Instant citrate dialysis powder and its preparation method

Abstract

The present application relates to the technical field of hemodialysis, in particular to a quick-dissolving citric acid dialysis powder and a preparation method thereof.The quick-dissolving citric acid dialysis powder provided by the present application comprises the following raw materials 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; and 500-1000 parts of pure water.The quick-dissolving citric acid dialysis powder provided by the present application uses high-purity citrate as the main component, and through optimization of the formula design and special process treatment, the solubility of the product is significantly improved, and the product can be completely dissolved in a short time, meeting the needs of rapid use in clinical practice.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of hemodialysis, in particular to a quick-dissolving citric acid dialysis powder and a preparation method thereof. BACKGROUND

[0002] In hemodialysis treatment, dialysis powder as a key raw material for preparing dialysis solution, its performance directly affects the effect and safety of dialysis treatment. Citric acid as an important component of dialysis powder, has the effects of regulating blood acid-base balance, anticoagulation, etc., and plays a key role in the dialysis process.

[0003] However, the traditional citric acid dialysis powder has many problems in practical application. On the one hand, the dissolution rate of the traditional citric acid dialysis powder is slow, which prolongs the preparation time of the dialysis solution, not only reduces the efficiency of the dialysis preparation work, but also may affect the timeliness of the patient's dialysis treatment. On the other hand, incomplete dissolution of the dialysis powder can lead to uneven composition of the dialysis solution, which in turn affects the removal of metabolic waste from the patient's body during dialysis, as well as the regulation of electrolytes and acid-base balance, and there is a certain safety hazard and uncertainty of treatment effect. SUMMARY

[0004] In order to solve the above technical problems, the present application provides a quick-dissolving citric acid dialysis powder and a preparation method thereof, which uses high-purity citrate as the main component, and through optimization of formula design and special process treatment, the dissolution performance of the product is significantly improved, and it can be completely dissolved in a short time to meet the demand of rapid use in clinic.

[0005] Therefore, the present application provides the following technical solutions,

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

[0007] In the present application, the addition of polyethylene glycol and glycerol in the formula of instant citrate dialysis powder can synergistically improve the solubility of instant citrate dialysis powder. Polyethylene glycol has good water solubility and strong hydrophilicity, can quickly adsorb on the surface of dialysis powder particles, reduce the interfacial tension between particles and water, make water more easily penetrate into the particles, thereby promoting the dissolution of dialysis powder. Glycerol also has hydrophilicity, it can form a thin layer of water film on the surface of dialysis powder particles, increase the wettability of particles, let water better contact the particles, accelerate the dissolution rate. The two work together, can make the dialysis powder particles more quickly wetted by water, lay the foundation for the subsequent dissolution process. And the molecular chain of polyethylene glycol has a certain flexibility and steric hindrance, it can form a network structure in the solution. This structure 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.) in it need to diffuse from the particle surface to the solution. The network structure of polyethylene glycol can provide more diffusion channels for ions, reduce the mutual collision and aggregation of ions, thereby accelerating the diffusion rate of ions and improving the dissolution rate of dialysis powder. Glycerol can reduce the viscosity of the solution, make the movement of ions in the solution more free, further promote the diffusion of ions. When polyethylene glycol and glycerol exist at the same time, their promotion effects on ion diffusion are mutually synergistic, so that the ions in the dialysis powder can be more quickly and uniformly dispersed in the solution, thereby improving the solubility of the dialysis powder. In addition, during the dissolution process of dialysis powder, particles are prone to aggregation, thereby affecting the dissolution effect. Polyethylene glycol and glycerol can adsorb on the surface of dialysis powder particles, form a protective film, prevent the mutual collision and aggregation of particles. Polyethylene glycol keeps a certain distance between particles through the steric hindrance effect of its molecular chain; glycerol forms a sticky layer on the surface of particles through its adhesive effect, hinders the approach of particles. The two work together, effectively prevent the aggregation of dialysis powder particles, so that the particles can be fully exposed to water, improve the dissolution efficiency.

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

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

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

[0011] In a second aspect, the present application provides a preparation method of the instant citrate dialysis powder in the optional embodiments, comprising the following steps:

[0012] S1: sodium chloride, calcium chloride, potassium chloride, magnesium chloride, glucose and 1 / 2 pure water are weighed according to the weight fraction, mixed, stirred uniformly to obtain a mixed solution A;

[0013] S2: citric acid, polyethylene glycol, glycerol and 1 / 2 pure water are weighed according to the weight fraction, mixed, heated, and cooled to room temperature to obtain a mixed solution B;

[0014] S3: the mixed solution B is added to the mixed solution A, fully mixed, evaporated, crystallized, dried, crushed, ground and sieved to obtain the instant citrate dialysis powder.

