Bicarbonate physiological balanced solution and preparation method thereof

Abstract

The invention discloses a bicarbonate physiological balanced solution which belongs to the field of infusion preparations and is prepared form the following raw materials: sodium chloride, potassium chloride, calcium chloride, magnesium sulfate, sodium bicarbonate, glucose, citric acid and trisodium citrate. All the raw materials are accurately weighed according to corresponding portions, and dissolved in water for injection; the volume is determined; medical standard CO2 gas is introduced; the pH value is adjusted; and the solution is filtered, filled, packed, sterilized, labeled and then stored at room temperature. The solution has the advantages that ion components and a penetration concentration are similar to those of extracellular fluid and have physiological performance. The balanced solution is suitable for supplementing the extracellular fluid by injection, intravenous drip or oral administration, has an adjustment function for acid-base balance, and is also used as a surgical washing fluid or buffering solution.

Description

technical field [0001] The invention relates to a large transfusion preparation, in particular to a bicarbonate physiological balance liquid. It is a balance solution whose ionic composition and osmotic pressure are closer to extracellular fluid. It is suitable for supplementing extracellular fluid through injection, intravenous infusion or oral route. It can regulate acid-base balance and can also be used as a surgical flushing fluid. or buffer solution. Background technique [0002] There are three main types of balance solutions currently used in the medical field: Ringer’s solution (RS), Lactated Ringer’s solution (LRS) and Acetated Ringer’s solution (ARS). [0003] From 1880 to 1883, Sydney Ringer (1835-1910), a British physiologist and clinician, accidentally used tap water to prepare frog myocardial perfusion fluid, and found that its myocardial contractility was stronger than that of saline prepared with distilled water. The contained traces of potassium / calcium io...

AI Technical Summary

Problems solved by technology

Disadvantages: ① Cl - Higher than the plasma content, a large amount of infusion will have adverse effects on the body, and will cause iatrogenic hyperchloremic metabolic acidosis (Hyperchloremic metabolic acidosis, HCMA)

②Free calcium Ca 2+ The content is as high as 2.0mmol / L or more, although it helps to promote blood coagulation and reduce perioperative blood loss, but a large amount of infusion (>3L) may shorten the blood coagulation time and cause the body's obvious hypercoagulable state

③There is no direct buffer base in its composition

Due to the limitations of the production process, most of the lactate in the commercially available lactated Ringer's solution is a racemate in which D-lactic acid and L-lactate are mixed in equal amounts, so it has a potential apoptosis-inducing effect

④ Hyperlactatemia A large amount of Lactated Ringer's solution infusion in a short period of time will cause hyperlactatemia, and the metabolism of exogenously input L-lactate in the body is an energy-consuming process (1 molecule of L-lactate is metabolized into equimolecular HCO 3 - Will consume 6 molecules of ATP) to generate HCO 3 - Neutralize H + into CO 2 There is a time lag when buffering with water (approximately 1.5 hours later), which is unfavorable for liver resection and liver transplantation, and it is also prone to hyperlactic acidemia when used as priming fluid in extracorporeal circulation

The solution of such gained has following defect: 1. normal human body pH scope is (7.35~7.45), and the tolerance of body to acid is better than the tolerance to alkali, and pH7.8 seriously exceeds the standard, so higher than the electrolyte of the normal acidity scope of human body The solution will cause or aggravate severe alkalosis and / or alkalemia; ②The concentration of bicarbonate ion exceeds the normal physiological range of the human body ([HCO 3 - ] is 23~27mmol / L), it is likely to cause obvious alkalemia and / or metabolic alkalosis when used for acute massive infusion; ③The range of calcium ion 0~2.5mmol / L is obviously unreasonable (normal serum The range of calcium ions is 1.375~1.75mmol / L), too high calcium ion content in the solution is obviously unfavorable to the body, not only affects blood coagulation, may promote the formation of microthrombus, but also increase ischemia / reperfusion injury

It can be seen that the electrolyte infusion formula composition described in JP-P7-304657 still does not conform to the physiological state of extracellular fluid, and its formula is unreasonable as a supplement of body fluid

[0013] In addition, the above-mentioned two announcements of the Japanese Patent Office (JP-9-124491A, JP-7-304657) are not only unreasonable in proportioning ingredients, but also too complicated in the technological process used.

CO alone 2 The production process for pH adjustment is very unstable, high CO 2 The pressure not only leads to unstable pH of the product, but also is difficult to control during the production process. If the gas escapes due to the decrease in solubility during the high-temperature sterilization process, it will cause the pH of the solution to fluctuate too much and precipitates are likely to precipitate. This defect also It has been indicated in its patent documents (when CO 2 Precipitation occurs when the pressure is lower than 50mmHg), and it has been confirmed by our experiments

Adopting citrate and calcium / magnesium ion to carry out complexation to avoid precipitation in the technical route of a key process production link is to control the pH of solution, but the scheme that Japanese Patent Office Japanese Patent Office Laid-Open 9-124491A announces thinks that organic strong acid citrate will neutralize bicarbonate ions, so it is proposed to simply use CO 2 The production process of adjusting pH adjustment (using high pressure, PCO 2 maintained at 50-300mmHg), but the CO 2 Excessive pressure brings many pH unstable factors in the process of production, so it may be necessary to adjust the pH of the solution with the help of NaOH, which will obviously seriously change the stability of the proportioning components in the solution

[0014] In summary, the two electrolyte solutions disclosed by the Japanese Patent Office are difficult to be accepted in clinical practice for the supplementation of human body fluids (i.e. transfusion)

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