TW531420B - Formulation studies with galactose injection - Google Patents
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531420 五、發明說明（1) 產業上之 利用 領域 本發明係一種安定性良好 之丰礼糖針劑注射液處方 背 景 作無論其物效 一二半乳糖 不同。肀 估肝臟功肖匕白、 年 J. Pharm. 法（galactose 乳糖的針劑注 常有限僅V ·〇 第4 6卷第1 〇 4 液之處方及安 針劑最適宜之 化劑與注射液 半乳糖和葡萄糖的化學結構非常類似 化學性質如溶解度、安定性都和葡萄糖 和葡萄糖之用途也大不相同。以半乳糖來J 研究論文已達百餘篇，如胡幼圃教授於 Sd·，第84卷第23卜235頁，以半乳糖單點 single-P〇lnt)能準確評估肝臟之功能。半 射液至今世界尚無，其安定性之研究也非 Bhargav 等人於 1 98 9 年^. j. H〇sp. pharm· -108頁，因此發明人乃針對半乳糖針劑注射 疋性做下深入之研究’以期望尋找出半乳糖 處方’選擇不同種類及濃度之緩衝液及抗氧 不同之酸鹼度值進行安定性試驗。 發明之目的 針對半乳糖針劑注射液，探討不同種類及濃度之緩/ 液’及抗氧化劑與不同之酸鹼度下，進行處方之 ^衝 驗。 女弋性試531420 V. Description of the invention (1) Industrial application Field The present invention is a formulation of Fenglitang injection injection with good stability. The background is different regardless of its effect. Estimated liver function Xiaobai, J. Pharm. Method (galactose injection of lactose is often limited injection only V · 〇 Volume 4 6 Volume 1 〇4 liquid prescription and ampule injection the most suitable chemical and galactose injection The chemical structure is very similar to that of glucose. Chemical properties such as solubility and stability are also very different from the uses of glucose and glucose. There have been more than 100 research papers on galactose, such as Professor Hu Youpu in Sd., Vol. 84, No. 23, p. 235, Gal-lactose single-point single-Pollnt) can accurately assess liver function. There is no semi-ejection solution in the world, and its stability research is not by Bhargav et al. 1989. ^. J. H〇sp. Pharm · -108 pages, so the inventor made the injection of galactose injection. In-depth research 'expecting to find a galactose prescription' choose different types and concentrations of buffer solutions and different pH values for antioxidants for stability tests. Purpose of the Invention For galactose injections, explore the different types and concentrations of slow / liquids', antioxidants, and different pH values to conduct prescription tests. Son-in-law sex test
531420 五、發明說明（2) 表例說明 表一 表二 表三 表四 表五 表六 表七 表八 處方卜1 0注射液顏色、酸鹼度、濃度變化 處方11-20注射液顏色、酸鹼度、濃度變化 處方2 1-30注射液顏色、酸鹼度、濃度變化 處方3 1-40注射液顏色、酸鹼度、濃度變化 處方4 1 - 5 0注射液顏色、酸鹼度、濃度變化 處方5 1 - 6 1注射液顏色、酸鹼度、濃度、吸光度變化 處方6 2 - 7 5注射液顏色、酸鹼度、濃度、吸光度變化 處方7 6 - 8 7注射液顏色、酸鹼度、濃度、吸光度變化531420 V. Description of the invention (2) Description of table examples Table 1 Table 2 Table 3 Table 4 Table 5 Table 6 Table 7 Table 8 Prescriptions 1 0 Injection color, pH, concentration change prescription 11-20 injection color, pH, concentration Change prescription 2 1-30 Injection color, pH, concentration change prescription 3 1-40 Injection color, pH, concentration change prescription 4 1-50 0 Injection color, pH, concentration change prescription 5 1-6 1 Injection color , PH, concentration, absorbance change prescription 6 2-7 5 Injection color, pH, concentration, absorbance change prescription 7 6-8 7 Injection color, pH, concentration, absorbance change
圖式說明 圖一 無抗氧化劑、無緩衝液半乳糖注射劑，其酸驗度與 時間之變化圖 a…處方51 b…處方52 c…處方53 圖Description of the Drawings Figure 1. Changes in acidity and time of galactose-free injections without antioxidants and buffers a… prescription 51 b… prescription 52 c… prescription 53
d…處方54 e…處方55 無緩衝液、添加抗氧化劑半乳糖注射劑，其酸驗度 _ 與時間之變化B1 _ a···處方56 b…處方57 c…處方58 d···處方59 e···處方60 f···處方61 0 , 0 1 Μ檸檬酸緩衝液、不同濃度硫酸氫鈉半乳糖注* 射劑，其酸鹼度與時間之變化圖 531420 五、發明說明（3) a…處方β 2 b ···處方β 3 c…處方64 d ···處方65 圖四〇· 01M檸檬酸緩衝液、不同濃度硫酸氫鈉半乳糖注 射劑，其酸驗度與時間之變化圖 a…處方66 b ···處方β7 c…處方68 d .··處方69 圖五0· 01M檸檬酸緩衝液、不同濃度硫酸氫鈉半乳糖注 射劑，其酸驗度與時間之變化圖 a…處方70 b ···處方71 c…處方72 d ···處方73 a…處方74 圖六〇· 〇 1 Μ三乙醇胺緩衝液、不同濃度硫酸氫鈉半乳糖 注射劑，其酸驗度與時間之變化圖 處方75 發明之詳細說明 本發明添加不同種類及 整成不同酸驗度之半乳糖針 良好之半乳糖針劑注射液處 )辰度之緩衝液，及抗氧化劑調 劑注射液，以安定性試驗評估 方。 配製注射液上，猶跑坐lrt ,，in％取+礼糖粉末添加緩衝液及抗氧化 片丨j ’均勻混合倒入第—刑Γ τ τ、 》_ 士 ^ ^(Type I)玻璃瓶内，立即取樣並 # 、 放入回壓蒸氣銷’以1 2 1 °C (1 · 2 kg/cm2)滅 囷15分鐘後取出，祐枷接 。 κ ^ 亚取樣。置於80 °C烘箱二週，其間每隔d… prescription 54 e… prescription 55 acid-free galactose injection with buffer solution, change in acidity _ change with time B1 _ a ... prescription 56 b ... prescription 57 c ... prescription 58 d ... prescription 59 e ... prescription 60 f ... prescription 61 0, 0 1 M citric acid buffer solution, galactose with different concentrations of sodium bisulfate injection * Injection, its change in pH and time Figure 531420 V. Description of the invention (3) a … Prescription β 2 b… prescription β 3 c… prescription 64 d… prescription 65 Figure 40. 01M citric acid buffer solution, sodium bisulfate galactose injections with different concentrations, change in acidity test and time a … Prescription 66 b… prescription β7 c… prescription 68 d… prescription 69 Figure 5: 01M citric acid buffer solution, sodium bisulfate galactose injections with different concentrations, change in acidity test and time a… prescription 70 b ... prescription 71 c ... prescription 72 d ... prescription 73 a ... prescription 74 Figure 60. 