JP3364932B2 - Infusion container - Google Patents

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to a container containing an infusion solution.
More specifically, it relates to a container containing an infusion solution for preparing an infusion solution containing a fat emulsion, a sugar, an amino acid and an electrolyte.

[0002]

2. Description of the Related Art Conventionally, in maintaining the life of a patient, oral nutrition and tube feeding are impossible or inadequate, or even if they are possible, the digestive absorption function of the patient is In the case of extremely poor conditions, or in the case of a pathological condition in which the passage of food through the digestive tract leads to aggravation of the original disease, intravenous administration of an infusion is performed for nutritional supplementation. As such infusion preparations, sugar infusions containing reducing sugars, amino acid infusions containing essential amino acids, electrolyte infusions containing minerals, fat emulsions containing vegetable oil emulsions, mixed vitamin preparations, etc. are commercially available. These infusion preparations are appropriately mixed and used at the time of use according to the patient's symptoms and the like. However, mixing the infusion preparation during use is a complicated operation for workers, and above all, there is a problem of bacterial contamination during mixing. From such a problem, an infusion preparation in which the above various infusions are mixed in advance has been proposed, and in particular, an infusion preparation containing sugar, an amino acid, an electrolyte and a fat emulsion, which are components necessary for nutritional supplementation to a patient, It is extremely useful clinically.

[0003]

However, sugar infusion solution, amino acid infusion solution, electrolyte infusion solution and fat emulsion have different conditions under which they can exist stably, and when these are mixed, various problems occur and they cannot be used as an infusion solution. For example, a fat emulsion is an unstable formulation, and when mixed with other infusion solution, coarsening of oil and fat particles and phase separation (creaming) are likely to occur. In particular, the divalent metal ion contained in the electrolyte infusion causes aggregation of the fat emulsion and particle disintegration. Further, the electrolyte infusion contains calcium and phosphoric acid which are components necessary for maintaining the electrolyte balance, but phosphoric acid reacts with calcium to form calcium phosphate,
Turbidity and precipitation are likely to occur. In order to prevent the formation of turbidity and precipitate, the electrolyte infusion solution is usually adjusted to a low pH (less than pH 5). When this electrolyte infusion and amino acid infusion are mixed, the strong buffering action of the amino acid causes pH on the amino acid side.
Is controlled, and a large amount of acid agent (for example, hydrochloric acid, acetic acid, etc.) is required to lower the pH of the infusion solution. However, since the use of a large amount of acid agent impairs the balance of infusion components, there is a limit to the amount of acid agent used, and it is not possible to make the infusion solution have a low pH. During sterilization, turbidity and precipitation easily occur. Furthermore, it is known that when an amino acid infusion solution and a sugar infusion solution are mixed and sterilized by heating, remarkable coloring occurs due to the Maillard reaction. As described above, when various infusions are mixed, various problems such as precipitation, deterioration, and coloring occur, so it is difficult to prepare in advance an infusion containing sugar, amino acid, electrolyte, and fat emulsion and store it. . Therefore, conventionally, a fat emulsion, a sugar infusion solution, an amino acid infusion solution and an electrolyte infusion solution are mixed and used at the time of use, and a stable infusion formulation containing a sugar, an amino acid, an electrolyte and a fat emulsion is desired. In view of the above circumstances, the present inventors have diligently studied a method for preparing a stable infusion formulation containing sugar, amino acid, electrolyte, and fat emulsion, and as a result, devised a combination of infusions containing these components, thereby providing excellent storage stability. With use, an infusion solution containing sugar, amino acid, electrolyte and fat emulsion can be easily obtained, and precipitation, deterioration,
The present invention has been completed by finding that various problems such as coloring can be solved. That is, it is an object of the present invention to provide a container containing an infusion solution which is useful when preparing an infusion solution containing a sugar, an amino acid, an electrolyte and a fat emulsion.

[0004]

The container for infusion of the present invention made to solve the above problems is a container in which two private chambers are formed by a separating means, and a fat emulsion and a sugar are provided in the first chamber. And an infusion solution containing an amino acid and an electrolyte is contained in the second chamber. In particular, the average particle size of the fat emulsion contained in the first chamber is preferably 0.17 μm or less, and the infusion solution contained in the second chamber is a polyhydric alcohol or a phosphate ester of sugar as a source of phosphorus. It is preferable to add the salt. The present invention has the above-described structure, and when used, the isolation means is removed, the first chamber and the second chamber are communicated with each other, and the infusion solution contained in the first chamber and the infusion solution contained in the second chamber are mixed. Thus, an infusion solution containing a fat emulsion, sugar, amino acid and electrolyte can be prepared.

