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WO2008105983A1 - Absorption de minéraux par l'estomac - Google Patents

Absorption de minéraux par l'estomac Download PDF

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Publication number
WO2008105983A1
WO2008105983A1 PCT/US2008/000615 US2008000615W WO2008105983A1 WO 2008105983 A1 WO2008105983 A1 WO 2008105983A1 US 2008000615 W US2008000615 W US 2008000615W WO 2008105983 A1 WO2008105983 A1 WO 2008105983A1
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Prior art keywords
metal
amino acid
stomach
subject
condition
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Inventor
Stephen D. Ashmead
H. Dewayne Ashmead
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Albion Laboratories Inc
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Albion International Inc
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    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K50/00—Feeding-stuffs specially adapted for particular animals
    • A23K50/30—Feeding-stuffs specially adapted for particular animals for swines
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K20/00—Accessory food factors for animal feeding-stuffs
    • A23K20/10—Organic substances
    • A23K20/142—Amino acids; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K20/00—Accessory food factors for animal feeding-stuffs
    • A23K20/20—Inorganic substances, e.g. oligoelements
    • A23K20/30—Oligoelements
    • 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
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/16—Inorganic salts, minerals or trace elements
    • A23L33/165—Complexes or chelates
    • 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
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/17—Amino acids, peptides or proteins
    • A23L33/175—Amino acids
    • 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
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs

Definitions

  • the present invention is generally drawn to methods of enhancing metal absorption in a subject experiencing a malabsorption condition of the gastrointestinal tract, or treating stomach condition by enhancing metal content in the stomach tissue.
  • Amino acid chelates are generally produced by the reaction between ⁇ -amino acids and metal ions having a valence of two or more to form a ring structure.
  • the positive electrical charge of the metal ion can be neutralized by the electrons available through the carboxylate or free amino groups of the ⁇ -amino acid.
  • chelate has been loosely defined as a combination of a metallic ion bonded to one or more ligands to form a heterocyclic ring structure. Under this definition, chelate formation through neutralization of the positive charge(s) of the metal ion may be through the formation of ionic, covalent or coordinate covalent bonding.
  • An alternative and more modern definition of the term "chelate” requires that the metal ion be bonded to the ligand solely by coordinate covalent bonds forming a heterocyclic ring. In either case, both are definitions that describe a metal ion and a ligand forming a heterocyclic ring.
  • Chelation can be confirmed and differentiated from mixtures of components or more ionic complexes by infrared spectra through comparison of the stretching of bonds or shifting of absorption caused by bond formation.
  • chelated products that are commercially utilized. The first is referred to as a "metal proteinate.”
  • the American Association of Feed Control officials (AAFCO) has defined a "metal proteinate” as the product resulting from the chelation of a soluble salt with amino acids and/or partially hydrolyzed protein.
  • Such products are referred to as the specific metal proteinate, e.g., copper proteinate, zinc proteinate, etc.
  • metal proteinates are erroneously referred to as "amino acid” chelates.
  • the second product when properly formed, is a stable product having one or more five-membered rings formed by a reaction between the amino acid and the metal.
  • the American Association of Feed Control Officials (AAFCO) has also issued a definition for metal amino acid chelates. It is officially defined as the product resulting from the reaction of a metal ion from a soluble metal salt with amino acids having 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.
  • the products are identified by the specific metal forming the chelate, e.g., iron amino acid chelate, copper amino acid chelate, etc.
  • the carboxyl oxygen and the ⁇ -amino group of the amino acid each bond with the metal ion.
  • a five-membered ring is defined by the metal atom, the carboxyl oxygen, the carbonyl carbon, the ⁇ -carbon and the ⁇ -amino nitrogen.
  • the actual structure will depend upon the ligand to metal mole ratio and whether the carboxyl oxygen forms a coordinate covalent bond or an ionic bond with the metal ion.
  • the ligand to metal molar ratio is at least 1 :1 and is preferably 2:1 or 3:1. However, in certain instances, the ratio may be 4:1.
