JP2008195737A - Infusion preparation containing trace of metal - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an integrated infusion preparation comprising an amino acid, sugar, copper, and an iodine ion which does not form precipitates from copper and an iodine ion in storage. <P>SOLUTION: The nutritious infusion preparation containing copper and an iodine ion has an air-permeable infusion container which is enclosed in a gas barrier outer bag substantially in the absence of oxygen and is constituted of a plurality of chambers divided by communicable partitioning means, the first chamber of the infusion container housing an amino acid-containing solution and the second chamber housing a sugar-containing solution, any one of the amino acid-containing solution and the sugar-containing solution containing copper and the other containing an iodine ion. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention relates to a nutritional infusion preparation comprising an infusion container having a plurality of rooms capable of preparing and blending medicines, and a method for stabilizing iodine ions or copper ions using the container.

Patients who are unable or inadequate for oral and enteral feeding are given intravenous high-calorie infusions. As infusion preparations used at this time, sugar preparations, amino acid preparations, electrolyte preparations, mixed vitamin preparations, fat emulsions and the like were commercially available, and were used by being appropriately mixed at the hospital at the time of use depending on the disease state etc. .
However, such a mixed injection operation in a hospital is complicated, and there is a problem that there is a high possibility of bacterial contamination during the operation, which is unsanitary. For this reason, an infusion container having a plurality of chambers partitioned by a partition means capable of communication has been developed and widely used in hospitals. As a product of this infusion container, for example, there is one in which an amino acid infusion is accommodated in one room and a glucose infusion is accommodated in another room. However, since the amino acid infusion is easily oxidatively decomposed by oxygen, the infusion container is a gas barrier. In a plastic film bag with oxygen scavenger.

  On the other hand, since the infusion solution does not contain trace metal elements (copper, iron, zinc, manganese, etc.), when the infusion solution is administered for a long time, the patient's lips are cracked or the hematopoietic function is reduced. The so-called trace metal deficiency develops. For this reason, in hospitals, the present situation is that trace metal elements are appropriately mixed just before administration of an infusion solution while having the problem of bacterial contamination.

In view of the present situation, the present inventors have started research on an infusion preparation in which a trace metal element is also contained in a chamber of an infusion container.
However, when a combination of amino acid infusion solution and trace metal elements, that is, in the absence of oxygen, if trace metal and iodine ions are accommodated in the same chamber, the trace metal and iodine ions that were conventionally considered to be stable are The present inventors have found that the reaction occurs and precipitation occurs.

  That is, conventionally, it was recognized that trace metals and iodine ions would not precipitate even when mixed in an aqueous medium. However, infusion preparations containing components that are susceptible to oxygen, such as amino acid preparations, are gas permeable. The container is covered with an outer bag that does not transmit gas together with the oxygen absorber until just before use so that it is not affected by oxygen as much as possible, and there is no oxygen in the outer bag and the infusion container. Under the conditions, the present inventors have found that when trace metals (especially copper) and iodine ions are accommodated in the same chamber, precipitation easily occurs and the commercial value of the infusion preparation is lost.

  The present invention contains a trace metal solution in one chamber of an infusion container under conditions where oxygen is not substantially present, and contains a trace metal and iodine ion during storage by storing an iodine ion solution, an amino acid solution, etc. in another chamber. The purpose is to provide an infusion preparation in which copper ions and iodine ions are stable without forming a precipitate.

  In view of the above problems, the present inventors adopt an infusion container having a multi-chamber infusion container that can separately accommodate a trace metal solution and an iodine ion solution, and various solutions stored in a plurality of infusion containers at the time of use. It was found that the above-mentioned problems can be solved by mixing them together.

  What achieves the above-mentioned object is, for example, an infusion container having a plurality of chambers that are communicably partitioned during use. Further, the infusion container includes a first chamber, a second chamber partitioned from the first chamber, a third chamber partitioned from the first chamber or the second chamber, and, if desired, the first chamber and the second chamber. And a fourth chamber partitioned from any one of the third chambers, a communicable portion is formed between the first chamber and the second chamber, and the closed chemical liquid flow communicating with the first chamber or the second chamber An infusion container having an outlet.

  A drug is accommodated in each chamber of the infusion container. Further, the communicable part is, for example, a weak seal part formed in the whole or a part of the communicable partition partitioning each chamber. Further, the communicable part may be a breakable flow path blocker provided in a partition wall that partitions the infusion container, and further presses a chamber of the infusion container that comes into contact with the communicable part from the outside. Thus, it is preferable that the chamber communicates with another adjacent chamber.

