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EP0057209A1 - Nouvelle preparation d'acide amine et therapie pour le traitement du "stress" et des blessures - Google Patents

Nouvelle preparation d'acide amine et therapie pour le traitement du "stress" et des blessures

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Publication number
EP0057209A1
EP0057209A1 EP19810902198 EP81902198A EP0057209A1 EP 0057209 A1 EP0057209 A1 EP 0057209A1 EP 19810902198 EP19810902198 EP 19810902198 EP 81902198 A EP81902198 A EP 81902198A EP 0057209 A1 EP0057209 A1 EP 0057209A1
Authority
EP
European Patent Office
Prior art keywords
amino acid
injury
pharmaceutical preparation
stress
amino acids
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Withdrawn
Application number
EP19810902198
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German (de)
English (en)
Other versions
EP0057209A4 (fr
Inventor
George L. Blackburn
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Individual
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Individual
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Filing date
Publication date
Application filed by Individual filed Critical Individual
Publication of EP0057209A1 publication Critical patent/EP0057209A1/fr
Publication of EP0057209A4 publication Critical patent/EP0057209A4/fr
Withdrawn legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/01—Hydrolysed proteins; Derivatives thereof

Definitions

  • This invention relates to a novel amino acid composition and its use in a method of treating a patient for stress or injury. Mare specifically, it relates to a branched chain amino acid composition having a pharmacological effect for treatment of patients suffering illness, sepsis, trauma or other injury.
  • the metabolic response to injury consists of many processes which have evolved over millions of years. The metabolic changes are best understood as a redistribution of nutrients frcm labile reserves to more active tissues for host defense and recovery.
  • Other metabolic responses to injury include hyperglycemia, increased rates of lipolysis, gluconeogenesis, and glycogenolysis (Balckburn, G.L. , Phinney, S.D., Surgical Physiology, Eidted by Burke J.F., Philadelphia, C.V. Mosby and Co., 1980; Wilirore, D.W. Surg.. Clin. North Am. 56, 999, (1976).
  • hyperglycemia hyperglycemia
  • lipolysis gluconeogenesis
  • glycogenolysis Balckburn, G.L. , Phinney, S.D., Surgical Physiology, Eidted by Burke J.F., Philadelphia, C.V. Mosby and Co., 1980; Wilirore, D.W. Surg..
  • Micronutrients such as zinc are also redistributed and increased uptake by the liver is important in potentiating enzymatic functions required during injury (Pekarek, R.S., Wannemacher, R.W. , Jr., Beisel, W.R. Proc. Soc. Exp. Biol. Med. , 140, 685, 1965) .
  • Increased hepatic synthesis of iron-binding proteins aids ly ⁇ iphocyte function as well as reducing the quantity of free iron available in pathogenic micro-organisms.
  • Increases in plaa ⁇ a copper concentration in the form of cerulcpla ⁇ min may be involved in the regulation of cate-dxjlamines, prostaglandins, and serotonin (P ⁇ wanda, M.C., Kenyon, R.H. , Moe, J.B. Proc. Soc. Exp. Biol. Mad. 151, 804, 1976)
  • Stress of injury such as trauma or sepsis often is accompanied fcy partial or complete dysfunction of the gastro-intestinal tract.
  • Patients suffering such dysfunction or who are subject to disuse of the gastro-intestinal tract because of physician's prescription are obliged to receive most or all of their daily nutritional requirements parenterally and/or enterally.
  • the object is to provide the patient with as much of the normal daily nutritional requirements as possible to sustain protein synthesis and avoid malnutrition. At the same time, energy expenditure and protein turnover are often increased.
  • the body is often required to draw upon its own resources to meet its metabolic needs.
  • mobilization of fat reserves occurs, within a few days of calorie restriction and is effective in minimizing protein losses.
  • the adaptive procedure is much less efficient in severe stress or injury, such as infections, thermal injury, and sepsis, where net loss of lean body mass may exceed 500 g/day (15-20 g urinary nitrogen excretion/day). This decreased ability of injured or infected organisms to utilize amino acids for protein synthesis is a ⁇ astributing factor in increase morbidity and mortality of seriously ill patients.
  • infusion solutions used for intravenous feeding have conventionally comprised an aqueous solution of a carbohydrate of high caloric content such as sucrose, glucose or the like.
  • a carbohydrate of high caloric content such as sucrose, glucose or the like.
  • Such methods of treatment are shown by IXidrick et al, Total Intravenous Feeding", Scientific American 73 (May, 1972), which suggests the infusion of 1000 calories (glucose) per liter of nutrient solution, and Shils, "Guidelines for Total ParenteralNutrition", J. American Med. Assoc.220 (B) (1972). It is known in the art, however, that during prolonged periods of illness, and notwithstanding conventional intravenous feeding, there can be a significant loss of body weight.
