US20060194877A1 - Creatine hydroxycitric acids salts and methods for their production and use in individuals - Google Patents

Creatine hydroxycitric acids salts and methods for their production and use in individuals Download PDF

Info

Publication number
US20060194877A1
US20060194877A1 US11/349,960 US34996006A US2006194877A1 US 20060194877 A1 US20060194877 A1 US 20060194877A1 US 34996006 A US34996006 A US 34996006A US 2006194877 A1 US2006194877 A1 US 2006194877A1
Authority
US
United States
Prior art keywords
creatine
hydroxycitrate
salt
salts
monohydrate
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Abandoned
Application number
US11/349,960
Other languages
English (en)
Inventor
Paul Gardiner
Marvin Heuer
Michele Molino
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
New Cell Formulations Ltd
Iovate T&P Inc
Original Assignee
Individual
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
Application filed by Individual filed Critical Individual
Priority to US11/349,960 priority Critical patent/US20060194877A1/en
Assigned to IOVATE T & P INC. reassignment IOVATE T & P INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: GARDINER, PAUL T., HEUER, MARVIN A., MOLINO, MICHELE
Assigned to NEW CELL FORMULATIONS LTD. reassignment NEW CELL FORMULATIONS LTD. CORRECTED ASSIGNMENT RECORDATION FORM TO CORRECT THE ASSIGNEE OF THE APPLICATION PREVIOUSLY RECORDED AT REEL/FRAME 017879, FRAME 0217. (ASSIGNMENT OF ASSIGNOR'S INTEREST) Assignors: GARDINER, PAUL T., HEUER, MARVIN A., MOLINO, MICHELE
Publication of US20060194877A1 publication Critical patent/US20060194877A1/en
Priority to US12/108,822 priority patent/US7772428B2/en
Abandoned legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
    • C07C59/235—Saturated compounds containing more than one carboxyl group
    • C07C59/245—Saturated compounds containing more than one carboxyl group containing hydroxy or O-metal groups
    • C07C59/285—Polyhydroxy dicarboxylic acids having five or more carbon atoms, e.g. saccharic acids
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A61P21/06—Anabolic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/02—Nutrients, e.g. vitamins, minerals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C279/00—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups
    • C07C279/04—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of guanidine groups bound to acyclic carbon atoms of a carbon skeleton
    • C07C279/14—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of guanidine groups bound to acyclic carbon atoms of a carbon skeleton being further substituted by carboxyl groups
    • 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 relates to a supplemental dietary ingredient that promotes increased muscle and exercise performance in individuals, reduces and/or prevents adiposity, improves exercise recovery, and/or suppresses the appetite leading to weight loss.
  • the present invention is also related to a method of promoting same by consuming the supplemental composition.
  • the invention also relates to a method for producing a supplemental composition.
  • Creatine monohydrate is a commonly used supplement. Creatine monohydrate is soluble in water at a rate of 75 ml of water per gram of creatine. Ingestion of creatine monohydrate thereof requires large amounts of water to also be ingested. Additionally, in aqueous solutions, creatine converts to creatinine via an irreversible, pH-dependent, non-enzymatic reaction. Aqueous and alkaline solutions contain an equilibrium mixture of creatine and creatinine. In acidic solutions, on the other hand, the formation of creatinine is complete. Creatinine is devoid of the ergogenic beneficial effects of creatine.
  • Hydrosoluble creatine monohydrate salts are obtainable and have been described elsewhere.
  • U.S. Pat. No. 5,973,199 incorporated herein in its entirety by reference, purports to describe hydrosoluble organic salts of creatine as single combination of one mole of creatine monohydrate with one mole of the following organic acids: citrate, malate, fumarate, tartarate, and malate.
  • the present invention provides methods for the production and use in individuals, e.g. animals and humans, of organic salts formed via the reaction of creatine (as used herein, this term shall refer to any type of creatine and shall not be limited to any particular form or anion) with hydroxycitric acid (also referred to “HCA”), the principle acid occurring in the rind of fruits from plants of the Garcinia genus (including, but not limited to, Garcinia cambogia, Garcinia indica , and Garcinia atrovirids ).
  • hydroxycitric acid also referred to “HCA”
  • creatine hydroxycitrates may provide improved hydrosolubility and possess ameliorated stability in water and in acidic solutions compared to creatine monohydrate.
  • the aforementioned creatine hydroxycitrates may be useful to increase muscle and exercise performance in individuals, athletes in particular, and to afford neuroprotective strategies addressing specific bioenergetic defects.
  • these creatine hydroxycitrates may contribute to reduce fatty acid synthesis by preventing the conversion of carbohydrate energy into triglycerides, thereby being particularly suitable to be used in conjunction with dietary and exercise regimens aimed at the reduction and/or prevention of excess adiposity leading to weight loss.
  • the creatine hydroxycitrates due to a stimulatory action of the HCA moiety on serotonergic output, may contribute to improved exercise recovery and suppress the appetite leading to weight loss.
  • the present invention provides stable hydrosoluble creatine hydroxycitric acid salts, e.g. creatine hydroxycitrates, and a method of producing same, that possess higher water solubility and stability in acidic solutions compared to creatine monohydrate.
  • the present invention may also provide creatine hydroxycitrates, and a method of producing the same, that may be administered orally to a mammal with a bioavailability equal to or higher than creatine or hydroxycitric acid administered singularly or as a combination, wherein the salts may synergistically increase the physiological benefits afforded by the single creatine and the hydroxycitric acid components.
