JPH1087497A - Peripheral intravenous transfusion solution - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject two-part transfusion solution inducing no phlebitis because of having a nearly neutral pH level when a reducing sugar-contg. solution and an amino acid-contg. solution are mixed together. SOLUTION: This peripheral intravenous transfusion solution is made up of (A) a reducing sugar-contg. solution and (B) a solution containing an amino acid composition at least comprising essential amino acids. In this case, the solution A contains part of an electrolyte so as to be <=10 in titratable acidity, being adjusted to pH3.7-5.0; while the solution B contains the rest of the electrolyte, being adjusted to pH6.5-8.0. The volume ratio A/B is (5:1) to (1:1). When the two solutions A and B are joined together, the mixture runs to pH6.0-7.2.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a nutritional infusion containing a reducing sugar, an amino acid and an electrolyte, and more particularly to a phlebitis due to a near neutral pH when mixed at the time of use. The present invention relates to an infusion for peripheral intravenous administration that does not.

[0002]

2. Description of the Related Art In many cases, patients after gastrointestinal surgery cannot be orally ingested. Therefore, nutritional management of such patients is generally performed by high caloric infusion (IVH) from a central vein. I have. IVH can promote the recovery and healing of patients by improving and maintaining the nutritional status of the patients mentioned above, and since its effect is enormous, it is now widely used in the field of surgical treatment. Widespread.

[0003] On the other hand, IVH has disadvantages such as the need for strict control, the risk of infection, and the risk of metabolic complications such as hyperglycemia. Patients with good nutritional status and relatively low invasiveness, and patients who have been incapable of taking oral food for a very short period of time, tend to recruit as much peripheral vein as possible.

[0004] In any case, the preparation used for the above nutritional supplement contains 1 sugar containing all sugars, amino acids and electrolytes.
Ideally in dosage form. However, when a reducing sugar such as glucose is used as a carbohydrate, a Maillard reaction occurs with an amino acid, which causes browning. Therefore, the reducing sugar is usually contained in one of the two-chamber containers together with the electrolyte, and the other is contained in the other chamber. It has been practiced to separate and contain amino acids into a formulation. In this type of preparation, the pH of each solution is usually adjusted to about pH 6 to 7 on the amino acid side, and the reducing sugar side is adjusted to about pH 5 to stabilize the sugar and prevent precipitation of phosphorus and calcium or magnesium. Alternatively, it is adjusted to a slightly lower pH.

[0005]

The above-mentioned preparations are administered by being mixed before use, and the liquid after mixing has a pH of less than 6 (usually
(pH about 5 to 5.5). However, such an acidic solution causes phlebitis when administered from a peripheral vein, and the tendency tends to increase as the administration time becomes longer. Phlebitis is not only a trivial problem that can be severely painful and force the patient to speak out, but also can cause blood clots and even pulmonary or cerebral embolism.

In order to prevent phlebitis, medical care is currently taking measures such as frequently changing the drip site. However, the number of operations is increased, the work is complicated, and a heavy burden is imposed on nurses. This is the actual situation.

Accordingly, an object of the present invention is to provide an infusion for peripheral venous administration which does not cause phlebitis when the solution on the reducing sugar side and the solution on the amino acid side have a pH close to neutrality.

[0008]

Under these circumstances, the present inventors have conducted intensive studies and as a result, have determined that the titration acidity of the reducing sugar side solution and the pH of both the reducing sugar side and amino acid side solutions are within a specific range. By adjusting the pH to, the pH of the mixed solution was successfully adjusted to a pH close to neutrality, and the present invention was completed.

That is, the present invention provides an infusion comprising two solutions, a solution (A) containing a reducing sugar and a solution (B) containing an amino acid composition comprising at least essential amino acids.
Solution (A) contains a part of the electrolyte so that its titratable acidity is 10 or less, and is adjusted to pH 3.7 to 5.0.
(B) contains the remainder of the electrolyte and is adjusted to pH 6.5 to 8.0, the volume ratio (A) :( B) of both solutions is 5: 1 to 1: 1 and both solutions are mixed. It is intended to provide an infusion for peripheral intravenous administration, which is sometimes pH 6.0 to 7.2.

