CN101721424B

CN101721424B - Bicarbonate physiological balanced solution and preparation method thereof

Info

Publication number: CN101721424B
Application number: CN2009102075618A
Authority: CN
Inventors: 曾因明; 鲁显福
Original assignee: Individual
Current assignee: Individual
Priority date: 2008-10-21
Filing date: 2009-10-20
Publication date: 2012-07-25
Anticipated expiration: 2029-10-20
Also published as: CN101721424A

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, citric acid, trisodium citrate and optional glucose. All the raw materials are accurately weighed according to corresponding portions, and dissolved in water for injection; the volume is determined; 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

Bicarbonate physiological balance liquid and preparation method thereof

Technical Field

The invention relates to a large transfusion preparation, in particular to a bicarbonate physiological balanced solution. Is a balanced solution with ion components and osmotic pressure more similar to that of extracellular fluid, is suitable for supplementing extracellular fluid by injection or intravenous drip or oral administration, has regulating effect on acid-base balance, and can be used as surgical flushing fluid or buffer solution.

Background

Currently, there are three main types of balancing solutions used in the medical field: ringer's Solution (RS), Lactated Ringer's Solution (LRS), and Ringer's acetate solution (ARS).

In 1880 + 1883, England physiologist and clinician Sydney Ringer (1835 + 1910) surprisingly prepared frog myocardial perfusate with tap water, found that myocardial contractility is stronger than that of normal saline prepared with distilled water, and analyzed the components to obtain that the myocardial contractility can be improved with trace potassium/calcium ions and bicarbonate contained in the tap water, so as to first put forward the concept of compound electrolyte solution, hence the name of Ringer's solution, also called compound sodium chloride solution. The ringer's solution has the advantages that: isotonic with blood plasma, Na⁺、K⁺The concentration was similar to that of plasma. The method has the following defects: (ii) Cl^-Above plasma level, mass infusion can cause adverse effects on the body and cause iatrogenic Hyperchloremic metabolic acidosis (HCMA). ② free calcium Ca²⁺The content is as high as 2.0m mol/L, which is helpful for promoting blood coagulation and reducing perioperative blood loss, but a large amount of infusion (> 3L) can shorten the blood coagulation time and cause obvious hypercoagulable state of the organism. ③ the components have no direct buffer alkali.

The addition of bicarbonate to ringer's solution was first thought to buffer tissue acidosis, but its use was hindered by the formation of precipitates with calcium/magnesium ions. In the early 30 s of the last century, Alexis Hartmann added lactic acid to ringer's solution to buffer the acid-base equilibrium, and ringer's solution was thus known and is also called Hartmann's solution. The lactic acid ringer's solution contains K as compared to ringer's solution⁺、Ca²⁺And Lactate^-Has buffering effect and overall hemodynamics effect to improve the survival rate of sepsis and traumatic hemorrhagic shock. The disadvantages are that: (ii) Na⁺The content (130m mol/L) and the total osmotic concentration (274mOsm/L) are lower than ECF, and a large amount of input can cause hyponatremia and reduce the osmotic pressure of extracellular fluid to cause interstitial edema, so that the medicine is unfavorable for patients at risk of cerebral edema. ② free calcium Ca²⁺The content is 2.0m mol/L, and the possibility of blood coagulation interference exists as common ringer's solution. ③ D-lactate contained in the ringer's lactate has potential apoptosis effect naturallyThe interfacial lactic acid has two optical isomers of D-lactic acid and L-lactic acid, the D-lactic acid is hardly metabolized in vivo and has direct toxic effect on liver cells, lung epithelial cells and neurons, and a large amount of input in a short time can increase apoptosis of alveolar epithelial cells and liver cells; the endogenous lactic acid capable of being metabolized is L-type, and is mainly metabolized in the liver to generate HCO with equal molecules₃ ^-Playing the role of buffering. Due to the limitations of production process and the like, most of lactate in the commercially available lactated ringer's solution is racemate of D-lactic acid and L-lactate which are mixed in equal amount, so that the lactate has potential apoptosis effect. High lactic acidemia high lactic acid blood-level is caused by large-scale infusion of ringer's solution in short time, and exogenously input L-lactate is metabolized in vivo as an energy-consuming process (1 molecule of L-lactic acid is metabolized to generate equal molecular HCO₃ ^-Will consume 6 molecules of ATP) to produce HCO₃ ^-Neutralization of H⁺To CO₂And a time lag in the buffering action of water (which is effective after about 1.5 hours), which is detrimental to liver resection and liver transplantation, and is also prone to hyperlactacidosis when used as a priming solution in extracorporeal circulation.