  • an amino acid chelate with a divalent metal can be represented at a ligand to metal molar ratio of 2:1 according to Formula 1 as follows:
  • the dashed lines represent coordinate covalent bonds, covalent bonds, or ionic bonds.
  • R when R is H 1 the amino acid is glycine, which is the simplest of the ⁇ -amino acids.
  • R could be representative of any other side chain that, when taken in combination with the rest of the ligand structure(s), results in any of the other twenty or so naturally occurring amino acids used in protein synthesis. All of the amino acids have the same configuration for the positioning of the carboxyl oxygen and the ⁇ -amino nitrogen with respect to the metal ion.
  • the chelate ring is defined by the same atoms in each instance, even though the R side chain group may vary.
  • the reason a metal atom can accept bonds over and above the oxidation state of the metal is due to the nature of chelation.
  • the nitrogen contributes to both electrons used in the bonding. These electrons fill available spaces in the d-orbitals of the metal ion forming a coordinate covalent bond.
  • a metal ion with a normal valency of +2 can be bonded by four bonds when fully chelated. In this state, the chelate is completely satisfied by the bonding electrons and the charge on the metal atom (as well as on the overall molecule) is zero.
  • the metal ion can be bonded to the carboxyl oxygen by either coordinate covalent bonds or ionic bonds.
  • the metal ion is preferably bonded to the ⁇ -amino group by coordinate covalent bonds only.
  • the structure, chemistry, bioavailability, and various applications of amino acid chelates are well documented in the literature, e.g. Ashmead et al., Chelated Mineral Nutrition, (1982), Chas. C. Thomas Publishers, Springfield, III.; Ashmead et al., Intestinal Absorption of Metal Ions, (1985), Chas. C. Thomas Publishers, Springfield, III.; U.S.
  • amino acid chelates in the field of mineral nutrition has been attributed to the fact that these chelates are readily absorbed from the intestines and into mucosal cells by means of active transport.
  • the minerals can be absorbed along with the amino acids as a single unit utilizing the amino acid(s) as a carrier molecule. Therefore, the problems associated with the competition of ions for active sites and the suppression of specific nutritive mineral elements by others can be avoided.
  • metal amino acid chelates have been used as a dietary supplement for a variety of nutritional metals and amino acids. Even though chelation generally offers better mineral absorbability in the intestines when they are properly functioning, absorption is a complex biological function influenced by many variables. Conditions or diseases that impair a body's normal absorption functionality can be especially difficult to treat, or when such conditions or diseases are present, delivery of essential minerals can be difficult. As such, methods that provide increased health benefits continue to be sought through ongoing research and development efforts.
  • a method of enhancing mineral absorption in a subject having a malabsorption condition of a gastrointestinal tract can comprise identifying the subject with the malabsorption condition of the gastrointestinal tract, and orally administering a metal amino acid chelate to the subject, wherein at least a portion of the metal is absorbed through stomach tissue and into the bloodstream of the subject.
  • a method of treating a stomach condition can comprise identifying a subject with a stomach condition that would benefit from absorption of a metal in the stomach, and orally administering a metal amino acid chelate to the subject.
  • the metal in this embodiment can be absorbed into stomach tissue, thereby providing enhanced metal content within the tissue.
  • the enhanced metal content can provide a therapeutic effect to the stomach which ameliorates the stomach condition or a symptom related to the stomach condition.
  • a method of enhancing mineral absorption in a human or animal subject having a medication-induced intestinal malabsorption condition can comprise identifying a subject taking medication that interferes with intestinal absorption of minerals; and orally administering a metal amino acid chelate to the subject, wherein at least a portion of the metal is absorbed through stomach tissue and into the bloodstream of the subject.
  • a chelate can include one or more of such chelates
  • an amount of metal can include reference to one or more amounts of metals
  • amino acid can include reference to one or more amino acids.
  • amino acid or "naturally occurring amino acid” shall mean amino acids that are known to be used for forming the basic constituents of proteins, including alanine, arginine, asparagine, aspartic acid, cysteine, cystine, glutamine, glutamic acid, glycine, histidine, hydroxyproline, isoleucine, leucine, lysine, methionine, ornithine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, valine, and combinations thereof.
