JPH0469341A - Sugar electrolytic solution for tpn - Google Patents

Abstract

PURPOSE:To obtain a transfusion solution, containing a sugar and specific electrolytic elements at specified concentrations and suitable for patients requiring strict control of blood potassium level. CONSTITUTION:An electrolytic solution for parenteral nutrition (TPN) containing a sugar and electrolytic elements at concentrations within the following ranges based on 1l aqueous solution. 100-700g (preferably 200-600g) sugar, 15-100mmol (preferably 40-90mmol) Na, 1-10mmol (preferably 2-9mmol) Ca, 1-8mmol (prefer ably 2-7mmol) Mg, 15-100mmol (preferably 40-90mmol) Cl, 0-20mmol (preferably 5-18mmol) P, 0-37mumol (preferably 5-30mumol) Zn without containing K as the electrolytic elements. The aforementioned transfusion solution can be safely administered to patients of advanced age readily causing hyperkalemia, patients suffering from renal insufficiency or renopathy, serious infectious diseases or multiple organ disorders while controlling blood potassium level.

Description

[Detailed description of the invention] Industrial application field The present invention is directed to a TP containing no potassium as an electrolyte element.
The present invention relates to an infusion solution that is a sugar electrolyte solution for N and is suitable for patients who need to strictly control blood potassium concentration.

Conventional technologies and their challenges Traditionally, in maintaining a patient's life, oral nutrition and tube feeding have been either impossible or insufficient, or even if they are possible, the patient's digestive and absorption functions have been compromised. Central parenteral nutrition therapy (TPN therapy) has been used in cases where the patient's condition is extremely poor or where passing food through the gastrointestinal tract may worsen the underlying disease. The infusions used in this therapy must contain nutrients necessary for life support, such as sugars, amino acids, fats, vitamins, and minerals. When used, electrolyte preparations, amino acids, fat emulsions, etc. are added to this solution for infusion.

As the electrolyte solution used as the above basic solution, various products are commercially available, such as Tribalene (Oita Pharmaceutical), Hikaritku solution (Terumo), and Paremental (Morishita Pharmaceutical), but these basic solutions are only standard solutions. It was developed based on patient characteristics and contains a certain concentration of potassium as an electrolyte element. However, administration of these commercially available electrolyte solutions was highly likely to induce hyperkalemia in some patients.

Patients who are more likely to induce hyperkalemia include the elderly (
patients with decreased renal function), patients with renal failure or renal impairment, patients with severe infections, patients with multiple organ failure, etc.
Caution must be used when administering potassium-containing preparations to such patients. In particular, administration of potassium is contraindicated in patients with renal failure who have impaired potassium excretion. This is because if severe hyperkalemia is induced, impulse conduction in the myocardium may be impaired, leading to ventricular fibrillation and death.

With conventional potassium-containing electrolyte solutions, it is possible to change the potassium concentration at will depending on the individual patient, but it is only cumbersome to do this depending on the patient's pathological condition. However, there was a problem of increased chances of bacterial contamination.

Means for Solving the Problems The purpose of the present invention is to provide safe treatment for elderly patients who are prone to hyperkalemia, patients with renal failure or renal impairment, patients with severe infections, patients with multiple organ failure, etc. , a potassium-free TP that can be administered while controlling blood potassium levels.
An object of the present invention is to provide a sugar electrolyte solution for N.

In view of the above circumstances, the present inventors conducted extensive research and found that the above object could be achieved by the following sugar electrolyte solution for TPN, thereby completing the present invention.

That is, according to the present invention, the concentration range in the aqueous solution is
100-7oog/l sodium 15
~100 mmol/l Calcium 1-10 mmol/l Magnesium 1-8 mmol/l Chlor 15-100 mmol/l Phosphorus
0-20 mmol/l zinc
A sugar electrolyte solution for TPN characterized in that it contains sugar and electrolyte elements of 0 to 35 micromol/l and does not contain potassium as an electrolyte element, more preferably the sugar is glucose alone or glucose and fructose and/or or xylitol, the above sugar electrolyte solution for TPN is provided.

More preferable blending ranges of sugar and electrolyte elements in the electrolyte solution of the present invention are as follows.

Sugar 2oo~6oog/l sodium
40-90 mmol/l calcium 2-
9 mmol/l Magnesium 2-7 mmol/
lchlor 40-90 mmol, / 1 phosphorus
5-18 mmol/l zinc
5 to 30 micromol/1 As the sugar component such as glucose, fructose, xylitol, etc. in the present invention, it is appropriate to use Japanese Pharmacopoeia crystals.

