JP2020050639A - Iron-containing infusion - Google Patents

Abstract

To provide iron-containing infusions that suppress the dissociation of iron from chondroitin sulfate/iron colloid while containing high concentrations of ascorbic acid (more than 100 mg per liter of infusion).SOLUTION: Provided is an iron-containing infusion containing chondroitin sulfate/iron colloid, ascorbic acid or a salt thereof, glycerophosphate, lactic acid or a salt thereof, and at least one selected from the group consisting of acetic acid, citric acid and succinic acid, the content of the ascorbic acid or a salt thereof being 100 to 200 mg/L, the lactate ion content being 20 to 38 mEq/L, the acetate ion content being 40 mEq/L or less, and the succinate ion content being 45 mEq/L or less.SELECTED DRAWING: None

Description

  The present invention relates to an iron-containing infusion.

  Iron is an essential trace metal involved in hemoglobin synthesis, systemic redox reactions, division, and proliferation. However, when iron becomes excessive, it produces highly toxic hydroxyl radicals by the Fenton reaction, and induces DNA damage and apoptosis. Therefore, iron metabolism is subtly controlled by many related molecules (Non-Patent Document 1).

  About 1 mg of iron per day is absorbed from the upper gastrointestinal tract, enters the blood, binds to transferrin and is transported throughout the body, but most of the iron used in the body regenerates red blood cell hemoglobin iron by the reticulum system. Covered by use. Erythrocytes have an average lifespan of 120 days, and 20 mg of iron per day is extracted from hemoglobin by reticulum macrophages and re-enters the blood via ferroportin, the only iron transport protein in vivo, for reuse. (Non-Patent Document 2).

  Hepcidin-25 is a peptide hormone discovered in the early 21st century, and negatively regulates iron metabolism by the hepcidin-25.ferroportin system.

  Ferroportin is an iron transport membrane protein present in retinal macrophages, upper small intestinal mucosal epithelial cells, hepatocytes, and the like, and is a receptor for hepcidin-25. Ferroportin, when bound to hepcidin-25, migrates into the cell and is degraded by lysosomes together with hepcidin. It takes 2 to 3 days for newly synthesized ferroportin reduced by the degradation, and during that time, the membrane distribution density of ferroportin decreases, and iron release from cells decreases.

  Hepcidin-25 is induced by inflammation and iron load, but if the serum hepcidin-25 concentration is continuously high, the use of iron is inhibited, resulting in a functional iron deficiency in which iron cannot be used for erythrocyte synthesis, resulting in anemia. Is known to be expressed (Non-Patent Document 3).

  When performing high-calorie infusion therapy, multivitamin preparations and trace-element preparations are added to the high-calorie infusion to administer vitamins and trace elements.

  Iron in trace element preparations is included in infusions in the form of chondroitin sulfate / iron colloid to avoid side effects due to free iron and to prevent the formation of precipitates of ferric hydroxide coarse molecules. (Non-patent documents 4, 5).

  In recent years, it has been reported that when a trace element preparation containing iron is added to a high-calorie infusion, iron is dissociated with time from chondroitin sulfate / iron colloid (Non-Patent Documents 6 and 7). Components that promote the dissociation of iron from chondroitin sulfate / iron colloid include reducing substances ascorbic acid, cysteine and sodium bisulfite (Non-Patent Documents 8 and 9).

  When an intravenous solution containing free iron dissociated from chondroitin sulfate / iron colloid is intravenously administered, hepcidin-25 is induced, and there is a risk of inhibiting the use of iron (Non-Patent Documents 6, 10, and 11).

"Iron Overload and Iron Chelation Therapy", p25-33 (2007) "Blood Frontier", 21 (6), p23-30 (2011) "Blood Frontier", 21 (6), p31-39 (2011) Pharmaceutical Journal, 28 (5), p83-88 (1992) "Pharmaceutical Interview Form, Trace Element Preparation for High Calorie Infusion. Eject" "Surgery and Metabolism and Nutrition", 48 (5), p149-157 (2014) "Surgery and metabolism and nutrition", 51 (6), p355-367 (2017) "Journal of Japanese Medicine", 33 (4), p57-60 (1997) “Yakuji 59” (extra edition), pp. 169-172 (2008) "Journal of the Japanese Society of Clinical Nutrition", 36 (1), p40-45 (2014) "Journal of the Japanese Society of Clinical Nutrition", 36 (4), p202-205 (2014)

  The guidelines for the vitamin requirement for high-calorie infusion therapy were set by the American Medical Association in 1975, and the recommended amount of ascorbic acid was 100 mg per day. It has been revised to 200 mg. Usually, 2 L of a high-calorie infusion is administered to an adult per day, so that the ascorbic acid concentration in the high-calorie infusion is 100 mg / L.

  Ascorbic acid is one of the components that promotes the dissociation of iron from chondroitin sulfate / iron colloid.Therefore, when the content of ascorbic acid in high-calorie infusions increases, iron from chondroitin sulfate / iron colloid increases. The environment is easy to dissociate. Administration of an infusion containing a large amount of dissociated free iron induces hepcidin-25 and inhibits iron utilization.

  In addition, high-calorie infusions generally contain reducing substances such as cysteine, acetylcysteine and sulfite together with ascorbic acid, and these reducing substances also promote the dissociation of iron from chondroitin sulfate / iron colloid. I do.

  As described above, various substances that promote the dissociation of iron from chondroitin sulfate / iron colloid are mixed in the high-calorie infusion solution. At present, there is no disclosure of an iron-containing infusion that suppresses dissociation of iron from chondroitin sulfate / iron colloid when a high-calorie infusion is mixed with a trace element preparation containing iron. Furthermore, there is no disclosure of an iron-containing infusion capable of replenishing a patient with iron while preventing induction of hepcidin-25 by suppressing dissociation of iron.

  In view of the above, an iron-containing infusion solution capable of suppressing dissociation of iron from chondroitin sulfate / iron colloid while containing 100 mg or more of ascorbic acid that promotes dissociation of iron from chondroitin sulfate / iron colloid in 1 L of the infusion solution. Development is required.

  Therefore, an object of the present invention is to provide an iron-containing infusion solution containing ascorbic acid at a high concentration (100 mg or more per liter of infusion) and suppressing dissociation of iron from chondroitin sulfate / iron colloid.

  The present inventors have intensively studied to achieve the above object. As a result, glycerophosphate and a predetermined amount of lactic acid or a salt thereof are added to an iron-containing infusion containing 100 to 200 mg of ascorbic acid per liter of the infusion, and an organic acid (acetic acid, citric acid or / and / or succinic acid) is further added. Was found to be able to greatly suppress the dissociation of iron from coexisting chondroitin sulfate / iron colloid.

