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WO1993010777A1 - Composition et methode permettant de reduire les contraintes d'oxydation cellulaire par radicaux libres chez les animaux homeothermes - Google Patents

Composition et methode permettant de reduire les contraintes d'oxydation cellulaire par radicaux libres chez les animaux homeothermes Download PDF

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Publication number
WO1993010777A1
WO1993010777A1 PCT/US1992/009587 US9209587W WO9310777A1 WO 1993010777 A1 WO1993010777 A1 WO 1993010777A1 US 9209587 W US9209587 W US 9209587W WO 9310777 A1 WO9310777 A1 WO 9310777A1
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Prior art keywords
animal
copper
free radical
amino acid
zinc
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H. Dewayne Ashmead
Harvey H. Ashmead
Robert B. Jeppson
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Albion Laboratories Inc
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Albion International Inc
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Priority to EP19920924342 priority Critical patent/EP0614361A4/en
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    • 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
    • A61K31/28—Compounds containing heavy metals
    • A61K31/315—Zinc compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/28—Compounds containing heavy metals
    • 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
    • A61K31/28—Compounds containing heavy metals
    • A61K31/295—Iron group metal compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/28—Compounds containing heavy metals
    • A61K31/30—Copper compounds
    • 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
    • A61K33/04—Sulfur, selenium or tellurium; Compounds thereof

