Instant citric acid dialysis powder and preparation method thereof

Abstract

The invention relates to the technical field of hemodialysis, in particular to instant citric acid dialysis powder and a preparation method thereof. The instant citric acid dialysis powder provided by the invention comprises the following raw materials in parts by weight: 150-350 parts of sodium chloride; 5-15 parts of calcium chloride; 2-10 parts of potassium chloride; 5-15 parts of magnesium chloride; 10 to 50 parts of citric acid; 20 to 40 parts of glucose; 5 to 15 parts of polyethylene glycol; 5 to 15 parts of glycerol; and 500 to 1000 parts of pure water. The instant citric acid dialysis powder provided by the invention adopts high-purity citrate as a main component, through optimized formula design and special process treatment, the dissolving property of the product is remarkably improved, and the product can be completely dissolved in a short time, so that the requirement of clinical rapid use is met.

Description

Technical Field

[0001] The present invention relates to the technical field of hemodialysis, and particularly relates to an instant soluble citrate dialysis powder and a preparation method thereof. Background Art

[0002] In hemodialysis treatment, dialysis powder is a key raw material for preparing dialysis fluid, and its performance directly affects the effect and safety of dialysis treatment. As an important component of dialysis powder, citrate plays a key role in regulating blood acid-base balance, anticoagulation, etc. during dialysis.

[0003] However, there are many problems with traditional citrate dialysis powder in practical applications. On the one hand, the dissolution rate of traditional citrate dialysis powder is relatively slow, which prolongs the preparation time of dialysis fluid, not only reducing the efficiency of dialysis preparation work, but also potentially affecting the timeliness of patients' dialysis treatment. On the other hand, incomplete dissolution of dialysis powder easily leads to uneven composition of dialysis fluid, thereby affecting the clearance effect of metabolic wastes in patients' bodies during dialysis, as well as the regulation of electrolyte and acid-base balance, presenting certain safety hazards and uncertainties in treatment effects. Summary of the Invention

[0004] In order to solve the above technical problems, the present invention provides an instant soluble citrate dialysis powder and a preparation method thereof. The dialysis powder uses high-purity citrate as the main component, and through optimizing the formula design and special process treatment, significantly improves the dissolution performance of the product, and can be completely dissolved in a short time to meet the clinical need for rapid use.

[0005] For this reason, the present invention provides the following technical solutions.

[0006] In a first aspect, in an optional embodiment, the present invention provides an instant soluble citrate dialysis powder, which comprises the following raw materials in parts by weight: 150 - 350 parts of sodium chloride; 5 - 15 parts of calcium chloride; 2 - 10 parts of potassium chloride; 5 - 15 parts of magnesium chloride; 10 - 50 parts of citric acid; 20 - 40 parts of glucose; 5 - 15 parts of polyethylene glycol; 5 - 15 parts of glycerol; 500 - 1000 parts of pure water.

[0007] In the present invention, polyethylene glycol and glycerol are added to the formula of the instant soluble citrate dialysis powder, which can synergistically improve the dissolution performance of the citrate dialysis powder. Polyethylene glycol has good water solubility and strong hydrophilicity, and can quickly adsorb on the surface of the dialysis powder particles, reducing the interfacial tension between the particles and water, making it easier for water to penetrate into the interior of the particles, thereby promoting the dissolution of the dialysis powder. Glycerol also has hydrophilicity, and it can form a thin water film on the surface of the dialysis powder particles, increasing the wettability of the particles, allowing water to better contact the particles and accelerating the dissolution rate. The combined action of the two can make the dialysis powder particles be wetted by water faster, laying a foundation for the subsequent dissolution process. Moreover, the molecular chain of polyethylene glycol has a certain flexibility and steric hindrance, and it can form a network structure in the solution, which helps the diffusion of ions in the solution. When the citrate dialysis powder dissolves, various ions (such as sodium ions, calcium ions, potassium ions, etc.) need to diffuse from the particle surface into the solution. The network structure of polyethylene glycol can provide more diffusion channels for the ions, reducing the mutual collision and aggregation between the ions, thereby accelerating the diffusion rate of the ions and increasing the dissolution rate of the dialysis powder. Glycerol can reduce the viscosity of the solution, making the movement of ions in the solution more free, further promoting the diffusion of ions. When polyethylene glycol and glycerol coexist, their promoting effects on ion diffusion are synergistic, enabling the ions in the dialysis powder to be more rapidly and uniformly dispersed in the solution, thereby increasing the solubility of the dialysis powder. In addition, during the dissolution process of the dialysis powder, the particles are prone to aggregation, which affects the dissolution effect. Polyethylene glycol and glycerol can adsorb on the surface of the dialysis powder particles to form a protective film, preventing the mutual collision and aggregation between the particles. Polyethylene glycol keeps a certain distance between the particles through the steric hindrance effect of its molecular chain; glycerol forms a viscous layer on the particle surface through its viscous action, hindering the approach of the particles. The combined action of the two effectively prevents the aggregation of the dialysis powder particles, enabling the particles to be fully exposed to water and improving the dissolution efficiency.