[0010]

DETAILED DESCRIPTION OF THE INVENTION In the present invention, a solution on the reducing sugar side is used.
In (A), the titratable acidity needs to be 10 or less, but more preferably 1 or less. If the titration acidity of the solution (A) exceeds 10, the pH when mixing both solutions tends to deviate from the above optimum range. Such titration acidity adjustment can be performed by selecting the type of electrolyte to be blended on the reducing sugar side, specifically, by blending as much of the strong electrolyte in the electrolyte as possible in the solution (A). Although it is carried out, it is particularly preferable to mix only a strong electrolyte.

Here, as the electrolyte used in the infusion of the present invention, the same compounds as those used in general electrolyte infusion can be used. Specifically, sodium sources include sodium chloride, sodium acetate, sodium citrate, sodium dihydrogen phosphate, disodium hydrogen phosphate, sodium sulfate, sodium lactate, and the like. Potassium sources include potassium chloride, potassium acetate , Potassium citrate, potassium dihydrogen phosphate, dipotassium hydrogen phosphate, potassium sulfate, potassium lactate, etc., and calcium sources such as calcium chloride, calcium gluconate, calcium pantothenate, calcium lactate, calcium acetate, magnesium, etc. As a source, magnesium sulfate, magnesium chloride, magnesium acetate, etc., as a phosphorus source, sodium dihydrogen phosphate, disodium hydrogen phosphate, sodium glycerophosphate, etc., as a chlorine source,
Examples of sodium chloride, potassium chloride, calcium chloride, magnesium chloride and the like, and examples of the zinc source include zinc sulfate, zinc chloride and the like, which may be in the form of a hydrate.

[0012] Of the above electrolytes, the solution (A) on the reducing sugar side preferably contains as many strong electrolytes as possible as described above. Specific examples of strong electrolytes include sodium chloride, sodium sulfate, and chloride. Potassium, potassium sulfate, calcium chloride, magnesium sulfate, magnesium chloride, zinc sulfate, zinc chloride and the like can be mentioned. The remaining electrolyte to be blended is the solution (B) on the amino acid side.
It is blended in. Incidentally, the electrolyte blended in the solution (B),
It does not matter whether it is a strong electrolyte or not.

In addition, when blending the electrolytes of the calcium source and the phosphorus source, in order to prevent precipitation by both,
It is preferable to mix them separately, for example, it is preferable to mix the calcium source into the reducing sugar side solution (A) and mix the phosphorus source into the amino acid side solution (B). Further, since the magnesium source may also form a precipitate with the phosphorus source, the magnesium source is converted to the reducing sugar side solution (A) in the same manner as described above.
It is preferable to mix them.

In the infusion of the present invention, the reducing sugar used in the solution (A) includes glucose, fructose, maltose and the like, and these can be used alone or in combination of two or more. Of these, glucose is preferably used from the viewpoint of blood sugar management and the like, and if necessary, an optimal amount of a non-reducing sugar such as xylitol, sorbitol, or glycerin may be added. The amount of the reducing sugar can be appropriately determined according to the purpose of use such as the administration route. However, the amount of the reducing sugar after mixing the solutions (A) and (B) should be 3 to 10 w / v%. Is preferred.

The reducing sugar solution (A) is prepared by using a small amount of a pH adjuster, if necessary, to obtain a pH of 3.7 to 5.0, preferably pH 4.0 to 5.0.
Adjusted to 4.5. When the pH of the solution (A) is less than 3.7, it is difficult to keep the pH when the two solutions are mixed in the above range, and when the pH exceeds 5.0, degradation of the reducing sugar causes quality deterioration such as coloring of the solution. May come.

On the other hand, the amino acid side solution (B) needs to contain an amino acid composition comprising at least essential amino acids, and each amino acid used is a pure crystalline amino acid similarly to a general amino acid infusion. Is preferred. These are usually used in the form of free amino acids, but may not be particularly in the free form, and are used in the form of pharmacologically acceptable salts, esters, N-acyl derivatives, salts of two kinds of amino acids or peptides. You can also.

The amino acid side solution (B) may be added with a small amount of a pH adjuster, if necessary, to obtain a solution having a pH of 6.5 to 8.0, preferably pH 6.5 to 8.0.
Adjusted to 7.4. If the pH of the solution (B) is less than 6.5, the pH after mixing cannot be maintained in the optimum range as described above,
If it exceeds 8.0, easily oxidizable amino acids such as L-cysteine become more unstable, which is not preferable.

