JP2008132317A - Dissolved oxygen-reducing liquid agent - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a dissolved oxygen reducing liquid agent for reducing the amount of dissolved oxygen, hardly deteriorated by oxidation and excellent in stability with the elapse of time. <P>SOLUTION: The dissolved oxygen reducing liquid agent is housed in a chemical liquid container comprising a plastic of which the oxygen permeability under the condition of a temperature of 25°C and humidity RH of 60% within 12 hr after steam or hot water sterilization treatment is 200 cm<SP>3</SP>/m<SP>2</SP>*24h*atm or above and the oxygen permeability under the condition of a temperature of 25°C and humidity RH of 60% within 12 hr when the oxygen permeability is in a steady state, is 100 cm<SP>3</SP>/m<SP>2</SP>*24h*atm or below. After the container is hermetically sealed and subjected to steam or hot water sterilization treatment, the chemical liquid container is preserved under an environment equipped with a deoxidation means to adjust the concentration of dissolved oxygen of the liquid agent when the oxygen permeability of the plastic reaches the steady state becomes 2 ppm or below. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention relates to a liquid agent in which the amount of dissolved oxygen is reduced.

  Nutritional supplementation for patients who are difficult to ingest is usually achieved by intravenous administration of an infusion containing sugars, amino acids, vitamins, electrolytes, fat emulsions, trace metal elements, and the like. Amino acids, vitamins, and the like contained in this infusion solution are easily oxidized components. In addition, a polyolefin-based resin known as a material for forming an infusion container is a material that easily transmits oxygen. For this reason, even when the infusion solution is stored, oxidation of easily oxidizable components such as amino acids and vitamins may proceed.

On the other hand, in order to stably store an infusion solution containing an easily oxidizable component, Patent Document 1 discloses that an infusion solution comprising an amino acid-containing aqueous solution is filled in a gas-permeable primary medical container and the medical There has been proposed an infusion preparation package characterized in that an infusion preparation filled in a primary container is housed in a secondary packaging container that does not substantially transmit oxygen together with an oxygen scavenger. Further, in Patent Document 2, an inorganic compound film is formed on at least one surface of a plastic film, the oxygen permeability is 1 cc / m ² · 24 hr · atm or less, the moisture permeability is 1 g / m ² · 24 hr · atm or less, and the light is transmitted. A film for a chemical container having a rate of 80% or more and a hue b value of 5 or less has been proposed.

Further, Patent Document 3 states that “it consists of a resin container having at least a flexible wall in which a discharge port is formed. The container wall is divided into an inner layer and an outer layer with an intermediate layer of polyvinyl alcohol as a boundary. The inner layer is a polyolefin layer having a thickness in the range of 50 to 800 μm, and the moisture permeability So (g / m ² 24 hrs: temperature 40 ° C., 90% RH) of the outer layer is Si (g / m 2). ² 24 hrs: temperature of 40 ° C., 90% RH), the infusion container having a gas barrier property, characterized in that the outer layer is provided in a package in the presence of a desiccant. The package is listed. According to this infusion container, water vapor in the outer layer is quickly released to the outside. For this reason, after the autoclave sterilization treatment, water vapor between the outer layer and the polyvinyl alcohol layer adjacent thereto can be reduced by an external desiccant, and as a result, the gas barrier property of the polyvinyl alcohol layer can be almost completely recovered within 24 hours. Further, water vapor that has permeated the innermost layer from the inside of the infusion container and reached the polyvinyl alcohol layer passes through the outer layer and quickly escapes from the polyvinyl alcohol layer to the outside, so that the gas barrier property of the polyvinyl alcohol layer does not deteriorate ( Paragraph [0007]).
JP-A 63-275346 Japanese Patent Laid-Open No. 11-285520 Japanese Patent Laid-Open No. 10-80464

  However, as in the case of the infusion solution package described in Patent Document 1, when the primary container has oxygen permeability, the primary container is left in the primary container after the secondary container is opened. It becomes impossible to prevent oxidative deterioration of the infusion solution. In addition, for example, when another drug is mixedly injected into the primary container, if bacterial contamination occurs by mistake, there is a possibility that the growth of the bacteria may be accelerated by permeation of oxygen from the outside of the primary container.

  The film for chemical containers described in Patent Document 2 is a film having excellent oxygen barrier properties. For this reason, the chemical container is sealed in a state where oxygen is contained in the head space or the content of dissolved oxygen is large, thereby preventing oxidative deterioration of the content and growth of aerobic bacteria. become unable. Note that the process of reducing the dissolved oxygen in the chemical solution before sealing the container and the process of replacing the head space with an inert gas such as nitrogen are time consuming and have the disadvantage of increasing costs. Furthermore, since the above-mentioned film for chemical containers is not sufficiently flexible, there is a possibility that pinholes are generated in the film due to, for example, an impact during transportation of the chemical container.

  According to the infusion container of patent document 3, as above-mentioned, the water vapor | steam of a polyvinyl alcohol layer can be reduced with the external desiccant, and the gas barrier property can be maintained. However, oxygen remaining in the infusion container after the autoclave sterilization treatment is not taken into consideration at all, and prevents oxidative deterioration of the contents due to oxygen remaining in the infusion container, proliferation of aerobic bacteria, and the like. I can't.

  An object of the present invention is to provide a liquid agent in which the amount of dissolved oxygen is reduced, alteration due to oxidation hardly occurs, and the stability over time is excellent.

In order to achieve the above object, the dissolved oxygen reducing liquid agent of the present invention is:
When the oxygen permeability at a temperature of 25 ° C. and a humidity of 60% RH is 200 cm ³ / m ² · 24 h · atm or more within 12 hours after steam sterilization or hot water sterilization and the oxygen permeability is in a steady state Is contained and sealed in a chemical container made of plastic having an oxygen permeability of 100 cm ³ / m ² · 24 h · atm or less at a temperature of 25 ° C. and a humidity of 60% RH,
The steam sterilization process or the hot water sterilization process has been performed,
The dissolved oxygen concentration is 2 ppm or less when the oxygen permeability of the plastic reaches a steady state after the steam sterilization treatment or the hot water sterilization treatment.

In the above-mentioned dissolved oxygen reducing liquid, the chemical container for containing and sealing the liquid has an oxygen permeability (temperature of 25 ° C., humidity of 60% RH) within 12 hours after steam sterilization or hot water sterilization. It shows a high value of 200 cm ³ / m ² · 24 h · atm or higher, and in a steady state, the oxygen permeability (temperature 25 ° C., humidity 60% RH) is a low value of 100 cm ³ / m ² · 24 h · atm or less. Made of plastic shown. For this reason, the high oxygen permeability of the plastic is between the time when the oxygen permeability of the plastic reaches a steady state after the chemical container containing and sealing the liquid is subjected to the steam sterilization treatment or the hot water sterilization treatment. By using this, it is possible to perform a process for reducing oxygen dissolved in the liquid agent and oxygen remaining in the chemical liquid container from the outside of the chemical liquid container. In addition, after the oxygen permeability of the plastic reaches a steady state, an increase in the dissolved oxygen amount of the liquid agent can be suppressed by utilizing the fact that the oxygen permeability of the plastic becomes extremely low. Further, according to the dissolved oxygen reducing liquid agent, after the steam sterilization treatment or the hot water sterilization treatment, the dissolved oxygen amount of the liquid agent is reduced to 2 ppm or less, or the dissolved oxygen amount of the liquid agent is reduced to 2 ppm or less in advance. By setting, the dissolved oxygen amount of the liquid agent can be maintained at a very low value over a long period of time, and deterioration due to oxidation of the liquid agent can be prevented.

It is preferable that the dissolved oxygen reduction liquid agent of this invention is preserve | saved in the environment which has a deoxygenation means after the said steam sterilization process or the said hot-water sterilization process.
In this case, after steam sterilization treatment or hot water sterilization treatment, that is, when the oxygen permeability of the plastic forming the chemical solution container is high, dissolved oxygen in the liquid agent or oxygen remaining in the chemical solution container Can be removed from the outside of the chemical solution container by the deoxygenating means. Furthermore, by storing the chemical container in an environment having a deoxygenating means, the oxygen permeability of the plastic forming the chemical container is shifted to a steady state while preventing the inflow of oxygen into the chemical container. Can do.

The dissolved oxygen reducing solution of the present invention is preferably an easily oxidizable solution, and more specifically, for example, selected from the group consisting of an amino acid-containing solution, a vitamin-containing sugar solution, and a fat-soluble vitamin-containing solution. It is suitable that it is at least one kind.
In the dissolved oxygen reducing liquid agent of the present invention, the amino acid-containing liquid is L-leucine, L-isoleucine, L-valine, L-lysine, L-threonine, L-tryptophan, L-methionine, L-cysteine, L- At least one amino acid selected from the group consisting of phenylalanine, L-tyrosine, L-arginine, L-histidine, L-alanine, L-proline, L-serine, L-glycine, L-aspartic acid, and L-glutamic acid It is preferable to contain.

In the solution for reducing dissolved oxygen of the present invention, the vitamin-containing sugar solution is composed of sugar, vitamin B ₁ , vitamin B ₂ , vitamin B ₆ , vitamin B ₁₂ , vitamin C, folic acid, niacin, biotin, and pantothenic acids. It is preferable to contain a water-soluble vitamin selected from the group consisting of
In the solution for reducing dissolved oxygen of the present invention, the fat-soluble vitamin-containing solution may contain at least one fat-soluble vitamin selected from the group consisting of vitamin A, vitamin D, vitamin E, and vitamin K. Is preferred.

