Compound dialysis composition and preparation method thereof

Abstract

The invention relates to the technical field of hemodialysis, in particular to a compound dialysis composition and a preparation method thereof. The invention provides a compound alpha ketoacid dialysis composition. The compound alpha ketoacid dialysis composition comprises calcium racemic ketoisoleucine, calcium ketoleucine, calcium ketophenylalanine, calcium ketovaline, calcium racemic methionine, L-lysine acetate, sodium chloride, potassium chloride, calcium chloride, magnesium chloride, sodium diacetate and sodium bicarbonate. According to the invention, the compound alpha keto acid component is added into the hemodialysis liquid, so that toxin removal and nutrition supplement can be realized at the same time when a patient is subjected to hemodialysis, a good treatment effect is achieved, and meanwhile, the pain caused by taking a large amount of medicine every day is avoided. Meanwhile, stimulation and damage to intestines and stomach can be avoided by avoiding oral administration, and the appetite of a patient is improved.

Description

Technical Field

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

[0002] In my country, approximately 12.49% of adults suffer from chronic kidney disease (CKD). The renal function of CKD patients continues to decline and will eventually develop into end-stage renal disease (ESRD). Maintenance hemodialysis (MHD) is one of the main methods for treating ESRD, but it cannot completely replace kidney function. Long-term use can lead to endocrine imbalance, acid-base metabolism disorders, and toxin accumulation in patients, seriously affecting the prognosis. Almost all HD patients have varying degrees of malnutrition, also known as protein energy consumption. This trend is more obvious in elderly MHD patients. The continuous deterioration of nutritional status is one of the main factors leading to an increased risk of cardiovascular and cerebrovascular diseases, infections, and hospitalization in MHD patients. The recommended dietary protein intake for dialysis patients is 1.2 g·kg -1 ·d -1 However, because dialysis patients often have symptoms such as persistent nausea, difficulty eating, and poor absorption, the actual dietary protein intake is lower than the recommended value, which aggravates the occurrence of malnutrition. At the same time, in order to reduce the burden on the kidneys, patients with renal insufficiency need to limit protein intake, which causes a deficiency of amino acids, especially essential amino acids, in the patient's body, reduces protein synthesis, and leads to malnutrition in the patient. Malnutrition in hemodialysis patients is an important factor in their complications and death. Therefore, on the premise of adequate dialysis, it is of great significance to correct the imbalance of amino acid metabolism in patients and improve malnutrition.

[0003] In clinical practice, compound α-keto acid drugs are used in combination with a low-protein diet to prevent and treat protein metabolism disorders caused by renal insufficiency. Keto acids can generate corresponding amino acids through combined amine reactions. Among the eight essential amino acids for the human body, except for lysine and threonine, the other six can be generated by the corresponding keto acids with ammonia, but the keto acids corresponding to essential amino acids cannot be synthesized in the body, so essential amino acids rely on food supply. Compound α-keto acid is a compound preparation containing a variety of essential amino acids, ketones and hydroxyamino acids in the form of calcium salts, which can provide essential amino acids and minimize the intake of amino nitrogen. Ketones or hydroxyamino acids themselves do not contain amino groups, and they use the nitrogen of non-essential amino acids to convert into amino acids, thereby reducing urea synthesis and the accumulation of uremic toxic products. Ketones or hydroxyamino acids do not cause ultrafiltration of the remaining renal units, and can improve renal hyperphosphatemia and secondary hyperparathyroidism, and improve renal osteodystrophy.

[0004] However, the current method of taking compound α-keto acids is oral, 3 times a day, and the oral dose is relatively large. Since compound α-keto acids have a strong odor, they may even affect the normal life of patients. In addition, most patients have poor appetite, so they often stop taking the drugs, which affects the efficacy. Long-term use of compound α-keto acid drugs also has the risk of causing hypercalcemia. In order to improve the comfort of patients, it is possible to consider taking α-keto acid drugs simultaneously during dialysis. Summary of the invention

[0005] In view of this, the present invention provides a compound dialysis composition and a preparation method thereof. The present invention adds the compound α-keto acid component to the hemodialysis solution, so that the patient can simultaneously achieve toxin removal and nutritional supplementation during hemodialysis, achieve good treatment effects while avoiding the pain of taking a large amount of medicine every day. At the same time, avoiding oral administration can avoid irritation and damage to the stomach and intestines, and improve the patient's appetite.

