EP0398879A1 - Aminosäurezusammensetzung für parenterale nährmittel und deren verwendung - Google Patents
Aminosäurezusammensetzung für parenterale nährmittel und deren verwendungInfo
- Publication number
- EP0398879A1 EP0398879A1 EP88909629A EP88909629A EP0398879A1 EP 0398879 A1 EP0398879 A1 EP 0398879A1 EP 88909629 A EP88909629 A EP 88909629A EP 88909629 A EP88909629 A EP 88909629A EP 0398879 A1 EP0398879 A1 EP 0398879A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- composition
- glutamine
- optionally
- alpha
- ketoglutarate
- 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.)
- Pending
Links
Classifications
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/404—Indoles, e.g. pindolol
- A61K31/405—Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
Definitions
- Amino acid composition for parenteral nutritional support and the use thereof.
- the present invention relates to a composition for therapeutic, especially postoperative and post ⁇ traumatic, parenteral nutritional support treatment, which composition, in addition to conventional amino acid components, also contains L-glutamine and/or its derivative alpha-ketoglutarate, and optionally L-asparagine and acetoacetate.
- parenteral nutritional sup ⁇ port In severe states of illness and injuries, and in postoperative states, parenteral nutritional sup ⁇ port is generally applied.
- preparations for intraveneous nutritional support generally con ⁇ tained an aqueous solution of a high caloric content carbohydrate, such as glucose and the like, and elec ⁇ trolytes.
- the nitrogen balance of the body In prolonged states of illness or in injuries and surgical operations, the nitrogen balance of the body must however be considered, i.e. the ratio of nitrogen loss to nitrogen intake.
- the parenteral nutritional support can be supplemented with amino acid supply to improve the nitrogen balance. Different amino acid compositions for parenteral supply are previously known, see e.g.
- said vital amide derivatives can be brought into a form suitable for administration by sterile filtration of an aqueous solution, followed by rapid cooling and cold storage limited to a few months.
- One alternative is freeze-dry- ing the sterile-filtered solution, yielding a sterile powder. Immediately before administration, this powder can be added to a conventional amino acid mixture. Also other forms of powder sterilisation, not relying on heat, are conceivable. The possibility of using the Na salt of the compounds in order to increase the solubility has also been considered.
- the invention thus relates to a composition for therapeutic, especially postoperative and posttraumatic, parenteral nutritional support treatment, which composi ⁇ tion is based on a conventional amino acid mixture, the composition comprising L-glutamine and/or alpha- ketoglutarate, and optionally L-asparagine and/or acetoacetate, the components of the composition, ex- pressed in g dry component/1 aqueous solution, being:
- composition being characterised in that it also contains 5-30 g/1 L-glutamine and/or 5-25 g/1 alpha- ketoglutarate, and optionally 0.5-10 g/1 L-asparagine and optionally 0.5-10 g/1 acetoacetate, or salts or esters thereof.
- a preferred amount of L-glutamine in the composi ⁇ tion of the present invention is 10-30 g/1 and an especially preferred amount is 15-25 g/1, specifically 20 g/1.
- a preferred amount of alpha-ketoglutarate in the composition of the present invention is 10-25 g/1, specifically 16.5 g/1.
- compositions have included the following suitable components (ex ⁇ pressed in g dry component/1 aqueous solution) :
- Example 1 2 3 4 5 glycine 5.9 5.9 5.9 5.9 5.9 aspartate 4.8 4.8 4.8 4.8 4.8 gluta ate 6.8 6.8 6.8 6.8 6.8 alanine 12 12 12 12 12 12 12 arginine 8.4 8.4 8.4 8.4 8.4 cysteine/cystine 0.42 0.42 0.42 0.42 histidine 5.1 5.1 5.1 5.1 isoleucine 4.2 4.2 4.2 4.2 4.2 4.2 4.2 leucine 5.9 5.9 5.9 5.9 l sine 6.8 6.8 6.8 6.8 6.8 6.8 methionine 4.2 4.2 4.2 4.2 4.2 4.2 4.2 4.2 phenylalanine 5.9 5.9 5.9 5.9 5.9 5.9 5.9 5.9 proline 8.0 8.0 8.0 8.0 serine 6.0 6.0 6.0 6.0 6.0 threonine 4.2 4.2 4.2 4.2 4.2 4.2 4.2 4.2 4.2 tryptophan 1.4 1.4 1.4 1.4 1.4 tyrosine 0.4 0.4
- alpha-ketoglutarate - 16.5 10 10 10 asparagine 2 4 acetoacetate - - - 2
- alpha-ketoglutarate should be included in the composition, it must be added in the form of its sodium salt or its esters, since it is otherwise ex ⁇ tremely sparingly soluble.
