1259772 玖、發明說明： 【發明所屬之技術領域】 本發明相關於一種藥用級之檸檬酸鐵及其製法、含有 #檬酸鐵之醫藥組成物和含有藥用級檸檬酸鐵之腊食營養 ΌΌ ° 【先前技術】 美國專利案5，7 5 3，7 0 6中揭露棒樣酸鐵化合物可用於 治療腎臟衰竭之病患及容易罹患磷酸過剩之患者上，捧樣 酉文鐵化合物可控制填酸新陳代謝而減少填酸滯留體内且控 制所造成之代謝酸過多中毒，依據說明書記載，擰檬酸鐵 購買自Sigma-Aldrich公司，於產品目錄中記載其包含 16·5% - 18.5%參價鐵，分子式為，分子量為 244.9，為具有透明鱗片而呈深紅色或淡棕色的粉末，具有 微鐵味，其係可緩慢溶解且可完全溶解於水中，並易溶解 於熱水中，但會因年久而減低溶解度（The inda， 12th 版，第 4068 頁）。 ，因此在製造上有其困難度，造成出產的 樂用級物質必須有一定的組成成分，因此 並無法達到此要求。 然而，雖然檸檬酸鐵於 於#檬酸鐵是鐵及檸檬酸之 (The Merck Index，12th 版， 所包括的鐵及檸檬酸具有不 市場上可經由採購而得，但由 結合物，而其組成比例不明確 第4068頁），表示檸檬酸鐵中 同比率且包含不同數目結晶水 品質不一，然而 市售的檸檬酸鐵 1259772 由於分子式固定才符合藥物管制法令及藥品主管機關 上市審查要求，有鑑於此，藥用級的產品需具有固定分= 組成，因此製備出具有固定分子組成的檸檬酸鐵係為一有 待解決之問題。 【發明内容】 本發明之目的是應用製造檸檬酸鐵方法，供給新穎藥 用級檸檬酸鐵，該方法是利用固態-固態反應而生產藥用級 檸檬酸鐵，該藥用級檸檬酸鐵包含一定的分子組成# — 之結晶水。 藥用級檸檬酸鐵可用於缺鐵性的治療，用以提供動物 體鐵質，如腎衰竭的病患容易引起鐵的缺乏，可用藥用級 檸檬酸鐵治療，另藥用級檸檬酸鐵亦可用於控制碟酸的代 謝以及代謝酸過多中毒，尤其是用於治療腎臟衰竭之病患 、惟患碟酸過剩之患者及容易罹患石粦酸過剩之串者上，其 係可與破酸於消化道中鍵結’防止碟酸於腸道中被吸收， 使磷酸不至於滯留於體内。 本發明相關於一種醫藥組成物，其係包括治療有效量 之藥用级檸檬酸鐵以及醫藥上可配合之載劑、賦形劑或稀 釋劑，該檸檬酸鐵之試驗式為F e C 6 Η 5 〇 7 · 3 5 H 0。 較佳地，本發明所述之醫藥組成物係可用以提供動物 體鐵質，更較佳地，本發明所述之醫藥組成物係可用於治 療缺鐵性、腎衰竭及磷酸過剩之疾病。 本發明亦相關於一種利用固態與固態反應製備藥用級 1259772 檸檬酸鐵之方法，包括： 混合固態檸檬酸及固態鐵鹽； 加入酒精於混合物中並進行過渡； 獲得固態藥用級檸檬酸鐵。 在本發明之一具體事實中，製備藥用級檸檬酸鐵之方 法中可進步將過濾後獲得之固態藥用級檸檬酸鐵加入 -或多次酒精混合再進行過濾而獲得不同純度之固態藥用 級檸檬酸鐵。 、、在本發明之較佳具體事實中，製備藥用級檸檬酸鐵之 中玄c得之固悲藥用級檸檬酸鐵可進一步進行烘乾 ，較佳地，該獲得之固態藥用級檸檬酸鐵可於60〇 c ^進 行烘乾。 該鐵鹽可為氣化鐵、硫 在本發明之較佳具體事實中 酸鐵或硝酸鐵。 本發明另亦相關於一種藥用級檸檬酸鐵，其性質均一 且具有試驗式為FeC6H5〇7 · 3 5H2〇。 一本务明另亦相關於一種膳食營養品，包含上述之藥用 級檸檬酸鐵。 /、 、、示上所述，本發明具有以下 •本發明之方法可製備藥用級檸檬酸鐵，其係具有 疋組攻成分，而目前市售之商品檸檬酸鐵之組成不 不能做為藥用。 2. 檬酸鍚^ 本發明之方法是利用固態_固態反應原理去合成檸 本方法只有一個步驟，易於操作及固定組成，並 1259772 可降低成本 【實施方式] 二製造藥用級之檸檬酸鐵，其合成操作程序應該少 一 /驟’ 控制其組成，·檸檬酸鐵係、由鐵鹽及桿樣 酸反應而製備，一般用於制一 用方、衣k樂用級檸檬酸鐵所使用之鐵 鹽包括氣化鐵、硫酸鐵或硝酸鐵等。 本文中所引述之文獻均以參考資料的方式併入本案。 本發明其他的特徵及優點將可明顯見 事實及申請專利範圍。 Μ 實例 下列實施例用於示範說明本發明。這些實施例不以任何方 式意欲限制本發明之範圍，但用於指示如何實施本發明的材料 及方法。 賞！備檸檬酸鐵 1 · 1利用含9個結晶水的硝酸鐵製備檸檬酸鐵 1.1 · 1方法 21 0 · 1 5克之含1個結晶水檸檬酸置於玻璃瓶内，將 404.02克之含9個結晶水的硝酸鐵加入此玻璃瓶内，並將 此玻璃瓶置於水浴内，攪拌固體四小時後，加入25〇 mL 之酒精於玻璃瓶内混合均勾，之後將此混合物過濾使溶解 於酒精中未反應之反應物除去，再將25〇 mL之酒精加入 1259772 此過濾過之固體並混合均勻，再經由過濾而留下固體，將 此固體在6〇°C烘乾箱烘乾過夜，其產率為54。/〇。 1.1.2結果 經由計算分子量得到Fe於FeC6H]3〇n中含量為 17.62%，而檢測產物發現Fe的含量為17.56%。 產品之解離溫度為1 8 7 -1 9 1。C。 1 · 1 · 3產品之安定性試驗 時間 溫度 40。(：士2。(：溼度 75%±5%RH 檸檬酸鐵 鐵 限制範圍 90-110% 16.5-18.5% 開始 99.70% 17.69% 第一個月 99.65% 17.68% 第二個月 99.58% 17.66% 第三個月 99/79% 17.70% 第六個月 ^0.37% -—----- 17.81% • 1用含6個結晶水的氯化鐵製備檸檬酸鐵 ^、口日日水的氯化鐵（ferric chloride hexahydrate ) 為1不〃或橘色之單斜結晶，易潮濕，熔點約3 70 C，易溶於 水、酒精、$ m 、***（The Merck Index，12仏版，第 4068 頁）。 以莫耳分子量比例為1 : !之含6個結晶水的氣化鐵 1259772 及含1個結晶水的檸檬酸置入含有酒精溶液的歐蘭麥氏瓶 中混合一小時，蒸發至約1 0毫升，然後置入冰箱結晶。 當氯化鐵及檸檬酸進行固態反應之初，產生透明針狀 結晶，但是在高濕度之下（約5 0 % )則變成液體。 1.3利用硫酸鐵製備檸檬酸鐵 硫酸鐵為灰白粉末、菱形結晶，易潮濕，慢溶於水， 而微溶於酒精’但不溶於丙酮、***，於商業產品中纟①常 含有約20%水且呈黃色（The Merck Index, 12th版，第4069 頁）。 硫酸鐵和檸檬酸反應與含6個結晶水的氣化鐵和檸檬 酸反應有相似情況。 1.4利用硝酸鐵製備檸檬酸鐵 含9個結晶水的硝酸鐵為淡紫羅蘭至灰白色，為有些 潮解的結晶，易溶於水、酒精、丙酮，而微溶於冷濃硝酸 ，熔點為 47〇C (The Merck Index，12th 版，第 4069 頁）。 以1 :】莫耳分子量比例之硝酸鐵及檸檬酸固態反應 四]1後’用酒精沖洗檸檬酸鐵結晶，然後混合物過濾， 而固體在6〇G C烘乾。 