  According to the dissolved oxygen reducing liquid agent of the present invention, the dissolved oxygen amount of the liquid agent can be maintained at an extremely low value. Therefore, it is possible to provide a liquid agent that suppresses deterioration due to oxidation of the liquid agent over a long period of time and has excellent temporal stability.

The dissolved oxygen reducing liquid agent of the present invention is
When the oxygen permeability at a temperature of 25 ° C. and a humidity of 60% RH is 200 cm ³ / m ² · 24 h · atm or more within 12 hours after steam sterilization or hot water sterilization and the oxygen permeability is in a steady state Is contained and sealed in a chemical container made of plastic having an oxygen permeability of 100 cm ³ / m ² · 24 h · atm or less at a temperature of 25 ° C. and a humidity of 60% RH,
The steam sterilization treatment or the hot water sterilization treatment is performed, and
The dissolved oxygen concentration is 2 ppm or less when the oxygen permeability of the plastic reaches a steady state after the steam sterilization treatment or the hot water sterilization treatment.

  In the dissolved oxygen-reducing liquid agent of the present invention, various liquid agents can be mentioned as the liquid agent accommodated and sealed in the chemical liquid container, and in particular, a liquid agent containing a drug that easily oxidizes (an easily oxidizable drug) is suitable. . Since the chemical container that contains the dissolved oxygen reducing liquid agent is a container that can highly suppress the invasion of oxygen from the outside, even an oxidizable drug can be stably stored and stored over time. it can.

The easily oxidizable drugs are various drugs containing components that are easily oxidized. Examples of the components that are easily oxidized include amino acids and vitamins.
Examples of amino acids include so-called essential amino acids, other amino acids, salts of these amino acids, esters, N-acyl compounds, and the like. Specifically, for example, L-leucine, L-isoleucine, L-valine, L-lysine, L-threonine, L-tryptophan, L-methionine, L-cysteine, L-phenylalanine, L-tyrosine, L-arginine , Amino acids such as L-histidine, L-alanine, L-proline, L-serine, L-glycine, L-aspartic acid and L-glutamic acid. These amino acids are, for example, inorganic acid salts such as L-arginine hydrochloride, L-cysteine hydrochloride, L-glutamine hydrochloride, L-histidine hydrochloride, L-lysine hydrochloride, such as L-lysine acetate, L -Organic acid salts such as lysine malate, for example, ester forms such as L-tyrosin methyl ester, L-methionone methyl ester, L-methionine ethyl ester, such as N-acetyl-L-cysteine, N-acetyl- N-substituted products such as L-tryptophan and N-acetyl-L-proline, such as L-tyrosyl-L-tyrosine, L-alanyl-L-tyrosine, L-arginyl-L-tyrosine, L-tyrosyl-L- It may be in the form of dipeptides such as arginine. Moreover, these amino acids may be contained independently and 2 or more types may be mixed and contained.

As vitamins, various vitamins can be mentioned. Specifically, for example, fat-soluble vitamins such as vitamin A, vitamin D, vitamin E, and vitamin K, and vitamin B ₁ , vitamin B ₂ , vitamin B ₆ , vitamin B ₁₂ , vitamin C, folic acid, niacin ( Nicotinic acids), biotin (vitamin H), and water-soluble vitamins such as pantothenic acids.

Examples of vitamin A include retinol, retinal, retinoic acid, and retinol esters (for example, retinol palmitate, retinol acetate, etc.), and preferably retinol palmitate. Examples of vitamin D include vitamin D ₁ , vitamin D ₂ (ergocalciferol), vitamin D ₃ (cholecalciferol), and active forms thereof (hydroxy derivatives), preferably cholecalciferol. . Examples of vitamin E include α-tocopherol, β-tocopherol, γ-tocopherol, δ-tocopherol, α-tocotrienol, β-tocotrienol, γ-tocotrienol, δ-tocotrienol, and esters thereof (for example, acetate ester, succinic acid). Ester, etc.), preferably tocopherol acetate. Examples of vitamin K include vitamin K ₁ (phylloquinone; generic name phytonadione), vitamin K ₂ (menaquinone), vitamin K ₃ (menadione), and preferably phytonadione.

Examples of vitamin B ₁ include thiamine and thiamine derivatives (eg, thiamine hydrochloride, prosultiamine, octothiamine, etc.), and preferably thiamine hydrochloride. Examples of vitamin B ₂ include riboflavin, riboflavin phosphate (phosphate ester of riboflavin) and its sodium salt, flavin mononucleotide, flavin adenine dinucleotide, and preferably riboflavin phosphate. The vitamin B _6, for example, pyridoxal, pyridoxine, pyridoxamine, such as pyridoxine hydrochloride and the like, preferably, be mentioned pyridoxine hydrochloride. The vitamin _{B 12,} for example, cyanocobalamin and the like. Examples of vitamin C include ascorbic acid and sodium ascorbate, and ascorbic acid is preferable. Examples of niacin include nicotinic acid and nicotinamide. Examples of pantothenic acids include pantothenic acid, its calcium salt, panthenol which is a reduced form, and preferably panthenol. Examples of vitamin P include flavonoids.

The above vitamins may be contained alone or in combination of two or more. Moreover, the said water-soluble vitamin may be mix | blended with the liquid agent containing an amino acid, or the liquid agent containing saccharides individually or in mixture of 2 or more types.
Specific examples of the liquid agent (easily oxidizable liquid agent) containing the oxidizable drug include amino acid-containing liquids, sugar liquids containing vitamins (vitamin-containing sugar liquids), fat-soluble vitamin-containing liquids, and the like. It is done.

As an amino acid containing liquid, the liquid agent which contains the amino acid of the said illustration individually or in mixture of 2 or more types is mentioned. In addition, the amino acid-containing liquid may contain, for example, an electrolyte, a water-soluble vitamin, and the like as optional components.
Examples of the water-soluble vitamins contained in the amino acid-containing liquid include the water-soluble vitamins exemplified above, and among them, nicotinamide and folic acid are preferable. These water-soluble vitamins are contained alone or in combination of two or more in the amino acid-containing solution. In addition, these water-soluble vitamins exist stably with each other in the presence of the amino acid.

Examples of the electrolyte contained in the amino acid-containing liquid include sodium ions (Na ⁺ ), magnesium ions (Mg ²⁺ ), potassium ions (K ⁺ ), calcium ions (Ca ²⁺ ), chloride ions (Cl ⁻ ), and iodine. Chloride ion (I ⁻ ), phosphate ion (specifically, hydrogen phosphate ion (HPO ₄ ²⁻ ) or dihydrogen phosphate ion (H ₂ PO ₄ ⁻ )), glycerophosphate ion (C ₃ H ₇ O ₃₎ Examples thereof include water-soluble salts that supply ions such as PO ₃ ²⁻ ). These electrolytes are contained alone or in admixture of two or more. Moreover, these electrolytes exist stably with each other in the coexistence with the amino acid.

  Examples of the water-soluble salt as a sodium ion source include sodium chloride, sodium acetate, sodium citrate, sodium lactate, sodium dihydrogen phosphate, disodium hydrogen phosphate, sodium glycerophosphate, sodium sulfate and the like. Examples of the water-soluble salt as a magnesium ion supply source include magnesium sulfate, magnesium chloride, magnesium acetate, and preferably magnesium sulfate. Examples of the water-soluble salt as a potassium ion source include potassium chloride, potassium iodide, potassium acetate, potassium citrate, potassium dihydrogen phosphate, dipotassium hydrogen phosphate, potassium glycerophosphate, potassium sulfate, potassium lactate and the like. Preferably, potassium acetate is mentioned. Examples of the water-soluble salt as a calcium ion supply source include calcium chloride, calcium gluconate, calcium pantothenate, calcium lactate, calcium acetate, and preferably calcium chloride.

  Examples of the water-soluble salt as a chloride ion supply source include sodium chloride, potassium chloride, calcium chloride and the like, and preferably calcium chloride. Examples of the water-soluble salt as an iodide ion supply source include sodium iodide, magnesium iodide, potassium iodide, calcium iodide and the like. Examples of the water-soluble salt as a phosphate ion source include sodium dihydrogen phosphate, disodium hydrogen phosphate, magnesium monohydrogen phosphate, magnesium dihydrogen phosphate, potassium dihydrogen phosphate, and dipotassium hydrogen phosphate. , Calcium monohydrogen phosphate, calcium dihydrogen phosphate and the like. Examples of the water-soluble salt as a glycerophosphate ion supply source include sodium glycerophosphate, potassium glycerophosphate, calcium glycerophosphate and the like.

  In addition, it is preferable that the water-soluble salt containing a calcium ion and the water-soluble salt containing a phosphate ion do not coexist as an electrolyte in an amino acid-containing liquid. In applications where both calcium ions and phosphate ions are administered simultaneously, a multi-chamber container having two or more storage parts is used as a chemical solution container, and a water-soluble salt containing calcium ions and a water-soluble substance containing phosphate ions are used. It is preferable that at least one of the salt and the salt is accommodated in an accommodating portion in which the amino acid-containing liquid is not accommodated.

  The amino acid-containing liquid may further contain, for example, an antioxidant and a pH adjuster. Examples of the antioxidant include sodium bisulfite. Examples of the pH adjuster include acids such as hydrochloric acid, acetic acid, lactic acid, malic acid, succinic acid, and citric acid, and alkalis such as sodium hydroxide and potassium hydroxide. You may mix | blend the acid and alkali of these pH adjusters as a water-soluble salt which is an ion supply source of electrolyte.

