Preparation for blood purification as well as preparation method and application thereof

Abstract

The invention provides a preparation for blood purification and a preparation method and application thereof.The preparation is in a solid state or a liquid state, L-malic acid serves as a pH regulator of the preparation, calcium citrate and calcium chloride are used for providing total calcium, the total calcium addition value of the preparation is 1.0-1.5 mmol / L, and the total calcium addition value of the preparation is 1.0-1.5 mmol / L. A dialysate for clinical application of the preparation contains ionized calcium and molecular calcium at the same time, the molar concentration ratio of the ionized calcium to the molecular calcium is 2-6, the ratio of the total calcium addition value to the molar concentration of the citrate radical is 10-12, the molar concentration ratio of the citrate radical to the L-malic acid is 0.05-0.15, and the molar concentration ratio of the citric acid radical to the L-malic acid is 0.05-0.15. The calcium chloride, the calcium citrate and the L-malic acid are reasonably proportioned, so that the supply of 80-85% of effective free calcium can be realized on the premise of ensuring a low total calcium addition value, thereby obviously reducing adverse reactions caused by low calcium or high calcium in the dialysis process, and effectively preventing and controlling dialysis syndromes and the problem of calcium ion disorder possibly occurring after dialysis.

Description

Technical Field

[0001] The present invention relates to the technical field of hemodialysis, and in particular to a blood purification preparation and a preparation method and application thereof. Background Art

[0002] As a treatment for chronic renal failure, blood purification technology is mainly used to achieve the exchange of solutes and water in the blood, thereby removing metabolic wastes such as creatinine and urea nitrogen from the body. The process also includes regulating water and electrolyte balance to achieve therapeutic effects.

[0003] The blood purification preparations in the prior art are usually composed of two parts, A and B, wherein A contains sodium chloride, potassium chloride, calcium chloride, magnesium chloride and pH regulator, and B is mainly composed of sodium bicarbonate or a mixture of sodium bicarbonate and sodium chloride. Due to high concentration, small volume, easy storage and transportation, blood purification concentrated powders or concentrated solutions prepared and preserved with concentrated powders have been widely used in the field of dialysis treatment.

[0004] Although blood purification concentrated powders have been widely used in clinical practice, in actual use, various blood purification preparations on the market still have a high risk of causing dialysis syndrome / complications, including nausea, vomiting, headaches, fatigue, anxiety, hypertension, hypotension and even heart failure, which cause serious troubles to patients. Studies have shown that the emergence of these problems is largely attributed to the use of acetic acid as a pH regulator, because acetic acid has a greater metabolic pressure on the patient's liver, which can easily cause headaches, blood pressure fluctuations and intolerance.

[0005] In order to deal with problems such as intolerance caused by the acetic acid component in blood purification preparations, the existing technology began to use citric acid as an alternative. However, citrate is very easy to chelate with calcium, resulting in a large amount of calcium ions chelated with citrate. In actual clinical applications, the calcium ion concentration cannot meet clinical needs, leading to problems such as hypocalcemia. Even if this problem is discovered, common remedial measures include increasing the calcium ion content in the preparation formula, or dynamically adjusting the amount of citric acid based on real-time monitoring data of blood gas calcium ions. However, the aforementioned solutions cannot effectively solve the calcium ion disorder problem caused by citric acid as a pH regulator, thereby greatly increasing the risk of hypocalcemia / hypercalcemia in patients.

[0006] Therefore, the various types of blood purification concentrated powders currently used in clinical treatment have not yet formed an effective strategy for preventing or controlling dialysis syndrome / complications and low calcium / high calcium problems caused by the blood purification process. Summary of the invention

[0007] The present invention is a solution to the above problems.

[0008] The invention provides a preparation for blood purification, which is a preparation in a solid state or a liquid state. The dialysate for clinical use of the preparation contains: 135-145 mmol / L of sodium ions, 2-4 mmol / L of potassium ions, 0.25-0.75 mmol / L of magnesium ions, 100-115 mmol / L of chloride ions, and 28-38 mmol / L of bicarbonate. The preparation is characterized in that the preparation further contains 3.0-7.0 mmol / L of glucose, 0.02-0.18 mmol / L of citrate, and 0.5-2 mmol / L of L-malic acid. The total calcium addition value of the preparation is 1.0-1.5 mmol / L. The dialysate for clinical use of the preparation contains both ionic calcium and molecular calcium, and the molar concentration ratio of the ionic calcium to the molecular calcium is 2-6, the ratio of the total calcium addition value to the molar concentration of citrate is 10-12, and the molar concentration ratio of the citrate to the L-malic acid is 0.05-0.15.

[0009] In a preferred embodiment, the preparation contains calcium citrate and calcium chloride, the mass ratio of calcium citrate to calcium chloride is 4-6 (preferably 4.5-5), and the molar concentration ratio of ionized calcium to molecular calcium in the final dialysate is 4.5-5.8, so as to ensure that while providing sufficient total calcium, excessive chelation is avoided, so that the proportion of effective free calcium in the final dialysate reaches 80-85%.

[0010] Furthermore, the dialysate for clinical use of the preparation contains: sodium ions 138 mmol / L, potassium ions 2.5 mmol / L, magnesium ions 0.5 mmol / L, chloride ions 109 mmol / L, bicarbonate 35 mmol / L, glucose 6.7 mmol / L, citrate 0.13 mmol / L, L-malic acid 1.1 mmol / L, and the total calcium added value of the preparation is 1.4 mmol / L.

[0011] The present invention also provides a solid preparation for blood purification, the solid preparation comprising A powder and B powder, the A powder comprising by weight: 205-215g of sodium chloride, 6.0-7.0g of potassium chloride, 5.8-6.3g of calcium chloride dihydrate, 3.0-4.0g of magnesium chloride hexahydrate, 20.5-48.5g of glucose, 0.2-1.8g of calcium citrate tetrahydrate, 2.5-9.5g of L-malic acid, and the B powder comprising by weight 67.2-90g of sodium bicarbonate. And wherein, the weight ratio of calcium chloride dihydrate to calcium citrate tetrahydrate is 4-6, and the weight ratio of L-malic acid to calcium citrate tetrahydrate is 3.5-4.5. Through the above ratio, the ideal distribution of ionic calcium and molecular calcium can be achieved in the final dialysate.

[0012] In a preferred embodiment, the A powder contains, by weight: 210.7 g sodium chloride, 6.5 g potassium chloride, 6.17 g calcium chloride dihydrate, 3.55 g magnesium chloride hexahydrate, 42 g glucose, 1.3 g calcium citrate tetrahydrate, and 5.16 g L-malic acid, and the B powder contains, by weight, 84 g sodium bicarbonate.