[0008] Preferably, the instant soluble citrate dialysis powder comprises the following raw materials in parts by weight: 150 - 200 parts of sodium chloride; 8 - 10 parts of calcium chloride; 4 - 6 parts of potassium chloride; 8 - 10 parts of magnesium chloride; 10 - 50 parts of citric acid; 20 - 40 parts of glucose; 5 - 10 parts of polyethylene glycol; 5 - 10 parts of glycerol; 800 - 1000 parts of pure water.

[0009] Furthermore, the instant soluble citrate dialysis powder comprises the following raw materials in parts by weight: 180 parts of sodium chloride; 10 parts of calcium chloride; 5 parts of potassium chloride; 10 parts of magnesium chloride; 30 parts of citric acid; 30 parts of glucose; 6 parts of polyethylene glycol; 8 parts of glycerol; 900 parts of pure water.

[0010] Preferably, the purity of the citric acid ≥ 99%; and / or, the molecular weight of the polyethylene glycol is 200 - 400.

[0011] In a second aspect, the present invention provides a method for preparing the instant citric acid dialysis powder in an optional embodiment, comprising the following steps:

[0012] S1: Weigh sodium chloride, calcium chloride, potassium chloride, magnesium chloride, glucose and 1 / 2 pure water according to their weight proportions, mix them, and stir them evenly to obtain a mixed solution A;

[0013] S2: Weigh citric acid, polyethylene glycol, glycerol and 1 / 2 pure water according to their weight proportions, mix them, heat them, and then cool them to room temperature to obtain a mixed solution B;

[0014] S3: adding mixed solution B to the mixed solution A, mixing them thoroughly, and then performing evaporation crystallization, drying, crushing, grinding and sieving to obtain instant citric acid dialysis powder.

[0015] Preferably, in step S2, the heating method is water bath heating; and / or the heating temperature is 50-70° C. and the heating time is 10-30 min. The cooling method is water bath cooling.

[0016] Preferably, in step S1, the stirring speed is 200-300 r / min; and / or the stirring time is 15-20 min.

[0017] Preferably, in step S3, the temperature of the evaporation crystallization is 60-70°C; and / or, the time of the evaporation crystallization is 2-3h. The drying method is vacuum drying; and / or, the drying temperature is 50-60°C, the vacuum degree is (-0.08)-(-0.09)MPa, and the time is 4-6 hours. The pulverization method is pulverized by a jet mill; and / or, the grinding method is ground by a ball mill, and the grinding time is 1-2h; and / or, the sieve is 100-120 mesh.

[0018] Compared with the prior art, the present invention has one of the following beneficial effects:

[0019] 1. The instant citric acid dialysis powder provided by the present invention adopts high-purity citrate as the main component. Through optimized formula design and special process treatment, the solubility performance of the product is significantly improved, and it can be completely dissolved in a short time, meeting the needs of rapid clinical use.

[0020] 2. The instant citric acid dialysis powder provided by the present invention has good stability and biocompatibility, can effectively exert local anticoagulant effect, and reduce the bleeding risk caused by traditional anticoagulants. The preparation method of the present invention is simple and efficient, and the obtained product is suitable for various blood purification treatments, especially for patients with bleeding tendency. DETAILED DESCRIPTION

[0021] In order to make the objectives, technical solutions and advantages of the present invention more clear and understandable, the present invention will be further described in detail below in conjunction with specific embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not used to limit the present invention.

[0022] In the following examples and comparative examples, citric acid was purchased from Nanjing Chemical Reagent Co., Ltd., polyethylene glycol was polyethylene glycol 200, purchased from Nanjing Chemical Reagent Co., Ltd., and polyvinylpyrrolidone was purchased from Nanjing Chemical Reagent Co., Ltd., with the model of K-30.

[0023] The technical solutions of the present invention will be described below in conjunction with the examples.

[0024] Example 1

[0025] This example provides a citric acid dialysis powder, which comprises the following raw materials in parts by weight:

[0026] 180 g of sodium chloride, 10 g of calcium chloride, 5 g of potassium chloride, 10 g of magnesium chloride, 30 g of citric acid, 30 g of glucose, 6 g of polyethylene glycol 200, 8 g of glycerol and 900 g of pure water.

[0027] The preparation method of the citric acid dialysis powder in this example comprises the following steps:

[0028] S1: According to the parts by weight of the formula, use an electronic balance to accurately weigh sodium chloride, calcium chloride, potassium chloride, magnesium chloride, glucose and 1 / 2 of the amount of pure water. Add the weighed sodium chloride, calcium chloride, potassium chloride, magnesium chloride and glucose into the first reaction kettle, and then add the weighed 1 / 2 of pure water. Turn on the stirring device, set the stirring speed at 250 r / min, and continuously stir for 20 min until all components are fully dissolved and mixed evenly to obtain a mixed solution A.