The pH of the amino acid-containing liquid is adjusted to be preferably 2.5 to 10, more preferably 5 to 8, for example, using a pH adjuster or the like as appropriate.
When an amino acid-containing liquid is stored in a mixture with a sugar liquid, the stability over time is impaired. Therefore, in applications in which an amino acid-containing solution and a sugar solution are administered simultaneously, for example, a multi-chamber container having two or more storage units is used as a chemical solution container, and the amino acid-containing solution and the sugar solution are separated and stored. To do.

Examples of the vitamins-containing sugar solution include liquids containing saccharides and water-soluble vitamins.
The saccharides contained in the vitamin-containing sugar solution include those commonly used in various infusion solutions, and are not particularly limited, but examples thereof include monosaccharides such as glucose, fructose, and galactose, and two sugars such as maltose, lactose, and sucrose. Examples thereof include saccharides, among which glucose is preferable. These saccharides are used alone or in admixture of two or more.

Examples of the water-soluble vitamins contained in the vitamin-containing sugar solution include the water-soluble vitamins exemplified above, and these water-soluble vitamins are contained alone or in combination of two or more. These water-soluble vitamins exist stably in the presence of the sugar solution.
Moreover, the vitamin containing sugar liquid may contain electrolyte etc. as arbitrary components.
Examples of electrolytes contained in vitamin-containing sugar solutions include water-soluble ions that supply ions such as sodium ions, magnesium ions, potassium ions, calcium ions, chloride ions, iodide ions, phosphate ions, and glycerophosphate ions. Salt. These electrolytes are contained alone or in admixture of two or more. Moreover, these electrolytes exist stably in the presence of the sugar solution.

  Examples of the water-soluble salt as a sodium ion supply source include the same ones as those contained in the amino acid-containing liquid, and preferably sodium chloride and sodium lactate. Examples of the water-soluble salt as the magnesium ion supply source include the same ones as those contained in the amino acid-containing liquid. Examples of the water-soluble salt as the potassium ion source include the same ones as those contained in the amino acid-containing liquid, and preferably potassium chloride, potassium iodide, and potassium dihydrogen phosphate. Examples of the water-soluble salt as the calcium ion supply source include the same as those contained in the amino acid-containing liquid.

  Examples of the water-soluble salt as a chloride ion supply source include the same ones as those contained in the amino acid-containing liquid, preferably sodium chloride and potassium chloride. Examples of the water-soluble salt as the iodide ion supply source include the same ones as those contained in the amino acid-containing liquid, and preferably potassium iodide. Examples of the water-soluble salt as the phosphate ion supply source include the same ones as those contained in the amino acid-containing solution, and preferably potassium dihydrogen phosphate. Examples of the water-soluble salt as a glycerophosphate ion source include the same ones contained in the amino acid-containing liquid.

The vitamin-containing sugar solution may further contain, for example, a pH adjuster, sugar alcohol, glycerin and the like.
Examples of the pH adjuster include the same ones as described above, and the acid and alkali of the pH adjuster may be blended as a water-soluble salt that is an ion source of the electrolyte.
Examples of the sugar alcohol include sorbitol, xylitol, maltitol, palatinit, lactitol, erythritol and the like.

The pH of the vitamin-containing sugar solution is adjusted to be preferably 2 to 6, more preferably 2.5 to 5, for example, using a pH adjuster as appropriate.
In the above description, the vitamin-containing sugar solution is exemplified as the easily oxidizable solution. However, saccharides are not necessarily mixed with vitamins. For example, liquids containing only saccharides, saccharides and electrolytes, and the like. It can also be supplied as a liquid preparation containing

Moreover, when the liquid agent (sugar solution) containing saccharides is mixed with an amino acid-containing solution and stored, the stability over time is impaired. Therefore, in applications in which a sugar solution and an amino acid-containing solution are administered simultaneously, for example, a multi-chamber container having two or more storage units is used as a chemical solution container, and the sugar solution and the amino acid-containing solution are separated and stored. To do.
Examples of the fat-soluble vitamin-containing liquid include liquid agents containing the above-described fat-soluble vitamins alone or in admixture of two or more. Furthermore, the fat-soluble vitamin-containing solution may contain vitamin B _2.

The fat-soluble vitamin-containing liquid may contain, as an optional component, for example, a surfactant for solubilizing the fat-soluble vitamin in an aqueous medium. Moreover, when fat-soluble vitamin is contained in an aqueous medium with the said surfactant, it may contain the water-soluble vitamin further as needed.
Examples of the surfactant include sorbitan fatty acid ester (specifically, polysorbate) which is a nonionic surfactant.

Examples of water-soluble vitamins include water-soluble vitamins similar to those described above.
Fat-soluble vitamins generally have poor dispersibility in amino acid-containing liquids and sugar liquids, and there is a risk that stability over time may be impaired when stored in a mixture with amino acid-containing liquids or sugar liquids. is there. Therefore, in a use in which a vitamin-containing liquid containing a fat-soluble vitamin and an amino acid-containing liquid or a sugar liquid are administered simultaneously, for example, a multi-chamber container having two or more storage units is used as a chemical liquid container. The containing liquid and the amino acid-containing liquid or sugar liquid are separated and stored.

As a preferred embodiment of the dissolved oxygen reducing liquid agent of the present invention, an amino acid-containing liquid, a vitamin-containing sugar liquid, and a fat-soluble vitamin-containing liquid are separately stored in a multi-chamber container having three or more storage parts. An embodiment is mentioned.
In such an embodiment, the contents of amino acids, saccharides, vitamins and electrolytes are not particularly limited, but in the whole solution, that is, in a state where the drugs in all the containers are mixed and actually used for intravenous administration or the like. The following range is preferable. In addition, among the values shown below, the amino acid content is a value converted with a free form of amino acid.

Amino acid L-leucine: 0.4 to 20.0 g / L, preferably 0.8 to 10.0 g / L.
L-isoleucine: 0.2 to 14.0 g / L, preferably 0.4 to 7.0 g / L.
L-valine: 0.1 to 16.0 g / L, preferably 0.3 to 8.0 g / L.
L-lysine: 0.2 to 14.0 g / L, preferably 0.5 to 7.0 g / L.
L-threonine: 0.1 to 8.0 g / L, preferably 0.3 to 4.0 g / L.
L-tryptophan: 0.04 to 3.0 g / L, preferably 0.08 to 1.5 g / L.
L-methionine: 0.1 to 8.0 g / L, preferably 0.2 to 4.0 g / L.
L-cysteine: 0.01 to 2.0 g / L, preferably 0.03 to 1.0 g / L.
L-phenylalanine: 0.2-12.0 g / L, preferably 0.4-6.0 g / L.
L-tyrosine: 0.01-2 g / L, preferably 0.02-1.0 g / L.
L-arginine: 0.2 to 14.0 g / L, preferably 0.5 to 7.0 g / L.
L-histidine: 0.1 to 8.0 g / L, preferably 0.3 to 4.0 g / L.
L-alanine: 0.2-14.0 g / L, preferably 0.4-7.0 g / L.
L-proline: 0.1 to 10.0 g / L, preferably 0.2 to 5.0 g / L.
L-serine: 0.1-6.0 g / L, preferably 0.2-3.0 g / L.
L-glycine: 0.1 to 12.0 g / L, preferably 0.3 to 6.0 g /
L-aspartic acid: 0.01 to 4.0 g / L, preferably 0.03 to 2.0 g / L.
L-glutamic acid: 0 to 6.0 g / L, preferably 0.1 to 3.0 g / L.

Sugar glucose: 20 to 800 g / L, preferably 50 to 400 g / L.
Vitamins Vitamin A: 400-6500 IU / L, preferably 800-6500 IU / L, more preferably about 800-4000 IU / L.
Vitamin D: 0.5-10.0 μg / L, preferably 1.0-10.0 μg / L, more preferably 1.0-6.0 μg / L as cholecalciphenol.
Vitamin E: As tocophenol acetate, 1.0 to 20.0 mg / L, preferably 2.5 to 20.0 mg / L, more preferably 2.5 to 12.0 mg / L.
Vitamin K: 0.2 to 4.0 mg / L as phytonadione, preferably 0.5 to 4.0 mg / L, more preferably 0.5 to 2.5 mg / L.
Vitamin B ₁ : 0.4-30.0 mg / L as thiamine hydrochloride, preferably 0.8-30.0 mg / L, more preferably 1.0-5.0 mg / L.
Vitamin B ₂ : As riboflavin, 0.5 to 6.0 mg / L, preferably 1.0 to 6.0 mg / L, more preferably 1.0 to 4.0 mg / L.
Vitamin _{B 6:} as pyridoxine hydrochloride, 0.5~8.0mg / L, preferably, 1.0~8.0mg / L, more preferably, 1.0 to 5.0 / L.
Vitamin B ₁₂ : 0.5 to 50.0 μg / L, preferably 1.0 to 20.0 μg / L, more preferably 1.0 to 10.0 μg / L as cyanocobalamin.
Nicotinic acids: As nicotinic acid amide, 5.0 to 80.0 mg / L, preferably 10.0 to 80.0 mg / L, more preferably 10.0 to 50.0 mg / L.
Pantothenic acids: 1.5 to 35.0 mg / L, preferably 3.0 to 30.0 mg / L as pantothenic acid.
Folic acid: 50 to 800 μg / L, preferably 100 to 800 μg / L, more preferably 100 to 120 μg / L.
Vitamin C: Ascorbic acid, 12 to 200 mg / L, preferably 25 to 200 mg / L, more preferably 25 to 120 mg / L.
Biotin: 5-120 μg / L, preferably 15-120 μg / L, more preferably 15-70 μg / L.