  • amino acid chelate refers to both the traditional definitions and the more modern definition of chelate as cited previously.
  • chelate is meant to include metal ions bonded to amino acid or proteinaceous ligands forming heterocyclic rings. Between the carboxyl oxygen and the metal, the bond can covalent or ionic, but is preferably coordinate covalent. Additionally, at the ⁇ -amino group, the bond is typically a coordinate covalent bond. Proteinates of naturally occurring amino acids are included in this definition. As used herein, the term "amino acid chelate” and “metal amino acid chelate” are used interchangeable, as by definition, a chelate requires the presence of a metal and a ligand configured in a ring structure.
  • the term "mineral,” “metal,” or “nutritionally relevant metal” refers to metals including divalent and trivalent metals that can be used as part of a nutritional supplement, are known to be beneficial to humans, and are substantially non-toxic when administered in traditional amounts, as is known in the art.
  • metals include iron, zinc, copper, manganese, calcium, magnesium, chromium, vanadium, selenium, silicon, molybdenum, tin, nickel, boron, cobalt, gold, silver, strontium, and combinations thereof.
  • proteinate when referring to a metal proteinate is meant to include compounds where the metal is chelated or complexed to hydrolyzed or partially hydrolyzed protein forming a heterocyclic ring. Coordinate covalent bonds, covalent bonds, and/or ionic bonds may be present between the metal and the proteinaceous ligand of the chelate or chelate/complex structure.
  • metal proteinates which include a ring structure are included when referring to amino acid chelates. However, when a proteinate is specifically mentioned, it does not include all types of amino acid chelates, as it only includes those with hydrolyzed or partially hydrolyzed protein.
  • malabsorption condition refers to a state of impaired absorption of nutrients and minerals in the gastrointestinal tract.
  • the main purpose of the gastrointestinal tract is the digestion and absorption of major nutrients (fat, carbohydrate, and protein), essential macro- and micro-nutrients (vitamins and trace minerals), water, and electrolytes.
  • Digestion involves mechanical, acidic, and/or enzymatic breakdown of food. Mechanical processes include chewing, gastric churning, and the to-and-fro mixing in the intestine.
  • Enzymatic hydrolysis is initiated by intraluminal processes requiring gastric, pancreatic, and biliary secretions. The final products of digestion are generally understood to be absorbed through the intestinal epithelial cells.
  • a defect in any one of these processes may produce a state of malabsorption in the intestines.
  • the term "stomach condition” generally refers to those conditions or diseases that originates in the stomach or affects the stomach, and which has an affect on intestinal absorption. For example, if the stomach does not function properly, intestinal absorption can be reduced, i.e., low acid content in stomach may not generate adequate conditions for intestinal absorption of minerals.
  • intestinal malabsorption condition generally refers to those malabsorption conditions or diseases that are more directly related to, originate in, or affect the intestine. Both of these types of malabsorption conditions are not necessary exclusive, i.e., it is possible for a malabsorption condition or disease to be classified as an intestinal malabsorption condition and a stomach condition.
  • the term "gastrointestinal tract,” “Gl tract,” or “digestive tract” refers to the system of organs within multicellular animals that takes in food, digests it to extract energy and nutrients, and expels the remaining waste.
  • the major functions of the Gl tract are digestion and excretion.
  • the upper Gl tract consists of the mouth, pharynx, esophagus, and stomach and the lower Gl tract comprises the organs beneath the stomach, e.g., the intestines, colon, and anus.
  • the small intestine comprises the duodenum, jejunum, and ileum and the large intestine comprises the cecum, colon (ascending colon, transverse colon, descending colon and sigmoid flexure), and rectum.
  • the term "about” is used to provide flexibility to a numerical range endpoint by providing that a given value may be “a little above” or “a little below” the endpoint.
  • a method of enhancing mineral absorption in a subject having a malabsorption condition of the gastrointestinal tract can include identifying a subject with a malabsorption condition of the gastrointestinal tract, and orally administering a metal amino acid chelate to the subject.
  • the metal can be absorbed through stomach tissue and subsequently into the bloodstream of the subject.
