EP0076841A4 - Verbesserte lösung für parenterale nährung. - Google Patents
Verbesserte lösung für parenterale nährung.Info
- Publication number
- EP0076841A4 EP0076841A4 EP19820901484 EP82901484A EP0076841A4 EP 0076841 A4 EP0076841 A4 EP 0076841A4 EP 19820901484 EP19820901484 EP 19820901484 EP 82901484 A EP82901484 A EP 82901484A EP 0076841 A4 EP0076841 A4 EP 0076841A4
- Authority
- EP
- European Patent Office
- Prior art keywords
- solution according
- glycerol
- xylitol
- sorbitol
- acetate
- 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.)
- Withdrawn
Links
- 235000016236 parenteral nutrition Nutrition 0.000 title description 14
- 235000001014 amino acid Nutrition 0.000 claims abstract description 52
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims abstract description 22
- 239000011575 calcium Substances 0.000 claims abstract description 22
- 229910052791 calcium Inorganic materials 0.000 claims abstract description 22
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims abstract description 22
- 239000003792 electrolyte Substances 0.000 claims abstract description 21
- 150000005846 sugar alcohols Polymers 0.000 claims abstract description 20
- 238000001556 precipitation Methods 0.000 claims abstract description 16
- 239000001506 calcium phosphate Substances 0.000 claims abstract description 12
- 229910000389 calcium phosphate Inorganic materials 0.000 claims abstract description 12
- 235000011010 calcium phosphates Nutrition 0.000 claims abstract description 12
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 claims abstract description 12
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 162
- 239000000243 solution Substances 0.000 claims description 100
- 150000001413 amino acids Chemical class 0.000 claims description 64
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 claims description 58
- 239000000758 substrate Substances 0.000 claims description 54
- 229940024606 amino acid Drugs 0.000 claims description 51
- 229910001868 water Inorganic materials 0.000 claims description 49
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 45
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 claims description 44
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 44
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 claims description 39
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 claims description 39
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 claims description 39
- 239000000600 sorbitol Substances 0.000 claims description 39
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 39
- 239000000811 xylitol Substances 0.000 claims description 39
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 claims description 39
- 229960002675 xylitol Drugs 0.000 claims description 39
- 235000010447 xylitol Nutrition 0.000 claims description 39
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 claims description 36
- IFQSXNOEEPCSLW-DKWTVANSSA-N L-cysteine hydrochloride Chemical compound Cl.SC[C@H](N)C(O)=O IFQSXNOEEPCSLW-DKWTVANSSA-N 0.000 claims description 30
- 229960004799 tryptophan Drugs 0.000 claims description 29
- 239000000203 mixture Substances 0.000 claims description 25
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 claims description 24
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 24
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 claims description 24
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 claims description 24
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 claims description 24
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- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 23
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 claims description 22
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 claims description 22
- 229960000583 acetic acid Drugs 0.000 claims description 22
- UEGPKNKPLBYCNK-UHFFFAOYSA-L magnesium acetate Chemical compound [Mg+2].CC([O-])=O.CC([O-])=O UEGPKNKPLBYCNK-UHFFFAOYSA-L 0.000 claims description 22
- 239000011654 magnesium acetate Substances 0.000 claims description 22
- 235000011285 magnesium acetate Nutrition 0.000 claims description 22
- 229940069446 magnesium acetate Drugs 0.000 claims description 22
- 239000001103 potassium chloride Substances 0.000 claims description 22
- 235000011164 potassium chloride Nutrition 0.000 claims description 22
- 239000011780 sodium chloride Substances 0.000 claims description 22
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims description 21
- 239000012362 glacial acetic acid Substances 0.000 claims description 21
- RWPGFSMJFRPDDP-UHFFFAOYSA-L potassium metabisulfite Chemical compound [K+].[K+].[O-]S(=O)S([O-])(=O)=O RWPGFSMJFRPDDP-UHFFFAOYSA-L 0.000 claims description 21