The volume ratio of the solutions (A) and (B) is (A):
(B) = 5: 1 to 1: 1, preferably (A) :( B) =
It is prepared in the range of 3: 1 to 1: 1. If the volume ratio is out of the above range, it is difficult to produce a stable preparation in consideration of the required dose of amino acids and reducing sugars and the solubility in water.

In the infusion of the present invention thus prepared,
Since the solution (A) has a pH of 3.7 to 5.0 and is on the more acidic side as compared with a conventional infusion solution, it is possible to advantageously prevent sugar decomposition, electrolyte precipitation, and the like. Nevertheless, when this solution (A) is mixed with solution (B), a near neutral pH of pH 6.0-7.2
And a transfusion solution that does not cause phlebitis can be obtained. Further, the infusion of the present invention has a pH of 6.
More preferably, it is set to be in the range of 5 to 7.2.

The infusion solution of the present invention is stabilized by setting both solutions in a specific pH range. If necessary, a stabilizer such as sodium hydrogen sulfite may be added to the solution (A). And (B) can be appropriately added.

More preferred examples of the infusion of the present invention include the following compositions in the composition of the liquid after mixing.

[0022]

[Table 2] Glucose 3-10 w / v% Na ⁺ 25-70 mEq / l K ⁺ 15-50 mEq / l Ca ²⁺ 3-15 mEq / l Mg ²⁺ 3-10 mEq / l Cl ^- 25- 70 mEq / l P 5-20 mmol / l Zn ²⁺ 0-30 μmol / l L-isoleucine 1.0-4.0 g / l L-leucine 2.0-7.0 g / l L-lysine 1.5-7.5 g / l L-methionine 0.5-2.5 g / l L-phenylalanine 1.0-4.0 g / l L-threonine 0.8-3.0 g / l L-tryptophan 0.2-1.2 g / l L-valine 0.7-4.2 g / l L-alanine 1.0-4.2 g / l L-arginine 1.4-5.5 g / l L-aspartic acid 0.1-1.7 g / l L-cysteine 0.1-0.7 g / l L-glutamic acid 0.1-3.0 g / l L-histidine 0.8-2.7 g / l L-proline 0.6-2.6 g / l L-serine 0.3-1.7 g / l L-tyrosine 0-0.5 g / l glycine 1.0-4.5 g / l

The container for accommodating the infusion of the present invention is not particularly limited. For example, a container in which a partition is formed by easily peelable welding (JP-A-2-4671 and JP-A-5-5138, etc.) (Such as JP-A-63-309263) or a partition provided with various openable communication means (such as JP-B-63-20550). Two-chamber containers separated by possible partitions. Among these, those in which the partition walls are formed by easily peelable welding are preferable because they are suitable for mass production and the communication work is easy.

The container may be made of various gas-permeable plastics commonly used for medical containers and the like.
For example, polyethylene, polypropylene, polyvinyl chloride, cross-linked ethylene / vinyl acetate copolymer, ethylene / α
-Olefin copolymers, blends and laminates of these polymers, and the like.

The infusion of the present invention into a container can be filled and stored according to a conventional method. For example, a method of filling each chamber in an inert gas atmosphere, closing the chamber, and sterilizing by heating is used. No. Here, the heat sterilization can employ a known method such as high-pressure steam sterilization or hot water shower sterilization, and can be performed in an atmosphere of an inert gas such as carbon dioxide or nitrogen as necessary.

Further, the infusion solution of the present invention housed in the above-mentioned container is preferably packaged in a gas-impermeable outer container together with a deoxidizer in order to reliably prevent deterioration, oxidation and the like. When a partition formed by easily peelable welding is used, it is preferable that the partition is packaged in a folded state at the partition so that the partition does not communicate with the external pressure. In addition, an inert gas filling packaging or the like can be performed as necessary.

As the material of the gas-impermeable outer container suitable for the packaging, films and sheets of various materials generally used can be used. Specific examples thereof include, for example, an ethylene / vinyl alcohol copolymer, polyvinylidene chloride, polyacrylonitrile, polyvinyl alcohol, polyamide, polyester, and the like, or a film or sheet made of a material containing at least one of these.