To avoid adverse effects of lactic acid accumulation, ringer's Acetate, marketed by Baite corporation of the United states in 1979, is known under the trade name "Bo Mai Li A" (PLASMA-LYTE, Baxter), namely Acetate (Acetate)^-) It is a compound electrolyte solution without calcium, and can be used as extracellular fluid crystal replenisher instead of lactate. In view of the risk of complicated hyperlactacidosis associated with the infusion of ringer's lactate, Bo Mai Li A is considered by Baiter as the most physiochemical compound electrolyte solution. Its advantages are that pH value is 7.4, and osmotic concentration is close to plasma (308 mOsm/L); cl^-And Na⁺Concentration close to plasma, K⁺And Mg²⁺The concentration is close to that of extracellular fluid; acetate and gluconate (twice the normal plasma values) containing bicarbonate precursor species can exert greater buffering capacity; the lactic acid is not contained, the blood sugar is not increased additionally, and the liver burden is not increased; extracorporeal circulation priming is rarely accumulated; in addition, the utility model has the advantages of being beneficial to keeping the core body temperature under the general anesthesia state, etc. However, studies have shown that ringer's acetate corrects metabolic acidosis and energy ATP supplyShould not be superior to ringer's lactate. It has the disadvantages that: contains no Ca²⁺Is an important defect calcium which is the most widely used signal molecule in cells and is involved in almost all vital activities in cells, not only an important second signal molecule, but also a self-regulating molecule for self-stabilizing regulation of various vital activities. It is presently believed that a non-physiological crystalloid solution, calcium-free, cannot be selected when selecting a supplement to functional extracellular fluids. ② the metabolism of acetic acid in the body of diabetic ketoacidosis patients and hepatectomy patients will be reduced to 1/3 and the metabolism is incomplete. ③ acetic acid has the effect of expanding blood vessels, and can be rapidly infused in large quantities to inhibit the cardiovascular system. And fourthly, the venous infusion of Bo Mai Li A can interfere the detection result of the invasive aspergillosis enzyme-linked immunosorbent assay, so that the venous infusion is contraindicated for blood diseases and tumor patients with the hidden danger of aspergillosis infection septicemia in order to avoid diagnosis errors.

The above balance is compared with the Plasma (Plasma)/Interstitial/Intracellular (Intracellular) components (see Table 1), and is subject to improvement.

Table 1: comparison of various equilibrium solutions with plasma/interstitial/intracellular fluid components (using Osmolarity Osmolarity, in mOsm/L).

Note:^*wherein plasma ionized calcium normally has a value of 1.0-1.2m mol/L (2.0-2.4mOsm/L), and ARS (Baxter) further contains 23m mol/L gluconic acid (Gluconate 23 mOsm/L).

The sodium bicarbonate is physiological buffering alkali which can rapidly exert the alkalization effect without the metabolic process of the organism, so the sodium bicarbonate is not added into the ringer's solution all the time, and the production process of the ringer's solution of the sodium bicarbonate cannot meet the production requirements of pharmaceutical products (HCO at room temperature) all the last three decades because of the precipitation problem₃ ^-Easily generate CO₃ ^2-，CO₂And H₂O 2HCO₃ ^-→CO₃ ^2-+CO₂+H₂O，CO₃ ^2-+Ca²⁺→CaCO₃↓); however, when sodium bicarbonate injection alone is intravenously infused HCO₃ ^-The fact that the calcium/magnesium ions are present in the mixed solution in a stable manner means that the bicarbonate can be stabilized, since the calcium/magnesium ions are instantaneously present as a buffer base in the plasma without intervening metabolic processes and in combination with the metabolism of divalent cations. Experiments have shown that under appropriate pH conditions (pH < 8.0) the appropriate amount of Citrate (Citrate) is added to the solution^3-) When it is, Citrate^3-Can be mixed with Ca²⁺、Mg²⁺The complexation reaction occurs to form a stable complex and avoid precipitation.