Thus, one aspect of the present invention is as follows:
(1) It contains chondroitin sulfate / iron colloid, ascorbic acid or a salt thereof, glycerophosphate, lactic acid or a salt thereof, and at least one selected from the group consisting of acetic acid, citric acid and succinic acid. The content of ascorbic acid or a salt thereof is 100 to 200 mg / L, the content of lactate ions is 20 to 38 mEq / L, the content of acetate ions is 40 mEq / L or less, An iron-containing infusion having a content of 45 mEq / L or less.

Another embodiment of the present invention is as follows:
(2) The iron-containing infusion according to (1), further comprising at least one reducing substance selected from the group consisting of cysteine, acetylcysteine, and sulfite;
(3) The iron-containing infusion according to (1) or (2), wherein the content of acetate ions is 25 mEq / L or less;
(4) The iron-containing infusion according to any of (1) to (3), wherein the content of citrate ion is 45 mEq / L or less;
(5) The iron-containing infusion according to any of (1) to (4), wherein the content of succinate ions is 25 mEq / L or less;
(6) The iron-containing infusion according to any one of the above (1) to (5), which contains chondroitin sulfate / iron colloid in an amount such that the daily dose of iron element per adult is 0.1 to 2 mg. Agent;
(7) The iron according to any of (1) to (6), further including at least one trace element compound selected from the group consisting of a manganese compound, a zinc compound, a copper compound, an iodine compound, and a selenium compound. Infusion containing;
(8) The iron-containing infusion according to any one of (1) to (7), further comprising at least one nutrient infusion component selected from the group consisting of sugar, electrolyte, and amino acid;
(9) The container is housed in a multi-chamber container having a plurality of chambers separated by partition walls that can be peeled off at the time of use, and the liquid containing the chondroitin sulfate / iron colloid is housed in one of the plurality of chambers. The iron-containing infusion agent according to any one of (1) to (8), wherein the liquid containing ascorbic acid or a salt thereof is contained in a chamber different from the chamber containing the liquid containing sulfuric acid / iron colloid. ;
(10) When a mixed solution of the solution containing the chondroitin sulfate / iron colloid and the solution containing the ascorbic acid or a salt thereof is stored at room temperature for 48 hours in a light-shielded state in which light having a wavelength of 450 nm or less is blocked, chondroitin The iron-containing infusion according to the above (9), wherein the dissociation rate of iron from the sulfuric acid / iron colloid is 40% or less;
(11) The liquid containing the chondroitin sulfate / iron colloid and the trace element compound is contained in a multi-chamber container having a plurality of chambers partitioned by partition walls that can be peeled off at the time of use. The iron-containing liquid according to (8), wherein the liquid containing the nutrient infusion agent component is contained in a chamber different from the chamber containing the liquid containing the chondroitin sulfate / iron colloid and the trace element compound. And (12) a mixture of a solution containing the chondroitin sulfate / iron colloid and the trace element compound and a solution containing the nutrient infusion component at room temperature in a light-shielded state in which light having a wavelength of 450 nm or less is blocked. The iron-containing infusion according to (11), wherein the dissociation rate of iron from the chondroitin sulfate / iron colloid is 40% or less when stored for 48 hours.

  The iron-containing infusion of the present invention contains a high concentration (100 mg or more per liter of infusion) of ascorbic acid, while suppressing dissociation of iron from chondroitin sulfate / iron colloid.

  The iron-containing infusion according to one embodiment of the present invention is a chondroitin sulfate / iron colloid, ascorbic acid or a salt thereof, glycerophosphate, lactic acid or a salt thereof, and acetic acid, citric acid and succinic acid. At least one selected from the group consisting of: ascorbic acid or a salt thereof in a content of 100 to 200 mg / L, a lactate ion content of 20 to 38 mEq / L, and an acetate ion content of It is 40 mEq / L or less, and the content of succinate ions is 45 mEq / L or less.

  The iron-containing infusion according to one embodiment of the present invention contains a high concentration (100 mg or more in 1 L of the infusion) of ascorbic acid and suppresses dissociation of iron from chondroitin sulfate / iron colloid. Specifically, the dissociation ratio of iron from chondroitin sulfate / iron colloid when stored at room temperature for 48 hours in a light-shielded state where light having a wavelength of 450 nm or less is blocked is as low as 40% or less. Thus, induction of hepcidin-25 by dissociated iron can be prevented, thereby promoting the use of iron in the patient's body.

  In the iron-containing infusion according to one embodiment of the present invention, the dissociation of iron from the chondroitin sulfate / iron colloid is suppressed, so that the induction of hepcidin-25 by the dissociated iron is suppressed. As a result, iron does not excessively accumulate in the intrareticular system, and an increase in the concentration of free iron in cells is suppressed. As a result, production of hydroxyl radicals is suppressed, and damage to DNA and induction of apoptosis are suppressed.

  Furthermore, since the iron-containing infusion according to one embodiment of the present invention contains ascorbic acid at a high concentration of 100 to 200 mg per liter of the infusion, the antioxidant action and the immune function of ascorbic acid (vitamin C) are reduced. It can effectively exert an improving effect, a collagen generating effect, a calcium absorbing and metabolizing effect, a sugar metabolizing effect, a histamine release suppressing effect caused by an allergic reaction, a stress reducing hormone generating effect, and the like.

  Hereinafter, the iron-containing infusion solution (hereinafter, also referred to as an infusion solution) according to the embodiment of the present invention will be described in detail. Note that the present invention is not limited to only the following embodiments. In this specification, “X to Y” indicating a range includes X and Y, and means “X or more and Y or less”.

[Chondroitin sulfate / iron colloid]
As the chondroitin sulfate / iron colloid (hereinafter also referred to as iron colloid), either a synthetic product or a commercially available product may be used. In the case of synthesizing an iron colloid, a known synthesis method can be adopted, and for example, a method of alternately adding an iron compound and sodium hydroxide to a solution of chondroitin sulfate is exemplified.

  As the iron compound used for synthesizing the iron colloid, any iron compound that is safe for a living body and soluble in a liquid such as water can be used without any particular limitation.

  Specific examples of the iron compound include ferric salts such as ferric chloride, ferric citrate, ferric nitrate, and ferric sulfate, and one or more of these are used. be able to. Among them, ferric chloride is preferably used from the viewpoint of abundant use results.

  The chondroitin sulfate used in the synthesis of the iron colloid may be in the form of a salt such as a sodium salt and a potassium salt. The amount of chondroitin sulfate used in forming the iron colloid is preferably 4 parts by mass or more based on 1 part by mass of the iron element contained in the solution.

  The content of chondroitin sulfate / iron colloid in the iron-containing infusion of the present invention may be such that the daily dose of iron element per adult is 0.1 to 2 (2.0) mg. Preferably, the amount is 0.1 to 1.5 mg, more preferably 0.1 to 1.2 mg.