  • a portion of this loss can be attributed to the mobilization of stored fat, which is not a serious health problem.
  • Another portion of the loss in body weight is attributable to a loss in the lean body mass, i.e., muscle, organs, etc.
  • This loss correlates to a loss of body nitrogen. More specifically, during a period of negative caloric balance, the lean body mass breaks down releasing amino acids which are converted by the liver into glucose and urea, the urea being excreted in urine. By determining the nitrogen content in urine, the decrease in lean body mass can be determined. By this method, a nitrogen balance can be made.
  • a negative nitrogen balance means a loss in lean body mass i.e., the body is losing more nitrogen than it is taking in.
  • a typical nutritional infusion solution comprises an aqueous solution of carbohydrates, fats and amino acids.
  • amino acids are parenterally administered with the infusion solution, as aforesaid, a negative nitrogen balance often is still encountered over a sustained period of time, with a concomitant reduction in lean body mass, though the negative nitrogen balance might not be as severe as it would be in the absence of the infused amino acids.
  • That method comprises parenteral feeding of amino acids to the patient while substantiallv elminating other sources-of-hiqh caloric nutrition (such as glucose) during the period in which the patient is parenterally fed, thereby intentionally creating a condition simulating starvation ketosis.
  • the method has for an object inducing a condition simulating starvation ketosis, whereas the prior methods have for an object avoidance of starvation (Dudrick et al and Shils, supra).
  • That novel hypocaloric method of treatment is based in part on the recognition that starvation ketosis occurring during severe negative caloric balance allows more adequate fat mobilization, whereby endogenous fat stores meet almost all the patient's energy requirements with little or no cataboli ⁇ m of lean body mass protein.
  • Parenteral administration of carbohydrate often is not possible in sufficient amount to meet energy requirements, and yet acts to impede fat mobilization. Consequently, such parenteral a ⁇ ministraticn of carbohydrate has the counter-productive effect of causing protein catabolism and net nitrogen loss.
  • Patent 3,832,465 an amino acid solution is disclosed for use with glucose, for administration especially to newborns, prematures and patients in the neonatal period, in which amino acids are present in proportion to the anabolic need of the body without heavily relying on the catabolic capability of the liver.
  • the amino acids composition is designed so that its administration does not change the pattern of the free amino acids of the peripheral blood.
  • a pharmaceutical preparation comprising an amino acid composition for treatment of a patient obliged to receive nutritional requiranents via parenteral or enteral administration, to optimize the nutritional regimen.
  • an amino acid composition which is compatible for prolonged use in the nitrogen-sparing alimentation of a patient suffering stress or injury and which amino acid composition will promote wound healing, host defense, imnune competence, non-sepsis and survival of the patient.
  • the invention described herein is a pharmaceutical preparation comprising a novel amino acid composition and a method of treatment aploying it, for treatment of a patient suffering stress or injury, especially during periods of partial or total dysfunction or disuse of the gastrointestinal tract, to promote wound healing, host defense, imnune competence, non-sepsis and survival.
  • the pharmaceutical preparation of the invention comprises an amino acid composition in which at least about 70% and preferably as much as 100% of the amino acid content is the branched chain amino acids, leucine, isoleucine and valine, in the relative proportions of about a:b:c wherein a, b and c are each independent of the other and have a value of from 1 to 2.
  • This novel branched chain amino acid composition can be enterally administered in any suitable hydrous concentrations.
  • it can comprise an infusion solution in which the total amino acid content is between about 2 and 6%, and preferably is 4%
  • this novel amino acid solution is presented in modular form suitable for use either alone or together with other infusion solutions as one component of a nutritional regimen.
  • Another aspect of the present invention comprises a method of treatment for a patient suffering stress or injury, especially during periods of partial or total dysfunction or disuse of the gastrointestinal tract, to promote wound healing, host defense, imnune competence, non-sepsis and survival.