[0029] S2: According to the parts by weight of the formula, use an electronic balance to accurately weigh citric acid, polyethylene glycol, glycerol and the other 1 / 2 of the amount of pure water. Add the weighed citric acid, polyethylene glycol, glycerol and 1 / 2 of pure water into the second reaction kettle, and adopt a water bath heating method. Place the second reaction kettle in a water bath pot, adjust the water temperature to 60 °C, and heat for 20 min to fully dissolve and mix all components. After heating, take out the second reaction kettle from the water bath pot and adopt a water bath cooling method. Put it into a water bath pot filled with cold water to cool the solution to room temperature to obtain a mixed solution B.

[0030] S3: Slowly add the mixed solution B to the mixed solution A. After the two solutions are fully mixed, transfer the mixed solution to an evaporator, adjust the temperature of the evaporator to 65 °C, and perform the evaporation crystallization operation for 2.5 h to gradually evaporate the water and precipitate the solute crystals. Then transfer the crystallized material to a vacuum drying oven, set the drying temperature to 55 °C, the vacuum degree to -0.08 MPa, and dry for 5 h. Then use an air jet mill to crush the dried material, put the crushed material into a ball mill for grinding for 1.5 h, and finally use a 100-mesh sieve to screen the ground material to obtain citric acid dialysis powder.

[0031] Example 2

[0032] This example provides a citric acid dialysis powder, which comprises the following raw materials in parts by weight:

[0033] 150 g of sodium chloride, 8 g of calcium chloride, 6 g of potassium chloride, 10 g of magnesium chloride, 50 g of citric acid, 20 g of glucose, 10 g of polyethylene glycol 200, 5 g of glycerol, and 1000 g of pure water.

[0034] The preparation method of the citric acid dialysis powder in this example comprises the following steps:

[0035] S1: According to the parts by weight of the formula, accurately weigh sodium chloride, calcium chloride, potassium chloride, magnesium chloride, glucose, and 1 / 2 of the amount of pure water using an electronic balance. Add the weighed sodium chloride, calcium chloride, potassium chloride, magnesium chloride, and glucose to the first reaction kettle, and then add the weighed 1 / 2 of the pure water. Turn on the stirring device, set the stirring speed at 250 r / min, and continuously stir for 20 min until all components are fully dissolved and mixed evenly to obtain the mixed solution A.

[0036] S2: According to the parts by weight of the formula, accurately weigh citric acid, polyethylene glycol, glycerol, and the other 1 / 2 of the amount of pure water using an electronic balance. Add the weighed citric acid, polyethylene glycol, glycerol, and 1 / 2 of the pure water to the second reaction kettle. Adopt the water bath heating method, place the second reaction kettle in a water bath pot, adjust the water temperature to 60 °C, and heat for 20 min to fully dissolve and mix all components. After heating is completed, take out the second reaction kettle from the water bath pot and adopt the water bath cooling method to place it in a water bath pot filled with cold water to cool the solution to room temperature to obtain the mixed solution B.

[0037] S3: Slowly add the mixed solution B into the mixed solution A. After the two solutions are fully mixed, transfer the mixed solution to an evaporator, adjust the temperature of the evaporator to 65 °C, and perform the evaporation crystallization operation for 2.5 h to gradually evaporate the water and precipitate the solute crystals. Then transfer the crystallized material to a vacuum drying oven, set the drying temperature to 55 °C, the vacuum degree to -0.08 MPa, and dry for 5 h. Then use an air jet mill to crush the dried material, put the crushed material into a ball mill for grinding for 1.5 h, and finally use a 100-mesh sieve to screen the ground material to obtain the citric acid dialysis powder.

[0038] Example 3

[0039] This example provides a citric acid dialysis powder, which includes the following raw materials in parts by weight:

[0040] 200 g of sodium chloride, 9 g of calcium chloride, 4 g of potassium chloride, 9 g of magnesium chloride, 10 g of citric acid, 40 g of glucose, 5 g of polyethylene glycol 200, 10 g of glycerol, and 800 g of pure water.

[0041] The preparation method of the citric acid dialysis powder in this example includes the following steps:

[0042] S1: According to the parts by weight of the formula, accurately weigh sodium chloride, calcium chloride, potassium chloride, magnesium chloride, glucose, and 1 / 2 of the amount of pure water using an electronic balance. Add the weighed sodium chloride, calcium chloride, potassium chloride, magnesium chloride, and glucose into the first reaction kettle, and then add the weighed 1 / 2 of the pure water. Turn on the stirring equipment, set the stirring speed to 250 r / min, and stir continuously for 20 min until all components are fully dissolved and mixed evenly to obtain the mixed solution A.

[0043] S2: According to the parts by weight of the formula, accurately weigh citric acid, polyethylene glycol, glycerol, and the other 1 / 2 of the amount of pure water using an electronic balance. Add the weighed citric acid, polyethylene glycol, glycerol, and 1 / 2 of the pure water into the second reaction kettle. Adopt the water bath heating method, place the second reaction kettle in a water bath pot, adjust the water temperature to 60 °C, and heat for 20 min to fully dissolve and mix all components. After heating is completed, take out the second reaction kettle from the water bath pot, and adopt the water bath cooling method to put it into a water bath pot filled with cold water to cool the solution to room temperature to obtain the mixed solution B.