  If the amount of chondroitin sulfate / iron colloid in the iron-containing infusion is 2.0 mg or less per day for each adult, iron does not become excessive and is accumulated in the body as ferritin or hemosiderin. No worries. On the other hand, if the amount of chondroitin sulfate / iron colloid in the iron-containing infusion is 0.1 mg or more per day for each adult, sufficient iron supplementation to the patient can be achieved.

[Ascorbic acid (salt)]
The iron-containing infusion of the present invention contains ascorbic acid (preferably, L-ascorbic acid, that is, vitamin C) or a salt thereof (hereinafter, also referred to as ascorbic acid (salt)) in an amount of 100 to 200 mg per liter of the iron-containing infusion. Contained in.

  When the content of ascorbic acid (salt) per 1 L of the iron-containing infusion is less than 100 mg, the above-mentioned effect of ascorbic acid is hardly exerted. On the other hand, when the content of ascorbic acid (salt) per liter of the iron-containing infusion exceeds 200 mg, the amount exceeds the required amount and is excreted without being used.

  Here, “per liter of iron-containing infusion” is the content per liter based on the total amount (total amount) of the iron-containing infusion at the time of administration to the patient. That is, when the infusion solution containing iron is contained in a multi-chamber container partitioned into a plurality of chambers, and the liquids and components contained in the plurality of chambers are mixed and administered to a patient, It means the content per 1 L of the whole liquid. Further, in this specification, the content represented by using the unit of “g / L”, “mg / L” or “mEq / L” means the same content as described above.

[Glycerophosphate]
The iron-containing infusion of the present invention contains glycerophosphate as a source of phosphorus. Conventional infusions contain potassium dihydrogen phosphate or dipotassium phosphate as a source of phosphorus, but the present inventors have promoted the dissociation of iron from chondroitin sulfate / iron colloid. I found to do. Specifically, when potassium dihydrogen phosphate is used in place of glycerophosphate, a large amount of iron dissociates from the chondroitin sulfate / iron colloid in a short time (specifically, after 24 hours of storage) (described later). Comparative Examples 3 and 4).

  As the glycerophosphate, glycerophosphate which is safe for a living body and is used for general injections and the like can be used. Specific examples include potassium glycerophosphate such as dipotassium glycerophosphate, sodium glycerophosphate such as disodium glycerophosphate, calcium glycerophosphate, magnesium glycerophosphate, and the like, and one or more of these may be used. it can.

  Among them, potassium glycerophosphate (dipotassium glycerophosphate) is preferably used as the glycerophosphate from the viewpoint of abundant use results.

  The content of the glycerophosphate in the iron-containing infusion of the present invention is 1 to 10 g (about phosphorus as 1 L) per liter of the iron-containing infusion from the viewpoint of replenishing phosphorus and preventing dissociation of iron from chondroitin sulfate / iron colloid. 63 to 625 mg), more preferably 1 to 8 g (about 63 to 500 mg as phosphorus), still more preferably 1 to 5 g (about 63 to 313 mg as phosphorus), and 1 to 2 g. (About 63 to 125 mg as phosphorus) is particularly preferred.

  When the content of glycerophosphate is 10 g / L or less, the dose of phosphorus is moderate, and energy metabolism and bone metabolism are smooth. On the other hand, when the glycerophosphate content is 1 g / L or more, the effect of preventing the dissociation of iron from the chondroitin sulfate / iron colloid is sufficiently exhibited. In addition, the dosage of phosphorus is sufficient, and sufficient phosphorus supply to the patient is achieved.

[Lactic acid (salt)]
The iron-containing infusion of the present invention contains lactic acid or a salt thereof (hereinafter also referred to as lactic acid (salt)). The combination of glycerophosphate and lactic acid or a salt thereof is advantageous in preventing dissociation of iron from chondroitin sulfate / iron colloid.

  Examples of the lactate include sodium lactate, potassium lactate, calcium lactate, and the like, and one or more of these can be used. Among them, sodium lactate is preferable from the viewpoint of abundant use results.

  In the iron-containing infusion of the present invention, the lactate ion content is 20 to 38 mEq / L (20 to 38 mEq per liter of the infusion). When the lactate ion content is less than 20 mEq / L or more than 38 mEq / L, iron is easily dissociated from the chondroitin sulfate / iron colloid (Comparative Examples 1 to 6 described later). From the viewpoint of further preventing the dissociation of iron from the chondroitin sulfate / iron colloid, the content of lactic acid or a salt thereof is preferably 35 mEq / L or less, more preferably 30 mEq / L or less.

  The infusion solution usually contains 28 mEq / L or more of an alkalizing agent (lactate ion, acetate ion, etc.) that is metabolized to bicarbonate ion. By setting the content of lactate ions to 20 to 38 mEq / L and appropriately mixing an organic acid described later, it is possible to achieve a compounding of an alkalizing agent of 28 mEq / L or more without fear of adversely affecting iron dissociation. is there.

[Organic acid]
The iron-containing infusion solution of the present invention contains at least one selected from the group consisting of acetic acid, citric acid and succinic acid. By adjusting the pH using such an organic acid, the effect of preventing the dissociation of iron from the chondroitin sulfate / iron colloid is further improved. Here, for example, including acetic acid is a concept including a form dissociated in an infusion solution. That is, the iron-containing infusion solution of the present invention contains ions derived from at least one selected from the group consisting of acetic acid, citric acid and succinic acid.

  In the iron-containing infusion of the present invention, the content of acetate ions is 40 mEq / L or less. If the acetate ion content exceeds 40 mEq / L, a large amount of iron dissociates from the chondroitin sulfate / iron colloid in a short time (specifically, after 24 hours of storage) (see Comparative Example 7 described later). From the viewpoint of further preventing the dissociation of iron from the chondroitin sulfate / iron colloid, the content of acetate ions is preferably 35 mEq / L or less, more preferably 30 mEq / L or less, and even more preferably 25 mEq / L. Or less, particularly preferably 20 mEq / L or less (lower limit: 0 mEq / L). Here, the content of acetate ions includes the content of acetate ions derived from acetate.

  In the iron-containing infusion of the present invention, the content of citrate ion is preferably 45 mEq / L or less (lower limit: 0 mEq / L). When the content of citrate ions is 45 mEq / L or less, the effect of preventing the dissociation of iron from the chondroitin sulfate / iron colloid becomes favorable. Here, the content of citrate ions includes the content of citrate ions derived from citrate.

  In the iron-containing infusion of the present invention, the content of succinate ion is 45 mEq / L or less. When the succinate ion content exceeds 45 mEq / L, a large amount of iron dissociates from chondroitin sulfate / iron colloid in a short time (specifically, after 24 hours of storage) (see Comparative Example 8 described later). From the viewpoint of further preventing the dissociation of iron from the chondroitin sulfate / iron colloid, the content of succinate ion is preferably 40 mEq / L or less, more preferably 35 mEq / L or less, and still more preferably 30 mEq / L or less. L or less, particularly preferably 25 mEq / L or less (lower limit: 0 mEq / L). Here, the content of succinate ion includes the content of succinate ion derived from succinate.

