Compound electrolyte injection based on fructose and preparation method thereof

Abstract

The invention relates to a fructose-based compound electrolyte injection and a preparation method thereof. Every 100 ml of the solution is prepared from the following components by weight: 0.7 g to 4.0 g of anhydrous fructose, 0.01 g to 0.04 g of MgCl2. 6H2O, 0.014 g to 0.059 g of CaCl2. 2H2O, 0.4 g to 0.6 g of NaCl, 0.012 g to 0.04 g of KC1, 0.1 g to 0.4 g of sodium lactate, 0.001 g to 0.2 g of sodium pyrosulfite, 6 g to 30 g of colloidal substance and the balance of water for injection. According to the scheme, the problems that an existing compound electrolyte injection is short in shelf life and single in function are solved. The colloidal substance does not react with fructose, Mg, Ca, Na, K salt and the like, does not influence the absorption and utilization of effective components, has small influence on the overall osmotic pressure of the fructose electrolyte injection, can supplement energy during clinical use, can further improve the anti-shock ability, and has a good application prospect. The use of an electrolyte injection and the use of an anti-shock liquid are avoided, and the infusion process is simplified, so that the infusion convenience and effectiveness are improved.

Description

Technical Field

[0001] The invention belongs to the field of medical technology, and in particular relates to a fructose-based compound electrolyte injection and a preparation method thereof. Background Art

[0002] Clinically, patients after surgery usually cannot eat a lot immediately and need to replenish water, electrolytes and calories from the vein. Electrolyte solutions are also needed in hemorrhagic shock caused by surgery or trauma.

[0003] Chinese patent CN100333728C discloses a compound electrolyte fructose injection, which is used for fluid replacement therapy during the polyuria period after renal transplantation. The solution uses fructose instead of glucose, selects an appropriate concentration range, and prepares a compound injection. Its components and proportions are as follows:

[0004]

[0005] This scheme uses fructose instead of glucose to ensure the body's energy supply and reduce the increase in blood sugar after surgery, which helps to reduce the burden on the kidneys. At the same time, it is also suitable for postoperative fluid replacement in diabetic patients. However, the shelf life of the compound electrolyte fructose injection in this scheme is short.

[0006] Chinese patent CN101947240A discloses a mixed sugar electrolyte pharmaceutical composition injection, the pharmaceutical composition includes 30 parts of glucose, 0.41 parts of sodium acetate, 15 parts of fructose, 0.185 parts of calcium chloride, 7.5 parts of xylitol, 0.255 parts of magnesium chloride, 0.87 parts of dipotassium hydrogen phosphate, 0.730 parts of sodium chloride, and 0.0007 parts of zinc sulfate. The mixed sugar electrolyte pharmaceutical composition recorded in the patent scheme also includes an antioxidant, which is selected from one of sodium bisulfite, sodium pyrosulfite, sodium sulfite, and sodium thiosulfate, preferably sodium bisulfite. The dosage range of the antioxidant is 0.01%-0.2% of the total volume of the injection (or the aqueous solution of the pharmaceutical composition). The scheme emphasizes that the mixed sugar electrolyte pharmaceutical composition not only provides the body with multiple electrolytes and mixed sugars at the same time, but also can effectively reduce blood sugar fluctuations, reduce other metabolic complications caused by single monosaccharide energy supply, and better provide the energy required by critically ill patients. In addition, it also has the characteristics of complete metabolism, high energy supply, and small blood sugar fluctuations. However, sulfites have potential toxic risks, mainly inducing hypersensitivity reactions and damaging tissues and organs.

[0007] Chinese patent CN104666333A discloses a peritoneal dialysis solution containing 1.5-4.25% glucose, 0.4-0.7% sodium chloride, 0.02-0.03% calcium chloride, 0.01-0.02% magnesium chloride, and 0.4-0.6% sodium lactate, wherein the pH value of the peritoneal dialysis solution is adjusted to 7.3-7.7 with an inorganic base. The scheme also states that it contains 0.001% to 0.01% sodium metabisulfite, sodium sulfite or sodium bisulfite. Although sodium metabisulfite is often used as an antioxidant in injections. It has unsaturated groups and is easily oxidized, so it can be used as an antioxidant in injections to help prevent other ingredients in the injection from being oxidized, thereby maintaining the quality and stability of the injection. Sodium metabisulfite also has a preservative effect, and undissociated sulfurous acid is believed to inhibit the growth of microorganisms such as yeast and bacteria, which is very important in the field of medicine. However, the use of sodium metabisulfite also needs to be strictly controlled to ensure its safety and effectiveness.

[0008] On the other hand, existing electrolyte injection components are mainly used to replenish the volume of patients after surgical operations. However, surgery, trauma, combat injuries, etc. can easily lead to hemorrhagic shock, and existing electrolyte solutions do not have anti-shock functions and cannot avoid the occurrence of shock. Summary of the invention

[0009] The compound electrolyte injection in the prior art has the problem of a short shelf life. Although the compound electrolyte injection with the addition of antioxidants has a longer shelf life, there are still problems with whether the antioxidants have toxicity risks and the effectiveness and safety of the dosage. In addition, the existing compound electrolyte injection has a relatively simple function, which is mainly to provide basic water, electrolytes and heat, and has no anti-shock function, and cannot avoid the occurrence of hemorrhagic shock caused by surgery, trauma, and combat injuries.

[0010] The purpose of the present invention is to provide a fructose-based compound electrolyte injection and a preparation method thereof in order to overcome the defects of the above-mentioned prior art.

[0011] The purpose of the present invention can be achieved by the following technical solutions:

[0012] The present application provides a fructose-based compound electrolyte injection, wherein the components and proportions of each 100 ml solution are as follows:

[0013]

[0014] Preferably, the fructose-based compound electrolyte injection of the present application has the following components and proportions per 100 ml of solution:

[0015]

[0016] In one embodiment of the present invention, the colloid substance is selected from dextran, hydroxyethyl starch or polyethylene glycol.

[0017] Compound Electrolyte Injection Compound Electrolyte Injection Compound Electrolyte Injection In the present application, sodium metabisulfite is added as an antioxidant, and the dosage of sodium metabisulfite is reduced in the present application to further improve biosafety.

[0018] In one embodiment of the present invention, the fructose-based composite electrolyte injection has the following components and proportions per 100 ml of solution:

[0019]

[0020]

[0021] Preferably, the fructose-based composite electrolyte injection has the following components and proportions per 100 ml of solution:

[0022]

[0023] The present application also provides a method for preparing a fructose-based compound electrolyte injection, comprising the following steps:

[0024] (1) Dissolve the fruit-free sugar in water for injection at a temperature below 50°C (e.g., 30-50°C, 40-50°C, 45°C), and mix and stir until completely dissolved;

[0025] (2) Add MgCl2·6H2O, CaCl2·2H2O, NaCl, KCl, sodium lactate, sodium pyrosulfite and colloidal substances to the mixed solution and stir until completely dissolved;

[0026] (3) Add water for injection;

[0027] (4) heating the mixture to 70-80° C., stirring for 20-30 min, and fine filtering with a 0.22 μm microporous filter membrane to obtain a fructose-based composite electrolyte injection;

[0028] (5) Packaging and sealing: The compound electrolyte injection is packaged in inner bags, and after the compound electrolyte injection is placed in the inner bags, nitrogen is filled into the inner bags to replace the air, so as to prevent the compound electrolyte injection from contacting the air, thereby further improving its shelf life;

[0029] (6) Sterilize the outer surface of the inner bag containing the compound electrolyte injection solution, put the inner bag into the outer bag, fill the outer bag with nitrogen to replace the air, and seal the outer bag. After sealing, the inside of the outer bag is sterile.

[0030] In one embodiment of the present invention, the dissolved oxygen in the entire preparation process is controlled within a range of less than 3 ppm.

[0031] In one embodiment of the present invention, the inner bag described in step (5) can be made of any infusion bag material in the prior art, such as a multi-layer co-extruded infusion bag (such as a non-PVC three-layer co-extruded infusion bag) or a polypropylene infusion bag or a vertical polypropylene infusion bag, etc. Preferably, in order to further reduce the loss of gas in the inner bag, the inner bag can be designed to be composed of a multi-layer co-extruded infusion bag substrate and a gas barrier material layer arranged on the outer surface of the multi-layer co-extruded infusion bag substrate, wherein the multi-layer co-extruded infusion bag substrate can be a non-PVC three-layer co-extruded infusion bag, etc., and the gas barrier material layer is a layer composed of a gas barrier material, and the gas barrier material can be high-barrier EVOH, silicon oxide or titanium oxide, etc. The outer bag can be designed as a gas-barrier sealing bag to block oxygen, and its material is a material with high barrier properties, such as a three-layer composite material of polypropylene, nylon and polyester. The gas permeability of this barrier outer bag is extremely weak, which can further improve the shelf life of the compound electrolyte injection.

[0032] In addition, since the packaging bag structure of the present application is to protect the inner bag and the outer bag, and the interior of the sealed outer bag is sterile, the inner bag can be directly used in an environment with high sterility requirements, such as in an operating room, which has the advantage of being easy to use.

[0033] In one embodiment of the present invention, in step (6), hot pressing sterilization at 115° C. for 30 min is preferably adopted.

[0034] In the preparation method of the present invention, unless otherwise specified, the steps, methods, devices or instruments used are all commonly known in the art, or can be easily obtained by those skilled in the art based on the teachings of this application and the common knowledge in the art.

[0035] Compared with the prior art, the present invention has the following advantages and beneficial effects:

[0036] (1) The electrolyte ingredients are complete, including fruit-free sugar, and contain Mg, Ca, Na, and K salts, so there is no need to temporarily add electrolytes to the liquid;

[0037] (2) When in use, only one type of liquid needs to be infused after surgery, and the packaging capacity can be increased as needed, which is easy to operate and reduces the possibility of errors when replacing the liquid. For example, a 1000ml large liquid bag can be prepared, which greatly saves the operating time required for fluid replacement therapy by nursing staff. Since the number of times of adding medicine and changing liquid is reduced, the risk of liquid contamination caused by this is avoided, and the probability of infection of patients is reduced;

[0038] (3) The isomer of glucose, fructose, is used in the liquid to provide energy instead of glucose. Since fructose is metabolized faster than glucose and its utilization in the body is not affected by insulin levels, the infusion of fructose-containing liquid can not only provide energy, but also effectively reduce blood sugar fluctuations, maintain the stability of the body's internal environment, and solve a series of problems caused by high urine sugar;

[0039] (4) Since diabetic patients have the problem of reduced insulin secretion, the present invention is also applicable to diabetic patients undergoing surgery. In the past, when such patients received fluid therapy, insulin had to be added to the sugar solution before infusion;

[0040] (5) The present invention can be used for fluid replacement therapy for patients after general surgery, and is also particularly suitable for replenishing a large amount of water and electrolytes lost by patients in the polyuria period after renal transplantation;

[0041] (6) Since the present application scheme adds sodium pyrosulfite as an antioxidant and the packaging is filled with nitrogen, the compound electrolyte injection has good quality stability and a long shelf life.

[0042] (7) The compound electrolyte injection of the present application also contains a colloidal substance, which is selected from dextran. The present application directly adds the colloidal substance to the compound electrolyte injection. Since the colloidal substance is a macromolecular substance with a particle diameter of 1 to 100 nm, it is not easy to pass through the capillary wall. Its particles remain in the blood vessels to generate colloidal osmotic pressure, retaining the liquid in the blood vessels, thereby increasing and effectively maintaining blood volume. In the state of acute blood loss of a certain amount, it has a significant anti-shock effect.

[0043] (8) The present application scheme directly adds the colloidal substance that has an anti-shock effect to the compound electrolyte injection solution, and strictly controls the dosage of each component. On the one hand, the addition of the colloidal substance has little effect on the overall osmotic pressure of the fructose electrolyte injection solution, and the osmotic pressure can be maintained at about 310mOsm / kg H2O. On the other hand, the presence of the colloidal substance will not react with fructose, Mg, Ca, Na, K salts, etc., and will not affect the absorption and utilization of the effective ingredients. On the other hand, when the present application scheme is used clinically, it can not only replenish energy, but also further improve the anti-shock ability, avoid the separate use of electrolyte injection solution and anti-shock solution, and simplify the infusion process, thereby improving the convenience and effectiveness of infusion.

[0044] (9) The anti-shock colloidal substance of the present application has a synergistic effect with the fructose, Mg, Ca, Na, K salt and other components of the compound electrolyte injection. Compared with the original compound fructose electrolyte injection, it can significantly improve the mean arterial pressure, central venous pressure, cardiac index and stroke volume index of the canine model of shock after fluid resuscitation. BRIEF DESCRIPTION OF THE DRAWINGS

[0045] Figure 1 The mean arterial pressure changes of the four groups of dogs at baseline, during hemorrhagic shock, and after resuscitation with four different fluids;

[0046] Figure 2 The changes of cardiac index in four groups of dogs at baseline, during hemorrhagic shock, and after resuscitation with four different fluids;

[0047] Figure 3 The changes in stroke index of the four groups of dogs at baseline, during hemorrhagic shock, and after resuscitation with four different fluids;

[0048] Figure 4 Shown are the changes in mean pulmonary artery pressure in the four groups of dogs at baseline, during hemorrhagic shock, and after resuscitation with four different fluids. DETAILED DESCRIPTION

[0049] The present invention is described in detail below with reference to the accompanying drawings and specific embodiments.

[0050] Examples 1, 2, 3, Comparative Examples 1, 2, 3

[0051] The formulations of Examples 1, 2, 3 and Comparative Examples 1, 2, 3 are shown in Table 1, wherein the unit not specified is g.

[0052] Table 1 Formula of Examples 1, 2, 3, Comparative Examples 1, 2, 3

[0053]

[0054] The preparation method of the composite electrolyte injection of Examples 1, 2, 3 and Comparative Examples 1, 2, 3 and 4 comprises the following steps:

[0055] (1) Dissolve the fruit-free sugar in 45°C water for injection and mix and stir until completely dissolved;

[0056] (2) Add MgCl2·6H2O, CaCl2·2H2O, NaCl, KCl, sodium lactate, sodium pyrosulfite and colloidal substances to the mixed solution and stir until completely dissolved;

[0057] (3) Add water for injection;

[0058] (4) heating the mixture to 80° C., stirring for 25 min, and fine filtering with a 0.22 μm microporous filter membrane to obtain a fructose-based composite electrolyte injection;

[0059] (5) Packaging and sealing: The compound electrolyte injection is packaged in inner bags, and after the compound electrolyte injection is placed in the inner bags, nitrogen is filled into the inner bags to replace the air, so as to prevent the compound electrolyte injection from contacting the air, thereby further improving its shelf life;

[0060] (6) Sterilize the outer surface of the inner bag containing the compound electrolyte injection solution, put the inner bag into the outer bag, fill the outer bag with nitrogen to replace the air, and seal the outer bag. After sealing, the inside of the outer bag is sterile.

[0061] The inner bags and outer bags of the above embodiments and comparative examples are all made of known materials.

[0062] Animal experiments have shown that after infusion of the injection solutions of Examples 1, 2, and 3 of the present invention, there were no significant changes in the electrolyte levels and pH in the blood of grass dogs before and after the infusion, and the blood sugar levels were also significantly lower than those of Comparative Examples 1, 2, 3, and 4.

[0063] In the clinical trial of the present invention, the values ​​of K ion, Na ion, Cl ion, Ca ion, carbon dioxide binding capacity, blood sugar and urine sugar in the blood of renal transplant patients at different time points after surgery were measured. + :3.5~5.1mmol / L;Na + :135~147mmol / L;Cl - :95~110mmol / L;Ca 2+ : 2.2~2.6mmol / L The normal range of carbon dioxide binding capacity (CO2-cp): 18-27mmol / L. The examples and comparative examples are all within the range.

[0064] Specifically, using the injection of Example 2, the blood electrolytes and carbon dioxide binding capacity of patients at different times before and after kidney transplantation are shown in Table 2. Using the injection of Example 2 and the injection of Comparative Example 2, the comparison of blood sugar and urine sugar (mmol / L) of the two groups of patients after kidney transplantation is shown in Table 3.

[0065] Table 2 Blood indexes of patients at different times before and after renal transplantation using the injection of Example 2

[0066]

[0067] Table 3 Comparison of blood sugar and urine sugar in two groups of patients with different fluid replacement regimens after renal transplantation (mmol / L)

[0068]

[0069] It can be seen from Table 2 and Table 3 that the K in the patient's blood + 、Na + , Cl - , Ca 2+, and the measured values ​​of carbon dioxide binding capacity were maintained within the normal range. The blood sugar and urine sugar were similar to those of the comparative example 2 without the addition of sodium pyrosulfite and dextran. This shows that the compound electrolyte fructose injection of Example 2 of the present invention (compared with the addition of sodium pyrosulfite and dextran in comparative example 2) can ideally maintain the water, electrolyte and acid-base balance in the patient's body, and play a role in lowering the patient's postoperative blood sugar and effectively reducing blood sugar fluctuations.

[0070] Test example of anti-shock effect (synergistic effect)

[0071] Experimental group 1: Lactated Ringer's solution group (commercial sodium lactate Ringer's injection, main ingredients: 3.10g sodium lactate, 6.00g sodium chloride, 0.30g potassium chloride, 0.2g calcium chloride per 1000ml, excipient is water for injection);

[0072] Experimental group 2: Dextran 40 glucose injection (a commercially available product, a sterile aqueous solution of dextran 40 and 5% glucose, the dextran 40 content indicated in the injection instructions is 6 g / 100 ml) group;

[0073] Experimental group 3: compound fructose electrolyte injection group (Comparative Example 1, abbreviated as compound fructose electrolyte injection in the attached figure);

[0074] Experimental group 4: compound electrolyte injection containing dextran (Example 2, abbreviated as dextran 40 fructose electrolyte injection in the attached drawings);

[0075] The specific experimental methods are as follows:

[0076] 48 healthy adult grass dogs, weighing 18-30 kg and with a body surface area of ​​0.71-0.9 m 2 , anesthetized with propofol (6 mg / kg) and fentanyl (5 ug / kg) and randomly divided into four groups.

[0077] The bilateral femoral arteries and femoral veins were separated. The left femoral artery was used to monitor mean arterial pressure (MAP) and draw blood, and the right femoral artery was used for bloodletting. The right femoral vein was used for medication (anesthesia with propofol (6 mg / kg) and fentanyl (5 ug / kg)) and blood drawing, and the left femoral vein was infused (anesthetized first, then bled to shock state, shock period was maintained for 30 minutes and then fluid resuscitation was performed, baseline indexes were measured after anesthesia, shock period indexes were measured 30 minutes after shock, and indexes were measured at 5 minutes, 60 minutes, and 120 minutes after fluid resuscitation). A thermistor-tipped catheter was placed through the external jugular vein to the pulmonary artery, and the pulmonary artery pressure (PAP) was measured by the thermodilution method.

[0078] Measurement indicators: mean arterial pressure MAP, cardiac index CI, stroke index SI, central venous pressure CVP, mean pulmonary artery pressure MPAP. Measure baseline indicators (observation indicators after anesthesia, before bleeding shock as the measurement baseline indicators), then perform bleeding at a rate of 5 ml / kg·min to reach 28 ml / kg of bleeding (about 40% of blood volume) to maintain MAP at 35-45 mmHg, the bleeding period is maintained for 30 minutes, and then re-measure the data of each indicator.

[0079] The patients were randomly divided into 4 groups according to the fluid replacement scheme: ① Lactated Ringer's solution group (lactated Ringer's solution group was supplemented according to the ratio of fluid replacement volume to blood loss volume of 3:1); ② Dextran 40 glucose injection group (injection volume was 6 ml / kg); ③ Compound fructose electrolyte injection group (Comparative Example 1) (volume ratio of fluid replacement volume to blood loss was 3:1); ④ Compound electrolyte injection containing dextran (Example 2) (6 ml / kg).

[0080] In the scheme of this application, the four different groups of fluid replacement amounts are determined according to the ingredients in the liquid. Ringer's and compound fructose are crystalloids that require a large amount of fluid replacement to achieve the anti-shock effect. The two groups of liquids containing dextran contain colloids, which can increase the plasma colloid osmotic pressure, transfer the interstitial fluid to the blood vessels, and synergistically promote the anti-shock effect of fluid replacement itself, so the dosage needs to be controlled. The index data of each group were measured again 5min, 60min, and 120min after infusion. During the experiment, anesthesia was performed first, and then bloodletting was performed until the shock state. After the shock period was maintained for 30 minutes, fluid resuscitation was performed. Baseline index measurements were performed after anesthesia, and shock period indicators were measured 30 minutes after shock. After fluid resuscitation, the indicators were measured at 5 minutes, 60 minutes, and 120 minutes. The animals were killed after the experiment.

[0081] The experimental results are as follows:

[0082] 1. Mean arterial pressure MAP (mmHg)

[0083] Changes in mean arterial pressure in the four groups of dogs at baseline, during hemorrhagic shock, and after resuscitation with four different fluids Figure 1 As shown, the results showed that the target MAP was successfully achieved and maintained in the four groups of dogs after bleeding, and the MAP recovery after fluid resuscitation in the four groups was similar, but the MAP of the compound electrolyte injection containing dextran (Example 2) was restored to a level close to that before bleeding.

[0084] 2. Cardiac index CI (L / min / m 2 )

[0085] Changes of cardiac index in the four groups of dogs at baseline, during hemorrhagic shock, and after resuscitation with four different fluids Figure 2As shown, the results showed that the cardiac index of the lactated Ringer's solution group and the compound fructose electrolyte injection group (Comparative Example 1) was significantly lower than that of the dextran glucose group and the compound electrolyte injection containing dextran (Example 2) after 5min and 60min of resuscitation, and the difference was not obvious after 120min. Only the lactated Ringer's solution group did not recover to the cardiac index level before bleeding after 120min.

[0086] 3. Stroke index SI (ml / m 2 )

[0087] Changes in stroke index of the four groups of dogs at baseline, during hemorrhagic shock, and after resuscitation with four different fluids Figure 3 As shown, the stroke index of the lactated Ringer's solution group and the compound fructose electrolyte injection group (Comparative Example 1) was significantly lower than that of the dextran 40 glucose injection and the compound electrolyte injection containing dextran (Example 2) after 5 minutes and 60 minutes of resuscitation, and the difference was not obvious after 120 minutes. None of the four groups recovered to the pre-bleeding level after 120 minutes.

[0088] 4. Central venous pressure (CVP) (mmHg)

[0089] The changes in central venous pressure of the four groups of dogs at baseline, during the hemorrhagic shock period and after resuscitation with four different fluids are shown in Table 4. The results show that the left cardiac venous pressure in the lactated Ringer's solution group and the compound fructose electrolyte injection group (Comparative Example 1) was significantly lower than that in the dextran 40 glucose injection and the compound electrolyte injection containing dextran (Example 2) after resuscitation for 5 minutes and 60 minutes, and the difference was not obvious after 120 minutes. Only the compound electrolyte injection containing dextran (Example 2) recovered to the pre-bleeding level after 120 minutes.

[0090] Table 4 Data related to central venous pressure (CVP)

[0091]

[0092]

[0093] *p<0.05 compared with the baseline level of the same group

[0094] Ringer's and compound fructose compared with glucose dextran and compound fructose dextran

[0095] 5. Mean pulmonary artery pressure MPAP (mmHg)

[0096] Changes in mean pulmonary artery pressure in the four groups of dogs at baseline, during hemorrhagic shock, and after resuscitation with four different fluids Figure 4As shown, after 5 minutes of resuscitation, the lactated Ringer's solution group was lower than the other groups, and after 5 and 60 minutes, the compound electrolyte injection containing dextran (Example 2) was significantly higher than the other groups. After 120 minutes, there was no significant difference, and only the compound electrolyte injection containing dextran (Example 2) returned to the pre-bleeding level.

[0097] In the above, the animal experiment established a hemorrhagic shock model for dogs, and fluid infusion was performed after the shock period. The fluid resuscitation was evaluated by measuring indicators such as mean arterial pressure and cardiac index. The bar graph data provided showed that the indicators of the embodiment recovered after resuscitation compared with the shock period. It can be seen that the compound electrolyte injection containing dextran in the present application scheme (Example 2) shows better hemodynamic effects in the resuscitation of hemorrhagic shock than the currently commonly used resuscitation fluids, and can provide additional advantages in improving resuscitation efficiency and organ protection.

[0098] The fructose-based compound electrolyte injection of Examples 1, 2, and 3 of the present application is colorless, has zero impurity content, an osmotic pressure of 310 mOsm / kg H2O, a pH of 5, no insoluble particulate matter content, is clear, can be stored at room temperature, and has a storage time of 2 years.

[0099] The above description of the embodiments is to facilitate the understanding and use of the invention by those skilled in the art. It is obvious that those skilled in the art can easily make various modifications to these embodiments and apply the general principles described herein to other embodiments without creative work. Therefore, the present invention is not limited to the above embodiments, and improvements and modifications made by those skilled in the art based on the disclosure of the present invention without departing from the scope of the present invention should be within the scope of protection of the present invention.

Claims

1. A fructose-based compound electrolyte injection, characterized in that: The components and proportions of each 100ml solution are as follows:

2. The fructose-based compound electrolyte injection according to claim 1, characterized in that: The components and proportions of each 100ml solution are as follows:

3. The fructose-based compound electrolyte injection according to claim 1, characterized in that: The colloid substance is selected from dextran, hydroxyethyl starch or polyethylene glycol.

4. The fructose-based compound electrolyte injection according to claim 1, characterized in that: The components and proportions of each 100ml solution are as follows:

5. A method for preparing a fructose-based composite electrolyte injection according to any one of claims 1 to 4, characterized in that: The steps include: (1) Dissolve the fruit-free sugar in water for injection at a temperature below 50°C and mix and stir until completely dissolved; (2) Add MgCl2·6H2O, CaCl2·2H2O, NaCl, KCl, sodium lactate, sodium pyrosulfite and colloidal substances to the mixed solution and stir until completely dissolved; (3) Add water for injection; (4) heating the mixture to 70-80° C., stirring for 20-30 min, and fine filtering with a 0.22 μm microporous filter membrane to obtain a fructose-based composite electrolyte injection; (5) Packaging and sealing: The compound electrolyte injection is packaged in inner bags, and after the compound electrolyte injection is placed in the inner bags, nitrogen is filled into the inner bags to replace the air, so as to prevent the compound electrolyte injection from contacting the air, thereby further improving its shelf life; (6) Sterilize the outer surface of the inner bag containing the compound electrolyte injection solution, put the inner bag into the outer bag, fill the outer bag with nitrogen to replace the air, and seal the outer bag. After sealing, the inside of the outer bag is sterile.

6. The method for preparing a fructose-based composite electrolyte injection according to claim 5, characterized in that: The dissolved oxygen in the entire preparation process is controlled within the range of less than 3ppm.

7. The method for preparing a fructose-based composite electrolyte injection according to claim 5, characterized in that: In step (6), hot pressing sterilization is performed at 115° C. for 30 min.

8. The method for preparing a fructose-based composite electrolyte injection according to claim 5, characterized in that: The inner bag described in step (5) is a non-PVC three-layer co-extruded infusion bag or a polypropylene infusion bag or a vertical polypropylene infusion bag.

9. The method for preparing a fructose-based composite electrolyte injection according to claim 5, characterized in that: The outer bag described in step (5) is an air-barrier sealed bag, and its material adopts a three-layer composite material of polypropylene, nylon and polyester.

10. The method for preparing a fructose-based composite electrolyte injection according to claim 5, characterized in that: The inner bag can be designed to be composed of a multi-layer co-extruded infusion bag base and a gas barrier material layer arranged on the outer surface of the multi-layer co-extruded infusion bag base, wherein the multi-layer co-extruded infusion bag base is a non-PVC three-layer co-extruded infusion bag, and the gas barrier material layer is a layer composed of gas barrier material, and the gas barrier material is high barrier EVOH, silicon oxide or titanium oxide.

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