- the glutamine can also be added in the form of the sodium salt thereof, thus improving its solubility.
- the invention also relates to the use of L-glutamine and/or its derivative alpha-ketoglutarate and optionally L-asparagine and/or acetoacetate for the preparation of a composition intended for therapeutic, especially postoperative and posttraumatic, parenteral nutritional support treatment, which use is characterised in that L-glutamine and/or alpha-ketoglutarate and optionally L-asparagine and/or acetoacetate or salts or esters thereof, dissolved in water and sterile-filtered, are added in cold-stored and freeze-dried form or other sterile powder form to a commercial amino acid nutrient solution immediately before the therapeutic treatment.
- L-glutamine, alpha-ketoglutarate and optionally L-asparagine and/or acetoacetate or salts or esters thereof are dissolved in sterile pyrogen-free water at 30-50°C.
- the solution is sterile-filtered and rapidly cooled and may thereafter be stored for a few months in a solution in a cooled state or for an even longer time in the frozen state, or stored after freeze-drying for several years in sterile powder form, until it should be used together with an amino acid solution of conventional commercial type, for instance of the Vamin ® type (amino acid nutrient compo ⁇ sition from KabiVitrum AB) .
- Carbohydrates and fatty substances can also be added to the infusion solution.
- alpha-ketogutarate When using alpha-ketogutarate, this must be added in the form of its sodium salt or its esters, which is also possible, but not necessary, in the case of L-glutamine.
- a newly prepared composition as above, either in large bags or in separate vials for each substrate, is then administered to patients exhibiting disordered nitrogen balance, resulting either from a surgical ope- ration or from an injury or illness, the administration being conducted during a period of from 2-4 days to several weeks or until the patient can start eating ordinary food, with a dosage of 120-170 kJ/kg body weight/day, including 0.1-0.2 g amino acid nitrogen/kg body weight/day.
- Urine was collected continuously and analysed for urea content. On the basis hereof, it is possible to calculate the nitrogen balance, see MacKenzie et al, A simple method for estimating nitrogen balance in hospitalized patients: A review and supporting data for a previously proposed technique. J. Am.Col. Nutr. _4:575-581 (1985). In the control group, the nitrogen balance was clearly negative each day during the mea ⁇ suring period of 3 days while, in the test group, it was statistically less negative, however with a substantial spread of the values for day 2. These values are given in the following Table as means deviation.
- the protein synthesis in skeletal muscle was estimated by determining the total ribosome concen ⁇ tration and the percentage proportion of polyribo- somes, see Wernerman et al: Size distribution of ribo- somes in biopsy specimens of human skeletal muscle during starvation. Metabolism 34, 7:665-669, 1985. In the control group, an appreciable reduction of these values was obtained while, in the test group, they remained substantially unchanged after the sur ⁇ gery, see the following Table where the values relate 'to day 3.
- the intracellular concentration of glutamine in skeletal muscle was affected by the TPN program containing glutamine.
- the glutamine concentration in mmole/1 intracel ⁇ lular water in skeletal muscle prior to surgery and on the third postoperative day was as follows:
- the above Tables show that the nitrogen balance and, thus, the postoperative recovery are favourably affected upon parenteral administration of the claimed composition as compared with the control group receiving a conventional composition.
- the Tables further show that the postoperative obligate reduction of the total ribosome concentration and the percentage proportion of polyribosomes could be prevented in the test group, and that the glutamine reduction in skeletal muscle was lower in the glutamine group.
- test group was also given 0.136 g alpha-ketoglutarate ( ⁇ -KG)/kg body weight/day. Thus, both groups were given isonitrogenous and isocaloric amounts of amino acid and energy. Electrolytes, tracer metals and vita ⁇ mins were administered to both groups.
- the daily nitrogen balance in means + SEM was as follows: ⁇ -KG -0.54+0.53 -1.65+1.86 -0.15+1.07 -2.33+1.30
- the glutamine concentration (in mmole/kg wet weight) in skeletal muscle was affected in the following manner.
- the present amino acid nutrient compositions thus have a very favourable effect on postoperative and posttraumatic states since they provide an im ⁇ proved nitrogen balance and unaltered protein syn ⁇ thesis capacity and, hence, promote a considerably quicker and improved recovery of patients than is the case of previously known amino acid nutrient com- positions.