〇1 Μ triethanolamine buffer solution, different concentrations of sodium bisulfate galactose injection, changes in acidity and time Figure prescription 75 Detailed description of the invention The present invention adds different types of galactose needles with different acidity Good galactose injections) Chendu's buffer solution and antioxidant injections should be evaluated by stability test. On the preparation of the injection, I still run and sit lrt, in% to take + gift sugar powder, add buffer and antioxidant tablets 丨 j 'uniformly pour into the first — penalty Γ τ τ, ”_ ^ ^ (Type I) glass bottle Inside, immediately take a sample and put it into the back pressure steam pin, extinguish it at 1 2 1 ° C (1 · 2 kg / cm2) for 15 minutes, and take it out. κ ^ subsampling. Place in an 80 ° C oven for two weeks, during which
第7頁 531420 五、發明說明（4) 一週取樣一次。所得之檢品，須測量酸鹼度值及於284 nm 波長下測量吸光度值，並進行半乳糖濃度分析。 半乳糖含量為總量之1 %至5 〇 %，較佳含量狀態為總量 之4%或40% ’不添加或添加緩衝液量之0.001%〜5%，不添加 或添加抗氧化劑含量為總量之〇 · 〇 〇 1〜5 %。選用緩衝液與抗 氧化劑’添加以下含量可調配成適當之注射液處方；0 · 0 1 · Μ〜1 Μ亞硫酸氫鈉（s〇d i um b i su 1 f i te )，或維生素丙（· vitamin C)抗氧化劑，或選用〇· 〇 i M〜i μ檸檬酸緩衝液 (c i t ra te buf f er)、石粦酸緩衝液（ph〇Spha t e buf f er )、醋 1 S夂緩衝液（acetate buffer)、碳酸緩衝液（carbonate buffer)及一乙醇版緩衝液（triethanolamine buffer)五 種之一，調整酸驗度值為4.〇至9.〇。而添加〇·〇1%檸檬酸 緩衝液（dtrate bu f f e r )，〇 · 5 % 亞硫酸氫鈉（sod i um bisulfite)酸鹼度值為4.5獲得安定之注射液處方。 配方卜1 0為濃度4%且不含任何緩衝液之半乳糖注射液 ，方，進行安定性研究，所獲得之結果於表一，從表一可 知知，加入維生素丙為抗氧化劑時，會使注射液於放置8 0 C ί哀境-週後’即產生顏色之改變；而當加入亞硫酸氫鈉丨 為抗氧化劑且酸驗度值調整至4·5時，置於8『c冑境一週 後，無顏色之改變。 配方11—30為加入五絲丁㈡， 重不同緩衝液及不同抗氧化劑形Page 7 531420 V. Description of the invention (4) Sampling once a week. The obtained test article shall measure the pH value and the absorbance value at a wavelength of 284 nm, and analyze the galactose concentration. The galactose content is 1% to 50% of the total amount, and the preferred content state is 4% or 40% of the total amount. 'No added or added buffer solution is 0.001% to 5%, and no added or added antioxidant content is The total amount of 〇.001 ~ 5%. Buffers and antioxidants can be selected to add the following content to formulate an appropriate injection formulation; 0 · 0 1 · Μ ~ 1 Μ sodium bisulfite (sodium bi su 1 fi te), or vitamin C (· vitamin C) Antioxidant, or 〇i 〇i M ~ i μ citric acid buffer solution (cit ra te buf fer), lysine acid buffer solution (ph〇Spha te buf fer er), vinegar 1 S 夂 buffer solution ( acetate buffer), carbonate buffer (carbonate buffer) and a triethanolamine buffer (triethanolamine buffer) one of five types, adjust the acidity test value of 4.0 to 9.0. Adding 0.01% citrate buffer (dtrate bu f f r r), 0.5% sodium bisulfite (sod i um bisulfite) pH value of 4.5 to obtain a stable injection formulation. Formulation 10 is a galactose injection with a concentration of 4% and no buffer solution. The stability study is performed. The results obtained are shown in Table 1. It can be seen from Table 1 that when vitamin C is added as an antioxidant, Make the injection solution change in color after placing it at 80 ° C, and when the sodium bisulfite is added as an antioxidant and the acidity value is adjusted to 4.5, put it in 8 "c 胄" After one week in the environment, there is no change in color. Formulas 11-30 are made by adding quincetin, different buffers and different antioxidants.
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A 五、發明說明（5) 成濃唐兔zM/ a ， x 棒樣酸二;主射w，五種不同緩衝液依， 及三乙醇：；二酸，液、醋酸緩衝液、碳酸㈣ 亞硫酸氫納及唯广兩種不同抗氧化劑為 究，所獲得之/ gim，進行安定性研 化劑的配；；表〉表三。對於加入維生素丙抗氧 於Λ λ-在一週後均產生顏色變化，安定性不好。對 ' 亞硫酸氫鈉抗氧化劑之配方，無論在任何一種緩衝' =於酸驗度值7·35或4·5環境下，顏色均無變化。但酸 双又值7· 35比酸鹼度值4· 5溶液，儲存二週後酸鹼度值變/ 化較明顯。配方15於80艽環境下儲存二週後，半乳糖濃度 有明頒改變’顯然安定性有問題。而配方1 4及2 6於8 〇。〇 環境下儲存二週後，有沉澱產生，而其共同之特性為於酸、 性且具有維生素丙存在下發生，故可能之原因為維生素丙 於酸性環境下，易與檸檬酸缓衝液及碳酸緩衝液產生物理 化學變化，而生成沉澱。觀察處方1-30以半乳糖於酸驗度 值4 · 5之檸檬酸緩衝液且含亞硫酸氫鈉抗氧化劑條件下， 以酸驗度值及顏色變化而言’有較佳之安定性。 處方31 -50為加入五種不同緩衝液及不同抗氧化劑形 成濃度為4%之半乳糖注射液處方’五種不同缓衝液依次為 檸檬酸緩衝液、填酸缓衝液、醋酸緩衝液、碳酸緩衝液及 三乙醇胺缓衝液濃度均為1 M，兩種不同抗氧化劑為亞硫酸 氫鈉及維生素丙濃度增為〇· 5M ’進行安定性研究，所獲得 之結果於表四、表五。對於加入0 · 5 Μ維生素丙抗氧化劑的 531420 五、發明說明（6) 處方，在一週後均產生顏色變化，安定性不好。對於加入 〇 5 Μ亞疏酸鼠納抗氧化劑之處方’當緩衝液濃度升高至 · 時，於—週後’注射液處方31、35、43及49有顏色 變化。與處方1 - 3 0相比較，處方3 1 - 5 0於8 0 t：二週後半乳 糖濃度變化量較大。除此，1 Μ碳酸緩衝液於酸鹼度值 7.35及三乙醇胺緩衝液於酸驗度值4.5下，儲存一週 後均發生顏色變化’因此，可得知當亞硫酸氫鈉與緩衝液-濃度一起增加時，處方之安定性會降低。於處方3 1 - 5 Q可. 歸納出除三乙醇胺緩衝液外，其餘四種高濃度緩衝液加入， 高濃度亞硫酸氫鈉抗氧化劑於酸驗度值4 · 5環境下，均較 安定，但以醋酸緩衝液及檸檬酸緩衝液環境下更佳。 1 - 气 表六、圖一、二中，處方5 1-55為半乳糖注射液不含 任何缓衝液及抗氧化劑於酸鹼度值5 · 0 2至8 · 5 2進行安定性 所得之結果’從表六中可知，在較低酸鹼度值下，滅菌前， 後酸鹼度值改變較少。