Definitions

  • This invention relates to compositions and methods of reducing free radical cellular oxidative stress in warm-blooded animals showing symptoms of free radical toxicity. More particularly, this invention relates to amino acid chelated mineral compositions containing one or more minerals selected from the group consisting of copper, zinc, iron and manganese and to methods of administering these compositions to strengthen and maintain the functioning of enzymes which help regulate the effects of oxidative bursts for killing or deactivating pathogens and foreign matter in neutrophils and macrophages. These enzymes function to adequately remove the superoxides, peroxides and hydroxides that are formed in the cells.
  • These enzymes are inclusive of, but not limited to, the superoxide dismutases (SOD) , catalase and glutathione peroxidase. As previously stated, they function to remove the superoxides, peroxides and hydroxides that are formed in the cells. Otherwise oxygen toxicity results.
  • SOD superoxide dismutases
  • the superoxide radical is formed during various metabolic processes, many of which are considered normal. Liver cells, muscle cells, leukocytes, erythrocytes, aerobic bacteria, any cell that undergoes oxidative cellular metabolism, all form superoxide radicals during normal metabolic processes. These oxygen radicals are converted to hydrogen peroxide by CuZn-superoxide dismutases (CuZnSOD) in the cells.
  • the hydrogen peroxide is then converted to oxygen and water by a catalase. If the hydrogen peroxide and the superoxide radical are allowed to combine, the more reactive and destructive hydroxide radical is formed.
  • the formation of one or more of the superoxide, hydrogen peroxide or hydroxide radicals becomes uncontrolled or the organism loses the ability to regulate these reactions, changes in cellular physiology result that become detrimental to the individual cells, organ systems, or the entire host or animal. Some of these changes include generalized tissue destruction, lameness and joint inflammation, DNA miscoding or degradation, lipid peroxidation, altered immune function and inactivation of important cellular enzymes.
  • the primary activated superoxide dismutase (SOD) in animals is CuZnSOD.
  • This metalloenzy e undergoes a reduction-oxidation exchange with the superoxide radical with the net result of dismutation of the superoxide radical to hydrogen peroxide and oxygen.
  • the metals for this activity are copper and zinc.
  • Other forms, i.e. MnSOD and FeSOD, are also known but occur primarily in bacteria and cellular mitochondria. Without the presence of copper, the eucaryotic cytocell SOD enzyme is virtually inactive in the animal. The activity of the CuZnSOD enzyme can be suppressed by the rapid accumulation of hydrogen peroxide. Therefore, it is essential that other enzymes which deplete hydrogen peroxide be functional within the cell to maintain SOD activity.
  • Catalase is a large molecular weight enzyme that contains four he e groups per molecule. Catalase is the primary enzyme necessary for the breakdown of hydrogen peroxide in the cell to oxygen and water and is found in all cells of the body that utilize oxygen. Glutathione peroxidase (GSH-Px) has a selenium dependent form which contains four moles of selenium per mole of the enzyme. The oxidative role of this enzyme is similar to catalase in that it converts hydrogen peroxide to water and oxygen. Wherever catalase or glutathione peroxidase activity is impaired there can be a toxic build-up of peroxides. This, in turn, can lead to a build-up of the hydroxide radical.
  • Glutathione peroxidase Glutathione peroxidase
  • the non-selenium glutathione peroxidase plays a role in controlling lipid peroxidation.
  • the primary form of glutathione peroxidase within the red blood cell is the selenium dependent form which maintains a linear relationship to selenium status within the animal and has been used to indicate whether or not a selenium deficiency exists.
  • oxygen radical production is detrimental.
  • One of the most useful purposes of oxygen radical, peroxide and hydroxide radical production is the role they play in the immune response when mono- or polymorphonuclear leukocytes engulf bacteria or immune complexes and destroy them.
  • oxygen radicals increase systemically, a more active immune response is initiated.
  • the buildup of oxygen radicals can be devastating to the animal, causing massive cellular destruction.
  • Coffey also states that copper amino acid complexes or chelates are capable of catalyzing the dismutation of the reactive oxygen radical in a fashion similar to CuZnSOD.
  • the superoxide dismutase activity of copper amino acid chelates has been reported by JOester, et al , FEBS Letters. (1972) 25:25, and Brigelius et al , FEBS Letters (1974) 47:72.
  • One factor which may contribute to the inability of the body to control free radical accumulation within oxygen consuming cells is that ionic mineral absorption in the gut requires an integral protein carrier molecule embedded in and transversing the mucosal membrane.
  • carrier proteins For iron, apoferritin is a suitable carrier. In the case of zinc, albumin is the carrier protein. For copper the carrier is ceruloplasmin and for manganese it is transmanganin. Both protein and albumin are necessary to transport mineral ions from the gut to the plasma.
  • a biological system as distinguished from tissues, can be affected through the proper oral in vivo administration of amino acid chelates.
  • a system is a set or series of interconnected or interdependent parts or entities (objects, organs, fluids, organisms, etc.) that function together in a common purpose or produce results impossible of achievement by one of them acting or operating alone.
  • objects, organs, fluids, organisms, etc. that function together in a common purpose or produce results impossible of achievement by one of them acting or operating alone.