[0013] Furthermore, the present invention also provides a liquid preparation for blood purification, which comprises liquid A and liquid B, characterized in that the liquid A is obtained by adding dialysis water to the A powder in the aforementioned solid preparation for blood purification and dissolving it to 1000 ml, and the liquid B is obtained by adding dialysis water to the B powder in the aforementioned solid preparation for blood purification and dissolving it to 1000 ml.

[0014] Furthermore, the present invention also provides a blood purification preparation, which is obtained by uniformly mixing the liquid A, liquid B and dialysis water in the aforementioned liquid preparation for blood purification in a ratio of 1:1.225:32.775.

[0015] In another embodiment, the present invention also provides a solid preparation for blood purification, the solid preparation comprising A powder and B powder, the A powder comprising by weight: 205-215g sodium chloride, 6.0-7.0g potassium chloride, 5.8-6.3g calcium chloride dihydrate, 3.0-4.0g magnesium chloride hexahydrate, 20.5-48.5g glucose, 0.2-1.8g calcium citrate tetrahydrate, 2.5-9.5g L-malic acid, 10-15g sodium malate, the B powder comprising by weight 52.5-70.2g sodium bicarbonate; and wherein the weight ratio of calcium chloride dihydrate to calcium citrate tetrahydrate is 4-6, and the weight ratio of L-malic acid to calcium citrate tetrahydrate is 3.5-4.5. Through the above ratio, the ideal distribution of ionic calcium and molecular calcium can be achieved in the final dialysate.

[0016] In a preferred embodiment, the A powder contains, by weight: 212.8 g of sodium chloride, 6.5 g of potassium chloride, 6.17 parts of calcium chloride dihydrate, 3.55 g of magnesium chloride hexahydrate, 35 g of glucose, 1.3 g of calcium citrate tetrahydrate, 5.16 g of L-malic acid, and 13.73 g of sodium malate; and the B powder contains, by weight, 65.45 g of sodium bicarbonate.

[0017] Furthermore, the present invention also provides a liquid preparation for blood purification, which comprises liquid A and liquid B, characterized in that the liquid A is obtained by adding dialysis water to the A powder in the aforementioned solid preparation for blood purification and dissolving it to 1000 ml, and the liquid B is obtained by adding dialysis water to the B powder in the aforementioned solid preparation for blood purification and dissolving it to 1000 ml.

[0018] Furthermore, the present invention also provides a blood purification preparation, which is obtained by uniformly mixing the liquid A, liquid B and dialysis water in the aforementioned liquid preparation for blood purification in a ratio of 1:1.26:32.74.

[0019] The present invention also provides a method for preparing a blood purification preparation, comprising the following steps:

[0020] (1) By weight, 205-215 g of sodium chloride, 6.0-7.0 g of potassium chloride, 5.8-6.3 g of calcium chloride dihydrate, 3.0-4.0 g of magnesium chloride hexahydrate, 20.5-48.5 g of glucose, 0.2-1.8 g of calcium citrate tetrahydrate, and 2.5-9.5 g of L-malic acid are sieved and mixed uniformly, and then sealed in a first container; and by weight, 67.2-90 g of sodium bicarbonate are sieved and sealed in a second container; or

[0021] By weight, 205-215 g of sodium chloride, 6.0-7.0 g of potassium chloride, 5.8-6.3 g of calcium chloride dihydrate, 3.0-4.0 g of magnesium chloride hexahydrate, 20.5-48.5 g of glucose, 0.2-1.8 g of calcium citrate tetrahydrate, 2.5-9.5 g of L-malic acid, and 10-15 g of sodium malate are sieved and mixed uniformly, and then sealed in a first container; and by weight, 52.5-70.2 g of sodium bicarbonate are sieved and sealed in a second container;

[0022] (2) adding dialysis water to dissolve the solid preparations in the first container and the second container to 1000 ml, respectively, to obtain concentrated solution A and concentrated solution B;

[0023] (3) Evenly mix concentrated solution A, concentrated solution B, and dialysis water in a ratio of 1:1.225:32.775 or 1:1.26:32.74.

[0024] Furthermore, after uniform mixing in step (3), a blood purification preparation for clinical use is obtained, wherein the blood purification preparation for clinical use contains: 135-145 mmol / L sodium ions, 2-4 mmol / L potassium ions, 0.25-0.75 mmol / L magnesium ions, 100-115 mmol / L chloride ions, 28-38 mmol / L bicarbonate, and further contains: 3.0-7.0 mmol / L glucose, 0.02-0.18 mmol / L citrate, and 0.5-2 mmol / L L-malic acid; wherein the total calcium addition value of the preparation is 1.0-1.5 mmol / L, the blood purification preparation for clinical use contains both ionic calcium and molecular calcium, and the molar concentration ratio of the ionic calcium to the molecular calcium is 2-6, the ratio of the total calcium addition value to the molar concentration of citrate is 10-12, and the molar concentration ratio of citrate to L-malic acid is 0.05-0.15.

[0025] The present invention also provides the use of the aforementioned blood purification preparation in the preparation of a blood purification treatment device.

[0026] The blood purification preparation provided by the present invention and its preparation method and application can achieve the following beneficial effects:

[0027] 1) When selecting a pH regulator, acetic acid is excluded, which effectively solves various intolerance problems caused by the burden of acetic acid metabolism in the liver. The present invention uses L-malic acid as a pH regulator. Malic acid is a key component of the human tricarboxylic acid cycle and a physiologically active organic acid. It has a positive effect on human metabolism and has no known adverse reactions.

[0028] 2) When selecting a pH adjuster, excluding the use of citric acid can effectively prevent citrate ions from forming chelates with calcium ions, magnesium ions, etc., compared with the formulation using citric acid as the pH adjuster, thereby avoiding the problem of calcium ion disorder caused by the chelation of a large amount of calcium ions in the final solution of clinical application, and helping to maintain the stability of calcium ion levels in dialysis patients.

[0029] 3) Providing an appropriate amount of chelated calcium by combining L-malic acid with an appropriate amount of calcium citrate helps maintain the dynamic balance of calcium in the patient's body.

[0030] 4) The ratio of calcium citrate to malic acid was optimized to ensure that calcium citrate and malic acid were completely dissolved after mixing, to prevent precipitation from forming, and to keep the pH value of the final solution within the normal range for the human body.