As the oxygen scavenger, various known oxygen scavengers, for example, those containing an iron compound such as iron hydroxide, iron oxide or iron carbide as an active ingredient can be used. As typical commercial product names, “Ageless” (manufactured by Mitsubishi Gas Chemical Company), “Modulan” (manufactured by Nippon Kayaku), “Sequel” (manufactured by Nippon Soda Co., Ltd.) and the like can be mentioned.

At the time of administration of the infusion solution of the present invention, other combination drugs such as various vitamins and trace elements (minerals) can be optionally added and blended, if necessary. Examples of the vitamins include water-soluble and fat-soluble ones, for example, retinol palmitate, thiamine hydrochloride, riboflavin, pyridoxine hydrochloride, cyanocobalamin, ascorbic acid, cholecasiferol, tocopherol acetate, nicotinamide, and calcium pantothenate. , Folic acid, biotin, phytonadione and the like.

[0030]

EXAMPLES Hereinafter, the present invention will be described in more detail with reference to examples, but the present invention is not limited thereto.

Example 1 Glucose, magnesium sulfate and calcium chloride were dissolved in distilled water for injection, and glucose 74 g / l, magnesium sulfate
A sugar electrolyte solution [solution (A)] having a composition of 1.03 g / l and calcium chloride of 0.61 g / l was prepared. The pH of this solution is 4.5 and the titratable acidity is
It was 0.1. On the other hand, the following crystalline amino acid and electrolyte were dissolved in distilled water for injection, and a small amount of acetic acid was used as a pH adjuster to adjust the pH to 7.0, thereby producing an amino acid electrolyte solution [solution (B)] having the following composition.

[0032]

[Table 3] L-isoleucine 8.0 g / l L-leucine 14.0 g / l L-lysine acetate 14.8 g / l L-methionine 3.9 g / l L-phenylalanine 7.0 g / l L-threonine 5.7 g / l L-tryptophan 2.0 g / l L-valine 8.0 g / l L-alanine 8.0 g / l L-arginine 10.5 g / l L-aspartic acid 1.0 g / l L-cysteine 1.0 g / l L-glutamic acid 1.0 g / l L-histidine 5.0 g / l L-proline 5.0 g / l L-serine 3.0 g / l L-tyrosine 0.5 g / l glycine 5.9 g / l sodium chloride 8.79 g / l sodium citrate 2.4 g / l potassium acetate 3.93 g / l phosphorus Dipotassium hydrogen oxyate 5.22 g / l Zinc sulfate 28.8 mg / l

The both solutions were aseptically filtered, and 600 ml of the solution (A) and 200 ml of the solution (B) were filled into each of the two polyethylene chambers, and the solution (B) was replaced with nitrogen and sealed. After that, autoclaving was performed according to a conventional method to obtain an infusion for peripheral intravenous administration. The pH of the solution after mixing the infusion solutions (A) and (B) was 6.7.

Example 2 Glucose, magnesium sulfate and calcium gluconate were dissolved in distilled water for injection, and a sugar electrolyte solution (solution) having a composition of 74 g / l of glucose, 0.82 g / l of magnesium sulfate, and 1.49 g / l of calcium gluconate was used. (A)) was prepared. To this solution, 500 ppm of sodium bisulfite was added as a stabilizer. The pH of this solution was 4.5 and the titratable acidity was 1.2. On the other hand, the following crystalline amino acid and electrolyte were dissolved in distilled water for injection, and a small amount of acetic acid was used as a pH adjuster to adjust the pH to 7.0, thereby producing an amino acid electrolyte solution [solution (B)] having the following composition.

