Trissel Lawrence A, Xu Quanyun, Zhang Yanping, Walter William V
Clinical Pharmaceutics Research Program, The University of Texas, M.D. Anderson Cancer Center, Houston, TX.
Int J Pharm Compd. 2003 Jan-Feb;7(1):71-7.
Numerous factors (including solution pH) that influence the amount of calcium and phosphates remaining in solution or precipitating from parenteral nutrition solutions have been identified. Increased solubility of calcium and phosphates can be achieved in parenteral nutrition formulations by using a suitable acidic additive to lower the pH from the natural unadjusted level. The purpose of this study was to evaluate the use of cysteine hydrochloride injection as an additive to FreAmine III-based parenteral nutrition solutions to increase the solubility of calcium and phosphates. In this study, five representative core parenteral nutrition formulations containing FreAmine III 1% to 5% were evaluated. Those formulations contained cysteine hydrochloride injection 0.5mL (25 mg) per gram of amino acids from FreAmine III to lower the pH. Varying amounts of calcium and phosphates were added to samples of the core formulations to identify the points at which precipitation just began to occur. Five series of concentrations with maxima of calcium 40 mEq/L and phosphates 40 mM/L were tested. The samples were evaluated by visual observation with the unaided eye and with a Tyndall beam to accentuate the visibility of small particles and low-level turbidity. The turbidity and particle content of samples not exhibiting visible particles or haze were measured electronically. Evaluations were performed initially and after 24 and 48 hours of storage at 23 deg C and 37 deg C. Samples were also stored for 30 days at 4 deg C, were warmed at room temperature, and were evaluated after warming and after additional storage of 24 and 48 hours at room temperature. The addition of cysteine hydrochloride injection 5 mL/L for each 1% of amino acids content reduced the pH of the core parenteral nutrition admixtures from 6.4 to 5.9. The solubility of calcium and phosphates was increased by approximately 30% by that reduction in pH. The compatibility-incompatibility concentration ranges for each of the five core formulations, in which calcium ranged up to 40 mEq/L and phosphates ranged up to 40 mmol/L at temperatures of 23 deg C and 37 deg C are presented in tables and figures. The addition of cysteine hydrochloride 0.5 mL (25 mg) per gram of amino acids from FreAmine III increased the solubility of calcium and phosphates about 30% by lowering the solution pH.
已确定许多影响肠外营养溶液中残留钙和磷酸盐量或从肠外营养溶液中沉淀的因素（包括溶液pH值）。通过使用合适的酸性添加剂将pH值从自然未调节水平降低，可以提高肠外营养制剂中钙和磷酸盐的溶解度。本研究的目的是评估将盐酸半胱氨酸注射液作为基于FreAmine III的肠外营养溶液的添加剂以提高钙和磷酸盐的溶解度。在本研究中，评估了五种含有1%至5% FreAmine III的代表性核心肠外营养制剂。这些制剂每克来自FreAmine III的氨基酸含有0.5mL（25mg）盐酸半胱氨酸注射液以降低pH值。向核心制剂样品中加入不同量的钙和磷酸盐，以确定刚开始出现沉淀的点。测试了钙最高浓度为40mEq/L和磷酸盐最高浓度为40mM/L的五个系列浓度。通过肉眼观察以及用丁达尔光束来突出小颗粒的可见性和低水平浑浊度对样品进行评估。对未表现出可见颗粒或雾度的样品的浑浊度和颗粒含量进行电子测量。最初以及在23℃和37℃储存24小时和48小时后进行评估。样品也在4℃储存30天，在室温下温热，并在温热后以及在室温下额外储存24小时和48小时后进行评估。每1%氨基酸含量加入5mL/L盐酸半胱氨酸注射液可使核心肠外营养混合物的pH值从6.4降至5.9。通过pH值的降低，钙和磷酸盐的溶解度提高了约30%。在23℃和37℃温度下，五种核心制剂中每种制剂的相容 - 不相容浓度范围（其中钙最高可达40mEq/L，磷酸盐最高可达40mmol/L）列于表格和图表中。每克来自FreAmine III的氨基酸加入0.5mL（25mg）盐酸半胱氨酸通过降低溶液pH值使钙和磷酸盐的溶解度提高了约30%。