Disclosure of Invention

Compared with the current clinical common preparation, the bicarbonate physiological balanced liquid has ion components and osmotic concentration which are more similar to those of extracellular fluid (ECF), is suitable for supplementing the extracellular fluid through an injection or intravenous drip way or an oral way, and has a regulating effect on acid-base balance; it can also be used as surgical washing solution or buffer solution.

The invention is realized by the following technical scheme: a bicarbonate physiological balance liquid is prepared by introducing CO during preparation₂Adjusting the pH value of the gas to prepare the ion with the molar concentrations of the ions as follows:

sodium ion Na⁺ 135-145m mol/L

Chloride ion Cl^- 105-120m mol/L

Potassium ion K⁺ 3-5.5m mol/L

Calcium ion Ca²⁺ 0.5-1.5m mol/L

Magnesium ion Mg²⁺ 0.7-1.1m mol/L

Sulfate ion SO₄ ^2- 0.7-1.1m mol/L

Bicarbonate ion HCO₃ ^- 23-27m mol/L

Citrate ion Citrate^3- 1.5-3m mol/L，

The equilibration fluid optionally contains glucose.

Based on the discovery of the application that the citrate stabilizes calcium and magnesium ions, the basic purpose of the invention can be realized only by meeting the requirement that the concentration of the citrate ions is within a certain range.

The researchers carried out further studies. If trisodium citrate is used alone to stabilize calcium and magnesium ions, the pH value is above 8.0, which is not in accordance with physiological requirements, and the pH value must be adjusted. However, when the solution is adjusted by using acids such as hydrochloric acid and sulfuric acid, decomposition of bicarbonate is caused, and particularly, the concentration of bicarbonate in the solution cannot meet the requirement in the process of heating sterilization or long-term storage; secondly, the introduction of a large amount of anions such as chlorine, sulfate radical and the like can cause the concentration of various ions in the solution to exceed the optimal range of the concentration of various ions in the physiological equilibrium solution. Thus, the researchers sought the best way to introduce and present citrate, and screened to the surprising discovery that when citric acid and carbon dioxide aqueous solution are both introduced into the system, an optimal effect is achieved. If the combination of citric acid and trisodium citrate is used alone to control the content and pH value of the citrate simultaneously, the use amount of citric acid is large to achieve the required pH value, which also causes the decomposition of bicarbonate radical. Although there are some methods of adjusting the pH of a solution using carbon dioxide, it has been found that the use of carbon dioxide alone to adjust a solution requires a significant partial pressure of carbon dioxide in the solution. CO2₂Too high a pressure brings about a plurality of pH instability factors in the process production. The use of carbon dioxide alone is therefore not an optimal choice.

It was found by chance that when the pH was controlled by charging a combination of carbon dioxide, citric acid and trisodium citrate in solution on the basis of meeting the overall citrate concentration within a certain range, it was surprising that not only the citrate concentration but also the pH in solution met the requirements, and above all the stability of the bicarbonate in solution was the best.

In order to achieve the purpose, the balance liquid is prepared by dissolving sodium chloride, potassium chloride, calcium chloride, magnesium sulfate, sodium bicarbonate, citric acid and trisodium citrate in water for injection according to a ratio. In order to achieve the above object, citric acid and trisodium citrate are used in a ratio of 1: 2.5-3.5, preferably 1: 3, by weight.

The product is obtained by the following method:

weighing raw materials in proportion for later use;

adding sodium chloride, potassium chloride, calcium chloride, magnesium sulfate, citric acid, trisodium citrate and optionally added glucose into water for injection, stirring and dissolving to obtain a preparation solution I;