除此，並根據USP XX I I版對於葡萄 糖（Dextrose)注射液主要分解產物羥基甲基呋喃 hydroxymethyl-furfural)與其它相關物質含量規定，在 葡萄糖濃度1 / 2 5 0 g/ml於284nm波長，以水為空白對照液 餐 下’吸光度值不超過〇 · 2 5。於本發明，配製半乳糖注射液船 濃度4%時，相對應吸光度值應不超過2· 5。以此為指標得 知，處方5 2滅菌前後酸鹼度值變化最小，也具有較低之吸· 光度值變化。因此，可知在低酸鹼度值環境下，安定性較％ 佳。處方56-61為探討加入不同濃度抗氧化劑之影響，由A. V. Description of the invention (5) Concentrated Tang rabbit zM / a, x stick-like acid II; main shot w, five different buffer solutions, and triethanol: diacid, liquid, acetate buffer solution, tritium carbonate Sodium bisulfate and Weiguang are the two different antioxidants. The obtained / gim is used to formulate stability research chemicals; Table> Table III. For the addition of Vitamin C and Antioxidant to λ λ-, the color changes after one week, and the stability is not good. Regarding the formulation of sodium bisulfite antioxidant, no matter what kind of buffering it is, there is no change in color under the acid test value of 7.35 or 4.5. However, the pH value of 7.35 is higher than the pH value of 4.5 solution, and the pH value changes / changes more obviously after two weeks of storage. After Formulation 15 was stored at 80 ° C for two weeks, there was a clear change in galactose concentration ’apparently there was a problem with stability. Formulas 14 and 26 are at 80. 〇 After two weeks of storage in the environment, precipitation occurs, and its common characteristics are that it occurs in the presence of acid, vitamin C, and vitamin C. Therefore, the possible reason is that vitamin C is easy to interact with citrate buffer and carbonic acid in an acidic environment. The buffer solution undergoes a physico-chemical change and a precipitate is formed. Observe that the formula 1-30 has better stability in terms of acidity value and color change under the condition of galactose in a citric acid buffer solution with an acidity value of 4 · 5 and containing sodium bisulfite antioxidant. Formulas 31 to 50 are galactose injections with five different buffers and different antioxidants to form a concentration of 4%. The five different buffers are citric acid buffer, acid filling buffer, acetic acid buffer, and carbonate buffer. The concentration of the solution and triethanolamine buffer solution were both 1 M, and the stability of two different antioxidants was sodium bisulfite and vitamin C increased to 0.5M '. The results obtained are shown in Tables 4 and 5. For the 531420 supplemented with 0.5 M vitamin C antioxidant 5. Description of the invention (6) The prescription produced a color change after one week, and the stability was not good. Regarding the prescription of the addition of the 05 M succinic acid zona antioxidant, when the concentration of the buffer solution was increased to ·, there was a color change in the formulations 31, 35, 43 and 49 after one week. Compared with prescriptions 1-3 0, prescriptions 3 1-50 at 80 t: the galactose concentration changes significantly after two weeks. In addition, 1 M carbonate buffer solution at pH 7.35 and triethanolamine buffer solution at pH 4.5, color changes after one week of storage '. Therefore, it can be seen that when sodium bisulfite increases with the buffer-concentration As a result, the stability of the prescription decreases. In the prescription 3 1-5 Q can be summarized. In addition to the triethanolamine buffer, the other four high-concentration buffers are added. High-concentration sodium bisulfite antioxidants are more stable under the acid test value of 4.5. But it is better to use acetic acid buffer and citric acid buffer. 1-Gas Table VI, Figures I and II, prescription 5 1-55 is galactose injection without any buffer and antioxidant at pH value 5 · 0 2 to 8 · 5 2 Results obtained from the stability of 'from As can be seen in Table 6, at lower pH values, the pH values changed less before and after sterilization. In addition, according to the USP XX II version for the content of hydroxymethyl-furfural and other related substances of the main decomposition product of glucose (Dextrose) injection, at a glucose concentration of 1/250 g / ml at a wavelength of 284nm, The water's blank control's meal's absorbance value does not exceed 0.25. In the present invention, when the concentration of the galactose injection solution is 4%, the corresponding absorbance value should not exceed 2.5. Using this as an index, we know that the change in pH value before and after sterilization of Formula 5 2 is the smallest, and it also has a low change in absorbance and luminosity value. Therefore, it can be seen that the stability is better than% in a low pH environment. Formulation 56-61 is to explore the effect of adding different concentrations of antioxidants.