- 229940043349 potassium metabisulfite Drugs 0.000 claims description 21
- 235000010263 potassium metabisulphite Nutrition 0.000 claims description 21
- 239000001632 sodium acetate Substances 0.000 claims description 21
- 235000017281 sodium acetate Nutrition 0.000 claims description 21
- VSGNNIFQASZAOI-UHFFFAOYSA-L calcium acetate Chemical compound [Ca+2].CC([O-])=O.CC([O-])=O VSGNNIFQASZAOI-UHFFFAOYSA-L 0.000 claims description 20
- 239000001639 calcium acetate Substances 0.000 claims description 20
- 235000011092 calcium acetate Nutrition 0.000 claims description 20
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- 239000008215 water for injection Substances 0.000 claims description 20
- FFEARJCKVFRZRR-UHFFFAOYSA-N L-Methionine Natural products CSCCC(N)C(O)=O FFEARJCKVFRZRR-UHFFFAOYSA-N 0.000 claims description 17
- 229960004452 methionine Drugs 0.000 claims description 17
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- 238000000034 method Methods 0.000 claims description 15
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- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 claims description 12
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- QDGAVODICPCDMU-UHFFFAOYSA-N 2-amino-3-[3-[bis(2-chloroethyl)amino]phenyl]propanoic acid Chemical compound OC(=O)C(N)CC1=CC=CC(N(CCCl)CCCl)=C1 QDGAVODICPCDMU-UHFFFAOYSA-N 0.000 claims 1
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- 235000003704 aspartic acid Nutrition 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 239000004227 calcium gluconate Substances 0.000 description 1
- 235000013927 calcium gluconate Nutrition 0.000 description 1
- 229960004494 calcium gluconate Drugs 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- NEEHYRZPVYRGPP-UHFFFAOYSA-L calcium;2,3,4,5,6-pentahydroxyhexanoate Chemical compound [Ca+2].OCC(O)C(O)C(O)C(O)C([O-])=O.OCC(O)C(O)C(O)C(O)C([O-])=O NEEHYRZPVYRGPP-UHFFFAOYSA-L 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 229960002433 cysteine Drugs 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- CHFUHGDBYUITQJ-UHFFFAOYSA-L dipotassium;2,3-dihydroxypropyl phosphate Chemical compound [K+].[K+].OCC(O)COP([O-])([O-])=O CHFUHGDBYUITQJ-UHFFFAOYSA-L 0.000 description 1
- 229960001484 edetic acid Drugs 0.000 description 1
- 229940037395 electrolytes Drugs 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 235000019197 fats Nutrition 0.000 description 1
- 239000000446 fuel Substances 0.000 description 1
- 230000004110 gluconeogenesis Effects 0.000 description 1
- 230000001890 gluconeogenic effect Effects 0.000 description 1
- 229960002989 glutamic acid Drugs 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 229960002743 glutamine Drugs 0.000 description 1
- 230000002157 hypercatabolic effect Effects 0.000 description 1
- 239000003978 infusion fluid Substances 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 229910017053 inorganic salt Inorganic materials 0.000 description 1
- 230000000290 insulinogenic effect Effects 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 239000002960 lipid emulsion Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 235000006109 methionine Nutrition 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 229960003104 ornithine Drugs 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- IBIRZFNPWYRWOG-UHFFFAOYSA-N phosphane;phosphoric acid Chemical compound P.OP(O)(O)=O IBIRZFNPWYRWOG-UHFFFAOYSA-N 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000011600 potassium glycerophosphate Substances 0.000 description 1
- 235000000491 potassium glycerophosphate Nutrition 0.000 description 1
- 239000003531 protein hydrolysate Substances 0.000 description 1
- WQGWDDDVZFFDIG-UHFFFAOYSA-N pyrogallol Chemical compound OC1=CC=CC(O)=C1O WQGWDDDVZFFDIG-UHFFFAOYSA-N 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- UQDJGEHQDNVPGU-UHFFFAOYSA-N serine phosphoethanolamine Chemical compound [NH3+]CCOP([O-])(=O)OCC([NH3+])C([O-])=O UQDJGEHQDNVPGU-UHFFFAOYSA-N 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 235000011008 sodium phosphates Nutrition 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 229960003080 taurine Drugs 0.000 description 1
- 235000021476 total parenteral nutrition Nutrition 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000036325 urinary excretion Effects 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 235000019154 vitamin C Nutrition 0.000 description 1
- 239000011718 vitamin C Substances 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
- 230000036642 wellbeing Effects 0.000 description 1
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
- A61K33/42—Phosphorus; Compounds thereof
Definitions
- the present invention relates to a solution suitable for administration to patients who require parenteral nutrition.