  • Selenium may optionally be administered. These enzymes function to adequately remove the superoxides, peroxides and hydroxides that are formed in the cells.
  • Bioavailable forms of copper, zinc, iron and manganese which are absorbed via the intestinal tract of a warm-blooded animal at a site other than the duodenum are those made by chelating the mineral with an amino acid or peptide ligand wherein the ligand to mineral ratio is at least 1:1 and preferably 2:1 or higher and wherein the molecular weight of the amino acid chelate formed is not greater than 1500 and preferably does not exceed 1000.
  • amino acid chelates are stable and are generally absorbed intact through the intestinal tract via active dipeptide transport.
  • Such amino acid chelates have a stability constant of between about 10 6 and 10 16 . A more detailed description of such chelates and the method by which they are absorbed is found below and is also documented in Ashmead et al .
  • mineral absorption from the intestinal tract occurs via at least two pathways.
  • a mineral salt after ingestion is solubilized and ionized in the acid pH of the stomach.
  • the metal cations passing from the stomach into the intestinal tract are absorbed, if at all, in the duodenum or upper portion of the small intestine. This requires a relatively low acid pH. It is believed that the metal cation is presented to the integral proteins in the brush border of mucosal cells of the duodenum.
  • the transport of the metal ion across the mucosal cell membrane is accomplished by an active transport system which involves chelating or complexing the cation to complex carrier proteins.
  • amino acid chelates In the field of animal nutrition, the American Association of Feed Control Officials has issued an official definition of "amino acid chelates” as being "the product resulting from the reaction of a metal ion from a soluble salt with amino acids with a mole ratio of one mole of metal to one to three (preferably two) moles of amino acids to form coordinate covalent bonds. The average weight of the hydrolyzed amino acids must be approximately 150 and the resulting molecular weight of the chelate must not exceed 800.” It is also documented that amino acid chelates can be prepared from metal ions which do not come from soluble salts. Ashmead, U.S. Patent 4,599,152 and Ashmead, U.S. Patent 4,830,716 both disclose methods of preparing pure amino acid chelates using metal sources other than soluble metal salts. However, it is not critical to the present invention in which manner the amino chelates are made.
  • Elemental salts are not as bioavailable has the amino acid chelates referred to, particularly when there is interference from heavy metals. However, if the enzyme and immune systems are not functioning properly, many of the drugs and or methods relied on to treat and prevent free radical toxicity are ineffectual and mortality may result.
  • Copper, zinc, manganese, iron and, optionally, selenium are the minerals of greatest concern which have a direct impact on maintaining and sustaining the activity and formation of catalase, CuZnSOD and GSH-Px. Besides being present in adequate quantities, the interrelationship of one mineral to another is important. Specific minerals may be present in adequate amounts according to assays of food sources. However, due to interference or competition, such minerals may not be biologically available. For example, it is known that excess molybdenum directly ties up copper. Manganese and iron compete for the same active ionic absorption sites in the small intestine. Manganese is readily excreted from the body, but there is no excretion mechanism for excess iron accumulation which also may contribute to an inhibitory affect on copper utilization.
  • the enzymes are present within the cell and are therefore reflective of the amounts and activity present at the time of cell formation.
  • the erythrocytes from which measurements are made are easily accessible for analysis of these enzymes it is important to consider the average life span of the erythrocyte in each species. This is because there is continuous erythropoiesis and the blood samples collected are an average of the nutritional status over the erythrocyte life span just prior to sample collection. In the bovine species, for example, this span is about 48-63 days for ages up to 3 months, 70-126 days from 3 months to near maturity and 160 for mature animals. It is therefore important that enzyme activity levels be monitored for at least a period of time that is equivalent to the erythrocyte life in a particular species.
  • the correct monitoring of oxidative enzyme activity and supplementation, as necessary, with critical trace elements selected from the group consisting of manganese, zinc, iron and copper in amino acid chelated form, with or without additional selenium supplementation, should lead to an improvement in nutrient utilization and immunity without resorting to the use of unproven drugs and/or chemicals which may have a detrimental impact on the animal.
  • the copper, zinc, iron and manganese amino acid compositions, with or without selenium, will preferably be administered to the warm blooded animal orally.
  • mixing of the chelates in the food, drinking water or other ration form given to the animal may be the preferred method of treatment.
  • the chelates may be mixed with salt (sodium chloride) when being administered to animal species.
  • the chelates may be administered in the form of tablets, capsules, powders, syrups, elixir or any other suitable form. They may be mixed with fillers, excipients, vitamins and other foodstuffs.
  • the exact amount of mineral to be administered, and the mole ratio of one mineral to another, may depend upon the particular symptoms and level of free radical oxidative stress being treated. Often, assay results of tissue and serum samples may have to be taken before a proper formulation can be made. Then the amount of minerals and their ratios may be adjusted by modification of feed supplementation and intake. To make a determination, the correct interpretation of data may be more important than the actual numbers generated in an assay and values would additionally need to be correlated to bioavailability and antagonistic parameters of one trace element to another or from one trace element to other minerals such as copper and iron.
