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WO1992011773A1 - Compositions et procedes permettant d'obtenir une reponse physiologique amelioree a l'effort - Google Patents

Compositions et procedes permettant d'obtenir une reponse physiologique amelioree a l'effort Download PDF

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Publication number
WO1992011773A1
WO1992011773A1 PCT/US1991/009793 US9109793W WO9211773A1 WO 1992011773 A1 WO1992011773 A1 WO 1992011773A1 US 9109793 W US9109793 W US 9109793W WO 9211773 A1 WO9211773 A1 WO 9211773A1
Authority
WO
WIPO (PCT)
Prior art keywords
composition
pyruvate
glyceroi
lactate
water
Prior art date
Application number
PCT/US1991/009793
Other languages
English (en)
Inventor
Melvin J. Fregly
Malcolm R. Privette
Robert Cade
Original Assignee
University Of Florida
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Priority claimed from US07/636,329 external-priority patent/US5147650A/en
Priority claimed from US07/770,679 external-priority patent/US5236712A/en
Priority claimed from US07/770,674 external-priority patent/US5238684A/en
Application filed by University Of Florida filed Critical University Of Florida
Publication of WO1992011773A1 publication Critical patent/WO1992011773A1/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L2/00—Non-alcoholic beverages; Dry compositions or concentrates therefor; Preparation or treatment thereof
    • A23L2/38—Other non-alcoholic beverages
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/20—Reducing nutritive value; Dietetic products with reduced nutritive value
    • A23L33/21—Addition of substantially indigestible substances, e.g. dietary fibres
    • 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