[0044] S3: Slowly add the mixed solution B to the mixed solution A. After the two solutions are fully mixed, transfer the mixed solution to an evaporator, adjust the temperature of the evaporator to 65 °C, and perform evaporation crystallization for 2.5 h to gradually evaporate the water and precipitate the solute crystals. Then transfer the crystallized material to a vacuum drying oven, set the drying temperature to 55 °C, the vacuum degree to -0.08 MPa, and dry for 5 h. Then use an air jet mill to crush the dried material, put the crushed material into a ball mill for grinding for 1.5 h, and finally use a 100-mesh sieve to screen the ground material to obtain citric acid dialysis powder.

[0045] Example 4

[0046] This example provides a citric acid dialysis powder, which includes the following raw materials in parts by weight:

[0047] 300 g of sodium chloride, 12 g of calcium chloride, 2 g of potassium chloride, 12 g of magnesium chloride, 30 g of citric acid, 13 g of glucose, 12 g of polyethylene glycol 200, 12 g of glycerol, and 500 g of pure water.

[0048] The preparation method of the citric acid dialysis powder in this example includes the following steps:

[0049] S1: According to the parts by weight of the formula, accurately weigh sodium chloride, calcium chloride, potassium chloride, magnesium chloride, glucose, and 1 / 2 of the amount of pure water using an electronic balance. Add the weighed sodium chloride, calcium chloride, potassium chloride, magnesium chloride, and glucose to the first reaction kettle, and then add the weighed 1 / 2 of the pure water. Turn on the stirring device, set the stirring speed to 250 r / min, and stir continuously for 20 min until all components are fully dissolved and mixed evenly to obtain the mixed solution A.

[0050] S2: According to the parts by weight of the formula, accurately weigh citric acid, polyethylene glycol, glycerol, and the other 1 / 2 of the amount of pure water using an electronic balance. Add the weighed citric acid, polyethylene glycol, glycerol, and 1 / 2 of the pure water to the second reaction kettle. Adopt the water bath heating method, place the second reaction kettle in a water bath pot, adjust the water temperature to 60 °C, and heat for 20 min to fully dissolve and mix all components. After heating is completed, take out the second reaction kettle from the water bath pot, and adopt the water bath cooling method to put it into a water bath pot filled with cold water to cool the solution to room temperature to obtain the mixed solution B.

[0051] S3: Slowly add the mixed solution B into the mixed solution A. After the two solutions are fully mixed, transfer the mixed solution to an evaporator, adjust the temperature of the evaporator to 65 °C, and perform the evaporation crystallization operation for 2.5 h to gradually evaporate the water and precipitate the solute crystals. Then transfer the crystallized material to a vacuum drying oven, set the drying temperature to 55 °C, the vacuum degree to -0.08 MPa, and dry for 5 h. Then use a jet mill to crush the dried material, put the crushed material into a ball mill for grinding for 1.5 h. Finally, use a 100-mesh sieve to screen the ground material to obtain the citric acid dialysis powder.

[0052] Comparative Example 1

[0053] This comparative example provides a citric acid dialysis powder, which comprises the following raw materials in parts by weight:

[0054] 180 g of sodium chloride, 10 g of calcium chloride, 5 g of potassium chloride, 10 g of magnesium chloride, 30 g of citric acid, 30 g of glucose, 14 g of polyethylene glycol 200, and 900 g of pure water.

[0055] The preparation method of the citric acid dialysis powder in this comparative example comprises the following steps:

[0056] S1: According to the parts by weight of the formula, accurately weigh sodium chloride, calcium chloride, potassium chloride, magnesium chloride, glucose, and 1 / 2 of the amount of pure water using an electronic balance. Add the weighed sodium chloride, calcium chloride, potassium chloride, magnesium chloride, and glucose into the first reaction kettle, and then add the weighed 1 / 2 of the pure water. Turn on the stirring equipment, set the stirring speed at 250 r / min, and continuously stir for 20 min until all components are fully dissolved and mixed evenly to obtain the mixed solution A.

[0057] S2: According to the parts by weight of the formula, accurately weigh citric acid, polyethylene glycol, glycerol, and the other 1 / 2 of the amount of pure water using an electronic balance. Add the weighed citric acid, polyethylene glycol, glycerol, and 1 / 2 of the pure water into the second reaction kettle, and adopt the water bath heating method. Place the second reaction kettle in a water bath pot, adjust the water temperature to 60 °C, and heat for 20 min to fully dissolve and mix all components. After heating, take out the second reaction kettle from the water bath pot, and adopt the water bath cooling method. Place it in a water bath pot filled with cold water to cool the solution to room temperature to obtain the mixed solution B.

[0058] S3: Slowly add the mixed solution B to the mixed solution A. After the two solutions are fully mixed, transfer the mixed solution to an evaporator, adjust the temperature of the evaporator to 65 °C, and perform the evaporation crystallization operation for 2.5 h to gradually evaporate the water and precipitate the solute crystals. Then transfer the crystallized material to a vacuum drying oven, set the drying temperature to 55 °C, the vacuum degree to -0.08 MPa, and dry for 5 h. Then use a jet mill to crush the dried material, put the crushed material into a ball mill for grinding for 1.5 h, and finally use a 100-mesh sieve to screen the ground material to obtain the citric acid dialysis powder.

