CA1075605A - Infusion solutions with salts of glycerophosphates - Google Patents
Infusion solutions with salts of glycerophosphatesInfo
- Publication number
- CA1075605A CA1075605A CA238,444A CA238444A CA1075605A CA 1075605 A CA1075605 A CA 1075605A CA 238444 A CA238444 A CA 238444A CA 1075605 A CA1075605 A CA 1075605A
- Authority
- CA
- Canada
- Prior art keywords
- solution
- glycerophosphate
- phosphorus
- sodium
- phosphate
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/24—Heavy metals; Compounds thereof
- A61K33/30—Zinc; Compounds thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/66—Phosphorus compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/14—Alkali metal chlorides; Alkaline earth metal chlorides
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Inorganic Chemistry (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
ABSTRACT OF THE DISCLOSURE
Infusion solutions have a glycerophosphate dissolved therein to provide the source of phosphorus therefor and thereby overcome problems of hypophosphataemia and hypercal-caemia. The presence of the glycerophosphate does not inhibit the ability to sterilize the infusion solutions, especially at pH's above 6.
Infusion solutions have a glycerophosphate dissolved therein to provide the source of phosphorus therefor and thereby overcome problems of hypophosphataemia and hypercal-caemia. The presence of the glycerophosphate does not inhibit the ability to sterilize the infusion solutions, especially at pH's above 6.
Description
~7~i~;05i The invention relates to solutions for parenteral perfusion ~or nutrition and/or supply,of calories, containing phosphorus, and for the treatment of hypophosphataemia and hypercalcaemia.
In parenteral nutrition, which iis usually carried out with perfusion solutions, which coIltain amino acids, carbohydrates, vitamins and essential minerals, it is also necessary to include an ade~uate supply of phosphorus (see, for example RVBERG R.L. Allen, et al.: Hypophosphatemia with H~pophosphaturia in Hyperalimentation. Surg. Forum~
In parenteral nutrition, which iis usually carried out with perfusion solutions, which coIltain amino acids, carbohydrates, vitamins and essential minerals, it is also necessary to include an ade~uate supply of phosphorus (see, for example RVBERG R.L. Allen, et al.: Hypophosphatemia with H~pophosphaturia in Hyperalimentation. Surg. Forum~
2~:87, 1971). The simul~aneous administration of essent1al nutrients, Pspecially amino acias, carbohydrates and minerals, together with calcium and phosphorus, is particular-ly important, and the availability o~ inorganic phosphate is absolutely essential for "total parenteral nu~rition" ~ -("hyperalimentation"). Because of the use of highly purified amino acids in present-day parenteral nutrition, this phosphorus~
~iciency is particulæly liable to manifest itself since, in contrast to the situation when casein hydrolysis products were employed, there is now no phosphate available from the raw materials.
Moreover, the administration of phosphorus is not only necessar~ to cover the daily requirements of parenteral nutrition, but also to treat existing hypophosphataemias and hypercalcaemias. (D. Schwander, Intravenose Applikation ;von Phosphat (Intravenous Administration of Phosphate), Med.
: ~ .
Neuheiten No. 3/4, 1973~.
Furthermore, it is ~nown that in carbohydrate therapy an undesired lowering of the inor~anic serum phosphate level may occur. CDer initiale Phosphatabfall im Serum von .~ .
Gesunden und Leberkranken nach intravenoser Verabreichung . ~ . ....................... , ~ , .
~ ~ -"', .~ .
von Hexosen und 2ucheralkoholen (The Initial Decrease in Phosphate in the Serum of Healthy Persons and Patients Sllffering from Liver Diseases, after Intravenous Adminis-tration of Hexoses and Sugar Alcohols), H.P. Wolf, W.
Queisser and K. Beck, Klin, Wochenschrift 47th year of publication, issue 20, pages 1084-1086, 1969)~
These reasons make clear the importance of the intravenous administration of sources of phosphorus.
Hitherto it was unfortunately only possible to inject phosphorus, during the perfusion, in the form of inorganic phosphate, or to mix it with other substrates, shortly before administration, under aseptic conditions in the dispensary. The high level of technical effort and expenditure on personnel required for this, and the great danger of bacterioloyical contamination ~S.J. Dudrick, American Journal of Hospital Pharmacy 28:82-91 (Feb.) 1971 necessarily imposes se~ere limits on its routine use in clinics.