That is, the present invention
(1) A nutritional infusion preparation containing trace metal and iodine ion, wherein the trace metal and iodine ion are isolated and contained in an infusion container substantially in the absence of oxygen,
(2) The infusion container is composed of a plurality of chambers that are air permeable and sealed in a gas barrier outer bag in the absence of oxygen, and are partitioned by a partition means capable of communicating with the infusion container. A nutritional infusion preparation as described in (1) above,
(3) The amino acid-containing solution is stored in the first chamber of the infusion container, the sugar-containing solution is stored in the second chamber, the trace metal-containing solution is stored in the third chamber, and the solution in the first chamber or / and the second chamber is The nutritional infusion preparation according to (2) above, further comprising iodine ions,
(4) The above condition characterized in that the condition in which no oxygen is present is achieved by sealing an oxygen scavenger in the outer bag, and / or by introducing an inert gas into the outer bag. (1) to (3) any one of the nutritional infusion preparations,
(5) The nutritional infusion preparation according to any one of (1) to (4) above, wherein the trace metal is copper,
(6) The nutrient infusion preparation according to any one of (3) to (5) above, wherein the sugar is glucose.
(7) The pH of the solution stored in the first chamber is 5 to 8, the pH of the solution stored in the second chamber is 2.5 to 5, and the pH of the solution stored in the third chamber is The nutritional infusion preparation according to any one of (3) to (6) above, which is 4 to 6.5,
(8) The nutritional infusion preparation according to (7) above, wherein the solution contained in the first chamber or the second chamber contains at least one of calcium ions or phosphorus as an electrolyte,
(9) The pH of a solution obtained by mixing the solution stored in the first chamber, the solution stored in the second chamber, and the solution stored in the third chamber is 4-7. (3) to (8) any one of the nutritional infusion preparations,
(10) The component composition when mixing the solution stored in the first chamber, the solution stored in the second chamber, and the solution stored in the third chamber is glucose 50 to 400 g / L, L- Leucine 0.8-10.0 g / L, L-isoleucine 0.4-7.0 g / L, L-valine 0.3-8.0 g / L, L-lysine 0.5-7.0 g / L, L-threonine 0.3-4.0 g / L, L-tryptophan 0.08-1.5 g / L, L-methionine 0.2-4.0 g / L, L-phenylalanine 0.4-6.0 g / L L, L-cysteine 0.03-1.0 g / L, L-tyrosine 0.02-1.0 g / L, L-arginine 0.5-7.0 g / L, L-histidine 0.3-4. 0 g / L, L-alanine 0.4 to 7.0 g / L, L-proline 0.2 to 5.0 g / L, L-serine 0.2-3.0 g / L, glycine 0.3-6.0 g / L, L-aspartic acid 0.03-2.0 g / L, L-glutamic acid 0-3.0 g / L, sodium 20-80 mEq / L, potassium 10-40 mEq / L, magnesium 2-20 mEq / L, calcium 2-20 mEq / L, phosphorus 2-20 mmol / L, chlorine 20-80 mEq / L, iron 5-100 μmol / L, copper 1-20 μmol / L, manganese 0-5 μmol / L, zinc 5-150 μmol / L, iodine 0.2-5 μmol / L, the nutritional infusion preparation according to any one of the above (3) to (9),
(11) In an infusion container having a fourth chamber defined by a partition means capable of communicating with at least one of the first chamber, the second chamber, and the third chamber, the solution contained in the fourth chamber is vitamin A, The nutritional infusion preparation according to any one of (3) to (10) above, which comprises one or more of vitamin E, vitamin D and vitamin K;
(12) Any one of the solution housed in the first chamber, the solution housed in the second chamber, and the solution housed in the third chamber is further added to vitamin B ₁ , biotin, vitamin C, vitamin B ₁₂ , folic acid, pantothenic acids, vitamin B ₆ , nicotinic acids and one or more of vitamin H, the nutritional infusion preparation according to (11) above,
(13) The component composition when the solution stored in the first chamber, the solution stored in the second chamber, the solution stored in the third chamber, and the solution stored in the fourth chamber are mixed. Glucose 50-400 g / L, L-leucine 0.8-10.0 g / L, L-isoleucine 0.4-7.0 g / L, L-valine 0.3-8.0 g / L, L-lysine 0 0.5-7.0 g / L, L-threonine 0.3-4.0 g / L, L-tryptophan 0.08-1.5 g / L, L-methionine 0.2-4.0 g / L, L- Phenylalanine 0.4-6.0 g / L, L-cysteine 0.03-1.0 g / L, L-tyrosine 0.02-1.0 g / L, L-arginine 0.5-7.0 g / L, L-histidine 0.3 to 4.0 g / L, L-alanine 0.4 to 7.0 g / L, L-proline 0.2 -5.0 g / L, L-serine 0.2-3.0 g / L, Glycine 0.3-6.0 g / L, L-Aspartic acid 0.03-2.0 g / L, L-glutamic acid 0 3.0 g / L, sodium 20-80 mEq / L, potassium 10-40 mEq / L, magnesium 2-20 mEq / L, calcium 2-20 mEq / L, phosphorus 2-20 mmol / L, chlorine 20-80 mEq / L, iron 5 ~ 100 μmol / L, copper 1-20 μmol / L, manganese 0-5 μmol / L, zinc 5-150 μmol / L, iodine 0.2-5 μmol / L, vitamin B ₁ 0.8-30 mg / L, vitamin B ₂ 1 .0~6.0mg / L, vitamin _B 6 _1.0~8.0mg / L, vitamin _B 12 _1.0~20μg / L, nicotinic acid amide 10 to 80 mg / L, pantothenic acid 3.0 30 mg / L, folic acid 100-800 μg / L, vitamin C 25-200 mg / L, vitamin A 800-6500 IU / L, vitamin D 1.0-10 μg / L, vitamin E 2.5-20 mg / L, vitamin K 0.5-4 mg / L L, biotin 15-120 μg / L, the nutritional infusion preparation according to (11) or (12) above,
(14) A method for stabilizing iodine ions or copper ions, wherein iodine ions and copper ions are separated and accommodated in an air-permeable infusion container in the absence of oxygen.
About.