酸鐵之t析法 經精確稱取的〇·5克檸檬酸鐵加於含有5 mL·鹽酸及 之心口液的有基燒瓶中溶解，必要時可加熱溶解 10 1259772 ，另加入3克碘化鉀及5 mL鹽酸，加入塞子使混合均勻 後放置1 5分鐘，用〇.丨N硫代硫酸鈉溶液滴定析出之碘， 加殿粉試液3mL為指示劑，到終點為止，同時，進行不含 檸檬酸鐵的空白試驗作為校正，其中每毫升之〇· 1N硫代 硫酸納洛液相當於5.585 mg之鐵，也相當於24·496 mg之 FeC6H507 。 _實H 檸檬酸鐵中之檸檬酸根的方法 3.1材料 3.1 · 1移動相： 0.05 Ν磷酸緩衝劑（用磷酸調整至ρΗ 2.2):甲醇= 95 : 5 0 3 · 1 · 2標準品溶液 取經精確稱定的100 mg之標準檸檬酸溶解於20 mL 水及5 mL鹽酸後，用水稀釋至50.0 mL並混合均勻，取 此溶液10.0 mL放置於50 mL之定量瓶内，用0.05%之依 地酸二納（€(161&1€(1丨80(1丨11111)(用石粦酸調整至？1^2.2)稀釋至 50.0 mL並混合均勻，再用0.45 um濾紙過濾，濃度約每 mL 含 2.0 mg 〇 3.1.3樣品溶液 取經精密稱定的約1 〇〇 mg之檸檬酸鐵加於5 mL鹽酸 及20 mL水的50 mL定量瓶内溶解，用水稀釋至50.0 mL 並混合均勻，取此溶液1 〇·〇 nlL放置於5〇 mL之定量瓶内 ，用0.05%之依地酸二鈉（用填酸調整至PH 2.2)稀釋至 1259772 50.0 mL並混合均勻，再用〇.45 um濾紙過濾。 3.1.4層析法系統 液態層析系統用4.6 mm xl5 cm Inertsil 5 ODS-2管柱 及2 2 Ο - nm檢示器’流速為約每分鐘i . q m L。 3.2方法 分別注射相同體積（20 uL)之標準品溶液及樣品溶液入 層析儀中分析並記錄峰，量其主峰，以每克樣品中含有多 少亳克檸檬酸根為單位，其方程式如下：1259772 玖, the invention description: [Technical field of the invention] The invention relates to a pharmaceutical grade ferric citrate and a preparation method thereof, a pharmaceutical composition containing the citrate iron, and a vinegar nutrition containing a pharmaceutical grade ferric citrate ΌΌ ° [Prior Art] US Patent No. 5,7 5 3,7 06 reveals that rod-like acid iron compounds can be used to treat patients with renal failure and patients who are prone to excess phosphoric acid. According to the instructions, iron citrate was purchased from Sigma-Aldrich and contained in the product catalogue. It contains 16.5% - 18.5% ginseng in the acid metabolism and reduces the acid retention in the body. Valence iron, molecular formula, molecular weight 244.9, is a dark red or light brown powder with transparent scales, has a micro-iron flavor, which can be slowly dissolved and completely soluble in water, and easily soluble in hot water, but The solubility will be reduced over time (The inda, 12th edition, p. 4068). Therefore, it is difficult to manufacture, and the production-grade material must have a certain composition, so this requirement cannot be achieved. However, although ferric citrate in iron and citric acid is the iron and citric acid (The Merck Index, 12th edition, the iron and citric acid included are not commercially available, but by the combination, and The composition ratio is not clear on page 4068), indicating that the same ratio of ferric citrate and different numbers of crystallization water are of different quality. However, the commercially available ferric citrate 1259772 is in compliance with the drug control law and the drug administration's listing review requirements due to the molecular formula. In view of this, pharmaceutical grade products need to have a fixed fraction = composition, so the preparation of a ferric citrate system having a fixed molecular composition is a problem to be solved. SUMMARY OF THE INVENTION The object of the present invention is to