  • Serum and liver assays as well as assays of the SOD, peroxidase and catalase enzymes will often serve to determine need for administration of copper, zinc, iron and manganese separately or in certain combinations and ratios. Also, the need to utilize selenium can be similarly determined.
  • An assay of the diet may also be important to determine mineral amounts in the diet and identify deficiencies and/or antagonistic factors which may affect trace minerals when administered. For example, it will be noted from the data and tests which follow as illustrative of the invention that iron was adequately present in the food ratios administered and the separate administration of iron amino acid chelate was not indicated.
  • the exact amount of amino acid chelate, which minerals to use and in what ratios, and whether to add selenium, are preferably determined on an empirical basis according to need using data, such as contained in Table 1, as a guideline.
  • the term, "effective amount" of one or more minerals is based on both the amount of mineral and the ratio of one mineral to another which had been determined to be required to meet the needs of a particular warm-blooded animal or group of animals, including humans, which are (1) vulnerable to oxidative stress or free radical toxicity, (2) are exhibiting certain symptoms of oxidative stress or (3) are affected by free radical toxicity.
  • compositions based on collected data over periods of time, it will be possible to pre-formulate compositions based on known needs of the animal species experiencing oxidative stress.
  • an "effective amount" of a composition can determine without undue experimentation what an "effective amount" of a composition is and how to administer it accordingly. It is not possible to categorically state that "x" mg of trace mineral per kg of animal body weight is what is needed to reduce symptoms of free radical oxidative stress. Nor is it possible to state, for example, that the ratio of Cu to Zn will be "a:b" in all instances.
  • Each animal species and form of free radical oxidative stress may require different amounts of minerals and/or ratios of minerals.
  • the chelate administered has a ligand to metal ratio of 2:1 or greater.
  • the chelate has a molecular weight not in excess of 1500 and in most cases, not in excess of 1000.
  • the stability constant in each instance is between about 10 6 and 10 16 .
  • Example 1 This example demonstrates the ability of chelated minerals to enhance oxidative enzyme activity to a member of the bovine species with the consequent result that reproductive ability was restored.
  • a three year old Simmental Bull who was not producing active spermatozoa was examined for oxidative enzyme activity through blood tests. Superoxides are required by sperm to maintain cell wall integrity while in the epididymis. However, unregulated oxygen radical production within sperm is highly damaging. After the first test the bull was placed on a ration which included zinc, manganese and copper amino acid chelates.
  • a mineral ration was prepared by mixing 120 lbs of an amino acid chelate mixture containing 8% zinc, 4% manganese and 1% copper with other ingredients including dicalcium phosphate, magnesium oxide, solulac, rice hulls, calcium carbonate, potassium chloride and various amounts of vitamins and other minerals, some of which were present in inorganic salt or oxide form and some of which were present as chelates or complexes.
  • the mineral ration mixture was made up to one ton of ration with the added ingredients.
  • the chelated mineral supplemented ration was then mixed with equal parts of salt (sodium chloride) and made available free choice to the bull. It was estimated that the average daily consumption of the mineral ration amounted to between about 2 and 3 ounces per day. At three time intervals of three weeks duration the bull was again bled and tested for oxidative enzyme activity with the results being recorded in Table 2 as follows:
  • PSS porcine stress syndrome
  • Typical clinical signs of PSS are hyperventilation, tachycardia, muscular rigidity and rapid increase in body temperature. It is brought on by stresses such as being transported, exercising and mating. PSS can also be induced in pigs (and in predisposed humans) , by exposure to halothane anesthesia. Halothane is known to produce potent free radicals which exacerbate inadequate antioxidant defense mechanisms. Financial losses attributed to PSS amount to millions of dollars each year. It is therefore of paramount importance to be able to identify susceptible animals and provide treatment to reduce and or eliminate this syndrome.
  • PSS mortality in susceptible pig herds ranges from about 3 to 5%.
  • This example illustrates the efficacy of amino acid chelates in a herd of dairy cows experiencing problems in reproductive efficiency.
  • Various feed ration changes and injections of vitamins failed to rectify the problem.
  • a cross section of blood samples from the herd was analyzed for RBC oxidative enzyme content and serum trace minerals. An extensive analysis was also done of the various feed ratios.
  • Table 3 contains results of the oxidative enzyme and trace mineral content of three of the cows which is exemplary of the herd. Cow One was dry, Cow Two had been lactating for about 40 days and Cow Three for about 165 days.
  • the mineral supplement containing the copper, zinc and manganese amino acid chelates and elemental selenium was then added to the feed ration to bring the overall copper, zinc and manganese contents of the ration to within a range of about 60-80, 130-160 and 90-110 ppm, respectively.