③ adding sodium bicarbonate into water for injection, dissolving, and introducing CO into water before or after dissolving sodium bicarbonate₂Until saturated or nearly saturated, obtaining a preparation liquid II; preferably, the water is at about 30 ℃, in which case carbon dioxide is used in order to lower the pH of the solution and to make the dissolved bicarbonate more stable during the preparation process;

fourthly, mixing the prepared liquid I and the prepared liquid II obtained in the second step and the third step, adding water for injection to constant volume to full volume, and introducing CO into the solution₂Adjusting the pH to 6.0-7.5, preferably to a pH between 6.7-7.3, most preferably to about 7.0; researches show that the generation of calcium and magnesium ion precipitation in the later sterilization and heating process can be obviously reduced after carbon dioxide is introduced in the step. The skilled person can perform filtration before or after adjusting the pH, depending on the implementation;

fifthly, encapsulating the solution obtained in the step IV; or,

calcium chloride, magnesium sulfate and glucose which is optionally added are encapsulated by adopting a medical non-PVC multilayer co-extrusion film infusion bag compartment immediate-dispensing type infusion packaging process: in the second step, calcium chloride, magnesium sulfate and glucose which is optionally added are not added into the preparation liquid I to be dissolved, and the calcium chloride, the magnesium sulfate and the glucose which is optionally added are encapsulated with the preparation liquid after the constant volume in a two-chamber or three-chamber separation chamber, and are extruded and uniformly mixed before use;

preferably, the method further comprises a sterilization step; for safety of operation, it is preferable that the temperature is lowered to room temperature for 2 hours after sterilization and then the product is taken out.

Calcium/magnesium ions necessary for tissue cell metabolism are contained in the components of the balance liquid, and the used raw materials of calcium chloride and magnesium sulfate are packaged by conventional infusion or by ready-to-use infusion, namely, the calcium chloride and the magnesium sulfate are packaged by a partition chamber of a medical non-PVC multi-layer co-extrusion film infusion bag and are uniformly extruded before use.

The balancing liquid contains calcium or magnesium ions which are fully subjected to a complexing reaction with citric acid to form complex calcium or magnesium, and no precipitate is formed.

The balance liquid also comprises components capable of providing glucose which is an energy metabolism substrate necessary for cell basal metabolism, and the value of the balance liquid is close to the normal blood glucose concentration, and the blood glucose concentration cannot be increased due to conventional infusion. The addition amount is 0g-50g of glucose or 0-278mmol/L of molar concentration in every 1000ml of bicarbonate physiological equilibrium solution.

After medical standard carbon dioxide gas is introduced into the balance solution to adjust the pH value, the balance solution is correspondingly subpackaged into 2000ml, 1000ml, 500ml, 250ml and 100 ml; and (3) packaging and autoclaving by adopting a glass bottle, a medical PVC bottle or a medical non-PVC multi-layer co-extrusion film infusion bag.

The physiological equilibrium bicarbonate solution has stable physicochemical properties at room temperature after sterilization and packaging, and does not need low-temperature storage.

Compared with the prior art, the invention has the following advantagesThe point and the application are as follows: the formula is more physiological, the bicarbonate can directly play the role of acid-base balance immediately after being input without metabolic energy consumption, and the hyperlactacidosis cannot be caused; the content of sodium ions and the osmotic concentration are closer to physiological values; cl^-The content is close to extracellular fluid and is lower than that of ringer's solution, so that iatrogenic hyperchloremic metabolic acidosis cannot be caused by large-scale infusion; contains magnesium ions with concentration similar to that of extracellular fluid, and is favorable for maintaining serum Mg²⁺The compound can activate various enzymes involved in sugar, protein and fat metabolism, and has positive effects of preventing immune stress and oxidative stress, and relieving insulin resistance and lipid peroxidation under stress state. ② has no inhibiting effect on cardiovascular system. And the influence on the environment in the organism, the tissue fluid overload and the intercellular edema is smaller, and better fluid selection is provided for supplementing the loss of functional extracellular fluid in the perioperative period. Fourthly, the medicine can be prepared into oral solution for supplementing extracellular fluid for children or adults, and can also be used as surgical washing fluid or buffer solution. Selecting proper amount of citric acid, citrate and carbon dioxide to adjust pH value without causing HCO₃ ^-Can significantly reduce (the reduction range is within normal physiological range), can significantly control the pH of the prepared solution, and the unique advantages of the selected technical improvement are that the process flow can be simplified, the pH adjustment can be carried out without using carbon dioxide with excessive pressure, and the electrolyte and HCO of the prepared equilibrium solution can be used₃ ^-The content is closer to the physiological state of the organism; proper citric acid can also play a good role in metabolic regulation when being infused into the body, and because the proper citric acid is taken as an important intermediate metabolite in the tricarboxylic acid cycle, the citric acid can play a role in substrate induction and is beneficial to the generation of energy. The theoretical disadvantage is that a large rapid infusion, e.g. > 5000ml/h, may cause a relative reduction in plasma free calcium, but in practice such rapid infusion is not clinically possible and so the chance of such deficiency actually occurring is rare; even so, when a large amount of the medicine is used, once hypocalcemia occurs, the medicine can be corrected by appropriately supplementing calcium chloride or calcium gluconate.