provide a fermented ferric citrate method for supplying novel pharmaceutical grade ferric citrate by using a solid-solid reaction to produce pharmaceutical grade ferric citrate, the pharmaceutical grade ferric citrate comprising A certain molecular composition #—the crystal water. Pharmaceutical grade ferric citrate can be used for iron deficiency treatment to provide iron in animals. Patients with renal failure are prone to iron deficiency. It can be treated with pharmaceutical grade ferric citrate, and other pharmaceutical grade ferric citrate. It can also be used to control the metabolism of acid and acid and excessive acidosis, especially for patients with kidney failure, patients with excess acidosis, and those who are prone to excessive sulphuric acid. Bonding in the digestive tract prevents the acid from being absorbed in the intestines, so that the phosphate does not stay in the body. The present invention relates to a pharmaceutical composition comprising a therapeutically effective amount of pharmaceutical grade ferric citrate and a pharmaceutically acceptable carrier, excipient or diluent, the test formula of ferric citrate being F e C 6 Η 5 〇7 · 3 5 H 0. Preferably, the pharmaceutical composition of the present invention can be used to provide animal iron. More preferably, the pharmaceutical composition of the present invention can be used for the treatment of diseases of iron deficiency, renal failure and excess phosphoric acid. The invention is also related to a method for preparing pharmaceutical grade 1257772 ferric citrate by solid state and solid state reaction, comprising: mixing solid citric acid and solid iron salt; adding alcohol to the mixture and performing transition; obtaining solid pharmaceutical grade ferric citrate . In a specific fact of the present invention, in the method for preparing pharmaceutical grade ferric citrate, the solid pharmaceutical grade ferric citrate obtained after filtration can be further added to or mixed with a plurality of alcohols and then filtered to obtain solid medicines of different purity. Use grade ferric citrate. In the preferred specific facts of the present invention, the preparation of the pharmaceutical grade ferric citrate may be further dried by the medicinal grade ferric citrate of Xuan C, preferably, the obtained solid pharmaceutical grade The ferric citrate can be dried at 60 〇c ^. The iron salt may be gasified iron or sulfur. In the preferred specific case of the present invention, iron or iron nitrate. The invention is also related to a pharmaceutical grade ferric citrate which is of uniform nature and has the experimental formula FeC6H5〇7 · 3 5H2 〇. A present invention is also related to a dietary supplement comprising the above-mentioned pharmaceutical grade ferric citrate. The invention has the following methods: The method of the invention can prepare pharmaceutical grade ferric citrate, which has the composition of the cockroach group, and the composition of the commercially available commercial ferrotitanium cannot be used as Medicinal. 