第10頁 531420 五、發明說明（7)Page 10 531420 V. Description of the invention (7)
表六可知當抗氧化劑濃度增高時，滅菌前後酸鹼度值及吸 光度值變化也最小，且加入抗氧化劑比不加抗氧化劑安定 性較好。處方62-65為半乳糖於0·01Μ檸檬酸緩衝液下、，調 整注射液不同酸驗度值及亞硫酸氫鈉抗氧化劑濃度，所得 結果列於表七，從表中可知，在酸性環境及丨％亞硫酸氫鈉 抗氧化劑）辰度下，滅菌前後酸鹼度值及吸光度值變化最小 。處方6 6 -6 9為半乳糖於〇.〇 1Μ磷酸緩衝液下，調整注射液 不同酸鹼度值及亞硫酸氫鈉抗氧化劑濃度，所得結果列於 表七，從表中I知，在酸性環境及丨％亞硫酸氫鈉^氧化劑 濃度下，滅菌前後酸鹼度值及吸光度值變化最小，安定性 較佳。處方70-73為半乳糖於0·01Μ醋酸緩衝液下，調整注 射液同酸驗度值及亞硫酸氫鈉抗氧化劑濃度，所得結果於 1%亞硫酸氫鈉抗氧化劑濃度下，滅菌前後酸鹼度值及吸光 度值變化較小’安定性較佳。處方74_75為半乳糖於〇.〇ιμ 二乙％胺緩衝液下，調整注射液不同酸鹼度值及亞硫酸氫 鈉^ =化劑濃度，發現於1%亞硫酸氫鈉抗氧化劑濃度下， 滅菌前後酸鹼度值及吸光度值變化較小，安定二較二。 ，處方卜75中，根據酸驗度（ρΗ)變化最小及溶液顏色 受化较少，選擇最理想之處方檸檬酸緩衝液為理相模式（ model system)。並將半乳糖（GaUct〇se)濃度提升“至 進仃研究。處方分別為76 —87，所得結果如下.由表八可知 =水環境下，半乳糖濃度提高時，溶液之黃顏：也隨之 加/米；在酿性爐捲祕炫你、、点ΠΓ . 、 531420 五、發明說明（8) " "一^ --- 鈉，滅菌前後對酸鹼度（pH)影響不大，但當亞硫酸氫鈉* 度大於0.5%時，注射液顏色較無變化，也可得到最小之吸 光度值變化；而在鹼性擰檬酸緩衝液下，無論加入亞硫酽 濃度多寡，8 0 C下儲存—週後，注射液之顏色均明顯 實施例1 在注射液處方配製上，首先稱取半乳糖粉末後，加入 所需濃度之緩衝液及抗氧化劑，均勻混合倒入第一型（f Type I)玻璃瓶内，立即取樣並予以封口，放入高壓蒸氣 銷’以121 C( 1.2 kg/cm2)滅菌η分鐘後取出，並取樣。 置於80°C烘箱二週，其間每隔一週取樣一次。所得之檢品 ，須測量酸鹼度值及於284 nm波長下測量吸光度值，並進 行半乳糖濃度分析。 實施例2 - 11Table 6 shows that when the concentration of antioxidants is increased, the changes in pH and absorbance values before and after sterilization are also the smallest, and the stability of adding antioxidants is better than that without antioxidants. Formulations 62-65 are galactose in 0.01M citric acid buffer solution, and adjust the different acid test values and the concentration of sodium bisulfite antioxidants in the injection. The results are shown in Table 7. And 丨% sodium bisulfite antioxidant), the changes in pH and absorbance values before and after sterilization are the smallest. Formula 6 6 -6 9 is galactose in 0.01M phosphate buffer solution, adjust the pH value of the injection solution and the concentration of sodium bisulfite antioxidant, the results are shown in Table VII, from the table I know that in an acidic environment Under the concentration of 丨% sodium bisulfite and oxidant, the changes in pH value and absorbance value before and after sterilization are the smallest, and the stability is better. Prescription 70-73 is galactose in a 0.01 M acetic acid buffer solution, adjusting the pH value of the injection and the sodium bisulfite antioxidant concentration. The results are obtained at 1% sodium bisulfite antioxidant concentration, pH before and after sterilization The values and absorbance values change less, and the stability is better. Prescription 74_75 is galactose in 〇〇μμ diethylamine buffer solution, adjust the pH value of injection and sodium bisulfite ^ = chemical agent concentration, found at 1% sodium bisulfite antioxidant concentration, before and after sterilization The pH value and absorbance value changed little, and the stability was two to two. According to Formula 75, according to the minimum change in acidity test (ρΗ) and the solution color is less affected, the most ideal square citric acid buffer solution is selected as the model system. And to increase the galactose (GaUctose) concentration into the study. The prescriptions were 76-87, and the results are as follows. From Table 8 it can be seen that when the galactose concentration increases in water, the yellow color of the solution: Add / m; in the brewing furnace roll secret, you point ΠΓ., 531420 V. Description of the invention (8) " " a ^ --- Sodium, the pH before and after sterilization has little effect, but When the sodium bisulfite * degree is greater than 0.5%, there is no change in the color of the injection solution, and the smallest change in absorbance can also be obtained; while in alkaline citric acid buffer solution, no matter how much thionite concentration is added, 8 0 C After storage—weeks, the color of the injection solution is obvious. Example 1 In formulating the injection solution, first weigh the galactose powder, add the required concentration of buffer and antioxidant, and mix evenly into the first type (f Type I) In a glass bottle, immediately take a sample and seal it, put it in a high-pressure steam pin, sterilize it at 121 C (1.2 kg / cm2) for η minutes, and take it out. Place it in an 80 ° C oven for two weeks, every other week. Take a sample once. The obtained sample must be measured at pH and at 284 nm. Length measured absorbance values, and thus the concentration of galactose-line analysis Example 2 - 11
比照實施例1，將半乳糖濃度維持4%，抗氧化劑選用 0.5%調整酸鹼度值為7.35製成處方i。而抗氧化劑選用 0. 5%、0. 1% 亞硫酸氫鈉（s〇dium bisulf he)之一種，或〇. 5%、、〇·丨％維生素丙（vitamin C)之—種，分別調整酸鹼度 值為7.35或4.5形成處方2〜iq。Comparing to Example 1, the concentration of galactose was maintained at 4%, and the antioxidant was adjusted to a pH of 7.35 using 0.5% to prepare a prescription i. The antioxidant is selected from 0.5%, 0.1% sodium bisulfite, or 0.5%, 0.00% vitamin C, and adjusted separately. A pH value of 7.35 or 4.5 forms a prescription 2 ~ iq.
第12頁 531420 五、發明說明（9) 12-31 實施例Page 12 531420 V. Description of the invention (9) 12-31 Examples
比照實施例1，將半乳糖濃度維持4%，抗氧化劑選用 0.1%亞疏酸氫納’或0.1%維生素丙，選用0·01%五種緩衝 液’如檸檬酸緩衝液（citrate buffer )、磷酸緩衝液 (phosphate buffer)、醋酸緩衝液（acetate buffer)、 三乙醇胺缓衝液（triethanolamine buffer)及石炭酸缓 衝液（carbonate buffer)之一種，分別調整酸鹼度值 為7·35或4·5形成處方11〜30，測量吸光度值，並進行半 實施例3 2 - 5 1 比照實施例1，將半乳糖濃度維持4%，抗氧化劑選用 0 · 5 %亞硫酸氫納，或〇 · 5 %維生素丙，選用1 %檸檬酸緩衝 液、磷酸緩衝液、醋酸缓衝液、碳酸緩衝液及三乙醇胺緩 衝液五種之一，分別調整酸鹼度值為7·35或4·5形成處方 3 1〜5 0，測量吸光度值，並進行半乳糖濃度分析。Comparing to Example 1, the galactose concentration was maintained at 4%, and the antioxidant was selected from 0.1% sodium bisulfite or 0.1% vitamin C, and 0.01% five buffer solutions such as citrate buffer (citrate buffer), One of phosphate buffer, acetate buffer, triethanolamine buffer, and carbonate buffer. Adjust the pH value to 7.35 or 4.5 to form prescription 11. ～ 30, measure the absorbance value, and perform half of Example 3 2-5 1 Compared with Example 1, maintain the galactose concentration at 4%, and choose 0.5% sodium bisulfite or 0.5% vitamin C as the antioxidant. Select one of five kinds of 1% citric acid buffer, phosphate buffer, acetate buffer, carbonate buffer, and triethanolamine buffer, and adjust the pH value to 7.35 or 4 · 5 to form prescription 3 1 ~ 50, measure Absorbance value and analysis of galactose concentration.