[0059] Comparative Example 2

[0060] This comparative example provides a citric acid dialysis powder, which comprises the following raw materials in parts by weight:

[0061] 180 g of sodium chloride, 10 g of calcium chloride, 5 g of potassium chloride, 10 g of magnesium chloride, 30 g of citric acid, 30 g of glucose, 14 g of glycerol and 900 g of pure water.

[0062] The preparation method of the citric acid dialysis powder in this comparative example comprises the following steps:

[0063] S1: According to the parts by weight of the formula, accurately weigh sodium chloride, calcium chloride, potassium chloride, magnesium chloride, glucose and 1 / 2 of the amount of pure water using an electronic balance. Add the weighed sodium chloride, calcium chloride, potassium chloride, magnesium chloride and glucose to the first reaction kettle, and then add the weighed 1 / 2 of the pure water. Turn on the stirring device, set the stirring speed at 250 r / min, and continuously stir for 20 min until all components are fully dissolved and mixed evenly to obtain the mixed solution A.

[0064] S2: According to the parts by weight of the formula, accurately weigh citric acid, polyethylene glycol, glycerol and the other 1 / 2 of the amount of pure water using an electronic balance. Add the weighed citric acid, polyethylene glycol, glycerol and 1 / 2 of the pure water to the second reaction kettle. Adopt the water bath heating method, place the second reaction kettle in a water bath pot, adjust the water temperature to 60 °C, and heat for 20 min to fully dissolve and mix all components. After heating, take out the second reaction kettle from the water bath pot, and adopt the water bath cooling method to put it into a water bath pot filled with cold water to cool the solution to room temperature to obtain the mixed solution B.

[0065] S3: Slowly add the mixed solution B to the mixed solution A. After the two solutions are fully mixed, transfer the mixed solution to an evaporator. Adjust the temperature of the evaporator to 65 °C and carry out the evaporation crystallization operation for 2.5 h to gradually evaporate the water and precipitate the solute crystals. Then transfer the crystallized material to a vacuum drying oven, set the drying temperature to 55 °C, the vacuum degree to -0.08 MPa, and dry for 5 h. Then use an air jet mill to crush the dried material, put the crushed material into a ball mill for grinding for 1.5 h, and finally use a 100-mesh sieve to screen the ground material to obtain the citric acid dialysis powder.

[0066] Comparative Example 3

[0067] This comparative example provides a citric acid dialysis powder, which comprises the following raw materials in parts by weight:

[0068] 180 g of sodium chloride, 10 g of calcium chloride, 5 g of potassium chloride, 10 g of magnesium chloride, 30 g of citric acid, 30 g of glucose, 6 g of Tween-80, 8 g of glycerol and 900 g of pure water.

[0069] The preparation method of the citric acid dialysis powder in this comparative example comprises the following steps:

[0070] S1: According to the parts by weight of the formula, accurately weigh sodium chloride, calcium chloride, potassium chloride, magnesium chloride, glucose and 1 / 2 of the amount of pure water using an electronic balance. Add the weighed sodium chloride, calcium chloride, potassium chloride, magnesium chloride and glucose to the first reaction kettle, and then add the weighed 1 / 2 of the pure water. Turn on the stirring equipment, set the stirring speed at 250 r / min, and continuously stir for 20 min until all components are fully dissolved and mixed evenly to obtain the mixed solution A.

[0071] S2: According to the parts by weight of the formula, accurately weigh citric acid, polyethylene glycol, glycerol and the other 1 / 2 of the amount of pure water using an electronic balance. Add the weighed citric acid, Tween-80, glycerol and 1 / 2 of the pure water to the second reaction kettle. Adopt the water bath heating method, place the second reaction kettle in a water bath pot, adjust the water temperature to 60 °C, and heat for 20 min to fully dissolve and mix all components. After heating, take out the second reaction kettle from the water bath pot and adopt the water bath cooling method to put it into a water bath pot filled with cold water to cool the solution to room temperature to obtain the mixed solution B.

[0072] S3: Slowly add the mixed solution B into the mixed solution A. After the two solutions are fully mixed, transfer the mixed solution to an evaporator, adjust the temperature of the evaporator to 65 °C, and perform evaporation crystallization for 2.5 h to gradually evaporate the water and precipitate the solute crystals. Then transfer the crystallized material to a vacuum drying oven, set the drying temperature to 55 °C, the vacuum degree to -0.08 MPa, and dry for 5 h. Then use an air jet mill to crush the dried material, put the crushed material into a ball mill for grinding for 1.5 h, and finally use a 100-mesh sieve to screen the ground material to obtain the citric acid dialysis powder.

[0073] Comparative Example 4

[0074] This comparative example provides a citric acid dialysis powder, which comprises the following raw materials in parts by weight:

[0075] 180 g of sodium chloride, 10 g of calcium chloride, 5 g of potassium chloride, 10 g of magnesium chloride, 30 g of citric acid, 30 g of glucose, 6 g of polyvinylpyrrolidone, 8 g of glycerol, and 900 g of pure water.