[0006] In order to achieve the above-mentioned object of the invention, the present invention provides the following technical solutions:

[0007] The invention provides a compound alpha-keto acid dialysis composition, comprising: racemic ketoisoleucine calcium, ketoleucine calcium, ketophenylalanine calcium, ketovaline calcium, racemic hydroxymethionine calcium, L-lysine acetate, sodium chloride, potassium chloride, calcium chloride, magnesium chloride, sodium diacetate and sodium bicarbonate.

[0008] In some embodiments of the present invention, the above-mentioned composite alpha-keto acid dialysis composition further comprises one or more of L-threonine, L-tryptophan, L-histidine and L-tyrosine.

[0009] In some embodiments of the present invention, the above-mentioned compound α-ketoacid dialysis composition includes, by weight: 90-150 parts of racemic ketoisoleucine calcium, 120-200 parts of ketoleucine calcium, 90-140 parts of ketophenylalanine calcium, 110-170 parts of ketovaline calcium, 80-130 parts of racemic hydroxymethionine calcium, 130-210 parts of L-lysine acetate, 70-90 parts of L-threonine, 30-40 parts of L-tryptophan, 50-70 parts of L-histidine, 40-50 parts of L-tyrosine, 1000-1200 parts of sodium chloride, 25-50 parts of potassium chloride, 20-60 parts of calcium chloride, 15-25 parts of magnesium chloride, 75-120 parts of sodium diacetate and 500-550 parts of sodium bicarbonate.

[0010] In some embodiments of the present invention, the above-mentioned composite α-keto acid dialysis composition comprises, by weight: component A and component B;

[0011] The component A comprises: 90-150 parts of racemic ketoisoleucine calcium, 120-200 parts of ketoleucine calcium, 90-140 parts of ketophenylalanine calcium, 110-170 parts of ketovaline calcium, 80-130 parts of racemic hydroxymethionine calcium, 130-210 parts of L-lysine acetate, 70-90 parts of L-threonine, 30-40 parts of L-tryptophan, 50-70 parts of L-histidine, 40-50 parts of L-tyrosine, 1000-1200 parts of sodium chloride, 25-50 parts of potassium chloride, 20-60 parts of calcium chloride, 15-25 parts of magnesium chloride and 75-120 parts of sodium diacetate;

[0012] The component B comprises: 500-550 parts of sodium bicarbonate.

[0013] In some embodiments of the present invention, the above-mentioned composite α-keto acid dialysis composition comprises, by weight: component A and component B;

[0014] The component A comprises: 90-150 parts of racemic ketoisoleucine calcium, 120-200 parts of ketoleucine calcium, 90-140 parts of ketophenylalanine calcium, 110-170 parts of ketovaline calcium, 80-130 parts of racemic hydroxymethionine calcium, 130-210 parts of L-lysine acetate, 70-90 parts of L-threonine, 30-40 parts of L-tryptophan, 50-70 parts of L-histidine, 40-50 parts of L-tyrosine, 1080 parts of sodium chloride, 27.7 parts of potassium chloride, 34.1 parts of calcium chloride, 18.9 parts of magnesium chloride and 90 parts of sodium diacetate;

[0015] The component B comprises: 540 parts of sodium bicarbonate.

[0016] The present invention also provides a dialysis solution of a compound alpha-keto acid, comprising: a liquid form of the compound alpha-keto acid dialysis composition.

[0017] The present invention also provides a method for preparing the above-mentioned dialysate, wherein the concentrated solutions of the component A and the component B are obtained respectively, and then mixed with dialysis water to obtain the dialysate of the compound α-keto acid.

[0018] In some embodiments of the present invention, in the above-mentioned preparation method, the volume ratio of the concentrated solution of component A, the concentrated solution of component B and the dialysis water is 1:1.225:32.77.

[0019] The present invention also provides the use of the above-mentioned compound α-keto acid dialysis composition, the above-mentioned dialysis fluid and / or the dialysis fluid obtained by the above-mentioned preparation method in the preparation of products for treating chronic kidney disease.

[0020] The beneficial effects of the present invention include:

[0021] (1) The present invention supplements the essential amino acids required by the human body by adding an amino acid composite component to the dialysate component, thereby improving the current malnutrition status of hemodialysis patients.

[0022] (2) Avoid the pain of taking medicine. Compound α-keto acid tablets need to be taken orally. Take 4 to 8 tablets three times a day, and swallow the whole tablet during meals. It can be seen that the large dosage and the bad smell cause pain to some patients. During the application process, patients may give up taking the medicine halfway, affecting the treatment effect.