  • the malabsorption condition can be an intestinal malabsorption condition.
  • the malabsorption condition can be a stomach condition that affects intestinal absorption.
  • a method of treating a stomach condition can comprise identifying a subject with a stomach condition that would benefit from absorption of a metal into stomach tissue, and orally administering a metal amino acid chelate to the subject, where the metal is absorbed into stomach tissue thereby providing enhanced metal content within the tissue, and where the enhanced metal content provides a therapeutic effect to the stomach which ameliorates the stomach condition or a symptom related to the stomach condition.
  • certain metals may perform better in treating certain conditions. For example, zinc can be used in treating ulcers. Other metals may be preferred for treating stomach conditions as disclosed herein. Administration of specific metals can be chosen based on relevant studies as are known in the art. Additionally, a physician or veterinarian can select and modify the present methods of treatment based on the needs of the subject.
  • a method of enhancing mineral absorption in a human or animal subject having a medication-induced intestinal malabsorption condition can comprise identifying a subject taking medication that interferes with intestinal absorption of minerals; and orally administering a metal amino acid chelate to the subject, wherein at least a portion of the metal is absorbed through stomach tissue and into the bloodstream of the subject.
  • chelation has been shown to increase the absorbability of minerals from the intestines via mucosal cells and active transport.
  • the minerals are often absorbed along with the amino acids as a single unit, thereby utilizing the amino acids as carrier molecules.
  • metal amino acid chelates can be used as an effective means for treating or delivering minerals to humans or animals having a malabsorption condition.
  • a human subject with cancer suffering nausea can be administered a zinc amino acid chelate, thereby increasing the subject's zinc intake through rapid stomach absorption even if the remaining zinc amino acid chelate is subsequently vomited.
  • the subject can receive minerals in the bloodstream, even if the amino acid chelate does not reach the intestines where mineral absorption has previously been reported to occur.
  • Other malabsorption conditions are also described herein, wherein the administration of amino acid chelates can benefit a subject similarly. It is noted that when discussing a method of treating a stomach condition or enhancing mineral absorption for an intestinal malabsorption condition or any other disclosed method, each of these discussions can be considered applicable to each of these embodiments, whether or not they are explicitly discussed in the context of that embodiment. Thus, for example, in discussing the metal amino acid chelates, those chelates can also be used in the method for treating a stomach condition or a method for treating an intestinal malabsorption condition, and vice versa.
  • Intestinal malabsorption conditions can be related to or can result from a number of conditions and/or diseases including cancer, cancer treatment, methotraxate (or other drug) administration, a retrovirus, a virus, surgical resection, stomach stapling, gastric bypass surgery, AIDS, hypochloridia, old age, intestinal inflammation, intestinal disease, inflammatory bowel disease, dysentery, Crohn's disease, Whipple's disease, sucrose intolerance, insufficiency of the pancreas, premature birth, or combinations thereof.
  • malabsorption can be the result of a subject taking medications that interfere with normal mineral absorption.
  • amino acid chelates or supplementing such a medication regimen together or at different times than the medication administration
  • the stomach absorption of the metal can provide needed mineral nutrition, in spite of medication-induced intestinal malabsorption issues that may be present.
  • Stomach conditions that can negatively affect intestinal absorption, or which can be treated with amino acid chelates by tissue absorption in the stomach, can be related to or can result from a number of conditions and/or diseases including an ulcer, helicobacter pylori bacteria, stomach cancer, a viral digestive infection, gastrointestinal bleeding, gastroenteritis, gastritis, hiatal hernia, gastroparesis, and combinations thereof.
  • the metal amino acid chelates used in the methods of the present invention can include numerous combinations of metals to ligands in the form of chelates and other compounds and complexes. Such arrangements are contemplated by the present invention and may be manufactured through generally known preparative complex and/or chelation methods.
  • the metals contemplated for use in the methods of the present invention are generally nutritionally relevant metals, as defined previously. Specific examples include, but are not limited to, iron, zinc, copper, manganese, calcium, magnesium, chromium, vanadium, selenium, molybdenum, nickel, boron, cobalt, strontium, and combinations thereof.