Landscapes
- Health & Medical Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Diabetes (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
SE8704217 | 1987-10-29 | ||
SE8704217A SE8704217D0 (sv) | 1987-10-29 | 1987-10-29 | Aminosyrakomposition for parenteral neringstillforsel |
Publications (1)
Publication Number | Publication Date |
---|---|
EP0398879A1 true EP0398879A1 (de) | 1990-11-28 |
Family
ID=20370052
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP88909629A Pending EP0398879A1 (de) | 1987-10-29 | 1988-10-28 | Aminosäurezusammensetzung für parenterale nährmittel und deren verwendung |
EP88850373A Expired - Lifetime EP0318446B1 (de) | 1987-10-29 | 1988-10-28 | Aminosäure-Zusammensetzung als Träger für die parenterale Ernährung |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP88850373A Expired - Lifetime EP0318446B1 (de) | 1987-10-29 | 1988-10-28 | Aminosäure-Zusammensetzung als Träger für die parenterale Ernährung |
Country Status (10)
Country | Link |
---|---|
EP (2) | EP0398879A1 (de) |
JP (1) | JP2728134B2 (de) |
AT (1) | ATE81468T1 (de) |
AU (1) | AU2623888A (de) |
CA (1) | CA1314232C (de) |
DE (1) | DE3875322T2 (de) |
ES (1) | ES2046331T3 (de) |
GR (1) | GR3006085T3 (de) |
SE (1) | SE8704217D0 (de) |
WO (1) | WO1989003688A1 (de) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6649746B1 (en) | 1999-05-07 | 2003-11-18 | University Of Virginia Patent Foundation | Biological production of stable glutamine, poly-glutamine derivatives in transgenic organisms and their use for therapeutic purposes |
Families Citing this family (23)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
SE8902544L (sv) * | 1989-07-17 | 1991-01-18 | Kabivitrum Ab | Beredning foer naeringstillfoersel, samt saett foer dess framsaellning |
AU8513191A (en) * | 1990-09-10 | 1992-03-30 | Austin L. Shug | Composition and method for protecting the heart during reperfusion |
SE9003844L (sv) * | 1990-12-03 | 1992-06-04 | Kabi Pharmacia Ab | Naeringstillsats |
US5374651A (en) * | 1991-09-27 | 1994-12-20 | Board Of Regents, The University Of Texas System | Methods and compositions for the treatment of hypotension with arginine free essential and essential amino acids and arginine derivatives |
US5334380A (en) * | 1991-09-27 | 1994-08-02 | Board Of Regents, The University Of Texas System | Anti-endotoxin, interleukin-1 receptor antagonist and anti-tumor necrosis factor antibody with arginine-free formulations for the treatment of hypotension |
US5286739A (en) * | 1991-09-27 | 1994-02-15 | Board Of Regents, University Of Texas System | Parenteral formulations for the inhibition of systemic hypotension associated with nitric oxide production or endothelial derived relaxing factor |
ATE174794T1 (de) * | 1991-09-27 | 1999-01-15 | Univ Texas | Parenteral anzuwendende aminosäuren enthaltende zubereitungen zur bekämpfung von hypotension und verwandten pathologien |
GB9121467D0 (en) * | 1991-10-10 | 1991-11-27 | Sandoz Nutrition Ltd | Improvements in or relating to organic compounds |
US5646187A (en) * | 1992-05-20 | 1997-07-08 | Ab Erik Vinnars | Use of alpha-ketoglutarate |
SE9201584D0 (sv) * | 1992-05-20 | 1992-05-20 | Vinnars Erik Ab | Use of alpha-ketoglutarate |
US5276018A (en) * | 1992-07-17 | 1994-01-04 | Brigham And Women's Hospital | Composition comprising amino acids and methods for decreasing muscle breakdown |
FR2711529B1 (fr) * | 1993-10-28 | 1996-07-05 | Clintec Nutrition Cy | Composition à base d'acides aminés destinée au traitement d'une infection ou d'une agression engendrant une réaction inflammatoire, chez les animaux et chez l'homme. |
SE9303691D0 (sv) * | 1993-11-09 | 1993-11-09 | Gramineer Ab | New beverage |
SE9402027D0 (sv) * | 1994-06-10 | 1994-06-10 | Pharmacia Ab | Energy substrates |