  The infusion container of the present invention can provide an infusion preparation that does not cause precipitation under the condition in which oxygen does not exist in the outer bag by filling the trace metal element and iodine ion in separate containers. In addition, by using the infusion container of the present invention, it is possible to eliminate the inconvenience of the mixing operation at the time of administration of the infusion preparation, the problem of bacterial contamination at the time of mixing, and to easily and aseptically mix each infusion preparation. it can.

  Below, the one aspect | mode of the infusion container which accommodates the nutrient infusion preparation which concerns on this invention is demonstrated concretely using figures. FIG. 1 is a plan view of an infusion container, showing an infusion container having four chambers (I to IV) in an outer bag 2, and an oxygen scavenger 10 is enclosed in the outer bag 2. The first chamber I is filled with an amino acid-containing solution, the second chamber II is filled with an iodine ion and sugar-containing solution, the third chamber III is filled with a trace metal-containing solution, and the fourth chamber IV is filled with a vitamin-containing solution. A communicable portion 5 is formed in the first chamber I and the second chamber II. By pressing the first chamber I or the second chamber II, the first chamber I and the second chamber do not come into contact with the outside air. II communicates. The third chamber III and the fourth chamber IV are suspended in the first chamber I, broken by being pressed from the outside, and communicated with the first chamber I. The closed drug solution outlet 9 communicating with the second chamber II is used for connection with an infusion set for injecting an internal drug solution into a patient, and for injecting another drug using a syringe or the like.

Below, an example of the infusion container which accommodates the nutritional infusion preparation which concerns on this invention is demonstrated in detail.
Each chamber of the infusion container containing the nutritional infusion preparation of the present invention is accommodated in an outer bag having a property of preventing gas and liquid from passing therethrough. In order to prevent oxidative degradation of amino acids, the infusion container is generally housed in a gas barrier outer bag together with an oxygen scavenger, but may be filled with an inert gas if necessary. Furthermore, when containing a photodegradable vitamin, it is preferable to provide the outer bag with a light-shielding property.
As a material suitable for the outer bag, a film or sheet of various commonly used materials can be used. For example, ethylene / vinyl alcohol copolymer, polyvinylidene chloride, polyacrylonitrile, polyvinyl alcohol, polyamide, polyester Examples thereof include a film or sheet containing at least one gas barrier material, etc., and can be appropriately selected and used. Moreover, when giving the said outer bag light-shielding property, it can implement by giving an aluminum laminate to the said film or sheet, for example.

Examples of the oxygen scavenger sealed in the outer bag include (1) iron carbide, iron carbonyl compound, iron oxide, iron powder, iron hydroxide or silicon iron coated with a metal halide, and (2) water. Alkaline earth metal oxide or alkaline earth metal carbonate, activated carbon and water, anhydride of compound having crystal water, mixture of alkaline substance or alcohol compound and nitrite, (3) ferrous compound, transition metal Salts, aluminum salts, alkali compounds containing alkali metals or alkaline earth metals, alkali compounds containing nitrogen or mixtures of ammonium salts and alkaline earth metals sulfites, (4) iron or zinc and sodium sulfate monohydrate (5) Iron, copper, tin, zinc or nickel; sodium sulfate and 7 water Or a mixture of metal halides, (6) a transition metal of period 4 of the periodic table; tin or antimony; and a mixture of water or a mixture of the mixture with a metal halide, (7) Alkali metal or ammonium sulfites, bisulfites or pyrosulfites; transition metal salts or aluminum salts; and mixtures with water can be used. From these known materials, it can be appropriately selected as desired.
A commercially available oxygen scavenger can be used, and examples of such a commercially available oxygen scavenger include AGELESS (manufactured by Mitsubishi Gas Chemical Company) and Modulan (manufactured by Nippon Kayaku Co., Ltd.).
As the oxygen scavenger, it is preferable to use it in a suitable air-permeable sachet as long as it is in powder form, and it may be used as it is without packaging if it is tableted.