  • the metal can be zinc.
  • the metal can be iron.
  • the metal can be copper.
  • the metal can be manganese.
  • the metal can be chromium.
  • amino acids that can be used in the present invention include, but are not limited to, alanine, arginine, asparagine, aspartic acid, cysteine, cystine, glutamine, glutamic acid, glycine, histidine, hydroxyproline, isoleucine, leucine, lysine, methionine, ornithine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, valine, dipeptides, tripeptides, tetrapeptides, and combinations thereof.
  • the amino acid can be glycine.
  • the amino acid can be methionine.
  • the amino acid chelated can be a metal proteinate.
  • the amino acid can be argnine or lysine.
  • the metal amino acid chelate can have an amino acid ligand to metal ratio from about 1 :1 to about 4:1. In one embodiment, the amino acid ligand to metal ratio can be from about 1:1 to about 3:1, or from about 1 :1 to about 2:1.
  • the metal amino acid chelates can have mixed amino acid ligands or the same amino acid ligands. Combinations of amino acids or metals can be used in mixed ligand and/or mixed metal compositions as well.
  • a mixed ligand composition of zinc methionine (1 :1 molar ratio) and zinc glycine (1:1 molar ratio) can be prepared.
  • a mixed metal composition of iron bisglycinate (1 :2 molar ratio) and copper bisglycinate (1 :2 molar ratio) can likewise be prepared.
  • the choice of ligands and/or metals can be specifically tailored for whatever mineral enhancement is desired, and/or whatever treatment regimen may be needed.
  • an amino acid composition can include a number of metals for administration to a subject having a malabsorption condition.
  • an amino acid composition can include an iron glycinate or bisglycinate, zinc glycinate or bisglycinate, and/or a copper glycinate or bisglycinate.
  • the methods of the present invention can also provide enhanced amino acid absorption through the stomach.
  • the methods of the present invention can be directed to administration to humans or animals.
  • the animal can be a mammal such as a human, or alternatively, a livestock mammal, such as a cow, horse, sheep, goat, or pig.
  • the animal can be poultry.
  • Other animals that can benefit from the methods of the present invention include, but are not limited to, a crustacean, a fish, a dog, or a cat.
  • additives are typically formulated within a common composition with the amino acid chelates to provide desired properties that may not be inherently present in the amino acid chelate itself.
  • maltodextrins can be added as a filler and a flow agent. Additionally, maltodextrins can help to reduce the hydroscopicity of the composition as a whole.
  • Grain flours such as rice flour or wheat flour
  • One type of filler that can be added is inulin, including low fiber inulin derived from chicory. Fumed silica, stearic acids, and/or talc can also be added as a flow controlling agents.
  • the metal amino acid chelates can include grain flours, maltodextrins, vegetable flours or powders, inulin, and combinations thereof.
  • compositions that can be added include organic acids. Citric acid, fumaric acid, succinic acid, tartaric acid, malic acid, lactic acid, gluconic acid, ascorbic acid, pantothenic acid, folic acid, lipoic acid, oxalic acid, maleic acid, formic acid, acetic acid, pyruvic acid, adipic acid, and alpha-ketoglutaric acid are each exemplary of such organic acids, though others can also be used. Free amino acids or amino acid salts can also be present in the composition. Additionally, mineral oils for dust control, binders for tableting (carboxymethyl cellulose, ethyl cellulose, glycerol, etc.), flavoring agents or taste- free additives for organoleptic properties, or the like can also be included.
  • the metal amino acid chelates of the present invention can include other classes of formulation additives such as vitamins, coenzymes, cofactors, herbs or herbal extracts, protein powders, or the like.
  • Vitamins that can be used include Vitamin A, the Vitamin B group of vitamins, e.g., folic acid, Vitamin Bi, Vitamin B 2 , Vitamin B3, Vitamin B 5 , Vitamin BQ, or Vitamin B 12 , Vitamin C, Vitamin D, Vitamin E, and the like.
  • Coenzymes can also be used, which are organic compounds that combine with apoenzymes to form active enzymes.
  • Cofactors that can be present include coenzymes and metals that are required for an enzyme to be active, some of which can be provided by the amino acid chelate itself.