  In one embodiment of the present invention, when the iron-containing infusion solution contains acetic acid, citric acid and succinic acid, the content of each ion is preferably within the above range. In such a case, the dissociation rate of iron over time can be kept low. Therefore, it is considered that the effect of dissociated iron can be suppressed even after long-term storage.

[Reducing substances]
The iron-containing infusion solution of the present invention preferably further contains at least one reducing substance selected from the group consisting of cysteine, acetylcysteine and sulfite, from the viewpoint of stabilizing the active ingredient. More preferably, it contains at least one of acetylcysteine and sulfite, and even more preferably, it contains acetylcysteine and sulfite.

  The content of cysteine and acetylcysteine (the total content when both are contained) is preferably 0.05 to 2.0 g, and preferably 0.1 to 1.0 g per liter of the iron-containing infusion. More preferably, it is even more preferably 0.2 to 0.5 g.

  Examples of the sulfite include sodium sulfite, sodium hydrogen sulfite, potassium sulfite, and the like. Among them, sodium bisulfite is preferable from the viewpoint of abundant use results. The content of the sulfite is preferably 0.01 to 0.5 g, more preferably 0.01 to 0.03 g, and more preferably 0.01 to 0.02 g per liter of the iron-containing infusion. Is even more preferred.

[Nutrient infusion ingredients]
The iron-containing infusion of the present invention preferably further contains at least one nutrient infusion component selected from the group consisting of sugar, electrolyte and amino acid.

(sugar)
The iron-containing infusion solution of the present invention preferably further contains sugar from the viewpoint of administering a calorific value to a patient. From the viewpoint of administering a sufficient amount of heat to the patient, the sugar content is preferably 50 to 250 g, more preferably 60 to 250 g, and more preferably 100 to 200 g per liter of the iron-containing infusion. Even more preferred.

  The sugar is not particularly limited as long as it is metabolized and utilized as a calorie source in a living body, and specific examples include glucose (glucose), fructose, xylitol, sorbitol, maltose, glycerol, and the like. One type may be used alone, or two or more types may be used in combination. Among them, glucose (glucose) is preferable because it is most easily used by living organisms as an energy source.

(Electrolytes)
The iron-containing infusion solution of the present invention preferably further contains an electrolyte from the viewpoint of electrolyte replenishment in hypercaloric infusion therapy. The content of the electrolyte is preferably 1 to 5 g per liter of the iron-containing infusion.

  As the electrolyte, those similar to the compounds used for general electrolyte infusion and the like can be used, and examples thereof include a sodium salt, a potassium salt, a magnesium salt, a calcium salt, a chloride and a phosphate. Specific examples of the electrolyte include sodium hydrogen carbonate, sodium carbonate, sodium dihydrogen phosphate, disodium hydrogen phosphate, sodium chloride, sodium sulfate, potassium chloride, potassium dihydrogen phosphate, dipotassium hydrogen phosphate, and calcium gluconate. , Calcium chloride, magnesium chloride, magnesium sulfate, sodium acetate, potassium acetate, magnesium acetate, sodium citrate, potassium citrate, sodium succinate, potassium succinate, and the like. One or more of these may be used. Can be used. These may be hydrates.

(amino acid)
The iron-containing infusion solution of the present invention preferably further contains an amino acid (excluding cysteine) in order to exhibit a sufficient function as an amino acid solution preparation for infusion. The amino acid content (total amount of all amino acids) is preferably 10 to 60 g, more preferably 15 to 50 g, and even more preferably 20 to 40 g per liter of the iron-containing infusion.

  Examples of the amino acids include various amino acids (essential amino acids and non-essential amino acids) conventionally contained in amino acid transfusions for the purpose of nutritional supplementation to the living body. Specifically, L-isoleucine, L-leucine, L-valine, L-lysine, L-methionine, L-phenylalanine, L-threonine, L-tryptophan, L-arginine, L-histidine, glycine, L-alanine , L-proline, L-aspartic acid, L-serine, L-tyrosine, L-glutamic acid and the like. These amino acids do not necessarily need to be used in the form of free amino acids, but include inorganic acid salts (eg, L-lysine hydrochloride, L-lysine sulfite, etc.), organic acid salts (eg, L-lysine acetate, L-lysine acetate, -Lysine malate, etc.), in vivo hydrolyzable esters (eg, L-tyrosine methyl ester, L-methionine methyl ester, L-methionine ethyl ester, etc.), N-substituted (eg, N-acetyl) -L-tryptophan, N-acetyl-L-cysteine, N-acetyl-L-proline, etc.). Further, dipeptides obtained by peptide bonds of the same or different amino acids (for example, L-tyrosyl-L-tyrosine, L-alanyl-L-tyrosine, L-arginyl-L-tyrosine, L-tyrosyl-L-arginine, etc.) It may be used in such a form. In particular, when all of the above amino acids are contained, they will have sufficient functions as an amino acid solution preparation for infusion. In this specification, cysteine is classified as a reducing substance.

[Trace element compounds]
The iron-containing infusion solution of the present invention may further contain at least one trace element compound selected from the group consisting of manganese compounds, zinc compounds, copper compounds, iodine compounds and selenium compounds. By further containing such a trace element compound, trace elements can be replenished in hypercaloric infusion therapy.

  Examples of the manganese compound include manganese chloride and manganese sulfate, and one or more of these can be used. Among them, manganese chloride is preferred.

  Examples of the zinc compound include zinc sulfate and zinc chloride, and one or more of these can be used. Among them, zinc sulfate is preferred.

  Examples of the copper compound include copper sulfate, copper chloride and the like, and one or more of these can be used. Among them, copper sulfate is preferred.

  Examples of the iodine compound include potassium iodide and sodium iodide, and one or more of these can be used. Among them, potassium iodide is preferred.

  Examples of the selenium compound include selenous acid, sodium selenite, and the like, and one or more of these can be used.

The content of the trace element compound in the iron-containing infusion solution of the present invention is preferably such that the daily dose of the element per adult is within the following range:
Manganese 0.01-0.3 mg, especially 0.02-0.2 mg
Zinc 0.5-10.0 mg, especially 1.0-8.0 mg
Copper 0.01-2.0mg, especially 0.05-1.0mg
Iodine 0.01-1.0 mg, especially 0.05-0.3 mg
Selenium 0.005-0.2 mg, especially 0.01-0.1 mg.