In the present invention having the above structure, the first
The chamber contains an infusion solution containing a fat emulsion and sugar. As the fat emulsion, an oil-in-water emulsion prepared by dispersing fats and oils in water using an emulsifier is used. The fat emulsion can be prepared according to a conventional method. For example, after adding an oil and fat and an emulsifier to water, the crude emulsion is prepared by stirring, and then the crude emulsion is subjected to a conventional method such as a high pressure emulsification method. Can be emulsified by. As the above-mentioned fat and oil, any fat and oil can be used as long as it is an edible oil, for example, vegetable oil (for example, soybean oil, cottonseed oil, safflower oil, corn oil,
Palm oil, perilla oil, perilla oil, etc.), fish oil (eg, cod liver oil, etc.), medium-chain fatty acid triglycerides [eg, panacetate (trade name), ODO (trade name), etc.] and chemically synthesized triglycerides [eg, 2- Chemically defined trig of linoleoyl-1,3-dioctanoylglycerol (8L8), 2-linoleoyl-1,3-didecanoylglycerol (10L10), etc.
and one or more kinds of fats and oils selected from the group “lycerides” are preferably used. As the emulsifier, egg yellow phospholipids, hydrogenated egg yolk phospholipids, one or more phospholipids selected from soybean phospholipid and hydrogenated soybean phospholipid
There is need use. Particularly preferred is a fat emulsion using soybean oil as an oil and fat and egg yolk phospholipid as an emulsifier.

In the present invention, the average particle size of the fat emulsion is
It is preferably adjusted to 0.17 μm or less. With this particle size, conventional fat emulsion (average particle size 0.2-0.3μ
Compared with m), the stability is enhanced, and especially the phase separation of the fat emulsion due to the difference in specific gravity can be effectively suppressed. A fat emulsion having an average particle size of 0.17 μm or less can be obtained by adding one or two kinds selected from glycerin and glucose during the preparation of the fat emulsion and emulsifying. Conventionally, for the preparation of a fat emulsion, a method of adding a fat and oil and an emulsifier to water, stirring to prepare a coarse emulsion, and then emulsifying the coarse emulsion by a high pressure emulsification method or the like is used. According to the method, it is difficult to easily obtain an emulsion having an average grain size of 0.2 μm or less. However, the inventors have found that glycerin and glucose have a specific action of promoting microparticulation, and according to the above production method, a fat emulsion having an average particle size of 0.17 μm or less can be easily prepared. be able to.

In order to explain the method for producing the above fat emulsion more specifically, one example thereof is to add oil and fat and an emulsifier to water, and also to add 1 or 2 kinds selected from glycerin and glucose and then stir. To prepare a crude emulsion, and then the crude emulsion is emulsified by a conventional method such as a high pressure emulsification method to prepare a fat emulsion. When the above emulsification is performed by a high-pressure emulsification method, for example, using an emulsifying machine such as Manton-Gaulin homogenizer, the crude emulsion is 20 ~ 700K
It is carried out by passing it 5 to 50 times under the condition of g / cm ² . In this method, glycerin and /
Or glucose may be present when emulsifying, for example,
Glycerin and / or was added to the crude emulsion prepared with oil and fat and emulsifier.
Alternatively, glucose may be added to emulsify. In addition,
The average grain size of the obtained emulsion can be measured by using a conventional measuring method such as a light scattering method.

In the above production method, the amount of fats and oils, emulsifiers and glycerin and / or glucose used is 0.1 to 30 W / V% of fats and oils (hereinafter, unless otherwise specified,% is W / V%)), preferably 1 to 20%, an emulsifier 0.01 to 10%, preferably 0.05 to 5%,
Glycerin and / or glucose are used in an amount adjusted to about 30 to 70%, preferably about 40 to 60% and an appropriate amount of water.