  • compositions can be in the form of tablets, capsules, powders, crystals, granules, liquids, or the like.
  • Shellacs or waxes can be used as tablet coatings.
  • Other encapsulating materials include vegetable sterols or gelatin.
  • compositions can also be included in liquid formulations that act to main the solubility of the amino acid chelate and/or other additives that may be present.
  • U.S. Patent No. 6,716,814 which is incorporated herein by reference in its entirety, describes a method enhancing the solubility of iron amino acid chelates and iron proteinates. Such methods and solubility enhancing compositions can be used with the methods of the present invention as well.
  • metal amino acid chelates in accordance with the methods previously disclosed. Additionally, some of the examples include studies performed showing the effects of metal amino acid chelates on animals in accordance with embodiments of the present invention.
  • a copper carbonate solution is prepared by adding 6.1 parts by weight of cupric carbonate to 80.9 parts by weight water. This solution is allowed to stand without agitation for about two hours. To this solution is added 8.2 parts by weight of a glycine, and the mixture is slowly stirred for about two more hours. A hazy blue solution is observed. To the hazy blue solution is added 65 parts by weight of a 15 wt% citric acid solution and the mixture is stirred until a clear blue solution is observed. This solution is spray dried resulting in a copper bisglycinate powder having a copper content of about 14 wt% and which melted at about 194°C. Upon being reconstituted in water, the pH of the resulting solution is about 7.5.
  • a solution is prepared including 10.1 parts by weight of glycine dissolved in 82.2 parts by weight water containing 1.0 part by weight sodium carbonate. To this solution is added 4.4 parts by weight zinc oxide. The molar ratio of glycine to zinc is 2:1. The reaction mixture is allowed to stand for about 14 hours and turned an opalescent color. After standing, the mixture is heated to about 70 0 C and is spray dried to obtain a zinc bisglycinate amino acid chelate powder having a melting point of about 209 0 C which turned red upon melting. The zinc content of the chelate is about 20 wt%. The dried product has a moisture content of about 7 wt%, and when reconstituted in water, has a pH of about 8.0.
  • Example 4 Preparation of a Zinc Methionine/Glycine Chelate
  • a mixture of 42.93 grams of zinc sulfate, 12 grams of methionine, and 30 grams of glycine are reacted in an aqueous environment for 60 minutes at a temperature of about 65 to 70 0 C.
  • the reaction of the zinc sulfate, methionine, and glycine produces a zinc amino acid chelate having a ligand component to metal molar ratio of about 2:1 , a theoretical average zinc content of about 26.8% by weight, and a glycine to methionine molar ratio of about 5:2. Due to the presence of the sulfate anion, the actual average zinc weight percentage is about 18.2%.
  • the pigs were surgically fitted with catheters into the carotid artery, portal vein, mesenteric vein, and pyloric stomach. Each pig was gastrically administered one of three forms of zinc, including i) zinc sulfate, ii) zinc methionate/zinc glycinate (1 :1 molar ratio of methionine chelated to zinc admixed with 1 :1 molar ratio of glycine chelated to zinc), and iii) zinc glycinate (1 :1 molar ratio of glycine chelated to zinc), into the pyloric stomach catheter. These zinc amino acid chelates can prepared using methods similar to those described in Examples 1 to 4.
  • the injections were administered during three 48-hour periods. Each 48- period including a 24 hour feeding period, followed by a 19.5 hour fasting, followed by a 4.5 hour infusion of para-aminohippuric acid, followed by an injection of 230 mg of zinc. Zinc concentrations were determined from blood samples collected simultaneously from the portal vein and carotid artery at specific time periods during and after the injection, as shown in FIG. 1.
  • the zinc concentrations in about the first hour correspond to zinc absorption in the stomach, while zinc concentrations well after about the first hour correspond to zinc absorption in the intestine.
  • zinc absorption from the traditional salt form i.e. zinc sulfate
  • was essentially non- existent in the first hour but peaked about 2.5 hours after injection, corresponding to normal intestinal absorption.
  • the zinc from both amino acid chelate compositions i.e.
