JP4453193B2 - Dialysis supplements - Google Patents

Description

[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a replenishment preparation for dialysis comprising L-carnitine or a salt thereof as an active ingredient, which is used for, for example, regular hemodialysis therapy of chronic uremic patients.
[0002]
[Prior art]
Hemodialysis is the most prevalent hemodialysis therapy and is applied to uremia and drug addiction.
This hemodialysis is the most proven and has excellent ability to remove small molecular weight substances, water and electrolytes, and acid-base balance abnormalities. This is possible to some extent by changing the dialysis conditions such as the liquid flow rate and dialysis time.
Since the operation is simple and uniform, there is an excellent point that simultaneous dialysis of a large number of people is easy and the therapeutic effect can be predicted to some extent.
Moreover, there is hemodiafiltration as a hemodialysis therapy. This hemodialysis therapy is a method of simultaneously performing hemofiltration while performing hemodialysis, and is applied to uremia and drug addiction.
This hemodiafiltration is superior in that it is possible to increase the substance removal efficiency from small molecule substances to medium / high molecular substances by supplementing the replenisher solution, usually performing 10 L or more blood filtration in one treatment. There is a point.
[0003]
[Problems to be solved by the invention]
In vivo, L-carnitine is synthesized in the kidney and the like.
Therefore, patients with chronic renal failure cannot synthesize in the kidney, and inevitably need to be taken from outside the body.
In addition, L-carnitine is an amine that is water-soluble and has a molecular weight as small as 162 Daltons, and is dialyzable, so that about 60% of the L-carnitine concentration in blood is reduced by hemodialysis.
By the way, L-carnitine is a substance involved in β-oxidation of fatty acids important for energy metabolism, particularly long-chain fatty acids, and is a substance involved in transport of fatty acids to the inner mitochondrial membrane.
Fatty acids in the cytoplasm are transported through the outer and inner mitochondrial membranes into the matrix, where they undergo β-oxidation and produce energy. In this transport mechanism, the inner membrane is at the rate-limiting step. ing.
In this inner membrane, L-carnitine plays a role in transporting fatty acids into the matrix. If the amount is insufficient, the transport of fatty acids into the matrix decreases, leading to a decrease in fatty acid energy metabolism, and the like.
Assuming that the weight of a dialysis patient is 50 kg and the total pre-dialysis L-carnitine concentration is 60 μmol / L, the blood volume is approximately 4 L, and the plasma is 2.6 L (assuming Ht is 35%). There are only 60 μmol / L × 2.6 L = 156 μmol in it. Although the outflow amount obtained from the difference in L-carnitine concentration before and after dialysis is 93.6 μmol, L-carnitine leaks out in an average of 900 μmol in one dialysis effluent.
That is, it is due to leakage from not only plasma but also skeletal muscles / tissues that are pooled in large quantities.
In addition, as a result of examining the transfer of plasma L-carnitine concentration from before dialysis to immediately after the end of dialysis and from the start of the next dialysis, it decreased significantly immediately after the end. Recovered by washing out and supplementing with food.
An object of the present invention is to improve fatty acid energy metabolism and the like by continuously performing L-carnitine supplementation during hemodialysis in hemodialysis patients maintaining chronic renal failure.
[0004]
[Means for Solving the Problems]
The invention of this application is a replenishment preparation for dialysis comprising L-carnitine as an active ingredient, and L-carnitine or a salt thereof is contained in L-carnitine as 40 to 300 mg in blood during one dialysis for 4 hours. The present invention relates to a replenishment preparation for dialysis characterized by being prepared for continuous administration.
[0005]
DETAILED DESCRIPTION OF THE INVENTION
The L-carnitine of the present invention is particularly preferably a replenishment preparation for dialysis prepared so that the dose of L-carnitine is 40 to 300 mg continuously administered into blood.
[0006]
Further, when the preparation of the present invention is a dialysate, it may be a concentration that can be used as it is, or a concentration that can be used as a dialysate after dilution.