Electrolyte sodium ion: 10 to 160 mEq / L, preferably 20 to 80 mEq / L.
Magnesium ion: 1 to 40 mEq / L, preferably 2 to 20 mEq / L.
Potassium ion: 5 to 80 mEq / L, preferably 10 to 40 mEq / L.
Calcium ions: 1 to 40 mEq / L, preferably 2 to 20 mEq / L.
Chloride ion: 10 to 160 mEq / L, preferably 20 to 80 mEq / L.
Iodide ion: 0 to 5 mEq / L, preferably 0.2 to 5 mEq / L.
Phosphate ion: 1 to 40 mmol / L, preferably 2 to 20 mmol / L.

In the present invention, the fat emulsion can be blended with the liquid as necessary, or can be contained in the chemical liquid container together with the liquid.
Examples of the fat emulsion include various known fat emulsions. Moreover, these fat emulsions may be contained alone or in combination of two or more.
Examples of fats and oils that form fat emulsions include those commonly used in fat emulsions, such as soybean oil, cottonseed oil, safflower oil, corn oil, coconut oil, perilla oil, and sesame oil. Examples include vegetable oils such as fish oil such as cod liver oil. These fats and oils may be used alone or in combination of two or more. Moreover, as an emulsifier which forms a fat emulsion, what is conventionally used for pharmaceutical preparations, such as a fat emulsion, is mentioned, Specifically, an egg yolk phospholipid, soybean phospholipid, etc. are mentioned, for example. These emulsifiers may be used alone or in combination of two or more.

The chemical container for containing and sealing the dissolved oxygen reducing liquid agent has an oxygen permeability of 200 cm ³ / m ² · 24 h at a temperature of 25 ° C. and a humidity of 60% RH within 12 hours after steam sterilization or hot water sterilization. It is made of a plastic having an oxygen permeability of 100 cm ³ / m ² · 24 h · atm or less at a temperature of 25 ° C. and a humidity of 60% RH when the oxygen permeability is in a steady state. .

Although the said chemical | medical solution container is not limited to this, For example, the container which has the flexibility or the softness | flexibility which can be deform | transformed according to the accommodation amount of a liquid agent so that a liquid agent can be accommodated in the state which reduced the volume of the head space as much as possible. It is preferable that
For the plastic forming the chemical solution container, the oxygen permeability at a temperature of 25 ° C. and a humidity of 60% RH within 12 hours after the steam sterilization treatment or hot water sterilization treatment was 200 cm ³ / m ² · 24 h · atm or more. Preferably, it is 500 cm ³ / m ² · 24 h · atm or more, and more preferably 700 cm ³ / m ² · 24 h · atm or more.

If the oxygen permeability at a temperature of 25 ° C. and a humidity of 60% RH within 12 hours after steam sterilization or hot water sterilization is below the above range, dissolved oxygen or It becomes difficult to remove oxygen contained in the head space of the chemical solution container from the chemical solution container, and the effect of suppressing oxidation of the liquid agent is reduced. The upper limit of the oxygen permeability after the steam sterilization treatment or the hot water sterilization treatment is not particularly limited, but is generally about 1000 cm ³ / m ² · 24 h · atm due to the properties of the plastic used for forming the chemical solution container. .

  The conditions for the steam sterilization treatment are, for example, a treatment temperature of 100 to 121 ° C., a treatment atmosphere is a steam saturated state, a treatment time is 10 to 60 minutes, and a treatment pressure is normal or atmospheric pressure. Under pressure of 4000 hPa or less. The conditions for the hot water sterilization treatment are, for example, that the atmospheric pressure during the treatment is normal pressure or pressurization, the hot water temperature is 100 to 120 ° C., and the treatment time is 10 to 60 minutes.

For the plastic forming the chemical container, the oxygen permeability at a temperature of 25 ° C. and a humidity of 60% RH when the oxygen permeability is in a steady state is 100 cm ³ / m ² · 24 h · atm or less, preferably 70 cm ³ / m ² · 24 h · atm or less, more preferably 30 cm ³ / m ² · 24 h · atm or less, and still more preferably 10 cm ³ / m ² · 24 h · atm or less.

When the oxygen permeability at a temperature of 25 ° C. and a humidity of 60% RH when the oxygen permeability is in a steady state exceeds the above range, after the steam sterilization treatment or hot water sterilization treatment, the chemical solution container is cooled, and then into the chemical solution container. It becomes impossible to suppress the permeation of oxygen and the accompanying oxidation of the liquid agent. The lower limit of the oxygen permeability when the oxygen permeability is in a steady state is preferably zero, but generally, it is about 5 cm ³ / m ² · 24 h · atm due to the properties of the plastic used for forming the chemical solution container. It is preferably about 1 cm ³ / m ² · 24 h · atm, more preferably about 0.5 cm ³ / m ² · 24 h · atm.

The “steady state” of oxygen permeability of plastic refers to the time lapse of oxygen permeability measured under certain conditions (temperature 25 ° C., humidity 60% RH) after plastic sterilization or hot water sterilization. The time when the change is within ± 5% per hour, preferably within ± 3%.
The oxygen permeability of the plastic is measured as the oxygen permeability (O ₂ GTR) according to method B ( _isobaric method) of “JIS K _7126-1987 “ Method for testing gas permeability of plastic films and sheets ”. Examples of the oxygen permeability measuring device include a trade name “OX-TRAN (registered trademark)” manufactured by MOCON, a trade name “OPT-5000” manufactured by LYSSY, and the like.

The oxygen permeability of the plastic forming the chemical container can be set to an appropriate value depending on the type and thickness of the plastic. When the plastic has a multilayer structure, the oxygen permeability can be set as appropriate depending on the layer configuration, the thickness of each layer, and the like.
Oxygen permeation at a temperature of 25 ° C. and humidity of 60% RH within 12 hours after steam sterilization or hot water sterilization, and oxygen permeation at a temperature of 25 ° C. and humidity of 60% RH when the oxygen permeability is in a steady state. Examples of the plastic that satisfies the above range include a polyol resin, and among them, an ethylene-vinyl alcohol copolymer is preferable.

  For example, the ethylene-vinyl alcohol copolymer preferably has an ethylene content of 10 to 45 mol%, more preferably 25 to 35 mol%. If the ethylene content of the ethylene-vinyl alcohol copolymer is below the above range, for example, there is a possibility that the oxygen permeability will not decrease even after cooling after steam sterilization treatment or hot water sterilization treatment, steam sterilization treatment or hot water sterilization. There is a risk that sufficient water resistance that can withstand the treatment cannot be secured. On the other hand, if the ethylene content of the ethylene-vinyl alcohol copolymer exceeds the above range, the oxygen permeability when the oxygen permeability is in a steady state is increased, and the permeation of oxygen into the chemical container may not be suppressed. Occurs. Furthermore, in this case, the plastic may be whitened by steam sterilization or hot water sterilization, and the transparency of the container may be significantly reduced.

  For the purpose of improving the heat resistance of the chemical solution container, for example, a polyamide-based resin such as nylon-6, tris (2,4-di-t-butylphenyl) phosphite, etc. The phosphorus antioxidant can be blended. What is necessary is just to set the compounding quantity of these polyamide-type resin and phosphorus antioxidant in the range which does not have influence with respect to the liquid agent accommodated in a chemical | medical solution container.

From the viewpoint of maintaining the basic properties as a chemical solution container, the plastic forming the chemical solution container has a polyol resin layer as an intermediate layer, and a polyolefin resin on the inner surface side of the chemical solution container from the intermediate layer. It is desirable that the multilayer structure has a sealing layer (innermost layer) and a protective layer (outermost layer) on the outer surface side of the chemical container relative to the intermediate layer.
The seal layer (innermost layer) is, for example, a layer that forms a welding surface when a chemical solution container is formed, and is a layer that is disposed inside the chemical solution container and is in direct contact with the chemical solution. Therefore, the plastic forming the sealing layer (innermost layer) has, for example, heat sealing properties (specifically, for example, heat sealing conditions such as heating temperature, heating time, pressure, etc., for example, sealing strength of the heat sealing portion). And stability over time, etc.) and safety against chemicals are required.

Specific examples of the plastic for forming the seal layer (innermost layer) include, for example, polyolefin resins.
Examples of the polyolefin resin include polyethylene (ethylene homopolymer), ethylene / α-olefin copolymer, polypropylene (propylene homopolymer), propylene / α-olefin random copolymer, propylene / α-olefin block copolymer, and the like. Examples of the α-olefin of the ethylene / α-olefin copolymer include α-olefins having 3 to 6 carbon atoms such as propylene, 1-butene, 1-pentene, 1-hexene and 4-methyl-1-pentene. As the α-olefin of the propylene / α-olefin random copolymer and the propylene / α-olefin block copolymer, for example, ethylene or, for example, 1-butene, 1-pentene, 1-hexene, 4-methyl Examples include α-olefins having 4 to 6 carbon atoms such as -1-pentene. These polyolefin resins may be used alone or in combination of two or more.

The polyolefin resin used for the seal layer is preferably polyethylene, polypropylene, a mixed resin thereof, or the like among the above examples.
Moreover, for example, when producing a bag-shaped chemical solution container (a so-called multi-chamber bag or the like) having a plurality of storage portions partitioned by a partition wall (easy peel seal portion) having easy peelability, In order to facilitate the formation, the sealing layer is preferably formed of a mixed resin of polyethylene and polypropylene.

  The protective layer (outermost layer) is a layer that forms the outer surface of the chemical solution container. Therefore, as a resin for forming the protective layer (outermost layer), for example, a viewpoint of preventing an intermediate layer made of a polyol resin from being directly affected by moisture during steam sterilization treatment or hot water sterilization treatment. Or, it may be appropriately selected from the viewpoint of maintaining a predetermined strength according to the shape and use of the chemical solution container.