Definitions

  • the "dehydration syndrome” is characterized by loss of appetite a limited capacity for work. Evidence of heat exhaustion becomes apparent wit losses of 5% of the body water, and at 7% disorientation and hallucinatio occur. Losses of body water of 10% or greater are extremely hazardous a lead to heat stroke and death if not treated immediately. Heat stroke accompanied by high body temperature (106-1 0°F) ; deep coma, and in mo cases there is complete absence of sweating, and failure of the major orga systems.
  • One metabolic change which is associated with continued physica exertion is a shifting of the type of compound used as the primary energy source.
  • the metabolism of fat is a primary energ source for the body.
  • carbohydrates are increasingly used as a source of readily available energy.
  • the body continues to utili carbohydrates as a major source of energy during prolonged periods of exercis If, however, the exercise is particularly strenuous or long in duration, th supply of readily available carbohydrates may become depleted and the body forced to utilize another source of energy.
  • the metabolism of proteins fills th energy void caused by the depletion of carbohydrates.
  • th metabolism of protein is not an efficient source of energy for the exercisin individual. Protein metabolism results in the utilization of amino acids.
  • Thi amino acid utilization can result in the depletion of essential amino acids in th plasma.
  • the loss of amino acids can detrimentally affect the person or anim in many ways.
  • One detrimental effect of the depletion of amino acids is reduction on the body's ability to repair tissue which is damaged in the cours of the strenuous exercise.
  • Osmotic pressure is primarily responsible for the direction and rate movement of water across membranes in the body.
  • the general concepts osmosis and osmotic pressure are very well known chemical phenomena where water moves across a semipermeable membrane in such a way as to make thermodynamic activity uniform across the entire system.
  • water will mo across a semipermeable membrane such that the net flow of water will be acro the membrane into the fluid which initially had the highest concentration solutes.
  • the allocation of water between digestive organs, blood plasma, a cells depends upon the relative osmotic pressures between these sites.
  • the subject invention relates to novel compositions and methods f ameliorating the adverse physiological effects which can result from physic exertion and heat exposure.
  • the subject invention can be used with humans an other animals. Described here is a novel fluid composition comprising
  • ( ⁇ ) is rapidly absorbed through the gastrointestinal tract; (in prevents the decrease of blood volume; and (rv) is an energy source wherein the concentration of said additional compound(s) is from about 0.5 to about 10%. More preferably, the concentration of said additional compoun may be from about 0.5% to about 5%.
  • glyceroi is glyceroi.
  • Other compound which may be used according to the subject invention include pyruvate, alanine and/or lactate, which are particularly useful because they function to enhance th energy available for working muscles.
  • the presence of pyruvate or lact improves performance and helps to prevent the detrimental breaking down protein as an energy source.
  • the compounds added to the electrolyte/gluc solution may be used in the solution individually or in combination. Also described here are unique methods, involving the use of the no fluid composition, for ameliorating the adverse effects which can result fr physical exertion, heat exposure, exposure to cold, and blood loss.
  • Figure 1 shows the changes in blood volume of three trials of hum subjects working at 75-80% of their maximal rate of oxygen uptake on a bicy ergometer. The trials are designated in the figure. One standard error is set at each mean. This figure shows that only the group which was given TQ 2 ( minutes before initiation of exercise [200 ml], at 15 min, 45 min, and every h hour thereafter) was able to maintain their blood volume during the period exercise.
  • Figure 2 shows that the pulse rate of the group receiving TQ 2 w maintained at a lower value than the other two trials during the course exercise.
  • the trials are the same as those shown in Figure 1.
  • One standa error is set off at each mean.
  • Figure 3 shows the high level of cardiac output achieved in connecti with the administration of TQ 2 .
  • Figure 4 shows the time required to reach a rectal temperature of 38° by the three trials shown in Figure 1, as well as an additional group receivi nothing per os (NPO) prior to the exercise.
  • Figure 5 shows the mean rates of sweating of the same four trials as Figure 3.
  • Figure 6 shows the respiratory quotient ([OC /JOJ) as a function exercise time. Respiratory quotient is an indication of the metabolic ener source being utilized.
  • Figure 7 shows the perceived difficulty (in arbitrary rating units) of t exercise as scored by observers during the exercise.
  • the invention described here is a novel composition which has be shown to improve the physiological response in animals, including humans, physical exercise and environmental exposure.
  • the inventi comprises a fluid which contains, as one of the ingredients, glyceroi or an est of glyceroi, or any other analog or derivative of glyceroi which is non-toxic animals, can be rapidly absorbed through the gastrointestinal tract, distribut into plasma and extracellular fluid, but is not transferred, or is transferr poorly, into the brain.
  • glyceroi refers to glycer itself and any ester, analog, or derivative which has the same function as glycer in the composition described here.
  • the composition may contain pyruvate.
  • Other compounds satisfying t aforementioned characteristics can be found in standard medical pharmacology reference books.
  • novel fluid's surprising and beneficial physiological effects on t body during exercise or environmental exposure include maintenance of bloo volume and cardiac output, readily available energy source, improved skin bloo flow, prevention or delay of onset of hyperthermia, increased rate of moveme of electrolytes across the gastrointestinal wall, reduction in the breakdown proteins and associated metabolism of essential amino acids, and decreased tim needed for repair of body tissue following strenuous exercise.
