WO2005096846A1 - Composition et procede d'amelioration de la biodisponibilite du calcium et du magnesium dans des complements alimentaires et des additifs alimentaires - Google Patents
Composition et procede d'amelioration de la biodisponibilite du calcium et du magnesium dans des complements alimentaires et des additifs alimentaires Download PDFInfo
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- WO2005096846A1 WO2005096846A1 PCT/US2004/007452 US2004007452W WO2005096846A1 WO 2005096846 A1 WO2005096846 A1 WO 2005096846A1 US 2004007452 W US2004007452 W US 2004007452W WO 2005096846 A1 WO2005096846 A1 WO 2005096846A1
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- calcium
- magnesium
- hydroxy
- methylbutyrate
- composition
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- 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
- A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
-
- 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
- A23L33/16—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 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
- A23L33/40—Complete food formulations for specific consumer groups or specific purposes, e.g. infant formula
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
Definitions
- the present invention relates to compositions and methods for preventing and/or treating conditions associated with calcium and/or magnesium deficiencies in humans or other animals.
- the invention relates to compositions comprising calcium and/or magnesium salts of 3-hydroxy-3-methylbutyric acid in a form suitable for administration to a subject in need thereof.
- calcium is essential for the maintenance of the functional integrity of the nervous, muscular, and skeletal systems, and cell membrane and capillary penneability.
- the calcium cation is an important activator in many enzymatic reactions and is essential to a number of physiologic processes including the transmission of nerve impulses; contraction of cardiac, smooth, and skeletal muscles; renal function; respiration; and blood coagulation.
- Calcium also plays a regulatory role in the release and storage of neurotransmitters and hormones, in the uptake and binding of amino acids, in vitamin B12 absorption, and in gastrin secretion.
- the calcium of bone is in a constant exchange with the calcium of plasma.
- Foods other than dairy products generally contribute less than 200 mg of calcium daily. However, beginning in young adulthood and continuing through later life, the general population rarely consumes milk in sufficient quantities to obtain the recommended dietary levels of calcium. This diminished consumption can be caused by lactose intolerance as well as by the unattractiveness of milk as a drink for social occasions. Vitamin and mineral supplementation is important primarily for those who have inadequate diets, including growing children. Older adults have an additional need fox calcium to help prevent age-related bone loss. Postmenopausal women need additional calcium due to hormonal changes which can accelerate the rate of bone loss leading to a further diminishment in bone mass. Therefore, supplementation of the diet with a highly bioavailable source of calcium is desirable.
- Osteoporosis is a condition in which an affected person's bones become increasingly porous, brittle, and subject to fracture, owing to loss of calcium and other mineral components. It is a common affliction in older persons, particularly postmenopausal women. Bone loss may also be associated with a variety of other conditions, including those brought on by long-term steroid therapy and certain endocrine disorders. If not countered, osteoporosis or bone loss may lead to fractures of the spine, hip, and long bones.
- U.S. Department of Agriculture consumption data suggest that 90% of adult women and 70% of adult men and teenagers do not meet the recommended daily intake (RDI) of calcium from dietary sources.
- RDI recommended daily intake
- the prevention and treatment of osteoporosis and systemic hypocalcemia generally requires the oral administration of calcium supplements to increase the amount of calcium available from dietary sources for intestinal absorption.
- the degree of absorption will depend on the calcium preparation used and on the timing of ingestion.
- the calcium compounds currently employed as dietary supplements vary widely in their elemental calcium content as well as in their solubility in aqueous media; the latter factor largely detennines the bio availability of the calcium.
- Bioavailability is defined as the efficiency with which a natural or manufactured source of an element delivers the element to storage or supplies it to metabolically active tissue.
- U.S. Pat. No. 5,468,506 teaches: "It is essential for the bioavailability of calcium that the calcium salts be soluble in the stomach and intestine.
- the phosphate salts of calcium employed as dietary supplements include: monobasic calcium phosphate monohydrate (calcium acid phosphate, Ca(H PO 4 ) » H 2 O; 16% by wt. elemental calcium); dibasic calcium phosphate dihydrate (calcium monohydrogen phosphate dihydrate, CaHPO 4 # 2H 2 O; 23% by wt. elemental calcium); and tribasic calcium phosphate (tricalcium phosphate, Ca 3 (PO 4 ) 2 ; 38% by wt. elemental calcium).
