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

Abstract

The application relates to the field of injection solutions, and particularly discloses a compound sodium acetate xylitol injection solution suitable for patients with traumatic stress hyperglycemia and a preparation method thereof. The compound sodium acetate xylitol injection solution comprises xylitol, sodium chloride, potassium chloride, magnesium chloride, potassium dihydrogen phosphate and sodium acetate. The formula composition and proportion of the injection solution are optimized, so that the injection solution can meet the requirements of traumatic patients for energy, electrolytes and acid-base balance regulation in the maintenance infusion stage, and can reduce the adverse effects caused by blood glucose fluctuation; meanwhile, the preparation process is optimized, the stability of the injection solution 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 trigger a stress response in the body, leading to insulin resistance and elevated blood sugar. Studies have shown that the incidence of stress-induced hyperglycemia and insulin resistance in the early stages after major surgery is approximately 60%. During this period, the body's metabolism and gluconeogenesis accelerate, and the ability of tissue cells to utilize sugar decreases, resulting in stress-induced hyperglycemia and insulin resistance. Sustained high blood sugar levels not only lead to increased catabolism, negative nitrogen balance, decreased lean tissue mass, poor wound healing, and increased infection rates, but also severely impact the body's internal environment and increase mortality.

[0003] Clinically, trauma patients often experience fluid imbalances due to preoperative abstinence from water and bowel preparation, as well as prolonged postoperative fasting. Trauma can also lead to a series of pathophysiological changes in microcirculation, neuroendocrine function, and other processes, leading to disturbances in the body's internal environment, including water and electrolyte levels. Fluid therapy for trauma patients not only maintains water and electrolyte balance, but also corrects acid-base imbalances, replenishes energy, reduces tissue protein breakdown, improves liver function, and prevents ketone body formation, thereby helping to maintain a stable internal environment.

[0004] Glucose is an important energy substance in the body and the primary energy source for tissue cells such as the brain and blood cells. However, using glucose as an energy source can have adverse effects on patients with post-traumatic stress hyperglycemia. Intravenous glucose infusion can increase blood sugar levels, which is detrimental to patients with impaired glucose tolerance and hyperglycemia. This is especially true for patients with post-traumatic stress hyperglycemia and insulin resistance. Elevated blood sugar levels can disrupt the blood-brain barrier, which is closely associated with the development of infection-related complications, inadequate nutrition, and multiple organ dysfunction syndrome, hindering patient recovery.

[0005] Xylitol is a normal intermediate in human carbohydrate metabolism and has multiple physiological effects. It can act as a regulator and nutrient for abnormal sugar, protein, and fat metabolism, providing energy to the body, promoting liver glycogen synthesis, directly penetrating tissues and participating in metabolism, correcting abnormalities in protein, fat, and steroid metabolism, promoting amino acid synthesis into protein, and lowering transaminase levels. In the treatment of diabetes, xylitol can stimulate pancreatic islet cells to secrete insulin and improve the morphology and function of damaged pancreatic tissue. Compared to glucose injection, xylitol injection has significant advantages in managing patients with traumatic stress-induced hyperglycemia.

[0006] Chinese patent CN101167743A proposes a compound xylitol electrolyte injection and its preparation method, which includes xylitol, sodium chloride, potassium chloride, magnesium chloride, sodium acetate, potassium dihydrogen phosphate, and water. Meanwhile, some injections containing xylitol have also appeared on the market. Although these injections can meet the fluid replacement needs of diabetic patients to a certain extent, they have high requirements for the storage environment and need to be stored in a dark and airtight environment at an ambient temperature not exceeding 25°C. The shelf life is relatively short (generally 1-2 years). Moreover, the clarity of the product decreases to varying degrees as the expiration date approaches, and the water loss rate is relatively high, 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 injection 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:

[0009] 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.