The preparation of a complete, sterilisable, phosphorus-containing parenteral nutrient solution which can be handled easily and safely has hitherto not proved possible. This was due, inter alia, to the calcium content and the relatively high pH value of these solutions lpH > 6).
In addition, heat sterilisation causes precipltation of calcium phosphate. Furthermore~ these solutions mostly also contain magnesium~ This also leads to precipitates of magnesium jammonium phosphate in the presence o inorganic .
phosphate and of the small amounts of ammonia (from the amino acids~ produced during stPrilisation, and as a result ~ -significantly .
~iciency is particulæly liable to manifest itself since, in contrast to the situation when casein hydrolysis products were employed, there is now no phosphate available from the raw materials.
Moreover, the administration of phosphorus is not only necessar~ to cover the daily requirements of parenteral nutrition, but also to treat existing hypophosphataemias and hypercalcaemias. (D. Schwander, Intravenose Applikation ;von Phosphat (Intravenous Administration of Phosphate), Med.
: ~ .
Neuheiten No. 3/4, 1973~.
Furthermore, it is ~nown that in carbohydrate therapy an undesired lowering of the inor~anic serum phosphate level may occur. CDer initiale Phosphatabfall im Serum von .~ .
Gesunden und Leberkranken nach intravenoser Verabreichung . ~ . ....................... , ~ , .
~ ~ -"', .~ .
von Hexosen und 2ucheralkoholen (The Initial Decrease in Phosphate in the Serum of Healthy Persons and Patients Sllffering from Liver Diseases, after Intravenous Adminis-tration of Hexoses and Sugar Alcohols), H.P. Wolf, W.
Queisser and K. Beck, Klin, Wochenschrift 47th year of publication, issue 20, pages 1084-1086, 1969)~
These reasons make clear the importance of the intravenous administration of sources of phosphorus.
Hitherto it was unfortunately only possible to inject phosphorus, during the perfusion, in the form of inorganic phosphate, or to mix it with other substrates, shortly before administration, under aseptic conditions in the dispensary. The high level of technical effort and expenditure on personnel required for this, and the great danger of bacterioloyical contamination ~S.J. Dudrick, American Journal of Hospital Pharmacy 28:82-91 (Feb.) 1971 necessarily imposes se~ere limits on its routine use in clinics.
The preparation of a complete, sterilisable, phosphorus-containing parenteral nutrient solution which can be handled easily and safely has hitherto not proved possible. This was due, inter alia, to the calcium content and the relatively high pH value of these solutions lpH > 6).
In addition, heat sterilisation causes precipltation of calcium phosphate. Furthermore~ these solutions mostly also contain magnesium~ This also leads to precipitates of magnesium jammonium phosphate in the presence o inorganic .
phosphate and of the small amounts of ammonia (from the amino acids~ produced during stPrilisation, and as a result ~ -significantly .
- 3 -~
- . . ...
.: ... : . . . . .
~756~5 limits the stability of the preparation even at low concen-~, trations. In addition, incompatibilities result if trace elements and inorganic phosphate are present, since precipitates (for example iron phosphate) can again be formed.
Even in perfusion solutions which are ~ree from electrolytes, precipitates with inorganic phosphate are frequently formed, since they may be caused by traces of, for example, calcium ions and iron ions, which may come rom the filters and/or the raw materials.
According to the present inventionl all these problems can surprisingly be eliminated if the perfusion sol ~ ution contains a glycerophosphate as source of phosphorus in ; addition to the other requisite ingredients. Surprisingly, it has also proved possible to prepare the solution with a ph ~ 6 and make it stable and heat-sterilizable.
The present invention accordingly provides, in one aspect, a stable, heat sterilizable solution for parenteral perfusion having a pH value greater than 6 for the treatment or prophylaxis of hypophosphataemia consisting essentially of amino acids,lcarbohydrates, essential minerals, and, as the source of phosphorus, a therapeutically active amount providing up to 95 mmols of phosphorus per liter of the solution of a water-soluble non-toxic glycerophosphate.
The present invention also provides, in another aspect, a sta~le, heat sterilizable solution for parenteral perfusion having a pH value greater than 6 for the treatment or prophylaxis of hypercalcaemia consisting essentially of ; amino acids, carbohydrates, essential minerals, and, as a source of phosphorus, a therapeutically active amolmt provi-ding up to 95 mmols of phosphorus per liter of the solution of a water-soluble non-toxic glycerophosphate selected from ~ 4 -~07s~a5 the group consisting of magnesium, sod.ium and potassium glycerophosphates.