[0035]

[Table 4] L-isoleucine 8.0 g / l L-leucine 14.0 g / l L-lysine acetate 14.8 g / l L-methionine 3.9 g / l L-phenylalanine 7.0 g / l L-threonine 5.7 g / l L-tryptophan 2.0 g / l L-valine 8.0 g / l L-alanine 8.0 g / l L-arginine 10.5 g / l L-aspartic acid 1.0 g / l L-cysteine 1.0 g / l L-glutamic acid 1.0 g / l L-histidine 5.0 g / l L-proline 5.0 g / l L-serine 3.0 g / l L-tyrosine 0.5 g / l glycine 5.9 g / l sodium chloride 4.22 g / l sodium acetate 8.96 g / l potassium chloride 5.06 g / l phosphoric acid Dipotassium hydrogen 2.71 g / l Zinc sulfate 9.1 mg / l

The both solutions were aseptically filtered, and 600 ml of the solution (A) and 200 ml of the solution (B) were filled in each of the two polyethylene chambers, and the solution (B) was purged with nitrogen and sealed. After that, autoclaving was performed according to a conventional method to obtain an infusion for peripheral intravenous administration. The pH of the solution after mixing the infusion solutions (A) and (B) was 6.7.

Example 3 Glucose, sodium chloride, magnesium sulfate, calcium chloride and zinc sulfate were dissolved in distilled water for injection, and the pH was adjusted to 4.0 using a trace amount of acetic acid as a pH adjuster.
4g / l, sodium chloride 2.93g / l, magnesium sulfate 1.03g
/ l, calcium chloride 0.61 g / l, zinc sulfate 9.6 mg / l, a sugar electrolyte solution [solution (A)] was prepared. The titration acidity of this solution was 0.2. On the other hand, the following crystalline amino acid and electrolyte were dissolved in distilled water for injection, and a small amount of acetic acid was used as a pH adjuster to adjust the pH to 7.0, thereby producing an amino acid electrolyte solution [solution (B)] having the following composition.

[0038]

Table 5 L-isoleucine 8.0 g / l L-leucine 14.0 g / l L-lysine acetate 14.8 g / l L-methionine 3.9 g / l L-phenylalanine 7.0 g / l L-threonine 5.7 g / l L-tryptophan 2.0 g / l L-valine 8.0 g / l L-alanine 8.0 g / l L-arginine 10.5 g / l L-aspartic acid 1.0 g / l L-cysteine 1.0 g / l L-glutamic acid 1.0 g / l L-histidine 5.0 g / l L-proline 5.0 g / l L-serine 3.0 g / l L-tyrosine 0.5 g / l glycine 5.9 g / l sodium citrate 2.4 g / l potassium acetate 3.93 g / l dipotassium hydrogen phosphate 5.22 g / l

The two solutions were aseptically filtered, and 600 ml of the solution (A) and 200 ml of the solution (B) were filled into each of the two polyethylene chambers, and the solution (B) was replaced with nitrogen and sealed. After that, autoclaving was performed according to a conventional method to obtain an infusion for peripheral intravenous administration. The pH of the solution after mixing the infusion solutions (A) and (B) was 6.7.

Example 4 Glucose, sodium chloride, potassium chloride, magnesium sulfate, calcium gluconate and zinc sulfate were dissolved in distilled water for injection, and the pH was adjusted using a trace amount of acetic acid as a pH adjuster.
As 4.0, glucose 74g / l, sodium chloride 1.76g / l,
A sugar electrolyte solution [solution (A)] having a composition of potassium chloride 2.11 g / l, magnesium sulfate 0.82 g / l, calcium gluconate 1.49 g / l, and zinc sulfate 3.8 mg / l was prepared. The titratable acidity of this solution is
7.5. On the other hand, the following crystalline amino acid and electrolyte were dissolved in distilled water for injection, and a small amount of acetic acid was used as a pH adjuster to adjust the pH to 7.0, thereby producing an amino acid electrolyte solution [solution (B)] having the following composition.

[0041]

[Table 6] L-isoleucine 8.0 g / l L-leucine 14.0 g / l L-lysine acetate 14.8 g / l L-methionine 3.9 g / l L-phenylalanine 7.0 g / l L-threonine 5.7 g / l L-tryptophan 2.0 g / l L-valine 8.0 g / l L-alanine 8.0 g / l L-arginine 10.5 g / l L-aspartic acid 1.0 g / l L-cysteine 1.0 g / l L-glutamic acid 1.0 g / l L-histidine 5.0 g / l L-proline 5.0 g / l L-serine 3.0 g / l L-tyrosine 0.5 g / l glycine 5.9 g / l sodium acetate 8.96 g / l dipotassium hydrogen phosphate 2.71 g / l

The two solutions were sterile-filtered, and 600 ml of the solution (A) and 250 ml of the solution (B) were filled in each of the two polyethylene chambers. The solution (B) was purged with nitrogen and sealed. After that, autoclaving was performed according to a conventional method to obtain an infusion for peripheral intravenous administration. The pH of the solution after mixing the infusion solutions (A) and (B) was 6.7.