[0010] The formula of the compound sodium acetate xylitol injection includes:

[0011] 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, add water for injection to 1000ml;

[0012] The preparation method of the compound sodium acetate xylitol injection comprises:

[0013] (1) Prepare the raw materials and auxiliary materials according to the above formula;

[0014] (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;

[0015] (3) Add the prescribed amount of xylitol to the base solution, stir evenly, then add the remaining 10-20% of water for injection and dilute to volume to obtain an intermediate solution;

[0016] (4) After pre-treating the intermediate solution, the pH value of the intermediate solution is adjusted to 5.0-6.5 using 8-12% hydrochloric acid solution, and fine filtration is performed to obtain a fine filtrate;

[0017] (5) The semen filtrate is packed in an infusion bag, sterilized, and stored in an outer bag with a water-blocking composite film coating on the surface.

[0018] Furthermore, the above-mentioned step of pre-treating the intermediate liquid includes:

[0019] 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;

[0020] The volume of the composite adsorbent accounts for 0.1-0.3% of the total volume of the intermediate liquid.

[0021] Furthermore, the composite adsorbent is obtained by mixing talc powder and modified montmorillonite powder in a mass ratio of 1:0.5-1, and the particle sizes of the talc powder and the modified montmorillonite powder are both 10-30 μm.

[0022] Furthermore, the preparation method of the modified montmorillonite powder is as follows:

[0023] (1) Dispersing montmorillonite powder in water and stirring at 60-70° C. for 4-5 hours to obtain a montmorillonite expanded body dispersion;

[0024] (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;

[0025] (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 to the dopamine solution to carry out a dopamine self-polymerization reaction to obtain a modified montmorillonite powder.

[0026] 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.

[0027] 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.

[0028] 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.

[0029] Furthermore, the fine filtration step includes:

[0030] The intermediate solution after pH adjustment 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.

[0031] 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.

[0032] In summary, this application has the following beneficial effects:

[0033] 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 energy, electrolyte and acid-base balance requirements of patients with traumatic stress hyperglycemia during the maintenance infusion stage; and xylitol does not require the assistance of insulin in the process of entering cells and being converted into D-xylulose and 6-phosphate glucose, which makes the metabolism of xylitol relatively independent of insulin regulation, and is more conducive to blood sugar regulation in patients with traumatic stress hyperglycemia.

[0034] 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, thereby improving 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, completely isolating the product from the external environment, creating a closed, light-shielding, and moisture-proof environment for product storage, reducing the water loss rate of the product during storage, and ensuring product quality.

[0035] 3. In a preferred embodiment of the present application, a composite adsorbent formed by mixing modified montmorillonite powder and talc powder is used to adsorb the intermediate liquid. On the one hand, talc 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 talc powder to enhance its adsorption effect. At the same time, due to its surface modification, the structure is stable and it has good biocompatibility.

[0036] 4. In a preferred embodiment of the present application, the modified montmorillonite powder is formed by expanding montmorillonite and reacting it with chitosan to form a chitosan / montmorillonite intercalation complex, followed by dopamine autopolymerization on the surface. Because chitosan molecules have abundant functional groups, this modified montmorillonite powder can interact with functional groups on the montmorillonite surface to form a stable intercalation structure, thereby enhancing the adsorption properties of the montmorillonite. Furthermore, the dopamine polymer coating formed on the surface not only enhances the surface properties and stability of the montmorillonite, preventing aggregation or precipitation, but also imparts good biocompatibility and high safety for use in injection solutions. DETAILED DESCRIPTION

[0037] The embodiments of the present invention will be described in detail below with reference to the 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. Specific conditions not specified in the examples are carried out according to conventional conditions or conditions recommended by the manufacturer. Reagents or instruments used without indicating the manufacturer are all conventional products that can be purchased commercially.

[0038] The following is a detailed description of the specific embodiments of the present invention. It should be understood that the specific embodiments described herein are only used to illustrate and explain the present invention and are not intended to limit the present invention.

[0039] Preparation example of modified montmorillonite powder

[0040] Preparation Example 1

[0041] This preparation example provides a modified montmorillonite powder, which is prepared by the following method:

[0042] (1) Montmorillonite powder (1 kg) with a particle size of 10-30 μm was dispersed in water and stirred at 65-67° C. for 4.5 h to obtain a montmorillonite expanded body dispersion with a concentration of 0.5 mg / mL.