[0031] 5) The ratio of calcium chloride to calcium citrate is optimized to maintain the content ratio of ionized calcium (also known as free calcium) and molecular calcium (also known as chelated calcium or complex calcium) in the final solution for clinical application within an ideal range, thereby providing appropriate calcium dynamic balance maintenance programs for different patients.

[0032] 6) On the basis of an appropriate amount of calcium citrate, the incidence of post-dialysis hypokalemia can be significantly reduced by moderately increasing the dose of potassium chloride.

[0033] 7) On the basis of determining the contents of calcium chloride, calcium citrate and L-malic acid, further optimize the glucose content to ensure the balance of transmembrane osmosis and diffusion of blood glucose in dialysis patients during dialysis, further stabilize the blood glucose and blood pressure of patients, and effectively reduce the probability of dialysis complications / syndrome. DETAILED DESCRIPTION

[0034] The present invention will be further described in detail below in conjunction with specific embodiments, but it is not intended to limit the scope of the present invention.

[0035] Embodiment 1:

[0036] Take 210.7 g of sodium chloride, 6.5 g of potassium chloride, 6.17 g of calcium chloride dihydrate, 3.55 g of magnesium chloride hexahydrate, 42 g of glucose, 1.3 g of calcium citrate tetrahydrate, and 5.16 g of L-malic acid, sieve them separately, mix them evenly, and seal them in container 1 to obtain solid powder preparation A. Take 84 g of sodium bicarbonate, sieve them, and seal them in container 2 to obtain solid powder preparation B.

[0037] The powder preparation A was dissolved in dialysis water to 1000 ml to obtain concentrated A solution; the powder preparation B was dissolved in dialysis water to 1000 ml to obtain concentrated B solution.

[0038] Evenly mix concentrated solution A, concentrated solution B and dialysis water in a ratio of 1:1.225:32.775 to obtain a final solution for use in dialysis treatment of patients.

[0039] Embodiment 2:

[0040] Take 212g of sodium chloride, 7g of potassium chloride, 6.3g of calcium chloride dihydrate, 3.6g of magnesium chloride hexahydrate, 44g of glucose, 1.5g of calcium citrate tetrahydrate, and 5.36g of L-malic acid, sieve them respectively, mix them evenly, and seal them in container 1 to obtain solid powder preparation A. Take 84g of sodium bicarbonate, sieve them, and seal them in container 2 to obtain solid powder preparation B.

[0041] The powder preparation A was dissolved in dialysis water to 1000 ml to obtain concentrated A solution; the powder preparation B was dissolved in dialysis water to 1000 ml to obtain concentrated B solution.

[0042] Then, the concentrated A solution, the concentrated B solution and the dialysis water are uniformly mixed in a ratio of 1:1.225:32.775 to obtain the final solution for the patient's dialysis treatment.

[0043] Embodiment 3:

[0044] Take 1053.5g of sodium chloride, 32.5g of potassium chloride, 30.85g of calcium chloride dihydrate, 17.75g of magnesium chloride hexahydrate, 210g of glucose, 6.5g of calcium citrate tetrahydrate, and 25.8g of L-malic acid, sieve them respectively, mix them evenly, and seal them in container 1 to obtain solid powder preparation A. Take 546g of sodium bicarbonate, sieve them, and seal them in container 2 to obtain solid powder preparation B.

[0045] The A powder preparation is dissolved and diluted with dialysis water to obtain concentrated A solution; the B powder preparation is dissolved and diluted with dialysis water to obtain concentrated B solution.

[0046] Evenly mix concentrated solution A, concentrated solution B and dialysis water in a ratio of 1:1.225:32.775 to obtain a final solution for use in dialysis treatment of patients.

[0047] Embodiment 4:

[0048] Sodium chloride, potassium chloride, calcium chloride dihydrate, magnesium chloride hexahydrate, glucose, calcium citrate tetrahydrate, L-malic acid and dialysis water are mixed to obtain concentrated solution A, wherein the concentrations of the components in the concentrated solution A are: sodium chloride 210.7 g / L, potassium chloride 6.5 g / L, calcium chloride 4.66 g / L, magnesium chloride 1.66 g / L, glucose 42 g / L, calcium citrate 1.12 g / L, and L-malic acid 5.16 g / L.

[0049] Sodium bicarbonate and dialysis water are mixed to obtain concentrated B solution, and the component concentration in the concentrated B solution is: sodium bicarbonate 84g / L.

[0050] Evenly mix concentrated solution A, concentrated solution B and dialysis water in a ratio of 1:1.225:32.775 to obtain a final solution for use in dialysis treatment of patients.

[0051] Embodiment 5:

[0052] Sodium chloride, potassium chloride, calcium chloride dihydrate, magnesium chloride hexahydrate, glucose, calcium citrate tetrahydrate, L-malic acid and dialysis water are mixed to obtain concentrated solution A, wherein the concentrations of the components in the concentrated solution A are: sodium chloride 212 g / L, potassium chloride 7 g / L, calcium chloride 4.76 g / L, magnesium chloride 1.69 g / L, glucose 44 g / L, calcium citrate 1.29 g / L, and L-malic acid 5.36 g / L.

[0053] Sodium bicarbonate and dialysis water are mixed to obtain concentrated B solution, and the component concentration in the concentrated B solution is: sodium bicarbonate 84g / L.

[0054] Evenly mix concentrated solution A, concentrated solution B and dialysis water in a ratio of 1:1.225:32.775 to obtain a final solution for use in dialysis treatment of patients.

[0055] Embodiment 6:

[0056] Sodium chloride, potassium chloride, calcium chloride dihydrate, magnesium chloride hexahydrate, glucose, calcium citrate tetrahydrate, L-malic acid and dialysis water are mixed to obtain concentrated solution A, wherein the concentrations of the components in the concentrated solution A are: sodium chloride 208 g / L, potassium chloride 6.1 g / L, calcium chloride 4.45 g / L, magnesium chloride 1.52 g / L, glucose 27 g / L, calcium citrate 1.12 g / L, and L-malic acid 4.9 g / L.

[0057] Sodium bicarbonate and dialysis water are mixed to obtain concentrated B solution, wherein the component concentration of the concentrated B solution is: sodium bicarbonate 80 g / L.

[0058] Evenly mix concentrated solution A, concentrated solution B and dialysis water in a ratio of 1:1.225:32.775 to obtain a final solution for use in dialysis treatment of patients.