As the sugar contained in the infusion solution contained in the first chamber, various sugars can be blended, but reducing sugar is preferably used. Examples of the reducing sugar include glucose, fructose, maltose, and the like, and these reducing sugars may be used as a mixture of two or more kinds. Further, a mixture obtained by adding sorbitol, xylitol, glycerin or the like to these reducing sugars may be used.

The infusion solution containing the fat emulsion and the sugar contained in the first chamber can be prepared by various methods. For example, the sugar may be added to the fat emulsion prepared by the above-mentioned method. Sugar may be added in advance when the emulsion is prepared. The composition of the infusion solution containing the fat emulsion and sugar depends on the concentration of the infusion solution (that is, the infusion solution containing the amino acid and the electrolyte) contained in the second chamber, the volume ratio of the infusion solution injected into the first chamber and the second chamber, and the like. It is appropriately adjusted, for example, fats and oils 0.1 to 30%, preferably 1 to 20%, more preferably 2 to 10%, emulsifiers 0.01 to 10%, preferably 0.05 to 5%,
More preferably about 0.1% to 1%, sugar 7-40% approximately, good Mashiku about 10-30%, and infusion consisting of an appropriate amount of water is exemplified.

The second chamber contains an infusion solution containing an amino acid and an electrolyte. Examples of the amino acids include various amino acids (essential amino acids, non-essential amino acids) conventionally contained in amino acid infusions for the purpose of nutritional supplementation to the living body, and examples thereof include L-isoleucine, L-leucine and L-.
Valine, L-lysine, L-methionine, L-phenylalanine, L-threonine, L-tryptophan, L-arginine, L-histidine, glycine, L-alanine,
L-proline, L-aspartic acid, L-serine, L-
Tyrosine, L-glutamic acid, L-cysteine and the like are exemplified. These amino acids do not necessarily have to be used in the form of free amino acids and may be used in the form of inorganic acid salts (eg L
-Lysine hydrochloride, etc.), organic acid salt (eg, L-lysine acetate, L-lysine malate, etc.), in vivo hydrolysable ester form (eg, L-tyrosine methyl ester, L-methionine methyl) Ester, L-methionine ethyl ester, etc.), N-substituted product (for example, N-acetyl-L-tryptophan, N-acetyl-L-cysteine, N-acetyl-L-proline, etc.), same or different amino acid as peptide Conjugated dipeptides (eg,
L-tyrosyl-L-tyrosine, L-alanyl-L-tyrosine, L-arginyl-L-tyrosine, L-tyrosyl-
L-arginine, etc.) and the like.

Examples of the electrolyte include various water-soluble salts conventionally used for infusion, and for example, various inorganic components (for example, various inorganic components required for maintaining the function of a living body and the electrolyte balance of body fluid). Examples thereof include water-soluble salts of sodium, potassium, calcium, magnesium, zinc, iron, copper, manganese, iodine, phosphorus and the like (for example, chloride, sulfate, acetate, gluconate, lactate, etc.). A hydrate may be added to these water-soluble salts.

In the above electrolyte component, a polyhydric alcohol or a phosphoric acid ester of sugar or a salt thereof is preferably used as a source of phosphorus. As the phosphate ester of polyhydric alcohol, glycerophosphate, mannitol-1-
Examples thereof include phosphoric acid and sorbitol-1-phosphoric acid. Further, examples of the phosphoric acid ester of sugar include glucose-6-phosphoric acid, fructose-6-phosphoric acid, and mannose-6-phosphoric acid. As the salts of these phosphoric acid esters, alkali metal salts such as sodium salts and potassium salts are preferably used. As a preferred phosphate salt,
The sodium salt or potassium salt of glycerophosphoric acid may be mentioned.

Preferred embodiments of the electrolyte component include the following compounds. Sodium: sodium chloride, sodium lactate, sodium acetate, sodium sulfate, sodium potassium glycerophosphate: potassium chloride, potassium glycerophosphate, potassium sulfate, potassium acetate, potassium lactate calcium: calcium gluconate, calcium chloride,
Calcium glycerophosphate, calcium lactate, calcium pantothenate, calcium magnesium acetate: magnesium sulfate, magnesium chloride,
Magnesium glycerophosphate, magnesium acetate, magnesium lactate phosphorus: potassium glycerophosphate, sodium glycerophosphate, magnesium glycerophosphate, calcium zinc glycerophosphate: zinc sulfate, zinc chloride, zinc gluconate, zinc lactate, zinc acetate