Example 5 Glucose, magnesium sulfate and calcium chloride were dissolved in distilled water for injection, and glucose 107 g / l, magnesium sulfate
A sugar electrolyte solution (solution (A)) having a composition of 1.23 g / l and calcium chloride 0.73 g / l was prepared. The pH of this solution is 4.5 and the titratable acidity is
It was 0.1. On the other hand, the following crystalline amino acid and electrolyte were dissolved in distilled water for injection, and a small amount of acetic acid was used as a pH adjuster to adjust the pH to 7.0, thereby producing an amino acid electrolyte solution [solution (B)] having the following composition.

[0044]

[Table 7] L-isoleucine 8.0 g / l L-leucine 14.0 g / l L-lysine acetate 14.8 g / l L-methionine 3.9 g / l L-phenylalanine 7.0 g / l L-threonine 5.7 g / l L-tryptophan 2.0 g / l L-valine 8.0 g / l L-alanine 8.0 g / l L-arginine 10.5 g / l L-aspartic acid 1.0 g / l L-cysteine 1.0 g / l L-glutamic acid 1.0 g / l L-histidine 5.0 g / l L-proline 5.0 g / l L-serine 3.0 g / l L-tyrosine 0.5 g / l glycine 5.9 g / l sodium chloride 5.66 g / l sodium citrate 1.94 g / l potassium acetate 2.30 g / l phosphorus Dipotassium hydrogen oxyate 5.22 g / l Zinc sulfate 19.2 mg / l

The two solutions were aseptically filtered, and 600 ml of the solution (A) and 300 ml of the solution (B) were filled in each of two polyethylene chambers. The solution (B) was replaced with nitrogen, and sealed. After that, autoclaving was performed according to a conventional method to obtain an infusion for peripheral intravenous administration. The pH of the solution after mixing the infusion solutions (A) and (B) was 6.6.

Example 6 Glucose, magnesium sulfate and calcium gluconate were dissolved in distilled water for injection, and a sugar electrolyte solution [solution containing 107 g / l of glucose, 1.03 g / l of magnesium sulfate, and 1.87 g / l of calcium gluconate] (A)] was prepared. The pH of this solution is 4.5,
The titratable acidity was 1.6. On the other hand, the following crystalline amino acid and electrolyte were dissolved in distilled water for injection, and a small amount of acetic acid was used as a pH adjuster to adjust the pH to 7.0, thereby producing an amino acid electrolyte solution [solution (B)] having the following composition.

[0047]

[Table 8] L-isoleucine 8.0 g / l L-leucine 14.0 g / l L-lysine acetate 14.8 g / l L-methionine 3.9 g / l L-phenylalanine 7.0 g / l L-threonine 5.7 g / l L-tryptophan 2.0 g / l L-valine 8.0 g / l L-alanine 8.0 g / l L-arginine 10.5 g / l L-aspartic acid 1.0 g / l L-cysteine 1.0 g / l L-glutamic acid 1.0 g / l L-histidine 5.0 g / l L-proline 5.0 g / l L-serine 3.0 g / l L-tyrosine 0.5 g / l glycine 5.9 g / l sodium chloride 2.72 g / l sodium acetate 9.27 g / l potassium chloride 5.22 g / l phosphoric acid Dipotassium hydrogen 2.72 g / l Zinc sulfate 9.6 mg / l

The both solutions were aseptically filtered, and 600 ml of the solution (A) and 300 ml of the solution (B) were filled in each of the two polyethylene chambers. The solution (B) was purged with nitrogen and sealed. After that, autoclaving was performed according to a conventional method to obtain an infusion for peripheral intravenous administration. The pH of the solution after mixing the infusion solutions (A) and (B) was 6.6.