[0043] (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.

[0044] (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 complex;

[0045] (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;

[0046] (5) The chitosan / montmorillonite intercalation complex obtained in step (3) was resuspended in a Tris-HCl buffer solution, and then slowly added dropwise to the dopamine solution in step (4). After self-polymerization at 45°C and 700 rpm for 16 hours, the mixture was centrifuged and washed, and dried in an oven at 60°C for 12 hours to obtain modified montmorillonite powder.

[0047] Preparation Example 2

[0048] This preparation example provides a modified montmorillonite powder, which is prepared by the following method:

[0049] (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.

[0050] (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.

[0051] (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 complex;

[0052] (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 adding it dropwise to 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 modified montmorillonite powder.

[0053] Preparation Example 3

[0054] This preparation example provides a modified montmorillonite powder, which is prepared by the following method:

[0055] (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.

[0056] (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.

[0057] (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 complex;

[0058] (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 adding it dropwise to 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 modified montmorillonite powder.

[0059] Comparative Preparation Example 1

[0060] This comparative preparation example provides a modified montmorillonite powder, which is prepared by the following method:

[0061] (1) Montmorillonite powder (1 kg) with a particle size of 10-30 μm was dispersed in water and stirred at 65-67° C. for 4.5 h to obtain a montmorillonite expanded body dispersion with a concentration of 0.5 mg / mL.

[0062] (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.

[0063] (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 complex, i.e., chitosan-modified montmorillonite powder, was obtained.

[0064] Comparative Preparation Example 2

[0065] This preparation example provides a modified montmorillonite powder, which is prepared by the following method:

[0066] (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;

[0067] (2) Montmorillonite powder (1 kg) with a particle size of 10-30 μm was dispersed in a Tris-HCl buffer solution, and then slowly added dropwise to the dopamine solution of step (1). After self-polymerization at 45°C and 700 rpm for 16 hours, the mixture was centrifuged and washed, and dried in an oven at 60°C for 12 hours to obtain dopamine-modified montmorillonite powder.

[0068] Example

[0069] Examples 1-5

[0070] This embodiment provides a compound sodium acetate xylitol injection suitable for patients with traumatic stress hyperglycemia, the preparation method of which comprises:

[0071] 1. Prepare the raw materials according to the formula in Table 1;

[0072] Table 1.

[0073]

[0074] (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;

[0075] (3) Add the prescribed amount of xylitol to the base solution, stir evenly, then add the remaining 15% of water for injection and adjust the volume to obtain an intermediate solution;

[0076] (4) The intermediate liquid was placed in a tank containing a composite adsorbent with a particle size of 10-30 μm (the volume of the composite adsorbent accounted for 0.2% of the total volume of the intermediate liquid), stirred for 3.5 hours for pretreatment, and the composite adsorbent was removed by filtration; wherein the composite adsorbent was obtained by mixing talc powder and modified montmorillonite powder in a mass ratio of 1:0.7, and the modified montmorillonite was provided by Preparation Example 1;

[0077] (5) The pH value of the pretreated intermediate solution was adjusted to 5.5-6.0 using a 10% hydrochloric acid solution, and the solution was first passed through a microfiltration membrane with a pore size of 0.45 μm. The resulting filtrate was then filtered twice through a microfiltration membrane with a pore size of 0.22 μm to obtain a refined filtrate.

[0078] (6) The semen filtrate is packed in an infusion bag, sterilized at 121°C for 12 minutes, and stored in an outer bag with a water-blocking composite film coating on the surface.