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

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

[0017] Preferably, in step S3, the evaporative crystallization temperature is 60-70℃; and / or, the evaporative crystallization time is 2-3h. The drying is performed by vacuum drying; and / or, the drying temperature is 50-60℃, the vacuum degree is (-0.08)-(-0.09)MPa, and the drying time is 4-6h. The crushing is performed by an airflow crusher; and / or, the grinding is performed by a ball mill, and the grinding time is 1-2h; and / or, the sieve mesh is 100-120mesh.

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

[0019] 1. The instant citrate dialysis powder provided by the present application uses high-purity citrate as the main component, significantly improves the solubility of the product through optimized formula design and special process treatment, and can be completely dissolved in a short time to meet the needs of rapid clinical use.

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

[0021] In order to make the objects, technical solutions and advantages of the present application clearer, the present application will be further described in detail below with specific examples. It should be understood that the specific examples described herein are only used to explain the present application and not to limit the present application.

[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 model number K-30.

[0023] The technical solutions of the present application will be described below with examples

[0024] Example 1

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

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

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

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

[0029] S2: According to the weight fraction of the formula, use an electronic balance to accurately weigh citric acid, polyethylene glycol, glycerol and another 1 / 2 amount of pure water, put the weighed citric acid, polyethylene glycol, glycerol and 1 / 2 pure water into the second reaction kettle, use water bath heating method, put the second reaction kettle into the water bath kettle, adjust the water temperature to 60℃, heat for 20min, so that each component is fully dissolved and mixed. After heating is completed, take the second reaction kettle out of the water bath kettle, use water bath cooling method, put it into the water bath kettle filled with cold water, cool the solution to room temperature, to obtain a mixed solution B.

[0030] S3: Slowly add mixed solution B to mixed solution A, mix the two solutions thoroughly, and then transfer the mixed solution to an evaporator. Adjust the temperature of the evaporator to 65°C, and perform evaporation crystallization for 2.5 hours to gradually evaporate the water and crystallize the solute. Then transfer the crystallized material to a vacuum drying oven, set the drying temperature to 55°C and the vacuum degree to -0.08 MPa, and dry for 5 hours. Use an air flow crusher to crush the dried material, put the crushed material into a ball mill for grinding for 1.5 hours, and finally sieve the ground material using a 100-mesh sieve to obtain the citric acid dialysis powder.

[0031] Example 2

[0032] This example provides a citric acid dialysis powder, which comprises the following raw materials 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 of this example comprises the following steps:

[0035] S1: According to the weight fraction 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. Put the weighed sodium chloride, calcium chloride, potassium chloride, magnesium chloride, and glucose into a first reaction kettle, and then add the weighed 1 / 2 pure water. Turn on the stirring equipment, set the stirring speed to 250 r / min, and continuously stir for 20 min until all the ingredients are fully dissolved and uniformly mixed to obtain mixed solution A.

[0036] S2: According to the weight fraction of the formula, use an electronic balance to accurately weigh citric acid, polyethylene glycol, glycerol, and the other 1 / 2 amount of pure water. Put the weighed citric acid, polyethylene glycol, glycerol, and 1 / 2 pure water into a second reaction kettle. Place the second reaction kettle in a water bath and adjust the water temperature to 60°C. Heat for 20 min to fully dissolve and mix all the ingredients. After heating, remove the second reaction kettle from the water bath and place it in a water bath containing cold water to cool the solution to room temperature to obtain mixed solution B.

[0037] S3: Slowly add mixed solution B to mixed solution A, mix the two solutions thoroughly, and then transfer the mixed solution to an evaporator. Adjust the temperature of the evaporator to 65°C, and perform evaporation crystallization for 2.5 hours to gradually evaporate the water and crystallize the solute. Then transfer the crystallized material to a vacuum drying oven, set the drying temperature to 55°C and the vacuum degree to -0.08 MPa, and dry for 5 hours. Use an air flow crusher to crush the dried material, put the crushed material into a ball mill for grinding for 1.5 hours, and finally sieve the ground material through a 100-mesh sieve to obtain the citric acid dialysis powder.