- the invention relates to a parenteral solution comprising pharmacologically acceptable amounts of amino acids and electrolytes, including calcium and phosphate, along with a polyhydric alcohol which provides a source of energy and prevents precipitation of calcium and phosphate.
- the present invention relates to a solution containing pharmacologically acceptable nutritionally effective amounts of amino acids and electrolytes and sufficient polyhydric alcohols and their derivatives selected from the group consisting of glycerol, sorbitol and xylitol, and combinations thereof, to prevent precipitation of calcium phosphate.
- Certain patients must receive all or most of their nutrition parenterally because of medical or surgical dysfunction of the gastrointestinal tract or in keeping with a physician's prescription. Such patients are temporarily incapable of ingesting protein, carbohydrates, fats, vitamins and other nutrients and must turn to endogenous sources and to nutrients provided parenterally for survival.
- One problem encountered with patients receiving parenteral nutrition is that the body begins to use endogenous sources of protein and fat, although the patients are on a parenteral diet which should be sufficient to prevent starvation.
- Intravenous amino acid solutions are administered clinically to patients requiring intravenous nutrition. They are usually administered along with glucose, fat, electrolytes, and vitamins. Co ⁇ mercial intravenous amino acid solutions are formulated in accordance with the amino acid requirements of man as delineated by William C. Rose and associates. [See Rose, FED. PROC. 8, 546 (1949); Rose et al., J. BIOL. CHEM., 217, 987 (1955).]
- U.S. Pat. No. 3,920,838 discloses a method of treatment of patients during periods of severe negative caloric balance due to dysfunction or disuse of the gastrointestinal tract. The method is based on the parenteral application of amino acids while substantially withholding the patient's intake of carbohydrates. The elimination of carbohydrates allows for the development of starvation ketosis in the patient, thus facilitating the utilization of fat stores and substantially reducing or even eliminating net nitrogen losses.
- Non-metabolizable chelating agents which prevent precipitation of calcium phosphate are ethylenedi amine tetra acetic acid (as its salts), water soluble polyethylene glycols, ethyl eneglycoldi acetic acid (as its salts) and saccharate salts.
- ethylenedi amine tetra acetic acid as its salts
- water soluble polyethylene glycols ethyl eneglycoldi acetic acid (as its salts)
- saccharate salts ethylenedi amine tetra acetic acid (as its salts)
- use of these compounds is undesirable since they cannot be metabolized and may have unwanted side effects if used in the quantities necessary to maintain sufficient amounts of calcium and phosphate in solution.
- glycerol exhibits a nitrogen sparing effect when administered intravenously in combination with amino acids.
- U.S. Patent No. 3,793,450 discloses that glycerol and other polyalcohols such as sorbitol and xylitol may be used as an osmotic agent in intravenously administered aqueous fat emulsions containing amino acids. These compounds improve the stability of the fat emulsions containing amino acids.
- Glycerol a three-carbon polyalcohol
- CIRCULATION cerebral infarction
- Glycerol has the following advantages when used in combination with the amino acids to promote protein sparing: It is (1) gluconeogenic and inhibits gluconeogenesis from amino acids, (2) insulinogenic to a small degree, (3) antiketotic, (4) chemically compatible with amino acids, and (5) higher in caloric density than dextrose. None of the above references discloses that calcium and phosphate may be administered together without precipitation problems when glycerol is used as the energy source in parenterai solutions.
- parenteral solutions incorporating glucose as the carbohydrate source is the intense browning or Maillard reaction which occurs in concentrated carbohydrate/ amino acid or carbohydrate/protein hydrolysate mixtures when they are steam sterilized.
- the parenteral solution can be steam sterilized without the occurrence of a browning effect, and it has been shown to be stable with no precipitation of calcium phosphate for at least 18 months at room temperature and at 40°C. Storage of an identical formulation without the glycerol or polyhydric alcohol or their derivatives eventually precipitates calcium phosphate.