  • the present invention provides a method of production for a supplemental dietary ingredient, and a method of producing the same, that provides bioavailable organic creatine salts, e.g., monocreatine, dicreatine, and tricreatine hydroxycitrate, also collectively describable as “creatine hydroxycitrates”.
  • the present invention provides for a supplemental dietary ingredient and a method of producing the same, in which the bioavailable organic creatine salts include one, two or three energy-enhancing cationic portions (represented by creatine, which as set forth above is not limited to any particular type or anion) per lipolytic/anti-lipogenic anionic portion (represented by hydroxycitrate), respectively.
  • the present invention may, according to one embodiment, provide creatine hydroxycitrates, and a method of producing the same, which possess ameliorated palatability.
  • the present invention also provides by the consumption of a supplemental composition containing creatine hydroxycitric acid, a method of promoting increased muscle and exercise performance in individuals.
  • the present invention may also provide, by the consumption of a supplemental composition containing a creatine hydroxycitric acid or derivative, a method of reducing and/or preventing adiposity.
  • the present invention may also provide, by the consumption of the supplemental composition containing creatine hydroxycitric acid or derivative, a method of improving exercise recovery.
  • the present invention may also provide, by the consumption of a supplemental composition containing a creatine hydroxycitric acid or derivative, a method for suppressing appetite leading to weight loss.
  • Supplementation with creatine hydroxycitrate may be utilized by individuals engaged in sports where a need exists to improve short-term anaerobic performance and/or achieve simultaneous muscle volumization and leanness. Moreover, due to HCA-induced stimulation of serotonergic output resulting from supplementation with creatine hydroxycitrates, recovery from exercise is enhanced and feeding urges (especially during strict dietary restriction) are ameliorated.
  • creatine hydroxycitrates by affording Neuroprotection, may be particularly useful in addressing specific bioenergetic defects in Huntington's and Parkinson's diseases, Duchene muscular dystrophy, and may be utilized clinically in patients with gyrate atrophy, and other various neuromuscular disorders, McArdle's disease, and congestive heart failure.
  • the present invention is directed towards isolated hydrosoluble salts of creatine formed via the reaction of creatine with hydroxycitric acids, e.g., creatine hydroxycitrates, the salts having ameliorated stability in water and acidic solutions compared to creatine monohydrate.
  • hydroxycitric acids e.g., creatine hydroxycitrates
  • the creatine hydroxycitrates are monocreatine, dicreatine, and tricreatine hydroxycitrate.
  • the monocreatine hydroxycitrate may include one creatine cation per hydroxycitrate anion.
  • the dicreatine hydroxycitrate may include two creatine cations per hydroxycitrate dianion.
  • the tricreatine hydroxycitrate may include three creatine cations per hydroxycitrate trianion.
  • the present invention may provide a method for enhancing muscle performance and exercise recovery and weight loss in individuals, e.g., athletes, wherein the method comprises administering a composition comprising any of the isolated salts described herein, singularly and in combination.
  • the present invention may also provide a method for affording neuroprotective strategies addressing specific bioenergetic defects, the method including administering a composition comprising any of the isolated salts described herein, singularly and in combination.
  • the present invention may also provide a method for affording recovery from fatigue and stress wherein the method includes administering a composition comprising any of the isolated salts described herein, singularly and in combination.
  • the present invention may also provided a method for reducing fatty acid synthesis by preventing the conversion of carbohydrate energy into triglycerides wherein the method includes administering a composition comprising any of the isolated salts described herein, singularly and in combination. Also, the present invention may provide a method for suppressing appetite leading to weight loss by stimulating serotonergic output wherein the method comprises administering a composition comprising any of the isolated salts described herein, singularly and in combination.
  • the present invention may also provide a method which advantageously includes the steps of combining with any of the isolated salts described herein one or more of the following dietary ingredients: Whey protein (isolates and/or concentrates and/ hydrolysates), casein (micellar casein, sodium and/or calcium caseinates), alpha lipoic acid, carbohydrates, free-form amino acids (branched-chain and/or essential and/or non-essential, amino acids) and salts, trivalent chromium and its organic salts and chelates (chromium polynicotinate and/or picolinate, and/or fumarate, citrate, etc.), vitamins and minerals, camellia sinensis leaf and its polyphenolic extracts (containing in particular: epigallocatechin gallate (EGCG), epigallocatechin (EGC), catechin (C), epicatechin (EC), epicatechin gallate (EG), etc.), caffeine and other thermogenics, bioflavonoids, condensed tannins, oligomeric proanthocyanidins,
  • the present invention relates to an isolated hydrosoluble salt of creatine and hydroxycitrate of the formula:
  • the hydrosoluble salt may have a molecular weight of 547.07, and a melting point of about 290° C.