[0038] Example 3

[0039] The present embodiment provides a citric acid dialysis powder, which comprises the following raw materials 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 of the present embodiment comprises the following steps:

[0042] S1: According to the weight fraction 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. Put the weighed sodium chloride, calcium chloride, potassium chloride, magnesium chloride, and glucose into a first reaction kettle, and then add the weighed 1 / 2 pure water. Turn on the stirring equipment, set the stirring speed to 250 r / min, and continuously stir for 20 min until all the ingredients are fully dissolved and uniformly mixed to obtain mixed solution A.

[0043] S2: According to the weight fraction of the formula, use an electronic balance to accurately weigh citric acid, polyethylene glycol, glycerol, and the other 1 / 2 amount of pure water. Put the weighed citric acid, polyethylene glycol, glycerol, and 1 / 2 pure water into a second reaction kettle. Place the second reaction kettle in a water bath and adjust the water temperature to 60°C. Heat for 20 min to fully dissolve and mix all the ingredients. After heating, remove the second reaction kettle from the water bath and place it in a water bath containing cold water to cool the solution to room temperature to obtain mixed solution B.

[0044] S3: Slowly add mixed solution B to mixed solution A, mix the two solutions thoroughly, and then transfer the mixed solution to an evaporator. Adjust the temperature of the evaporator to 65°C, and perform evaporation crystallization for 2.5 hours to gradually evaporate the water and crystallize the solute. Then transfer the crystallized material to a vacuum drying oven, set the drying temperature to 55°C and the vacuum degree to -0.08 MPa, and dry for 5 hours. Use an air flow crusher to crush the dried material, put the crushed material into a ball mill for grinding for 1.5 hours, and finally sieve the ground material through a 100-mesh sieve to obtain the citric acid dialysis powder.

[0045] Example 4

[0046] The present embodiment provides a citric acid dialysis powder, which comprises the following raw materials 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 of the present embodiment comprises the following steps:

[0049] S1: According to the weight fraction 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. Put the weighed sodium chloride, calcium chloride, potassium chloride, magnesium chloride, and glucose into a first reaction kettle, and then add the weighed 1 / 2 pure water. Turn on the stirring equipment, set the stirring speed to 250 r / min, and continuously stir for 20 min until all the ingredients are fully dissolved and uniformly mixed to obtain mixed solution A.

[0050] S2: According to the weight fraction of the formula, use an electronic balance to accurately weigh citric acid, polyethylene glycol, glycerol, and the other 1 / 2 amount of pure water. Put the weighed citric acid, polyethylene glycol, glycerol, and 1 / 2 pure water into a second reaction kettle. Place the second reaction kettle in a water bath and adjust the water temperature to 60°C. Heat for 20 min to fully dissolve and mix all the ingredients. After heating, remove the second reaction kettle from the water bath and place it in a water bath containing cold water to cool the solution to room temperature to obtain mixed solution B.

[0051] S3: Slowly add mixed solution B to mixed solution A, mix the two solutions thoroughly, and then transfer the mixed solution to an evaporator. Adjust the temperature of the evaporator to 65°C, and perform evaporation crystallization for 2.5 hours to gradually evaporate the water and crystallize the solute. Then transfer the crystallized material to a vacuum drying oven, set the drying temperature to 55°C and the vacuum degree to -0.08 MPa, and dry for 5 hours. Use an air flow crusher to crush the dried material, put the crushed material into a ball mill for grinding for 1.5 hours, and finally sieve the ground material through a 100-mesh sieve 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 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 of this comparative example comprises the following steps:

[0056] S1: According to the weight fraction 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. Put the weighed sodium chloride, calcium chloride, potassium chloride, magnesium chloride, and glucose into a first reaction kettle, and then add the weighed 1 / 2 pure water. Turn on the stirring equipment, set the stirring speed to 250 r / min, and continuously stir for 20 min until all the ingredients are fully dissolved and uniformly mixed to obtain mixed solution A.

[0057] S2: According to the weight fraction of the formula, use an electronic balance to accurately weigh citric acid, polyethylene glycol, glycerol, and the other 1 / 2 amount of pure water. Put the weighed citric acid, polyethylene glycol, glycerol, and 1 / 2 pure water into a second reaction kettle. Place the second reaction kettle in a water bath and adjust the water temperature to 60°C for heating for 20 min to fully dissolve and mix all the ingredients. After heating, take the second reaction kettle out of the water bath, place it in a water bath containing cold water, and cool the solution to room temperature to obtain mixed solution B.