[0023] The present invention adds the compound α-keto acid component to the hemodialysis fluid, so that the patient can simultaneously achieve toxin removal and nutritional supplementation during hemodialysis, achieve good treatment effects and avoid the pain of taking a large amount of medicine every day. At the same time, avoiding oral administration can avoid irritation and damage to the stomach and intestines, and improve the patient's appetite.

[0024] (3) Reduce side effects. Each tablet of compound α-keto acid tablets contains 50 mg of total calcium. Taking a large amount every day may cause the side effect of hypercalcemia. This new dialysis powder can control the calcium dosage through the formula of calcium chloride to avoid the incidence of hypercalcemia. DETAILED DESCRIPTION

[0025] The invention discloses a compound dialysis composition and a preparation method thereof.

[0026] It should be understood that the expression "one or more of..." includes each of the items recited after the expression individually and in various different combinations of two or more of the recited items, unless otherwise understood from the context and usage. The expression "and / or" in combination with three or more recited items should be understood to have the same meaning, unless otherwise understood from the context.

[0027] The use of the terms "comprising", "having" or "containing", including their grammatical synonyms, should generally be understood as open and non-restrictive, for example not excluding other unrecited elements or steps, unless otherwise specifically stated or otherwise understood from the context.

[0028] It should be understood that the order of steps or the order in which certain actions are performed is not important as long as the present invention remains operable. In addition, two or more steps or actions may be performed simultaneously.

[0029] The use of any and all examples or exemplary language, such as "for example" or "including", herein is intended only to better illustrate the invention and does not limit the scope of the invention unless otherwise claimed. No language in this specification should be construed as indicating that any non-claimed element is essential to the practice of the invention.

[0030] In addition, the numerical ranges and parameters used to define the present invention are approximate values, and the relevant values ​​in the specific embodiments have been presented as accurately as possible. However, any numerical value inherently inevitably contains standard deviations due to individual test methods. Therefore, unless otherwise expressly stated, it should be understood that all ranges, quantities, values ​​and percentages used in this disclosure are modified by "about". Here, "about" generally means that the actual value is within plus or minus 10%, 5%, 1% or 0.5% of a specific value or range.

[0031] In Example 1, Example 2 and Effect Example 1, Effect Example 2 of the present invention, all the raw materials and reagents used can be purchased from the market.

[0032] The present invention will be further described below in conjunction with embodiments:

[0033] Example 1 Preparation of compound keto acid composition

[0034] According to the following formula, each component was weighed separately, and then continuously stirred and mixed in a hopper mixer for 15 hours to prepare a compound α-keto acid composition.

[0035] Table 1

[0036]

[0037] Example 2 Preparation of compound dialysis composition

[0038] Weigh 1080 g of sodium chloride, 27.7 g of potassium chloride, 34.1 g of calcium chloride, 18.9 g of magnesium chloride, 90 g of sodium diacetate, and 1-2 g of the compound α-keto acid composition (Formula 1-7), use PE bags to pack and seal, and prepare Agent A.

[0039] Weigh 540 g of sodium bicarbonate, pack it in a PE bag, and seal it to prepare Agent B.

[0040] Dissolve the whole package of A into 5.3LA concentrate, and the whole package of B into 6.5LB concentrate. Prepare the dialysis solution according to the ratio of A concentrate: B concentrate: dialysis water = 1: 1.225: 32.775 for dialysis use.

[0041] The compound dialysis compositions prepared from the compound keto acid compositions of formulas 1-5 can all be well dissolved to form dialysis fluids.

[0042] After the compound dialysis composition prepared from the compound keto acid composition of Formula 6-7 is dissolved, a small amount of precipitate will remain.

[0043] Effect Example 1 Detection of compound dialysis composition

[0044] The amino acid components were detected by high performance liquid chromatography (HPLC), and potassium, calcium, sodium, magnesium and chloride were detected by ion chromatography.

[0045] Content of each component in the final compound dialysis composition:

[0046] Ketoleucine 110-150 μmol / L;

[0047] Ketoisoleucine 55-80 μmol / L;

[0048] Ketophenylalanine 30-80 μmol / L;

[0049] Ketovaline 200-300 μmol / L;

[0050] Racemic hydroxymethionine 10-30 μmol / L;

[0051] Lysine 110-200 μmol / L;

[0052] Threonine 80-150 μmol / L;

[0053] Tryptophan 20-150 μmol / L;

[0054] Histidine 50-100 μmol / L;

[0055] Sodium 125-145mmol / L;

[0056] Potassium 2-3mmol / L;

[0057] Calcium 1.25-1.75mmol / L;

[0058] Magnesium 0.25-1.0mmol / L;

[0059] Chlorine 100-115mmol / L.