2. citric acid 钖 ^ The method of the present invention utilizes the solid-state solid-state reaction principle to synthesize the lemon. The method has only one step, is easy to operate and fixes the composition, and 1259772 can reduce the cost. [Embodiment] 2. Production of pharmaceutical grade ferric citrate The synthetic operation procedure should be less than one / the second to control its composition, · ferric citrate, prepared by the reaction of iron salt and rod-like acid, generally used for the production of a square of iron, ferric citrate The iron salt includes gasified iron, iron sulfate or iron nitrate. The documents cited herein are incorporated herein by reference. Other features and advantages of the present invention will be apparent from the facts and claims.实例 Examples The following examples are intended to illustrate the invention. These examples are not intended to limit the scope of the invention in any way, but are intended to indicate how to practice the materials and methods of the invention. reward! Preparation of ferric citrate 1 · 1 Preparation of ferric citrate using ferric nitrate containing 9 water of crystallization 1.1 · 1 Method 21 0 · 1 5 g of citric acid containing 1 crystal water in a glass bottle, containing 40 crystals of 404.02 g Water ferric nitrate was added to the glass bottle, and the glass bottle was placed in a water bath. After stirring the solid for four hours, 25 mL of alcohol was added and mixed in a glass bottle, and then the mixture was filtered to dissolve in alcohol. Unreacted reactants were removed, and 25 mL of alcohol was added to 1259772. The filtered solid was mixed well, and then filtered to leave a solid. The solid was dried in a 6 ° C drying oven overnight. The rate is 54. /〇. 1.1.2 Results The content of Fe in FeC6H]3〇n was 17.62% by calculation of molecular weight, and the content of Fe was found to be 17.56%. The dissociation temperature of the product is 1 8 7 -1 9 1 . C. 1 · 1 · 3 Product stability test Time Temperature 40. (:士2.(: Humidity 75%±5%RH Ferric citrate limit range 90-110% 16.5-18.5% Start 99.70% 17.69% First month 99.65% 17.68% Second month 99.58% 17.66% Three months 99/79% 17.70% Sixth month ^0.37% ------- 17.81% • 1 Preparation of ferric citrate with ferric chloride containing 6 crystal waters Ferric chloride hexahydrate is monotonic crystal of 1 or orange, easy to wet, melting point about 3 70 C, soluble in water, alcohol, $ m, ether (The Merck Index, 12 仏, page 4068) The gasified iron containing 12 crystallization water with a molecular weight ratio of 1:977 and the citric acid containing one crystal water were placed in a ohmam bottle containing an alcohol solution and mixed for one hour, and evaporated to about 10 ml, then placed in the refrigerator to crystallize. When the ferric chloride and citric acid were solid-phase reaction, transparent needle crystals were produced, but under high humidity (about 50%) became liquid. 