- solutions are disclosed herein which contain pharmacologically acceptable nutritionally effective amounts of amino acids and electrolytes, which include calcium and phosphate ions, and sufficient polyhydric alcohol selected from the group consisting of glycerol, sorbitol and xylitol, to prevent precipitation of calcium phosphate, wherein the improvement comprises retaining in solution calcium and phosphate ions in pharmacologically acceptable nutritionally effective amounts.
- the present invention relates to a novel solution suitable for administration to patients who require parenteral nutrition. Additionally, this invention relates to a solution containing a complete amino acid and electrolyte pattern including calcium and phosphate along with a polyalcohol energy source, such as glycerol, xylitol or sorbitol, or combinations thereof, which is suitable for administration to patients who require intravenous nutrition.
- a polyalcohol energy source such as glycerol, xylitol or sorbitol, or combinations thereof
- the present invention relates to a solution containing pharmacologically acceptable nutritionally effective amounts of amino acids and electrolytes which include calcium and phosphate ions, and sufficient polyhydric alcohol selected from the group consisting of glycerol, sorbitol and xylitol, and combinations thereof, to prevent precipitation of calcium phosphate, wherein the improvement comprises retaining in solution calcium and phosphate ions in pharmacologically acceptable nutritionally effective amounts.
- the solution contains pharmacologically acceptable nutritionally effective amounts of essential and non-essential amino acids, glycerol, and electrolytes, including calcium and phosphate.
- Pharmacologically acceptable amounts refers to amounts which are not toxic.
- Nutritionally effective amounts refers to amounts which will promote health and well-being. These amounts may vary depending on the purpose for which the solution is administered.
- the solution preferably contains 2.5 to 13 percent weight/volume of L-amino acids and/or their organic and inorganic salt equivalents, the major intra- and extracellular electrolytes in concentrations sufficient for maintenance of normal values, and 2 to 10 percent glycerol, a metabolizable antiketotic energy substrate chemically compatible with amino acids, which acts as a stabilizing agent for the chemically incompatible calcium and phosphate ions.
- glycerol is unique in that it is antiketotic; that is, it prevents patients from becoming ketotic when metabolizing amino acids alone or amino acids and fat.
- Antiketotic compounds other than glycerol which stabilize calcium and phosphate and prevent metabolic ketoacidosis are the polyhydric alcohols sorbitol and xylitol, which may be used in place of or in combination with glycerol.
- concentrations of the ingredients of the present solution may vary depending on the purpose for which the solution is administered.
- concentration of amino acids, electrolytes and polyhydric alcohol energy substrates are acceptable for the purposes of the present invention:
- Glycerol or Sorbitol, or Xylitol, or combinations thereof, provided that the concentration of any one energy substrate does not exceed 100 g/l Phosphoric Acid 85% 0.212 0.264 ml
- the solution has the following composition:
- the concentration of glycerol in the above solution is 30-90 g/l.
- the formulations of this invention may include both essential and non-essential amino acids, but the inclusion of some non-essential amino acids, including but not limited to aspartic acid, glutamic acid, ornithine, asparagine, glutamine, tyrosine and taurine, is desirable.
- amino acids used in practicing the present invention are preferably pure crystalline amino acids.
- the amino acids should be in their L-form, rather than the D-form or a mixture of D and L.
- amino acids are employed as free amino acids, but can be amino acid salts or derivatives.
- L-lysine acetate may be used, and derivatives of L-tyrosine which are converted to tyrosine in the body may also be used.
- part of the L-methionine in the present invention may be replaced by D-methionine, a mixture of EL-methionine being used on an equivalent basis to L-methionine.
- D-Methionine has approximately 75% of the nutritional value of L-methionine, and this percentage can be used to determine the desirable equivalent range for a mixture of DL-methionine.
- the formulation may include preservatives or stabilizers, as required, such as sodium bisulfite, ascorbic acid (vitamin C), or other compatible preservative agents. Nitrogen gas may also be used to preserve the solution.
- the formulations are preferably free of ammonia. When prepared from crystalline amino acids, the resultant formulation will be low in free ammonia. In general, the formulations preferably contain less than 0.02% free ammonia.