[0058] S3: Slowly add mixed solution B to mixed solution A, mix the two solutions thoroughly, and then transfer the mixed solution to an evaporator. Adjust the temperature of the evaporator to 65°C, and perform evaporation crystallization for 2.5 hours to gradually evaporate the water and crystallize the solute. Then transfer the crystallized material to a vacuum drying oven, set the drying temperature to 55°C and the vacuum degree to -0.08 MPa, and dry for 5 hours. Use an air flow crusher to crush the dried material, put the crushed material into a ball mill for grinding for 1.5 hours, and finally sieve the ground material through a 100-mesh sieve to obtain citric acid dialysis powder.

[0059] Comparative Example 2

[0060] This comparative example provides a citric acid dialysis powder, which comprises the following raw materials 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 of this comparative example comprises the following steps:

[0063] S1: According to the weight fraction 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. Put the weighed sodium chloride, calcium chloride, potassium chloride, magnesium chloride, and glucose into a first reaction kettle, and then add the weighed 1 / 2 pure water. Turn on the stirring equipment, set the stirring speed to 250 r / min, and continuously stir for 20 min until all the ingredients are fully dissolved and uniformly mixed to obtain mixed solution A.

[0064] S2: According to the weight fraction of the formula, use an electronic balance to accurately weigh citric acid, polyethylene glycol, glycerol, and the other 1 / 2 amount of pure water. Put the weighed citric acid, polyethylene glycol, glycerol, and 1 / 2 pure water into a second reaction kettle. Place the second reaction kettle in a water bath and adjust the water temperature to 60°C for heating for 20 min to fully dissolve and mix all the ingredients. After heating, take the second reaction kettle out of the water bath, place it in a water bath containing cold water, and cool the solution to room temperature to obtain mixed solution B.

[0065] S3: Slowly add mixed solution B to mixed solution A, mix the two solutions thoroughly, and then transfer the mixed solution to an evaporator. Adjust the temperature of the evaporator to 65°C, and perform evaporation crystallization for 2.5 hours to gradually evaporate the water and crystallize the solute. Then transfer the crystallized material to a vacuum drying oven, set the drying temperature to 55°C and the vacuum degree to -0.08 MPa, and dry for 5 hours. Use an air flow crusher to crush the dried material, put the crushed material into a ball mill for grinding for 1.5 hours, and finally sieve the ground material through a 100-mesh sieve 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 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 of this comparative example comprises the following steps:

[0070] S1: According to the weight fraction 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. Put the weighed sodium chloride, calcium chloride, potassium chloride, magnesium chloride, and glucose into a first reaction kettle, and then add the weighed 1 / 2 pure water. Turn on the stirring equipment, set the stirring speed to 250 r / min, and continuously stir for 20 min until all the ingredients are fully dissolved and uniformly mixed to obtain mixed solution A.

[0071] S2: According to the weight fraction of the formula, use an electronic balance to accurately weigh citric acid, polyethylene glycol, glycerol, and the other 1 / 2 amount of pure water. Put the weighed citric acid, Tween-80, glycerol, and 1 / 2 pure water into a second reaction kettle. Place the second reaction kettle in a water bath and adjust the water temperature to 60°C. Heat for 20 min to fully dissolve and mix all the ingredients. After heating, remove the second reaction kettle from the water bath and place it in a water bath containing cold water to cool the solution to room temperature to obtain mixed solution B.

[0072] S3: Slowly add mixed solution B to mixed solution A, mix the two solutions thoroughly, then transfer the mixed solution to an evaporator, adjust the temperature of the evaporator to 65°C, and perform evaporation crystallization for 2.5 hours, so that the water gradually evaporates and the solute crystallizes. 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 hours. Then use an air flow crusher to crush the dried material, put the crushed material into a ball mill for grinding, and grind for 1.5 hours. Finally, use a 100-mesh sieve to sieve the ground material to obtain citric acid dialysis powder.