  Moreover, oxygen may be removed by filling the outer bag with an inert gas, and examples of such an inert gas include helium gas and nitrogen gas.

  The infusion container that contains the nutritional infusion preparation of the present invention has a plurality of chambers. As a material for forming each chamber, any resin that does not cause a problem in stability of stored medicines may be used. A portion that forms a relatively large volume chamber is a flexible thermoplastic resin such as soft polypropylene or a copolymer thereof, polyethylene. And / or copolymers thereof, vinyl acetate, partially saponified polyvinyl alcohol, mixtures of polypropylene and polyethylene or polybutene, olefinic resins or partially crosslinked polyolefins such as ethylene-propylene copolymers, styrenic elastomers, and polyesters such as polyethylene terephthalate In addition, materials such as soft vinyl chloride resin, a material mixed with an appropriate resin among them, and a sheet obtained by molding the material in multiple layers including other materials such as nylon can be used.

  It is preferable that the partition which divides each chamber becomes what can open | release a chemical | medical agent without touching external air by pressing one infusion container which contacts the communicable part at the time of use from the outside. For example, by pressing one of the plurality of chambers of the infusion container from the outside, the partition between the other chambers is partially peeled off, and the drugs in both chambers are mixed by communicating with the other chambers.

In the infusion container 1 of FIG. 1, the first chamber I or the second chamber II has a larger capacity than the third chamber III or the fourth chamber IV. Such a large-capacity chamber can accommodate, for example, a high-calorie infusion, and the first chamber I or the second chamber II is filled with a high-concentration amino acid-containing solution or sugar-containing solution.
In the present invention, the amino acid-containing solution and the sugar-containing solution are preferably filled in separate chambers. For example, when the first chamber I is filled with the amino acid-containing solution, the sugar-containing solution is the second solution. Chamber II is preferably filled.

  Examples of amino acids contained in the amino acid-containing solution filled in the first chamber I or the second chamber II include essential amino acids, non-essential amino acids and / or salts, esters or N-acyl forms of these amino acids. It is done. Specifically, for example, L-isoleucine, L-leucine, L-lysine, L-methionine, L-phenylalanine, L-threonine, L-tryptophan, L-valine, L-alanine, L-arginine, L-aspartic acid Amino acids such as L-cysteine, L-glutamic acid, L-histidine, L-proline, L-serine, L-tyrosine, and L-glycine. These amino acids include inorganic acid salts such as L-arginine hydrochloride, L-cysteine hydrochloride, L-glutamine hydrochloride, L-histidine hydrochloride, L-lysine hydrochloride, L-lysine acetate, L-lysine. Organic acid salts such as malate, ester forms such as L-tyrosine methyl ester, L-methionone methyl ester, L-methionine ethyl ester, N-acetyl-L-cysteine, N-acetyl-L-tryptophan, N- Also in the form of N-substitutes such as acetyl-L-proline, dipeptides such as L-tyrosyl-L-tyrosine, L-alanyl-L-tyrosine, L-arginyl-L-tyrosine, L-tyrosyl-L-arginine good.

  The pH of the amino acid-containing solution is about 2.5 to 10, preferably about 5 using a normal pH adjusting agent, for example, acids such as hydrochloric acid, acetic acid, lactic acid, malic acid, citric acid, and alkalis such as sodium hydroxide as appropriate. It is preferable to prepare to -8.