[0007]
The method for supplementing L-carnitine during dialysis is a continuous infusion of L-carnitine into the dialysis circuit during dialysis, preferably adding L-carnitine into the replenisher, and the dosage is dialysis. An amount commensurate with the amount of L-carnitine leaking into it is optimal, and 40 to 300 mg (about 250 to 1850 μmol) of L-carnitine and / or a salt thereof is administered at a time during dialysis. 150 mg is particularly preferred.
By replenishing L-carnitine in this way, leakage of L-carnitine accompanying cell disruption that occurs even during dialysis can be prevented.
Moreover, the same effect as continuous injection can be expected during dialysis by adding L-carnitine to the dialysate.
The concentration is preferably 50 to 100 μmol / L close to the plasma concentration.
[0008]
The replenishment preparation for dialysis is particularly preferably prepared by adding L-carnitine to the hemodialysis solution and hemodiafiltration replenisher in advance, but may be added to the hemodialysis solution and hemodiafiltration replenisher.
[0009]
It is particularly preferable to contain L-carnitine or a salt thereof at a concentration of 1 to 100 μmol / L.
[0010]
Particularly preferred is a dialysis supplement for use in dialysis of chronic uremic patients.
[0011]
A replenishment preparation for dialysis prepared to continuously administer L-carnitine or a salt thereof as L-carnitine in the blood to 1 to 2500 mg in the blood and / or dialyze from the dialysate into the blood is used as a dialysate as it is. It is particularly preferable.
[0012]
Sodium ion 130-150 meq / L, potassium ion 0-3.5 meq / L, calcium ion 0-4 meq / L, magnesium ion 0-2 meq / L, chloride ion 90-120 meq / L Examples of L and organic acid include acetate ion 0-40 meq / L, lactic acid 0-40 meq, citric acid 0-40 meq, glucose 0-2 g / L, HCO ₃ ion 25-40 meq / L. It is particularly preferable to use a dialysate adjusted so as to be 1 to 100 μmol / L of L and L-carnitine or a salt thereof.
[0013]
The replenishment preparation for dialysis of the invention of this application is particularly preferably powder or solid from the viewpoint of stability.
[0014]
【Example】
Hereinafter, the invention of the present application will be specifically described with reference to examples. However, the invention of the present application is not limited to the examples.
Example 1
Each component of Agent A shown below was dissolved in an appropriate amount of water, and the pH was adjusted to 4.7 with hydrochloric acid to 30 L. After filtering this liquid, 9 L each was filled into a plastic container for dialysis to obtain A liquid.
Further, 672 g of sodium hydrogen carbonate was put in a polyethylene bag to make a B agent. This B agent package was dissolved in 11.5 L of water to obtain a B solution.
Next, 26 volumes of water was added to 1 volume of B solution to dilute, and 1 volume of A solution was added to 34 volumes of this diluted solution to obtain a dialysis perfusate.
Content of each component of agent A in 30 L 6443 g of sodium chloride
157 g of potassium chloride
Calcium chloride dihydrate 230g
Magnesium chloride hexahydrate 107g
Sodium acetate 860g
1050 g of glucose
L-carnitine 8.5g
[0015]
Example 2
A three-agent combination preparation consisting of A-1, Agent A-2 and Agent B having the following composition was prepared.
A-1 sodium chloride 1961g
47g of potassium chloride
Calcium chloride dihydrate 58g
Magnesium chloride hexahydrate 32g
233 g of sodium acetate
L-carnitine chloride 3.11g
A-2 drug glucose 315g
B agent sodium bicarbonate 738g
This 1-pack of A-1 and 1-pack of A-2 were dissolved in water to give a 9 L aqueous solution (A solution). At this time, the pH was adjusted to 4.7 with glacial acetic acid.
Moreover, B agent package was melt | dissolved in 11.5L of water, and it was set as B liquid.