- the monobasic phosphate salt is moderately soluble in water, but it forms acidic solutions that have a bitter taste, while the dibasic and tribasic phosphate salts are virtually insoluble in water and consequently have poor bioavailability.
- the phosphate salts of calcium may exacerbate hyperphosphataemia and metastatic calcification (see C.Y.C. Pak "Calcium Disorders: Hypercalcemia and Hypocalcemia” in J.P. Kokko, R.L. Tannen, eds. Fluids and Electrolytes (Philadelphia: W.B. Saunders, 1990), pp. 596-630; K.A. Hruska and J.
- Calcium glycerophosphate (CaC 3 H 0 6 ; 19% by wt. elemental calcium), is soluble in 50 parts of water at 20°C, forming an alkaline solution. Like the simple phosphate salts, calcium glycerophosphate may exacerbate ri perpliosphataemia and metastatic calcification. Calcium citrate tetrahydrate (Ca 3 (C s _H 5 O 7 ) '4H 2 O; 21% by wt.
- U.S. Pat. No. 6,287,607 teaches the use of potassium calcium citrates, complex salts that contain a molar ratio of potassium to calcium of either 1 :1 or 4: 1 (corresponding to elemental calcium contents of 15% and 7% by wt., resp ectively), as highly soluble compounds that offer improved bioavailability of calch-im despite their modest calcium content.
- delivering significant amounts of potassium may undesirably alter the sodium-to-potassium ratio of blood electrolytes.
- An excess of potassium (“hyperkalemia") is associated with cardiac arrhythmia.
- the solubility of calcium gluconate in water can be increased to 20% by weight or more by adding a complexing agent like boric acid.
- a complexing agent like boric acid.
- Magnesium is important for the proper functioning of nerves and muscles. It is an essential constituent of many enzyme systems, particularly those involved with energy generation. The body's largest stores are found in the sleeleton. The recommended daily intake (RDI) of magnesium ranges from 300 to 400 milligrams in most countries; 70% of the US population do not meet the RDI.
- Magnesium salts are not well absorbed from the gastrointestinal tract, accounting for the fact that the most common magnesium supplement, magnesium sulfate (MgSO 4 ), is also employed as an osmotic laxative.
- the present invention provides calcium and magnesium compositions useful as dietary supplements and food additives and methods .for administering the compositions to prevent or treat disorders associated with hypocalcen ⁇ ia and/or hypomagnesia.
- the compositions of the present invention comprise calcium and/or magnesium salts of 3- hydroxy-3-methylbutyric acid in a form suitable for administration to a subject in need thereof.
- Methods for treatment of hypocalcemia and/or hypomagnesia comprising administration of a therapeutically effective regimen of calcium and/or magnesium salts of 3- hydroxy-3-methylbutyric acid to a patient in need of such treatment are also provided.
- one aspect of the invention relates to a method for preventing and/or treating a condition associated with calcium and/or magnesium deficiency in a human or other animal subject.
- the method includes administering a safe and effective amount of calcium 3-hydroxy-3-methylbutyrate, magnesium 3-h_ydroxy-3-methylbutyrate or mixtures thereof to a subject.
- conditions treated or prevented include, but are not limited to, osteoporosis, hypertension and bone loss.
- a method for providing a nutritionally supplemental amount of calcium and ma-jgnesium to a human or other animal subject is described.
- This method includes administering a safe and effective amount of a mineral supplement comprising calcium 3-hydroxy-3-methylbutyrate and magnesium 3- hydroxy-3-methylbutyrate to a human or other animal subject.
- a bioavailable and water- soluble composition for conjointly administering bioa-vailable calcium and magnesium in an oral form to a human patient or other animal in need thereof is provided.
- the composition includes (a) calcium in a water-soluble form, (b) magnesium in a water-soluble form, and (c) an edible organic acid component comprising 3-hydroxy-3 ⁇ methylbutyric acid.