In the solutions of the present invention useful for the treatment or prophylaxis of hypophosphataemia, the phosphorus may be present as sodium, potassium, magnesium or calcium glycerophosphate, or as a combination of these.
In the case of solutions useful for the treatment or prophylaxis of hypercalcaemia, the glycerophosphate salt is selected from the magnesium, sodium and potassium salts, 10or combinations thereof. By combining the various salts it is possible, for a given intended phosphorus content, so to provide part of the cation requirements of the solution and to provide the remainder of the latter by addition of other salts containing the desired ' ' ,, '~
.
~ 4a -....... , . . :
: .
~56~5 cations. It has been demonstrated that glycexophosphates are on the one hand effective phosphate donors and on the other hand toxicologically harmless when used in the requisite amount.
The effectiveness has been demonstrated by the experimental results shown graphically in the Figure.
Curve 1 shows the liberation of inorganic phosphate after injection o glycerophosphate. Curve II shows the complete normalisation o~ the serum inorganic phosphate level following simultaneous injection of fructose and glycero-phosphate, while Curve III shows that the administration of fructose alone, in the same amount, causes a drop in the phosphate level.
In vitro experiments have shown that at pH 7.4 both acid phosphata~e and alkaline phosphatase splits glycero-phosphate to form glycerine and inorganic phosphate.
Further it has ~een found ln vitro that the phospha- -tases present in blood plasma produce a time-dependent, satisfactory splitting of the glycerophosphate. Thus, for example, addi~ion of 1~ mol of glycerophosphate to 250~1~
.
of plasma at an incubation temperature of 37C causes the liberation of about 50% of the glycerine and in~rganic phosphate after one hour and 75% after two hours.
Toxicity te6ts have demonst~ated that glycerophosphates are toxicologically harmless. The actute toxicity is about the same for ~- and ~ -sodium glycerophosphate (LD50= 3.8 ~and 3.4 g/kg, respectively, in ratsl. In dogs, the subacute toxicity is of a similar order of magn1tude. Doses of up to 2 g~kg administered intravenously were tolerated without any symptoms over the course of 14 days.
.!
The Examples given below of perfusion solutions ~ 5 :
:
:. . . . .. ..
1~7561~
containing glycerophosphate illustrate the inventionO
The solutions can be prepared in the usual manner in accordance with the present state of the technique of preparation (of such solutions) and are heat-sterilisable, sterile, free from pyrogen and stable.
Laevulose 60.00 g/l G1UCQSe monohydrate 33.00 g/l Xylitol 30.00 g/l 10 Sodium glycerophosphate.5H2O 9.184 g/l Potassiwm chloride 1.864 g/l Magnesium chloride.6H2O . - 0.610 g/l Zinc sulphate.7H2O 0.022 g/l Vitamin Bl chloride.HCl 0.004 g/l L,Malic acid 2.270 g/l Laevulose 100.00 g/l Glucose monohydrate 55.00 g/l ~ .
Xylitol 50.00 g/l . ~ , .
20 Calcium glycerophosphate 0.630 g/1 Sodium glycerophosphate.5H2O 5o204 g/l EXAMP~E 3 Sodium glycerophosphate.5H2O . 3.061 g/l .: Sodium chloride . 0.409 g/l `:
.
: : Sodium acetate.3H2O 1.905 g/l Potassium chloriae~ 1.118 g~l : P~tasaium acetate . 0.491 g/l Sodium hydroxide ~ 0.420 g/l Potassium h~droxide 0.561 g~l Calcium chloride.2H2~ 0.36~ g/1 Magnesium acetate.4H2O 0~643 g/1 .