The infusion solution containing the amino acid and the electrolyte contained in the second chamber can be prepared by various methods. For example, various amino acids and electrolytes to be mixed are dissolved in purified water such as water for injection. It is prepared by
The composition of the infusion solution containing the amino acid and the electrolyte depends on the concentration of the infusion solution (that is, the infusion solution containing the fat emulsion and sugar) contained in the first chamber, the volume ratio of the infusion solution injected into the first chamber and the second chamber, etc. Although appropriately adjusted, for example, the total amount of amino acids is about 1 to 15%, preferably about 2 to 13%, more preferably about 3 to 12%, as an electrolyte, sodium 50 to 180 mEq / l, potassium 40 to 135 mEq / l. Degree, calcium 10-50mEq / l,
Magnesium 5 to 30 mEq / l, chlorine 0 to 225 mEq / l,
An infusion solution consisting of about 3 to 40 mEq / l of phosphorus, about 0 to 100 μmol / l of zinc, and an appropriate amount of water is exemplified.

The amount of the infusion solution contained in the first and second chambers, and the types, blending ratios and concentrations of the fat emulsion, sugar, amino acid and electrolyte in each infusion solution are used, the disease of the patient to be administered,
The composition can be appropriately adjusted according to the symptom and the like, but it is preferably adjusted to have the following composition range when the infusion solutions contained in the first chamber and the second chamber are mixed. Oil 5 to 50 g / l Emulsifier 0.5 to 10 g / l Sugar 50 to 250 g / l L-isoleucine 0.5 to 5 g / l L-leucine 0.5 to 7 g / l L-valine 0. 5 to 5 g / l L-lysine 0.5 to 7 g / l L-methionine 0.1 to 4 g / l L-phenylalanine 0.3 to 5 g / l L-threonine 0.3 to 5 g / l L-tryptophan 0.1 to 1 g / l L-arginine 0.3 to 7 g / l L-histidine 0.2 to 3 g / l glycine 0.2 to 3 g / l L-alanine 0.3 to 5 g / l L-proline 0.2 to 5 g / l L-aspartic acid 0.03 to 2 g / l L-serine 0.2 to 3 g / l L-tyrosine 0.03 to 0.5 g / l L-glutamic acid 0.03 to 2 g / l L-cysteine 0.03 to 1 / L Sodium 15-60 mEq / l Potassium 10-50 50 mEq / l Calcium 3-15 mEq / l Magnesium 2-10 mEq / l Chlorine 0-80 mEq / l Phosphorus 1-15 mEq / l Zinc 0-30 μmol / l

The liquid properties of the infusion solution contained in the first chamber and the second chamber are not particularly limited, but p is preferable from the viewpoint of safety for the living body.
H should be adjusted to 5.0 to 8.0, preferably 5.5 to 7.0.
In particular, when a polyhydric alcohol or a phosphoric acid ester of sugar or a salt thereof is used as a phosphorus supply source in the infusion solution contained in the second chamber, the precipitation is effectively suppressed even at a relatively high pH. be able to. The pH adjuster used for adjusting the pH of each of the above infusions is not particularly limited as long as it is physiologically acceptable, and various acid agents can be used, but organic acids are preferably used. Examples of the organic acid include citric acid, gluconic acid, lactic acid, malic acid, maleic acid, malonic acid and the like. Particularly, an organic acid having a chelating power for a divalent metal ion is preferable, and citric acid is preferable. Is used.

In addition, an anti-coloring agent (eg, thioglycerol, dithiothreitol, etc.) is added to the infusion solution contained in the first chamber and the second chamber in order to prevent coloring during sterilization and storage. The amount of anti-coloring agent added is usually 1
It is less than about%. The anti-coloring agent may be added to the infusion solution in the first chamber, the infusion solution in the second chamber, or both. Furthermore, a buffer such as L-histidine, tris (hydroxymethyl) aminomethane or the like may be added to the infusion solution contained in the first chamber, and the addition amount of these is usually about 1% or less. . In addition, one or both of the infusion solutions contained in the first chamber and the second chamber may contain vitamins (for example, vitamin A, vitamin B, vitamin C, vitamin D, vitamin E,
Vitamin Ks, etc.) may be added.

The infusion solution contained in the first chamber and the second chamber may be aseptically pre-sterilized by heat sterilization and the like and may be aseptically filled and sealed in each chamber, but preferably the first chamber and the second chamber. Two
A method is used in which each chamber is filled with an infusion solution (preferably in the presence of an inert gas), sealed, and then sterilized.
Sterilization can be carried out according to a conventional method, for example, a heat sterilization method such as high-pressure steam sterilization, hot water immersion sterilization, hot water shower sterilization and the like. Examples of the container used in the present invention include a glass container, a plastic (for example, polypropylene, polyethylene, ethylene-vinyl acetate copolymer, polyvinyl chloride, etc.) container, and the like, which is particularly made of a material that can withstand heat sterilization. Containers are preferred.

[0020]

The present invention will be described in more detail with reference to the drawings showing examples, but the present invention is not limited to these examples. FIG. 1 is a schematic view showing one embodiment of a container containing an infusion solution of the present invention. In the figure, the container 1 is made of a plastic material or the like and has two private chambers, a first chamber 2 and a second chamber 3. The first chamber 2 contains an infusion solution 4 containing a fat emulsion and sugar, and the second chamber 3 contains an infusion solution 5 containing an amino acid and an electrolyte.
The first chamber 2 and the second chamber 3 are provided in a communication part 6 that connects them so that the infusion solution 4 contained in the chamber 2 and the infusion solution 5 contained in the second chamber 3 are not mixed. It is isolated by isolation means such as 7. Also, in the container 1,
Port 8 for injecting infusion solution 4 into first chamber 2, second chamber 3
A port 9 for injecting the infusion solution 5 and a port 10 for taking out the infusion solution after mixing are provided. If necessary, other agents can be mixed in through these ports.

The above-mentioned infusion solution-containing container is obtained as follows. First, the communication part 6 of the container 1 is shut off by an isolation means such as a pinch cock 7 to isolate the first chamber 2 and the second chamber 3,
Then, an infusion solution containing the fat emulsion and the sugar is injected into the first chamber 2 through the port 8, and an infusion solution containing the amino acid and the electrolyte is injected into the second chamber 3 through the port 9. The first
It is preferable to inject the infusion solutions 4 and 5 into the chamber 2 and the second chamber 3 under a stream of an inert gas (eg, nitrogen gas, argon gas, etc.). Infusions 4 and 5 into the first chamber 2 and the second chamber 3
After the injection is completed, the ports 8 and 9 are respectively sealed and then sterilized to obtain the infusion solution-containing container shown in FIG. The sterilization can be performed according to a conventional method, for example, a heat sterilization method such as high-pressure steam sterilization, hot water immersion sterilization, hot water shower sterilization, etc., and a plastic container is used as in this example. in case of,
It is preferable to sterilize under an atmosphere substantially free of oxygen.

The infusion solution-containing container of the present invention thus obtained can be stored in that state, and the pinch cock 7 can be used at the time of use.
Is removed to allow the first chamber 2 and the second chamber 3 to communicate with each other, and the infusion solutions 4 and 5 contained therein are mixed to aseptically prepare an infusion solution containing a fat emulsion, sugar, amino acid and electrolyte. can do. Then, the above mixed infusion is aseptically taken out from the port 8 through a tube (not shown) and administered to a living body.

FIG. 2 is a schematic view showing another embodiment of the infusion solution containing container according to the present invention. In the figure, the container 11 is made of a rectangular plastic material or the like, and is isolated by a large screw cock 16 to separate the first chamber 12 and the second chamber 1.
Two private chambers 3 are formed. The first chamber 12 contains an infusion solution 14 containing a fat emulsion and sugar, and the second chamber 13 contains an infusion solution 15 containing an amino acid and an electrolyte. Room 1
Since the second and second chambers 13 are isolated from each other, the infusion solution 14 contained in the first chamber 12 and the infusion solution 15 contained in the second chamber 13 are not mixed. Also, in the container 11,
A port 17 for injecting the infusion solution 14 into the first chamber 12, a port 18 for injecting the infusion solution 15 into the second chamber 13, and a port 19 for taking out the infusion solution after mixing are provided. If necessary, other agents can be mixed in through these ports. The method of manufacturing and using the infusion solution-containing container shown in FIG. 2 is substantially the same as those of the infusion solution-containing container shown in FIG.