As electrolyte components, for example, for sodium, electrolytes containing elemental sodium such as sodium chloride, sodium phosphate, sodium lactate, sodium acetate, and sodium citrate are used, and for calcium, electrolytes containing elemental sodium such as calcium chloride, calcium gluconate, calcium lactate, and calcium acetate are used. For magnesium, use an electrolyte containing elemental calcium, such as magnesium chloride or magnesium sulfate; for phosphorus, use glycerophosphoric acid, disodium hydrogen phosphate (anhydrous or dodecahydrate), sodium dihydrogen phosphate (anhydrous or For chloride, use an electrolyte containing elemental phosphorus such as sodium chloride, calcium chloride, magnesium chloride, zinc chloride, etc. For zinc, use an electrolyte containing elemental zinc such as zinc sulfate, zinc chloride, etc. I can give an example. Any commercially available electrolyte components can be used. Incidentally, it is preferable that the sodium and chlorine are blended at equimolar concentrations.

The sugar electrolyte solution for TPN of the present invention must contain sugar and electrolyte within the above-mentioned specific ranges, and in order to prevent the decomposition of sugar and the formation of calcium phosphate precipitates, pH adjusters such as hydrochloric acid, phosphoric acid, lactic acid, etc. , an organic acid or a mineral acid such as citric acid or acetic acid is further blended to adjust the pH of the liquid to 4.0 to 5.5.
It is preferable to adjust it to Furthermore, in order to actively prevent the decomposition of sugar, a small amount of sodium bisulfite, sodium sulfite, etc. may be added as a stabilizer.

In patients with renal impairment, phosphorus excretion is insufficient, so long-term administration of large amounts of phosphorus-containing preparations may induce hyperphosphatemia.

Therefore, in the present invention, the phosphorus concentration can be reduced to zero or to a low concentration.

When TPN therapy is carried out over a long period of time, trace element deficiencies may appear, so a trace amount of electrolyte containing trace elements such as iron, copper, iodine, and manganese is added to the sugar electrolyte solution for TPN of the present invention. You can also.

The sugar electrolyte solution of the present invention is prepared by a conventional method.

For example, preferably, an electrolyte containing a predetermined amount of sugar and a specific element is dissolved in water for injection, and the pH is adjusted to 4.0 with an organic or mineral acid.
Adjust to 0 to 5.5, add water for injection to make the specified liquid volume,
The solution thus obtained is filtered through a membrane filter with a pore size of 0.45 μm and placed in a plastic container or glass vial that complies with the Japanese Pharmacopoeia's Infusion Plastic Container Test Method. It is prepared by sterilization according to the same method.

Therefore, the present invention also provides a container, particularly preferably a plastic infusion bag, containing the above-mentioned specific sugar electrolyte solution.

This particularly preferred plastic infusion bag includes, for example, "Revised High Calorie Infusions for Pharmaceutical Field" published on 3420/1986, pp. 129-135 (Published by Iyaku Journal Co., Ltd.) and published on February 1, 1989. This includes those using the bags described in "Preparation and Procedures for High Calorie Infusions", pages 112-113 (published by the same company). The material of the bag is not particularly limited, but polyolefin resins such as polyethylene and polypropylene are usually preferred.

By using the above-mentioned infusion bag, the complicated operations and bacterial contamination problems associated with conventional Kawasaki point/mixed injection can be solved all at once, and the target blood potassium concentration can be controlled strictly. The desired infusion agent is provided as appropriate for the patient who needs to be managed.

The dosage and administration method of the sugar electrolyte solution for TPN of the present invention are as follows:
There are no particular limitations, and as a guideline, 500 to 2000 zA'7 days per adult via the central vein,
The amount can be increased or decreased as appropriate depending on the patient's weight, age, nutritional status, pathological condition, etc.

The sugar electrolyte solution for TPN of the present invention can be administered via the central vein in the same manner as conventional sugar electrolyte solutions for TPN of this type. That is, the sugar electrolyte solution of the present invention is prepared by appropriately adding commonly used amino acids, fat emulsions, vitamins, minerals, etc., and further adding potassium-containing drugs as necessary.
For example, an appropriate amount of an injection solution (Tanabe Pharmaceutical), potassium chloride solution for correction (Otsuka Pharmaceutical), dipotassium phosphate solution for correction (Otsuka Pharmaceutical), etc. can be added to asparagus and administered via the central vein.

The amount of potassium added above can be determined as appropriate depending on the patient's disease and symptoms or the measured value of blood potassium, thereby preventing hyperkalemia and hypokalemia. I can do it.