  • This novel method comprises the administration to the patient, via enteral or preferably, via parenteral infusion, of the novel amino acid composition of the present invention.
  • This method of treatment can comprise the entire nutritional therapy for the patient, or may comprise one part thereof.
  • the present invention comprises both administration of the novel amino acid composition and, simultaneously, the development and maintenance of a metabolic state simulating caloric starvation, by substantially withholding exogenous carbohydrates from the patient.
  • the present invention is characterized by improved wound healing, host defense immune competence, non-sepsis and/or survival by promoting protein synthesis in the patient. More specifically, both whole body protein, especially muscle and, most importantly, liver protein synthesis are promoted by the present invention.
  • the invention is further characterized by reduction or near elimination of net nitrogen losses or even by net nitrogen gain, obtained most significantly by increased protein synthesis in both muscle and liver.
  • the invention described herein is based partly upon the recognition that the visceral tissues and secretory liver proteins, including albumin and transferrin, are critical to effective and successful patient wound healing, host defense, imnune competence, non-sepsis and survival. Accordingly, increased liver protein synthesis will improve wound healing, etc.
  • the invention is also based upon the discovery that the synthesis of whole body proteins, including liver proteins, during periods of stress or injury, is promoted and improved by the adtiiinistrati ⁇ n, either alone or in conjunction with other nutritional components, of the novel amino acid composition of the present invention consisting essentially of at least about 70% and preferably as much as 100% branched-chain amino acids (BCAA) .
  • This invention is based, in part, on newly discovered aspects of the body's response to stress or injury, involving the redistribution of body cell mass (protein and intracellular electrolytes) to sustain anabolic processes in most visceral organs, i.e. liver, bone marrow, kidney, gastrointestinal tract, lymph nodes, and other reticulo-endothelial system tissues.
  • body cell mass protein and intracellular electrolytes
  • This redistribution of body cell mass has now surprisingly been discovered to be, in turn, dependent upon muscle energy metabolism and its interaction with oxidation of branched chain amino acids.
  • Fig. 1 is a diagramatic illustration of the experimental method used to estabish a stress model.
  • Fig. 2 is a graphical illustration of whole body protein dynamics in the stressed and unstressed body.
  • Fig. 3 is a graphical illustration of protein synthesis rates of individual tissues in the stressed and unstressed body.
  • Fig. 4 is a graphical illustration of plasma substrate concentrations in the stressed and unstressed body.
  • Fig. 5 is a graphical illustration of the attainment, over time, of an isotopic steady state in the percent recovery of infused isotope in expired breath fr ⁇ n the unstressed body and from the stressed body receiving one of various diets.
  • Fig. 6 is a graphical illustration of whole body protein dynamics in the stressed body receiving one of various diets.
  • Fig. 7 is a graphical illustration of liver protein synthesis rates in the stressed body receiving one of various diets.
  • Fig. 8 is a graphical illustration of muscle protein synthesis rates in the stressed body receiving one of various diets.
  • Fig. 9 is a graphical illustration of upper small intestine protein synthesis rates in the stressed body receiving one of various diets.
  • Fig. 10 is a graphical illustration of pancreas protein synthesis rates in the stressed body receiving one of various diets.
  • Fig. 11 is a graphical illustration of the net nitrogen balance in the stressed body receiving one of various diets.
  • Fig. 12 is a graphical illustration of plasma substrate concentrations in the stressed body receiving one of various diets.
  • Fig. 13 graphically illustrates urinary nitrogen loss in septic rats receiving one of various diets.
  • Statistical analysis of data presented in the drawings was performed using analysis of variance (ANOVA) , and least significa ⁇ t differences (LSD) .
  • ANOVA analysis of variance
  • LSD least significa ⁇ t differences
  • Superscripts, a, b, and c designate differences at the 95% confidence level.
  • the term "patient” is intended to mean any patient treated or treatable with or in accordance with the present invention.
  • the reason for treatment by parenteral administration of amino acids is not critical, it being understood that such treatment is necessitated by the condition of the patient, whether it be due to trauma, sepsis, illness or other injury or stress.