[0073] Comparative Example 4

[0074] This comparative example provides a citric acid dialysis powder, which comprises the following raw materials 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 of this comparative example comprises the following steps:

[0077] S1: According to the weight fraction 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. Put the weighed sodium chloride, calcium chloride, potassium chloride, magnesium chloride, and glucose into a first reaction kettle, then add the weighed 1 / 2 pure water. Turn on the stirring equipment, set the stirring speed to 250 r / min, and continue stirring for 20 min until all the ingredients are fully dissolved and uniformly mixed to obtain mixed solution A.

[0078] S2: According to the weight fraction of the formula, use an electronic balance to accurately weigh citric acid, polyethylene glycol, glycerol, and the other 1 / 2 amount of pure water. Put the weighed citric acid, polyvinylpyrrolidone, glycerol, and 1 / 2 pure water into a second reaction kettle. Place the second reaction kettle in a water bath and adjust the water temperature to 60°C. Heat for 20 min to fully dissolve and mix all the ingredients. After heating, remove the second reaction kettle from the water bath and place it in a water bath containing cold water to cool the solution to room temperature to obtain mixed solution B.

[0079] S3: Slowly add mixed solution B to mixed solution A, mix the two solutions thoroughly, and then transfer the mixed solution to an evaporator. Adjust the temperature of the evaporator to 65°C, and perform evaporation crystallization for 2.5 hours to gradually evaporate the water and crystallize the solute. Then transfer the crystallized material to a vacuum drying oven, set the drying temperature to 55°C and the vacuum degree to -0.08 MPa, and dry for 5 hours. Use an air flow crusher to crush the dried material, put the crushed material into a ball mill for grinding for 1.5 hours, and finally sieve the ground material through a 100-mesh sieve to obtain the citric acid dialysis powder.

[0080] Comparative Example 5

[0081] This comparative example provides a citric acid dialysis powder, which comprises the following raw materials 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 of this comparative example comprises the following steps:

[0084] S1: According to the weight fraction 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. Put the weighed sodium chloride, calcium chloride, potassium chloride, magnesium chloride, and glucose into a first reaction kettle, and then add the weighed 1 / 2 pure water. Turn on the stirring equipment, set the stirring speed to 250 r / min, and continuously stir for 20 min until all the ingredients are fully dissolved and uniformly mixed to obtain mixed solution A.

[0085] S2: According to the weight fraction of the formula, use an electronic balance to accurately weigh citric acid, polyethylene glycol, glycerol, and the other 1 / 2 amount of pure water. Put the weighed citric acid, polyethylene glycol, propylene glycol, and 1 / 2 pure water into a second reaction kettle. Place the second reaction kettle in a water bath and adjust the water temperature to 60°C. Heat for 20 min to fully dissolve and mix all the ingredients. After heating, remove the second reaction kettle from the water bath and place it in a water bath containing cold water to cool the solution to room temperature to obtain mixed solution B.

[0086] S3: Slowly add mixed solution B to mixed solution A, mix the two solutions thoroughly, and then transfer the mixed solution to an evaporator. Adjust the temperature of the evaporator to 65°C, and perform evaporation crystallization for 2.5 hours to gradually evaporate the water and crystallize the solute. Then transfer the crystallized material to a vacuum drying oven, set the drying temperature to 55°C and the vacuum degree to -0.08 MPa, and dry for 5 hours. Use an air flow crusher to crush the dried material, put the crushed material into a ball mill for grinding for 1.5 hours, and finally sieve the ground material through a 100-mesh sieve to obtain the citric acid dialysis powder.

[0087] Comparative Example 6

[0088] This comparative example provides a citric acid dialysis powder, which comprises the following raw materials 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 of this comparative example comprises the following steps:

[0091] S1: According to the weight fraction 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. Put the weighed sodium chloride, calcium chloride, potassium chloride, magnesium chloride, and glucose into a first reaction kettle, and then add the weighed 1 / 2 pure water. Turn on the stirring equipment, set the stirring speed to 250 r / min, and continuously stir for 20 min until all the ingredients are fully dissolved and uniformly mixed to obtain mixed solution A.

[0092] S2: According to the weight fraction of the formula, use an electronic balance to accurately weigh citric acid, polyethylene glycol, glycerol, and the other 1 / 2 amount of pure water. Put the weighed citric acid, polyethylene glycol, D-sorbitol, and 1 / 2 pure water into a second reaction kettle. Place the second reaction kettle in a water bath and adjust the water temperature to 60°C. Heat for 20 min to fully dissolve and mix all the ingredients. After heating, remove the second reaction kettle from the water bath and place it in a water bath containing cold water to cool the solution to room temperature to obtain mixed solution B.