[0060] Effect Example 2 Stability Test

[0061] The compound dialysis compositions of formula 1 to formula 5 of Example 1 were stored according to the preparation method of Example 2, and stability tests were performed at 6 months and 9 months respectively to test the dissolution of each component in the formula and the change of each ion concentration. After long-term storage for 9 months, the components of each example formula can still be completely dissolved, and the change of ion concentration in the prepared dialysate components meets the requirements. (Deviation from the initial ion concentration / ratio ± 5%)

[0062] Table 2

[0063]

[0064] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. A compound α-keto acid dialysis composition, characterized in that: include: Calcium ketoisoleucine, calcium ketoleucine, calcium ketophenylalanine, calcium ketovaline, calcium ketohydroxymethionine, L-lysine acetate, sodium chloride, potassium chloride, calcium chloride, magnesium chloride, sodium diacetate and sodium bicarbonate.

2. The composite α-keto acid dialysis composition according to claim 1, characterized in that: It also includes one or more of L-threonine, L-tryptophan, L-histidine and L-tyrosine.

3. The composite α-keto acid dialysis composition according to claim 2, characterized in that: The invention comprises, by weight, 90-150 parts of racemic ketoisoleucine calcium, 120-200 parts of ketoleucine calcium, 90-140 parts of ketophenylalanine calcium, 110-170 parts of ketovaline calcium, 80-130 parts of racemic hydroxymethionine calcium, 130-210 parts of L-lysine acetate, 70-90 parts of L-threonine, 30-40 parts of L-tryptophan, 50-70 parts of L-histidine, 40-50 parts of L-tyrosine, 1000-1200 parts of sodium chloride, 25-50 parts of potassium chloride, 20-60 parts of calcium chloride, 15-25 parts of magnesium chloride, 75-120 parts of sodium diacetate and 500-550 parts of sodium bicarbonate.

4. The composite α-keto acid dialysis composition according to claim 3, characterized in that: Calculated by weight, it includes: component A and component B; The component A comprises: 90-150 parts of racemic ketoisoleucine calcium, 120-200 parts of ketoleucine calcium, 90-140 parts of ketophenylalanine calcium, 110-170 parts of ketovaline calcium, 80-130 parts of racemic hydroxymethionine calcium, 130-210 parts of L-lysine acetate, 70-90 parts of L-threonine, 30-40 parts of L-tryptophan, 50-70 parts of L-histidine, 40-50 parts of L-tyrosine, 1000-1200 parts of sodium chloride, 25-50 parts of potassium chloride, 20-60 parts of calcium chloride, 15-25 parts of magnesium chloride and 75-120 parts of sodium diacetate; The component B comprises: 500-550 parts of sodium bicarbonate.

5. The composite α-keto acid dialysis composition according to claim 3 or 4, characterized in that: Calculated by weight, it includes: component A and component B; The component A comprises: 90-150 parts of racemic ketoisoleucine calcium, 120-200 parts of ketoleucine calcium, 90-140 parts of ketophenylalanine calcium, 110-170 parts of ketovaline calcium, 80-130 parts of racemic hydroxymethionine calcium, 130-210 parts of L-lysine acetate, 70-90 parts of L-threonine, 30-40 parts of L-tryptophan, 50-70 parts of L-histidine, 40-50 parts of L-tyrosine, 1080 parts of sodium chloride, 27.7 parts of potassium chloride, 34.1 parts of calcium chloride, 18.9 parts of magnesium chloride and 90 parts of sodium diacetate; The component B comprises: 540 parts of sodium bicarbonate.

6. A dialysis solution of a compound α-keto acid, characterized in that: include: The liquid form of the compound alpha-keto acid dialysis composition as claimed in claim 5.

7. The method for preparing a dialysate according to claim 6, characterized in that: The concentrated solutions of the component A and the component B are obtained respectively, and then mixed with dialysis water to obtain the dialysis solution of the compound α-keto acid.

8. The preparation method according to claim 7, characterized in that: The volume ratio of the concentrated solution of component A, the concentrated solution of component B and the dialysis water is 1:1.225:32.

77.

9. Use of the compound α-keto acid dialysis composition according to any one of claims 1 to 5, the dialysis fluid according to claim 6 and / or the dialysis fluid obtained by the preparation method according to claim 7 or 8 in the preparation of a product for treating chronic kidney disease.

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