AU1409299A (en) * | 1997-11-13 | 1999-06-07 | University Of Florida | Use of ketoacids together with amino acids for enhancing muscle performance and recovery from fatigue |
US6905707B2 (en) | 1998-05-28 | 2005-06-14 | Medical Research Institute | Controlled release arginine alpha ketoglutarate |
US20020147237A1 (en) * | 2001-01-31 | 2002-10-10 | Lars Wiklund | Preservation of bodily protein |
WO2004096207A1 (ja) * | 2003-04-30 | 2004-11-11 | Ajinomoto Co., Inc. | 体温低下抑制剤 |
JP4528925B2 (ja) * | 2003-05-30 | 2010-08-25 | 独立行政法人理化学研究所 | アミノ酸組成物及び補液 |
WO2005027898A1 (ja) * | 2003-09-19 | 2005-03-31 | Riken | アミノ酸組成物 |
EP1806134B1 (de) | 2004-09-17 | 2012-07-11 | Ajinomoto Co., Inc. | Mittel und nahrungsmittel zur prävention/verbesserung von funktionalen verdauungsstörungen |
JP5177785B2 (ja) * | 2004-11-02 | 2013-04-10 | 味の素株式会社 | 周術期患者用薬剤 |
PL379512A1 (pl) * | 2006-04-21 | 2007-10-29 | Sgp & Sons Ab | Nowe metody i ich zastosowanie |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS5916817A (ja) * | 1982-07-16 | 1984-01-28 | Eisai Co Ltd | アミノ酸輸液 |
JPS5927817A (ja) * | 1982-08-05 | 1984-02-14 | Tanabe Seiyaku Co Ltd | アミノ酸輸液 |
JPS6178719A (ja) * | 1984-09-25 | 1986-04-22 | Tanabe Seiyaku Co Ltd | 総合輸液剤 |
EP0250559A1 (de) * | 1985-12-18 | 1988-01-07 | VEECH, Richard L. | Parenterale nahrungstherapie mit aminosäuren |
JPS62221621A (ja) * | 1986-03-24 | 1987-09-29 | Tanabe Seiyaku Co Ltd | 総合輸液剤 |
-
1987
- 1987-10-29 SE SE8704217A patent/SE8704217D0/xx unknown
-
1988
- 1988-10-28 EP EP88909629A patent/EP0398879A1/de active Pending
- 1988-10-28 CA CA000581559A patent/CA1314232C/en not_active Expired - Fee Related
- 1988-10-28 WO PCT/SE1988/000578 patent/WO1989003688A1/en not_active Application Discontinuation
- 1988-10-28 EP EP88850373A patent/EP0318446B1/de not_active Expired - Lifetime
- 1988-10-28 DE DE8888850373T patent/DE3875322T2/de not_active Expired - Fee Related
- 1988-10-28 JP JP63508896A patent/JP2728134B2/ja not_active Expired - Lifetime
- 1988-10-28 ES ES198888850373T patent/ES2046331T3/es not_active Expired - Lifetime
- 1988-10-28 AU AU26238/88A patent/AU2623888A/en not_active Abandoned
- 1988-10-28 AT AT88850373T patent/ATE81468T1/de not_active IP Right Cessation
-
1992
- 1992-10-26 GR GR920402414T patent/GR3006085T3/el unknown
Non-Patent Citations (1)
Title |
---|
See references of WO8903688A1 * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6649746B1 (en) | 1999-05-07 | 2003-11-18 | University Of Virginia Patent Foundation | Biological production of stable glutamine, poly-glutamine derivatives in transgenic organisms and their use for therapeutic purposes |
Also Published As
Publication number | Publication date |
---|---|
AU2623888A (en) | 1989-05-23 |
EP0318446B1 (de) | 1992-10-14 |
EP0318446A1 (de) | 1989-05-31 |
DE3875322T2 (de) | 1993-05-13 |
WO1989003688A1 (en) | 1989-05-05 |
DE3875322D1 (de) | 1992-11-19 |
CA1314232C (en) | 1993-03-09 |
JP2728134B2 (ja) | 1998-03-18 |
GR3006085T3 (de) | 1993-06-21 |
JPH03500775A (ja) | 1991-02-21 |
ES2046331T3 (es) | 1994-02-01 |
SE8704217D0 (sv) | 1987-10-29 |
ATE81468T1 (de) | 1992-10-15 |
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Legal Events
Date | Code | Title | Description |
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PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
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STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: REQUEST FOR EXAMINATION WAS MADE |
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17P | Request for examination filed |
Effective date: 19900421 |
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AK | Designated contracting states |
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XX | Miscellaneous (additional remarks) |
Free format text: VERFAHREN ABGESCHLOSSEN INFOLGE VERBINDUNG MIT 88850373.7/0318446 (EUROPAEISCHE ANMELDENUMMER/VEROEFFENTLICHUNGSNUMMER) VOM 25.03.91. |