  • the body' physiological response to exercise or environmental exposure is greatly enhance compared to the response when the body receives no fluids, receives only wate or receives fluids such as GATORADE ® which contain electrolytes and a suga source in addition to water.
  • GATORADE ® which contain electrolytes and a suga source in addition to water.
  • the term "ameliorating the adverse effects of physica exertion or environmental exposure” refers to the achievement of one or mor of the following: prevention of plasma volume decrease, increased respirator quotient, reduced rate of increase of rectal temperature, reduced pulse rate, o increased cardiac output; combined with either enhanced endurance o performance, lower perceived difficulty of a physical task, or an enhanced abili to withstand heat exposure or chronic exposure to cold.
  • the many advantages of the novel fluid composition (designated TQ ⁇ described here are clearly sho in Figures 1 through 7.
  • the TQ 2 which was administered to exercis individuals in order to achieve the results discussed below was primarily wat
  • the composition comprised glucose (4%), potassium meq/I), sodium (26 meq/l), phosphate (4 meq/1), and glyceroi (3%).
  • T decrease in sweat rate is significant because this suggests that the body is bei cooled more efficiently. This can be attributed to increased blood volume whi results in improved peripheral circulation and movement of blood near the sk surface. This surface circulation is very important in the effective dissipation body heat. Further evidence suggests that the use of TQ 2 results in an increase in t proportion of energy derived from carbohydrates as opposed to energy deriv from the metabolism of fat or protein. This unexpected and advantageous res can be seen from Figure 6 which shows the respiratory quotient as a function time. Respiratory quotient, which is defined as the ratio of carbon dioxi output to oxygen input, is an indication of the type of compounds which being metabolized as an energy source for the exercising person or animal. metabolism of carbohydrates, the respiratory quotient is 1.0.
  • the respirat quotient for metabolism of fats or proteins is less than 1.0. If fat is the prim source of energy, then the respiratory quotient is approximately 0.6. respiratory quotient of approximately 0.8 can be expected if the cells are burni half fat and half carbohydrates. Thus, the higher respiratory quotients shown Figure 6 for TQ 2 indicate that these individuals are utilizing a greater proporti of carbohydrates as their energy source.
  • the increased use of carbohydrates c have important physiological advantages, especially when strenuous exercise maintained over a long period of time. For example, carbohydrate metabolis is preferable to fat metabolism because it is a quicker and more efficient sour of immediate energy. Further, carbohydrates are preferred as an energy sour over proteins because protein metabolism can cause the depletion of essenti amino acids. The depletion of amino acids can have adverse physiologic effects including a reduction in the body's ability to repair muscle which damaged in the course of exercise.
  • pyruvate may be added to the novel composition. It has also been found that by administerin pyruvate, it is possible to maintain a relatively steady concentration of pyruvat for use by cells as an energy source. Addition of a small amount of pyruvat given at frequent intervals, improves performance and endurance, apparentl because it enhances entrance of acetyl CoA into the Krebs cycle.
  • the Kreb cycle is a well known, but very complicated, biochemical pathway which provide a working muscle with its energy source. A detailed description of the Kreb cycle can be found in most biochemistry textbooks, including Lehninge
  • Pyruvate normally is formed from glucose but, during vigorous exercise pyruvate may not be formed fast enough to keep up with cellular demand
  • Lactate may be used instead of, or in addition to, pyruvate in the curre invention.
  • Alanine may also be used instead of, or in addition to, lactate pyruvate in the current invention.
  • FIG. 7 An additional important indicator of the novel fluid composition effectiveness is illustrated in Figure 7.
  • This figure shows a significant loweri of the perceived difficulty of long term exercise among individuals to whom T is administered.
  • All individuals naturally perceive an increase difficulty of exercise as the exercise is maintained for long periods of tim individuals who were given TQ 2 showed a significantly reduced rate of increa in the perceived difficulty of the exercise.
  • the trial ingesting water showed t normal perceived difficulty within 90 minutes of beginning exercise while in t trial receiving GATORADE ® reached the same level of perceived difficulty aft 150 minutes of exercise.
  • the trial receiving TQ 2 reached this level after 1 minutes.
  • the lower difficulty perceived by individuals receiving TQ 2 could lea to enhanced physical performance, especially when long term exercise, such marathons, are involved.
  • the electrolytes of the composition can be selected, for example, from the group consisting of sodium, potassium, phosphate, bicarbonate, sulfate, chloride, calcium, and magnesium.
  • the fluid may contain from about 1 meq/t to about 5 meq/1 potassium and from about 15 meq/1 to about 30 meq/1 sodium.
  • the composition may contain about 2 meq/I potassium and about 26 meqf sodium.
  • the composition may contain phosphate in concentrations varying from about 2 meq/1 to about 8 meq/1. Specifically, the phosphate concentration may be about 4 meq/l.
  • the novel fluid may also contain citric acid, citrate, preservatives, flavorings, artificial sweeteners, vitamins, minerals, and other compounds appropriate in a beverage of this type.
  • the novel fluid may also be carbonated.
  • the concentration of pyruvate, lactate, alanine, or any combinati thereof may be from about 0.5% to about 10%.