實施例5 2 - 5 7 在注射液處方配製上，首先稱取半乳糖粉末後，不含 任何緩衝液及抗氧化劑，調整酸鹼度值於5 · q 2至8 · 5 2形成 處方5 1〜5 5 °均勻混合倒入Type I玻璃瓶内立即取樣並予Example 5 2-5 7 In formulating injection solutions, first weigh galactose powder without any buffer and antioxidant, and adjust pH value to 5 · q 2 to 8 · 5 2 to form prescription 5 1 ~ 5 5 ° homogeneously mixed and poured into a Type I glass bottle
第13頁 531420Page 13 531420
以封口 ，放入高壓蒸氣鍋，以1 2 1 °c ( 1 · 2 kg/Cm2) * 分鐘後取出，並取樣。置於8 0 °C烘箱二週，其間々/Y5菌1 5 取樣一次。所得之檢品，根據USP XXI I版斟认# (Dextrose) 注射液主要分解產物羥基甲 | π夫喃（ 5-hydroxymethyl -furfural)與其它相關物質含量規— 在葡萄糖濃度1/250 g/ml於284 nm波長，以水為* ^句白對日召 液下，測量吸光度值，並進行半乳糖濃度分析。 … 實施例5 8 - 6 4Sealed, put into a high pressure steam cooker, take out at 1 2 1 ° c (1 · 2 kg / Cm2) * minutes, and take a sample. Place in an oven at 80 ° C for two weeks, during which time 々 / Y5 bacteria are sampled once. The obtained test product is based on USP XXI I version ## Dextrose. The main decomposition product of hydroxymethyl | 5-hydroxymethyl-furfural and other related substances content specification-at glucose concentration of 1/250 g / ml Under the wavelength of 284 nm, water was used to measure the absorbance value under the Japanese dialysate solution, and the galactose concentration was analyzed. … Examples 5 8-6 4
比照實施例52-57，將半乳糖濃度維持4%，抗氧化^ 選用ο · ο 1 % 、ο · 1 %、1 %亞硫酸氫納’或偏亞石危酸 <气納7 ( sodium metabi sul f i te)之一，分另丨"周整酸驗度值為5 或4 · 4 8形成處方5 6〜6 1，測量吸光度值，並進行半乳糖、'農 度分析。 實施例6 5 - 7 9 比照實施例5 2 - 5 7，將半乳糖濃度維持4%，抗氧化劑 | 選用0 · 0 1 %、0 · 1 %、1 %亞硫酸氫納，選用〇 · 〇 1 %檸樣酸、緩❿ 衝液、_酸緩衝液、醋酸緩衝液、碳酸缓衝液及三乙醇胺 緩衝液五種之一，分別調整酸鹼度值為7· 42或4. 32形成· 處方6 2〜7 5，測量吸光度值，並進行半乳糖濃度分析。 ·Comparing to Examples 52-57, the galactose concentration was maintained at 4%, and the antioxidant ^ was selected from ο · ο 1%, ο · 1%, 1% sodium bisulfite 'or metasulphite dangerous acid < air sodium 7 (sodium metabi sul fi te), divided into "quotation of weekly acid test value of 5 or 4 · 4 8 to form a prescription 5 6 ~ 61 1, measure the absorbance value, and perform galactose, 'agronomic analysis. Example 6 5-7 9 Compared with Examples 5 2-5 7, the galactose concentration was maintained at 4%. Antioxidant | Choose 0. 0 1%, 0. 1%, 1% sodium bisulfite, choose 〇. 〇 1% citrate-like acid, slow buffer solution, _acid buffer, acetate buffer, carbonate buffer and triethanolamine buffer. Adjust the pH value to 7. 42 or 4. 32. Formulation 6 2 ~ 7 5. Measure the absorbance value and analyze the galactose concentration. ·
第14頁 531420Page 531 420
第15頁 531420 五、發明說明（12) 表一Page 15 531420 V. Description of the invention (12) Table 1
Formulation 1 2 3 4 5 6 7 8 9 10 Cone. Gal.(% ) 4 4 4 4 4 4 4 4 4 4 Water(ml) 100 100 100 100 100 100 100 100 100 100 Sol. pH 7.35 7.35 4.5 4.5 7.35 7.35 4.5 4.5 7.35 4.5 Bisulfite(M) 0.5 0.5 0.1 0.1 Vit. C(M) 0.5 0.5 0.1 0.1 -週後顏色 氺氺 ***** 氺氺氺氺 氺氺 氺氺氺 氺氺氺 氺 * 二週後pH 7.11 6.56 1.69 5.44 4.50 6.02 3.04 5.91 2.92 3.72 滅菌前濃度(％ ) 2.082 2.853 滅菌後濃度(％ ) 2.216 2.549 一週後濃度(％ ) 2.365 2.430 二週後濃度(％ ) 1.620 2.252Formulation 1 2 3 4 5 6 7 8 9 10 Cone. Gal. (%) 4 4 4 4 4 4 4 4 4 4 Water (ml) 100 100 100 100 100 100 100 100 100 100 Sol. PH 7.35 7.35 4.5 4.5 7.35 7.35 4.5 4.5 7.35 4.5 Bisulfite (M) 0.5 0.5 0.1 0.1 Vit. C (M) 0.5 0.5 0.1 0.1-week after color 氺 氺 ***** 氺 氺 氺 氺 氺 氺 氺 氺 氺 氺 氺 氺 氺 * 2 weeks Post-pH 7.11 6.56 1.69 5.44 4.50 6.02 3.04 5.91 2.92 3.72 Concentration before sterilization (%) 2.082 2.853 Concentration after sterilization (%) 2.216 2.549 Concentration after one week (%) 2.365 2.430 Concentration after two weeks (%) 1.620 2.252
* :代表顏色深淺，％愈多顏色愈深*: Represents the color shade, the more the% the darker the color
第16頁 531420 五、發明說明（13)Page 16 531420 V. Description of the invention (13)