1.3 Preparation with iron sulfate Ferric citrate ferric sulfate is a gray powder, rhombohedral crystal, easy to wet, slowly soluble in water, and slightly soluble in alcohol 'but not soluble in acetone Ether, in commercial products, 纟1 often contains about 20% water and is yellow (The Merck Index, 12th edition, page 4069). Reaction of iron sulphate and citric acid with gasified iron and citric acid containing 6 water of crystallization A similar situation is obtained. 1.4 Preparation of ferric citrate using ferric nitrate Iron nitrate containing 9 crystal waters is light violet to grayish white, which is some deliquescent crystal, soluble in water, alcohol and acetone, and slightly soluble in cold concentrated nitric acid. 47 〇C (The Merck Index, 12th edition, page 4069). The solid reaction of ferric nitrate and citric acid in a molecular weight ratio of 1 : 1 followed by 'rinsing ferric citrate crystals with alcohol, and then filtering the mixture. The solid is dried at 6 〇 GC. The acid iron is precipitated by accurately weighing 〇·5 g of ferric citrate and dissolved in a base flask containing 5 mL of hydrochloric acid and heart-filled liquid, and dissolved if necessary. 10 1259772, add 3 grams of potassium iodide and 5 mL of hydrochloric acid, add the plug to make the mixture evenly, then let it stand for 15 minutes, titrate the precipitated iodine with 〇.丨N thiosulfate solution, add 3mL of the powder test solution as indicator, to the end point So far, at the same time, do not The blank test containing ferric citrate was used as a calibration, in which each nanoliter of 〇·1N sodium thiosulfate was equivalent to 5.585 mg of iron, which is equivalent to 24.496 mg of FeC6H507. _ Real H citrate in ferric citrate Method 3.1 Material 3.1 · 1 mobile phase: 0.05 Ν Phosphate buffer (adjusted to ρΗ 2.2 with phosphoric acid): Methanol = 95 : 5 0 3 · 1 · 2 Standard solution is accurately dissolved in 100 mg of standard citric acid After diluting with water to 5 mL of hydrochloric acid and 5 mL of hydrochloric acid, dilute to 50.0 mL with water and mix well. Take 10.0 mL of this solution and place it in a 50 mL quantitative bottle with 0.05% edetate dihydrate (€(161&1€( 1丨80(1丨11111) (Adjusted with samaric acid? 1^2.2) Dilute to 50.0 mL and mix well, then filter with 0.45 um filter paper. The concentration is about 2.0 mg per mL. 3.1.3 sample solution. Accurately weighed about 1 〇〇mg of ferric citrate and added to 5 mL. Dissolve in a 50 mL dosing bottle of hydrochloric acid and 20 mL of water, dilute to 50.0 mL with water and mix well. Place 1 〇·〇nlL in a 5 mL bottle and use 0.05% disodium edetate. Dilute to 1259772 50.0 mL with acid adjustment to pH 2.2) and mix well, then filter with 〇.45 um filter paper. 