- the formulations of the present invention are designed to provide maintenance quantities of the major intracellular and extracellular ions.
- Salts of metabolizable organic weak acids and inorganic salts are utilized in combination to provide a solution which is steam sterilizable and which remains stable and acceptable for intravenous administration.
- Potassium metabisulfite is used as a source of potassium, as part of the antioxidant system, and as a means to adjust the pH.
- the pH range of the solution claimed in this disclosure is that which is used in good clinical practices.
- the formulations may be advantageously prepared in the form of sterile aqueous solutions adapted for intravenous administration.
- the solutions will be sterile, pyrogen-free, and at a suitable pH for intravenous administration.
- the most desirable pH for the solution may vary, but, in general, the pH of the solution can range from 5.0 to 7.8.
- peripheral intravenous infusion techniques may be used.
- the solutions described herein can be administered into a central vein, a procedure known clinically as hyperalimentation. In this technique, either a subclavian or internal jugular indwelling catheter may be used.
- Infusion solutions prepared for intravenous administration use can contain from 2 to 14 weight percent of total amino acids based on the solution.
- the optimum concentration of total emino acids will be from 2.5 to 4.5 weight percent based on the solution as prepared for protein conservation of mildly stressed surgical patients, 4.0 to 9.0 weight percent based on the solution for patients who require hyperalimentation, and 8.0 to 13.0 weight percent based on the solution for hyperalimentation of hypercatabolic patients.
- full protein nutrition can be provided by administration from about 1 to 3 liters of solution per patient during each 24 hours.
- the maximum amount which may be administered will depend on the amino acid tolerance of the particular patient.
- the desirable clinical procedure will be to begin the infusion at a daily level below full protein nutrition, and to gradually increase the amount administered.
- the administration can be started at levels equivalent to about 20 to 25 grams of protein per day (24 hrs.), and then increased to at least 40 to 50 equivalent grams of protein per day, providing the patient tolerates the infusion.
- the average patient will be able to tolerate at least the equivalent of 50 grams of protein per 24 hrs., and in some cases, much higher administration levels, up to as high as 100 to 140 grams of protein equivalents, may be feasible.
- the equivalency of amino acids to protein can be calculated by determining the total grams of amino acid nitrogen, and then multiplying this amount by 6.25 to obtain the grams of equivalent protein.
- EXAMPLE 1 A sterile, non-pyrogenic, stable solution suitable for intravenous infusion into patients requiring parenteral nutrition is prepared from the following amino acids, energy substrates, electrolytes and water in the following concentrations:
- Glycerol or Sorbitol, or Xylitol, or combinations thereof, provided that the concentration of any one energy substrate does not exceed 100 g/l Phosphoric Acid 85% 0.212 - 0.264 ml
- EXAMPLE 2 A sterile, non-pyro genie, stable solution suitable for intravenous infusion into patients requiring parenteral nutrition is prepared from the following amino acids, energy substrates, electrolytes and water in the following concentrations:
- Glycerol or Sorbitol, or Xylitol, or combinations thereof, provided that the concentration of any one energy substrate does not exceed 100 g/l
- Solutions made by using this order of addition and composition can be packaged in standard intravenous containers and steam sterilized. Standard sterilization cycles and equipment can be used.
- EXAMPLE 3 A sterile, non-pyrogenic, stable solution suitable for intravenous infusion into patients requiring parenteral nutrition is prepared from the following amino acids, energy substrates, electrolytes and water in the following concentrations: Compound g/l
- Glycerol or Sorbitol, or Xylitol, or combinations thereof, provided that the concentration of any one energy substrate does not exceed 100 g/1 Phosphoric Acid 85% 0.212 - 0.264 ml
- Solutions made by using this order of addition and composition can be packaged in standard intravenous containers and steam sterilized. Standard sterilizations cycles and equipment can be used.
- EXAMPLE 4 A sterile, non-pyrogenic, stable solution suitable for intravenous infusion into patients requiring parenteral nutrition is prepared from the following amino acids, energy substrates, electrolytes and water in the following concentration:
- Glycerol or Sorbitol, or Xylitol, or combinations thereof, provided that the concentration of any one energy substrate does not exceed 100 g/l Phosphoric Acid 85% 0.212 - 0.264 ml
- Solutions made by using this order of addition and composition can be packaged in standard intravenous containers and steam sterilized. Standard sterilization cycles and equipment can be used.