  • the present invention relates to a method for at least one of promoting increased muscle and exercise performance in individuals, reducing and/or preventing adiposity, improving exercise recovery and suppressing the appetite of an individual leading to weight loss, the method including the step of consuming a supplemental dietary composition containing creatine hydroxycitric acid in the form of an isolated hydrosoluble salt of creatine and hydroxycitrate.
  • the hydrosoluble salt may have a molecular weight of 547.07, and a melting point of about 290° C.
  • the present invention relates to a supplemental dietary composition for at least one of promoting increased muscle and exercise performance in individuals, reducing and/or preventing adiposity, improving exercise recovery and suppressing the appetite of an individual leading to weight loss
  • the supplemental dietary composition including creatine hydroxycitric acid in the form of an isolated hydrosoluble salt of creatine and hydroxycitrate.
  • the salt may have a molecular weight of 547.07, and a melting point of about 290° C.
  • Extra creatine in the muscle may also increase the rate of regeneration of phosphocreatine following high-intensity anaerobic exercise, which may result in less fatigue with repeated bursts of activity in training or in many sport competitions.
  • creatine supplementation may result in positive physiologic effects on skeletal muscle, such as: performance improvements during brief high-intensity anaerobic exercise, increased strength and ameliorated body composition in physically active subjects.
  • These benefits have been applied to disease models of Huntington's, Parkinson's, Duchene muscular dystrophy, and utilized clinically in patients with gyrate atrophy, various neuromuscular disorders, McArdle's disease, and congestive heart failure. See, for instance, Persky, A. M., and Brazeau, G. A., “Clinical pharmacology of the dietary supplement creatine monohydrate”. Pharmacol Rev 53(2):161-176, 2001.
  • Hydroxycitric acid has been shown to inhibit the activity of ATP citrate lyase, the extramitochondrial enzyme responsible for the conversion of carbohydrate energy into fats, and therefore it is believed to suppress fatty acid synthesis, lipogenesis, and induce weight loss; see, for instance Jena, B. S., et al., “Chemistry and Biochemistry of ( ⁇ )-Hydroxycitric Acid from Garcinia”. J Agric Food Chem 50:10-20, 2002. Additional evidence has also been presented to the extent that hydroxycitric acid may reduce food intake by means of a stimulatory action on serotonergic output, which ultimately induces satiety and reduced the urge of the individual feed; see, for instance Preuss, H.
  • the present invention according to various embodiments thereof (refer to examples 1 to 4) provides stable hydrosoluble creatine hydroxycitric acids salts, e.g., creatine hydroxycitrates, such as tricreatine hydroxycitrate, and a method for producing the same, that possess higher water solubility and stability in acidic solutions compared to creatine monohydrate.
  • creatine hydroxycitric acids salts e.g., creatine hydroxycitrates, such as tricreatine hydroxycitrate
  • the present invention provides creatine hydroxycitrates, such as tricreatine hydroxycitrate, and a method for producing the same, that may be administered orally to a mammal with a bioavailability equal to or higher than creatine or hydroxycitric acid administered singularly or as a combination, wherein the salts may synergistically increase the physiological benefits afforded by the single creatine and the hydroxycitric acid components.
  • creatine hydroxycitrates such as tricreatine hydroxycitrate
  • a method for producing the same may be administered orally to a mammal with a bioavailability equal to or higher than creatine or hydroxycitric acid administered singularly or as a combination, wherein the salts may synergistically increase the physiological benefits afforded by the single creatine and the hydroxycitric acid components.
  • the present invention provides for a supplemental dietary ingredient, and a method for producing the same, that provides bioavailable organic creatine salts, e.g., creatine hydroxycitrates.
  • bioavailable organic creatine salts include one, two, or three energy-enhancing cationic portions (represented by creatine) per lipolytic/anti-lipogenic anionic portion (represented by hydroxycitrate), respectively.
  • the present invention may provide creatine hydroxycitrates, and a method for producing the same, which possess ameliorated palatability.
  • the present invention also provides, by the consumption of a supplemental dietary composition containing creatine hydroxycitric acid, a method of promoting increased muscle and exercise performance in individuals.
  • the present invention may also provide, by the consumption of a supplemental dietary composition containing creatine hydroxycitric acid, a method of reducing and/or preventing adiposity.
  • the present invention may also provide, by the consumption of a dietary supplemental composition containing creatine hydroxycitric acid, a method of improving exercise recovery.
  • the present invention may also provide, by the consumption of a supplemental dietary composition containing creatine hydroxycitric acid, a method of suppressing the appetite of an individual, leading to weight loss.
  • supplementation with creatine hydroxycitrates may be particularly suitable in sports where a need exists to improve short-term anaerobic performance and/or achieve simultaneous muscle volumization and leanness.
  • supplementation with creatine hydroxycitrates may be particularly suitable to enhance recovery from exercise and minimize feeding urges (especially during strict dietary restriction).
  • creatine hydroxycitrates by affording Neuroprotection, may be particularly suitable in addressing specific bioenergetic defects in Huntington's and Parkinson's diseases, Duchene muscular dystrophy, and may be utilized clinically in patients with gyrate atrophy, various neuromuscular disorders, McArdle's disease, and congestive heart failure.
  • the supplemental ingredient, creatine hydroxycitrate may be consumed in any form.