In addition, with respect to the protective layer (outermost layer) or the entire layer provided on the outer side of the chemical liquid container from the intermediate layer of the multilayer film, the intermediate layer made of the polyol-based resin is not directly affected by moisture. In view of the effects of the present invention, it is required to set the water vapor permeability to some extent.
The water vapor permeability of the protective layer or the entire layer provided on the outer side of the chemical liquid container from the intermediate layer of the multilayer film is preferably 1 to 50 g / m ^{2 at} a temperature of 25 ° C. and a humidity of 90% RH, for example. · 24 h, more preferably 3 to 30 g / m ² · 24 h, and still more preferably 3 to 10 g / m ² · 24 h. The water vapor transmission rate is measured in accordance with JIS K _7129-1992 “Test method for water vapor transmission rate of plastic film and sheet (instrument measurement method)” according to method A (humidity sensor method).

  Specific examples of the resin for forming the protective layer (outermost layer) include polyolefin resins, polyamide resins, and polyester resins. Examples of the polyolefin resin include the same ones as described above. Examples of polyamide resins include nylon-6, nylon-6,6, nylon-6,10 nylons, and the like. Examples of the polyester resin include polyethylene terephthalate and polybutylene terephthalate.

  In the case where the plastic forming the chemical solution container is a multilayer film, as a specific embodiment thereof, for example, as described above, the innermost layer forming the inner surface side of the chemical solution container has a seal layer made of a polyolefin resin. And having a protective layer on the outermost layer on the outer surface side of the chemical container, and having an intermediate layer made of a polyol-based resin between the sealing layer and the protective layer. A multilayer film having a laminated structure is exemplified.

Moreover, it is preferable that the multilayer film further has a low water-absorbing layer made of a low water-absorbing resin on the inner surface side (seal layer side) of the chemical container than the intermediate layer. In this case, the intermediate layer made of a polyol resin can be made less susceptible to the influence of moisture in the chemical solution.
Examples of the low water-absorbing resin include polycyclic olefins.
Polycyclic olefins have a very low water absorption rate, specifically 0.01% or less, and are therefore suitable for achieving the purpose of reducing the influence of moisture in the intermediate layer made of polyol resin. is there. Incidentally, the water absorption, JIS _{K 7209 -2000} - is measured according to the "plastic Determination of water absorption" of the provisions of Method B (water absorption rate after immersion in boiling water).

  Specific examples of the polycyclic olefin include, for example, a copolymer of ethylene and a dicyclopentadiene compound (or a hydrogenated product thereof), a copolymer of ethylene and a norbornene compound (or a hydrogenated product thereof), cyclohexane Examples include a ring-opening polymer of a pentadiene compound (or a hydrogenated product thereof) and a polycyclic olefin such as a ring-opening copolymer composed of two or more cyclopentadiene compounds (or a hydrogenated product thereof). Among them, a hydrogenated product of a copolymer of ethylene and a norbornene compound and a hydrogenated product of a ring-opening (co) polymer of one or more cyclopentadiene derivatives are preferable. These polycyclic olefins may be used alone or in combination of two or more.

The multilayer film may further be provided with an elastomer layer containing an elastomer for the purpose of imparting flexibility, transparency and impact resistance to the chemical solution container, for example.
Examples of the elastomer include polyolefin elastomers such as polyethylene elastomer and polypropylene elastomer, and styrene-ethylene / butylene-styrene block copolymer (SEBS), styrene-butadiene-styrene block copolymer (SBS), Styrene-isoprene-styrene block copolymer (SIS), modified SEBS modified with maleic acid, styrene-ethylene / propylene-styrene block copolymer (SEPS), styrene-ethylene / butylene block copolymer (SEB) And styrene-based elastomers such as styrene-ethylene / propylene block copolymer (SEP). Among them, polyethylene-based elastomers are preferable.

The plastic forming the chemical solution container is not limited to this, but is formed into a film by an extrusion method such as a T-die method or an inflation method. By forming a chemical container using the film thus obtained, a chemical container excellent in flexibility and flexibility can be formed.
As a suitable aspect of the multilayer film which forms a chemical | medical solution container, the aspect shown to following (I)-(III) is mentioned, for example.

  (I) From the inner side (innermost layer) side I to the outer side (outermost layer) side O of the chemical solution container, in order, a sealing layer 1 made of a mixed resin of polyethylene and polypropylene, a layer 2 made of polyethylene, and a poly ring A low water-absorbing layer 3 made of olefin, an intermediate layer 4 made of an ethylene-vinyl alcohol copolymer, and a protective layer 5 made of polyethylene, and between the low water-absorbing layer 3 and the intermediate layer 4, and A multilayer film having a seven-layer structure, comprising two adhesive layers 6 and 7 each made of an adhesive resin between the intermediate layer 4 and the protective layer 5 (see FIG. 1).

  (II) From the inner side (innermost layer) side I to the outer side (outermost layer) side O of the chemical container, in order, a sealing layer 1 made of a mixed resin of polyethylene and polypropylene, a layer 2 made of polyethylene, and ethylene- An intermediate layer 4 made of a vinyl alcohol copolymer and a protective layer 5 made of polyethylene are provided, and further, between the layer 2 and the intermediate layer 4 made of polyethylene, and between the intermediate layer 4 and the protective layer 5 A multilayer film having a 6-layer structure (see FIG. 2), which includes two adhesive layers 8 and 7 each made of an adhesive resin.

(III) From the inner surface (innermost layer) side I to the outer surface (outermost layer) side O of the chemical liquid container, in order, the layer 2 made of polyethylene, the low water absorption layer 3 made of polycyclic olefin, and ethylene-vinyl alcohol A multilayer film having a four-layer structure comprising an intermediate layer 4 made of a copolymer and a protective layer 5 made of polyethylene (see FIG. 3).
In the multilayer film shown in the above (I) and (II), the adhesion between the low water absorption layer 3 and the intermediate layer 4 and the adhesion between the intermediate layer 4 and the protective layer 5 are two adhesive layers 6, This is achieved by interposing 7. Moreover, adhesion between the layers can be achieved by a method of simply applying an adhesive between the layers without interposing an adhesive layer.

  In the multilayer film shown in (III) above, adhesion between the low water absorption layer 3 and the intermediate layer 4 and adhesion between the intermediate layer 4 and the protective layer 5 are achieved by applying an adhesive between the respective layers. Yes. Further, adhesion between the respective layers can be achieved by interposing an adhesive layer made of an adhesive resin, as in the case of the multilayer film shown in the above (I) and (II). In the multilayer film shown in (III) above, the layer 2 made of polyethylene is the innermost layer and serves as a seal layer.

Examples of the adhesive resin that forms the adhesive layer include adhesive polyolefin, and specifically, for example, adhesive polyolefin (trade name “Admer (registered trademark)” series) manufactured by Mitsui Chemicals, Inc. Is mentioned.
Examples of the adhesive include a polyurethane resin. Specifically, for example, a polyurethane resin manufactured by Mitsui Chemicals Polyurethanes Co., Ltd. (trade name “Takelac (registered trademark)” series, product name “Takenate (registered trademark)” ) ”Series).

In the multilayer film, the thickness of each layer is not particularly limited, and the oxygen permeability after the steam sterilization treatment or the hot water sterilization treatment and the oxygen permeability in a steady state satisfy the above range as the whole chemical solution container. Should be set.
Although not limited to this, for example, when the chemical container is formed as a bag-type container described later, the thickness of the intermediate layer is 3 to 20 μm, and the thickness of the entire multilayer film is about 180 to 300 μm. It is preferable.

As an aspect of the chemical container, for example, a flat aspect excellent in flexibility and flexibility, that is, a so-called bag type, for example, the container itself can maintain its shape while having flexibility. A mode having strength, that is, a so-called bottle type and the like can be mentioned. Of these, a bag-type chemical container is preferable.
The formation method of these chemical | medical solution containers is not specifically limited, What is necessary is just to select various formation methods suitably according to the form of a chemical | medical solution container.

The bag-type chemical solution container may be, for example, a chemical solution container having only one chemical solution storage unit, or a so-called multi-chamber container having a plurality of storage units partitioned by weak seal portions.
As a suitable aspect of a chemical | medical solution container, the bag type chemical | medical solution container shown in FIG. 4 and FIG. 5 is mentioned, for example.

  Referring to FIG. 4, the bag-type chemical solution container 10 is formed by superposing two plastic films of a front side film and a back side film on each other and heat-sealing the peripheral portions of the plastic films. The peripheral strong seal part 11 and the accommodating part 12 for accommodating the liquid agent, which are partitioned by the peripheral strong seal part 11, are provided. In addition, a cylindrical member 13 that is sandwiched between the front surface side film and the back surface side film and communicates with the housing portion 12 and the outside of the chemical solution container 10 is provided in a part of the peripheral edge strong seal portion 11. The tubular member 13 is tightly plugged by an elastic body that can be pierced with a hollow needle, for example.

  Referring to FIG. 5, the multi-chamber container 15 in the bag type chemical container is composed of two plastic films of a front side film and a back side film, and the peripheral portions of the plastic films are strongly heat sealed to each other. The peripheral strong seal part 16 formed by doing and the accommodating part for accommodating the liquid agent divided by this peripheral strong seal part 16 are provided. The weak seal portion 18 extending in the width direction between the pair of side strong seal portions 17 extending in the width direction perpendicular to the longitudinal direction of the two plastic films among the peripheral strong seal portions 16. The housing portion is partitioned by the weak seal portion 18 into a first housing portion 19 disposed below the front view and a second housing portion 20 disposed above the front view. .