[0093] S3: slowly add the mixed solution B into the mixed solution A, after mixing the two solutions well, transfer the mixed solution into an evaporator, adjust the temperature of the evaporator to 65℃, and perform evaporation crystallization operation for 2.5 hours, so that the water is gradually evaporated and the solute is crystallized. Then transfer the crystallized material to a vacuum drying oven, set the drying temperature to 55℃, the vacuum degree to -0.08 MPa, and dry for 5 hours. Then use an air flow crusher to crush the dried material, put the crushed material into a ball mill for grinding, and grind for 1.5 hours. Finally, use a 100-mesh sieve to sieve the ground material to obtain the citric acid dialysis powder.

[0094] Comparative Example 7

[0095] The present comparative example provides a citric acid dialysis powder, which comprises the following raw materials by weight:

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

[0097] The preparation method of the citric acid dialysis powder of the present comparative example comprises the following steps:

[0098] S1: according to the weight fraction of the formula, use an electronic balance to accurately weigh sodium chloride, calcium chloride, potassium chloride, magnesium chloride, glucose, citric acid, polyethylene glycol, glycerol and pure water, put the weighed sodium chloride, calcium chloride, potassium chloride, magnesium chloride, glucose, citric acid, polyethylene glycol and glycerol into a reaction kettle, then add the weighed pure water. Turn on the stirring equipment, set the stirring speed to 250 r / min, and continuously stir for 20 min until all the ingredients are fully dissolved and uniformly mixed to obtain a mixed solution. Then use water bath heating method, put the reaction kettle in a water bath, adjust the water temperature to 60℃, and heat for 20 min to make all the ingredients fully dissolved and mixed. After heating, take the reaction kettle out of the water bath, use water bath cooling method, put it into the water bath containing cold water, cool the solution to room temperature, and obtain the mixed solution.

[0099] S3: transfer the mixed solution into an evaporator, adjust the temperature of the evaporator to 65℃, and perform evaporation crystallization operation for 2.5 hours, so that the water is gradually evaporated and the solute is crystallized. Then transfer the crystallized material to a vacuum drying oven, set the drying temperature to 55℃, the vacuum degree to -0.08 MPa, and dry for 5 hours. Then use an air flow crusher to crush the dried material, put the crushed material into a ball mill for grinding, and grind for 1.5 hours. Finally, use a 100-mesh sieve to sieve the ground material to obtain the citric acid dialysis powder.

[0100] Experimental Example

[0101] The citric acid dialysis powder prepared in Examples 1-4 and Comparative Examples 1-7 was subjected to a solubility test, and the specific method was as follows:

[0102] The temperature of the constant temperature water bath was set to 37°C (simulating the human body temperature environment, close to the clinical use scene), and preheated for 15 minutes. 5.000 g of the citric acid dialysis powder prepared in Examples 1-4 and Comparative Examples 1-7 was weighed with an electronic balance, 200 mL of deionized water was accurately measured with a pipette gun, and was added to a 250 mL conical flask with a stopper. The conical flask was placed in the constant temperature water bath and preheated for 5 minutes. The weighed dialysis powder was quickly poured into the preheated conical flask with a stopper, and the stopwatch was started at the same time, and immediately fixed the conical flask on the magnetic stirrer, and set the stirring speed to 200 r / min. During the continuous stirring process, the turbidity of the solution was measured every 10 seconds with a turbidimeter, and the time and turbidity value of each measurement were recorded until the turbidity of the solution was stable (the turbidity change of continuous 3 times measurement was not more than 5%), the timing was stopped, and the total dissolution time was recorded. The results are shown in Table 1:

[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, 2, it can be seen that the addition of polyethylene glycol and glycerol in the formula of the instant citric acid dialysis powder can synergistically improve the solubility of the citric acid dialysis powder. By comparing the data of Example 1 and Comparative Examples 3-6, it can be seen that although the replacement of polyethylene glycol and glycerol with other substances can also improve the solubility of the citric acid dialysis powder, it is far inferior to the solubility of the instant citric acid dialysis powder formula with the addition of polyethylene glycol and glycerol. By comparing the data of Example 1 and Comparative Example 7, it can be seen that the solubility of the citric acid dialysis powder prepared by one-step method is far inferior to the solubility of the citric acid dialysis powder prepared by two-step method of the present application. Therefore, the addition of polyethylene glycol and glycerol in the citric acid dialysis powder can significantly shorten the dissolution time, and the absence or replacement of one of the ingredients will result in a decrease in dissolution efficiency, and the preparation of the citric acid dialysis powder by two-step method can greatly improve the solubility of the citric acid dialysis powder.