  • Each piglet was fed a semi-purified diet containing 19 ppm copper as an amino acid chelate, prepared similarly as described in accordance with Examples 1 to 4. Absorption of the copper from the amino acid chelate was determined using the Cr 2 O 3 indicator method. Access to feed was ad libitum for 21 days. Distilled water was also supplied ad libitum. All piglets were housed in stainless steel cages.
  • Example 7 Zinc Absorption Pig Study Forty-six, 32 day-old cross bred pigs, weighing 7.2 ⁇ 0.3kg, were placed on a zinc depleted diet containing 17 mg Zn/kg feed for 32 days. All water supplied was deionized water. At the end of 24 days on the zinc depleted diet, all pigs received supplemental zinc in their diets sourced from either ZnSO 4 or a zinc amino acid chelate prepared similarly as described in accordance with Examples 1 to 4. The zinc supplements were fed at 5, 15, or 45 mg Zn/kg feed. Additionally, 0.25% chromic oxide was included in the supplement. On day 32, six pigs (one from each Zn source) was randomly selected and sacrificed about 3 hours following the last meal.
  • the gastrointestinal tract was removed and segmented into the stomach, proximal small intestine, medial small intestine, distal small intestine, cecum, proximal colon, and distal colon. Digesta were expressed from each segment. The segment was subsequently rinsed to insure complete digesta collection.
  • the digesta were dried, ground, and then assayed for chromium and zinc using an atomic absorption spectrophotometer. The feed was also assayed. From this data, apparent absorption of zinc from either source was determined. Most of the absorbed zinc from either source was absorbed from the proximal and medial segments of the small intestine. Total zinc absorption in zinc deficient pigs was significantly higher from the zinc amino acid chelate (87.1 %) compared to ZnSO 4 (70.2%), (P ⁇ 0.01 ).
  • Zinc from the amino acid chelate was also absorbed from the stomach. No zinc from the sulfate source was absorbed in the stomach. The overall difference was significant (P ⁇ 0.05).
  • zinc absorption from the stomach was 16.8% of the ingested amount.
  • 15 ppm zinc sourced from the ZnSO 4 provided a negative zinc absorption from the stomach (-20.4%).
  • zinc absorption sourced from the amino acid chelate from the stomach was 14.6% compared to a -16.1 % when the ZnSO 4 was supplemented.

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  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

L'invention concerne des procédés pour améliorer l'absorption de minéraux chez un sujet atteint d'un état de mauvaise absorption gastro-intestinale. Selon un premier mode de réalisation, l'état de mauvaise absorption peut être un état de mauvaise absorption intestinale ou stomacale. Selon un autre mode de réalisation, un procédé de traitement des états stomacaux augmentant la teneur en minéraux dans le tissu stomacal peut fournir un effet thérapeutique sur l'estomac et améliorer l'état stomacal ou un symptôme lié à l'état stomacal.