  In addition, a small bag 21 having a substantially rectangular shape in front view for storing the liquid agent is provided inside the second storage unit 20. The pouch 21 includes a peripheral weak seal portion 22 formed by superimposing two plastic films of a front surface film and a back surface film on each other, and weakly heat-sealing the peripheral portion of each plastic film, and the peripheral weakness. A container for storing a liquid medicine partitioned by the seal portion 22, and the container includes a peripheral weak seal portion 22 and a weak seal portion 24 installed between a pair of long sides 23 of the peripheral weak seal portion 22. Thus, it is divided into two small accommodating portions 25 and 26. Further, in the sachet 21, the films on both sides of the front side film and the back side film of the sachet 21 are respectively fixed to the front side film and the back side film forming the multi-chamber container 15.

  The weak seal portion 18 provided between the first accommodating portion 19 and the second accommodating portion 20 presses one of the two accommodating portions 19 and 20 and is a liquid agent accommodated in the accommodating portions 19 and 20. It is opened by applying hydraulic pressure. Further, the peripheral weak seal portion 22 of the pouch 21 is opened in conjunction with the opening of the weak seal portion 18 and the accompanying opening between the two storage portions 19 and 20. Thereby, the liquid agent separately accommodated in the 1st accommodating part 19, the 2nd accommodating part 20, and the two small accommodating parts 25 and 26 of the small bag 21 is mixed mutually.

The two plastic films forming the chemical solution container shown in FIG. 4 and the two plastic films forming the multi-chamber container 15 shown in FIG. 5 include a plastic film or multilayer for forming the above chemical solution container. A film is used.
Further, the two plastic films forming the sachet 21 of the multi-chamber container 15 shown in FIG. 5 are not limited to this, but preferably include oxygen permeable plastic. By forming the sachet 21 from an oxygen-permeable plastic, oxygen easily permeates between the sachet 21 and the second accommodating part 20, so that the dissolved oxygen contained in the sachet 21 is accommodated in two. It can be reduced in the same manner as the liquid agent accommodated in the parts 19 and 20.

Examples of the oxygen permeable plastic include polyolefins such as polyethylene and polypropylene, polycyclic olefins, etc., which have established safety and are widely used as materials for medical containers.
In addition, the chemical | medical solution container itself provided with the small bag arrange | positioned in one accommodating part like the multi-chamber container 15 shown in FIG. 5 is well-known, As an example, it describes in international publication WO2003 / 092574 pamphlet, for example. Examples thereof include a medical multi-chamber container and a medical multi-chamber container described in JP-T-2005-523772.

  As in the multi-chamber container 15 shown in FIG. 5, the drug solution container including the sachet disposed in the one storage unit is not limited to this. For example, the fat-soluble vitamin-containing liquid or the like is accommodated in the sachet 21. Embodiments are preferred. In addition, when the sachet is divided into two small accommodating portions, but not limited to this, for example, in one small accommodating portion 25, the fat-soluble vitamin-containing liquid is accommodated, and in the other accommodating portion 26, A mode in which a trace metal element-containing liquid is accommodated is preferable.

As described above, the dissolved oxygen-reducing liquid agent is stored and sealed in the chemical container, and then subjected to steam sterilization treatment or hot water sterilization treatment. Further, after the steam sterilization treatment or hot water sterilization treatment, The dissolved oxygen concentration when the oxygen permeability of the plastic reaches a steady state is 2 ppm or less.
Specific examples of the steam sterilization include a high pressure steam sterilization (autoclave) method. Specific examples of the hot water sterilization treatment include a hot water immersion sterilization method and a hot water shower sterilization method.

The chemical liquid container (chemical liquid container) that contains the liquid drug is steam sterilized or hot water sterilized so that the chemical liquid container is heated for a certain period of time, increasing the oxygen permeability of the plastic that forms the chemical liquid container. Can be made. Specifically, the oxygen permeability at a temperature of 25 ° C. and a humidity of 60% RH is 200 cm ³ / m ² · 24 h · atm or more within 12 hours after steam sterilization treatment or hot water sterilization treatment of a plastic container. Can be set to

The treatment conditions of the steam sterilization treatment or hot water sterilization treatment for the chemical solution container may be appropriately set according to, for example, the type and amount of the liquid agent accommodated in the chemical solution container, the material of the plastic forming the chemical solution container, the thickness, and the like .
Therefore, although not particularly limited, for example, the treatment conditions for the steam sterilization treatment may be set to the above-mentioned conditions. Preferably, the treatment temperature is 100 to 121 ° C., the treatment time is 10 to 60 minutes, and the atmospheric pressure during the treatment. May be set under a pressure of 2000 to 3500 hPa. Moreover, what is necessary is just to set the process conditions of a hot-water sterilization process to said conditions. In the hot water sterilization process, hot water is sprayed or sprayed onto the chemical solution container.

  Steam sterilization or hot water sterilization is preferably performed in an inert gas atmosphere. In this case, the head space of the chemical container can be replaced to some extent by the inert gas during the steam sterilization process or the hot water sterilization process. The amount of oxygen to be removed from the head space can be reduced in advance.

The inert gas is not particularly limited, but for example, a gas such as nitrogen and argon that is less likely to cause oxidative decomposition and other alteration (preferably not to cause) is preferable.
After the above-described steam sterilization treatment or hot water sterilization treatment is performed on the chemical solution container (chemical solution container) that stores the liquid agent, the liquid agent is used until the oxygen permeability of the plastic forming the chemical solution container reaches a steady state. Is stored in an environment having a deoxygenating means. Thereby, when the oxygen permeability of the plastic forming the chemical solution container reaches a steady state, the dissolved oxygen concentration of the liquid agent can be adjusted to 2 ppm or less.

The dissolved oxygen concentration of the liquid agent is 2 ppm or less after the oxygen permeability of the plastic reaches a steady state after the steam sterilization treatment or the hot water sterilization treatment.
After the steam sterilization treatment or the hot water sterilization treatment, it usually takes 7 days, preferably 10 days, more preferably 14 days until the oxygen permeability of the plastic forming the chemical container reaches a steady state. It takes time. Therefore, in order to reduce the amount of dissolved oxygen contained in the chemical solution container and the oxygen content in the head space of the chemical solution container, after the steam sterilization treatment or the hot water sterilization treatment, deoxygenation is performed over the above period. What is necessary is just to preserve | save a chemical | medical solution container in the environment which has a means.

The deoxygenating means is a means for reducing oxygen content in a sealed environment by reacting with oxygen or adsorbing oxygen, and specifically includes, for example, a deoxygenating agent.
Examples of the oxygen scavenger include various known oxygen scavengers. Specifically, for example, oxygen scavengers containing iron compounds such as iron hydroxide, iron oxide and iron carbide as active ingredients, and low molecular phenols. And oxygen scavengers containing activated carbon as active ingredients. Commercially available products include, for example, the product name “AGELESS (registered trademark)” manufactured by Mitsubishi Gas Chemical Co., Ltd., the product name “MODURAN” manufactured by Nippon Kayaku Co., Ltd., and “SECURL (registered) manufactured by Nippon Soda Co., Ltd. Trademark) ”,“ Tamotsu (registered trademark) ”manufactured by Oji Chemical Co., Ltd., trade name“ Vitalon ”manufactured by Toa Synthetic Chemical Industry Co., Ltd., trade name“ Sansocut ”manufactured by Finetech Co., Ltd., Toyo Seikan Co., Ltd. The product name "Oxyguard" manufactured by Co., Ltd. can be mentioned.

The treatment for reducing the dissolved oxygen in the liquid agent by the deoxygenation means is preferably performed in a sealed environment with an exterior body having an oxygen barrier.
Examples of the exterior body having an oxygen barrier include an aluminum laminate film.
According to said dissolved oxygen reduction liquid agent, the dissolved oxygen amount of the liquid agent accommodated in the chemical solution container and the oxygen content in the head space of the chemical solution container can be reduced, and the oxidative deterioration of the liquid agent can be suppressed. Therefore, the above-mentioned dissolved oxygen reducing solution is suitable as a solution for stabilizing an oxidizable agent such as an amino acid-containing solution, a vitamin-containing sugar solution, a fat-soluble vitamin-containing solution, and a fat emulsion over a long period of time. is there.

Next, an Example and a comparative example are given and this invention is demonstrated.
Preparation of liquid formulation Formulation Example 1 (Preparation of amino acid-containing liquid)
The following amino acid, the following electrolyte, and the following antioxidant were dissolved in distilled water for injection, adjusted to pH 6.8 with succinic acid, and then purged with nitrogen (bubbled). Furthermore, the following water-soluble vitamins were blended and subjected to aseptic filtration to prepare an amino acid-containing solution.

The components contained in the amino acid-containing liquid are as follows. In addition, the value in parenthesis has shown the content in 300 mL of amino acid containing liquids.
Amino acids: L-leucine (4.2 g), L-isoleucine (2.40 g), L-valine (2.40 g), L-lysine acetate (4.44 g; 3.15 g as L-lysine), L- Threonine (1.71 g), L-tryptophan (0.60 g), L-methionine (1.17 g), N-acetyl-L-cysteine (0.40 g; 0.30 g as L-cysteine), L-phenylalanine (2.10 g), L-tyrosin (0.15 g), L-arginine (3.15 g), L-histidine (1.50 g), L-alanine (2.40 g), L-proline (1.50 g) , L-serine (0.90 g), L-glycine (1.77 g), L-aspartic acid (0.30 g), and L-glutamic acid (0.30 g).
Electrolytes: calcium chloride (0.37 g; as Ca ²⁺ , 5.03 mEq), magnesium sulfate (0.62 g; Mg ²⁺ as 5.03 mEq), and potassium acetate (1.08 g; K ⁺ as 11.0 mEq) .
Water soluble vitamins: nicotinamide (20 mg), and folic acid (0.2 mg).
Antioxidant: sodium bisulfite (15 mg).