[0059] Embodiment 7:

[0060] Take 210g of sodium chloride, 6.5g of potassium chloride, 6.3g of calcium chloride dihydrate, 3.55g of magnesium chloride hexahydrate, 42g of glucose, 1.2g of calcium citrate tetrahydrate, and 4.9g of L-malic acid, sieve them respectively, mix them evenly, and seal them in container 1 to obtain solid powder preparation A. Take 84g of sodium bicarbonate, sieve them, and seal them in container 2 to obtain solid powder preparation B.

[0061] The powder preparation A was dissolved in dialysis water to 1000 ml to obtain concentrated A solution; the powder preparation B was dissolved in dialysis water to 1000 ml to obtain concentrated B solution.

[0062] Then, the concentrated A solution, the concentrated B solution and the dialysis water are uniformly mixed in a ratio of 1:1.225:32.775 to obtain the final solution for the patient's dialysis treatment.

[0063] Embodiment 8:

[0064] Take 212.8g of sodium chloride, 6.5g of potassium chloride, 6.17g of calcium chloride dihydrate, 3.55g of magnesium chloride hexahydrate, 35g of glucose, 1.3g of calcium citrate tetrahydrate, 5.16g of L-malic acid, and 13.73g of sodium malate, sieve them respectively, mix them evenly, and seal them in container 1 to obtain solid powder preparation A. Take 65.45g of sodium bicarbonate, sieve them, and seal them in container 2 to obtain solid powder preparation B.

[0065] The powder preparation A was dissolved in dialysis water to 1000 ml to obtain concentrated A solution; the powder preparation B was dissolved in dialysis water to 1000 ml to obtain concentrated B solution.

[0066] The concentrated A solution, the concentrated B solution and the dialysis water were uniformly mixed in a ratio of 1:1.26:32.74 to obtain the final solution for the dialysis treatment of the patient.

[0067] Embodiment 9:

[0068] Take 215g of sodium chloride, 6.8g of potassium chloride, 6.5g of calcium chloride dihydrate, 3.7g of magnesium chloride hexahydrate, 38g of glucose, 1.4g of calcium citrate tetrahydrate, 5.4g of L-malic acid, and 13.45g of sodium malate, sieve them separately, mix them evenly, and seal them in container 1 to obtain solid powder preparation A. Take 63.45g of sodium bicarbonate, sieve them, and seal them in container 2 to obtain solid powder preparation B.

[0069] The powder preparation A was dissolved in dialysis water to 1000 ml to obtain concentrated A solution; the powder preparation B was dissolved in dialysis water to 1000 ml to obtain concentrated B solution.

[0070] The concentrated A solution, the concentrated B solution and the dialysis water were uniformly mixed in a ratio of 1:1.26:32.74 to obtain the final solution for the dialysis treatment of the patient.

[0071] Embodiment 10:

[0072] Take 1064g of sodium chloride, 32.5g of potassium chloride, 30.85g of calcium chloride dihydrate, 17.75g of magnesium chloride hexahydrate, 175g of glucose, 6.5g of calcium citrate tetrahydrate, 25.8g of L-malic acid, and 68.65g of sodium malate, sieve them respectively, mix them evenly, and seal them in container 1 to obtain solid powder preparation A. Take 327.25g of sodium bicarbonate, sieve them, and seal them in container 2 to obtain solid powder preparation B.

[0073] The A powder preparation is dissolved and diluted with dialysis water to obtain concentrated A solution; the B powder preparation is dissolved and diluted with dialysis water to obtain concentrated B solution.

[0074] The concentrated A solution, the concentrated B solution and the dialysis water were uniformly mixed in a ratio of 1:1.26:32.74 to obtain the final solution for the dialysis treatment of the patient.

[0075] Embodiment 11:

[0076] Sodium chloride, potassium chloride, calcium chloride dihydrate, magnesium chloride hexahydrate, glucose, calcium citrate tetrahydrate, L-malic acid, sodium malate and dialysis water are mixed to obtain concentrated solution A, wherein the concentrations of the components in the concentrated solution A are: sodium chloride 212.8 g / L, potassium chloride 6.5 g / L, calcium chloride 4.66 g / L, magnesium chloride 1.66 g / L, glucose 42 g / L, calcium citrate 1.12 g / L, L-malic acid 5.16 g / L, and sodium malate 13.73 g / L.

[0077] Sodium bicarbonate and dialysis water are mixed to obtain concentrated B solution, and the component concentration in the concentrated B solution is: sodium bicarbonate 65.45 g / L.

[0078] The concentrated A solution, the concentrated B solution and the dialysis water were uniformly mixed in a ratio of 1:1.26:32.74 to obtain the final solution for the dialysis treatment of the patient.

[0079] Embodiment 12:

[0080] Sodium chloride, potassium chloride, calcium chloride dihydrate, magnesium chloride hexahydrate, glucose, calcium citrate tetrahydrate, L-malic acid, sodium malate and dialysis water are mixed to obtain concentrated A solution, wherein the concentrations of the components in the concentrated A solution are: sodium chloride 215 g / L, potassium chloride 7 g / L, calcium chloride 4.76 g / L, magnesium chloride 1.69 g / L, glucose 44 g / L, calcium citrate 1.29 g / L, L-malic acid 5.36 g / L, and sodium malate 15 g / L.

[0081] Sodium bicarbonate and dialysis water are mixed to obtain concentrated B solution, and the component concentration in the concentrated B solution is: sodium bicarbonate 62.35 g / L.

[0082] The concentrated A solution, the concentrated B solution and the dialysis water were uniformly mixed in a ratio of 1:1.26:32.74 to obtain the final solution for the dialysis treatment of the patient.

[0083] Embodiment 13:

[0084] Sodium chloride, potassium chloride, calcium chloride dihydrate, magnesium chloride hexahydrate, calcium citrate tetrahydrate, L-malic acid, and glucose are mixed and diluted to obtain concentrated solution A, sodium bicarbonate is diluted to obtain concentrated solution B, and solution A and solution B are mixed and diluted according to the ratio required by the dialysis machine to obtain the final solution for dialysis.

[0085] The components in the final solution are as follows: sodium ion 138mmol / L, potassium ion 2.5mmol / L, magnesium ion 0.5mmol / L, chloride ion 109mmol / L, bicarbonate 35mmol / L, glucose 6.7mmol / L, citrate 0.13mmol / L, L-malic acid 1.1mmol / L, of which the total calcium addition value is 1.4mmol / L. The standardized calcium ion content in the final solution measured by blood gas analyzer is 1.16mmol / L.