[Additive]
The iron-containing infusion of the present invention may contain, if necessary, water-soluble vitamins (for example, vitamin B1 (thiamine), vitamin B2, vitamin B6 (pyridoxine, etc.), biotin, vitamin B12, nicotinamide, pantothenic acid, folic acid, etc. ) And fat-soluble vitamins (for example, vitamin A, vitamin D, vitamin E, vitamin K, etc.). The content of each vitamin can be the same amount as that used in conventional high-calorie infusions. The vitamin may be in the form of a salt or a derivative.

  The iron-containing infusion solution of the present invention can further contain a fat emulsion, if necessary. Examples of the fat emulsion include an oil-in-water (O / W) emulsion prepared by using a suitable emulsifier which is physiologically acceptable for vegetable oil such as soybean oil.

  Further, as long as the effects of the present invention are not impaired, known additives usually used in infusion solutions, such as other pH adjusters, solvents, and stabilizers, can be further contained. Examples of the solvent include polysorbate 80 and polysorbate 20.

[Production method]
Although the iron-containing infusion of the present invention is not particularly limited, for example, the above-mentioned chondroitin sulfate / iron colloid, ascorbic acid (salt), glycerophosphate, lactic acid (salt), acetic acid, citric acid and / or And succinic acid. Specifically, the above-mentioned chondroitin sulfate / iron colloid, ascorbic acid (salt), glycerophosphate, lactic acid (salt), acetic acid, citric acid and / or succinic acid, and if necessary, other components Are collectively or sequentially mixed. The mixing temperature and the mixing time can be appropriately adjusted, and a known mixing means can be used.

[Physical properties]
The pH of the iron-containing infusion solution of the present invention is preferably 4.5 to 7.5, more preferably 4.5 to 7.0, and even more preferably 4.5 to 6.5.

  The iron-containing infusion solution of the present invention preferably has a total daily calorific value of the infusion solution to one adult per day of 500 to 2000 kcal, more preferably 600 to 1500 kcal.

[Containment form]
The iron-containing infusion solution of the present invention may be in a form housed in one chamber (one-chamber type) or in a form housed in a plurality of chambers (multi-chamber type).

  The iron-containing infusion solution according to one embodiment of the present invention contains a liquid containing chondroitin sulfate / iron colloid in one of a multi-compartment container having a plurality of chambers partitioned by partition walls that can be peeled off at the time of use, It is preferable that a liquid containing ascorbic acid or a salt thereof is contained in a chamber different from the chamber containing the liquid containing chondroitin sulfate / iron colloid. By adopting such a storage form, dissociation of iron from iron colloid by ascorbic acid can be further prevented, and the infusion solution can be stably stored for a long period of time.

  In the above embodiment, when a mixed solution of a solution containing chondroitin sulfate / iron colloid and a solution containing ascorbic acid or a salt thereof is stored at room temperature for 48 hours in a light-shielded state in which light having a wavelength of 450 nm or less is blocked, chondroitin The dissociation rate of iron from the sulfuric acid / iron colloid is preferably 40% or less. Here, the dissociation rate of iron is a value calculated by a method described in Examples described later. In addition, since a multi-chamber infusion is usually administered within 48 hours after mixing, it is sufficient that the effect of preventing iron dissociation is ensured in 48 hours.

  When the above-mentioned trace element compound is contained in the infusion solution of the present invention, it may be blended with a solution containing chondroitin sulfate / iron colloid from the viewpoint of preventing precipitation of coarse particles.

  When the infusion solution of the present invention contains the above-mentioned reducing substance, the liquid containing the reducing substance is preferably contained in a chamber different from the chamber containing the liquid containing chondroitin sulfate / iron colloid. By adopting such a housing form, dissociation of iron from the iron colloid by the reducing substance can be prevented, and the iron colloid can be stably stored for a long period of time.

  In addition, the iron-containing infusion solution according to one embodiment of the present invention is housed in a multi-chamber container having a plurality of chambers partitioned by partition walls that can be peeled off at the time of use, and one of the plurality of chambers includes chondroitin sulfate.・ The liquid containing the nutrient infusion component is contained in a room that contains the liquid containing the iron colloid and the trace element compound, and is different from the room that contains the liquid containing the chondroitin sulfate / iron colloid and the trace element compound. preferable. By adopting such a storage form, dissociation of iron from the iron colloid by the nutrient infusion component can be further prevented, and the infusion can be stably stored for a long time.

  In the above embodiment, a mixture of a solution containing chondroitin sulfate / iron colloid and a trace element compound and a solution containing a nutrient infusion agent component were stored at room temperature for 48 hours in a light-shielded state where light having a wavelength of 450 nm or less was blocked. In this case, the dissociation rate of iron from the chondroitin sulfate / iron colloid is preferably 40% or less. Here, the dissociation rate of iron is a value calculated by a method described in Examples described later.

  When the iron-containing infusion solution of the present invention is of a multi-chamber type, the nutritional infusion component may be housed in one room or may be housed in a plurality of compartments. From the viewpoint of preventing the progress of the Maillard reaction, the sugar and the amino acid are preferably housed separately.

  A multi-chamber container having a plurality of chambers separated by partition walls that can be separated at the time of use is, for example, polyethylene, polypropylene, polyolefin such as cyclic polyolefin, polystyrene-based thermoplastic elastomer, vinyl chloride-based thermoplastic elastomer, polyester-based thermoplastic A multi-chamber bag-shaped container by a conventionally known method using a single-layer or multi-layer sheet or film made of one or more of an elastomer, a polyamide-based thermoplastic elastomer, a silicone-based thermoplastic elastomer, and the like. And so on.

  Filling and storing in a container can be performed according to a conventional method, and examples include a method of filling an infusion agent in an inert gas atmosphere, plugging, and sterilizing by heating. As the heat sterilization method, a known method such as high-pressure steam sterilization, hot water sterilization, and hot water shower sterilization can be appropriately adopted. Further, the operation conditions of the sterilization method, for example, the sterilization time, the sterilization temperature, and the like can be the same as the normal sterilization operation conditions. Furthermore, the heat sterilization can be performed in an atmosphere of an inert gas such as nitrogen, if necessary.

  Further, in order to surely prevent the infusion such as oxidation of the present invention from deteriorating, the container accommodating the infusion can be packaged together with the oxygen scavenger in an outer container that is substantially impermeable to oxygen. At this time, it is preferable to use plastic having gas permeability as a material of the container for storing the infusion solution. Various known oxygen scavengers can be used. For example, those containing an iron compound such as iron hydroxide, iron oxide or iron carbide as an active ingredient can be used. Commercial products include Ageless (produced by Mitsubishi Gas Chemical Co., Ltd.), Modulan (produced by Nippon Kayaku Co., Ltd.), and Secur (produced by Nippon Soda Co., Ltd.).

  Hereinafter, the present invention will be specifically described with reference to examples, but the present invention is not limited to the following examples.

  In the following examples, potassium glycerophosphate is dipotassium glycerophosphate, and lysine malate is L-form (that is, L-lysine malate).