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Inorganic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US25518381A | 1981-04-17 | 1981-04-17 | |
US255183 | 1994-06-07 |
Publications (2)
Publication Number | Publication Date |
---|---|
EP0076841A1 EP0076841A1 (de) | 1983-04-20 |
EP0076841A4 true EP0076841A4 (de) | 1984-01-16 |
Family
ID=22967204
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP19820901484 Withdrawn EP0076841A4 (de) | 1981-04-17 | 1982-04-12 | Verbesserte lösung für parenterale nährung. |
Country Status (4)
Country | Link |
---|---|
EP (1) | EP0076841A4 (de) |
JP (1) | JPS58500526A (de) |
IT (1) | IT1147849B (de) |
WO (1) | WO1982003552A1 (de) |
Families Citing this family (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4574085A (en) * | 1981-05-15 | 1986-03-04 | Baxter Travenol Laboratories, Inc. | Method for using dialysis solution containing glycerol |
DE3578124D1 (de) * | 1984-01-18 | 1990-07-19 | Oehmke Martin | Niedrig osmotisches hypokalorisches waessriges praeparat fuer die infusion. |
US4871718A (en) * | 1987-12-29 | 1989-10-03 | Raymond A. Roncari | Composition of matter for increasing intracellular ATP levels and physical performance levels and for increasing the rate of wound repair |
JP2720165B2 (ja) * | 1988-03-24 | 1998-02-25 | 日本製薬株式会社 | ぶどう糖電解質配合剤 |
US5206269A (en) * | 1992-03-20 | 1993-04-27 | Clintec Nutrition Co. | Highly concentrated amino acid solution |
HUT72422A (en) * | 1994-04-20 | 1996-04-29 | Beres Export Import Rt | Aquous concentrate and process for its preparation |
WO2008134828A2 (en) | 2007-05-04 | 2008-11-13 | Katholieke Universiteit Leuven | Tissue degeneration protection |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE2518888A1 (de) * | 1975-04-28 | 1976-11-11 | Lentia Gmbh | Verfahren zur herstellung von phosphathaeltigen, insbesondere vollbilanzierenden infusionsloesungen |
GB2029220A (en) * | 1978-09-04 | 1980-03-19 | Otsuka Pharma Co Ltd | Amino acid solutions for patients with cancers |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB1256162A (en) * | 1968-08-16 | 1971-12-08 | Braun Fa B | Improvements in and relating to liquid products for intravenous administration |
US3920838A (en) * | 1973-09-04 | 1975-11-18 | Flatt Jean Pierre | Amino acid therapy |
DE2433173C3 (de) * | 1974-07-10 | 1980-02-07 | J. Pfrimmer & Co, 8520 Erlangen | Verwendung von Cholansaurederivaten |
FR2380028A1 (fr) * | 1977-02-10 | 1978-09-08 | Cotte Jean Marie | Procede de preparation d'une solution pour alimentation enterale ou parenterale |
-
1982
- 1982-04-12 WO PCT/US1982/000447 patent/WO1982003552A1/en not_active Application Discontinuation
- 1982-04-12 JP JP57501516A patent/JPS58500526A/ja active Pending
- 1982-04-12 EP EP19820901484 patent/EP0076841A4/de not_active Withdrawn
- 1982-04-19 IT IT48250/82A patent/IT1147849B/it active
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE2518888A1 (de) * | 1975-04-28 | 1976-11-11 | Lentia Gmbh | Verfahren zur herstellung von phosphathaeltigen, insbesondere vollbilanzierenden infusionsloesungen |
GB2029220A (en) * | 1978-09-04 | 1980-03-19 | Otsuka Pharma Co Ltd | Amino acid solutions for patients with cancers |
Also Published As
Publication number | Publication date |
---|---|
IT1147849B (it) | 1986-11-26 |
WO1982003552A1 (en) | 1982-10-28 |
IT8248250A0 (it) | 1982-04-19 |
EP0076841A1 (de) | 1983-04-20 |
JPS58500526A (ja) | 1983-04-07 |
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