- the term “comprising” means that the described composition or process includes the components or steps recited but is open to the inclusion of additional components or steps.
- the terms “consisting essentially of and “consisting of are embodied in the term “comprising.”
- pharmaceutically acceptable refers to a composition that is suitable for use with humans and/or animals without undue adverse side effects (such as toxicity, irritation, or allergic response) commensurate with a reasonable benefit/risk ratio.
- safe and effective amount refers to a quantity of a component which is sufficient to yield a desired therapeutic response wititiout undue adverse side effects commensurate with a reasonable benefit/risk ration when used in the manner of this invention.
- the specific "safe and effective amount” will vary with such factors as the particular condition being treated, the physical condition of th-e patient, the duration of the treatment, the nature of any concurrent therapy, and the specific formulations employed.
- nutritional or “nutritionally-supplemental amount” herein is meant that the mineral and vitamin sources used in the practice of this invention provide a nourishing amount of magnesium and/or calcium. This is supplemental ox in addition to the amount found in the average diet.
- This supplemental amount typically will comprise at least about 3%> of the Recommended Dietary Intake (RDI) of calcium and/or magnesium. More generally, the mineral supplements disclosed herein will contain at least 10%, more typically about 50% to 300%) of the Recommended Dietary Intake (RDI) per unit dose of the supplement.
- the term "elemental” as used herein means of or pertaining to the element referred to.
- the elements involved in the present invention are primarily calcium, magnesium and other minerals beneficial for human consumption. Elemental percentage indicates the percentage of elemental calcium, magnesium, etc. present in a composition. Accordingly, the elemental percentage of calcium in calcium carbonate does not include the percentage of carbonate present.
- the compositions of the present invention are soluble at high concentrations.
- solubility means capable of being dissolved, going into a liquid state from a solid state.
- solubility of a mineral is an indicator of how bioavailable that mineral is. (See Schaafsma, G., "Bioavailability of Calcium and Magnesium,” European J. of Clinical Nutrition, 1977, “It is clear that availability for absorption requires calcium to be solubilized, either in free ionic or complexed form.) Solubility also plays an important role in the preparation of foods and beverages containing these s pplements.
- the calcium salt of 3-hydroxy-3-methylbutyric acid forms a monohydrate with the chemical formula Ca(C 5 H 9 O 3 ) 2 » H 2 O.
- CaHMB calcium hydroxymethylbutyrate
- dissolves readily in water forming a 27% by weight saturated aqueous solution at 20°C.
- a high degree of solubility conesponds to a high degree of bioavailabilty As indicated above, a high degree of solubility conesponds to a high degree of bioavailabilty.
- the figure graphically compares the amount of elemental calcium present in a saturated aqueous solution- of CaHMB at 20°C.
- the calcium salt of 3-hydroxy-3-methylbutyric acid can be prepared by reacting a slight (i.e. 5%>) stoichiometric excess calcium oxide ("unslaked lime”) or calcium hydroxide (“slaked lime”) with an aqueous solution containing free 3-bLydroxy-3-methylbutyric acid, preferably at an elevated temperature of 40 to 70 degrees C.
- unslaked lime or calcium hydroxide
- slaked lime calcium carbonate can be employed.
- the unreacted excess oxide, hydroxide, or carbonate can be removed by filtration and the calcium salt 3-hydroxy-3-methylbutyric acid is recovered by crystallizing, spray-drying, or freeze-drying (lyopholizing) the resulting filtrate.
- the taste of calcium hydroxy-methylbutyrate (“CaHI B”) is not objectionable and can be easily masked.
- CaHMB non-toxic, but the hydroxymethylbutyrate anion is reputed to have a number of other beneficial physiological effects, including binding phosphates in the treatment of uremia (M.F.
- the magnesium salt of 3-hydroxy-3-methylbutyric acid (synonyms: beta-hydroxy- beta-methylbutyric acid; 3 -hydroxy-iso valeric acid) has the chemical formula Mg(CsH O 3 ) 2 .