<< Example 1 >>
(1) Dissolve the electrolytes and vitamins described in the column of Solution A in Table 1 below with glucose in water for injection, add sodium lactate and glacial acetic acid, perform filtration, and perform solution A ( pH 4.5) was prepared.

  (2) Dissolve sodium riboflavin phosphate, ascorbic acid, a 50% solution of potassium glycerophosphate as a phosphorus compound and sodium bisulfite described in the column of solution B in Table 1 below together with amino acids in water for injection, and citric acid After adjusting the pH to 6.5 with hydrate and succinic acid, filtration was performed to prepare a solution B shown in the table.

  (3) Retinol palmitate, ergocalciferol, tocopherol acetate, and phytonadione were dissolved in polysorbate 80 and polysorbate 20 to prepare a fat-soluble vitamin / surfactant mixture. Cyanocobalamin, folic acid, biotin and D-sorbitol are dissolved in water for injection, and the fat-soluble vitamin / surfactant mixture prepared above is added thereto, followed by stirring and mixing, and citric acid hydrate and sodium hydroxide are added. Then, the solution was adjusted to pH 6.0, filtered, and the solution C shown in Table 1 was prepared.

  (4) Chondroitin sulfate sodium salt was dissolved in water for injection, and an aqueous solution of ferric chloride hexahydrate and sodium hydroxide were alternately added to prepare a chondroitin sulfate / iron colloid solution. Manganese chloride tetrahydrate, copper sulfate pentahydrate, zinc sulfate heptahydrate and potassium iodide were added to the chondroitin sulfate / iron colloid solution, the pH was adjusted to 5.8 with sodium hydroxide, and filtration was performed. Was prepared.

  (5) A polypropylene four-chamber container (bag) partitioned into four chambers by a partition that can be peeled off at the time of use is prepared, the first chamber is filled with 693 mL of solution A, and the second chamber is filled with 300 mL of solution B. After filling, the third chamber was filled with 3 mL of solution C, and the fourth chamber was filled with 4 mL of solution D, to produce a high calorie infusion solution.

  (6) The bag containing the high-calorie infusion solution obtained in the above (5) is subjected to high-pressure steam sterilization according to a conventional method, and then packaged with an oxygen-impermeable outer packaging material together with a deoxygenating agent. I got

<< Example 2 >>
In the same manner as in Example 1, solutions A, B, C, and D described in the column of Example 2 in Table 1 were prepared, and each solution was partitioned by a partition that can be peeled off at the time of use. After filling in each of the solutions (bags), the solution was subjected to high-pressure steam sterilization according to a conventional method, and packaged with an oxygen-impermeable outer packaging material together with a deoxidizer to produce the high-calorie infusion solution of Example 2.

  For each of the high-calorie infusions obtained in Examples 1 and 2, the bag was pressed from the outside to separate the partition, and all the solutions A to D filled in the four chambers were mixed. From a chondroitin sulfate / iron colloid at the time of storage for 24 hours and 48 hours at room temperature with a cover (transmittance of light of wavelength 450nm about 1%, light of wavelength 600nm or more about 50%) Was determined by the method described in [Dissociation rate of iron from chondroitin sulfate / iron colloid].

<< Comparative Example 1 >>
A liquid having the component composition shown in the column of Comparative Example 1 in Table 2 (total amount adjusted to 900 mL with water for injection) was filtered through a 0.22 μm membrane filter, and this was aseptically filled into an infusion bag (one-chamber type). Immediately after producing an infusion solution in which all components in the infusion solution are mixed, a light-shielding cover (having a transmittance of light of 450 nm wavelength of about 1% and a transmittance of light of wavelength 600 nm of about 50%) ) Was attached. The rate of dissociation of iron from chondroitin sulfate / iron colloid at the time of storage at room temperature for 24 hours and 48 hours was determined by the method shown in [Dissociation rate of iron from chondroitin sulfate / iron colloid].

<< Comparative Example 2 >>
A liquid having the component composition shown in the column of Comparative Example 2 in Table 2 was aseptically filled in an infusion bag (one-chamber type) to produce an infusion solution in which all components in the infusion solution were mixed. The dissociation rate of iron from chondroitin sulfate / iron colloid was determined in the same manner as in Comparative Example 1.

<< Comparative Example 3 >>
A liquid having a component composition shown in the column of Comparative Example 3 in Table 3 was produced in the same manner as in Comparative Example 1, and the dissociation ratio of iron from chondroitin sulfate / iron colloid was determined.

<< Comparative Example 4 >>
A liquid having the component composition shown in the column of Comparative Example 4 in Table 3 was aseptically filled in an infusion bag (one-chamber type) to produce an infusion solution in which all components in the infusion solution were mixed. Similarly to Comparative Example 1, the dissociation rate of iron from the chondroitin sulfate / iron colloid was determined.

<< Comparative Example 5 >>
A liquid having the component composition shown in the column of Comparative Example 5 in Table 4 was aseptically filled into an infusion bag (one-chamber type) to produce an infusion solution in which all components in the infusion solution were mixed. Similarly to Comparative Example 1, the dissociation rate of iron from the chondroitin sulfate / iron colloid was determined.

<< Comparative Example 6 >>
A liquid having the component composition shown in the column of Comparative Example 6 in Table 4 was aseptically filled into an infusion bag (one-chamber type) to produce an infusion in which all the components in the infusion were mixed. Similarly to Comparative Example 1, the dissociation rate of iron from the chondroitin sulfate / iron colloid was determined.

[Dissociation rate of iron from chondroitin sulfate / iron colloid]
(I) Measurement of total iron concentration:
About the infusion agent obtained in Examples 1 and 2 and Comparative Examples 1 to 6 before being stored at room temperature for 48 hours, after adding thioglycolic acid, the mixture was heated to 60 ° C and chondroitin sulfate / iron colloid was obtained. All iron was dissociated, and the total iron concentration (CA) was measured by the nitroso-PSAP method.

(Ii) Measurement of non-colloidal iron concentration:
The infusion solution stored at room temperature for 24 hours and 48 hours with the light-shielding cover attached was subjected to centrifugal filtration at 5000 × g for 30 minutes using a centrifugal filter unit “Amicon Ultra-4 (30K)”, and the resulting product was obtained. Using the filtrate, the non-colloidal iron concentration (CB) was measured by the nitroso-PSAP method.

(Iii) Calculation of dissociation rate of iron from chondroitin sulfate / iron colloid:
The dissociation rate of iron (dissociation rate of iron) from chondroitin sulfate / iron colloid was determined by the following equation (I).