[0076] The preparation method of the citric acid dialysis powder in this comparative example comprises the following steps:

[0077] S1: According to the parts by weight of the formula, accurately weigh sodium chloride, calcium chloride, potassium chloride, magnesium chloride, glucose, and 1 / 2 of the amount of pure water using an electronic balance. Add the weighed sodium chloride, calcium chloride, potassium chloride, magnesium chloride, and glucose into the first reaction kettle, and then add the weighed 1 / 2 of the pure water. Turn on the stirring device, set the stirring speed at 250 r / min, and continuously stir for 20 min until all components are fully dissolved and mixed evenly to obtain the mixed solution A.

[0078] S2: According to the parts by weight of the formula, accurately weigh citric acid, polyethylene glycol, glycerol, and the other 1 / 2 of the amount of pure water using an electronic balance. Add the weighed citric acid, polyvinylpyrrolidone, glycerol, and 1 / 2 of the pure water into the second reaction kettle, and use a water bath heating method. Place the second reaction kettle in a water bath pot, adjust the water temperature to 60 °C, and heat for 20 min to fully dissolve and mix all components. After heating, take out the second reaction kettle from the water bath pot, and use a water bath cooling method. Place it in a water bath pot filled with cold water to cool the solution to room temperature to obtain the mixed solution B.

[0079] S3: Slowly add the mixed solution B to the mixed solution A. After the two solutions are fully mixed, transfer the mixed solution to an evaporator, adjust the temperature of the evaporator to 65 °C, and perform the evaporation crystallization operation for 2.5 h to gradually evaporate the water and precipitate the solute crystals. Then transfer the crystallized material to a vacuum drying oven, set the drying temperature to 55 °C, the vacuum degree to -0.08 MPa, and dry for 5 h. Then use an air jet mill to crush the dried material, put the crushed material into a ball mill for grinding for 1.5 h, and finally use a 100-mesh sieve to screen the ground material to obtain the citric acid dialysis powder.

[0080] Comparative Example 5

[0081] This comparative example provides a citric acid dialysis powder, comprising the following raw materials in parts by weight:

[0082] 180 g of sodium chloride, 10 g of calcium chloride, 5 g of potassium chloride, 10 g of magnesium chloride, 30 g of citric acid, 30 g of glucose, 6 g of polyethylene glycol 200, 8 g of propylene glycol, and 900 g of pure water.

[0083] The preparation method of the citric acid dialysis powder in this comparative example comprises the following steps:

[0084] S1: According to the parts by weight of the formula, accurately weigh sodium chloride, calcium chloride, potassium chloride, magnesium chloride, glucose, and 1 / 2 of the amount of pure water using an electronic balance. Add the weighed sodium chloride, calcium chloride, potassium chloride, magnesium chloride, and glucose to the first reaction kettle, and then add the weighed 1 / 2 of the pure water. Turn on the stirring device, set the stirring speed at 250 r / min, and stir continuously for 20 min until all components are fully dissolved and mixed evenly to obtain the mixed solution A.

[0085] S2: According to the parts by weight of the formula, accurately weigh citric acid, polyethylene glycol, glycerol, and the other 1 / 2 of the amount of pure water using an electronic balance. Add the weighed citric acid, polyethylene glycol, propylene glycol, and 1 / 2 of the pure water to the second reaction kettle. Using the water bath heating method, place the second reaction kettle in a water bath pot, adjust the water temperature to 60 °C, and heat for 20 min to fully dissolve and mix all components. After heating is completed, take out the second reaction kettle from the water bath pot and use the water bath cooling method to place it in a water bath pot filled with cold water to cool the solution to room temperature to obtain the mixed solution B.

[0086] S3: Slowly add the mixed solution B to the mixed solution A. After the two solutions are fully mixed, transfer the mixed solution to an evaporator, adjust the temperature of the evaporator to 65 °C, and perform evaporation crystallization for 2.5 h to gradually evaporate the water and precipitate the solute crystals. Then transfer the crystallized material to a vacuum drying oven, set the drying temperature to 55 °C, the vacuum degree to -0.08 MPa, and dry for 5 h. Then use an air jet mill to crush the dried material, put the crushed material into a ball mill for grinding for 1.5 h, and finally use a 100-mesh sieve to screen the ground material to obtain citric acid dialysis powder.

[0087] Comparative Example 6

[0088] This comparative example provides a citric acid dialysis powder, which comprises the following raw materials in parts by weight:

[0089] 180 g of sodium chloride, 10 g of calcium chloride, 5 g of potassium chloride, 10 g of magnesium chloride, 30 g of citric acid, 30 g of glucose, 6 g of polyethylene glycol 200, 8 g of D-sorbitol, and 900 g of pure water.

[0090] The preparation method of the citric acid dialysis powder in this comparative example comprises the following steps:

[0091] S1: According to the parts by weight of the formula, accurately weigh sodium chloride, calcium chloride, potassium chloride, magnesium chloride, glucose, and 1 / 2 of the amount of pure water using an electronic balance. Add the weighed sodium chloride, calcium chloride, potassium chloride, magnesium chloride, and glucose to the first reaction kettle, and then add the weighed 1 / 2 of the pure water. Turn on the stirring device, set the stirring speed to 250 r / min, and stir continuously for 20 min until all components are fully dissolved and mixed evenly to obtain the mixed solution A.