  • the overall range of mineral supplement consumed each day will vary between about 0.25 and 0.75 lbs/animal. It becomes evident that with the amino acid chelate content being limited to about 1 and 1.5%, the total amounts of amino acid chelates consumed per animal per day can vary between about 1 and 5 grams/animal/day.
  • Example 4 A beef cattle study was made of forty two and three year old first-calf purebred heifers to determine the effects that amino acid chelates of copper, manganese and zinc would have, (when compared to the same amount of minerals in inorganic form) , on cycling activity as determined by visual standing heats, first service conception rate, weaning weights and superoxide dismutase activity in the red blood cells.
  • the herd selected for the study (consisting of 15 Angus, 12 Horned Herefords, 5 Polled Herefords, 5 Brangus and 3 Simmental heifers) , had been experiencing fertility problems despite the fact that the cattle had been fed ratios containing protein and energy levels in excess of NRC requirements.
  • the fertility rate as measured by females pregnant 90 days after the breeding season was less than 75%.
  • the animals were placed on a free choice mineral supplementation program consisting of a 50:50 salt:mineral supplement mixture for a one year period. All heifers were maintained in the same pasture and received the same hay and protein supplement.
  • the base diet excluding the mineral supplement, contained 31 ppm zinc, 81 ppm manganese and 5.6 ppm copper.
  • the mineral supplement contained 8-9% calcium [CaP0 4 ] , 8% phosphorus [CaP0 4 ] , 3% potassium [KC1 and amino acid complex], 4.75% magnesium [MgO and amino acid chelate] .
  • the group was divided into two treatment groups. Utilization of the amino acid chelate supplement for a one year period prior to the beginning of this test sufficiently equalized the starting point and removed bias on the randomization of heifer selection into the groups. At the beginning of the trial, blood samples were drawn and cow-calf pairs were randomly assigned to one of the two groups by breed, calving date, and body condition score to minimize the effects across treatments. Each group was placed into adjacent 45 acre pastures divided from each other by an electric fence. The heifers received a base nutritional program of 20 lbs native grass hay and 5 lbs of a 20% crude protein range supplement.
  • the mineral treatments consisted of administering the same amounts of copper, zinc and manganese with one group receiving the minerals in the form of amino acid chelates and the other group receiving only inorganic minerals. These minerals were incorporated into a 20% crude protein supplement fortified with 14,687 I.U. of vitamin A, 3125 I.U. of vitamin D 3 , 150 I.U. of vitamin E and 2.5 mg of selenium per pound and were administered at the rate of 1 lb of fortified supplement per heifer per day. In addition to these handfed ratios, a free choice supplement containing 66% dicalcium phosphate, 29% sodium chloride, and 5% cottonseed meal was provided.
  • the diets were formulated to supply a total of 18 ppm copper, 71 ppm zinc and 89 ppm manganese. As in the previous examples, iron was deemed to be adequate so no iron amino acid chelate was utilized.
  • a breeder supplement containing additional minerals was utilized for two weeks prior to breeding at the rate of 2 oz/heifer/day.
  • the minerals in the breed supplement were also divided into chelated and inorganic groups. Amounts of copper, manganese and zinc in the fortified supplement and breeder supplement are given in Table 4. / / /
  • each heifer was injected with 2 cc of Synchro- Mate B (Norgestomet plus estradiol valerate) and implanted with a Synchro-Mate B implant.
  • the implant was removed on the 10th day after insertion and a blood sample was withdrawn from each heifer at this time.
  • the heifers were observed four times daily for signs of estrus beginning on the 11th day and were artificially inseminated about 12 hours after the observed heat.
  • the respective breeder supplements were discontinued after the 14th day of administration, but the mineral supplement was continued for a total period of 75 days, after which a third blood sample was taken. Before completion of the test, three heifers were removed from the study.
  • the amino acid chelate supplemented heifers exhibited more standing heats and had a greater percentage conceiving on first service than the inorganic mineral supplemented cows.
  • the weaning weight of calves from heifers in the amino acid chelate supplemented group averaged 48 lbs higher than from the inorganic mineral supplemented group which translates into significantly greater income to the producer.
  • the amino acid chelated supplemented heifers exhibited increased SOD activity from start to finish of the trial while the inorganic trace mineral supplemented females exhibited decreased enzymatic activity during the course of the trial. It is to be remembered that the serum copper levels of all heifers were within normal range at the beginning of the study due to the fact that the chelates had been administered. The study therefore shows that serum copper levels do not necessarily correlate with SOD activity levels, i.e. "normal" serum copper levels do not mean bioavailability of all the copper in the serum.
  • the cell activity of the CuZnSOD which is an erythrocyte enzyme, is principally dictated by the copper status of the animal at the time of erythrocyte synthesis.
  • the invention is not to be limited solely to the description and examples. There are modifications which may become apparent to one skilled in the art in view of the description contained herein.
  • the minerals, in the form of amino acid chelates may be administered transdermally, with or without the aid of penetration enhancers.
  • Such administration for transdermal absorption could be done in the form of a patch, form- filled liquid seal or simply as a creme or ointment. Therefore, the invention is to be limited in scope only by the following claims and their functional equivalents.