Next, 26 volumes of water was added to 1 volume of B solution to dilute, and 1 volume of A solution was added to 34 volumes of this diluted solution to obtain a dialysis perfusate.
[0016]
Example 3
Each component of Agent A shown below was dissolved in an appropriate amount of water, and the pH was adjusted to 4.7 with hydrochloric acid to 30 L. After filtering this liquid, 9 L each was filled into a plastic container for dialysis to obtain A liquid.
Further, 672 g of sodium hydrogen carbonate was put in a polyethylene bag to make a B agent. This B agent package was dissolved in 11.5 L of water to obtain a B solution.
Next, 26 volumes of water was added to 1 volume of B solution for dilution, and 1 volume of A solution was added to 34 volumes of this diluted solution.
Further, 2.5 g of L-carnitine was added to this solution to prepare a perfusion solution for hemodialysis.
Content of each component of agent A in 30 L sodium chloride 6443 g
Potassium chloride 157 g
Calcium chloride dihydrate 230 g
Magnesium chloride hexahydrate 107 g
Sodium acetate 860 g
Glucose 1050 g
[0017]
Example 4
Each component shown below was dissolved in an appropriate amount of water to make 50 L. After filtering this liquid, it filled into a plastic container 1L at a time, sealed, and then sterilized by high-pressure steam. A clear, colorless and stable replenishment formulation for dialysis was obtained.
Sodium chloride 292.2 g
Potassium chloride 7.45 g
Calcium chloride dihydrate 13.95 g
Magnesium chloride hexahydrate 7.6 g
L-sodium lactate 212.9 g
L-carnitine 0.486g
[0018]
Example 5
Each component shown below was dissolved in an appropriate amount of water to make 50 L. After filtering this solution, 1 L was filled in a plastic container, sealed, and then autoclaved.
In 1 L of this preparation, 0.01 g of L-carnitine was added to prepare a replenisher for filtration type / diafiltration type artificial kidney.
Sodium chloride 292.2 g
Potassium chloride 7.45 g
Calcium chloride dihydrate 13.95 g
Magnesium chloride hexahydrate 7.6 g
L-sodium lactate 212.9 g
[0019]
【The invention's effect】
With the replenishment preparation for dialysis of this application, L-carnitine is dialyzed instead of L-carnitine present in the living body by adding L-carnitine to the continuous infusion during dialysis and the dialysate. Therefore, there is an excellent effect that L-carnitine in plasma can be prevented from being dialyzed, and at the same time, outflow of L-carnitine from skeletal muscle / tissue can be prevented.

Claims (7)

A replenishment preparation for dialysis comprising L-carnitine as an active ingredient, wherein L-carnitine or a salt thereof is continuously administered into blood as L-carnitine during a 4-hour dialysis. A replenishment preparation for dialysis characterized by being prepared.   The dialysis supplement preparation according to claim 1, wherein the dialysis supplement preparation is an aqueous solution.   The replenishment preparation for dialysis according to claim 1 or 2, wherein the replenishment preparation for dialysis is added to a hemodiafiltration replenisher.   The replenishment preparation for dialysis according to any one of claims 1 to 3, comprising L-carnitine or a salt thereof at a concentration of 1 to 100 µmol / L.   The replenishment preparation for dialysis according to any one of claims 1 to 4, which is a replenishment preparation for dialysis for use in dialysis of chronic uremic patients. Sodium ion 130-150 meq / L, potassium ion 0-3.5 meq / L, calcium ion 0-4 meq / L, magnesium ion 0-2 meq / L, chloride ion 90-120 meq / L L, acetate ion 0 to 40 meq / L, glucose 0 to 2 g / L, HCO ₃ ion 25 to 40 meq / L, and L-carnitine or its salt 1 to 100 μmol / L The replenishment preparation for dialysis according to any one of claims 1 to 5 .   The replenishment preparation for dialysis according to claim 1, which is in a powder form or a solid form.