<< Test result 1 >>
Table 5 shows the results of the iron dissociation rates of the infusion agents of Examples 1 and 2 and Comparative Examples 1 to 6. In Table 5, lactate ion (lactic acid in Table 5), acetate ion (acetic acid in Table 5), citrate ion (citrate in Table 5), succinate ion (succinic acid in Table 5) per 1 L of the infusion solution Acid) (mEq / L).

The infusion solution of Example 1 (the phosphorus formulation is dipotassium glycerophosphate, containing 23 mEq / L of lactic acid, 5.8 mEq / L of acetic acid, 10.05 mEq / L of citric acid, and 2.6 mEq / L of succinic acid) The dissociation of iron after mixing was 25.8% for 24 hours storage and 28.0% for 48 hours storage;
The infusion solution of Example 2 (the phosphorus formulation is dipotassium glycerophosphate, containing 28 mEq / L lactic acid, 6.8 mEq / L acetic acid, 10.05 mEq / L citric acid, and 8.8 mEq / L succinic acid) The dissociation rate of the iron after mixing was 24.6% for 24 hours storage and 28.6% for 48 hours storage;
The infusion solution of Comparative Example 1 (the phosphorus formulation is dipotassium glycerophosphate, does not contain lactic acid, contains 28 mEq / L of acetic acid, and contains 0.07 mEq / L of citric acid) has a dissociation rate of iron after mixing. , 28.8% for 24 hours storage and 45.2% for 48 hours storage;
The infusion agent of Comparative Example 2 (comprising soybean oil in the composition of Comparative Example 1) had a high iron dissociation rate after mixing of 31.4% for 24 hours storage and 47.8% for 48 hours storage. Yes, not affected by the presence or absence of soybean oil;
The infusion agent of Comparative Example 3 (the phosphorus formulation was potassium dihydrogen phosphate, lactic acid was 11 mEq / L, acetic acid was 39 mEq / L, and citric acid was 8 mEq / L) was stored for 24 hours after mixing. The dissociation rate was as high as 86.1% and 97.5% for 48 hours storage;
The infusion agent of Comparative Example 4 (the phosphorus formulation is potassium dihydrogen phosphate, lactic acid is 14 mEq / L, acetic acid is 48 mEq / L, and citric acid is 12 mEq / L) has a dissociation rate of iron after mixing. The value was as high as 78.2% after 24 hours storage and 95.8% after 48 hours storage.

  Infusion solution of Comparative Example 5 (phosphorus is dipotassium glycerophosphate, lactic acid is 40 mEq / L, acetic acid is 0.07 mEq / L, citric acid is 5.7 mEq / L, succinic acid is 1.1 mEq / L. A), the dissociation rate of iron after mixing was as high as 34.3% for 24 hours storage and 50.5% for 48 hours storage.

  Infusion solution of Comparative Example 6 (phosphorus compound form is dipotassium glycerophosphate, lactic acid is 40 mEq / L, acetic acid is 16.1 mEq / L, citric acid is 13.3 mEq / L, and succinic acid is 1.0 mEq / L. A), the dissociation rate of iron after mixing was as high as 33.2% after 24 hours storage and 52.1% after 48 hours storage.

  That is, in Examples 1 and 2, the iron dissociation rate was 30% or less when stored for 24 hours, was 40% or less when stored for 48 hours, and increased from 24 hours to 48 hours. The minute values were as low as 2.2% and 4.0%. On the other hand, when lactic acid (salt) is not contained (Comparative Examples 1 and 2), or when potassium dihydrogen phosphate is used instead of dipotassium glycerophosphate and the lactate ion content is less than 20 mEq / L ( In Comparative Examples 3 and 4), the dissociation rate of iron during storage for 24 hours was higher than that in Examples 1 and 2, and was higher when stored for 48 hours, and was 48 hours after storage for 24 hours. The increase during storage was also high at 11.4% to 17.6%. When the lactate ion content exceeds 38 mEq / L (40 mEq / L) (Comparative Examples 5 and 6), the dissociation rate of iron during storage for 24 hours is lower than that in Examples 1 and 2. The value was high at the time of storage for 48 hours, and the increase from storage for 24 hours to storage for 48 hours was also high at 16.2% to 18.9%.

<< Example 3 >>
(1) The electrolytes and vitamins described in the column of solution A in Table 6 below were dissolved together with glucose in water for injection, and the solution was filtered to prepare a solution A (pH 4.5) shown in the table.

  (2) Sodium riboflavin phosphate, ascorbic acid, 50% potassium glycerophosphate as a phosphorus compound and sodium bisulfite described in the column of solution B in Table 6 below are dissolved in water for injection together with amino acids, followed by filtration. Then, a solution B shown in the table was prepared.

  (3) Retinol palmitate, ergocalciferol, tocopherol acetate, and phytonadione were dissolved in polysorbate 80 and polysorbate 20 to prepare a fat-soluble vitamin / surfactant mixture. In water for injection, cyanocobalamin, folic acid, biotin and D-sorbitol are dissolved, and the fat-soluble vitamin / surfactant mixture prepared above is added thereto, followed by stirring and mixing, sodium hydroxide is added, and filtration is performed. A solution C shown in Table 6 was prepared.

  (4) Chondroitin sulfate sodium salt was dissolved in water for injection, and an aqueous solution of ferric chloride hexahydrate and sodium hydroxide were alternately added to prepare a chondroitin sulfate / iron colloid solution. Manganese chloride tetrahydrate, copper sulfate pentahydrate, zinc sulfate heptahydrate and potassium iodide were added to the chondroitin sulfate / iron colloid solution, sodium hydroxide was added, and filtration was performed. D was prepared.

  The solutions A, B, C and D were mixed, the pH was adjusted to 6 by adding glacial acetic acid, and the total volume was adjusted to 1000 mL with water for injection, and this was aseptically filled into an infusion bag (one-chamber type). Thus, an infusion solution in which all components in the infusion solution were mixed was produced. Immediately, a light-shielding cover (transmittance of light having a wavelength of 450 nm of about 1% and light having a wavelength of 600 nm of about 50%) was attached. The rate of dissociation of iron from chondroitin sulfate / iron colloid at the time of storage at room temperature for 24 hours and 48 hours was determined by the method shown in [Dissociation rate of iron from chondroitin sulfate / iron colloid].

<< Example 4 >>
A liquid having the component composition shown in the column of Example 4 of Table 6 was prepared in the same manner as in Example 3 except that the pH was adjusted to 6 by adding citric acid hydrate, and the dissociation rate of iron from chondroitin sulfate / iron colloid was prepared. I asked.
Was.

<< Example 5 >>
A liquid having a component composition shown in the column of Example 5 in Table 6 was prepared in the same manner as in Example 3 except that the pH was adjusted to 5 by adding citric acid hydrate, and the dissociation rate of iron from chondroitin sulfate / iron colloid was prepared. I asked.