3.1.4 Chromatography system The liquid chromatography system uses a 4.6 mm x l5 cm Inertsil 5 ODS-2 column and a 2 2 Ο - nm detector. The flow rate is approximately . q m L per minute. 3.2 Method The same volume (20 uL) of the standard solution and the sample solution were separately injected into the chromatograph to analyze and record the peak, and the main peak was measured in units of gram citrate per gram of sample. The equation is as follows:
Ru/RsxWst/Wux 189.1 1/192.13Ru/RsxWst/Wux 189.1 1/192.13
Ru及Rs是樣品及標準品峰面積。Ru and Rs are sample and standard peak areas.
Wst及Wu是標準品及樣品中之重量。 在操作過程中，重複注射標準品溶液及樣品溶液之相 斜&準偏差小於2.0%。 分析產品檸檬酸鐵之組成成分 商品檸檬酸鐵購自Sigma-Aldrich公司，將商品檸檬 -哉用實施例2之鐵滴定法及實施例3之檸檬酸根層析法 刀別分析鐵含量及檸檬酸含量，於表I顯示市售商品檸檬 酸鐵之分析結果，其中檸檬酸鐵的含量由兩種方式計算而 吁’其一係利用由滴定所檢測之鐵含量，而檸檬酸以一比 旲耳分子比率自鐵滴定計算而得，另亦自利用層析法所 Ί寻之檸檬酸根及用滴定所測得之鐵的含量計算總合，從 义兩種分析之檸檬酸鐵差異極大，不易決定其組成。 12 1259772 表I:分析市售檸檬酸鐵產品的結果Wst and Wu are the weights of the standards and samples. During the operation, the standard deviation of the standard solution and the sample solution was less than 2.0%. Analysis of the product composition of ferric citrate Commodity ferric citrate was purchased from Sigma-Aldrich, and the commercial lemon-rhenium was analyzed by the iron titration method of Example 2 and the citrate chromatography method of Example 3 to analyze the iron content and citric acid. The content, in Table I, shows the analysis results of commercially available commercial ferric citrate, in which the content of ferric citrate is calculated by two methods, and the one is using the iron content detected by titration, and the citric acid is one by one. The molecular ratio is calculated from the iron titration, and the total amount of citrate and the content of iron measured by titration are calculated from the chromatographic method. The difference between the two types of ferric citrate is extremely large and difficult to determine. Its composition. 12 1259772 Table I: Analysis of results of commercially available ferric citrate products
Lot No. 試驗式 鐵 (滴定) 檸檬酸 (HPLC) 檸檬 酸鐵 (滴定) 檸檬酸 鐵 (HPLC+ 滴定） 檸檬酸 鐵 差異性（ 單位:％) Wako SKL1164 FeC6H507 • nH20 17.61 65.21 77.22 82.82 5.60 Sigmal 30H00375 FeC6H507 • nH20 17.80 62.78 78.06 80.58 2.52 Sigma2 20K0950 FeC6H507 • nH2〇 17.75 66.73 77.84 84.48 6.64 Fulka 364546/1 FeC6H507 • nH2〇 18.96 67.27 83.18 86.23 3.05 理論值 FeC6H507 • 3·5Η20 18.13 ^60.42 Ι783Γ β為了合乎藥用級檸檬酸鐵，擰檬酸鐵之檸檬酸根及鐵 3里比率（1 ·狀189 1 1/55 85=3 39 ’由實施例1製備出 四批擰檬酸鐵，用兩種分析法分析檸檬酸鐵，其結果顯示 :表Π，其中檸檬酸鐵以一比一莫耳分子比率自鐵滴定計 另亦自檸檬酸根及鐵之含量計算總合，$兩種分析 “豕酸鐵之i異是L48%，表示產品檸檬酸 ，且 〇所 了保‘鐵之至異性小 /、有间，口貝，故可利用本發 ，同時方法製備檸檬酸鐵 分析鐵及": 晶水數目’由這四批擰檬酸鐵 :析鐵及一根的結果表示棒樣酸鐵中含有參個半結晶 13 1259772 表II··分析本發明所製作之檸檬酸鐵的結果Lot No. Test iron (titration) Citric acid (HPLC) Ferric