Example 7 Glucose, sodium chloride, magnesium sulfate, calcium chloride and zinc sulfate were dissolved in distilled water for injection, and a small amount of acetic acid was used as a pH adjuster to adjust the pH to 4.0.
07g / l, sodium chloride 2.83g / l, magnesium sulfate 1.23
A sugar electrolyte solution (solution (A)) having a composition of g / l, calcium chloride 0.73 g / l, and zinc sulfate 9.6 mg / l was prepared. The titration acidity of this solution was 0.2. On the other hand, the following crystalline amino acid and electrolyte were dissolved in distilled water for injection, and a small amount of acetic acid was used as a pH adjuster to adjust the pH to 7.0, thereby producing an amino acid electrolyte solution [solution (B)] having the following composition.

[0050]

[Table 9] L-isoleucine 8.0 g / l L-leucine 14.0 g / l L-lysine acetate 14.8 g / l L-methionine 3.9 g / l L-phenylalanine 7.0 g / l L-threonine 5.7 g / l L-tryptophan 2.0 g / l L-valine 8.0 g / l L-alanine 8.0 g / l L-arginine 10.5 g / l L-aspartic acid 1.0 g / l L-cysteine 1.0 g / l L-glutamic acid 1.0 g / l L-histidine 5.0 g / l L-proline 5.0 g / l L-serine 3.0 g / l L-tyrosine 0.5 g / l glycine 5.9 g / l sodium citrate 1.94 g / l potassium acetate 2.30 g / l dipotassium hydrogen phosphate 5.22 g / l

The two solutions were aseptically filtered, and 600 ml of the solution (A) and 300 ml of the solution (B) were filled in each of the two polyethylene chambers. The solution (B) was purged with nitrogen and sealed. After that, autoclaving was performed according to a conventional method to obtain an infusion for peripheral intravenous administration. The pH of the solution after mixing the infusion solutions (A) and (B) was 6.6.

Example 8 Glucose, sodium chloride, potassium chloride, magnesium sulfate, calcium gluconate and zinc sulfate were dissolved in distilled water for injection, and the pH was adjusted using a trace amount of acetic acid as a pH adjuster.
As 4.0, glucose 107 g / l, sodium chloride 1.36 g / l,
A sugar electrolyte solution [solution (A)] having a composition of 2.61 g / l potassium chloride, 1.03 g / l magnesium sulfate, 1.87 g / l calcium gluconate, and 4.8 mg / l zinc sulfate was prepared. The titratable acidity of this solution is
8.0. On the other hand, the following crystalline amino acid and electrolyte were dissolved in distilled water for injection, and a small amount of acetic acid was used as a pH adjuster to adjust the pH to 7.0, thereby producing an amino acid electrolyte solution [solution (B)] having the following composition.

[0053]

[Table 10] L-isoleucine 8.0 g / l L-leucine 14.0 g / l L-lysine acetate 14.8 g / l L-methionine 3.9 g / l L-phenylalanine 7.0 g / l L-threonine 5.7 g / l L-tryptophan 2.0 g / l L-valine 8.0 g / l L-alanine 8.0 g / l L-arginine 10.5 g / l L-aspartic acid 1.0 g / l L-cysteine 1.0 g / l L-glutamic acid 1.0 g / l L-histidine 5.0 g / l L-proline 5.0 g / l L-serine 3.0 g / l L-tyrosine 0.5 g / l glycine 5.9 g / l sodium acetate 9.27 g / l dipotassium hydrogen phosphate 2.72 g / l

The two solutions were sterile-filtered, and 600 ml of the solution (A) and 300 ml of the solution (B) were filled in each of the two polyethylene chambers. The solution (B) was replaced with nitrogen, and sealed. After that, autoclaving was performed according to a conventional method to obtain an infusion for peripheral intravenous administration. The pH of the solution after mixing the infusion solutions (A) and (B) was 6.6.

Example 9 Glucose, sodium chloride, sodium lactate, magnesium sulfate, calcium gluconate and zinc sulfate were dissolved in distilled water for injection, and the pH was adjusted using a trace amount of acetic acid as a pH adjuster.
As 5.0, glucose 107 g / l, sodium chloride 1.14 g /
l, sodium lactate 3.27 g / l, magnesium sulfate 0.89 g /
1, a saccharide electrolyte solution [solution (A)] having a composition of 1.60 g / l calcium gluconate and 2.0 mg / l zinc sulfate was prepared. The titration acidity of this solution was 2.0. On the other hand, the following crystalline amino acid and electrolyte were dissolved in distilled water for injection to prepare an amino acid electrolyte solution [solution (B)] having the following composition at pH 8.0.