Formulation 11 12 13 14 15 16 17 18 19 20 Cone. Gal.(% ) 4 4 4 4 4 4 4 4 4 4 Citrate(M) 0.01 0.01 0.01 0.01 Phosphate(M) 0.01 0.01 0.01 0.01 Acetate(M) 0.01 0.01 Carbonate(M) Triethanolamine(M) pH 7.35 7.35 4.5 4.5 7.35 7.35 4.5 4.5 7.35 7.35 Bisulfite (M) 0.1 0.1 0.1 0.1 0.1 Vit. C (M) 0.1 0.1 0.1 0.1 0.1 一週後顏色 氺氺氺 氺氺氺氺 氺氺 氺氺 氺氺 二週後pH 4.38 3.68 3.22 3.53 3.42 2,92 3.17 2.90 3.73 2.86 沉澱 + 滅菌前濃度(％ ) 2.788 2.519 2.498 2.635 2.198 滅菌後濃度(％ ) 2.221 2.348 2.305 2.944 2.377 一週後濃度(％ ) 1.999 2.641 2.053 2.233 2.334 二週後濃度(％ ) 2.341 2.475 1.947 2.775 3.164 * :代表顏色深淺，愈多顏色愈深；+ :代表沉澱量多寡 531420 五、發明說明（14) 表三Formulation 11 12 13 14 15 16 17 18 19 20 Cone. Gal. (%) 4 4 4 4 4 4 4 4 4 4 Citrate (M) 0.01 0.01 0.01 0.01 Phosphate (M) 0.01 0.01 0.01 0.01 Acetate (M) 0.01 0.01 Carbonate (M) Triethanolamine (M) pH 7.35 7.35 4.5 4.5 7.35 7.35 4.5 4.5 7.35 7.35 Bisulfite (M) 0.1 0.1 0.1 0.1 0.1 Vit. C (M) 0.1 0.1 0.1 0.1 0.1 Color after one week 氺 氺 氺 氺 氺 氺 氺 氺氺 氺 氺 氺 氺 pH after two weeks 4.38 3.68 3.22 3.53 3.42 2,92 3.17 2.90 3.73 2.86 Precipitation + concentration before sterilization (%) 2.788 2.519 2.498 2.635 2.198 Concentration after sterilization (%) 2.221 2.348 2.305 2.944 2.377 Concentration after one week (% ) 1.999 2.641 2.053 2.233 2.334 Concentration (%) after two weeks 2.341 2.475 1.947 2.775 3.164 *: Represents the color depth, the more the color becomes darker; +: Represents the amount of precipitation 531420 V. Description of the invention (14) Table 3
Formulation 21 22 23 24 25 26 27 28 29 30 Cone. Gal.(% ) 4 4 4 4 4 4 4 4 4 4 Citrate(M) Phosphate(M) Acetate(M) 0.01 0.01 Carbonate(M) 0.01 0.01 0.01 0.01 Triethanolamine(M) 0.01 0.01 0.01 0.01 pH 4.5 4.5 7.35 7.35 4.5 4.5 7.35 7.35 4.5 4.5 Bisulfite (M) 0.1 0.1 0.1 0.1 0.1 Vit. C (M) 0.1 0.1 0.1 0.1 0.1 一週後顏色 氺氺 氺氺氺 氺氺氺 氺氺氺 氺氺氺 二週後pH 3.54 2.67 4.00 3.08 2.94 2.54 3.38 2.62 3.12 2.44 沉澱 + 滅菌前濃度<7〇) 2.502 2.436 3.128 2.671 2.212 滅菌後濃度(％ ) 2.693 2.848 3.027 3.134 2.970 一週後濃度(％ ) 2.019 2.533 2.610 2.537 2.595 二週後濃度(％ ) 3.012 2.640 2.716 2.633 2.781 第18頁 531420 五、發明說明（15)Formulation 21 22 23 24 25 26 27 28 29 30 Cone. Gal. (%) 4 4 4 4 4 4 4 4 4 4 4 Citrate (M) Phosphate (M) Acetate (M) 0.01 0.01 Carbonate (M) 0.01 0.01 0.01 0.01 Triethanolamine (M) 0.01 0.01 0.01 0.01 pH 4.5 4.5 7.35 7.35 4.5 4.5 7.35 7.35 4.5 4.5 Bisulfite (M) 0.1 0.1 0.1 0.1 0.1 Vit. C (M) 0.1 0.1 0.1 0.1 0.1 Color after one week 氺 氺 氺 氺 氺 氺 氺 氺氺 氺 氺 氺 氺 氺 After two weeks, pH 3.54 2.67 4.00 3.08 2.94 2.54 3.38 2.62 3.12 2.44 Precipitation + concentration before sterilization <7〇) 2.502 2.436 3.128 2.671 2.212 Concentration after sterilization (%) 2.693 2.848 3.027 3.134 2.970 Concentration after one week ( %) 2.019 2.533 2.610 2.537 2.595 Concentration after two weeks (%) 3.012 2.640 2.716 2.633 2.781 Page 18 531420 V. Description of the invention (15)
表四Table four
Formulation 31 32 33 34 35 36 37 38 39 40 Cone. Gal.(% ) 4 4 4 4 4 4 4 4 4 4 Citrate (Μ) 1 1 1 1 Phosphate (Μ) 1 1 1 1 Acetate (Μ) 1 1 Carbonate (Μ) Triethanolamine(M) pH 7.35 7.35 4.5 4.5 7.35 7.35 4.5 4.5 7.35 7.35 Bisulfite (Μ) 0.5 0.5 0.5 0.5 0.5 Vit. C (Μ) 0.5 0.5 0.5 0.5 0.5 一週後顏色 氺 ***** ***** 氺 ***** 氺氺氺氺 二週後pH 5.84 5.48 4.48 4.41 6.15 5.70 3.76 3.50 5.54 5.23 沉澱 + 滅菌前濃度(％ ) 2.476 2.427 2.410 滅菌後濃度(％ ) 1.392 2.190 1.716 一週後濃度(％ ) 1.208 2.177 1.471 二週後濃度(％ ) 0.700 1.873 0.798 :代表顏色深淺，％愈多顏色愈深；+ :代表沉殿量多寡 第19頁 531420 五、發明說明（16) 表五Formulation 31 32 33 34 35 36 37 38 39 40 Cone. Gal. (%) 4 4 4 4 4 4 4 4 4 4 Citrate (Μ) 1 1 1 1 Phosphate (Μ) 1 1 1 1 Acetate (Μ) 1 1 Carbonate (Μ) Triethanolamine (M) pH 7.35 7.35 4.5 4.5 7.35 7.35 4.5 4.5 7.35 7.35 Bisulfite (Μ) 0.5 0.5 0.5 0.5 0.5 Vit. C (Μ) 0.5 0.5 0.5 0.5 0.5 Color after one week 氺 ***** ** *** 氺 ***** pH pH after two weeks 5.84 5.48 4.48 4.41 6.15 5.70 3.76 3.50 5.54 5.23 Precipitation + concentration before sterilization (%) 2.476 2.427 2.410 concentration after sterilization (%) 1.392 2.190 1.716 concentration after one week (%) 1.208 2.177 1.471 Concentration after two weeks (%) 0.700 1.873 0.798: represents the color shade, the more% the color becomes darker; +: represents the amount of Shen Dian page 531420 5. Description of the invention (16) Table 5