[0086] Embodiment 14:

[0087] Sodium chloride, potassium chloride, calcium chloride dihydrate, magnesium chloride hexahydrate, calcium citrate tetrahydrate, L-malic acid, and glucose are mixed and diluted to obtain concentrated solution A, sodium bicarbonate is diluted to obtain concentrated solution B, and solution A and solution B are mixed and diluted according to the ratio required by the dialysis machine to obtain the final solution for dialysis.

[0088] The components in the final solution are as follows: sodium ion 138mmol / L, potassium ion 2.4mmol / L, magnesium ion 0.5mmol / L, chloride ion 109mmol / L, bicarbonate 35mmol / L, glucose 6.7mmol / L, citrate 0.12mmol / L, L-malic acid 1.05mmol / L, of which the total calcium addition value is 1.42mmol / L. The standardized calcium ion content in the final solution measured by blood gas analyzer is 1.17mmol / L.

[0089] Embodiment 15:

[0090] Sodium chloride, potassium chloride, calcium chloride dihydrate, magnesium chloride hexahydrate, calcium citrate tetrahydrate, L-malic acid, glucose, and sodium malate are mixed and diluted to obtain concentrated solution A, sodium bicarbonate is diluted to obtain concentrated solution B, and solution A and solution B are mixed and diluted according to the ratio required by the dialysis machine to obtain the final solution for dialysis.

[0091] The components in the final solution are as follows: sodium ion 136mmol / L, potassium ion 2.6mmol / L, magnesium ion 0.4mmol / L, chloride ion 109mmol / L, bicarbonate 35mmol / L, glucose 6.2mmol / L, citrate 0.13mmol / L, L-malic acid 1.3mmol / L, of which the total calcium addition value is 1.45mmol / L. The standardized calcium ion content in the final solution measured by blood gas analyzer is 1.17mmol / L.

[0092] According to an embodiment of the present invention, sodium chloride, potassium chloride, calcium chloride and magnesium chloride are conventional ingredients in blood purification preparations, which provide necessary electrolytes such as sodium ions, potassium ions, calcium ions, magnesium ions and chloride ions for the final purified fluid (dialysis fluid) for clinical applications.

[0093] In the formula of the present invention, L-malic acid is used as a pH regulator to replace traditional acetic acid or citric acid. Unlike the scheme of using acetic acid as a pH regulator, malic acid is an important substance in the tricarboxylic acid cycle in the human body, a physiological organic acid, which is beneficial to human metabolism and has no adverse reactions. Compared with the scheme of using citric acid as a pH regulator, malic acid will not form a large number of chelates with calcium ions and magnesium ions in the dialysate, thereby avoiding the reduction of calcium ion concentration caused by the chelation of a large number of calcium ions in the final solution of clinical application, thereby causing calcium ion disorder problems, which helps to maintain the stability of calcium ion levels in dialysis patients.

[0094] An appropriate amount of chelated calcium is provided by combining L-malic acid with an appropriate amount of calcium citrate. In the process of preparing concentrated solution A, calcium citrate significantly improves its solubility under the action of malic acid. After dissolution, calcium ions and citrate ions are released. A part of the calcium ions and calcium ions in calcium chloride provide ionic calcium for the final solution, and the other part chelates with citrate ions to form soluble molecular calcium (chelated calcium).

[0095] The present invention defines all calcium components in the formula as total calcium, and the total calcium content is defined as total calcium added value. The total calcium added value is provided by calcium chloride and calcium citrate in the formula. The total calcium added value is 1.0-1.5 mmol / L, preferably 1.3-1.5 mmol / L, and more preferably 1.4 mmol / L. The total calcium added value of the present invention is equal to or lower than the standard of total calcium added value in each formula of the prior art.

[0096] The formula of the present invention is mixed with dialysis water in proportion to obtain a final dialysis solution that can be directly used in clinical practice. Total calcium coexists in the form of ionized calcium and molecular calcium in the final clinical dialysis solution, and the molar concentration ratio of ionized calcium to molecular calcium in the final solution is 2 to 6, and the value is preferably 4.5 to 5.8, that is, the effective calcium ion content in the final solution should account for 80 to 85% of the total calcium added amount, and the molecular calcium content should account for 15 to 20% of the total calcium added amount, which can better provide a dynamic balance of the calcium ion system.

[0097] The formula of the present invention was used as an experimental example (Example 1 to Example 3) and the conventional formula of the prior art (Comparative Example 1 to Comparative Example 5) were mixed with dialysis water in proportion to obtain a dialysate that can be directly used in clinical practice, and the ionized calcium and total calcium contents of the obtained dialysates were measured respectively.

[0098] The specific measurement method is as follows: for the samples in the examples and comparative examples, each group of samples is divided into two parts, and tested using a biochemical analyzer and a blood gas analyzer respectively.

[0099] Among them, the detection data of the biochemical analyzer comes from the Beckman CoulterAU5800 fully automatic biochemical analyzer, which uses spectrophotometry to detect calcium ions. The detection principle is to use a specific color developer to react with calcium ions. This reaction will generate a colored complex, the depth of its color is proportional to the concentration of calcium ions. By detecting the degree of absorption of light by the colored complex at a specific wavelength, the concentration of calcium ions can be calculated according to the Lambert-Beer law (absorbance is proportional to the concentration of the solution). For example, some color developers can combine with calcium ions to produce characteristic absorption peaks in the visible light range, and the instrument quantifies calcium ions by accurately measuring the absorbance of this absorption peak. Because in the process of detecting calcium ion concentration by spectrophotometry, the commonly used color developer is o-cresolphthalein complexone (0-CPC). In addition to chelating with calcium ions in the dialysate, this color developer also forms chelates with calcium ions in calcium citrate in the dialysate, thereby showing absorbance changes on the spectrophotometer. Therefore, the calcium ion content of the dialysate detected by the biochemical analyzer includes both ionic calcium and molecular calcium.

[0100] The test data of the blood gas analyzer comes from the Siemens RAPIDPoint 500 blood gas analyzer. The final dialysate is collected from the dialysis machine and then added to the pretreatment reagent that is compatible with the blood gas analyzer. The reagent contains a fluorescent substance that can bind to ionized calcium. When the fluorescent substance binds to the ionized calcium, it will emit a specific light signal. The blood gas analyzer will measure the intensity of this signal and calculate the concentration of ionized calcium in the patient's blood based on it. Because the blood gas analyzer performs pre-analysis factors (such as the sample being exposed to air) that may change the pH value of the sample before measurement, the measured ionized calcium concentration (such as CO2) may be different from the actual concentration. 2 The loss of calcium will alkalinize the sample and artificially reduce the measured ionized calcium concentration). Considering the influence of pH on the results, the blood gas analyzer will measure the pH value at the same time as the ionized calcium concentration is determined, and then calculate the standardized calcium ion concentration at pH 7.4. The calcium ion concentration measured by the blood gas analyzer reflects the content of free calcium.