  • amino acid as used herein is intended to mean those amino acids used in patient therapy such as those L-amino acids, both essential and non-essential, conventionally infused into patients along with glucose, ⁇ he term is intended to include -keto analogs, di- ⁇ or tripeptides.
  • branched chain amino acid and "BCAA” refer to the amino acids valine, leucine, and isoleucine, collectively.
  • nitrogen balance refers to the difference between intake and excretion of nitrogen. A negative nitrogen balance therefore refers, to a loss situation where the excretion of nitrogen exceeds intake.
  • starvation means the condition known in the art to exist in a patient as a result of deprivation and lack of nourishment. As used in relation to patients treated in accordance with this invention, it is used in a slightly different sense as the patient will exhibit the energy metabolism of starvation, such as ketosis, due to hypocaloric feeding.
  • parenteral administration is used in its conventional sense to include intravenous infusion to peripheral veins as well as other methods known to the art.
  • the novel BCAA composition of the present invention provides a significant advance over known infusion solutions and known nutritional therapies in promoting and even optimizing increased protein synthesis. Both whole body protein synthesis, especially muscle, and, most importantly, liver protein synthesis are increased more efficiently than with such known solutions and therapies. While it is known in the art that liver protein synthesis is of vital importance to effective wound healing, host defense, immune competence non-sepsis and survival, it is highly surprising and contrary to the teaching in the art that administration of BCAA could significantly and even most efficiently increase liver protein synthesis.
  • an aqueous amino acid solution is limited to about 4% concentration at pH 6 and to about 6% at pH as low as 2 or as high as 9.
  • novel BCAA composition of the present invention can be presented in the form of an infusion at a concentration of from about 2% to 6% but preferably about 4% and is at about pH 6.
  • the 6% solution while within the scope of the invention, is less preferred in view of the necessity of pre-infusion pH-adjustment.
  • reference herein will be to the 4% solution with the understanding that solutions of from 2 to 6% are intended to be included therein.
  • the novel BCAA composition of the present invention provides such a nutritional therapy. It has now been discovered that this novel composition, whether used alone or together with other nutrients, provides, on a weight-for-weight basis, the greatest increase in liver protein synthesis and, consequently, the most efficient support for patient wound healing, host defense, imnune competence, non-sepsis and survival.
  • Figs. 1 to 4 show a "stress model," that is, a profile of the body's physiological response to stress or injury. Specifically, a comparison of healthy versus traumatized rats is presented for its applicability to mammals generally, and to humans particularly.
  • Fig.1 graphically illustrates the experimental method employed to establish the stress model. The following example further describes the method.
  • Example 1 Generalized CD rats (200-250 gm) underwent venous canulation and were returned to metabolic units where they received normal saline, 35 ml/day, and were allowed to consume standard laboratory chow and water ad libitum for four days. The rats were then fasted overnight, following which pancreatitis was induced in all but a control group. For the next 30 hours both control rats and pancreatitis rats were fasted. During the final 6 hours of feeding, all rats received ccntinous infusion of L-(U-14 C)Eyrosine to determine whole body amino acid oxidation and fractional synthesis of whole body protein. The rats were then sacrificed.
  • Fig. 2 graphically illustrates and compares the whole body protein dynamics in the traumatized and non-traumatized fasting rats. Protein breakdown, synthesis and oxidation were increased in the traumatized rats. Net nitrogen loss was also increased over the fasting control.
  • Fig. 3 illustrates and compares the percent per day protein synthesis rates of individual tissues. The body's response to stress is shown to include increased synthesis of muscle, upper small intestine and especially liver protein.. As would be expected, pancreas protein synthesis is lowered in the pancreatitis rats. A significant aspect of the stress model is illustrated in Fig. 4, showing the plasma concentration levels of glucose and of hydroxybutyrate, a ketone body produced by the liver.
  • the present invention now provides a nutritional composition and nutritional therapy for a stressed body which supports and increases the fractional synthesis of whole body protein, especially muscle and, more iirportantly, mixed liver proteins, more effectively than known nutritional solutions and therapies. Moreover, the present invention reduces net nitrogen loss more efficiently than other previously known therapies.