The infusion solution containing container shown in FIGS. 1 and 2 is one embodiment of the present invention, and is not limited to these. The shape and size of the container can be changed as appropriate.
Also, the isolation means is not limited to the above example,
For example, in FIG. 1, a clip or the like may be used instead of the pinch cock 7, and a ball stopper may be further provided in the communication portion 6 to separate the first chamber 2 and the second chamber 3.

The container containing an infusion solution of the present invention may be packaged with an oxygen impermeable membrane material in order to prevent alteration of the infusion solution in the container. As the oxygen impermeable membrane material, for example, a three-layer laminate film including an ethylene-vinyl alcohol copolymer film, a polyvinyl alcohol film, a polyvinylidene chloride film or the like as an intermediate layer (for example, the outer layer is a polyester film, a stretched nylon film). , A laminated film made of a stretched polypropylene film or the like, and an inner layer made of an unstretched polypropylene film),
Laminated film containing an aluminum layer (for example, polyester film-aluminum layer-laminated film composed of unstretched polypropylene film), laminated film containing an inorganic vapor deposition film (eg polyester film-silicon deposited film-unstretched polypropylene film, stretched nylon) Film-silicon vapor deposition film-unstretched polypropylene film, polyester film-aluminum vapor deposition film-unstretched polypropylene film, alumina vapor deposition polyester film-polyvinylidene chloride film-unstretched polypropylene film, and the like). Further, an oxygen absorber (eg, Ageless, trade name) may be contained between the outer packaging and the container, and further vacuum packaging, inert gas (eg nitrogen gas, etc.) filling packaging may be performed according to a conventional method. It is also possible to

The infusion solution containing a fat emulsion, sugar, amino acid and electrolyte obtained by mixing the infusion solutions contained in the first chamber and the second chamber has good storability, precipitation formation, alteration, coloring, etc. It can be stored for about 1 week without causing
The infusion solution is intravenously administered to a patient as it is or after diluting it with water, or alone or in combination with a drug or the like as necessary. Furthermore, it can be used for administration in a dosage form such as oral administration and enteral administration.

Hereinafter, the present invention will be described in more detail based on production examples.
However, the present invention is not limited to these examples.
There is no. Production example 1(1) Preparation of infusion solution containing fat emulsion and sugar Soybean oil 66 g, egg yolk phospholipid 9.5 g and glucose 500 g in water
After homogenizing with a homomixer, add water and mix well.
The amount was set to 1000 ml to obtain a crude emulsion. Obtained crude emulsion
The Manton Gorin homogenizer (made by Gorin Co.,
15M-8TA type) until the average particle size becomes 0.17 μm or less
An emulsion was obtained by emulsification. Add water to 500 ml of the obtained emulsion
The total volume was 1000 ml. The composition of the obtained infusion solution is shown in Table 1.
You

[0028]

[0029](2) of infusion solution containing amino acid and electrolyte
Preparation Injectable water heated to approximately 80 ° C under a nitrogen stream under Table 2 and Table
Amino acid and electrolyte shown in 3 should be adjusted to each concentration.
Add and dissolve, adjust pH to 6.2 with citric acid
It was

[0030]

[Table 2]

[0031]

[Table 3]

[0032](3) Preparation of infusion container Use a polypropylene container with the shape shown in Figure 1.
I was there. After shutting off the communication part 6 with the pinch cock 7, the first chamber
Infusion 6 containing the fat emulsion and sugar obtained in (1) above in 2
Inject 00 ml from port 8 while filling with nitrogen gas,
After entering, the port 8 was sealed. On the other hand, in the second chamber 3, the above
300 ml of infusion solution containing amino acid and electrolyte obtained in
Inject from port 9 while filling with nitrogen gas, and after injection,
Port 9 was sealed. High pressure is applied to the container 1 containing each infusion solution.
Perform steam sterilization (115 ℃, 30 minutes), then cool to room temperature
Then, a container containing the infusion solution of the present invention was obtained.