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Abstract

Méthode permettant de réduire les contraintes d'oxydation cellulaire par radicaux libres chez les animaux homéothermes présentant des symptômes de toxicité causés par les radicaux libres. La méthode consiste à: confirmer la présence chez l'animal de contraintes d'oxydation cellulaire causées par des radicaux libres; déterminer quels oligoéléments minéraux sélectionnés dans le groupe constitué de cuivre, de zinc, de fer et de manganèse avec ou sans sélénium, sont nécessaires pour renforcer et maintenir le fonctionnement des enzymes liées aux accès d'oxydation des granulocytes neutrophiles et des macrophages présents dans l'animal; préparer une composition contenant des quantités efficaces d'au moins un des minéraux susmentionnés (cuivre, zinc, fer et manganèse) sous forme d'un chélate aminoacide présentant un rapport ligand/minéral d'au moins 1:1, un poids moléculaire d'au plus 1500 daltons et une constante de stabilité comprise entre 10?6 et 1016¿, avec ou sans des quantités facultatives de sélénium pouvant être présent soit sous forme d'un chélate aminoacide ou de sélénium inorganique; administrer la composition à l'animal, de préférence par voie orale. L'existence de contraintes d'oxydation cellulaires par radicaux libres est confirmée de préférence par l'analyse directe de l'activité des enzymes d'oxydation sélectionnées dans le groupe constitué de CuZnSOD, de glutathion-peroxydase et de catalase.
PCT/US1992/009587 1991-11-25 1992-11-05 Composition et methode permettant de reduire les contraintes d'oxydation cellulaire par radicaux libres chez les animaux homeothermes Ceased WO1993010777A1 (fr)