Concrete mode of installation

Comparative example 1

Weighing 6.2g of sodium chloride (NaCl), 0.3g of potassium chloride (KCl) and calcium chloride (CaCl)₂·2H₂O)0.22g, magnesium sulfate (MgSO)₄·7H₂O)0.25g, adding a proper amount of water for injection, and stirring to dissolve;

② sodium bicarbonate (NaHCO) is weighed₃)2.3g of the mixture is added with a proper amount of water for injection (already-used medical CO)₂(ii) a Water temperature is about 30 ℃), stirring and dissolving;

thirdly, mixing the first and the second preparation solutions, adding water for injection to a constant volume of 1000ml, introducing medical standard CO₂Gas (about 60 minutes), adjusting the pH value to 6.0-7.5;

fourthly, filtering, encapsulating and sterilizing for 20 minutes at 120 ℃ in a conventional way;

fifthly, after sterilization, the temperature is reduced to the room temperature for more than 2 hours, and the mixture is taken out after boiling.

Experiments prove that: the particles before and after filtration are not qualified in the determination (the number of particles with the diameter more than or equal to 2 mu m is more than 3000/ml), and precipitates are generated by visual observation.

Comparative example 2

Weighing 6.2g of sodium chloride (NaCl), 0.3g of potassium chloride (KCl) and calcium chloride (CaCl)₂·2H₂O)0.22g, magnesium sulfate (MgSO)₄·7H₂O)0.25g, trisodium citrate (Na)₃C₆H₅O₇·2H₂O)0.6g, adding a proper amount of water for injection, stirring and dissolving;

② sodium bicarbonate (NaHCO) is weighed₃)2.3g of the mixture is added with a proper amount of water for injection and stirred to be dissolved;

mixing the first and second preparation solutions, adding water for injection to a constant volume of 1000ml, filtering, and encapsulating;

fourthly, sterilizing for 20 minutes at 120 ℃ in a conventional way;

taking out the mixture by boiling, observing meat and determining particles to reach the requirements of relevant pharmaceutics of pharmacopoeiaNo precipitate is generated; measured out [ HCO₃ ^-]In the normal physiological range, but the pH measurements were all greater than 8.0.

The conclusion is drawn from the above experiments: the citrate has a stabilizing effect on calcium and magnesium ions (no precipitate is generated).

Comparative example 3

Weighing 6.2g of sodium chloride (NaCl), 0.3g of potassium chloride (KCl) and calcium chloride (CaCl)₂·2H₂O)0.22g, magnesium sulfate (MgSO)₄·7H₂O)0.25g, citric acid (C)₆H₈O₇)0.6g, adding a proper amount of water for injection, stirring and dissolving;

mixing the first step and the second step, adding water for injection to a constant volume of 1000ml, wherein bubbles overflow immediately, the pH of the measured solution is obviously reduced (both are less than 5.0) along with the increase of the addition amount of the citric acid, neutralizing and titrating the citric acid by NaOH, adjusting the pH value to 7.0, filtering and encapsulating;

fourthly, sterilizing for 20 minutes at 120 ℃ in a conventional way;

fifthly, after sterilization, the temperature is reduced to room temperature and the pot is opened, the meat looks at and the particle measurement both reach the requirements of relevant pharmaceutics of pharmacopeia without precipitation; but actually measured [ HCO ]₃ ^-]Is 10-23m mol/L (and [ HCO)₃ ^-]Decreasing with increasing citric acid addition).