  • the concentrati of pyruvate, lactate, alanine, or any combination thereof is between about and about 1.5%.
  • composition of the subject invention can also be used as a tempor substitute for blood.
  • this fluid can be given to replenish the blood volume.
  • .Also duri heart surgery or other surgical procedures where a heart-lung machine is use the novel composition can be used to prime the heart-lung machine, there helping the patient to maintain plasma volume and to provide energy to he ameliorate the physiological trauma of surgery.
  • .Also by maintaining vascul volume, complications such as post-surgical acute renal failure can be minimize
  • the composition will comprise, preferabl water, electrolytes, glucose, and glyceroi. Sucrose and citric acid are to avoided when the composition is given intravenously.
  • the composition of the subject invention may also comprise pyruvat lactate, alanine, or any combination thereof.
  • TQ 2 composition used in this experiment consisted water, electrolytes, 3% glucose, about 2% glyceroi, and about 2% pyruvate.
  • T pH of the solution was about 7.0, and the osmotic pressure was about 2 milliosmol.
  • a pH of approximately 7.0 can be maintained by use of appropriate buffer system such as NaH 2 P0 4 :Na 2 HP0 4 in a ratio of 1:4.
  • a fluid composition similar to that described in Example 1 may b administered to animals which are subject to strenuous exercise such as race uHi ⁇ ug.t.x miXm. xi mm.1 WO ⁇ .. J.11C c ⁇ u »-.uj ⁇ ua ⁇ .nj ⁇ ui uie iiuiu aa vc ⁇ as m concentrations of its components may depend upon what type of animal i receiving the treatment.
  • the teachings of this document combined with th expertise of one skilled in the biological and medical sciences would enable th
  • SUBSTITUTE SHEET practitioner to adjust the composition of the fluid in order to accommodate th needs of a particular animal.
  • the administration of the novel fluid could be orally, intravenously, or by other means capable of delivering the fluid to the tissues of the recipient animal. If the fluid is to be delivered orally, such a composition could contain flavoring which would make the fluid attractive to the animal. For example, for horses, the fluid could be flavored with an oat extract.
  • Example 5 To enhance the beneficial effects of the novel fluid composition described here, caffeine may be added.
  • the concentration of caffeine may range from about 50 mgfl to about 5000 mg 1.
  • Example 6 The novel fluid composition described here may also be used to help maintain the weight and health of agricultural animals subjected to heat stress.
  • Heat stress may occur, for example, on the open range, in zoos, and during the transportation of animals.
  • novel fluid composition described here may also be used to alleviate the effects of volume depletion which is a problem which has been observed in astronauts.
  • glyceroi in a heverage could also be used in areas of cold environment where it would reduce tissue damage due to frostbite and extreme cold.
  • a glyceroi beverage would allow distribution of the glyceroi into the tissues, particularly in the extremities, fingers and toes, which are affected most by crystallization in the tissues and by diminished blood flow.
  • Glyceroi has been found to be distributed throughout the body in ten minutes after ingestion; thus, it could be used to rapidly provide protection from extreme cold. This could be especially useful, for example, for football players who must play in cold climates, but who cannot or do not wish to wear gloves or other protective covering.
  • the subject composition can be utilized to achieve proper water allocation and prevent blood plasma volume depletion, it can be used to ameliorate the effects of dehydration caused by exposure to cold temperatures.
  • the novel composition can be used advantageously by skiers or by army personnel in cold climates.
  • the optimal rate of administration of the novel composition described here can depend upon the physiological characteristics of the individual receiving the fluid, the nature of the physical exertion or exposure, and the environmental conditions. However, a standard rate of application would be approximately 170 to 260 ml of fluid every 15 to 20 minutes, starting approximately 15 minutes before the exercise or exposure is commenced. If significant sweating is occurring, as would be expected in hot environments or with physical exertion, the intake of fluid should be adjusted so that the volume ingested approximates the amount of fluid lost through sweating. When the fluid is ingested to alleviate the dehydration accompanying prolonged exposure to cold temperature, the quantity of fluid ingested may be less than that which is necessary to achieve the desired effects in hot climates.
  • the ratio of ingredients in the composition may also be adjusted for changing environmental or physiological conditions. For example, in cold weather, the composition may contain a greater concentration of glyceroi and a reduced concentration of electrolytes. Also, for individuals who desire a lower calorie drink, the sugar may be replaced with an artificial sweetener such as aspartame. For individuals who are concerned about high blood pressure, the drink can contain reduced concentrations of sodium.
  • composition of the subject invention may also be prepared in a dehydrated, powder, or concentrate form for convenience of sale or shipment When formulated in this way, the product could be reconstituted by the addition of water.
  • the preparation of such a product in the dehydrated, powder, or concentrate form is well known to those skilled in the art. See for example, U.S. Patent Nos. 4,042,684 and 4,322,407. .Although glyceroi cannot be provided in powder form, it can be provided separately or in a mixture of the other ingredients in a reduced water volume to facilitate bulk shipping.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Nutrition Science (AREA)
  • Engineering & Computer Science (AREA)
  • Food Science & Technology (AREA)
  • Polymers & Plastics (AREA)
  • Inorganic Chemistry (AREA)
  • Mycology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