  • the dosage form of the supplemental composition may be provided as, e.g., a capsule, a tablet, a caplet, a liquid beverage, a powder beverage mix, a dietary gel, or as ready-to-eat bar or drink product.
  • the preferred dosage forms are capsules or powder.
  • the dosage may be provided in accordance with customary processing techniques for herbal and/or dietary supplements in any of the forms mentioned above.
  • a supplemental composition may contain a variety of additional active ingredients and excipients.
  • the present invention provides stable hydrosoluble creatine HCA salts, e.g., creatine hydroxycitrates, which possess higher water solubility and stability in acidic solutions compared to creatine monohydrates.
  • the present invention may also provide creatine hydroxycitrates that may be administered orally to a mammal with a bioavailability equal to or higher than that of creatine or HCA when administered singularly or in combination, wherein the salts may synergistically increase the physiological benefits afforded by the single creatine or the HCA components.
  • preferred alcohols include methyl alcohol, ethyl alcohol, propyl alcohol and isopropyl alcohol. Also, ethyl acetate (acetic acid ethyl ester) may be employed. Most preferably, methyl alcohol is employed.
  • Hydroalcoholic solution of ( ⁇ )-HCA are preferred in order to reduce the conversion of creatine into creatinine during the time necessary for the reaction to be completed. Water ( ⁇ )-HCA solution could be alternatively used as a media to which creatine monohydrate is added. The reaction however, would yield salts with lower creatine content.
  • the present invention may provide certain advantages over conventional dietary supplement ingredients and method of producing the same.
  • the creatine hydroxycitrates of the present invention may have improved hydrosolubility and possess ameliorated stability in water and acidic solutions compared to creatine monohydrate.
  • creatine hydroxycitrates of the present invention may be useful to increase muscle and exercise performance in individuals, athletes in particular, and to afford neuroprotective strategies addressing specific bioenergetic defects.
  • the creatine hydroxycitrates of the present invention may contribute to reduce fatty acid synthesis by preventing the conversion of carbohydrate energy into triglycerides, thereby being particularly suitable to be used in conjunction with dietary exercise regimens aimed at the reduction and/or prevention of excess adiposity leading to weight loss. Still further, the creatine hydroxycitrates of the present invention, due to the stimulatory action of the HCA moiety on serotonergic output, may contribute to improved exercise recovery and suppress the appetite of an individual, leading to weight loss.
  • the fruits rinds of G. cambogia and G. indica may contain 20-30% ( ⁇ )-HCA (Reference: Lewis, Y. S., and Neelakantan S. ( ⁇ )-Hydroxycitric acids.
  • the principle acid in the fruit is Garcinia cambogia. Pytochemistry 4:619-625, 1965).
  • the fruit rinds of G. cambogia and G. indica may preferably contain a minimum of about 15% ( ⁇ )-HCA.
  • Step 1) 1.3875 kg of Garcinia fruit rind is extracted with 4.1625 l of methyl alcohol at about flux temperature for 3.5 hrs. the first extract is therefore collected following filtration with a cloth filter;
  • Step 2 An additional 4.1625 l of methyl alcohol is added to the Garcinia fruit rind and refluxed for 3.5 hrs. This is filtered as above to collect the second extract;
  • Step 3 An additional 4.1625 l of methyl alcohol is added again to the Garcinia fruit rind and refluxed for an additional 3.5 hrs. This is filtered as above to collect the third extract;
  • Step 5 The combined extracts are treated with 4.1625 l of methyl alcohol to which 112.2 g of potassium hydroxide (2 mol elemental K) and 149.13 g creatine monohydrate (1 mol) are added at a pH between 9 and 10. This is again refluxed for 3.5 hrs. to attain a constant pH of 10 in order to precipitate (mono)-creatine dipotassium hydroxycitrate monohydrate;
  • Step 6 The precipitate is filtered and washed with 1.3875 l of methyl alcohol;
  • Step 7) The precipitate is dried under vacuum at about 70° C.
  • step 5 the combined extracts in step 5 are treated with 4.1625 l of methyl alcohol to which 56.1 g of potassium hydroxide (1 mol elemental K) and 298.26 g creatine monohydrate (2 mol) are added at a ph of about 9-10. This is refluxed for 3.5 hrs. to attain constant pH of 10 in order to precipitate dicreatine (mono) potassium hydroxycitrate monohydrate. Steps 6 and 7 are repeated.
  • step 5 the combined extracts in step 5 are treated with 4.1625 l of methyl alcohol to which 447.39 g of creatine monohydrate (2 mol) are added at a ph of about 9-10. This is refluxed for 3.5 hrs. to attain a constant pH of 10 in order to precipitate tricreatine hydroxycitrate monohydrate. Steps 6 and 7 are repeated.
  • (Mono)-creatine dipotassium hydroxycitrate monohydrate preferably does not have less than about 50% ( ⁇ )-HCA and potassium and creatine content of about 20 and 10%, respectively, by weight on an anhydrous basis.
  • the lactone content may be in the vicinity of not more than about 2%.
  • Dicreatine (mono) potassium hydroxycitrate monohydrate preferably does not have less than about 50% ( ⁇ )-HCA and a potassium and creatine content of about 10 and 20%, respectively, by weight on an anhydrous basis.
  • the lactone content may be in the vicinity of not more than about 2%.
  • Tricreatine hydroxycitrate monohydrate preferable does not have less than about 50% ( ⁇ )-HCA and a creatine content of about 30% by weight on an anhydrous basis.
  • the lactone content may be in the vicinity of not more than about 2%.
  • Free ( ⁇ )-HCA can easily be generated from calcium, sodium and potassium hydroxycitrate salts, by passing an aqueous solution of said salt through a cation exchange resin, e.g., Zeocarb® 225.
  • a cation exchange resin e.g., Zeocarb® 225.
  • Tricreatine hydroxycitrate may be manufactured as follows:
  • Step 1) Start with 10.84 l of anhydrous methyl alcohol
  • Step 2 With stirring, an aqueous solution containing 1,084 g of hydroxycitric acid (5.2 moles), obtained after passing the ( ⁇ )-HCA salt through a cation exchange resin, are added to the anhydrous methyl alcohol. The resulting mixture is stirred for approximately 45 minutes;
  • Step 3 2,362 g (15.6 moles) or creatine monohydrate are added to the hydroxycitric acid/ methyl alcohol mixture. This mixture is stirred for approximately four (4) hours;
  • Step 4 At the end of the four hours, the crystallized product is separated from the reaction mixture by centrifugation and washed with anhydrous methyl alcohol to remove all the impurities;
  • Step 5 the finished product is dried under vacuum at 70° C.
  • the resulting product is tricreatine hydroxycitrate, having three creatine cations per hydroxycitrate (tri)-anion.
  • Creatine monohydrate has a molecular weight of 149.13; therefore the amount of creatine monohydrate added is 15.6 gram-moles.
  • the stoichiometric ratio of creatine to hydroxycitric acid is 3:1.
  • the creatine assay for the material should be in the range of 60-70%.
  • reaction mixture includes 5.2 moles of hydroxycitric acid
  • monocreatine hydroxycitrate, and dicreatine hydroxycitrate having one and two creatine cations per hydroxycitrate anion, respectively, can be obtained.
  • the preferred alcohols include methyl alcohol, ethyl alcohol, propyl and isopropyl alcohol. Also ethyl acetate (acetic acid ethyl ester) can be employed. Especially preferred is methyl alcohol.
  • Hydroalcoholic solutions of ( ⁇ )-HCA are preferred in order to reduce the conversion of creatine into creatinine during the time necessary for the reaction to be completed. Water ( ⁇ )-HCA solutions could be alternatively used as media to which creatine monohydrate is added. The reaction however, would yield salts with lower creatine content.
  • Tripotassium hydroxycitrate monohydrate has a molecular weight of 340.41 g per mole.
  • Creatine hydrochloride has a theoretical molecular weight of 167.57 g per mole.
  • Step 1) 3.5 g of tripotassium hydroxycitrate monohydrate (0.01 mol) is mixed in sufficient deionized water to a final volume of 300 ml;
  • Step 2 To the solution described above, creatine hydrochloride is added in an amount of 5.03 g (0.03 mol) and solution is stirred for 45 minutes;
  • Step 3 The resulting product is tricreatine hydroxycitrate (5.8-6%), having three creatine cations per hydroxycitrate (tri)-anion.
  • Step 4) Potassium chloride, also obtains via this reaction, can be precipitated with the addition of alcohol (ethanol, methanol) and removed by filtration.
  • the stoichiometric ratio of creatine to hydroxycitric acid is 3:1.
  • Step 1) A solution is made by dissolving 1 mol (340.41 g) of tripotassium hydroxycitrate in a final volume of 2 l of deionized water to form an 0.5M solution;
  • Step 2) 1 mol of anhydrous citric acid (192.13 g) is added to the tripotassium hydroxycitrate solution in step 1. The solution is then heated at 30° C.;
  • Step 3 Upon cooling, tripotassium citrate precipitates. This is removed by filtration;
  • Step 5 3 moles of creatine monohydrate (447.39 g) can then be obtained by adding 2 l of anhydrous methyl alcohol and then combined with the solution of free ( ⁇ )-HCA. The mixture is stirred for 4 hrs. in order to obtain tricreatine hydroxycitrate;
  • Step 6 At the end of the 4 hrs., the crystallized product is separated from the reaction mixture by centrifugation and washed with anhydrous methyl alcohol;
  • Step 7) The finished product is then dried under vacuum at 70° C.
  • Dicreatine and monocreatine hydroxycitrate can be obtained by adding 2 or 1 mol of creatine monohydrate respectively to the mixture of anhydrous methyl alcohol and ( ⁇ )-HCA, which is then stirred for 4 hrs.
  • Step 1) Garcinia rind is loaded into static extractors and extracted with water at a ratio between 5:1 and 7:1 for 60 minutes;
  • Step 2) The water is then drained to storage tank and 4 washes are preformed;
  • Step 3) The rind is discarded
  • Step 4) A precipitation with calcium hydroxide is preformed and the calcium salt of hydroxycitric acid is recovered;
  • Step 5 The calcium hydroxycitric acid is treated with an acidic medium and filtered. Liquid hydroxycitric acid is recovered;
  • Step 6 Liquid hydroxycitric acid is reacted with creatine and then spray dried;
  • Step 8) The tricreatine HCA powder is sieved through a number 40 mesh, tested and packaged.
  • a typical yield via this process results in an HPLC assay of about 30-35% ( ⁇ )-hydroxycitric acid and between about 30 and 40% creatine.
  • the standard specification may be for not less than about 30% ( ⁇ )-hydroxycitric acid and not less than 30% creatine. There preferably is not more than 8% of the product lost upon drying and not more than 10 ppm heavy metals.
  • the product may be a fine powder with an “off-white” to “buff” colour.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Veterinary Medicine (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Diabetes (AREA)
  • Nutrition Science (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Neurology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Mycology (AREA)
  • Food Science & Technology (AREA)
  • Polymers & Plastics (AREA)
  • Endocrinology (AREA)
  • Child & Adolescent Psychology (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicinal Preparation (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Coloring Foods And Improving Nutritive Qualities (AREA)
US11/349,960 2005-02-07 2006-02-07 Creatine hydroxycitric acids salts and methods for their production and use in individuals Abandoned US20060194877A1 (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
US11/349,960 US20060194877A1 (en) 2005-02-07 2006-02-07 Creatine hydroxycitric acids salts and methods for their production and use in individuals
US12/108,822 US7772428B2 (en) 2005-02-07 2008-04-24 Creatine hydroxycitric acids salts and methods for their production and use in individuals