The conclusion is drawn from the above experiments: the technical route of using citric acid alone in combination with calcium and magnesium ions is not feasible. Although the problem of precipitation when calcium and magnesium ions and bicarbonate ions in the electrolyte solution are co-dissolved can be avoided, the pH value in the solution is obviously reduced (both are less than 5.0 and exceed the compensation range allowed by physiological requirements) along with the increase of the addition amount of citric acid, [ HCO ]₃ ^-]The citric acid neutralizes sodium bicarbonate to produce CO₂Gas form escaping from solution, [ HCO₃ ^-]And the pH drops; range of fluctuation thereofThis has a very negative effect on the stability of the bicarbonate ions in the dispensed electrolyte solution, outside the physiologically tolerable range, and is not physiologically desirable.

Comparative example 4

thirdly, mixing the first and the second preparation liquid, adding water for injection to a constant volume of 1000ml, and introducing medical CO₂Until the pH value reaches the physiological pH range, the pH value is found to be also along with CO₂The partial pressure value is increased and decreased;

filtering, filling and sealing, and sterilizing for 20 minutes at 120 ℃ in a conventional way;

in the experiment, the pressure of the carbon dioxide in the container is increased after heating, so as to prevent burst and fully dissolve the carbon dioxide and the prepared solution, and therefore, the carbon dioxide is taken out after being sterilized and cooled to room temperature (more than about 2 hours);

the conclusion is drawn from the above experiments: the visual observation and the particle measurement both meet the requirements of relevant pharmaceutics of pharmacopeia, and no precipitate exists; determination of [ HCO ] in the resulting solution₃ ^-]The fluctuation range of (A) is 20-35m mol/L, and the fluctuation range of the measured pH value is 6.0-8.0. The conclusion is drawn from the above experiments: solutions containing trisodium citrate alone and pH adjusted with medical carbon dioxide alone will be due to CO₂Dissolved to lower the pH, but CO is present at high pressure₂Hydrogen ions are ionized after the hydrogen ions are dissolved in the aqueous solution, and bicarbonate ions are also added; in this test, [ HCO ] was observed₃ ^-]With CO₂An increase in partial pressure; when the CO2 partial pressure is more than 120mmHg, [ HCO ] contained in the solution₃ ^-](> 30mmHg) clearly exceeds the physiological demand range(23-27mmHg)。

Example 1

Weighing 6.2g of sodium chloride (NaCl), 0.3g of potassium chloride (KCl) and calcium chloride (CaCl)₂·2H₂O)0.22g, magnesium sulfate (MgSO)₄·7H₂O)0.25g, citric acid (C)₆H₈O₇)0.2g trisodium citrate (Na)₃C₆H₅O₇·2H₂O)0.6g, adding a proper amount of water for injection, stirring and dissolving;

thirdly, mixing the first and the second preparation solutions, adding water for injection to a constant volume of 1000ml, introducing medical standard CO₂The gas was such that the pH of the resulting solution ranged from 7.0, at which point CO was measured₂Adjusting the partial pressure value to 70mmHg, and performing sealed filtration and encapsulation;

fourthly, sterilizing for 20 minutes at 120 ℃ in a conventional way;

fifthly, the pressure of the carbon dioxide in the container is increased after the product is heated, in order to prevent burst and fully dissolve the carbon dioxide and the prepared solution,

therefore, after sterilization, the temperature is required to be reduced to the room temperature for more than 2 hours, and the sterilized product can be taken out after being boiled and then is labeled or packaged with a label;

the experimental results are as follows: the content of each ion of the obtained bicarbonate physiological balance liquid is actually measured to be Na⁺ 139m mol/L，Cl^- 113mmol/L，K⁺4m mol/L，Ca²⁺1.5m mol/L，Mg²⁺1m mol/L，SO4^2-1m mol/L，HCO₃ ^-26mmol/L，Citrate^3-3m mol/L; the pH value is measured to be 7.00 by a pH instrument under the condition of room temperature and 28 ℃;

and (3) stability investigation: standing at room temperature under natural illumination; the measured stability data after 60 days show that all components, pH and osmotic pressure in the solution obtained by the completely airtight packaging process are stable and do not change obviously; the color of the solution is unchanged, and no precipitate is generated.