Formulation 41 42 43 44 45 46 47 48 49 50 Cone. Gal.(% ) 4 4 4 4 4 4 4 4 4 4 Citrate (Μ) Phosphate (Μ) Acetate (Μ) 1 1 Carbonate (Μ) 1 1 1 1 Triethanolamine(M) 1 1 1 1 pH 4.5 4.5 7.35 7.35 4.5 4.5 7.35 7.35 4.5 4.5 Bisulfite (M) 0.5 0.5 0.5 0.5 0.5 Vit. C (M) 0.5 0.5 0.5 0.5 0.5 一週後顏色改變 ***** 氺氺 ***** ***** ***氺 氺 * 氺 * * * 二週後pH 4.32 4.11 6.94 6.74 4.84 1.78 5.97 4.28 1.68 1.78 沉澱 + + + 滅菌前濃度<7〇) 3.013 2.501 2.279 滅菌後濃度(％ ) 2.677 2.089 1.962 一週後濃度(％ ) 2.061 1.604 1.152 二週後濃度(％ ) 1.992 0,926 0.653 * :代表顏色深淺，％愈多顏色愈深；+ :代表沉®量多寡 531420 五、發明說明（17) 表 /\ Formulation 51 52 53 54 55 56 57 58 59 60 61 Cone· Gal.(% ) 4 4 4 4 4 4 4 4 4 4 4 Bisulfite(% ) 0.01 0.1 1 Metabisulfite(% ) 0.01 0.1 1 滅菌前pH 6.44 5.02 7.01 8.52 7.69 5.93 5.45 4.48 5.65 5.67 4.53 滅菌後pH 3.86 4.5 3.98 3.98 3.89 3.20 2.63 3.04 3.49 2.52 2.57 二週顏色改變 氺氺 氺 氺木 氺氺 氺氺 氺 氺 滅菌前吸光度値 0.022 0.027 0.016 0.030 0.024 0.013 0.007 0.020 0.019 0.006 0.023 滅菌後吸光度値 0.040 0.039 0.034 0.050 0.036 0.046 0.019 0.039 0.058 0.024 0.132 第一週吸光度値 0.065 0.346 0.386 0.452 0.450 0.355 0.110 0.104 0.362 0.128 0.227 第二週吸光度値 1.107 0.624 0.719 0.827 1.157 0.612 0.207 0.107 0.566 0.347 0.198 滅菌前濃度(％ ) 100 100 100 100 滅菌後濃度(％ ) 80.8 88.5 88.7 112.1 一週後濃度(％ ) 112.2 69.1 93.9 90.9 二週後濃度(％ ) 97.7 83.1 98.0 59.0 拒絕理由 顏色 顏色 顏色 顏色 顏色 顏色 pH pH 顏色 pH pH :代表顏色深淺愈多_色愈深；吸光度値測定：USP XXII p.408，4% Dextrose 溶液所含5-HMF應不超過2.5爲合格 ifFormulation 41 42 43 44 45 46 47 48 49 50 Cone. Gal. (%) 4 4 4 4 4 4 4 4 4 4 Citrate (Μ) Phosphate (Μ) Acetate (Μ) 1 1 Carbonate (Μ) 1 1 1 1 Triethanolamine (M) 1 1 1 1 pH 4.5 4.5 7.35 7.35 4.5 4.5 7.35 7.35 4.5 4.5 Bisulfite (M) 0.5 0.5 0.5 0.5 0.5 Vit. C (M) 0.5 0.5 0.5 0.5 0.5 Color change after one week ***** 氺 氺***** ***** *** 氺 氺 * 氺 * * * Two weeks later pH 4.32 4.11 6.94 6.74 4.84 1.78 5.97 4.28 1.68 1.78 Precipitation + + + Concentration before sterilization < 7〇) 3.013 2.501 2.279 Sterilization Post-concentration (%) 2.677 2.089 1.962 Concentration after one week (%) 2.061 1.604 1.152 Concentration after two weeks (%) 1.992 0,926 0.653 *: Represents the lightness and darkness of the color, the more the color becomes, the darker the color; +: Represents the amount of Shen® 531420 Description of the invention (17) Table / Formula 51 52 53 54 55 56 57 58 59 60 61 Cone · Gal. (%) 4 4 4 4 4 4 4 4 4 4 4 Bisulfite (%) 0.01 0.1 1 Metabisulfite (%) 0.01 0.1 1 Before sterilization pH 6.44 5.02 7.01 8.52 7.69 5.93 5.45 4.48 5.65 5.67 4.53 pH after sterilization 3.86 4.5 3.98 3.98 3.89 3.20 2.63 3.04 3.49 2.52 2.57 Two-week color change The absorbance of cypress wood 氺 氺 氺 氺 before sterilization 値 0.022 0.027 0.016 0.030 0.024 0.013 0.007 0.020 0.019 0.006 0.023 Absorbance after sterilization 値 0.040 0.039 0.034 0.050 0.036 0.046 0.019 0.039 0.058 0.024 0.132 Absorbance in the first week 値 0.065 0.346 0.386 0.452 0.450 0.355 0.110 0.104 0.362 0.128 0.227 Absorbance in the second week 値 1.107 0.624 0.719 0.827 1.157 0.612 0.207 0.107 0.566 0.347 0.198 Before sterilization Concentration (%) 100 100 100 100 Concentration (%) after sterilization 80.8 88.5 88.7 112.1 Concentration (%) after one week 112.2 69.1 93.9 90.9 Concentration (%) after two weeks 97.7 83.1 98.0 59.0 Reason for rejection Color Color Color Color Color pH pH pH Color pH pH: stands for the more and more darker the color _ the darker the color; the absorbance 値 measurement: USP XXII p.408, 5-HMF contained in 4% Dextrose solution should not exceed 2.5 to be qualified if
IIIISIIIIS
第21頁 531420 五、發明說明（18)Page 21 531420 V. Description of the invention (18)
拒絕理由 二週後濃度(％) 一週後濃度(％ ) 滅菌後濃度(％ ) 滅菌前濃度(％ ) 第二週吸光度値 第一週吸光度値 滅菌後吸光度値 滅菌前吸光度値 顏色改變 滅菌後pH 滅菌前pH Bisulfite(% ) Cone. Gal.(% ) Formulation H g o ΕΓ 3 i. > s B CD 2 s o 3 CD 顏色 2.501 1.710 0.660 0.017 冰木木 4.86 7.38 0.01 0.01 On to 濃度 67.5 79.4 80.9 〇 0.290 0.288 0.114 0.017 4.64 6.09 0.01 〇\ LO 吸光度 74.0 〇〇 to 1—^ -0 〇 2.282 0.136 0.023 0.013 3.59 4.47 0.01 0.01 73.9 93.7 76.0 t—^ 〇 0.060 0.036 0.017 0.026 3.58 4.32 0.01 G\ 顏色 2.501 2.366 0.745 0.024 * * * 4.16 7.19 0.01 0.01 〇\ 〇\ T5 102.1 131.9 116.9 ο 0.234 0.195 0.146 0.021 3.59 5.85 - 0.01 顏色 0.604 0.344 0.058 0.014 * 3.42 4.36 0.01 0.01 Os oo 157.2 97.5 108.4 ο 0.092 0.086 0.026 0.014 3.06 4.45 h—* 0.01 On Ό 顏色 0.840 0.357 0.066 0.015 氺氺氺 4.77 6.45 0.01 0.01 86.4 78.6 73.3 ο 0.047 0.029 0.018 0.011 3.64 5.40 0.01 h—* 顏色 0.544 0.289 0.052 0.014 * * 3.90 4.32 0.01 0.01 fo 89.0 87.7 96.5 h—^ o 0.083 0.065 0.021 0.017 3.14 4.35 »—A 0.01 顏色 1.707 0.491 0.038 0.013 氺氺氺 4.22 7.42 0.01 0.01 87.8 85.0 93.7 o 0.072 0.050 0.026 0.013 3.28 5.58 0.01Reason for rejection Concentration after two weeks (%) Concentration after one week (%) Concentration after sterilization (%) Concentration before sterilization (%) Absorbance in the second week 吸 absorbance