[0092] S2: According to the parts by weight of the formula, accurately weigh citric acid, polyethylene glycol, glycerol, and the other 1 / 2 of the amount of pure water using an electronic balance. Add the weighed citric acid, polyethylene glycol, D-sorbitol, and 1 / 2 of the pure water to the second reaction kettle. Adopt the water bath heating method, place the second reaction kettle in a water bath pot, adjust the water temperature to 60 °C, and heat for 20 min to fully dissolve and mix all components. After heating, take out the second reaction kettle from the water bath pot and adopt the water bath cooling method to put it into a water bath pot filled with cold water to cool the solution to room temperature to obtain the mixed solution B.

[0093] S3: Slowly add the mixed solution B to the mixed solution A. After the two solutions are fully mixed, transfer the mixed solution to an evaporator, adjust the temperature of the evaporator to 65 °C, perform an evaporation crystallization operation for 2.5 h to gradually evaporate the water and precipitate the solute crystals. Then transfer the crystallized material to a vacuum drying oven, set the drying temperature to 55 °C, the vacuum degree to -0.08 MPa, and dry for 5 h. Then use an air jet mill to crush the dried material, put the crushed material into a ball mill for grinding for 1.5 h, and finally use a 100-mesh sieve to screen the ground material to obtain the citric acid dialysis powder.

[0094] Comparative Example 7

[0095] This comparative example provides a citric acid dialysis powder, which includes the following raw materials in parts by weight:

[0096] 180 g of sodium chloride, 10 g of calcium chloride, 5 g of potassium chloride, 10 g of magnesium chloride, 30 g of citric acid, 30 g of glucose, 6 g of polyethylene glycol 200, 8 g of glycerol, and 900 g of pure water.

[0097] The preparation method of the citric acid dialysis powder in this comparative example includes the following steps:

[0098] S1: According to the parts by weight of the formula, accurately weigh sodium chloride, calcium chloride, potassium chloride, magnesium chloride, glucose, citric acid, polyethylene glycol, glycerol, and pure water using an electronic balance. Add the weighed sodium chloride, calcium chloride, potassium chloride, magnesium chloride, glucose, citric acid, polyethylene glycol, and glycerol to a reaction kettle, and then add the weighed pure water. Turn on the stirring device, set the stirring speed at 250 r / min, and stir continuously for 20 min until all components are fully dissolved and mixed evenly to obtain a mixed solution. Then, use a water bath heating method, place the reaction kettle in a water bath pot, adjust the water temperature to 60 °C, and heat for 20 min to fully dissolve and mix all components. After heating is completed, take out the reaction kettle from the water bath pot, and use a water bath cooling method to place it in a water bath pot filled with cold water to cool the solution to room temperature to obtain a mixed solution.

[0099] S3: Transfer the mixed solution to an evaporator, adjust the temperature of the evaporator to 65 °C, perform an evaporation crystallization operation for 2.5 h to gradually evaporate the water and precipitate the solute crystals. Then transfer the crystallized material to a vacuum drying oven, set the drying temperature to 55 °C, the vacuum degree to -0.08 MPa, and dry for 5 h. Then use an air jet mill to crush the dried material, put the crushed material into a ball mill for grinding for 1.5 h, and finally use a 100-mesh sieve to screen the ground material to obtain the citric acid dialysis powder.

[0100] Experimental Example

[0101] The dissolution performance test of the citric acid dialysis powder prepared in Examples 1-4 and Comparative Examples 1-7 was performed as follows:

[0102] Set the temperature of the thermostatic water bath to 37°C (simulating the human body temperature environment, close to the clinical use scenario), and preheat for 15 minutes. Use an electronic balance to weigh 5.000g of the citric acid dialysis powder prepared in Examples 1-4 and Comparative Examples 1-7, respectively, use a pipette to accurately measure 200mL of deionized water, add it to a 250mL stoppered conical flask, and place the conical flask in a thermostatic water bath to preheat for 5 minutes. Pour the weighed dialysis powder quickly into the preheated stoppered conical flask, start the stopwatch at the same time, and immediately fix the conical flask on the magnetic stirrer, setting the stirring speed to 200r / min. During continuous stirring, measure the turbidity of the solution with a turbidimeter every 10 seconds, record the time and turbidity value of each measurement, until the turbidity of the solution is stable (the turbidity change does not exceed 5% for 3 consecutive measurements), stop the timing, and record the total dissolution time. See Table 1 for results:

[0103] Table 1 Total dissolution time of citric acid dialysis powder of Examples 1-4 and Comparative Examples 1-7

[0104] Total dissolution time (s) Example 1 62 Example 2 66 Example 3 65 Example 4 67 Comparative Example 1 125 Comparative Example 2 114 Comparative Example 3 90 Comparative Example 4 92 Comparative Example 5 83 Comparative Example 6 85 Comparative Example 7 102