  • the present invention provides a pharmacological effect not due merely to the ing ⁇ stion of ⁇ -amino nitrogen, is apparent from the fact that the same results are not obtained even with isonitrogenous diets consisting of L-alanine, (which amino acid might have been expected to produce optimum results since it is metabolized in both liver and muscle and thus supports protein sparing mechanisms in both.) Moreoever, since BCAA are not metabolized in the liver, the effectiveness of the present invention to promote liver protein synthesis is highly surprising. That this pharmacological effect is not reproduceable by any other amino acid configurations in similar amounts is believed due to the unique ketogenic nature of the BCAA.
  • the BCAA are ketogenic precursers which allow the stressed body to utilize ketone bodies which are being depleted by the injury or stress.
  • Fig. 4 shows the depletion of the ketone body hydroxybutyrate in the stress model of Example 1.
  • non-protein energy substrates including glucose
  • Evperinsulinemia results and fosters reesterificaticn of free fatty acids within the adipocyte, thereby decreasing net free fatty acid release and thus its oxidation rate.
  • Deficiencies in these competing endogenous energy fuels in the stressed body create an energy deficit met by increased branched chain amino acid oxidation.
  • immunoglobulins and C-3 complement all of which are important for host defense and recovery from injury, sepsis, infection and other acute illness.
  • oxidation of branched chain amino acids during periods of post injury and starvation may be a rate limiting step in the mobilization and redistribution of body amino acids for synthesis of visceral an acute phase proteins.
  • novel BCAA composition of the present invention preferably consists essentially only of branched chain amino acids, alternately it can comprise some amount of other essential or non-essential amino acids or other components such as other nutritional components, for exa ⁇ -pie glucose.
  • novel BCAA solution can comprise as much as 20 or even 30% of amino acids other than the branched chain amino acids. It should be recognized however, that a corresponding decrease in the efficiency of the infusion solution to promote wound healing etc., would be expected with reduction in the total amount of BCAA intake.
  • the ratio of the branched chain amino acids in the novel composition of the invention i.e., A:B:C wherein A, B and C each independently of the others has a value of from 1 to 2, provides the maximum efficacy and efficiency in promoting wound healing, non-sepsis, imnune competence and survival, while thhe compositions outside that ratio range would be efficacious, but less efficient.
  • the ratio A:B:C, as defined, is necessitated, for optimal efficiency, by the integration of the individual metabolism of each BCAA, and by the amino acid pool size and turnover rate. According to the nutritional therapy aspect of the present invention, such other nutritional components may be presented via the same solution with the BCAA or via separate solutions administered simultaneously or alternately with the novel BCAA composition.
  • the novel BCAA composition is preferably administered by parenteral infusion, such as by I.V. While peripheral vein infusion is preferred as the more routine method, administration can alternately be via the central vein or the portal vein system.
  • the method of treatment of this invention can comprise the enteral alimentation of the BCAA composition in various hydrous concentrations, administered, for example, using an artificial gut systan typically used for such enteral feeding. In this use, the BCAA need not be fully dissolved into solution, and thus concentrations considerably higher than 2 to 6% can be used and such higher concentration solutions are within the scope of the invention.
  • the novel BCAA solution of the present invention will be most useful when the patient must rely on nutritional intake via parenteral administration.
  • the BCAA composition of the invention can be presented as a BCAA solution as described above.
  • the solution is preferably infused in the maximum amount tolerable by the patient. Typically no more than 500 to 1000 ml per day of the novel BCAA solutin would be administered, but even 150C and/or more can be administered. If other infusion solutions are also administered, there would be a corresponding decrease in the amount of the BCAA solution.
  • the rate of infusion is preferably adjusted so that from about 20 to 40 grams of BCAA are delivered per day, or approximately .3 to .7 gm of BCAA per kg body weight per day.
  • the BCAA composition of the present invention is presented as a BCAA solution, it is most preferably in the form of a modular unit adapted for direct connection to I.V. tubing for parenteral infusion.
  • the modular unit can conveniently contain, for example, 500 ml of the novel BCAA solution.