in the first week 吸 absorbance after sterilization 値 absorbance before sterilization 値 color change pH after sterilization Before sterilization pH Bisulfite (%) Cone. Gal. (%) Formulation H go ΕΓ 3 i. ≫ s B CD 2 so 3 CD Color 2.501 1.710 0.660 0.017 Icewood 4.86 7.38 0.01 0.01 On to concentration 67.5 79.4 80.9 〇0.290 0.288 0.114 0.017 4.64 6.09 0.01 〇 LO absorbance 74.0 〇〇to 1— ^ -0 〇2.282 0.136 0.023 0.013 3.59 4.47 0.01 0.01 73.9 93.7 76.0 t— ^ 〇0.060 0.036 0.017 0.026 3.58 4.32 0.01 G \ color 2.501 2.366 0.745 0.024 * * * 4.16 7.19 0.01 0.01 〇 \ 〇 \ T5 102.1 131.9 116.9 ο 0.234 0.195 0.146 0.021 3.59 5.85-0.01 Color 0.604 0.344 0.058 0.014 * 3.42 4.36 0.01 0.01 Os oo 157.2 97.5 108.4 ο 0.092 0.086 0.026 0.014 3.06 4.45 h— * 0.01 On Ό Color 0.840 0.357 0.066 0.015 氺 氺 氺 4.77 6.45 0.01 0.01 86. 4 78.6 73.3 ο 0.047 0.029 0.018 0.011 3.64 5.40 0.01 h— * color 0.544 0.289 0.052 0.014 * * 3.90 4.32 0.01 0.01 fo 89.0 87.7 96.5 h— ^ o 0.083 0.065 0.021 0.017 3.14 4.35 »—A 0.01 color 1.707 0.491 0.038 0.013 氺 氺氺 4.22 7.42 0.01 0.01 87.8 85.0 93.7 o 0.072 0.050 0.026 0.013 3.28 5.58 0.01
第22頁 531420 五、發明說明（19) --ii - - 顏法砘pf簦陆 husp XXII ρ.408 Μ% Dextrose 磙漭^ni>5-HMF ϋ->1饀餡 2.5ΜΦ 菡 拒絕理由 第二週吸光度値 第一週吸光度値 滅菌後吸光度値 滅菌前吸光度値 一週顏色改變 第二週後pH 第一週後pH 滅菌候pH 滅菌前pH Bisulfite(% ) Q r-f- 3 a H CD* i 2- p- 3 1. ο ? Cone. Gal. Formulation 顏色 3.647 1.370 0.219 0.201 * k) 3.59 4.70 3.98 ο 〇 顏色 丨5.352 1.572 0.627 0.184 氺氺氺 3.67 4.33 6.78 : 7.24 _ 1 0.01 0.01 顏色 50.74 13.30 1.810 0.083 * * 4.40 5.01 8.47 8.49 Η—^ 0.01 00 0.204 0.147 0.063 0.047 3.61 3.70 4.29 4.31 Η—* 0.01 'Ο 1顏色 13.28 5.808 0.259 0.167 氺氺氺 4.22 4.57 ! 7.78 7.86 0.05 0.01 g 顏色 1.781 0.690 0.220 0.164 * 4.01 4.30 4.33 4.47 ! 0.05 0.01 00 !顏色 21.76 4.142 0.269 0.173 氺木氺 4.16 4.69 7.30 丨 7.87 0.025 o.oi 1 00 to 顏色 4.890 1.885 0.196 0.169 * 4.11 4.17 4.52 ! 4.48 0.025 0.01 00 LO !顏色 10.95 3.218 0.223 0.186 氺氺氺 4.29 4.76 6.85 7.22 0.01 0.01 QO 顏色 3.581 0.961 0.221 0.178 * 4.13 4.34 4.53 4.49 0.01 0.01 00 LT\ 顏色 60.72 23.42 1.208 0.112 *** 4.11 4.45 8.29 8.29 ο 0.01 00 G\ 0.294 0.175 0.090 0.062 3.62 4.00 4.52 4.50 ο Lh 0.01 00 <1 第23頁Page 22 531420 V. Description of the invention (19) --ii--Yan Fa 砘 pf 簦 Lu husp XXII ρ.408 Μ% Dextrose 磙 漭 ^ ni > 5-HMF ϋ- > 1 饀 stuffing 2.5ΜΦ 菡 Rejection reason Absorbance in the second week 吸 Absorbance in the first week 后 Absorbance after sterilization 値 Absorbance before sterilization 颜色 Color change in one week pH in the second week after pH pH in the first week after sterilization pH Bisulfite (%) Q rf- 3 a H CD * i 2- p- 3 1. ο? Cone. Gal. Formulation Color 3.647 1.370 0.219 0.201 * k) 3.59 4.70 3.98 ο 〇 Color 丨 5.352 1.572 0.627 0.184 氺 氺 氺 3.67 4.33 6.78: 7.24 _ 1 0.01 0.01 Color 50.74 13.30 1.810 0.083 * * 4.40 5.01 8.47 8.49 Η- ^ 0.01 00 0.204 0.147 0.063 0.047 3.61 3.70 4.29 4.31 Η- * 0.01 '〇 1 color 13.28 5.808 0.259 0.167 氺 氺 氺 4.22 4.57! 7.78 7.86 0.05 0.01 g color 1.781 0.690 0.220 0.164 * 4.01 4.30 4.33 4.47! 0.05 0.01 00! Color 21.76 4.142 0.269 0.173 Tochigi 氺 4.16 4.69 7.30 丨 7.87 0.025 o.oi 1 00 to Color 4.890 1.885 0.196 0.169 * 4.11 4.17 4.52! 4.48 0.025 0.01 00 LO! Yan Color 10.95 3.218 0.223 0.186 氺 氺 氺 4.29 4.76 6.85 7.22 0.01 0.01 QO Color 3.581 0.961 0.221 0.178 * 4.13 4.34 4.53 4.49 0.01 0.01 00 LT \ Color 60.72 23.42 1.208 0.112 *** 4.11 4.45 8.29 8.29 ο 0.01 00 G \ 0.294 0.175 0.090 0.062 3.62 4.00 4.52 4.50 ο Lh 0.01 00 < 1 page 23
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| Publication number | Priority date | Publication date | Assignee | Title |
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| TWI691719B (en) * | 2018-10-19 | 2020-04-21 | 香港商阿瓦隆 海帕波有限公司 | A system of rapid quantitative detection galactose and use thereof |
| CN111068074A (en) * | 2018-10-19 | 2020-04-28 | 阿瓦隆·海帕波有限公司 | Galactose oral composition and application thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TWI691719B (en) * | 2018-10-19 | 2020-04-21 | 香港商阿瓦隆 海帕波有限公司 | A system of rapid quantitative detection galactose and use thereof |
| CN111068074A (en) * | 2018-10-19 | 2020-04-28 | 阿瓦隆·海帕波有限公司 | Galactose oral composition and application thereof |
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