[0101] According to the above measurement method, the final measured values ​​are shown in Table 1.

[0102] Table 1

[0103]

[0104] From the comparative experiment, it can be seen that although the total calcium addition value of the present invention is lower than that of the comparative example (1.5-1.8 mmol / L), when the calcium ion content in the final dialysate is detected by a blood gas analyzer, it is found that the calcium ion chelation degree is between 15% and 20%, and 80% to 85% of the total calcium exists in the dialysate in the form of free calcium. Since only free calcium in human blood is directly involved in the physiological metabolic activities of the human body, it means that the effective calcium ion ratio of the present invention can reach 80% to 85%, that is, 1.1 to 1.2 mmol / L of effective calcium ions can be provided.

[0105] On the other hand, in the comparison example, although the total calcium added value is higher, a large amount of calcium ions are chelated, and the chelation degree is as high as about 40%, which makes the free calcium account for only about 60%. Even if the total calcium added value is above 1.5mmol / L, the actual calcium ions that can be provided are only about 1.0mmol / L. Some formulas are as low as about 0.8mmol / L, which are all lower than the lower limit of the free calcium content range required by the normal human body.

[0106] The inventor of the present invention has found through extensive research and experiments that the existing citric acid-containing formulas all have the problems described in the comparative example. However, since the dialysate components are usually tested using a biochemical analyzer, the calcium content of the existing formulas meets or even exceeds the range required by the human body, whether from the calcium ion addition value of the formula or the calcium ion content detected using a biochemical analyzer. Therefore, this problem is usually not easy to detect. The inventor overcame prejudice and repeatedly tested with a blood gas analyzer and found that the root of the problem was that the proportion of free calcium that such formulas can actually provide is too low. As shown in Table 1, the comparative example has too low a free calcium content due to excessive chelation. Even when ion calcium is insufficient, other forms of calcium can be decomposed to supplement it, but the human body's calcium ion balance system has been disrupted, and the repeated dialysis process leads to calcium ion disorder in the patient, which in turn leads to frequent low calcium / high calcium problems.

[0107] In addition, in the existing formulas, even if the chelation effect of citrate and calcium ions is taken into account, in the scheme using citric acid as a pH regulator, the solution usually adopted is to increase the calcium ion content in the formula to compensate for the loss caused by chelation, for example, by increasing the calcium chloride content in the dialysis preparation and increasing the total calcium addition value (such as the total calcium 1.8 mmol / L scheme in Comparative Examples 3 and 5 in Table 1). On the surface, increasing the total calcium addition value can offset the effect of reduced ion calcium content caused by chelation of citrate ions and calcium ions to a certain extent (the standard calcium ion content in Comparative Examples 3 and 5 can reach 1.09mmol / L and 1.02mmol / L, respectively). However, the inventors of the present invention found in long-term dialysis clinical trials that this method only temporarily alleviates the problem of calcium ion chelation. Due to the continuous dialysis, the high total calcium content in the final solution can easily cause hypercalcemia and may activate the human body's calcitonin CT system, causing the thyroid parafollicular cells to secrete calcitonin CT to reduce blood calcium levels; even after the end of dialysis, the secretion of calcitonin will continue for a period of time and cause the human body's blood calcium level to continue to decrease. This continuous effect of calcitonin causes the human body's parathyroid hormone PTH system to continue to be stimulated to secrete PTH after the end of dialysis. PTH acts on osteoclasts, which can remove calcium from bones to maintain an appropriate blood calcium level and compensate for the effects caused by the continuous action of calcitonin CT. Since the PTH system is stimulated and acts for a period of time, the patient's bone calcium is damaged during this period of time; and since dialysis patients usually undergo dialysis treatment several times a week, the body's PTH system is repeatedly triggered, and patients undergoing long-term dialysis treatment may have hyperparathyroidism, resulting in continuous loss of bone calcium. Therefore, simply increasing the calcium ion content in the formula cannot effectively solve the problem of calcium ion disorder.

[0108] In summary, the formula of the present invention can provide a higher proportion of effective calcium ions with a lower total calcium addition value, which helps to provide a stable calcium ion environment and avoid calcium ion disorder problems. In addition, the formula of the present invention can provide a chelation degree of 10-15%, so that the calcium in this proportion of the total calcium addition value is chelated to form molecular calcium, and the formed molecular calcium coexists with ionic calcium. In this form, when the ionic calcium content is insufficient, the molecular calcium formed by citrate chelation will decompose to produce ionic calcium to provide supplementation, thereby providing a suitable calcium dynamic balance maintenance plan for different patients.

[0109] In a preferred embodiment, in the final solution, the concentration range of L-malic acid is 0.5 to 4 mmol / L. After further optimization, the concentration range is determined to be 0.55 to 2.0 mmol / L, wherein the optimal concentration is 1.1 mmol / L. This concentration can maintain a suitable pH value and effectively inhibit the formation of precipitation between calcium ions and magnesium ions and carbonate ions, thereby promoting the removal of toxins in the body, and while helping to promote the dissolution of calcium citrate, a small amount of chelated calcium is generated to maintain the stability of calcium ion exchange. The experimental results are shown in Table 2.

[0110] Table 2

[0111]

[0112] The preparation of the present invention does not contain citric acid, but contains an appropriate amount of calcium citrate, and calcium citrate is used in combination with L-malic acid to dissolve calcium citrate. Calcium citrate is slightly soluble in water, and its solubility is improved under the action of malic acid.

[0113] When preparing concentrated A solution, calcium citrate is dissolved to release calcium ions and citrate ions. By adding an appropriate amount of calcium citrate to A powder or A solution, an appropriate amount of citrate ions can be provided in the final solution, and this part of the citrate can react with the calcium ions by chelation. In this way, ionic calcium and molecular calcium are provided in the final solution for dialysis at the same time, wherein the content of ionic calcium is 1.15-1.5mmol / L, preferably 1.15-1.45mmol / L, preferably 1.2-1.4mmol / L, preferably 1.2mmol / L, and the content of total calcium addition value is lower than the dialysis formula in the prior art (usually 1.5-1.8mmol / L). On this basis, the formula of the present invention also provides an appropriate amount of molecular calcium in the form of molecular calcium by chelation of citrate, and the calcium ions that can be dissociated in the molecular calcium are preferably 0.16-0.2mmol / L. To this end, the content of calcium citrate and calcium chloride is maintained at a certain ratio so that the content of citrate in the final solution is 0.02-0.5 mmol / L, preferably 0.05-0.25 mmol / L, more preferably 0.1-0.15 mmol / L, and more preferably 0.13 mmol / L. In view of the fact that both calcium chloride and calcium citrate tetrahydrate make important contributions to the calcium ion supply of the human body, this study explores the mass ratio of the two in the formulation. Through experimental data analysis, it was determined that the mass ratio of calcium chloride to calcium citrate tetrahydrate was 4 to 6, of which the better ratio range was 4.5 to 5, and the best ratio was 4.75.