It is preferable that the amino acid is blended in the following blending amount (in terms of free form) in a solution obtained by mixing all the solutions.
L-leucine about 0.4-20.0 g / L, preferably about 0.8-10.0 g / L, L-isoleucine about 0.2-14.0 g / L, preferably about 0.4-7. 0 g / L, L-valine about 0.1-16.0 g / L, preferably about 0.3-8.0 g / L, L-lysine about 0.2-14.0 g / L, preferably about 0.0. 5 to 7.0 g / L, about 0.1 to 8.0 g / L of L-threonine, preferably about 0.3 to 4.0 g / L, about 0.04 to 3.0 g / L of L-tryptophan, Preferably about 0.08-1.5 g / L, L-methionine about 0.1-8.0 g / L, preferably about 0.2-4.0 g / L, L-phenylalanine about 0.2-12. 0 g / L, preferably about 0.4 to 6.0 g / L, L-cysteine about 0.01 to 2.0 g / L, preferably about 0.03 to 1.0 g L, L-tyrosine about 0.01-2 g / L, preferably about 0.02-1.0 g / L, L-arginine about 0.2-14.0 g / L, preferably about 0.5-7. 0 g / L, about 0.1-8.0 g / L of L-histidine, preferably about 0.3-4.0 g / L, about 0.2-14.0 g / L of L-alanine, preferably about 0.0. 4 to 7.0 g / L, L-proline about 0.1 to 10.0 g / L, preferably about 0.2 to 5.0 g / L, L-serine about 0.1 to 6.0 g / L, preferably Is about 0.2 to 3.0 g / L, glycine is about 0.1 to 12.0 g / L, preferably about 0.3 to 6.0 g / L, and L-aspartic acid is about 0.01 to 4.0 g / L. , Preferably about 0.03 to 2.0 g / L, L-glutamic acid about 0 to 6.0 g / L, preferably about 0 to 3.0 g / L. Preferred.

  The sugar contained in the sugar-containing solution filled in the first chamber I or the second chamber II may be one conventionally used for various infusions, for example, monosaccharides such as glucose and fructose, and two sugars such as maltose. Saccharides are exemplified. Of these, reducing sugars such as glucose, fructose, and maltose are preferable, and glucose is particularly preferable in terms of blood glucose control. These reducing sugars may be used as a mixture of two or more, and a mixture obtained by adding sorbitol, xylitol, glycerin and the like to these reducing sugars may be used.

  The sugar-containing solution has a pH of about 2 to 6, preferably about 2.5 using a normal pH adjuster, for example, acids such as hydrochloric acid, acetic acid, lactic acid, malic acid, citric acid, and alkalis such as sodium hydroxide as appropriate. It is preferable to adjust to -5.

  It is preferable to mix these sugars in a mixed solution of all the solutions so as to be about 20 to 800 g / L, preferably about 50 to 400 g / L.

  The amino acid-containing solution and / or the sugar-containing solution further contains iodine ions. Examples of the iodine ion supply source include potassium iodide and sodium iodide, and potassium iodide is preferably used.

In the infusion container 1 of FIG. 1, it is preferable that the third chamber III partitioned from the first chamber I or the second chamber II is filled with the trace metal-containing solution. The third chamber III can be accommodated and used in the first chamber I or the second chamber II. As a storage method, for example, the third chamber III may be suspended in the liquid in the first chamber I or the second chamber II, but the end of the peripheral seal portion of the third chamber III is stored on the side (first It is preferable to hang it by sandwiching and sealing the periphery of the chamber I or the second chamber II). In this case, in order to facilitate sealing, the material of the chamber in which the trace metal-containing solution is accommodated is generally the same as the material of the innermost layer of the accommodating chamber.
In addition, the chamber containing the trace metal-containing solution in the above case is provided with an easy-open seal or a wall thickness of 100 μm or less so that it can be opened or broken by pressing from the outside of the chamber at the time of use. It is preferable to do this.

Examples of the trace metal include copper, iron, manganese, and zinc. Iron is preferably filled as a colloid and copper, manganese, and zinc are dissolved in water. However, manganese and zinc can also be used by mixing with an amino acid-containing solution or a sugar-containing solution.
In the trace metal-containing solution, examples of the copper supply source include copper sulfate and the like, and about 0.5 to 40 μmol / L, preferably about 1 to 20 μmol / L in a solution in which all the solutions are mixed. It is preferable to blend in.
Examples of the iron supply source include ferric chloride, ferric sulfate, and the like. In a mixed solution of all solutions, about 2 to 200 μmol / L, preferably about 5 to 100 μmol / L. It is preferable to mix.
Examples of the supply source of manganese include manganese chloride, manganese sulfate, and the like. In the mixed solution, all solutions are mixed so that the concentration is about 0 to 10 μmol / L, preferably about 0 to 5 μmol / L. preferable.
Examples of the zinc supply source include zinc chloride and zinc sulfate, and the mixture of all the solutions is about 2 to 300 μmol / L, preferably about 5 to 150 μmol / L. preferable.

  The trace metal-containing solution has a pH of about 3.5 to 7.5, preferably using an ordinary pH adjuster, for example, acids such as hydrochloric acid, acetic acid, lactic acid, malic acid, citric acid, and alkalis such as sodium hydroxide. It is preferable to adjust to about 4 to 6.5.