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US65104905P 2005-02-07 2005-02-07
US11/349,960 US20060194877A1 (en) 2005-02-07 2006-02-07 Creatine hydroxycitric acids salts and methods for their production and use in individuals

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US12/108,822 Division US7772428B2 (en) 2005-02-07 2008-04-24 Creatine hydroxycitric acids salts and methods for their production and use in individuals

Publications (1)

Publication Number Publication Date
US20060194877A1 true US20060194877A1 (en) 2006-08-31

Family

ID=36776915

Family Applications (2)

Application Number Title Priority Date Filing Date
US11/349,960 Abandoned US20060194877A1 (en) 2005-02-07 2006-02-07 Creatine hydroxycitric acids salts and methods for their production and use in individuals
US12/108,822 Expired - Fee Related US7772428B2 (en) 2005-02-07 2008-04-24 Creatine hydroxycitric acids salts and methods for their production and use in individuals

Family Applications After (1)

Application Number Title Priority Date Filing Date
US12/108,822 Expired - Fee Related US7772428B2 (en) 2005-02-07 2008-04-24 Creatine hydroxycitric acids salts and methods for their production and use in individuals

Country Status (8)

Country Link
US (2) US20060194877A1 (fr)
EP (1) EP1846368A4 (fr)
JP (1) JP2008529979A (fr)
CN (1) CN101115714A (fr)
AU (1) AU2006209849B2 (fr)
CA (1) CA2595907C (fr)
MX (1) MX2007009450A (fr)
WO (1) WO2006081682A1 (fr)

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20070031526A1 (en) * 2005-08-05 2007-02-08 Bioderm Research Topical Deodorant Compositions Based on Hydroxycitric Acid
US20080254198A1 (en) * 2004-11-08 2008-10-16 Bio-Engineered Supplements & Nutrition, Inc. Method of Preparing Creatine Ester Salts and Uses Thereof
US20080306159A1 (en) * 2007-06-05 2008-12-11 Daugherty F Joseph Enteric coated, soluble creatine and polyethylene glycol composition for enhanced skeletal uptake of oral creatine
US20110257089A1 (en) * 2008-10-24 2011-10-20 N.V. Nutricia Liquid high-fat protein composition
JP2018138914A (ja) * 2011-12-07 2018-09-06 グラクソスミスクライン エルエルシー 全身骨格筋量の定量方法
US10386371B2 (en) 2011-09-08 2019-08-20 The Regents Of The University Of California Metabolic flux measurement, imaging and microscopy
US10466253B2 (en) 2004-02-20 2019-11-05 The Regents Of The University Of California Molecular flux rates through critical pathways measured by stable isotope labeling in vivo, as biomarkers of drug action and disease activity
US20210369656A1 (en) * 2020-06-02 2021-12-02 Glykon Technologies Group, Llc Methods and pharmaceutical preparations for elevating ketone utilization