<< Example 6 >>
A liquid having the component composition shown in the column of Example 6 in Table 6 was prepared in the same manner as Example 3 except that succinic acid was added to adjust the pH to 6, and the dissociation ratio of iron from chondroitin sulfate / iron colloid was determined. .

<< Comparative Example 7 >>
A liquid having the component composition shown in the column of Comparative Example 7 in Table 6 was prepared in the same manner as in Example 3 except that glacial acetic acid was added to adjust the pH to 5, and the dissociation rate of iron from chondroitin sulfate / iron colloid was determined. .

<< Comparative Example 8 >>
A liquid having the component composition shown in the column of Comparative Example 8 in Table 6 was prepared in the same manner as in Example 3 except that succinic acid was added to adjust the pH to 5, and the dissociation rate of iron from chondroitin sulfate / iron colloid was determined. .

<< Test result 2 >>
Table 7 shows the results of the iron dissociation rate. In Table 7, the contents (mEq / L) of lactate ion, acetate ion, citrate ion, and succinate ion per 1 L of the infusion solution are shown.

The iron dissociation rate of the infusion solution of Example 3 (containing 28 mEq / L of lactic acid and 20 mEq / L of acetic acid) was 25.4% for 24 hours storage and 33.2% for 48 hours storage;
The iron dissociation rate of the infusion solution of Example 4 (containing 28 mEq / L of lactic acid and 18 mEq / L of citrate) was 17.1% for 24 hours storage and 25.5% for 48 hours storage;
The dissociation rate of iron of the infusion solution of Example 5 (containing 28 mEq / L of lactic acid and 41 mEq / L of citrate) was 26.9% for 24 hours storage and 33.5% for 48 hours storage;
The dissociation rate of iron of the infusion solution of Example 6 (containing 28 mEq / L of lactic acid and 22 mEq / L of succinic acid) was 23.0% after 24 hours storage and 31.4% after 48 hours storage;
The dissociation rate of iron of the infusion solution of Comparative Example 7 (containing 28 mEq / L of lactic acid and 41 mEq / L of acetic acid) was as high as 44.3% after 24 hours storage and 53.1% after 48 hours storage;
The dissociation rate of iron of the infusion solution of Comparative Example 8 (containing 28 mEq / L of lactic acid and 49 mEq / L of succinic acid) was as high as 39.6% after 24 hours storage and 48.0% after 48 hours storage. .

  That is, when the content of the acetate ion exceeds 40 mEq / L (Comparative Example 7) or when the content of the succinate ion exceeds 45 mEq / L (Comparative Example 8), compared to Examples 3 to 6, The iron dissociation rate after storage for 24 hours was high.

  Although the iron-containing infusion of the present invention contains ascorbic acid, which promotes dissociation of iron from chondroitin sulfate / iron colloid, at a high concentration of 100 to 200 mg per liter of the infusion, chondroitin sulfate / iron colloid is used. Iron dissociation rate from iron is low. Thus, induction of hepcidin-25 by dissociated iron can be prevented, thereby promoting the use of iron in patients.

  Furthermore, since the iron-containing infusion of the present invention contains ascorbic acid at a high concentration of 100 to 200 mg per liter of the infusion, the antioxidant effect of ascorbic acid (vitamin C), the effect of improving the immune function, the effect of collagen It can be effectively used as an infusion solution because it can effectively exert its production action, calcium absorption and metabolism action, sugar metabolism action, histamine release inhibitory action caused by allergic reaction, hormone producing action to reduce stress, etc. is there.

  The iron-containing infusion solution of the present invention can be administered to a parenteral nutrition patient who needs supplementation of iron as a trace element. Further, the iron-containing infusion of the present invention suppresses the dissociation of iron from chondroitin sulfate / iron colloid in a high calorie infusion, thereby avoiding induction of hepcidin by dissociated free iron and inhibiting iron metabolism. The patient can be replenished without any iron.

Claims (12)

Chondroitin sulfate / iron colloid, ascorbic acid or a salt thereof, glycerophosphate, lactic acid or a salt thereof, and acetic acid, at least one selected from the group consisting of citric acid and succinic acid,
The content of the ascorbic acid or the salt thereof is 100 to 200 mg / L, the content of the lactate ion is 20 to 38 mEq / L, the content of the acetate ion is 40 mEq / L or less, and the content of the succinate ion is An iron-containing infusion having an amount of 45 mEq / L or less.   2. The iron-containing infusion according to claim 1, further comprising at least one reducing substance selected from the group consisting of cysteine, acetylcysteine and sulfite.   The iron-containing infusion according to claim 1 or 2, wherein the content of acetate ions is 25 mEq / L or less.   The iron-containing infusion according to any one of claims 1 to 3, wherein the content of citrate ion is 45 mEq / L or less.   The iron-containing infusion according to any one of claims 1 to 4, wherein the content of the succinate ion is 25 mEq / L or less.   The iron-containing infusion according to any one of claims 1 to 5, comprising the chondroitin sulfate / iron colloid in an amount such that a daily dose of iron element per adult is 0.1 to 2 mg. Agent.   The iron-containing infusion according to any one of claims 1 to 6, further comprising at least one trace element compound selected from the group consisting of a manganese compound, a zinc compound, a copper compound, an iodine compound, and a selenium compound.   The iron-containing infusion according to any one of claims 1 to 7, further comprising at least one nutrient infusion component selected from the group consisting of sugar, electrolyte, and amino acid.   A liquid containing the chondroitin sulfate / iron colloid is contained in one of a plurality of chambers, the liquid containing the chondroitin sulfate / iron colloid. The iron-containing infusion according to any one of claims 1 to 8, wherein the liquid containing the ascorbic acid or a salt thereof is stored in a chamber different from the chamber in which the liquid containing a colloid is stored.   When a mixed solution of the liquid containing the chondroitin sulfate / iron colloid and the liquid containing the ascorbic acid or a salt thereof is stored at room temperature for 48 hours in a light-shielded state in which light having a wavelength of 450 nm or less is blocked, chondroitin sulfate / iron The iron-containing infusion according to claim 9, wherein the dissociation rate of iron from the colloid is 40% or less.   It is housed in a multi-chamber container having a plurality of chambers separated by partition walls that can be separated at the time of use, and a liquid containing the chondroitin sulfate / iron colloid and the trace element compound is housed in one of a plurality of chambers, The infusion solution containing iron according to claim 8, wherein the solution containing the nutrient infusion agent component is housed in a room different from the room in which the solution containing the chondroitin sulfate / iron colloid and the trace element compound is housed.   When a mixture of the liquid containing the chondroitin sulfate / iron colloid and the trace element compound and the liquid containing the nutrient infusion agent component are stored at room temperature for 48 hours in a light-shielded state where light having a wavelength of 450 nm or less is blocked, The iron-containing infusion according to claim 11, wherein the dissociation rate of iron from the chondroitin sulfate / iron colloid is 40% or less.