The sugar-containing solution, amino acid-containing solution or trace metal-containing solution described above may contain an electrolyte. Examples of such electrolytes include water-soluble salts of inorganic components such as sodium, potassium, magnesium, calcium, chlorine, and phosphorus, such as chloride, sulfate, acetate, gluconate, lactate, and glycerophosphate. Can be mentioned.
Examples of the sodium ion source include sodium chloride, sodium acetate, sodium citrate, sodium dihydrogen phosphate, disodium hydrogen phosphate, sodium sulfate, sodium lactate and the like. It is preferable to add 10 to 160 mEq / L, preferably about 20 to 80 mEq / L.
Examples of the potassium ion source include potassium chloride, potassium acetate, potassium citrate, potassium dihydrogen phosphate, dipotassium hydrogen phosphate, potassium sulfate, calcium lactate and the like. It is preferable to blend so as to be 5 to 80 mEq / L, preferably about 10 to 40 mEq / L.
Examples of the calcium ion source include calcium chloride, calcium gluconate, calcium pantothenate, calcium lactate, calcium acetate and the like, and about 1 to 40 mEq / L, preferably about 2 to 2 in a mixed solution. It is preferable to blend so as to be 20 mEq / L.

Examples of the magnesium ion supply source include magnesium sulfate, magnesium chloride, magnesium acetate, and the like. In the mixed solution, all the solutions are mixed so as to be about 1 to 40 mEq / L, preferably about 2 to 20 mEq / L. It is preferable to do this.
Examples of the phosphorus source include sodium dihydrogen phosphate, disodium hydrogen phosphate, potassium glycerophosphate, etc., and about 1 to 40 mmol / L, preferably about 2 to 20 mmol / L in a mixed solution of all the solutions. It is preferable to blend so that.
Examples of the chloro ion supply source include sodium chloride, potassium chloride, calcium chloride, magnesium chloride, and the like, which is about 10 to 160 mEq / L, preferably about 20 to 80 mEq / L in a mixed solution of all the solutions. It is preferable to blend as described above.

  Regarding calcium ions and phosphorus in the electrolyte, it is preferable to mix only one of them when filling the same chamber as the amino acid-containing solution. When filling the same chamber as the sugar-containing solution, both the calcium ion supply source and the phosphorus supply source may be filled.

  The pH of the solution when the amino acid-containing solution, sugar-containing solution, and trace metal-containing solution are mixed is preferably about 2 to 10, preferably about 4 to 7.

The present invention may further contain a fat-soluble vitamin solution in the fourth chamber IV as desired. Examples of such fat-soluble vitamins include vitamin A, vitamin D, and vitamin E, and vitamin K can also be added as necessary.
Examples of vitamin A include ester forms such as palmitic acid ester and acetic acid ester. Examples of vitamin D include vitamin D ₁ , vitamin D ₂ , vitamin D ₃ (cholecalciferol), and active forms thereof (hydroxy derivatives). Examples of vitamin E (tocopherol) include ester forms such as acetate ester and succinate ester. Examples of vitamin K (phytonadione) include derivatives such as phytonadione, menatetrenone, and menadione.

  These fat-soluble vitamins are prepared by mixing all the solutions, vitamin A is about 400-13000 IU / L, preferably about 800-6500 IU / L, vitamin D is about 0.5-20 μg / L, preferably About 1.0 to 10 μg / L, Vitamin E is about 1.0 to 40 mg / L, preferably about 2.5 to 20 mg / L, Vitamin K is about 0.2 to 8 mg / L, preferably about 0.5 It is preferable to blend ~ 4mg / L.

Further, the water-soluble vitamin may be accommodated in the same chamber as the first chamber, the second chamber, the third chamber, or the fourth chamber. Examples of such water-soluble vitamins include vitamin B ₁ , vitamin B ₂ , folic acid, biotin, vitamin C, vitamin ₁₂ , pantothenic acids, vitamin B ₆ , nicotinic acids and vitamin H.
Such vitamins may be derivatives, and specific examples of vitamin B ₁ include thiamine hydrochloride, prosultiamine, octothiamine and the like. Examples of vitamin B ₂ include phosphate esters, sodium salts thereof, flavin mononucleotides, flavin adenine dinucleotides, and the like. Examples of vitamin C include ascorbic acid and sodium ascorbate. Examples of pantothenic acids include the form of panthenol, which is a calcium salt or a reduced form, in addition to the free form. Examples of vitamin B ₆ include salt forms such as pyridoxine hydrochloride. Examples of nicotinic acids include nicotinic acid and nicotinic acid amide. The vitamin _{B 12,} for example, cyanocobalamin and the like.