citrate (titration) Ferric citrate (HPLC + titration) Ferric citrate difference (unit: %) Wako SKL1164 FeC6H507 • nH20 17.61 65.21 77.22 82.82 5.60 Sigmal 30H00375 FeC6H507 • nH20 17.80 62.78 78.06 80.58 2.52 Sigma2 20K0950 FeC6H507 • nH2〇17.75 66.73 77.84 84.48 6.64 Fulka 364546/1 FeC6H507 • nH2〇18.96 67.27 83.18 86.23 3.05 Theoretical value FeC6H507 • 3·5Η20 18.13 ^60.42 Ι783Γ β for pharmaceutical grade citric acid Iron, iron citrate citrate and iron 3 liter ratio (1 · 189 1 1 / 55 85 = 3 39 ' Four batches of ferric acid iron were prepared from Example 1, and two analytical methods were used to analyze ferric citrate The results show that: the surface enthalpy, the ferric citrate ratio is calculated from the iron titration and the total content of citrate and iron from the iron titration, and the two analyses "the difference between the iron citrate and the iron is L48" %, which means that the product is citric acid, and the 〇 了 ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' 'From the four batches of citric acid iron: iron and an analysis result showing the rod-like ferric containing a semicrystalline 131259772 parameter table II ·· analysis result of the present invention is produced ferric citrate
Lot No. 試驗式 鐵 (滴定） 檸檬酸 (HPLC) 檸檬酸 鐵 (滴定） 檸檬酸 鐵 (HPLC+ 滴定） 檸檬酸 鐵 差異性（ 單位··％) F920620 FeC6H5〇7 • 3.5 H20 17.72 61.56 77.72 79.28 1.56 911125-2 FeC6H5〇7 • 3·5 H2〇 17.73 63.55 77.75 81.28 3.53 911115-A FeC6H507 • 3.5 H20 17.84 60.42 78.23 78.26 0.03 911115-B FeC6H507 • 3.5 H20 18.46 63.30 80.95 ^81.76 0.81 理論值 FeC6H507 • 3.5 H20 18.13 60.42 78.55 p平均 17.94 62.21 78.66 80.14 1.48 相對標準 偏差 1.97% 239% 1.96% 2.06% 根據本發明可作之不同修正及變化對於熟習該項技術 者而s均顯然不會偏離本發明的範圍與精神。雖然本發明 已敛述特定的較佳具體事實，必須瞭解的是本發明不應被 不當地限制於該等特定具體事實上。事實上，在實施本發 明之已述模式方面，對於熟習該項技術者而言顯而易知之 不同修正亦被涵蓋於下列申請專利範圍之内。 【圖式簡單說明】 (一）圖式部分 14 1259772 (二）元件代表符號Lot No. Test iron (titration) Citric acid (HPLC) Ferric citrate (titration) Ferric citrate (HPLC + titration) Ferric citrate difference (unit··%) F920620 FeC6H5〇7 • 3.5 H20 17.72 61.56 77.72 79.28 1.56 911125-2 FeC6H5〇7 • 3·5 H2〇17.73 63.55 77.75 81.28 3.53 911115-A FeC6H507 • 3.5 H20 17.84 60.42 78.23 78.26 0.03 911115-B FeC6H507 • 3.5 H20 18.46 63.30 80.95 ^81.76 0.81 Theoretical value FeC6H507 • 3.5 H20 18.13 60.42 78.55 p average 17.94 62.21 78.66 80.14 1.48 Relative standard deviation 1.97% 239% 1.96% 2.06% Different modifications and variations are possible in light of the present invention without departing from the scope and spirit of the invention. Although the present invention has been described with reference to certain preferred specific embodiments, it should be understood that the invention should not be In fact, the various modifications that are obvious to those skilled in the art are also covered by the following claims. [Simple description of the diagram] (1) Schema part 14 1259772 (2) Component symbol