Families Citing this family (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20080003208A1 (en) * 2006-05-11 2008-01-03 Avicena Froup, Inc. Creatine-ligand compounds and methods of use thereof
WO2008101310A1 (fr) * 2007-02-20 2008-08-28 Multi Formulations Ltd. Créatine-acides gras
US7511162B2 (en) 2007-02-20 2009-03-31 Multi Formulations Ltd. Preparation of amino acid-fatty acid anhydrides
WO2008101309A1 (fr) * 2007-02-20 2008-08-28 Multi Formulations Ltd. Composés créatine-acides gras
US7314945B1 (en) 2007-02-20 2008-01-01 Multi Formulations Ltd. Creatine-fatty acids
US7319157B1 (en) 2007-02-20 2008-01-15 Multi Formulations Ltd. Creatine-fatty acids
US7714154B2 (en) 2007-05-10 2010-05-11 Northern Innovations And Formulations Corp. Preparation of amino acid-fatty acid anhydrides
WO2009076741A1 (fr) * 2007-12-18 2009-06-25 Multi Formulations Ltd. Esters de créatinol-acide gras
DE102010053748B4 (de) * 2010-12-08 2023-08-03 Jörg Schierholz Pharmazeutische Zusammensetzung zur Behandlung von Übergewicht
EP2852390A1 (fr) 2012-05-21 2015-04-01 Chemi Nutra Inc. Compositions et procédés pour l'augmentation de la force et de la masse musculaire
WO2013177458A1 (fr) 2012-05-23 2013-11-28 Chemi Nutra Compositions destinées à augmenter la force, la masse musculaire et la masse corporelle maigre
CN104725218A (zh) * 2015-03-02 2015-06-24 李玉山 一种藤黄果中羟基柠檬酸的提取纯化方法
WO2017075289A1 (fr) 2015-10-27 2017-05-04 Cytozyme Animal Nutrition, Inc. Compositions pour l'alimentation animale et procédés associés
US10674746B2 (en) 2015-10-27 2020-06-09 Cytozyme Animal Nutrition, Inc. Animal nutrition compositions and related methods
CN109758445B (zh) * 2019-02-15 2021-07-02 王铁鹏 一种提高肌酸对兴奋性神经毒性保护效果的方法
CN112264192B (zh) * 2020-11-18 2021-10-22 东北大学 一种锡石浮选组合抑制剂及其应用
CN112264195B (zh) * 2020-11-18 2021-10-12 东北大学 一种锡石矿物浮选抑制剂及其应用

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5925278A (en) * 1996-08-23 1999-07-20 Hewlett-Packard Company Universal power supply for multiple loads
US5973199A (en) * 1994-08-04 1999-10-26 Flamma S.P.A. Hydrosoluble organic salts of creatine
US6166249A (en) * 1996-12-20 2000-12-26 Skw Trostberg Aktiengesellschaft Creatine pyruvates
US6211407B1 (en) * 2000-05-03 2001-04-03 Pfanstiehl Laboratories, Inc. Dicreatine citrate and tricreatine citrate and method of making same
US20040185069A1 (en) * 2003-03-22 2004-09-23 Gupta Shyam K. Hydroxycitric acid derivatives for body slimming and tone firming compositions
US6838562B2 (en) * 2003-04-01 2005-01-04 Sal Abraham Process for preparing a creatine heterocyclic acid salt and method of use

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050256192A1 (en) * 2004-04-30 2005-11-17 Gardiner Paul T Nutritional composition for enhancing lean muscle stimulus, growth, strength and recovery, creating and prolonging intense muscle pumps, supporting endurance, strength, performance, size and stamina, providing a transducer effect for nitric oxide, increasing nutrient delivery and/or promoting increased vascular response in an individual
US20080089962A1 (en) * 2004-09-24 2008-04-17 Multi Formulations Ltd. Nutritional composition for facilitating muscle pumps
AU2005244162B2 (en) * 2004-05-07 2010-12-09 Thermo Formulations Ltd. Nutritional composition for increasing creatine uptake in skeletal muscle

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5973199A (en) * 1994-08-04 1999-10-26 Flamma S.P.A. Hydrosoluble organic salts of creatine
US5925278A (en) * 1996-08-23 1999-07-20 Hewlett-Packard Company Universal power supply for multiple loads
US6166249A (en) * 1996-12-20 2000-12-26 Skw Trostberg Aktiengesellschaft Creatine pyruvates
US6211407B1 (en) * 2000-05-03 2001-04-03 Pfanstiehl Laboratories, Inc. Dicreatine citrate and tricreatine citrate and method of making same
US20040185069A1 (en) * 2003-03-22 2004-09-23 Gupta Shyam K. Hydroxycitric acid derivatives for body slimming and tone firming compositions
US6838562B2 (en) * 2003-04-01 2005-01-04 Sal Abraham Process for preparing a creatine heterocyclic acid salt and method of use

Cited By (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10466253B2 (en) 2004-02-20 2019-11-05 The Regents Of The University Of California Molecular flux rates through critical pathways measured by stable isotope labeling in vivo, as biomarkers of drug action and disease activity
US20080254198A1 (en) * 2004-11-08 2008-10-16 Bio-Engineered Supplements & Nutrition, Inc. Method of Preparing Creatine Ester Salts and Uses Thereof
US20070031526A1 (en) * 2005-08-05 2007-02-08 Bioderm Research Topical Deodorant Compositions Based on Hydroxycitric Acid
CN101835468B (zh) * 2007-06-05 2012-07-04 克莱萨有限责任公司 用于改善口服肌酸的骨骼吸收的肠溶包衣的可溶性肌酸和聚乙二醇组合物
US20100203090A1 (en) * 2007-06-05 2010-08-12 Daugherty F Joseph Enteric coated, soluble creatine and polyethylene glycol composition for enhanced skeletal uptake of oral creatine
WO2008151249A3 (fr) * 2007-06-05 2010-01-07 Phenolics, Llc Composition soluble de créatine et de polyéthylène glycol à enrobage gastro-résistant pour un captage renforcé par le squelette de la créatine par voie orale
US10226429B2 (en) 2007-06-05 2019-03-12 Cryxa Llc Enteric coated, soluble creatine and polyethylene glycol composition for enhanced skeletal uptake of oral creatine
US10231933B2 (en) 2007-06-05 2019-03-19 Cryxa Llc Enteric coated, soluble creatine and polyethylene glycol composition for enhanced skeletal uptake of oral creatine
US20080306159A1 (en) * 2007-06-05 2008-12-11 Daugherty F Joseph Enteric coated, soluble creatine and polyethylene glycol composition for enhanced skeletal uptake of oral creatine
US20110257089A1 (en) * 2008-10-24 2011-10-20 N.V. Nutricia Liquid high-fat protein composition
US10386371B2 (en) 2011-09-08 2019-08-20 The Regents Of The University Of California Metabolic flux measurement, imaging and microscopy
JP2018138914A (ja) * 2011-12-07 2018-09-06 グラクソスミスクライン エルエルシー 全身骨格筋量の定量方法
US20210369656A1 (en) * 2020-06-02 2021-12-02 Glykon Technologies Group, Llc Methods and pharmaceutical preparations for elevating ketone utilization
US11957649B2 (en) * 2020-06-02 2024-04-16 Glykon Technologies Group, Llc Methods and pharmaceutical preparations for elevating ketone utilization

