause allergies. Result: As shown in the fourth figure, the mark composition of the present invention is applied to the skin 10 hours after the start of the bath, the color drop is the slightest, and the color rendering effect is also the best. The labeling composition, as the reagent stays in the skin for a shorter period of time, also indirectly affects the subsequent coloring time. Unintentionally limited by any theory, scorpion is known as a natural cross-linking: it is presumed to be coated. After covering the skin, it will have a parental effect with the protein shell in the epidermis or dermis, which is beneficial to its stable presence on the skin. Therefore, after the composition of the hair on the skin is applied to the skin, it takes time and skin to reverse ^ w When the reaction effect is not completed, it is washed by the detergent, which will disperse the dye of the dye, and reduce the pigment content on the surface of the skin, and the color effect is poor. Therefore, the mark of the present invention After the composition is applied, it should be taken at least half a day before bathing in order to maintain its labeling effect. X, scorpionin is originally colorless, and t is blue when combined with the amino acid of the skin protein composition (see, Example 1) The result shown), therefore, in order to enable immediate display of the '5-position' in the skin-before, an additional conventional dye can be added to the skin-marking composition of the present invention, and the label can be made by the action of the vibrin. Can be longer

I3260UU 期穩定存在皮膚上。 表丁、合以上之實驗纟士 。,以梔子素(geniPin)做為人體或 動物皮膚標記之染料, 達彳優於習知或市售標記染料的 皮膚持久性,且經過沖法 後10天’仍可看到原本之標記位 置。再者,因為梔子藍色音 邑素本身即為一種安全的食用色素, ,且梔子素已知為一種無毒性天然交聯劑,故本發明之標 成物使用在皮膚上’亦具有不產生過敏及,或刺激性的 優點。The I3260UU period is stable on the skin. The experimental gentleman of the above and above. GeniPin is used as a dye for human or animal skin markings. It is superior to the skin durability of conventional or commercially available marking dyes, and the original marking position can still be seen 10 days after the punching. . Furthermore, since the blue scorpion is a safe food coloring, and the scorpion is known as a non-toxic natural crosslinking agent, the standard of the present invention is also used on the skin. Does not produce allergies and, or irritating advantages.

12 132660.0 • < * 【圖式簡單說明】 第一圖為顯示抱子素溶液(10%、7%、5% ' 2%與1%), 以及市售雄獅墨水(作為控制組),在塗覆至於皮膚上(以 tip點在皮膚上)後,於所指定時間點(第〇、1、2、2 5、 12 小時、1、2、3、4、5、6、7、8、9、10、U 及 12 天) 之呈色程度及掉色現象的照片。圖片由左至右為5牌(雄獅 墨水)、10%、7%、5%、2%及1%梔子素溶液。 第二圖為顯示本發明酒精性及油性標記組成物,在塗覆 至於皮膚上(以毛細管點在皮膚上)I,於所指定時間點 (第卜2、3、10及14天)之附著程度及掉色現象的照片。 第三圖係將每天收集到的相片利用影像軟體分析,以數 值會製得之®表。A為以油性標心成物進行試驗所得之結 果。B為以酒精性標記組成物進行試驗所得之結果。° 到的之附著程度及掉色現象 【主要元件符號說明】 進行;:圖列不本發明標記組成物塗抹於皮膚後1 〇小時於 進订洗冻,之後於所指定時間 J寺始 到的夕糾益如由上^ *占(第〇、6及Μ天)觀察 1312 132660.0 • < * [Simple description of the diagram] The first picture shows the boswell solution (10%, 7%, 5% ' 2% and 1%), and the commercially available lion ink (as the control group), After being applied to the skin (point on the skin with a tip), at the specified time point (〇, 1, 2, 2 5, 12 hours, 1, 2, 3, 4, 5, 6, 7, 8) , 9, 10, U, and 12 days) Photographs of the degree of coloration and discoloration. The picture is from left to right for 5 cards (lion ink), 10%, 7%, 5%, 2% and 1% scorpion solution. The second figure shows the adhesion of the alcoholic and oily marking compositions of the present invention to the skin (with capillary spots on the skin) I at the specified time points (days 2, 3, 10 and 14). Photograph of degree and discoloration. The third picture is a daily analysis of the photos collected by the image software using the image software. A is the result of testing with an oily target. B is the result of testing with an alcohol-labeled composition. ° Adhesion degree and fading phenomenon [Description of main component symbols]: The chart is not applied to the skin after 1 〇 hours of application, and after the designated time, the temple begins. Correction is as follows: ^ 占 (Dijon, 6 and Μ天) observation 13

Claims (1)

99年4月9曰修正版 、申請專利範園:胚£9 —種梔子素(genipin)使用做為人體或動物皮膚標記染料 之新用途。 —種用於人體或動物皮膚之標記組成物,其包含栀子素為 標記染料,及醫藥上可接受之載劑或稀釋劑。 根據申請專利範圍第2項之標記組成物,其進一步包含一 種適用於人體或動物皮膚之額外的染料。 根據申請專利範圍第2項之標記組成物,其中該稀釋劑為 適用於人體或動物皮膚之油性溶劑β. 根據申請專職㈣2項之標記組絲,其中該稀釋劑為 適用於人體或動物皮膚之酒精性溶劑。April 9, 1999 revised version, patent application garden: embryo £9 - genipin (genipin) used as a new use of human or animal skin marker dyes. A marker composition for use on human or animal skin comprising scorpionin as a marker dye and a pharmaceutically acceptable carrier or diluent. The marking composition according to item 2 of the patent application further comprises an additional dye suitable for use on human or animal skin. According to the marking composition of claim 2, wherein the diluent is an oily solvent suitable for human or animal skin. β. According to the application of the full-time (4) 2 item marking silk, wherein the diluent is suitable for human or animal skin. Alcoholic solvent.
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