[0033](4) Infusion solution prepared using the container of the present invention
Stability test Pinchco of the communication part 6 of the container containing the infusion solution obtained in (3) above
The hook 7 is removed, and the liquid in the first chamber 2
Mix well with the infusion solution in the second chamber 3 to get fat emulsion, sugar,
An infusion solution containing a mino acid and an electrolyte was obtained. Thus obtained
The composition of the infusion solution (composition per liter of infusion solution) is shown in Table 4.
Show. Store the infusion solution obtained above at 25 ° C for 1 week.
Changes in appearance, mean particle size of fat emulsion and turbidity
did. The results are shown in Table 5. As a control,
Inject 300 ml of water for injection into 2 chamber 3, sterilize in the same manner, and mix.
The infusion solution was used. The average particle size of fat emulsion is determined by the light scattering method.
Therefore, the turbidity was measured by the absorbance at 620 nm (1 cm cell).

[0034]

[Table 4]

[0035]

As shown in Table 5, no change in appearance, particle size and turbidity was observed, which revealed that the infusion solution prepared using the container of the present invention had high stability.

Production Example 2 An infusion solution having the composition shown in Table 6 below was prepared according to (1) of Production Example 1. In the same manner as in Production Example 1, except that the fat emulsion in Table 6 used in place of the fat emulsion in Table 1 used in Production Example 1 and the electrolyte in Table 7 used in place of the electrolyte in Table 3 were used,
A container containing an infusion solution was prepared. The pinch cock 7 of the communication part 6 of the container containing the infusion solution obtained above is removed, and the infusion solution of the first chamber 2 and the infusion solution of the second chamber 3 are thoroughly mixed through the communication part 6 to obtain a fat emulsion, sugar, amino acid. And an infusion solution containing an electrolyte were obtained. The composition of the infusion solution thus obtained (composition per liter of infusion solution) is shown in Table 4. In addition, the stability test of the obtained infusion solution was performed in the same manner as in Production Example 1. As a result, excellent stability was exhibited as in Production Example 1.

[0038]

[0039]

[Table 7]

Production Example 3 To 66 g of soybean oil and 9.5 g of egg yolk phospholipid was added an appropriate amount of water, and the mixture was stirred with a homomixer to a total volume of 1000 ml with water. The obtained crude emulsion was emulsified with a Manton Gorin homogenizer (manufactured by Gorin Co., 15M-8TA type) to prepare a fat emulsion. To 500 ml of this fat emulsion, 250 g of glucose was added, and water was added to make the total amount 1000 ml. The composition of the obtained fat emulsion is shown in Table 8. An infusion solution container was prepared in the same manner as in Production Example 1 except that the fat emulsion in Table 8 used in place of the fat emulsion in Table 1 used in Production Example 1 was used. The pinch cock 7 of the communication part 6 of the container containing the infusion obtained above is removed to remove the communication part 6
The infusion solution in the first chamber 2 and the infusion solution in the second chamber 3 were thoroughly mixed with each other to obtain an infusion solution containing a fat emulsion, sugar, an amino acid and an electrolyte (pH about 6.0). The stability test of the thus obtained infusion solution was carried out in the same manner as in Production Example 1. As a result, excellent stability was exhibited as in Production Example 1.

[0041]

Production Example 4 Production Example 2 in place of the amino acid / electrolyte solution used in Production Example 1
A container containing an infusion solution was prepared in the same manner as in Production Example 1 except that the amino acid / electrolyte solution used in 1. was used. Remove the pinch cock 7 of the communicating part 6 of the container containing the infusion obtained above,
The infusion solution in the first chamber 2 and the infusion solution in the second chamber 3 were thoroughly mixed through the communication part 6 to obtain an infusion solution containing a fat emulsion, sugar, amino acid and an electrolyte (pH about 6.0). The stability test of the thus obtained infusion solution was carried out in the same manner as in Production Example 1.
As a result, excellent stability was exhibited as in Production Example 1.

Production Example 5 A container containing an infusion solution was prepared in the same manner as in Production Example 1 except that the fat emulsion shown in Table 6 was used instead of the fat emulsion shown in Table 1 used in Production Example 1. The pinch cock 7 of the communication part 6 of the container containing the infusion solution obtained above is removed, and the infusion solution of the first chamber 2 and the infusion solution of the second chamber 3 are sufficiently mixed through the communication part 6 to obtain a fat emulsion,
An infusion solution containing sugar, amino acid, and electrolyte was obtained (pH about 6.0). The stability test of the thus obtained infusion solution was carried out in the same manner as in Production Example 1. As a result, excellent stability was exhibited as in Production Example 1.