[0114] In addition, there is a significant correlation between the content of calcium citrate tetrahydrate and the content of L-malic acid. Through a large number of experimental studies, we determined the correlation between the content of malic acid and the content of calcium citrate tetrahydrate, and determined that the weight ratio of the two ranges from 3.5 to 4.5. After further optimization, the ratio range was determined to be 3.8 to 4.2, and further optimized to 3.9 to 4.0, with the optimal ratio value being 3.97. This ratio can ensure that the mixture of calcium citrate and malic acid is completely dissolved, effectively prevent the formation of precipitates, and maintain the pH value of the final solution within the normal physiological range of the human body.

[0115] In the formulation of the present invention, an appropriate amount of glucose is added to the dialysate, and the concentration range is set to 2-11mmol / L, the better choice is 2-10mmol / L, the further optimized range is 3-7mmol / L, and the optimal concentration is 6.7mmol / L. The addition of glucose helps to maintain the stability of the glucose level in the patient's blood. It can be used as an energy source and is conducive to maintaining osmotic pressure, thereby assisting the stability of the patient's blood pressure. A large number of experiments have verified that when the glucose concentration in the dialysate is lower than the lower limit, the patient is prone to symptoms such as calf cramps, hypoglycemia and hypotension during dialysis; and when the concentration exceeds the upper limit, it may cause the patient's blood sugar level to rise, induce hyperglycemia, and increase the risk of inflammation. Selecting a glucose concentration within the above-mentioned optimization range can significantly increase the ultrafiltration volume, enhance the dialysis clearance efficiency, and provide patients with a more comfortable treatment experience.

[0116] The blood purification composition provided by the present invention was used in clinical trials, 268 patients were screened, 260 were actually enrolled, and a total of 260 were included in statistical analysis to evaluate effectiveness and safety, including 132 cases in the experimental group and 128 cases in the control group.

[0117] Among them, the effectiveness indicator is the standard-reaching rate of blood electrolytes after purification. The primary efficacy evaluation (PPS) data set shows that the standard-reaching rate of the test group using the blood purification composition provided by the present invention is 94.7%, and that of the control group is 92.97%. The standard-reaching rate of the test group is better than that of the control group, as shown in Table 3.

[0118] Table 3

[0119]

[0120] During dialysis and clinical observation, no adverse events such as nausea, vomiting, headache, convulsion, infection, etc. occurred in the test group using the blood purification composition provided by the present invention, and some subjects reported that the symptoms of itching and fatigue were relieved after use. The test data show that the composition of the present invention can meet the needs of different types of dialysis patients and can be widely used in clinical practice.

[0121] The present invention has at least the following significant advantages and improved effects:

[0122] Improved pH regulation and calcium balance mechanism: L-malic acid is used as a pH regulator to avoid the metabolic burden on the liver caused by acetic acid, and reduce the problem of excessive chelation of calcium ions when citric acid is used in large quantities; by using it in combination with an appropriate amount of calcium citrate, it ensures that part of the calcium exists in a chelated state to form a sustained-release "molecular calcium", and ensures that most of the calcium exists in the form of free ions, thereby maintaining an effective supply of calcium ions in the dialysate at 80-85%.

[0123] Precise control of key parameters: The present invention stipulates the total calcium addition value (1.0-1.5 mmol / L), the molar ratio of ionic calcium to molecular calcium (2-6, preferably 4.5-5.8), and the molar ratios of total calcium to citrate, and citrate to L-malic acid (10-12 and 0.05-0.15, respectively). These parameters have been verified through a large number of comparative experiments, ensuring sufficient supply of effective calcium ions while avoiding the clinical risks caused by high or low calcium.

[0124] The results of the comparative experiment show that although the total calcium addition value of the present invention is lower than that of some existing solutions, the effective free calcium in the final dialysate is 80-85% as detected by the blood gas analyzer, while the free calcium in the traditional formula is only 56-61%. In addition, clinical trial data show that the preparation of the present invention has significant advantages in reducing the adverse reactions of hypokalemia and hypocalcemia.

[0125] It should be noted that the terms "include", "comprises" or any other variations thereof are intended to cover non-exclusive inclusion, so that a process, method, commodity or device including a series of elements includes not only those elements, but also other elements not explicitly listed, or also includes elements inherent to such process, method, commodity or device. In the absence of further restrictions, the elements defined by the sentence "comprises a ..." do not exclude the existence of other identical elements in the process, method, commodity or device including the elements.

[0126] The above description is only an embodiment of the present invention and is not intended to limit the present invention. For those skilled in the art, the present invention may have various modifications and variations. Any modification, equivalent substitution, improvement, etc. made within the spirit and principle of the present invention should be included in the scope of the claims of the present invention.

Claims

1. A blood purification preparation, which is a solid or liquid preparation, wherein the final dialysate after being prepared with dialysis water contains: sodium ions 135-145 mmol / L, potassium ions 2-4 mmol / L, magnesium ions 0.25-0.75 mmol / L, chloride ions 100-115 mmol / L, bicarbonate 28-38 mmol / L, characterized in that: The invention also comprises 3.0-7.0 mmol / L of glucose, 0.02-0.18 mmol / L of citrate, and 0.5-2 mmol / L of L-malic acid, wherein L-malic acid is used as a pH regulator in the preparation, and calcium citrate and calcium chloride are used to provide total calcium, and the total calcium addition value is 1.0-1.5 mmol / L. The dialysate of the preparation for clinical application comprises ionized calcium and molecular calcium at the same time, and the molar concentration ratio of the ionized calcium to the molecular calcium is 2-6, and the ratio of the total calcium addition value to the molar concentration of citrate is 10-12, and the molar concentration ratio of citrate to L-malic acid is 0.05-0.

15.

2. The blood purification preparation according to claim 1, characterized in that The mass ratio of calcium citrate to calcium chloride in the preparation is 4-6, and the molar concentration ratio of ionized calcium to molecular calcium in the final dialysate is 4.5-5.