On décrit de nouveaux procédés et de nouvelles compositions susceptibles d'être utilisées comme substitut sanguin pour contrecarrer les effets physiologiques adverses de la réduction du volume sanguin. Les nouvelles compositions comprennent des fluides contenant de l'eau, des électrolytes, du glycérol et des sources additionnelles d'énergie.
PCT/US1991/009793 1990-12-31 1991-12-30 Compositions et procedes permettant d'obtenir une reponse physiologique amelioree a l'effort WO1992011773A1 (fr)

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
US07/636,329 US5147650A (en) 1988-07-29 1990-12-31 Compositions and methods for achieving improved physiological response to exercise
US636,329 1990-12-31
US07/770,679 US5236712A (en) 1988-07-29 1991-10-03 Compositions and methods for achieving improved physiological response to exercise
US770,674 1991-10-03
US07/770,674 US5238684A (en) 1988-07-29 1991-10-03 Compositions and methods for achieving improved physiological response to exercise
US770,679 1991-10-03

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WO1992011773A1 true WO1992011773A1 (fr) 1992-07-23

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WO (1) WO1992011773A1 (fr)

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0680317A1 (fr) * 1991-11-27 1995-11-08 Stanko, Ronald T., M.D. Procede de traitement d'un patient souffrant d'un traumatisme cardiaque
WO1996020719A3 (fr) * 1994-12-30 1996-09-06 East And Midlothian Nhs Trust Solution de substitution pour liquide organique
GB2344996A (en) * 1998-12-23 2000-06-28 Sueddeutsche Kalkstickstoff A solid stable aggregate formed from a pyruvate component and a carbohydrate component
GB2345247A (en) * 1998-12-23 2000-07-05 Sueddeutsche Kalkstickstoff Pyruvic acid formulations
EP2252281A2 (fr) * 2008-02-15 2010-11-24 President and Fellows of Harvard College Solution de substitution sanguine
US8945823B2 (en) 2007-02-17 2015-02-03 The United States Of America As Represented By The Department Of Veterans Affairs Compositions and methods for tissue preservation

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1048724A (en) * 1964-03-06 1966-11-16 Feed Serv Livestock Feeds for ruminants
GB1252781A (en) * 1967-06-07 1971-11-10 Stokely Van Camp Inc Composition of matter for limiting dehydration and fatigue during periods of physical exertion
US4042684A (en) * 1976-03-23 1977-08-16 Annika Britt Kahm Dietetic beverage
US4322407A (en) * 1978-12-11 1982-03-30 Vitapharm Pharmaceutical Pty. Ltd. Electrolyte drink
WO1982003773A1 (fr) * 1981-04-27 1982-11-11 Baxter Travenol Lab Solution de dialyse contenant du glucose, des acides amines et de l'insuline
EP0353065A1 (fr) * 1988-07-29 1990-01-31 University Of Florida Compositions et procédés pour obtenir une réaction physiologique améliorée à des efforts physiques
GB2228412A (en) * 1989-02-28 1990-08-29 Syntex Inc Nicardipine pharmaceutical composition for parenteral administration