Example 2

Weighing 6.2g of sodium chloride (NaCl), 0.3g of potassium chloride (KCl) and calcium chloride (CaCl)₂·2H₂O)0.11g, magnesium sulfate (MgSO)₄·7H₂O)0.25g, citric acid (C)₆H₈O₇)0.1g trisodium citrate (Na)₃C₆H₅O₇·2H₂O)0.3g, adding a proper amount of water for injection, stirring and dissolving;

thirdly, mixing the first and the second preparation solutions, adding water for injection to a constant volume of 1000ml, introducing medical standard CO₂The gas was such that the pH of the resulting solution ranged from 7.0, at which point CO was measured₂Adjusting the partial pressure value to be about 70mmHg, and carrying out sealed filtration and encapsulation;

fourthly, sterilizing for 20 minutes at 120 ℃ in a conventional way;

the experimental results are as follows: the content of each ion of the obtained bicarbonate physiological balance liquid is actually measured to be Na⁺136m mol/L，Cl^-111.5mmol/L，K⁺4m mol/L，Ca²⁺0.75m mol/L，Mg²⁺1m mol/L，SO₄ ^2-1m mol/L，HCO₃ ^-26mmol/L，Citrate^3-1.5m mol/L; the pH value is measured to be 7.00 by a pH instrument under the condition of room temperature and 28 ℃;

and (3) stability investigation: standing at room temperature under natural illumination; the measured stability data after 60 days show that the components and pH value of the solution obtained by the completely airtight packaging process are not changed; no precipitate is generated.

Example 3

Weighing 6.2g of sodium chloride (NaCl), 0.3g of potassium chloride (KCl) and calcium chloride (CaCl)₂·2H₂O)0.22g, magnesium sulfate (MgSO)₄·7H₂O)0.25g, glucose (C)₆H₁₂O₆)0.9g of citric acid (C)₆H₈O₇)0.2g trisodium citrate (Na)₃C₆H₅O₇·2H₂O)0.6g, adding a proper amount of water for injection, stirring and dissolving;

thirdly, mixing the first and the second preparation solutions, adding water for injection to a constant volume of 1000ml, introducing medical standard CO₂The gas is such that the pH of the resulting solution is in the range of 6.0 to 7.5 (preferably pH7.0, where CO is measured at the time₂Adjusting the partial pressure value to 70mmHg), sealing, filtering, and encapsulating;

fourthly, sterilizing for 20 minutes at 120 ℃ in a conventional way;

the experimental results are as follows: the content of each ion of the obtained bicarbonate physiological balance liquid is actually measured to be Na⁺139m mol/L，Cl^- 113mmol/L，K⁺4m mol/L，Ca²⁺1.5m mol/L，Mg²⁺1m mol/L，SO₄ ^2-1m mol/L，HCO₃ ^-26mmol/L，Citrate^3-3m mol/L and 5m mol/L Glucose; the pH value is measured to be 7.00 by a pH instrument under the condition of room temperature and 28 ℃;

Claims

1. A bicarbonate physiological balanced solution, which is characterized in that: the content of each ion of the physiological equilibrium solution is actually measured to be Na⁺136m mol/L，Cl-111.5m mol/L，K⁺4m mol/L，Ca²⁺0.75m mol/L，Mg²⁺1m mol/L，SO₄ ^2-1m mol/L，HCO₃ ^-26m mol/L，Citrate^3-1.5m mol/L; the pH value is measured to be 7.00 by a pH instrument under the condition of room temperature and 28 ℃;

the physiological equilibrium solution is prepared by the following process:

weighing 6.2g of NaCl,KCl 0.3g, CaCl calcium chloride dihydrate₂·2H₂O0.11g, magnesium sulfate heptahydrate MgSO₄·7H₂0.25g of O and citric acid C₆H₈O₇0.1g trisodium citrate dihydrate Na₃C₆H₅O₇·2H₂0.3g of O, adding a proper amount of water for injection, and stirring to dissolve;

② sodium bicarbonate NaHCO is weighed₃2.3g, adding already-available medical CO₂Proper amount of water for injection with the water temperature of 30 ℃ is stirred and dissolved;

fourthly, sterilizing for 20 minutes at 120 ℃ in a conventional way;

fifthly, after the product is heated, the pressure of carbon dioxide in the container is increased to prevent burst and to ensure that the carbon dioxide and the prepared solution are fully dissolved, so that the product can be taken out after the temperature is reduced to room temperature for more than 2 hours after sterilization, and then the product is pasted with a label or a seal and packaged.