8.

3. The blood purification preparation according to claim 1 or 2, characterized in that: The final dialysate after the preparation is prepared with dialysis water contains: sodium ion 138mmol / L, potassium ion 2.5mmol / L, magnesium ion 0.5mmol / L, chloride ion 109mmol / L, bicarbonate 35mmol / L, glucose 6.7mmol / L, citrate 0.13mmol / L, L-malic acid 1.1mmol / L, and the total calcium addition value is 1.4mmol / L.

4. A solid preparation for blood purification, comprising powder A and powder B, wherein the powder A comprises, by weight: Sodium chloride 205-215g, potassium chloride 6.0-7.0g, calcium chloride dihydrate 5.8-6.3g, magnesium chloride hexahydrate 3.0-4.0g, glucose 20.5-48.5g, calcium citrate tetrahydrate 0.2-1.8g, L-malic acid 2.5-9.5g, the B powder contains sodium bicarbonate 67.2-90g by weight; or, The A powder comprises, by weight: 205-215 g of sodium chloride, 6.0-7.0 g of potassium chloride, 5.8-6.3 g of calcium chloride dihydrate, 3.0-4.0 g of magnesium chloride hexahydrate, 20.5-48.5 g of glucose, 0.2-1.8 g of calcium citrate tetrahydrate, 2.5-9.5 g of L-malic acid, and 10-15 g of sodium malate; the B powder comprises, by weight: 52.5-70.2 g of sodium bicarbonate; In addition, the weight ratio of calcium chloride dihydrate to calcium citrate tetrahydrate in the A powder is 4-6, and the weight ratio of L-malic acid to calcium citrate tetrahydrate is 3.5-4.

5.

5. The blood purification preparation according to claim 4, characterized in that: The A powder contains, by weight: 210.7 g of sodium chloride, 6.5 g of potassium chloride, 6.17 g of calcium chloride dihydrate, 3.55 g of magnesium chloride hexahydrate, 42 g of glucose, 1.3 g of calcium citrate tetrahydrate, and 5.16 g of L-malic acid, and the B powder contains, by weight: 84 g of sodium bicarbonate; or, The A powder contains, by weight: 212.8 g of sodium chloride, 6.5 g of potassium chloride, 6.17 g of calcium chloride dihydrate, 3.55 g of magnesium chloride hexahydrate, 35 g of glucose, 1.3 g of calcium citrate tetrahydrate, 5.16 g of L-malic acid, and 13.73 g of sodium malate; the B powder contains, by weight: 65.45 g of sodium bicarbonate.

6. A liquid preparation for blood purification, comprising liquid A and liquid B, characterized in that: The A liquid is obtained by dissolving the A powder in the solid preparation for blood purification according to claim 4 or 5 with dialysis water to 1000 ml, and the B liquid is obtained by dissolving the B powder in the solid preparation for blood purification according to claim 3 or 4 with dialysis water to 1000 ml.

7. A blood purification preparation, characterized in that: The blood purification preparation is obtained by uniformly mixing the liquid A, liquid B and dialysis water in the liquid preparation for blood purification in claim 6 in a ratio of 1:1.225:32.775 or 1:1.26:32.

74.

8. The blood purification preparation according to claim 7, characterized in that The preparation contains: 135-145 mmol / L of sodium ions, 2-4 mmol / L of potassium ions, 0.25-0.75 mmol / L of magnesium ions, 100-115 mmol / L of chloride ions, 28-38 mmol / L of bicarbonate, and also contains: 3.0-7.0 mmol / L of glucose, 0.02-0.18 mmol / L of citrate, and 0.5-2 mmol / L of L-malic acid; wherein the preparation provides total calcium with calcium citrate and calcium chloride, the total calcium addition value is 1.0-1.5 mmol / L, the molar concentration ratio of ionic calcium to molecular calcium in the preparation is 2-6, the ratio of the total calcium addition value to the molar concentration of citrate is 10-12, and the molar concentration ratio of citrate to L-malic acid is 0.05-0.

15.

9. A method for preparing a blood purification preparation, characterized in that: The following steps are included: (1) By weight, 205-215 g of sodium chloride, 6.0-7.0 g of potassium chloride, 5.8-6.3 g of calcium chloride dihydrate, 3.0-4.0 g of magnesium chloride hexahydrate, 20.5-48.5 g of glucose, 0.2-1.8 g of calcium citrate tetrahydrate, and 2.5-9.5 g of L-malic acid are sieved and mixed uniformly, and then sealed in a first container; and by weight, 67.2-90 g of sodium bicarbonate are sieved and sealed in a second container; or By weight, 205-215 g of sodium chloride, 6.0-7.0 g of potassium chloride, 5.8-6.3 g of calcium chloride dihydrate, 3.0-4.0 g of magnesium chloride hexahydrate, 20.5-48.5 g of glucose, 0.2-1.8 g of calcium citrate tetrahydrate, 2.5-9.5 g of L-malic acid, and 10-15 g of sodium malate are sieved and mixed uniformly, and then sealed in a first container; and by weight, 52.5-70.2 g of sodium bicarbonate are sieved and sealed in a second container; (2) adding dialysis water to dissolve the solid preparations in the first container and the second container to 1000 ml, respectively, to obtain concentrated solution A and concentrated solution B; (3) The concentrated solution A, the concentrated solution B, and the dialysis water are uniformly mixed in a ratio of 1:1.225:32.775 or 1:1.26:32.74 to obtain a blood purification preparation that can be used clinically.

10. The method for preparing the blood purification preparation according to claim 9, characterized in that: The blood purification preparation for clinical use contains: 135-145 mmol / L sodium ions, 2-4 mmol / L potassium ions, 0.25-0.75 mmol / L magnesium ions, 100-115 mmol / L chloride ions, 28-38 mmol / L bicarbonate, and also contains: 3.0-7.0 mmol / L glucose, 0.02-0.18 mmol / L citrate, and 0.5-2 mmol / L L-malic acid; wherein the total calcium addition value of the preparation is 1.0-1.5 mmol / L, the blood purification preparation for clinical use contains both ionic calcium and molecular calcium, and the molar concentration ratio of the ionic calcium to the molecular calcium is 2-6, the ratio of the total calcium addition value to the molar concentration of citrate is 10-12, and the molar concentration ratio of citrate to L-malic acid is 0.05-0.

15.

11. Use of the blood purification preparation according to any one of claims 1 to 3 and 7 to 8 in the preparation of a blood purification treatment device.

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