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1048724A (en) * 1964-03-06 1966-11-16 Feed Serv Livestock Feeds for ruminants
GB1252781A (en) * 1967-06-07 1971-11-10 Stokely Van Camp Inc Composition of matter for limiting dehydration and fatigue during periods of physical exertion
US4042684A (en) * 1976-03-23 1977-08-16 Annika Britt Kahm Dietetic beverage
US4322407A (en) * 1978-12-11 1982-03-30 Vitapharm Pharmaceutical Pty. Ltd. Electrolyte drink
WO1982003773A1 (fr) * 1981-04-27 1982-11-11 Baxter Travenol Lab Solution de dialyse contenant du glucose, des acides amines et de l'insuline
EP0353065A1 (fr) * 1988-07-29 1990-01-31 University Of Florida Compositions et procédés pour obtenir une réaction physiologique améliorée à des efforts physiques
GB2228412A (en) * 1989-02-28 1990-08-29 Syntex Inc Nicardipine pharmaceutical composition for parenteral administration

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
European Journal of Applied Physiology, vol. 55, no. 6, 1986, M. GLEESON et al.: "Comparison of the effects of pre-exercise feeding of glucose, glycerol and placebo on endurance and fuel homeostasis in man", pages 645-653, see whole document (cited in the application) *
European Journal of Applied Physiology, vol. 57, no. 5, 1988, R.J. MAUGHAN et al.: "Influence of a 36 h fast followed by refeeding with glucose, glycerol or placebo on metabolism and performance during prolonged exercise in man", pages 570-576, see the whole document (cited in the application) *
Journal of Applied Physiology, vol. 34, no. 3, 1973, D.L. COSTILL et al.: "Rapid fluid replacement following thermal dehydration", pages 299-303, see whole document (cited in the application) *
Journal of Applied Physiology, vol. 63, no. 1, July 1987, M.L. RIEDESEL et al.: "Hyperhydration with glycerol solutions", pages 2262-2268, see whole document (cited in the application) *
Medicine and Science in Sports and exercise, vol. 15, no. 3, 1983, J.M. MILLER et al.: "Effect of glycerol feeding on endurance and metabolism during prolonged exercise in man", pages 237-242, see whole document (cited in the application) *

Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0680317A1 (fr) * 1991-11-27 1995-11-08 Stanko, Ronald T., M.D. Procede de traitement d'un patient souffrant d'un traumatisme cardiaque
EP0680317A4 (fr) * 1991-11-27 2000-12-06 Stanko Ronald T M D Procede de traitement d'un patient souffrant d'un traumatisme cardiaque
WO1996020719A3 (fr) * 1994-12-30 1996-09-06 East And Midlothian Nhs Trust Solution de substitution pour liquide organique
US5846572A (en) * 1994-12-30 1998-12-08 East & Midlothian Nhs Trust Body fluid replacement solution
GB2344996A (en) * 1998-12-23 2000-06-28 Sueddeutsche Kalkstickstoff A solid stable aggregate formed from a pyruvate component and a carbohydrate component
GB2345247A (en) * 1998-12-23 2000-07-05 Sueddeutsche Kalkstickstoff Pyruvic acid formulations
US8945823B2 (en) 2007-02-17 2015-02-03 The United States Of America As Represented By The Department Of Veterans Affairs Compositions and methods for tissue preservation
EP2252281A2 (fr) * 2008-02-15 2010-11-24 President and Fellows of Harvard College Solution de substitution sanguine
EP2252281A4 (fr) * 2008-02-15 2011-08-24 Harvard College Solution de substitution sanguine
US8563233B2 (en) 2008-02-15 2013-10-22 President And Fellows Of Harvard College Blood substitute solution

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