PCT/US2008/000615 2007-02-27 2008-01-16 Absorption de minéraux par l'estomac Ceased WO2008105983A1 (fr)

Applications Claiming Priority (2)

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US90414207P 2007-02-27 2007-02-27
US60/904,142 2007-02-27

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WO2008105983A1 true WO2008105983A1 (fr) 2008-09-04

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PCT/US2008/000615 Ceased WO2008105983A1 (fr) 2007-02-27 2008-01-16 Absorption de minéraux par l'estomac

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ITMI20111555A1 (it) * 2011-08-29 2013-03-01 Cevolani Daniele S R L Mangimi e composizioni per uso veterinario e/o zootecnico
WO2016025448A3 (fr) * 2014-08-13 2016-04-07 Akeso Biomedical, Inc. Composés et compositions antimicrobiens ainsi que leurs utilisations
CN106278916A (zh) * 2016-09-05 2017-01-04 河北东华冀衡化工有限公司 一种甘氨酸铜的制备方法
WO2017027742A1 (fr) * 2015-08-11 2017-02-16 Akeso Biomedical, Inc. Compositions dinhibition de la formation de biofilm destinées à l'amélioration de prise de poids du bétail
WO2019136150A1 (fr) * 2016-02-17 2019-07-11 Akeso Biomedical, Inc. Compositions d'inhibition de biofilm destinées à l'amélioration de prise de poids du bétail
CN112409202A (zh) * 2020-12-23 2021-02-26 河南九天生物科技有限公司 一种治疗和预防缺铁性贫血的氨基酸Fe（Ⅲ）螯合物及工艺
WO2025006825A1 (fr) * 2023-06-28 2025-01-02 Cargill, Incorporated Protéines minérales destinées à être utilisées dans des aliments pour animaux, et leurs procédés de production

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Cited By (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ITMI20111555A1 (it) * 2011-08-29 2013-03-01 Cevolani Daniele S R L Mangimi e composizioni per uso veterinario e/o zootecnico
US9961886B2 (en) 2014-08-13 2018-05-08 Akeso Biomedical, Inc. Antimicrobial compounds and compositions, and uses thereof
WO2016025448A3 (fr) * 2014-08-13 2016-04-07 Akeso Biomedical, Inc. Composés et compositions antimicrobiens ainsi que leurs utilisations
US10327423B2 (en) 2014-08-13 2019-06-25 Akeso Biomedical, Inc. Antimicrobial compounds and compositions, and uses thereof
US10264766B2 (en) 2014-08-13 2019-04-23 Akeso Biomedical, Inc. Antimicrobial compounds and compositions, and uses thereof
US10301339B2 (en) 2015-08-11 2019-05-28 Akeso Biomedical, Inc. Biofilm inhibiting compositions enhancing weight gain in livestock
US10647736B2 (en) 2015-08-11 2020-05-12 Akeso Biomedical, Inc. Antimicrobial preparation and uses thereof
US9975914B2 (en) 2015-08-11 2018-05-22 Akeso Biomedical, Inc. Antimicrobial preparation and uses thereof
US10106567B2 (en) 2015-08-11 2018-10-23 Akeso Biomedical, Inc. Biofilm inhibiting compositions enhancing weight gain in livestock
WO2017027738A1 (fr) * 2015-08-11 2017-02-16 Akeso Biomedical, Inc. Préparations antimicrobiennes et leurs utilisations
WO2017027742A1 (fr) * 2015-08-11 2017-02-16 Akeso Biomedical, Inc. Compositions dinhibition de la formation de biofilm destinées à l'amélioration de prise de poids du bétail
US11311511B2 (en) 2015-08-11 2022-04-26 Akeso Biomedical, Inc. Biofilm inhibiting compositions enhancing weight gain in livestock
US10793587B2 (en) 2015-08-11 2020-10-06 Akeso Biomedical, Inc. Biofilm inhibiting compositions enhancing weight gain in livestock
US10377785B2 (en) 2015-08-11 2019-08-13 Akeso Biomedical, Inc. Biofilm inhibiting compositions enhancing weight gain in livestock
US10555531B2 (en) 2015-08-11 2020-02-11 Akeso Biomedical, Inc. Biofilm inhibiting compositions enhancing weight gain in livestock
CN108024563A (zh) * 2015-08-11 2018-05-11 艾索生物医药公司 提高家畜中重量增加的生物膜抑制组合物
US10653658B2 (en) 2015-08-11 2020-05-19 Akeso Biomedical, Inc. Biofilm inhibiting compositions enhancing weight gain in livestock
WO2019136150A1 (fr) * 2016-02-17 2019-07-11 Akeso Biomedical, Inc. Compositions d'inhibition de biofilm destinées à l'amélioration de prise de poids du bétail
CN106278916A (zh) * 2016-09-05 2017-01-04 河北东华冀衡化工有限公司 一种甘氨酸铜的制备方法
CN112409202A (zh) * 2020-12-23 2021-02-26 河南九天生物科技有限公司 一种治疗和预防缺铁性贫血的氨基酸Fe（Ⅲ）螯合物及工艺
WO2025006825A1 (fr) * 2023-06-28 2025-01-02 Cargill, Incorporated Protéines minérales destinées à être utilisées dans des aliments pour animaux, et leurs procédés de production

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