Formulation Example 2 (Preparation of sugar solution)
The following sugar and the following electrolyte were dissolved in distilled water for injection, and the pH was adjusted to 4.0 with acetic acid, followed by nitrogen substitution (nitrogen bubbling). Furthermore, the following water-soluble vitamins were blended and subjected to aseptic filtration to prepare a sugar solution.
The components contained in the sugar solution are as follows. The value in parentheses indicates the content in 696 mL of sugar solution.
Sugar: glucose (175 g).
Electrolytes: sodium chloride (2.05 g; as Na ⁺ 35.0 mEq), sodium lactate (1.65 g; Na ⁺ as 14.7 mEq), potassium chloride (0.746 g; K ⁺ as 10.0 mEq / L ), Potassium iodide (0.083 g; as K ⁺ , 0.50 mEq), and potassium dihydrogen phosphate (0.821 g; K ⁺ as 6.03 mEq).
Water-soluble vitamins: thiamine hydrochloride (1.95 mg), pyridoxine hydrochloride (2.45 mg), cyanocobalamin (2.5 μg), and panthenol (7.0 mg).

Formulation Example 3 (Preparation of vitamin-containing liquid)
The following fat-soluble vitamins are blended with polysorbate 80 and polysorbate 20 (both sorbitan fatty acid esters and nonionic surfactants), dissolved in distilled water for injection, and further blended with ascorbic acid and biotin. The pH was adjusted to 6-6.5 with citric acid and sodium hydroxide. Next, riboflavin sodium phosphate was blended and sterile filtered to obtain a vitamin-containing solution.

The components contained in the vitamin-containing liquid are as follows. In addition, the value in parenthesis has shown the content in 4 mL of vitamin containing liquids.
Fat-soluble vitamins: Vitamin A oil (1650 IU (vitamin A units)), cholecalciferol (0.0025 mg), tocopherol acetate (5.0 mg), and phytonadione (1.0 mg).
Water-soluble vitamins: sodium riboflavin phosphate (2.3 mg), ascorbic acid (50 mg), biotin (0.030 mg).
Nonionic surfactant: polysorbate 80 (20 mg), polysorbate 20 (4 mg).

Formulation Example 4 (Preparation of trace metal element-containing liquid)
A colloidal agent (sodium chondroitin sulfate), iron (III) chloride hexahydrate, and sodium hydroxide were blended in distilled water for injection to prepare an iron colloid solution. Furthermore, a predetermined amount of copper sulfate pentahydrate, manganese chloride, and zinc sulfate are blended in this iron colloid solution in a state dissolved in distilled water for injection, and the pH is adjusted to 5.5 to sodium hydroxide. Adjusted to 6. This was filtered by a conventional method to prepare a trace metal element-containing liquid.

The components contained in the trace metal element-containing liquid and the content in 4 mL of the trace metal element-containing liquid are as follows.
Iron (III) chloride hexahydrate: 4.730 mg
Manganese chloride tetrahydrate: 0.09895 mg
Zinc sulfate heptahydrate: 8.625 mg
Copper sulfate pentahydrate: 0.624mg
Formation of Chemical Solution Container Each component constituting the plastic for forming the chemical solution container is as follows.
PE-1: ethylene / 1-butene copolymer, density 0.940 g / cm ³ , water vapor permeability 7 g / m ² · 24 h (25 ° C., 90% RH, 20 μm), trade name “Ultzex (registered trademark)” 4020B ", manufactured by Prime Polymer Co., Ltd.
PE-2: ethylene / 1-butene copolymer (density 0.920 g / cm ³ , trade name “Ultzex (registered trademark) 2010”, manufactured by Prime Polymer Co., Ltd.) 45% by weight, ethylene / 1-butene Copolymer (density 0.885 g / cm ³ , trade name “Tuffmer (registered trademark) A0585X”, manufactured by Prime Polymer Co., Ltd.) 50% by weight, polyethylene homopolymer (density 0.965 g / cm ³ , trade name “ EVEX-1: Ethylene vinyl alcohol, ethylene content 27 mol%, trade name “EVAL (registered trademark) L101”, Co., Ltd. Made by Kuraray.
EVOH-2: ethylene vinyl alcohol, ethylene content 44 mol%, trade name “EVAL (registered trademark) E105”, manufactured by Kuraray Co., Ltd.
COP: Norbornene-based ring-opening polymer hydrogenated product, water absorption of less than 0.01%, trade name “Zeonor (registered trademark) 1020R”, manufactured by Nippon Zeon Co., Ltd.
PP: polypropylene, density 0.900 g / cm ³ , trade name “B355”, manufactured by Prime Polymer Co., Ltd.
NY: Nylon-6, trade name “Amilan (registered trademark) CM1017”, manufactured by Toray Industries, Inc.
PE-PP: a mixture of 85% by weight of the above PE (1) and 15% by weight of a polypropylene homopolymer (density 0.910 g / cm ³ , trade name “J103WA”, manufactured by Prime Polymer Co., Ltd.) Carboxylic acid-modified polyethylene, density 0.905 g / cm ³ , water vapor permeability 10 g / m ² · 24 h (25 ° C., 90% RH, 20 μm), adhesive polyolefin made by Prime Polymer Co., Ltd., trade name “Admer (registered) Trademark) ".
PBT: Polybutylene terephthalate, water vapor permeability 23 g / m ² · 24 h (25 ° C., 90% RH, 10 μm), manufactured by Mitsubishi Engineer Plastics Co., Ltd.

Example 1
(1) Production of pouch Intermediate layer (thickness 10 μm) made of COP, inner layer (thickness 20 μm) made of PE-1 laminated on one side surface in the thickness direction of the intermediate layer, and the one side A plastic film having a total thickness of 50 μm, comprising an outer layer (thickness 20 μm) made of PE-PP, laminated on the other surface opposite to the surface, was produced by coextrusion molding. The resulting three-layer plastic film was cut into a substantially rectangular shape.

  Next, referring to FIG. 5, the two peripheral plastic films of the three-layer structure are overlapped so that the inner layers face each other, and the peripheral edge thereof is heat-sealed, whereby the peripheral weak seal portion 22. And a flat flexible sachet 21 was obtained. Of the peripheral weak seal portion 22 of the pouch, a weak seal portion 24 is formed between the pair of long sides 23 and extends in parallel with the pair of short sides 23 at the center in the longitudinal direction of the pair of long sides 23. The inside of the sachet 21 was partitioned into two small accommodating portions 25 and 26.

In addition, in the pair of long sides 23 of the peripheral weak seal portion 22 of the pouch 21, one unsealed portion that communicates with each of the small accommodating portions 25 and 26 remains, and the unsealed portion is connected to each small accommodating portion. It was set as the filling port of the liquid agent in 25,26.
Next, 4 mL of the vitamin-containing solution prepared in Formulation Example 3 is filled into the small container 25 on one side from the filling port connected to the small container 25 on the one side, and the filling port is heated in a nitrogen atmosphere. Sealed. Furthermore, 4 mL of the trace metal element-containing liquid prepared in Formulation Example 4 above is filled into the other small container 26 from the filling port connected to the other small container 26, and the above filler is filled in a nitrogen atmosphere. Heat sealed.

(2) Production of Chemical Solution Container and Chemical Solution Container A seven-layer plastic film (see FIG. 1) having a layer configuration shown in Sample 1 in Table 1 below was produced by coextrusion molding.
Next, referring to FIG. 5, the two seven-layer plastic films are cut into a substantially rectangular shape, overlapped so that the inner layers of each plastic film face each other, and the periphery is heat-sealed. The peripheral strong seal portion 16 is formed, and the pair of side strong seal portions 17 is formed at the center in the longitudinal direction of the pair of side strong seal portions 17 extending in the longitudinal direction of the plastic film. A weak seal portion 18 is formed between the first accommodating portion 19 and the second accommodating portion 20. The accommodating portion is defined by the strong peripheral seal portion 16.

Prior to the formation of the peripheral strong seal portion 16, the sachet 21 obtained in (1) above is inserted into the formation region of the second housing portion 20, and the outer surface in the vicinity of one long side 23 of the sachet 21, 2 The inner surface of the housing portion 20 near the weak seal portion 18 was fixed by heat sealing.
In the strong peripheral edge seal portion 16, the liquid agent discharge / injection tubular members 13 are arranged one by one so as to be connected to the first storage portion 19 and the second storage portion 20, respectively. The unsealed portions were left one by one so as to be continuous with each of the second accommodating portions 20, and the unsealed portions were used as liquid agent filling ports into the first accommodating portion 19 and the second accommodating portion 20.

  Next, in a nitrogen atmosphere, the first container 19 is filled with 300 mL of the amino acid-containing solution prepared in Formulation Example 1, and the second container 20 is charged with 696 mL of the sugar solution prepared in Formulation Example 2. After filling, the unsealed part was heat-sealed to obtain a total amount of 1004 mL of a chemical container. The headspace volume was about 30 mL, and nitrogen substitution (about 50%) was performed so that the oxygen concentration became 10%.