Effects of the Invention According to the use of the sugar electrolyte solution for TPN of the present invention, since it does not contain potassium as an electrolyte element, it can be used to measure pathological conditions and blood potassium concentration in patients who are prone to hyperkalemia. Depending on the value, it becomes possible to administer potassium in a finely tuned manner, and the effect of preventing hyperkalemia is achieved.

EXAMPLES Examples will be given below to further clarify the present invention, but the present invention is not limited thereto.

Example 1 Glucose 79.8g, fructose 40.2g, xylitol 1
9.8g, sodium chloride 1.560g.

Sodium dihydrogen phosphate 0.438 g, disodium hydrogen phosphate (12 hydrate) 0.438 g, calcium chloride (dihydrate) 0.300 g, magnesium chloride (6 hydrate) 0.414 g, zinc sulfate (7 hydrate) 2.280 g of sodium bisulfite and 0.240 g of hydrogen sulfite were dissolved in water for injection, an appropriate amount of lactic acid was added to adjust the pH to 4.6, and water for injection was further added to bring the total volume to 600 zl. This aqueous solution was filtered through a membrane filter with a pore size of 0.45 μm, placed in a plastic container (11) that complies with the Japanese Pharmacopoeia Plastic Infusion Container Test Method, and then sterilized in an autoclave at 105° C. for 40 minutes.

The concentrations of sugar and electrolyte elements in the electrolyte solution of the present invention thus obtained were as follows.

Sugar 233g/A'sodium
58.5 mmol/l calcium
3.4 mmol/l Magnesium 3.4 mmol/l! Chlor 58.1 mmol/l
Phosphorus 8.1 mmol/l zinc
13.2 micromol/1 example
2 Glucose 66.8g, fructose 33.2g, xylitol 1
6.8g, sodium chloride 0.968g.

Sodium dihydrogen phosphate 0.372g, disodium hydrogenphosphate (decahydrate) 0.324g, calcium chloride (
dihydrate) 0.244g, magnesium chloride (hexahydrate) 0
．． Dissolve 340 g, zinc sulfate (heptahydrate) 1.920 g, and sodium bisulfite 0.200 g in water for injection, add an appropriate amount of lactic acid to adjust the pH to 4.6, and then add water for injection to bring the total amount to 400 g. / Closed. Hereinafter, a sugar electrolyte solution for TPN of the present invention was prepared in the same manner as in Example 1.

The concentrations of sugar and electrolyte elements in the electrolyte solution of the present invention thus obtained were as follows.

Sugar 292g//Sodium
58.5 mmol/l calcium 4
．． 2 mmol/! Magnesium 4.2 mmol/l Chlor 58.1 mmol/l Phosphorus 10.0 mmol/1 zinc
16.7 micromol/l Example 3 60 g of brox sugar, 30 g of fructose, 15 g of xylitol,
Sodium chloride 0.643g, calcium chloride (dihydrate) 0.294g, magnesium chloride (hexahydrate) 0.40
7 g and 0.500 g of sodium bisulfite were dissolved in water for injection, an appropriate amount of lactic acid was added to adjust the pH to 4.6, and water for injection was further added to bring the total volume to 1000 yl. This aqueous solution was filtered through a membrane filter with a pore size of 0.45 μm.
After filtration, 400z/ of the resultant solution was filled into a plastic container (11) that complies with the Japanese Pharmacopoeia Plastic Infusion Container Test Method, and the sugar electrolyte solution for TPN of the present invention was prepared in the same manner as in Example 1.

The concentrations of sugar and electrolyte elements in the electrolyte solution of the present invention thus obtained were as follows.

Sugar 105g/A'sodium
15.8 mmol/l calcium
2.0 mmol/l magnesium 2.0 mmol/l chloride 19.0 mmol/l Example 4 600 g glucose, 3.74 g sodium chloride.

Sodium dihydrogen phosphate 1.67 g, disodium hydrogen phosphate (12 hydrate) 1.44 g, calcium chloride (dihydrate) 1.32 g, magnesium chloride (6 hydrate) 1.42
g and 8.6 μl of zinc sulfate (heptahydrate) were dissolved in water for injection, an appropriate amount of lactic acid was added to adjust the pH to 4.6, water for injection was further added to make the total volume 1000 zl, and the following Example 3 was prepared. In the same manner, a sugar electrolyte solution for TPN of the present invention was prepared.

The concentrations of sugar and electrolyte elements in the sugar electrolyte solution of the present invention thus obtained were as follows.

Sugar 600g/A'sodium
86.0 mmol/l calcium 9
0.0 mmol/l magnesium 7.0 mmol/l chloro 95.9 mmol/l phosphorus 17.9 mmol/l zinc
29.9 micromol/l Example 5 225 g glucose, 1.46 g sodium chloride.