' . . `; .` ~' : : ' : ' ~L075G05 L-Isoleucine 0.755 g/l L-Leucine 1.100 g/l L-Lysine.HCl. 1.250 g/l L-Methionine 1.050 g/l L-Phenylalanine lolO0 g/l L-Threonine 0.500 g/l L-Tryptophane 0.225 g/l L-~Iistidine 0.500 g/l L-Arginine 2.000 gJl L-Alanine 3.000 g/l L-Proline 3.500 g/l L-Glutamic acid 4.500 g/l L-Valine 0.750 g/l Glycine 5.000 g/l Sorbitol 125.000 g/l Nicotinic acid amide 0.020 g/l Pyridoxine hydrochloride 0.015 g/l Na riboflavin-5'-phosphate 0.002 g/1 20Potassium glycerophosphate : 1.692 g/1 Sodium glycerophosphate 5.204 g/1 Calcium glycerophosphate 0.630 g/1 Sodium chloride 0.409 g/l : Potassîum chloride 0.372 g/l Potassium acetate 0.491 g/l Sodium hydroxide , 0.410 g/l Potassium hydroxide 0.561 g/1 Sodium acetate.3H2O 1.224 gJl . 30 _ 7 -.
~07S61)5 Magnesium acetate~4H20 0.643 gh L~Isoleucine 0.775 g/l L,Leucine . ~.1.100 g/l h-Lysine.HCl 1O250 g~1 .
L,~Iethionine 1,050 ~/1 L,Phenylalanine 1.100 g/l L-Threonine 0.500 g/l L-Tr~ptophane 0.225 g/l ~-~istidine 0~500 g/l L-Arginine 2O000 g/l L,~lanine .3~000 g/l . .
L-Proline 3O500 g/l ~
.
~-Glutamic acid 4~500 g/1 L Valine 0.750 g/l Glycine S.000 g/l Sorbitol 70.000 g/l ~yli~ol . ~.0~0 ~
Glycerine 35O000 g/l ~icotinic acid amide 0.020 g~l Pyridoxine hydrochloride 0~015 g~l ~a riboflavin-5'-phosphate 0.002 g/l : ~
.' ', ' : :
~ . .
, . .
1 '' ~, ' ' . I
.
,,1 ~ ` ' . ' , . -: ,
- . . ...
.: ... : . . . . .
~756~5 limits the stability of the preparation even at low concen-~, trations. In addition, incompatibilities result if trace elements and inorganic phosphate are present, since precipitates (for example iron phosphate) can again be formed.
Even in perfusion solutions which are ~ree from electrolytes, precipitates with inorganic phosphate are frequently formed, since they may be caused by traces of, for example, calcium ions and iron ions, which may come rom the filters and/or the raw materials.
According to the present inventionl all these problems can surprisingly be eliminated if the perfusion sol ~ ution contains a glycerophosphate as source of phosphorus in ; addition to the other requisite ingredients. Surprisingly, it has also proved possible to prepare the solution with a ph ~ 6 and make it stable and heat-sterilizable.
The present invention accordingly provides, in one aspect, a stable, heat sterilizable solution for parenteral perfusion having a pH value greater than 6 for the treatment or prophylaxis of hypophosphataemia consisting essentially of amino acids,lcarbohydrates, essential minerals, and, as the source of phosphorus, a therapeutically active amount providing up to 95 mmols of phosphorus per liter of the solution of a water-soluble non-toxic glycerophosphate.
The present invention also provides, in another aspect, a sta~le, heat sterilizable solution for parenteral perfusion having a pH value greater than 6 for the treatment or prophylaxis of hypercalcaemia consisting essentially of ; amino acids, carbohydrates, essential minerals, and, as a source of phosphorus, a therapeutically active amolmt provi-ding up to 95 mmols of phosphorus per liter of the solution of a water-soluble non-toxic glycerophosphate selected from ~ 4 -~07s~a5 the group consisting of magnesium, sod.ium and potassium glycerophosphates.
In the solutions of the present invention useful for the treatment or prophylaxis of hypophosphataemia, the phosphorus may be present as sodium, potassium, magnesium or calcium glycerophosphate, or as a combination of these.
In the case of solutions useful for the treatment or prophylaxis of hypercalcaemia, the glycerophosphate salt is selected from the magnesium, sodium and potassium salts, 10or combinations thereof. By combining the various salts it is possible, for a given intended phosphorus content, so to provide part of the cation requirements of the solution and to provide the remainder of the latter by addition of other salts containing the desired ' ' ,, '~
.
~ 4a -....... , . . :
: .
~56~5 cations. It has been demonstrated that glycexophosphates are on the one hand effective phosphate donors and on the other hand toxicologically harmless when used in the requisite amount.
The effectiveness has been demonstrated by the experimental results shown graphically in the Figure.