Also Published As

Publication number Publication date
EP1846368A1 (fr) 2007-10-24
AU2006209849B2 (en) 2010-11-25
EP1846368A4 (fr) 2008-01-23
AU2006209849A1 (en) 2006-08-10
CA2595907C (fr) 2009-04-14
US20080300309A1 (en) 2008-12-04
MX2007009450A (es) 2007-10-23
CN101115714A (zh) 2008-01-30
US7772428B2 (en) 2010-08-10
WO2006081682A1 (fr) 2006-08-10
CA2595907A1 (fr) 2006-08-10
JP2008529979A (ja) 2008-08-07

Similar Documents

Publication Publication Date Title
US7772428B2 (en) Creatine hydroxycitric acids salts and methods for their production and use in individuals
EP0825871B1 (fr) Compositions pharmaceutiques et/ou dietetiques possedant une activite antioxydante et contenant de la carnosine ou ses derives et des acides amines ramifies
US7943186B2 (en) Hydroxycitric acid compositions, pharmaceutical and dietary supplements and food products made therefrom, and methods for their use in reducing body weight
AU717533B2 (en) Magnesium (-)hydroxycitrate, preparation process, uses and compositions, in particular pharmaceutical compositions, containing it
US20110218244A1 (en) CREATINE ß-ALANINATE: A NOVEL SALT FOR INCREASING ATHLETIC PERFORMANCE
US5863939A (en) Creatine ascorbates and a method of producing them
WO2007094497A1 (fr) Agent d'amelioration du syndrome metabolique
US8466198B2 (en) Compositions comprising creatine salts and methods of use thereof
US20130096193A1 (en) Creatine beta-alaninate: a novel salt for increasing athletic performance
US20210261493A1 (en) Crystal of amino acid salt of 3-hydroxyisovaleric acid and production method thereof
JP4047935B2 (ja) Ｌ−カルニチンもしくはアルカノイル−ｌ−カルニチンと２−アミノエタンスルホン酸との非吸湿性塩を含有する経口投与に適した固体状組成物
JP2001524078A (ja) Ｌ−カルニチンもしくはアルカノイル−ｌ−カルニチンの酒石酸マグネシウム塩を含有する経口投与に適した固体状組成物
WO2000015051A1 (fr) Compositions d'acide hydroxycitrique
WO2001091590A1 (fr) Supplement alimentaire dote d'une activite antioxydante et contenant une carnitine d'alkanoyle et une combinaison de polyphenols extraits du cacao
KR20030059211A (ko) 타우린 클로라이드 및 글리신 클로라이드와의 ｌ-카르니틴및 알카노일 ｌ-카르니틴의 비 흡습성 염을 함유하는 경구투여에 적합한 고형 조성물
EP3829324B1 (fr) Mélanges d'acides cétoniques à chaîne ramifiée (bcka) et procédé de production de tels mélanges
US7511173B2 (en) Creatine salt with enhanced nutritional and therapeutic efficacy and compositions containing same
WO2018208647A1 (fr) Sels de créatine au goût modifié , composés, compositions et leurs utilisations
CN116889281A (zh) 一种用于提高骨密度的和金钙配方

Legal Events

Date Code Title Description
AS Assignment

Owner name: IOVATE T & P INC., CANADA

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:GARDINER, PAUL T.;HEUER, MARVIN A.;MOLINO, MICHELE;REEL/FRAME:017879/0217;SIGNING DATES FROM 20060329 TO 20060403

AS Assignment

Owner name: NEW CELL FORMULATIONS LTD., CANADA

Free format text: CORRECTED ASSIGNMENT RECORDATION FORM TO CORRECT THE ASSIGNEE OF THE APPLICATION PREVIOUSLY RECORDED AT REEL/FRAME 017879, FRAME 0217. (ASSIGNMENT OF ASSIGNOR'S INTEREST);ASSIGNORS:GARDINER, PAUL T.;HEUER, MARVIN A.;MOLINO, MICHELE;REEL/FRAME:018098/0553;SIGNING DATES FROM 20060329 TO 20060403

STCB Information on status: application discontinuation

Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION