Compound sodium acetate xylitol injection suitable for patients with traumatic stress hyperglycemia and preparation method of compound sodium acetate xylitol injection

Abstract

The invention relates to the field of injections, and particularly discloses a compound sodium acetate xylitol injection suitable for patients with traumatic stress hyperglycemia and a preparation method of the compound sodium acetate xylitol injection. The compound sodium acetate and xylitol injection comprises xylitol, sodium chloride, potassium chloride, magnesium chloride, monopotassium phosphate and sodium acetate. The formula composition and proportion of the injection are optimized, so that the injection can meet the requirements of trauma patients on energy, electrolyte and acid-base balance adjustment in a maintenance infusion stage, and can reduce adverse effects caused by blood sugar fluctuation; meanwhile, by optimizing the preparation process, the stability of the injection in the storage process is improved, and the water loss rate is reduced.

Description

Technical Field

[0001] The present application relates to the field of injections, and more specifically, to a compound sodium acetate xylitol injection suitable for patients with traumatic stress hyperglycemia and a preparation method thereof. Background Art

[0002] Severe trauma can cause the body to produce a stress response, insulin resistance, and elevated blood sugar. Studies have shown that the incidence of stress hyperglycemia and insulin resistance in the early stage after major surgical operations is about 60%. During this period, the body's metabolism is accelerated, glycogenolysis is accelerated, and the ability of tissue cells to use sugar decreases, resulting in stress hyperglycemia and insulin resistance. Continuous high blood sugar not only leads to increased catabolism, negative nitrogen balance, reduced lean tissue mass, poor wound healing, and increased infection rates, but also seriously affects the stability of the body's internal environment and increases the mortality rate of patients.

[0003] Clinically, trauma patients often experience fluid imbalance due to preoperative fasting, intestinal preparation, and long-term fasting after surgery. Trauma can also cause a series of pathological and physiological changes in the body's microcirculation, neuroendocrine system, and other internal environmental disorders, followed by disorders of the body's water, electrolytes, and other internal environments. In addition to maintaining water and electrolyte balance, fluid therapy for trauma patients also needs to correct acid-base disorders, replenish the energy needed by the human body, reduce tissue protein decomposition, improve liver function, and prevent ketone body production, which helps maintain a stable internal environment.

[0004] Glucose is an important energy substance in the body and the main energy source for tissue cells such as brain and blood cells. However, for traumatic stress hyperglycemia, glucose as an energy source can have adverse effects. Intravenous infusion of glucose can increase blood sugar, which is not good for patients with impaired glucose tolerance and hyperglycemia, especially for patients with post-traumatic stress hyperglycemia and insulin resistance. Increased blood sugar may disrupt the blood-brain barrier and is closely related to the occurrence of infection-related complications, insufficient nutrition supply, multiple organ dysfunction syndrome, etc., which is not conducive to the patient's recovery.

[0005] Xylitol is a normal intermediate in human carbohydrate metabolism and has multiple physiological effects. It can be used as a regulator and nutrient for abnormal sugar, protein, and fat metabolism, provide energy to the body, promote liver glycogen synthesis, directly penetrate into tissues to participate in metabolism, correct abnormal protein, fat, and steroid metabolism, promote amino acid synthesis of protein, and reduce transaminase. In the treatment of diabetes, xylitol can stimulate pancreatic cells to secrete insulin and improve the morphology and function of damaged pancreatic tissue. Compared with glucose injection, xylitol injection has obvious advantages in controlling patients with traumatic stress hyperglycemia.

[0006] Chinese patent CN101167743A proposes a compound xylitol electrolyte injection and a preparation method thereof, which includes xylitol, sodium chloride, potassium chloride, magnesium chloride, sodium acetate, potassium dihydrogen phosphate and water. At the same time, some injections containing xylitol are also available on the market. Although this type of injection can meet the fluid replenishment needs of diabetic patients to a certain extent, this type of injection has high requirements for the storage environment and needs to be stored in a light-proof and airtight environment not exceeding 25°C. The validity period is relatively short (generally 1-2 years). Moreover, the clarity of the product will decrease to varying degrees as it approaches the validity period, and the water loss rate will be relatively large, making it difficult to ensure product quality. Summary of the invention

[0007] In order to improve the problem of instability and high water loss rate of existing xylitol injections during long-term storage, the present application provides a compound sodium acetate xylitol injection suitable for patients with traumatic stress hyperglycemia and a preparation method thereof.

[0008] This application adopts the following technical solutions: In a first aspect, the present application provides a method for preparing a compound sodium acetate xylitol injection suitable for patients with traumatic stress hyperglycemia.

[0009] The formula of the compound sodium acetate xylitol injection includes: By weight, xylitol: 10.0-100.0g, sodium chloride: 0.2922-2.9224g, potassium chloride: 0.1044-1.0440g, magnesium chloride: 0.1017-1.0168g, potassium dihydrogen phosphate: 0.2722-2.7220g, sodium acetate: 0.5443-5.4432g, water for injection is added to 1000ml; The preparation method of the compound sodium acetate xylitol injection comprises: (1) Prepare raw materials and auxiliary materials according to the above formula; (2) Take 80-90% of the prescribed amount of water for injection, cool it to 55-60° C., add the prescribed amount of sodium chloride, potassium chloride, magnesium chloride, potassium dihydrogen phosphate and sodium acetate while stirring, and stir evenly to obtain a base solution; (3) Add the prescribed amount of xylitol to the base liquid, stir evenly, add the remaining 10-20% of water for injection, and dilute to obtain an intermediate solution; (4) After pre-treating the intermediate liquid, adjusting the pH value of the intermediate liquid to 5.0-6.5 using 8-12% hydrochloric acid solution, and fine filtering to obtain a fine filtrate; (5) The seminal filtrate is packed in an infusion bag, sterilized, and stored in an outer bag having a water-blocking composite film coating on the surface.

[0010] Furthermore, the above-mentioned step of pre-treating the intermediate liquid includes: The intermediate liquid is placed in a tank containing a composite adsorbent and stirred for 3-4 hours, and then filtered to remove the composite adsorbent; The volume of the composite adsorbent accounts for 0.1-0.3% of the total volume of the intermediate liquid.

[0011] Furthermore, the composite adsorbent is obtained by mixing talcum powder and modified montmorillonite powder in a mass ratio of 1:0.5-1, and the particle sizes of the talcum powder and the modified montmorillonite powder are both 10-30 μm.

[0012] Furthermore, the preparation method of the modified montmorillonite powder is as follows: (1) dispersing montmorillonite powder in water and stirring at 60-70° C. for 4-5 hours to obtain a montmorillonite expanded body dispersion; (2) dispersing chitosan in an acetic acid solution, heating to form a chitosan solution, slowly dripping the chitosan solution into the montmorillonite expanded body dispersion, and continuing to stir at 60-70° C. for 18-24 hours to perform an intercalation reaction to obtain a chitosan / montmorillonite intercalation complex; (3) dissolving dopamine hydrochloride in a buffer solution with a pH of 8-9 to obtain a dopamine solution, slowly adding a suspension containing a chitosan / montmorillonite intercalation complex into the dopamine solution to perform a dopamine self-polymerization reaction to obtain a modified montmorillonite powder.

[0013] Furthermore, in the above process of preparing the chitosan / montmorillonite intercalation composite, the mass ratio of montmorillonite powder to chitosan is 1:0.4-0.5.

[0014] Furthermore, in the above-mentioned dopamine self-polymerization reaction, the reaction temperature is 40-50° C., the reaction time is 12-18 hours, and continuous stirring is performed at 600-800 rpm during the reaction.

[0015] Furthermore, in the above-mentioned dopamine self-polymerization reaction, the mass ratio of the chitosan / montmorillonite intercalation complex to the dopamine hydrochloride is 1:0.1-0.2.

[0016] Furthermore, the fine filtration step comprises: The intermediate solution after adjusting the pH is first passed through a microfiltration membrane with a pore size of 0.45 μm, and the obtained filtrate is then filtered through a microfiltration membrane with a pore size of 0.22 μm for 1-2 times to obtain a refined filtrate.

[0017] In a second aspect, the present application also provides a compound sodium acetate xylitol injection suitable for patients with traumatic stress hyperglycemia, which is prepared by the above-mentioned preparation method.

[0018] In summary, this application has the following beneficial effects: 1. The present application optimizes the formula composition of xylitol injection and adjusts the ratio of xylitol, electrolytes (potassium, sodium) and sodium acetate, so that the injection can simultaneously meet the needs of patients with traumatic stress hyperglycemia for energy, electrolytes and regulation of acid-base balance during the maintenance infusion stage; and xylitol does not require the help of insulin in the process of entering cells and converting into D-xylulose and 6-phosphate glucose, which makes the metabolism of xylitol relatively independent of insulin regulation, and is more helpful for blood sugar regulation in patients with traumatic stress hyperglycemia.

[0019] 2. This application optimizes the preparation process of xylitol injection, increases the amount of water for injection in the initial prescription of the solution (80-90% of the prescription amount), which helps to reduce the stirring time; at the same time, all raw materials except xylitol are added together at 55-65°C, which reduces the configuration steps, increases the solubility, prevents the sedimentation of the raw materials, and reduces the cooling time of the water for injection. Afterwards, the intermediate liquid is pretreated, and pyrogens, microorganisms, impurities, etc. in the liquid medicine are removed by adding biocompatible adsorption materials to improve the stability of the injection during storage. Finally, the sterilized product is packaged and stored in an outer bag with a water-blocking composite film coating on the surface, which completely isolates the product from the external environment, creates a closed, light-shielding, and moisture-proof environment for product storage, reduces the water loss rate of the product during storage, and ensures product quality.

[0020] 3. In a preferred embodiment of the present application, a composite adsorbent formed by mixing modified montmorillonite powder and talcum powder is used to adsorb the intermediate liquid. On the one hand, talcum powder has good dispersibility and can effectively physically adsorb impurities in the drug solution, which helps to improve the stability and uniformity of the drug solution; on the other hand, the modified montmorillonite powder can further cooperate with talcum powder to enhance its adsorption effect. At the same time, due to its surface modification, the structure is stable and it has good biocompatibility.

[0021] 4. In a preferred embodiment of the present application, the modified montmorillonite powder is formed by expanding montmorillonite and forming a chitosan / montmorillonite intercalation complex with chitosan, and then performing a dopamine self-polymerization reaction on the surface. Since the chitosan molecule has rich functional groups, the modified montmorillonite powder can interact with the functional groups on the surface of montmorillonite to form a stable intercalation structure, thereby enhancing the adsorption performance of montmorillonite; at the same time, due to the dopamine polymer coating formed on its surface, the surface properties and stability of montmorillonite can be enhanced to prevent its agglomeration or precipitation, and the modified montmorillonite has good biocompatibility and is highly safe for use in injections. DETAILED DESCRIPTION

[0022] The embodiments of the present invention will be described in detail below in conjunction with examples. However, those skilled in the art will understand that the following examples are only used to illustrate the present invention and should not be construed as limiting the scope of the present invention. The specific conditions not specified in the examples are carried out according to conventional conditions or conditions recommended by the manufacturer. The reagents or instruments used without indicating the manufacturer are all conventional products that can be purchased commercially.

[0023] The specific embodiments of the present invention are described in detail below. It should be understood that the specific embodiments described herein are only used to illustrate and explain the present invention, and are not used to limit the present invention.

[0024] Preparation example of modified montmorillonite powder Preparation Example 1 This preparation example provides a modified montmorillonite powder, which is prepared by the following method: (1) Disperse montmorillonite powder (1 kg) with a particle size of 10-30 μm in water and stir at 65-67° C. for 4.5 h to obtain a montmorillonite expanded body dispersion with a concentration of 0.5 mg / mL.

[0025] (2) Disperse 0.4 kg of chitosan in acetic acid solution and heat to form a chitosan solution with a concentration of 0.1 mg / ml.

[0026] (3) slowly dripping the chitosan solution of step (2) into the montmorillonite expanded body dispersion of step (1), stirring at 65° C. for 20 h for intercalation reaction, washing and drying to obtain 1.03 kg of chitosan / montmorillonite intercalation composite; (4) dissolving 0.15 kg of dopamine hydrochloride in a Tris-HCl buffer solution having a pH of 8-9 to obtain a dopamine solution; (5) The chitosan / montmorillonite intercalation complex obtained in step (3) is resuspended in a Tris-HCl buffer solution, and then slowly added dropwise to the dopamine solution in step (4), and a self-polymerization reaction is carried out at 45° C. and 700 rpm for 16 hours, followed by centrifugation and washing, and then placed in an oven at 60° C. and dried for 12 hours to obtain a modified montmorillonite powder.

[0027] Preparation Example 2 This preparation example provides a modified montmorillonite powder, which is prepared by the following method: (1) Montmorillonite powder (1 kg) with a particle size of 10-30 μm was dispersed in water and stirred at 60° C. for 5 h to obtain a montmorillonite expanded body dispersion with a concentration of 0.5 mg / mL.

[0028] (2) Disperse 0.5 kg of chitosan in acetic acid solution and heat to form a chitosan solution with a concentration of 0.1 mg / ml.

[0029] (3) slowly dripping the chitosan solution of step (2) into the montmorillonite expanded body dispersion of step (1), stirring at 70° C. for 18 h for intercalation reaction, washing and drying to obtain 1.07 kg of chitosan / montmorillonite intercalation composite; (4) dissolving 0.2 kg of dopamine hydrochloride in a Tris-HCl buffer solution with a pH of 8-9 to obtain a dopamine solution; (5) resuspending the chitosan / montmorillonite intercalation complex obtained in step (3) in a Tris-HCl buffer solution, and then slowly dropping it into the dopamine solution in step (4), performing a self-polymerization reaction at 50° C. and 600 rpm for 12 hours, centrifuging and washing, and placing it in an oven at 60° C. to dry for 12 hours to obtain a modified montmorillonite powder.

[0030] Preparation Example 3 This preparation example provides a modified montmorillonite powder, which is prepared by the following method: (1) Montmorillonite powder (1 kg) with a particle size of 10-30 μm was dispersed in water and stirred at 70° C. for 4 h to obtain a montmorillonite expanded body dispersion with a concentration of 0.5 mg / mL.

[0031] (2) Disperse 0.4 kg of chitosan in acetic acid solution and heat to form a chitosan solution with a concentration of 0.1 mg / ml.

[0032] (3) slowly dripping the chitosan solution of step (2) into the montmorillonite expanded body dispersion of step (1), stirring at 60° C. for 24 h for intercalation reaction, washing and drying to obtain 1.01 kg of chitosan / montmorillonite intercalation composite; (4) dissolving 0.1 kg of dopamine hydrochloride in a Tris-HCl buffer solution with a pH of 8-9 to obtain a dopamine solution; (5) resuspending the chitosan / montmorillonite intercalation complex obtained in step (3) in a Tris-HCl buffer solution, and then slowly dropping it into the dopamine solution in step (4), performing a self-polymerization reaction at 40° C. and 800 rpm for 18 hours, centrifuging and washing, and placing it in an oven at 60° C. to dry for 12 hours to obtain a modified montmorillonite powder.

[0033] Comparative Preparation Example 1 This comparative preparation example provides a modified montmorillonite powder, which is prepared by the following method: (1) Disperse montmorillonite powder (1 kg) with a particle size of 10-30 μm in water and stir at 65-67° C. for 4.5 h to obtain a montmorillonite expanded body dispersion with a concentration of 0.5 mg / mL.

[0034] (2) Disperse 0.4 kg of chitosan in acetic acid solution and heat to form a chitosan solution with a concentration of 0.1 mg / ml.

[0035] (3) The chitosan solution of step (2) was slowly dripped into the montmorillonite expanded body dispersion of step (1), and the mixture was stirred at 65° C. for 20 h for intercalation reaction. After washing and drying, 1.03 kg of chitosan / montmorillonite intercalation composite, i.e., chitosan-modified montmorillonite powder, was obtained.

[0036] Comparative Preparation Example 2 This preparation example provides a modified montmorillonite powder, which is prepared by the following method: (1) dissolving 0.15 kg of dopamine hydrochloride in a Tris-HCl buffer solution having a pH of 8-9 to obtain a dopamine solution; (2) Dispersing montmorillonite powder (1 kg) with a particle size of 10-30 μm in a Tris-HCl buffer solution, then slowly adding the solution to the dopamine solution in step (1), performing a self-polymerization reaction at 45° C. and 700 rpm for 16 h, centrifuging and washing, and drying in an oven at 60° C. for 12 h to obtain dopamine-modified montmorillonite powder. Example

[0037] Examples 1-5 This embodiment provides a compound sodium acetate xylitol injection suitable for patients with traumatic stress hyperglycemia, and the preparation method thereof comprises: 1. Prepare the raw materials and auxiliary materials according to the formula in Table 1; Table 1. (2) Take 85% of the prescribed amount of water for injection, cool it to 55-60° C., add the prescribed amount of sodium chloride, potassium chloride, magnesium chloride, potassium dihydrogen phosphate and sodium acetate while stirring, and stir evenly to obtain a base solution; (3) Add the prescribed amount of xylitol to the base liquid, stir evenly, add the remaining 15% of water for injection, and adjust the volume to obtain an intermediate solution; (4) placing the intermediate liquid in a tank containing a composite adsorbent having a particle size of 10-30 μm (the volume of the composite adsorbent accounts for 0.2% of the total volume of the intermediate liquid), stirring for 3.5 hours for pretreatment, and filtering to remove the composite adsorbent; wherein the composite adsorbent is a mixture of talcum powder and modified montmorillonite powder in a mass ratio of 1:0.7, and the modified montmorillonite is provided by Preparation Example 1; (5) The pH value of the pretreated intermediate solution was adjusted to 5.5-6.0 using a 10% hydrochloric acid solution, and the intermediate solution was first filtered through a microfiltration membrane with a pore size of 0.45 μm. The filtrate was then filtered twice through a microfiltration membrane with a pore size of 0.22 μm to obtain a refined filtrate.

[0038] (6) The seminal filtrate is packaged in an infusion bag, sterilized at 121° C. for 12 min, and stored in an outer bag having a water-blocking composite film coating on the surface.

[0039] Example 6 This embodiment provides a compound sodium acetate xylitol injection suitable for patients with traumatic stress hyperglycemia, and the preparation method thereof comprises: (1) Prepare the raw materials according to the formula of Example 1 in Table 1; (2) Take 80% of the prescribed amount of water for injection, cool it to 55-60° C., add the prescribed amount of sodium chloride, potassium chloride, magnesium chloride, potassium dihydrogen phosphate and sodium acetate while stirring, and stir evenly to obtain a base solution; (3) Add the prescribed amount of xylitol to the base liquid, stir evenly, add the remaining 20% ​​of water for injection, and adjust the volume to obtain an intermediate solution; (4) placing the intermediate liquid in a tank containing a composite adsorbent having a particle size of 10-30 μm (the volume of the composite adsorbent accounts for 0.1% of the total volume of the intermediate liquid), stirring for 4 hours for pretreatment, and filtering to remove the composite adsorbent; wherein the composite adsorbent is a mixture of talcum powder and modified montmorillonite powder in a mass ratio of 1:1, and the modified montmorillonite is provided by Preparation Example 2; (5) The pH value of the pretreated intermediate solution was adjusted to 6.0-6.5 using 8% hydrochloric acid solution, and the intermediate solution was first filtered through a microfiltration membrane with a pore size of 0.45 μm. The filtrate was then filtered once through a microfiltration membrane with a pore size of 0.22 μm to obtain a refined filtrate.

[0040] (6) The seminal filtrate is packaged in an infusion bag, sterilized, and stored in an outer bag having a water-blocking composite film coating on the surface.

[0041] Example 7 This embodiment provides a compound sodium acetate xylitol injection suitable for patients with traumatic stress hyperglycemia, and the preparation method thereof comprises: (1) Prepare the raw materials according to the formula of Example 1 in Table 1; (2) Take 90% of the prescribed amount of water for injection, cool it to 55-60° C., add the prescribed amount of sodium chloride, potassium chloride, magnesium chloride, potassium dihydrogen phosphate and sodium acetate while stirring, and stir evenly to obtain a base solution; (3) Add the prescribed amount of xylitol to the base liquid, stir evenly, add the remaining 10% of water for injection, and adjust the volume to obtain an intermediate solution; (4) placing the intermediate liquid in a tank containing a composite adsorbent having a particle size of 10-30 μm (the volume of the composite adsorbent accounts for 0.3% of the total volume of the intermediate liquid), stirring for 3 h for pretreatment, and filtering to remove the composite adsorbent; wherein the composite adsorbent is a mixture of talcum powder and modified montmorillonite powder in a mass ratio of 1:0.5, and the modified montmorillonite is provided by Preparation Example 3; (5) The pH value of the pretreated intermediate solution was adjusted to 5.0-5.5 using 12% hydrochloric acid solution, and the intermediate solution was first filtered through a microfiltration membrane with a pore size of 0.45 μm. The filtrate was then filtered twice through a microfiltration membrane with a pore size of 0.22 μm to obtain a refined filtrate.

[0042] (6) The seminal filtrate is packaged in an infusion bag, sterilized, and stored in an outer bag having a water-blocking composite film coating on the surface.

[0043] Comparative Example Comparative Example 1 The difference between this comparative example and Example 1 is that in step (4), an equal amount of talcum powder is used instead of modified montmorillonite as the adsorbent for pretreatment.

[0044] Comparative Example 2 The difference between this comparative example and Example 1 is that in step (4), equal amounts of talcum powder and montmorillonite (unmodified) are compounded as adsorbents for pretreatment.

[0045] Comparative Example 3 The difference between this comparative example and Example 1 is that in step (4), equal amounts of chitosan-modified montmorillonite powder and talcum powder provided in Comparative Preparation Example 1 are compounded as adsorbents for pretreatment.

[0046] Comparative Example 4 The difference between this comparative example and Example 1 is that in step (4), an equal amount of dopamine-modified montmorillonite powder provided in Comparative Preparation Example 2 and talcum powder are compounded as adsorbents for pretreatment.

[0047] Performance testing Investigate the stability, safety and water loss rate of injection 1. Accelerated testing The injection samples provided in Example 1 and Comparative Examples 1-5 were placed in a thermostat at 50° C., and samples were taken at 0, 1, 3, and 6 months, respectively, to examine product properties, pH value, osmotic pressure, water loss rate, and degradation products. The results are shown in Table 2: Table 2. As can be seen from Table 2, the injection product provided in Example 1 did not change in shape during the accelerated test, the pH and osmotic pressure only changed slightly, the water loss rate was low, and the content of related degradation substances was low. Compared with Example 1, the various properties of the injection products provided in Comparative Examples 1-4 changed to varying degrees in the 3rd and 6th months of the accelerated test, and the amplitude was large, especially in terms of properties, the clarity decreased, and white flocculent suspended matter appeared in Comparative Examples 1 and 2. This shows that the composite adsorbent formed by compounding talcum powder and modified montmorillonite powder (chitosan and dopamine double modified) in the preparation process of the injection solution is used to pretreat the drug solution, which can improve the stability of the drug solution during storage.

[0048] 2. Safety Experiment (1) Hemolysis test The red blood cells of New Zealand rabbits were selected to perform a hemolysis test on the injection solution provided in Example 1.

[0049] The results showed that under the experimental conditions, the test sample had no obvious in vitro hemolytic and coagulogenic effects on rabbit red blood cells.

[0050] (2) Guinea pig systemic allergy test Guinea pigs were intraperitoneally injected with the injection sample provided in Example 1 for three consecutive times every other day, and the sensitization volume was 0.5 ml / guinea pig. Guinea pigs were challenged by intravenous injection of 2 times the sensitization dose on the 14th and 21st days after the last sensitization, and the challenge volume was 1.0 ml / guinea pig.

[0051] The results showed that under the conditions of this experiment, the systemic allergic reaction of the test sample in guinea pigs was negative.

[0052] 3. Clinical Application Examples 70 patients with traumatic stress hyperglycemia were selected as research subjects. All patients met the WHO diagnostic criteria and were randomly divided into three groups: xylitol group, glucose + insulin group and normal saline group. (1) There were 30 cases in the xylitol group, including 20 males and 10 females, with an average age of 49.3±2.4 years and an average disease course of 5.2±1.8 years. The administration method was: 500 mL of the xylitol injection provided in Example 1 of the present application was administered on an empty stomach, and the patient was intravenously dripped once a day, and the drip was completed within 2 hours; (2) There were 30 cases in the glucose + insulin group, including 18 males and 12 females. The average age of the patients was 51.1±1.7 years old, and the average course of disease was 5.4±2.1 years. The administration method was: 500 mL of the glucose injection provided in Example 1 was administered on an empty stomach, and 8 u of insulin was added thereto. The patient was intravenously dripped once a day, and the drip was completed within 2 hours; (3) There were 10 cases in the normal saline group, including 5 males and 5 females, with an average age of 53.4±3.3 years and an average disease course of 5.8±1.2 years. The patients in the normal saline group were given 500 mL of normal saline on an empty stomach, and then the therapeutic drugs were added, once a day, and the solution was dripped in 2 hours.

[0053] All patients were given blood sugar measurements before intravenous drip and again 2 hours after the injection. The results were statistically analyzed.

[0054] The results show that: Xylitol group: By comparing the blood sugar levels of patients before intravenous infusion and 2 hours after infusion, it can be seen that the blood sugar level of patients decreased slightly 2 hours after intravenous infusion, but there was no significant difference (>0.05). Patients showed symptoms of reduced general fatigue, accompanied by symptoms of polyphagia, thirst and relief of hunger.

[0055] Glucose + insulin group: By comparing the blood sugar levels of patients before intravenous infusion and 2 hours after infusion, it can be seen that the blood sugar of patients increased significantly 2 hours after infusion, and the blood sugar fluctuations of patients were relatively large, with significant differences (<0.01).

[0056] This shows that the xylitol injection provided in the present application can not only meet the needs of diabetic patients with traumatic stress hyperglycemia for energy, electrolytes and regulation of acid-base balance during the maintenance infusion stage, but also reduce the adverse effects of blood sugar fluctuations.

[0057] This specific embodiment is merely an explanation of the present application and is not a limitation of the present application. After reading this specification, those skilled in the art may make modifications to the present embodiment without any creative contribution as needed, but such modifications are protected by the patent law as long as they are within the scope of the claims of the present application.

Claims

1. A method for preparing a compound sodium acetate xylitol injection suitable for patients with traumatic stress hyperglycemia, characterized in that: The formula of the compound sodium acetate xylitol injection comprises: By weight, xylitol: 10.0-100.0g, sodium chloride: 0.2922-2.9224g, potassium chloride: 0.1044-1.0440g, magnesium chloride: 0.1017-1.0168g, potassium dihydrogen phosphate: 0.2722-2.7220g, sodium acetate: 0.5443-5.4432g, water for injection is added to 1000ml; The preparation method of the compound sodium acetate xylitol injection comprises: (1) Take 80-90% of the prescribed amount of water for injection, cool it to 55-60°C, add the prescribed amount of sodium chloride, potassium chloride, magnesium chloride, potassium dihydrogen phosphate and sodium acetate while stirring, and stir evenly to obtain a base solution; (2) Adding the prescribed amount of xylitol to the base liquid, stirring evenly, adding the remaining 10-20% of water for injection, and adjusting the volume to obtain an intermediate liquid; (3) After pre-treating the intermediate liquid, adjusting the pH value of the intermediate liquid to 5.0-6.5 using 8-12% hydrochloric acid solution, and fine filtering to obtain a fine filtrate; (4) The refined filtrate is packaged in an infusion bag, sterilized, and stored in an outer bag having a water-blocking composite film coating on the surface.

2. The method for preparing the compound sodium acetate xylitol injection suitable for patients with traumatic stress hyperglycemia according to claim 1, characterized in that: The step of pre-treating the intermediate liquid comprises: The intermediate liquid is placed in a tank containing a composite adsorbent and stirred for 3-4 hours, and then filtered to remove the composite adsorbent; The volume of the composite adsorbent accounts for 0.1-0.3% of the total volume of the intermediate liquid.

3. The method for preparing the compound sodium acetate xylitol injection suitable for patients with traumatic stress hyperglycemia according to claim 2, characterized in that: The composite adsorbent is obtained by mixing talcum powder and modified montmorillonite powder in a mass ratio of 1:0.5-1, and the particle sizes of the talcum powder and the modified montmorillonite powder are both 10-30 μm.

4. The method for preparing the compound sodium acetate xylitol injection suitable for patients with traumatic stress hyperglycemia according to claim 2 or 3, characterized in that: The preparation method of the modified montmorillonite powder is: Disperse montmorillonite powder in water, stir at 60-70°C for 4-5h to obtain a montmorillonite expanded body dispersion; Dispersing chitosan in an acetic acid solution, heating to form a chitosan solution, slowly dripping the chitosan solution into the montmorillonite expanded body dispersion, and continuing to stir at 60-70° C. for 18-24 hours to perform an intercalation reaction to obtain a chitosan / montmorillonite intercalation complex; Dopamine hydrochloride is dissolved in a buffer solution with a pH of 8-9 to obtain a dopamine solution, and a suspension containing a chitosan / montmorillonite intercalation complex is slowly added to the dopamine solution to perform a dopamine self-polymerization reaction to obtain the modified montmorillonite powder.

5. The method for preparing the compound sodium acetate xylitol injection suitable for patients with traumatic stress hyperglycemia according to claim 4, characterized in that: In the process of preparing the chitosan / montmorillonite intercalation composite, the mass ratio of the montmorillonite powder to the chitosan is 1:0.4-0.

5.

6. The method for preparing the compound sodium acetate xylitol injection suitable for patients with traumatic stress hyperglycemia according to claim 4, characterized in that: In the dopamine self-polymerization reaction, the reaction temperature is 40-50° C., the reaction time is 12-18 hours, and continuous stirring is performed at 600-800 rpm during the reaction.

7. The method for preparing the compound sodium acetate xylitol injection suitable for patients with traumatic stress hyperglycemia according to claim 4, characterized in that: In the dopamine self-polymerization reaction, the mass ratio of the chitosan / montmorillonite intercalation complex to the dopamine hydrochloride is 1:0.1-0.

2.

8. The method for preparing the compound sodium acetate xylitol injection suitable for patients with traumatic stress hyperglycemia according to claim 1, characterized in that: The fine filtration step comprises: The intermediate solution after adjusting the pH is first passed through a microfiltration membrane with a pore size of 0.45 μm, and the obtained filtrate is then filtered through a microfiltration membrane with a pore size of 0.22 μm for 1-2 times to obtain the refined filtrate.

9. A compound sodium acetate xylitol injection suitable for patients with traumatic stress hyperglycemia, characterized in that: It is prepared by the preparation method according to any one of claims 1 to 8.

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