[0079] Example 6

[0080] This embodiment provides a compound sodium acetate xylitol injection suitable for patients with traumatic stress hyperglycemia, the preparation method of which comprises:

[0081] (1) Prepare the raw materials according to the formula of Example 1 in Table 1;

[0082] (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;

[0083] (3) Add the prescribed amount of xylitol to the base solution, stir evenly, then add the remaining 20% ​​of water for injection and dilute to volume to obtain an intermediate solution;

[0084] (4) The intermediate liquid was placed in a tank containing a composite adsorbent with a particle size of 10-30 μm (the volume of the composite adsorbent accounted for 0.1% of the total volume of the intermediate liquid), stirred for 4 hours for pretreatment, and the composite adsorbent was removed by filtration; wherein the composite adsorbent was obtained by mixing talc powder and modified montmorillonite powder in a mass ratio of 1:1, and the modified montmorillonite was provided by Preparation Example 2;

[0085] (5) The pH value of the pretreated intermediate solution was adjusted to 6.0-6.5 using 8% hydrochloric acid solution, and the solution was first passed through a microfiltration membrane with a pore size of 0.45 μm. The obtained filtrate was then filtered once through a microfiltration membrane with a pore size of 0.22 μm to obtain a refined filtrate.

[0086] (6) The semen filtrate is packed in an infusion bag, sterilized, and stored in an outer bag with a water-blocking composite film coating on the surface.

[0087] Example 7

[0088] This embodiment provides a compound sodium acetate xylitol injection suitable for patients with traumatic stress hyperglycemia, the preparation method of which comprises:

[0089] (1) Prepare the raw materials according to the formula of Example 1 in Table 1;

[0090] (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;

[0091] (3) Add the prescribed amount of xylitol to the base solution, stir evenly, then add the remaining 10% of water for injection and dilute to volume to obtain an intermediate solution;

[0092] (4) The intermediate liquid was placed in a tank containing a composite adsorbent with a particle size of 10-30 μm (the volume of the composite adsorbent accounted for 0.3% of the total volume of the intermediate liquid), stirred for 3 hours for pretreatment, and the composite adsorbent was removed by filtration; wherein the composite adsorbent was obtained by mixing talc powder and modified montmorillonite powder in a mass ratio of 1:0.5, and the modified montmorillonite was provided by Preparation Example 3;

[0093] (5) The pH value of the pretreated intermediate solution was adjusted to 5.0-5.5 using 12% hydrochloric acid solution, and the solution was first passed through a microfiltration membrane with a pore size of 0.45 μm. The obtained filtrate was then filtered twice through a microfiltration membrane with a pore size of 0.22 μm to obtain a refined filtrate.

[0094] (6) The semen filtrate is packed in an infusion bag, sterilized, and stored in an outer bag with a water-blocking composite film coating on the surface.

[0095] Comparative Example

[0096] Comparative Example 1

[0097] The difference between this comparative example and Example 1 is that in step (4), an equal amount of talc is used instead of modified montmorillonite as the adsorbent for pretreatment.

[0098] Comparative Example 2

[0099] The difference between this comparative example and Example 1 is that in step (4), equal amounts of talc powder and montmorillonite (unmodified) are compounded as adsorbents for pretreatment.

[0100] Comparative Example 3

[0101] The difference between this comparative example and Example 1 is that in step (4), equal amounts of the chitosan-modified montmorillonite powder provided in Comparative Preparation Example 1 and talc powder are compounded as adsorbents for pretreatment.

[0102] Comparative Example 4

[0103] The difference between this comparative example and Example 1 is that in step (4), equal amounts of the dopamine-modified montmorillonite powder provided in Comparative Preparation Example 2 and talc powder are compounded as adsorbents for pretreatment.

[0104] Performance testing

[0105] Investigate the stability, safety and water loss rate of injection

[0106] 1. Accelerated testing

[0107] The injection samples provided in Example 1 and Comparative Examples 1-5 were placed in a thermostat at 50°C. 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:

[0108] Table 2.

[0109]

[0110] As shown in Table 2, the injection product provided in Example 1 did not change in shape during the accelerated test, with only slight changes in pH and osmotic pressure, a low water loss rate, and a low content of related degradation substances. Compared to Example 1, the various properties of the injection products provided in Comparative Examples 1-4 changed to varying degrees in the third and sixth months of the accelerated test, with larger amplitudes. In particular, the clarity decreased, and white flocculent suspended matter appeared in Comparative Examples 1 and 2. This demonstrates that the present application pre-treats the medicinal solution with a composite adsorbent formed by compounding talcum powder and modified montmorillonite powder (chitosan and dopamine dual-modified) during the preparation of the injection, which can improve the stability of the medicinal solution during storage.