  • the BCAA composition can be anhydrous form, suitable for mixing with water and, if desired, other nutrients.
  • a modular unit can contain a pre-measured amount of the BCAA composition in anhydrous form, and be adapted to receive that volume of water (sterile water if for parenteral infusion) suitable to compose a unit dose of the novel BCAA composition as a solution or other hydrous concentration.
  • water sterile water if for parenteral infusion
  • these branched chain amino acids can be o-fceto analogs, di- or tripeptides and can be combined in aqueous solution with other amino acids, suitable electrolytes, fats, carbohydrates, alcohols, pS adjusters and the like, typically used in parenteral administration, without departing from the scope of the invention.
  • BCAA composition of the present invention will be effective and useful in any nutritional therapy to promote wound healing, etc. in a stressed body
  • one most preferred aspect of the present invention is a method of treatment comprising administration of the BCAA composition and simultaneously developing and maintaining the natural a metabolic state of injury, illness, etc., whereby.endogenous fat is readily mobilized, as previously described.
  • the novel BCAA solution is administered while substantially limiting or totally withholding exogenous high calorienutrients such as carbohydrates from the patient to limit the counter regulatory effects of such exogenous calories..
  • BCAA composition of the present invention in such therapy has now been discovered to promote or even to optimize patient wound healing, nost defense, imnune competence, non-sepsis and survival in a patient suffering partial or total dysfunction or disuse of the gastrointestinal tract, by as presently understood, most efficently increasing whole body protein synthesis, including muscle and especially liver protein synthesis, while minimizing net nitrogen loss or even producing a net nitrogen gain.
  • Sprague-Dawley CD rats were prepared to the point of trauma as described in Example 1. Following the inductions of pancreatitis in all but a control group, the pancreatitis rats were each given one of 5 diets for a 30 hour period: 1) fasting; 2) BCAA (200 mg N) ; 3) L-alanine (200 mg N) ; 4) glucose (7.2 cal); and 5) fat (7.2 cal) . The control group was fasted.
  • Fig. 5 shows the steady state attained in the percentage recovery of the infused isotope in the expired breath of the rats.
  • the BCAA diet produced the greatest reduction of endogenous tyrosine oxidation, to a degree not obtained by the isonitrogenous L-alanine diet. Taking the kinetics of tyrosine metabolism as representative of amino acid in general, the BCAA diet most improved the reutilization of amino acids released by protein breakdown, and, correspondingly, most reduced the oxidation of endogenous amino acids.
  • Fig. 6 graphically illustrates and compares whole body protein dynamics in the stressed and unstressed rats. It can be seen that oxidation of whole body protein in lowest and roughly equivalent for the two isonitrogenous diets, that is, the BCAA and the L-alanine diets. Of critical significance however, is the increased whole body protein synthesis produced only by the BCAA diet. More specifically, Figs. 7-10 graphically illustrated and compare the protein synthesis rats in the stressed rats receiving the various diets. The hypocaloric, 100% BCAA infusion solution shows the most effective promotion of protein synthesis in pancreas (except for the glucose diet), upper small intestine, muscle and most importantly, liver. Fig. 11 graphically illustrates and compares the nitrogen balance achieved with the various diets. The hypocaloric 100% BCAA diet results in the most favorable nitrogen balance.
  • Fig. 12 graphically illustrates and compares the effect of the various diets on plasma glucose and ketone body concentrations in the stressed body.
  • the hypocaloric, 100% ECAA diet is shown to promote a hetogenic state, rather than a glucogenic state.
  • the novel BCAA composition and method of treatment of the present invention are unique in the ability to reduce net nitrogen loss by a nitrogen sparing mechanism which promotes patient recovery and survival more efficiently than can be achieved with any other known isonitrogenous, isocaloric nutriticnl therapy.
  • phagccytic activity and decrease in loss of all amino acids in the urine supporting the importance of branched chain amino acid c ⁇ iiposition as enhancing visceral tissue function (i.e., liver, bone marrow, and kidney).
  • Fasted-septic rats were infused with is ⁇ volenic diets containing: 1) BCAA (210 mg Nitrogen/day); 2) L-Alanine (210 mg Nitrogen/day); or 3) were fasted.
  • the nitrogen sparing mechanism can not be explained as merely the result of providing ⁇ -amino acid nitrogen and/or amino acid calories.
  • the increased levels of the BCAA are accompanied by a markedly improved nitrogen balance a net nitrogen gain, whereas the complete amino acid mixture resulted in a net nitrogen loss.