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Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1995031197A1 (fr) * 1994-05-13 1995-11-23 Monsanto Company Procedes d'utilisation de catalyseurs de decomposition deperoxynitrite et compositions pharmaceutiques a cet effet
WO1998015281A1 (fr) * 1996-10-08 1998-04-16 Hartford Hospital Provocation d'une reaction au stress cellulaire au moyen de sels de metaux lourds
FR2766712A1 (fr) * 1997-08-01 1999-02-05 Aguettant Lab Composition de preference solution antioxydante et medicaments en faisant application
US6245758B1 (en) 1994-05-13 2001-06-12 Michael K. Stern Methods of use for peroxynitrite decomposition catalysts, pharmaceutical compositions therefor
US7153503B1 (en) 1998-12-19 2006-12-26 Janeel Henderson Comprehensive dietary supplement
RU2535086C1 (ru) * 2013-10-11 2014-12-10 Федеральное государственное бюджетное образовательное учреждение высшего профессионального образования "Московская государственная академия ветеринарной медицины и биотехнологии имени К.И. Скрябина" (ФГБОУ ВПО МГАВМиБ) Способ коррекции окислительного стресса при профилактике и лечении железодефицитной анемии телят в условиях хронического инкорпорированного облучения
US20220174988A1 (en) * 2019-04-23 2022-06-09 Scott L. Crain Amino acid chelates for reducing oxidative stress

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7592304B2 (en) 1999-10-01 2009-09-22 Dmi Life Sciences, Inc. Metal-binding compounds and uses therefor

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4863898A (en) * 1986-02-06 1989-09-05 Albion International, Inc. Amino acid chelated compositions for delivery to specific biological tissue sites

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4774089A (en) * 1985-06-14 1988-09-27 Albion International, Inc. Stimulation of gonadotropic hormones with mineral mixtures containing amino acid chelates

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4863898A (en) * 1986-02-06 1989-09-05 Albion International, Inc. Amino acid chelated compositions for delivery to specific biological tissue sites

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
FASEBJ.1:441-445; 1987, MACHLIN, L.J. et al., "Free Radical Tissue Damage: Protective Role of Antioxidant Nutrients", see page 443, column 2 and Table 2 and page 444, columns 1-2. *
See also references of EP0614361A4 *

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1995031197A1 (fr) * 1994-05-13 1995-11-23 Monsanto Company Procedes d'utilisation de catalyseurs de decomposition deperoxynitrite et compositions pharmaceutiques a cet effet
US6245758B1 (en) 1994-05-13 2001-06-12 Michael K. Stern Methods of use for peroxynitrite decomposition catalysts, pharmaceutical compositions therefor
WO1998015281A1 (fr) * 1996-10-08 1998-04-16 Hartford Hospital Provocation d'une reaction au stress cellulaire au moyen de sels de metaux lourds
US5955111A (en) * 1996-10-08 1999-09-21 Hartford Hospital Methods and compositions for inducing production of stress proteins
AU735055B2 (en) * 1996-10-08 2001-06-28 Hartford Hospital Induction of a cellular stress response with heavy metal salts
FR2766712A1 (fr) * 1997-08-01 1999-02-05 Aguettant Lab Composition de preference solution antioxydante et medicaments en faisant application
US7153503B1 (en) 1998-12-19 2006-12-26 Janeel Henderson Comprehensive dietary supplement
RU2535086C1 (ru) * 2013-10-11 2014-12-10 Федеральное государственное бюджетное образовательное учреждение высшего профессионального образования "Московская государственная академия ветеринарной медицины и биотехнологии имени К.И. Скрябина" (ФГБОУ ВПО МГАВМиБ) Способ коррекции окислительного стресса при профилактике и лечении железодефицитной анемии телят в условиях хронического инкорпорированного облучения
US20220174988A1 (en) * 2019-04-23 2022-06-09 Scott L. Crain Amino acid chelates for reducing oxidative stress

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