Disodium hydrogen phosphate (12 hydrate) 1.44 g.

Calcium gluconate (monohydrate) 0.45g, magnesium sulfate (7hydrate) 0.86g and zinc sulfate (7hydrate)
Dissolve 2.9■ in water for injection, add an appropriate amount of citric acid, and adjust the pH.
Adjust to 4.6 and add water for injection to bring the total amount to 500z.
1, and a sugar electrolyte solution for TPN of the present invention was prepared in the same manner as in Example 1.

The concentrations of sugar and electrolyte elements in the sugar electrolyte solution of the present invention thus obtained were as follows.

Sugar 450 g/l sodium
66, IS remol/l calcium
2.0: Lycell/l Magnesium 7.0 mmol/l Chlor 50.0: Lycell/l Phosphorus 8. OS remol/l zinc
20.2 micromol/l Example 6 200 g glucose 1 150 g fructose, 50 g xylitol
g1 Sodium chloride 3.94 g, sodium dihydrogen phosphate 0.56 g, disodium hydrogen phosphate (12 hydrate) 0
．． 48g, calcium chloride (dihydrate) 0.29g, magnesium chloride (hexahydrate) 1.22g, zinc sulfate (heptahydrate) 8.6g, and sodium bisulfite 0.50g were dissolved in water for injection. A suitable amount of acid was added to adjust the pH to 4.6, and water for injection was further added to bring the total amount to 1000z/. This aqueous solution was filtered through a membrane filter with a pore size of 0.45 μm, and the 500zA' was filtered into a plastic container (1
1), and in the same manner as in Example 1, the TPN of the present invention was prepared.
A sugar electrolyte solution was prepared.

The concentrations of sugar and electrolyte elements in the sugar electrolyte solution of the present invention thus obtained were as follows.

Sugar 400g/l sodium
79.6” Lycell/l Calcium 2
．． 0: Lycell/l Magnesium 6. OS remol/l chlor 83.4" resel/l phosphorus 6.O; remol,/l zinc
29.9 micromol, / 1 Example 7 100 g of glucose, 50 g of fructose, 25 g of xylitol,
Sodium chloride 0.98g, sodium dihydrogen phosphate 1
．． 39g, disodium hydrogen phosphate (decahydrate) 1.2
1g, calcium chloride (dihydrate) 0.882g, magnesium chloride (hexahydrate) 0. 407 g, zinc sulfate (7
water salt) 1.44■ and sodium bisulfite 0.50g
was dissolved in water for injection, an appropriate amount of lactic acid was added to adjust the pH to 4.6, further water for injection was added to make a total volume of 1000 z/ml, and the sugar electrolyte solution for TPN of the present invention was prepared in the same manner as in Example 6. did.

The concentrations of sugar and electrolyte elements in the sugar electrolyte solution of the present invention thus obtained were as follows.

Sugar 175g/A'sodium
39.9 mmol/l calcium
6.0 mmol//Magnesium 2.0 mmol/l Chlor 32.8 mmol/l
Phosphorus 15.0 mmol/l zinc
5. 0 micro7 l/l (hereinafter referred to as
(above) Satoshi Uematsu, Commissioner of the Patent Office Patent Application No. 178868 of 1990 2 Name of the invention Sugar electrolyte solution for TPN 3 Relationship to the case of the person making the amendment Patent applicant #≠# Committee Otsuchi Tomi Seiko Co., Ltd. 4 4 Agent Sawanotsuru Building Dai 06 (20) 2-1-2 Hirano-cho, Chuo-ku, Osaka
3) 0941 Self-issued 6 Item 1 “Detailed explanation of the invention” in the specification to be amended Contents of the amendment 1 Page 2 of the specification, lines 4-5, line 14 of the same page, bottom line of the same page, page 8 In line 16, line 1 on page 10, line 8 on page 12, line 14 on page 14, and line 2 on page 18, the words ``infusion'' will be corrected to ``infusion.''

2. On page 9, lines 15-16 of the specification, the phrase ``1 time of use'' is corrected to ``added at 1 use.''

(that's all)

Claims (2)

[Claims] (1) The concentration range in the aqueous solution is sugar 100-700 g/l, sodium 15-100 mmol/l, calcium 1-10 mmol/l, magnesium 1-8 mmol/l chloro 15-100 mmol/l, phosphorus 0-20 mmol/l A sugar electrolyte solution for TPN, characterized in that it contains sugar and an electrolyte element of 0 to 35 micromol/l of zinc, and does not contain potassium as an electrolyte element. (2) The sugar electrolyte solution for TPN according to claim (1), wherein the sugar is glucose alone or glucose, fructose, and/or xylitol.