[0111] 2. Safety Experiment

[0112] (1) Hemolysis test

[0113] The red blood cells of New Zealand rabbits were used to perform a hemolysis test on the injection solution provided in Example 1.

[0114] 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.

[0115] (2) Guinea pig systemic allergy test Guinea pigs were intraperitoneally injected with the injection solution provided in Example 1 for three consecutive times every other day, with the sensitization volume being 0.5 ml / guinea pig. On the 14th and 21st days after the last sensitization, guinea pigs were challenged with an intravenous injection of 2 times the sensitization dose, with the challenge volume being 1.0 ml / guinea pig.

[0116] The results showed that under the conditions of this experiment, the systemic allergic reaction of the test sample in guinea pigs was negative.

[0117] 3. Clinical Application Examples

[0118] 70 patients with traumatic stress-induced 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.

[0119] (1) The xylitol group consisted of 30 patients, including 20 males and 10 females. The average age of the patients was 49.3±2.4 years, and the average disease course was 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, via intravenous drip once a day, and the drip was completed within 2 hours.

[0120] (2) The glucose + insulin group consisted of 30 patients, including 18 males and 12 females. The average age of the patients was 51.1 ± 1.7 years, and the average disease duration 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 units of insulin were added to it. The patients were given an intravenous drip once a day, and the drip was completed within 2 hours.

[0121] (3) The normal saline group included 10 patients, including 5 males and 5 females. The average age of the patients was 53.4±3.3 years, and the average disease duration was 5.8±1.2 years. The patients in the normal saline group were given 500 mL of normal saline on an empty stomach, and the therapeutic drug was added to the solution once a day, with the solution dripped in 2 hours.

[0122] All patients had their blood sugar measured before intravenous drip and again 2 hours after the injection. The results were statistically analyzed.

[0123] The results show that:

[0124] Xylitol group: By comparing the patients' blood sugar levels before and 2 hours after intravenous infusion, it can be seen that the patients' blood sugar levels decreased slightly 2 hours after intravenous infusion, but there was no significant difference (>0.05). The patients showed symptoms of reduced general fatigue, accompanied by symptoms of polyphagia, thirst and hunger.

[0125] 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 levels of patients increased significantly 2 hours after infusion, and the blood sugar fluctuations of patients were relatively large, with a significant difference (<0.01).

[0126] This shows that the xylitol injection provided in the present application can not only meet the energy, electrolyte and acid-base balance requirements of diabetic patients with traumatic stress hyperglycemia during the maintenance infusion phase, but also reduce the adverse effects of blood sugar fluctuations.

[0127] 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 non-creative modifications to the present embodiment as needed, but as long as they are within the scope of the claims of the present application, they are protected by the patent law.

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 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, add water for injection 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) placing the intermediate liquid in a tank containing a composite adsorbent and stirring for 3-4 hours for pretreatment, filtering to remove the composite adsorbent, 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) After the semen filtrate is filled in an infusion bag, sterilized, and stored in an outer bag having a water-blocking composite film coating on the surface; Wherein, the composite adsorbent in step (3) is obtained by mixing talc powder and modified montmorillonite powder in a mass ratio of 1:0.5-1; the preparation method of the modified montmorillonite powder is: Disperse montmorillonite powder in water and stir at 60-70°C for 4-5 hours 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 carry out a dopamine self-polymerization reaction to obtain the modified montmorillonite powder.

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 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 particle sizes of the talc 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 1, 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.

5. The method for preparing the compound sodium acetate xylitol injection suitable for patients with traumatic stress hyperglycemia according to claim 1, 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.

6. The method for preparing the compound sodium acetate xylitol injection suitable for patients with traumatic stress hyperglycemia according to claim 1, 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.

7. 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 pH adjustment 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.

8. A compound sodium acetate xylitol injection suitable for patients with traumatic stress hyperglycemia, characterized in that: The invention discloses a novel cellulose acetate copolymer comprising the steps of: preparing the cellulose acetate copolymer by the preparation method according to any one of claims 1 to 7.

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