[0056]

[Table 11] L-isoleucine 8.0 g / l L-leucine 14.0 g / l L-lysine acetate 13.1 g / l L-methionine 3.9 g / l L-phenylalanine 7.0 g / l L-threonine 5.7 g / l L-tryptophan 2.0 g / l L-valine 8.0 g / l L-alanine 8.0 g / l L-arginine 10.5 g / l L-aspartic acid 1.0 g / l L-cysteine 1.0 g / l L-glutamic acid 1.0 g / l L-histidine 5.0 g / l L-proline 5.0 g / l L-serine 3.0 g / l L-tyrosine 0.5 g / l glycine 5.9 g / l dipotassium hydrogen phosphate 5.8 g / l

The two solutions were aseptically filtered, and 700 ml of the solution (A) and 300 ml of the solution (B) were filled into each of the two polyethylene chambers. The solution (B) was purged with nitrogen and sealed. After that, autoclaving was performed according to a conventional method to obtain an infusion for peripheral intravenous administration. The pH of the solution after mixing the infusion solutions (A) and (B) was 7.2.

[0058]

EFFECT OF THE INVENTION The infusion for peripheral venous administration of the present invention has a pH close to neutral when the reducing sugar side solution and the amino acid side solution are mixed at the time of use, so that the onset of phlebitis can be prevented.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁶ Identification code FI A61K 31/425 A61K 31/425 33/06 33/06 33/42 33/42

Claims (7)

[Claims] 1. A solution containing a reducing sugar-containing solution (A) and an amino acid composition comprising at least an essential amino acid
In the two-solution infusion of (B), the solution (A) contains a part of the electrolyte so that its titratable acidity is 10 or less, and the pH is
The solution (B) contains the remainder of the electrolyte and is adjusted to pH 6.5 to 8.0, and the volume ratio (A) :( B) of both solutions is 5: 1 to 1 1: 1, when both solutions are mixed
An infusion for peripheral intravenous administration, which has a pH of 6.0 to 7.2. 2. The infusion for peripheral venous administration according to claim 1, wherein the electrolytes contained in the solution (A) are all strong electrolytes. 3. The infusion for peripheral intravenous administration according to claim 1, wherein the titration acidity of the solution (A) is 1 or less. 4. The electrolyte according to claim 1, wherein the calcium salt is a solution (A).
The infusion for peripheral intravenous administration according to any one of claims 1 to 3, wherein the phosphorus compound is formulated in the solution (B). 5. The method according to claim 1, wherein the magnesium salt is a solution in the electrolyte.
The infusion for peripheral intravenous administration according to any one of claims 1 to 4, wherein the infusion is formulated in (A) and the phosphorus compound is formulated in solution (B). 6. The composition after mixing the solutions (A) and (B) is as follows: Glucose 3-10 w / v% Na ⁺ 25-70 mEq / l K ⁺ 15-50 mEq / l Ca ^{2 + 3 to} 15 mEq / l Mg ²⁺ 3 to 10 mEq / l Cl ^- 25 to 70 mEq / l P 5 to 20 mmol / l Zn ²⁺ 0 to 30 μmol / l L-isoleucine 1.0 to 4.0 g / l L -Leucine 2.0-7.0 g / l L-lysine 1.5-7.5 g / l L-methionine 0.5-2.5 g / l L-phenylalanine 1.0-4.0 g / l L-threonine 0.8-3.0 g / l L-tryptophan 0.2-1.2 g / l L-valine 0.7-4.2 g / l L-alanine 1.0-4.2 g / l L-arginine 1.4-5.5 g / l L-aspartic acid 0.1-1.7 g / l L-cysteine 0.1-0.7 g / l L -Glutamic acid 0.1-3.0 g / l L-histidine 0.8-2.7 g / l L-proline 0.6-2.6 g / l L-serine 0.3-1.7 g / l L-tyrosine 0-0.5 g / l Glycine 1.0-4.5 g / The infusion for peripheral intravenous administration according to any one of claims 1 to 5, which is l. 7. A heat-sterilized product.
The infusion for peripheral venous administration according to any one of the above.