[0106] Although the principles of the present application have been described in detail above in connection with the preferred embodiments of the present application, those skilled in the art should understand that the above-mentioned embodiments are only illustrative implementations of the present application, and are not a limitation on the scope of the present application. The details in the embodiments do not constitute a limitation on the scope of the present application, and any equivalent changes, simple replacements, etc. based on the technical solutions of the present application, which are obvious, fall within the scope of protection of the present application.

Claims

1. An instant citrate dialysis powder, characterized in that, The preparation method comprises the following steps: S1: according to the weight fraction, sodium chloride, calcium chloride, potassium chloride, magnesium chloride, glucose and 1 / 2 pure water are weighed and mixed, and then stirred uniformly to obtain a mixed solution A; S2: according to the weight fraction, citric acid, polyethylene glycol, glycerol and 1 / 2 pure water are mixed, heated, and then cooled to room temperature to obtain a mixed solution B; S3: the mixed solution B is added to the mixed solution A, and then fully mixed, evaporated, crystallized, dried, crushed, ground and sieved to obtain the instant citric acid dialysis powder. The preparation method comprises the following steps: S1: according to the weight fraction, sodium chloride, calcium chloride, potassium chloride, magnesium chloride, glucose and 1 / 2 pure water are weighed and mixed, and then stirred uniformly to obtain a mixed solution A; S2: according to the weight fraction, citric acid, polyethylene glycol, glycerol and 1 / 2 pure water are mixed, heated, and then cooled to room temperature to obtain a mixed solution B; S3: the mixed solution B is added to the mixed solution A, and then fully mixed, evaporated, crystallized, dried, crushed, ground and sieved to obtain the instant citric acid dialysis powder. The preparation method comprises the following steps: S1: according to the weight fraction, sodium chloride, calcium chloride, potassium chloride, magnesium chloride, glucose and 1 / 2 pure water are weighed and mixed, and then stirred uniformly to obtain a mixed solution A; S2: according to the weight fraction, citric acid, polyethylene glycol, glycerol and 1 / 2 pure water are mixed, heated, and then cooled to room temperature to obtain a mixed solution B; S3: the mixed solution B is added to the mixed solution A, and then fully mixed, evaporated, crystallized, dried, crushed, ground and sieved to obtain the instant citric acid dialysis powder. In step S2, the heating is performed by water bath heating; and / or, The heating temperature is 50-70 DEG C, and the heating time is 10-30 min; and / or, In step S2, the cooling is performed by water bath cooling.

2. The instant citrate dialysis powder according to claim 1, characterized in that In step S1, the stirring speed is 200-300 r / min; and / or, The stirring time is 15-20 min. In step S3, the evaporating and crystallizing temperature is 60-70 DEG C; and / or, The evaporating and crystallizing time is 2-3 h. In step S3, the drying is performed by vacuum drying; and / or, The drying temperature is 50-60 DEG C, the vacuum degree is (-0.08)-(-0.09) MPa, and the drying time is 4-6 hours. In step S3, the crushing is performed by an air flow crusher; and / or, The grinding is performed by a ball mill, and the grinding time is 1-2 h; and / or, ​ ​ 3. The instant citrate dialysis powder according to claim 1, characterized in that ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ 4. Instant citrate dialysis powder according to any one of claims 1-3, characterized in that, ​ 5. A process for the preparation of an instant citrate dialysis powder as claimed in any one of claims 1 to 4, characterized in that, ​ ​ ​ ​ 6. The process for the preparation of an instant citrate dialysis powder according to claim 5, characterized in that, ​ ​ ​ 7. The process for the preparation of an instant citrate dialysis powder according to claim 5, characterized in that, ​ ​ 8. The process for the preparation of an instant citrate dialysis powder according to claim 5, characterized in that, ​ ​ 9. The process for the preparation of an instant citrate dialysis powder according to claim 5, characterized in that, ​ ​ 10. The process for the preparation of instant citrate dialysis powder according to claim 5, characterized in that, ​ ​ The screen used for sieving is 100-120 mesh. The screen used for sieving is 100-120 mesh.