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  • Pharmacology & Pharmacy (AREA)
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Abstract

Nouvelle composition d'acide amine a chaine ramifiee nutritive et son utilisation pour le traitement d'un patient souffrant de "stress" ou d'une blessure, specialement utile pour l'administration parenterale ou anterale d'un patient souffrant d'un mauvais fonctionnement ou d'un arret de fonctionnement total ou partiel du systeme gastro intestinal. La nouvelle composition favorise et meme optimalise la cicatrisation des blessures d'un patient, la suffisance immune; la defense contre les corps etrangers et/ou la survie. L'acide amine comprend environ 70 a 100% de valine, d'isoleucine, et de leucine, collectivement, dans un rapport de A a B a C, respectivement ou A, B, et C ont chacun une valeur de 1 a 2 environ. La nouvelle composition s'utilise de preference sous la forme d'une solution d'injection par voie parenterale ayant une concentration de 2 a 6% environ, de preference 4%.
EP19810902198 1980-07-31 1981-07-31 Nouvelle preparation d'acide amine et therapie pour le traitement du "stress" et des blessures. Withdrawn EP0057209A4 (fr)

Applications Claiming Priority (2)

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US17418980A 1980-07-31 1980-07-31
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EP0057209A4 EP0057209A4 (fr) 1982-11-25

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US5646187A (en) * 1992-05-20 1997-07-08 Ab Erik Vinnars Use of alpha-ketoglutarate
RU2038077C1 (ru) * 1992-06-26 1995-06-27 Нонна Дмитриевна Кислякова Средство, обладающее адаптогенной активностью
US6469753B1 (en) 1996-05-03 2002-10-22 Starsight Telecast, Inc. Information system
IT1289754B1 (it) * 1996-12-16 1998-10-16 Professional Dietetics Srl Composizioni a base di aminoacidi
NZ334627A (en) 1999-03-12 2002-07-26 Horticulture & Food Res Inst A therapeutic composition containing a therapeutic agent such as an anthelmintic and an antistress agent such as metyrapone or a nitric oxide promoter for increasing efficacy of therapeutic agents and animal growth
ITTO20010804A1 (it) * 2001-08-08 2003-02-08 Professional Dietetics Srl Composizioni a base di aminoacidi, idonee alla terapia per la cicatrizzazione e/o riparazione di ferite e lesioni, in particolare per l'appl
JPWO2005094813A1 (ja) * 2004-03-31 2008-02-14 味の素株式会社 腎疾患用薬剤

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Cited By (1)

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US9166714B2 (en) 2009-09-11 2015-10-20 Veveo, Inc. Method of and system for presenting enriched video viewing analytics

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EP0057209A4 (fr) 1982-11-25

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