[0044]

As described above, in the present invention, the two isolated chambers are pre-filled with the infusion solution containing the fat emulsion and the sugar and the infusion solution containing the amino acid and the electrolyte. It is possible to prepare an infusion solution containing sugar, amino acid, electrolyte and fat emulsion simply by removing the above. Moreover, although the obtained infusion solution contains each of these components, precipitation, phase separation, alteration, etc. It shows high stability without causing Therefore, according to the present invention, an infusion solution having excellent stability and safety can be obtained,
Further, since the operation of mixing the fat emulsion, the sugar, the amino acid and the electrolyte is not required, the operation is simplified and the bacterial contamination at the time of mixing can be prevented.

[Brief description of drawings]

FIG. 1 is a schematic view showing an embodiment of a container containing an infusion solution of the present invention.

FIG. 2 is a schematic view showing another embodiment of the infusion solution-containing container of the present invention.

[Explanation of symbols]

1, 11 containers 2, 12 First room 3, 13 Second room 4,14 Infusion containing fat emulsion and sugar 5,15 Infusion containing amino acid and electrolyte 6 communication section 7, 16 isolation means 8, 9, 10, 17, 18, 19 ports

Front Page Continuation (72) Inventor Ryoichiro Murashima Invitation to Hirakata City 2-25-1 Otani Midori Cross Central Research Institute (72) Inventor Shunichi Abe Invitation to Hirakata City 2-25-1 Otani Midori Co., Ltd. CROSS Central Research Institute (72) Inventor Kazumasa Yokoyama Invited by Hirakata City 2-25-1 Otani Midori CROSS Central Research Laboratory (56) Reference JP-A-2-241457 (JP, A) JP-A-1- 34917 (JP, A) JP-A-3-161430 (JP, A) JP-A-49-124057 (JP, A) JP-B 37-6542 (JP, B1) JP-B 63-63534 (JP, B1) (58) Fields surveyed (Int.Cl. ⁷ , DB name) A61J 1/00 313 A61K 9/107

Claims (9)

(57) [Claims] 1. A container in which two separate chambers are formed by an isolation means, a first chamber contains an infusion solution containing a fat emulsion and sugar, and a second chamber contains an infusion solution containing an amino acid and an electrolyte. Is contained in the first chamber, and the infusion solution contained in the first chamber is 0.1 to 30 (W / V)% of oil and fat, 0.01 to 10 (W / V) of phospholipid.
% And sugar 7 to 40 (W / V)%, the phospholipid
Quality of egg yolk phospholipids, hydrogenated egg yolk phospholipids, soybean phospholipids
One or two selected from quality and hydrogenated soybean phospholipids
A container containing an infusion solution, which is the above phospholipid . 2. The infusion liquid contained in the first chamber is oil or fat.
0.1-30 (W / V)%, phospholipid 0.01-10 (W / V)% and sugar 10-30
The infusion solution-containing container according to claim 1, which is an infusion solution containing (W / V)%. 3. The infusion solution contained in the second chamber contains a total amount of amino acids of 1 to 15 (W / V)% and sodium 5 as an electrolyte.
0-180mEq / l, potassium 40-135mEq / l, calcium 10-5
0mEq / l, magnesium 5-30mEq / l, chlorine 0-225mEq / l,
The infusion solution-containing container according to claim 1 or 2, which is an infusion solution containing 3 to 40 mEq / l of phosphorus and 0 to 100 µmol / l of zinc. 4. The infusion solution container according to claim 3, wherein a polyhydric alcohol or a phosphoric acid ester of sugar or a salt thereof is blended as a phosphorus source. 5. The container with an infusion solution according to claim 1, wherein the fat emulsion contained in the infusion solution contained in the first chamber has an average particle size of 0.17 μm or less. 6. The pH of one or both of the infusion solutions contained in the first chamber and the second chamber is adjusted to 5.0 to 8.0 by using an organic acid. A container containing an infusion solution described in Crab. 7. The infusion solution-containing container according to claim 6, wherein the organic acid is citric acid. 8. The phospholipid is egg yolk phospholipid or hydrogenated.
The infusion solution-containing container according to any one of claims 1 to 7, which is egg yolk phospholipid . 9. The infusion solution-containing container according to claim 1, which is a heat-sterilized infusion solution-containing container.