(3) Steam sterilization treatment and dissolved oxygen reduction treatment The chemical solution container obtained in (2) above is placed in a sterilization kettle and heated in a steam-saturated nitrogen atmosphere (temperature 110 ° C., pressure 2700 hPa) for 30 minutes. Was subjected to high-pressure steam sterilization treatment. The oxygen concentration in the nitrogen atmosphere was adjusted to 2% or less.
Next, the chemical liquid container subjected to the steam sterilization treatment was housed in an outer bag together with an oxygen scavenger (trade name “AGELESS (registered trademark)” manufactured by Mitsubishi Gas Chemical Co., Ltd.) and stored for 20 days.

The outer bag is a bag made of a multilayer film having a three-layer structure in which the inner layer is made of polyethylene, the intermediate layer is made of polyvinyl alcohol, and the outer layer is made of stretched polypropylene, and oxygen permeation is performed at a temperature of 25 ° C. and a humidity of 60% RH. The degree was 0.1 cm ³ / m ² · 24 h · atm or less, and the water vapor permeability at a temperature of 25 ° C. and a humidity of 90% RH was 0.5 g / m ² · 24 h. The outer bag was adjusted so that the volume of the internal space was about 300 to 500 mL, and the oxygen concentration in the outer bag was 2% or less by nitrogen replacement. After the high-pressure steam sterilization treatment, the time until the drug solution bag was accommodated in the outer bag and sealed was within one hour.

Example 2
A six-layer plastic film (see FIG. 2) having a layer structure shown in Sample 2 in Table 1 below was produced by coextrusion molding.
Next, a chemical container was prepared in the same manner as in (2) of Example 1 except that the two plastic films having the 6-layer structure were used, and in the same manner as in (3) of Example 1, steam was used. Sterilization treatment and dissolved oxygen reduction treatment were performed.

Example 3
A seven-layer plastic film (see FIG. 1) having a layer structure shown in Sample 3 in Table 1 below was produced by coextrusion molding. In addition, the water vapor permeability of the laminate composed of the protective layer 5 and the adhesive layer 7 of this multilayer film was 4.1 g / m ² · 24 h (25 ° C., 90% RH).

Next, a chemical solution container was prepared in the same manner as in (1) of Example 1 except that two plastic films having the seven-layer structure were used, and in the same manner as in (3) of Example 1, steam was used. Sterilization treatment and dissolved oxygen reduction treatment were performed.
Example 4
A seven-layer plastic film (see FIG. 1) having a layer structure shown in Sample 4 in Table 2 below was produced by coextrusion molding. The water vapor permeability of the multilayer film composed of the protective layer 5 and the adhesive layer 7 of the multilayer film was 7.0 g / m ² · 24 h (25 ° C., 90% RH).

Subsequently, the chemical | medical solution container was produced like Example (1) except having used two said 7-layer structure plastic films.
The outer layer bag is a bag made of a multilayer film having a three-layer structure in which an intermediate layer is made of an ethylene / vinyl alcohol copolymer, and an inner layer and an outer layer are made of polyethylene, at a temperature of 25 ° C. and a humidity of 60% RH. oxygen permeability of ^{a 0.5cm 3 / m 2 · 24h ·} atm, temperature 25 ° C., the oxygen permeability of a humidity 90% RH ^was used as a ^{3cm 3 / m 2 · 24h ·} atm Except for this, steam sterilization treatment and dissolved oxygen reduction treatment were performed in the same manner as (3) of Example 1.

Example 5
A 6-layer plastic film (see FIG. 2) having a layer structure shown in Sample 5 in Table 2 below was produced by coextrusion molding. In addition, the water vapor permeability of the multilayer body including the protective layer 5 and the adhesive layer 7 of this multilayer film was 5.1 g / m ² · 24 h (25 ° C., 90% RH).

Next, a chemical container was prepared in the same manner as in (1) of Example 1 except that the two plastic films having the six-layer structure were used, and in the same manner as in (3) of Example 1, steam was used. Sterilization treatment and dissolved oxygen reduction treatment were performed.
Example 6
A seven-layer plastic film (see FIG. 1) having a layer structure shown in Sample 6 in Table 2 below was produced by coextrusion molding. In addition, the water vapor permeability of the laminate composed of the protective layer 5 and the adhesive layer 7 of this multilayer film was 3.2 g / m ² · 24 h (25 ° C., 90% RH).

Next, a chemical solution container was prepared in the same manner as in (1) of Example 1 except that two plastic films having the seven-layer structure were used, and in the same manner as in (3) of Example 1, steam was used. Sterilization treatment and dissolved oxygen reduction treatment were performed.
Comparative Example 1
A seven-layer plastic film (see FIG. 1) having a layer structure shown in Comparative Sample 1 in Table 3 below was produced by coextrusion molding.

Next, a chemical solution container was prepared in the same manner as in (1) of Example 1 except that two plastic films having the seven-layer structure were used, and in the same manner as in (3) of Example 1, steam was used. Sterilization treatment and dissolved oxygen reduction treatment were performed.
Comparative Example 2
A five-layer plastic film having the layer structure shown in Comparative Sample 2 in Table 3 below and having no adhesive layer was produced by coextrusion molding.

Next, a chemical container was prepared in the same manner as in (1) of Example 1 except that the two plastic films having the five-layer structure were used, and in the same manner as in (3) of Example 1, steam was used. Sterilization treatment and dissolved oxygen reduction treatment were performed.
Evaluation Test for Dissolved Oxygen Reduction Treatment The surface of the chemical container after high-pressure steam sterilization treatment was dehydrated with warm air of about 40 ° C. for 1 minute. Furthermore, the sample was left in an environment of temperature 25 ° C. and humidity 60% RH, and the oxygen concentration of the liquid in the chemical container was measured with a nondestructive oxygen concentration meter (product name “Fibox 3”, manufactured by PreSens). The oxygen concentration was measured after 6 hours from the steam sterilization, and then every day after the steam sterilization. For measurement of oxygen permeability, a trade name “OX-TRAN (registered trademark)” manufactured by MOCON was used.

As a result, the oxygen concentration of the content liquid was able to be reduced to 2 ppm or less by passing about 7 days after storing and sealing in the outer bag for any of the chemical liquid containers of Examples and Comparative Examples. .
The measurement result about the oxygen permeability of the multilayer film used by the said Example and comparative example is shown to Tables 1-3.

In Tables 1 to 3, in the description of the “layer configuration of multilayer film” column, the upper part indicates the type of plastic on which each layer is formed, and the lower part (numerical value in parentheses) indicates the thickness of each layer. The unit of “water vapor permeability” is [g / m ² · 24 h], and the unit of “oxygen permeability” is [cm ³ / m ² · 24 h · atm].
In addition, although the said invention was provided as embodiment of illustration of this invention, this is only a mere illustration and must not be interpreted limitedly. Modifications of the present invention apparent to those skilled in the art to which the invention belongs will fall within the scope of the claims.

  The dissolved oxygen reducing solution of the present invention is suitable as a solution for stably storing an amino acid-containing solution, a vitamin-containing sugar solution, a fat-soluble vitamin-containing solution, a fat emulsion and the like over a long period of time.

FIG. 1 is a schematic cross-sectional view showing an example of plastic forming a chemical solution container. FIG. 2 is a schematic cross-sectional view showing an example of plastic forming the chemical solution container. FIG. 3 is a schematic cross-sectional view showing an example of plastic forming the chemical solution container. FIG. 4 is a front view showing an example of a chemical solution container. FIG. 5 is a front view showing an example of a chemical solution container.

Explanation of symbols

  10: Chemical container, 15 Chemical container.

Claims (7)

When the oxygen permeability at a temperature of 25 ° C. and a humidity of 60% RH is 200 cm ³ / m ² · 24 h · atm or more within 12 hours after steam sterilization or hot water sterilization and the oxygen permeability is in a steady state Is contained and sealed in a chemical container made of plastic having an oxygen permeability of 100 cm ³ / m ² · 24 h · atm or less at a temperature of 25 ° C. and a humidity of 60% RH,
The steam sterilization process or the hot water sterilization process has been performed,
The dissolved oxygen reducing liquid agent, wherein the dissolved oxygen concentration is 2 ppm or less when the oxygen permeability of the plastic reaches a steady state after the steam sterilization treatment or the hot water sterilization treatment.   2. The dissolved oxygen-reducing liquid agent according to claim 1, which is stored in an environment having a deoxygenation means after the steam sterilization treatment or the hot water sterilization treatment.   It is an easily oxidizable liquid agent, The dissolved oxygen reduction liquid agent of Claim 1 or 2 characterized by the above-mentioned.   The dissolved oxygen-reducing liquid agent according to any one of claims 1 to 3, which is at least one selected from the group consisting of an amino acid-containing liquid, a vitamin-containing sugar liquid, and a fat-soluble vitamin-containing liquid.   The amino acid-containing liquid is L-leucine, L-isoleucine, L-valine, L-lysine, L-threonine, L-tryptophan, L-methionine, L-cysteine, L-phenylalanine, L-tyrosine, L-arginine, It contains at least one amino acid selected from the group consisting of L-histidine, L-alanine, L-proline, L-serine, L-glycine, L-aspartic acid, and L-glutamic acid. The dissolved oxygen reducing liquid agent according to claim 4. The vitamin-containing sugar solution is a saccharide and a water-soluble vitamin selected from the group consisting of vitamin B ₁ , vitamin B ₂ , vitamin B ₆ , vitamin B ₁₂ , vitamin C, folic acid, niacin, biotin, and pantothenic acids, The dissolved oxygen-reducing liquid agent according to claim 4, wherein the dissolved oxygen-reducing liquid agent is contained.   The said fat-soluble vitamin containing liquid contains at least 1 sort (s) of fat-soluble vitamin chosen from the group which consists of vitamin A, vitamin D, vitamin E, and vitamin K of Claim 4 characterized by the above-mentioned. Dissolved oxygen reducing liquid.

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