The vitamin is preferably blended in the following blending ratio in a solution obtained by mixing all the solutions. Vitamin B ₁ about 0.4-60 mg / L, preferably about 0.8-30 mg / L, Vitamin B ₂ about 0.5-12 mg / L, preferably about 1.0-6.0 mg / L, Vitamin B ₆ About 0.5-16 mg / L, preferably about 1.0-8.0 mg / L, Vitamin B ₁₂ about 0.5-40 μg / L, preferably about 1.0-20 μg / L, About nicotinamide 5.0 to 160 mg / L, preferably about 10 to 80 mg / L, pantothenic acids about 1.5 to 60 mg / L, preferably about 3.0 to 30 mg / L, folic acid about 50 to 160 μg / L, preferably about 100-800 μg / L, vitamin C about 12.5-400 mg / L, preferably about 25-200 mg / L, biotin about 7.5-240 μg / L, preferably about 15-120 μg / L.

  When the nutritional infusion preparation of the present invention is administered to a patient, the outer bag is broken and the first chamber, the second chamber, and the third chamber, or the first chamber, the second chamber, the third chamber, and the fourth chamber are communicated. Mix the chemicals in each chamber.

[Example 1]
Glucose and an electrolyte solution were dissolved in distilled water for injection, and the pH was adjusted to 4.4 with acetic acid, followed by filtration to prepare a solution (A) having the composition shown in Table 1.
Further, each crystalline amino acid and electrolyte were dissolved in distilled water for injection, and the pH was adjusted to 6.5 with acetic acid, followed by filtration to prepare solutions (B) having the compositions shown in Tables 2 and 3. To the solution (B), sodium bisulfite was added as a stabilizer so as to have a concentration of 50 mg / L.
Separately, a predetermined amount of ferric chloride was added to an aqueous distilled solution of chondroitin sulfate for injection while alternately adding an aqueous distilled solution of ferric chloride for injection and an aqueous distilled solution of sodium hydroxide for injection. . After adding a predetermined amount of copper sulfate and manganese chloride to this solution, the pH is adjusted to 5.3 with sodium hydroxide or hydrochloric acid, the volume is adjusted with distilled water for injection, and the solution having the composition shown in Table 4 (C) was prepared. In addition, sodium chondroitin sulfate was added so as to have a concentration of 2.5 g / L.
A sachet formed from a polyethylene film having a thickness of 50 μm was filled with 2 mL of the solution (C) and welded. This sachet was previously sandwiched in a polyethylene container first chamber I as the third chamber III in FIG. Each of the first chamber I and the second chamber II was separately filled with 600 mL of the solution (A) and 300 mL of the solution (B) under nitrogen substitution, sealed, and then subjected to high-temperature steam sterilization according to a conventional method. I got an infusion. This was packaged in a light-shielding nylon multilayer bag together with an oxygen scavenger (Mitsubishi Gas Chemical Company, trade name Ageless). In the present embodiment, the fourth chamber IV shown in FIG. 1 is lacking.

[Example 2]
Glucose and an aqueous electrolyte solution were dissolved in distilled water for injection, and the pH was set to 4.4 with acetic acid to prepare a sugar electrolyte solution. Further, vitamin B ₁ (thiamine hydrochloride), vitamin B ₆ (pyridoxine hydrochloride), vitamin B ₁₂ (cyanocobalamin), panthenol and biotin are dissolved in distilled water for injection, mixed with the above-mentioned sugar electrolyte solution, and filtered. Then, a solution (A) having the composition shown in Table 1 was prepared.
Also, each crystalline amino acid, nicotinamide, folic acid and electrolyte were dissolved in distilled water for injection, adjusted to pH 6.0 with acetic acid, filtered, and solutions (B) having the compositions shown in Tables 2 and 3 Was prepared. To the solution (B), sodium bisulfite was added as a stabilizer so as to have a concentration of 50 mg / L.
Separately, vitamin A (retinol palmitate), vitamin D ₃ (cholecalciferol), vitamin E (tocopherol acetate) and vitamin K (phytonadione) were added to polysorbate 80 (concentration 10 g / L in solution (D)) and Solubilized in polysorbate 20 (concentration 2 g / L in solution (D)), dissolved in distilled water for injection, and further added vitamin B ₂ (riboflavin sodium phosphate) and vitamin C (ascorbic acid) After adjusting the pH to 6 with sodium, the solution (D) having the composition shown in Table 5 was prepared by filtration.
Separately, a solution (C) having the composition shown in Table 4 was prepared in the same manner as in Example 1.
Two sachets formed from a 50 μm thick polyethylene film were filled with 4 mL of the solution (C) and 4 mL of the solution (D), respectively, and welded. These sachets were sandwiched in the first chamber I made of polyethylene as in the third chamber III and the fourth chamber IV shown in FIG. The first chamber I and the second chamber II were separately filled with 600 mL of the solution (A) and 300 mL of the solution (B) under nitrogen substitution, respectively, sealed, and then autoclaved according to a conventional method. Got. This was packaged in a light-shielding nylon multilayer bag together with an oxygen scavenger (Mitsubishi Gas Chemical Company, trade name Ageless).