Curve 1 shows the liberation of inorganic phosphate after injection o glycerophosphate. Curve II shows the complete normalisation o~ the serum inorganic phosphate level following simultaneous injection of fructose and glycero-phosphate, while Curve III shows that the administration of fructose alone, in the same amount, causes a drop in the phosphate level.
In vitro experiments have shown that at pH 7.4 both acid phosphata~e and alkaline phosphatase splits glycero-phosphate to form glycerine and inorganic phosphate.
Further it has ~een found ln vitro that the phospha- -tases present in blood plasma produce a time-dependent, satisfactory splitting of the glycerophosphate. Thus, for example, addi~ion of 1~ mol of glycerophosphate to 250~1~
.
of plasma at an incubation temperature of 37C causes the liberation of about 50% of the glycerine and in~rganic phosphate after one hour and 75% after two hours.
Toxicity te6ts have demonst~ated that glycerophosphates are toxicologically harmless. The actute toxicity is about the same for ~- and ~ -sodium glycerophosphate (LD50= 3.8 ~and 3.4 g/kg, respectively, in ratsl. In dogs, the subacute toxicity is of a similar order of magn1tude. Doses of up to 2 g~kg administered intravenously were tolerated without any symptoms over the course of 14 days.
.!
The Examples given below of perfusion solutions ~ 5 :
:
:. . . . .. ..
1~7561~
containing glycerophosphate illustrate the inventionO
The solutions can be prepared in the usual manner in accordance with the present state of the technique of preparation (of such solutions) and are heat-sterilisable, sterile, free from pyrogen and stable.
Laevulose 60.00 g/l G1UCQSe monohydrate 33.00 g/l Xylitol 30.00 g/l 10 Sodium glycerophosphate.5H2O 9.184 g/l Potassiwm chloride 1.864 g/l Magnesium chloride.6H2O . - 0.610 g/l Zinc sulphate.7H2O 0.022 g/l Vitamin Bl chloride.HCl 0.004 g/l L,Malic acid 2.270 g/l Laevulose 100.00 g/l Glucose monohydrate 55.00 g/l ~ .
Xylitol 50.00 g/l . ~ , .
20 Calcium glycerophosphate 0.630 g/1 Sodium glycerophosphate.5H2O 5o204 g/l EXAMP~E 3 Sodium glycerophosphate.5H2O . 3.061 g/l .: Sodium chloride . 0.409 g/l `:
.
: : Sodium acetate.3H2O 1.905 g/l Potassium chloriae~ 1.118 g~l : P~tasaium acetate . 0.491 g/l Sodium hydroxide ~ 0.420 g/l Potassium h~droxide 0.561 g~l Calcium chloride.2H2~ 0.36~ g/1 Magnesium acetate.4H2O 0~643 g/1 .
' . . `; .` ~' : : ' : ' ~L075G05 L-Isoleucine 0.755 g/l L-Leucine 1.100 g/l L-Lysine.HCl. 1.250 g/l L-Methionine 1.050 g/l L-Phenylalanine lolO0 g/l L-Threonine 0.500 g/l L-Tryptophane 0.225 g/l L-~Iistidine 0.500 g/l L-Arginine 2.000 gJl L-Alanine 3.000 g/l L-Proline 3.500 g/l L-Glutamic acid 4.500 g/l L-Valine 0.750 g/l Glycine 5.000 g/l Sorbitol 125.000 g/l Nicotinic acid amide 0.020 g/l Pyridoxine hydrochloride 0.015 g/l Na riboflavin-5'-phosphate 0.002 g/1 20Potassium glycerophosphate : 1.692 g/1 Sodium glycerophosphate 5.204 g/1 Calcium glycerophosphate 0.630 g/1 Sodium chloride 0.409 g/l : Potassîum chloride 0.372 g/l Potassium acetate 0.491 g/l Sodium hydroxide , 0.410 g/l Potassium hydroxide 0.561 g/1 Sodium acetate.3H2O 1.224 gJl . 30 _ 7 -.
~07S61)5 Magnesium acetate~4H20 0.643 gh L~Isoleucine 0.775 g/l L,Leucine . ~.1.100 g/l h-Lysine.HCl 1O250 g~1 .
L,~Iethionine 1,050 ~/1 L,Phenylalanine 1.100 g/l L-Threonine 0.500 g/l L-Tr~ptophane 0.225 g/l ~-~istidine 0~500 g/l L-Arginine 2O000 g/l L,~lanine .3~000 g/l . .
L-Proline 3O500 g/l ~
.