[0105] Conclusion: By comparing the data of Example 1 and Comparative Examples 1 and 2, it can be seen that adding polyethylene glycol and glycerol to the formula of instant citric acid dialysis powder can synergistically improve the solubility of citric acid dialysis powder. By comparing the data of Example 1 and Comparative Examples 3-6, it can be seen that replacing polyethylene glycol and glycerol with other substances respectively can also improve the solubility of citric acid dialysis powder, but it is far inferior to the solubility of adding polyethylene glycol and glycerol to the formula of instant citric acid dialysis powder. By comparing the data of Example 1 and Comparative Example 7, it can be seen that the solubility of citric acid dialysis powder prepared by one-step method is far inferior to the solubility of citric acid dialysis powder prepared by two-step method of the present invention. It can be seen that adding polyethylene glycol and glycerol to citric acid dialysis powder can significantly shorten the dissolution time, and the lack or replacement of one of the components alone will lead to a decrease in dissolution efficiency, and the two-step method is used to prepare citric acid dialysis powder, which can greatly improve the solubility of citric acid dialysis powder.

[0106] Although the principles of the present invention are described in detail above in conjunction with the preferred embodiments of the present invention, those skilled in the art should understand that the above embodiments are merely explanations of the exemplary implementations of the present invention, and are not intended to limit the scope of the present invention. The details in the embodiments do not constitute limitations on the scope of the present invention, and any obvious changes such as equivalent transformations, simple replacements, etc. based on the technical solution of the present invention, without departing from the spirit and scope of the present invention, fall within the protection scope of the present invention.

Claims

1. An instant citrate dialysis powder, characterized in that, It includes the following raw materials in parts by weight: 150 - 350 parts of sodium chloride; 5 - 15 parts of calcium chloride; 2 - 10 parts of potassium chloride; 5 - 15 parts of magnesium chloride; 10 - 50 parts of citric acid; 20 - 40 parts of glucose; 5 - 15 parts of polyethylene glycol; 5 - 15 parts of glycerol; 500 - 1000 parts of pure water.

2. The instant dissolving citrate dialysis powder according to claim 1, wherein It includes the following raw materials in parts by weight: 150 - 200 parts of sodium chloride; 8 - 10 parts of calcium chloride; 4 - 6 parts of potassium chloride; 8 - 10 parts of magnesium chloride; 10 - 50 parts of citric acid; 20 - 40 parts of glucose; 5 - 10 parts of polyethylene glycol; 5 - 10 parts of glycerol; 800 - 1000 parts of pure water.

3. The instant soluble citrate dialysis powder according to claim 1, wherein It includes the following raw materials in parts by weight: 180 parts of sodium chloride; 10 parts of calcium chloride; 5 parts of potassium chloride; 10 parts of magnesium chloride; 30 parts of citric acid; 30 parts of glucose; 6 parts of polyethylene glycol; 8 parts of glycerol; 900 parts of pure water.

4. The instant-dissolving citrate dialysis powder according to any one of claims 1-3, characterized in that The purity of the citric acid is ≥99%; and / or, The molecular weight of the polyethylene glycol is 200 - 400.

5. A method for preparing the instant dialysis powder of citric acid according to any one of claims 1-4, characterized in that, It includes the following steps: S1: Weigh sodium chloride, calcium chloride, potassium chloride, magnesium chloride, glucose and 1 / 2 of the pure water according to the parts by weight, mix them, and stir evenly to obtain a mixed solution A; S2: Weigh citric acid, polyethylene glycol, glycerol and 1 / 2 of the pure water according to the parts by weight, mix them, heat them, and then cool them to room temperature to obtain a mixed solution B; S3: Add the mixed solution B to the mixed solution A, make them fully mixed, and then carry out evaporation crystallization, drying, pulverization, grinding and sieving to obtain the instant citric acid dialysis powder.

6. The preparation method of the instant citrate dialysis powder according to claim 4, characterized in that, In step S2, the heating method is water bath heating; and / or, The heating temperature is 50 - 70°C, and the time is 10 - 30 min; and / or, In step S2, the cooling method is water bath cooling.

7. The preparation method of the instant citrate dialysis powder according to claim 4, characterized in that, In step S1, the stirring speed is 200 - 300 r / min; and / or, The stirring time is 15 - 20 min.

8. The preparation method of the instant citrate dialysis powder according to claim 4, wherein, In step S3, the evaporation crystallization temperature is 60 - 70°C; and / or, The evaporation crystallization time is 2 - 3 h.

9. The preparation method of the instant citrate dialysis powder according to claim 4, characterized in that In step S3, the drying method is vacuum drying; and / or, The drying temperature is 50 - 60°C, the vacuum degree is (-0.08) - (-0.09) MPa, and the time is 4 - 6 hours.

10. The preparation method of the instant citrate dialysis powder according to claim 4, wherein In step S3, the pulverization method is pulverization with a jet mill; and / or, The grinding method is grinding with a ball mill, and the grinding time is 1 - 2 h; and / or, The sieve mesh for sieving is 100 - 120 meshes.