[Test Example 1] Stability test An infusion preparation containing copper ions and iodine ions in the same chamber and an infusion preparation contained in separate chambers were prepared and stored at 60 ° C for 2 to 4 weeks. The change in stability was compared.

(1) When copper ion and iodine ion are placed in the same chamber Except that potassium iodide is added to the solution (C), an amino acid-containing solution, a glucose-containing solution, and a copper ion-containing trace metal are the same as in Example 1. The solution was adjusted to produce an infusion preparation. The infusion preparation was stored at 60 ° C. for 2 weeks, and the change in trace metal stability at this time is shown in Table 6.

(2) When copper ions and iodine ions are put in separate chambers Amino acid-containing solution, glucose-containing solution, and copper ion-containing trace metal are the same as in Example 1 except that potassium iodide is added to the solution (B). The solution was adjusted to produce an infusion preparation. The infusion preparation was stored at 60 ° C. for 2 to 4 weeks, and the change in trace metal stability at this time is shown in Table 7.

(3) When copper ions and iodine ions are put in separate chambers In the same manner as in Example 1, an amino acid-containing solution, a glucose-containing solution, and a copper ion-containing trace metal solution were prepared to prepare an infusion preparation. The infusion preparation was stored at 60 ° C. for 2 to 4 weeks, and changes in trace metal stability at this time are shown in Table 8.

  From Tables 6 to 8, when copper ions and iodine ions were accommodated in the same room, crystals were observed after 2 weeks, and the content of ions in the infusion preparation decreased. In addition, when the copper ions and iodine ions were accommodated in separate chambers, the decrease in the ion content was less than when they were accommodated in the same chamber.

  The infusion container of the present invention can provide an infusion preparation that does not cause precipitation under conditions where oxygen is not present in the outer bag by filling the trace metal element and iodine ion in separate containers. In addition, by using the infusion container of the present invention, it is possible to eliminate the inconvenience of the mixing operation at the time of administration of the infusion preparation, the problem of bacterial contamination at the time of mixing, and to easily and aseptically mix each infusion preparation. it can.

It is a top view of the Example of the infusion container which concerns on this invention.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Infusion container 2 Outer bag 5 Communication possible part 9 Chemical solution outlet 10 Oxygen absorber I First chamber of infusion container II Second chamber of infusion container III Third chamber of infusion container IV Fourth chamber of infusion container

Claims (7)

  An infusion container that is air permeable is enclosed in a gas barrier outer bag substantially in the absence of oxygen, and is composed of a plurality of chambers partitioned by a partition means that can communicate with the infusion container. The first chamber contains an amino acid-containing solution, the second chamber contains a sugar-containing solution, and either the amino acid-containing solution or the sugar-containing solution contains copper, and the other contains iodine ions. A nutritional infusion preparation containing copper and iodine ions.   2. The oxygen-free condition is achieved by encapsulating an oxygen scavenger in the outer bag and / or is achieved by introducing an inert gas into the outer bag. The nutritional infusion preparation described.   The nutritional infusion preparation according to claim 1 or 2, wherein the sugar is glucose.   The pH of the solution accommodated in the first chamber is 5 to 8, and the pH of the solution accommodated in the second chamber is 2.5 to 5. The nutritional infusion preparation described.   The nutritional infusion preparation according to claim 4, wherein the solution contained in the first chamber or the second chamber contains at least one of calcium ions and phosphorus as an electrolyte.   The pH of the solution which mixed the solution accommodated in the 1st chamber and the solution accommodated in the 2nd chamber is 4-7, The nutrition infusion preparation in any one of Claims 1-5 characterized by the above-mentioned. .   When the solution stored in the first chamber and the solution stored in the second chamber are mixed, the blending amount of sugar, amino acid, copper and iodine is 50 to 400 g / L of glucose, L-leucine 0.8 to 10.0 g / L, L-isoleucine 0.4-7.0 g / L, L-valine 0.3-8.0 g / L, L-lysine 0.5-7.0 g / L, L-threonine 3 to 4.0 g / L, L-tryptophan 0.08 to 1.5 g / L, L-methionine 0.2 to 4.0 g / L, L-phenylalanine 0.4 to 6.0 g / L, L-cysteine 0.03-1.0 g / L, L-tyrosine 0.02-1.0 g / L, L-arginine 0.5-7.0 g / L, L-histidine 0.3-4.0 g / L, L -Alanine 0.4-7.0 g / L, L-proline 0.2-5.0 g / L, L-serine 0.2- 0.0 g / L, glycine 0.3-6.0 g / L, L-aspartic acid 0.03-2.0 g / L, L-glutamic acid 0-3.0 g / L, copper 1-20 μmol / L, iodine 0 The nutritional infusion preparation according to any one of claims 1 to 6, which is 2 to 5 µmol / L.

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