~-Glutamic acid 4~500 g/1 L Valine 0.750 g/l Glycine S.000 g/l Sorbitol 70.000 g/l ~yli~ol . ~.0~0 ~
Glycerine 35O000 g/l ~icotinic acid amide 0.020 g~l Pyridoxine hydrochloride 0~015 g~l ~a riboflavin-5'-phosphate 0.002 g/l : ~
.' ', ' : :
~ . .
, . .
1 '' ~, ' ' . I
.
,,1 ~ ` ' . ' , . -: ,
Claims (6)
1. A stable, heat sterilizable solution for parenteral perfusion having a pH value greater than 6 for the treatment or prophylaxis of hypophosphataemia consisting essentially of amino acids, carbohydrates, essential minerals, and, as the source of phosphorus, a therapeutically active amount providing up to 95 mmols of phosphorus per liter of the solution of a water-soluble non-toxic glycerophosphate.
2. The solution of claim 1, also containing one or more assimilable polyols.
3. The solution of claim 2, wherein said polyol is selected from the group consisting of sorbitol, xylitol, glycerine and mixtures thereof.
4. The solution of claim 1, 2 or 3, wherein the glycerophosphate is selected from the group consisting of a calcium, magnesium, sodium and potassium salt.
5. The solution of claim 1, 2 or 3, also containing a calcium salt other than a glycerophosphate.
6. A stable, heat sterilizable solution for parenteral perfusion having a pH value greater than 6 for the treatment or prophylaxis of hypercalcaemia consisting essentially of amino acids, carbohydrates, essential minerals, and, as a source of phosphorus, a therapeutically active amount providing up to 95 mmols of phosphorus per liter of the solution of a water-soluble non-toxic glycerophosphate selected from the group consisting of magnesium, sodium and potassium glycerophosphates.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE2502735A DE2502735B2 (en) | 1975-01-23 | 1975-01-23 | Use of glycerophosphates |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1075605A true CA1075605A (en) | 1980-04-15 |
Family
ID=5937143
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA238,444A Expired CA1075605A (en) | 1975-01-23 | 1975-10-22 | Infusion solutions with salts of glycerophosphates |
Country Status (4)
| Country | Link |
|---|---|
| CA (1) | CA1075605A (en) |
| DE (1) | DE2502735B2 (en) |
| GB (1) | GB1516738A (en) |
| ZA (1) | ZA755795B (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8431086B2 (en) | 2006-07-20 | 2013-04-30 | Baxter International Inc. | Medical fluid access device with antiseptic indicator |
| US8485727B2 (en) | 2005-08-02 | 2013-07-16 | Baxter International Inc. | Multiple chamber container |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5916818A (en) * | 1982-07-20 | 1984-01-28 | Shimizu Seiyaku Kk | Solution for fluid therapy by administration through vein |
| SE8701662L (en) * | 1987-04-22 | 1988-10-23 | Gelder Nico M Van | SETTING AND AGENTS FOR TREATING NEUROLOGICAL DISEASES, EXAMPLE, MIGRAEN THROUGH THE OPERATION OF NERV CELLS |
| EP1032403B1 (en) * | 1997-10-24 | 2012-05-02 | John P. Blass | Nutritional supplement for cerebral metabolic insufficiencies |
| GB2544782B (en) * | 2015-11-26 | 2020-07-15 | Fontus Health Ltd | Solution |
-
1975
- 1975-01-23 DE DE2502735A patent/DE2502735B2/en not_active Withdrawn
- 1975-09-11 ZA ZA00755795A patent/ZA755795B/en unknown
- 1975-09-25 GB GB39423/75A patent/GB1516738A/en not_active Expired
- 1975-10-22 CA CA238,444A patent/CA1075605A/en not_active Expired
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8485727B2 (en) | 2005-08-02 | 2013-07-16 | Baxter International Inc. | Multiple chamber container |
| US8431086B2 (en) | 2006-07-20 | 2013-04-30 | Baxter International Inc. | Medical fluid access device with antiseptic indicator |
Also Published As
| Publication number | Publication date |
|---|---|
| GB1516738A (en) | 1978-07-05 |
| ZA755795B (en) | 1976-09-29 |
| DE2502735B2 (en) | 1978-11-23 |
| AU8450175A (en) | 1977-03-10 |
| DE2502735A1 (en) | 1976-08-05 |
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