- MgHMB magnesium hydroxymethylbutyrate monohydrate
- the magnesium salt of 3-hydroxy-3-methylbutyric acid can be prepared by reacting a 5% stoichiometric excess of basic magnesium carbonate (approximate composition (MgCO 3 ) 4 'Mg(OH) 2 -5H 2 O , equivalent to 40 to 42% MgO) with an aqueous solution containing free 3-hydroxy-3-methylbutyric acid, preferably at an elevated temperature of 40 to 70 degrees C.
- basic magnesium carbonate approximately 4 'Mg(OH) 2 -5H 2 O , equivalent to 40 to 42% MgO
- magnesium oxide or magnesium hydroxide can be employed.
- the unreacted excess carbonate, oxide, or hydroxide can be removed by filtration and the magnesium salt of 3-hydroxy-3-methylbutyric acid can be recovered " by crystallizing, spray- drying, or freeze-drying (lyopholizing) the resulting filtrate.
- Both the calcium and the magnesium salts of 3-hydroxy-3-methylbutyric acid are stable powders with long shelf lives. If pure, they dissolve in water to form aqueous solutions of nearly neutral or slightly alkaline pH. They are highly soluble over a broad range of pH values.
- Various oral dosage forms of calcium and magnesium hydrox;y-3-methylbutyrates may be used in the present invention.
- the calcium and the magnesium salts of 3-hydroxy-3- methylbutyric acid may be in unit dosage forms or in multiple dosage form.
- Such dosage forms comprise a safe and effective amount of the calcium and/or magnesium hydroxy-3- methylbutyrates and a pharmaceutically acceptable carrier.
- the pharmace ⁇ tically acceptable earner may be present at a level of from about 0.1 % to about 99%>, more paxticularly from about 0.1% to about 75%, and in certain embodiments, from about 0.1% to about 50% by weight of the composition.
- Unit dosage forms i.e., compositions containing an amount of calcium and/or magnesium hydroxy-3-methylbutyrates suitable for administration in one s gle dose, according to sound medical practice
- Unit dosage forms preferably contain from about 730 mg (milligrams) to about 7,300 mg of calcium hydroxy-3-methylbutyrate, conesponding to from about 100 mg to about 1,000 mg of calcium on an elemental basis, and from about 200 mg to about 2,000 mg magnesium hydroxy-3-methylbutyrate, corresponding to from about 19 mg to about 190 mg of magnesium on an elemental basis.
- the unit dosage forms in accordance with certain aspects of the present invention contain from about 730 mg to about 2,300 mg of calcium hydroxy-3-methylbutyrate and from 200 mg to about 600 mg of magnesium hydroxy-3- methylbutyrate.
- Solid dosage forms include tablets, capsules, granules and bulk powders. Aside from the calcium and magnesium hydroxy-3 -methylbutyrates, tablets may contain, as carriers, suitable binders, lubricants, diluents, disintegrating agents, coloring agents, flavoring agents, flow-inducing agents, melting agents, and mixtures thereof.
- Liquid oral dos ge forms include aqueous solutions, emulsions, suspensions, solutions and/or suspensions reconstituted from non-effervescent granules and effervescent preparations reconstituted from effervescent granules.
- Such oral dosage forms may contain, as carriers (for example), suitable solvents, preservatives, emulsifying agents, suspending agents, diluents, sweeteners, melting agents, coloring agents, flavoring agents, and mixtures thereof.
- suitable solvents for example
- preservatives for example
- emulsifying agents for example, suspending agents, diluents, sweeteners, melting agents, coloring agents, flavoring agents, and mixtures thereof.
- Specific examples of phannaceutically acceptable earners and excipients that may be used to formulate oral dosage forms of the present invention are described in U.S. Pat. No. 3,903,297, Robert, issued Sep. 2, 1975, incorporated by reference herein.
- the present invention also provides methods for the administration of a calcium and/or magnesium supplement to a human or other animal subject in need thereof, comprising administering to said subject a safe and effective amount of the calcium and/or magnesium hydroxy-3-methylbutyrates of this invention. Preferably ⁇ , from about 730 mg to about 2,300 mg of calcium hydroxy-3-methylbutyrate is administered per day.
- administering refers to any method which, in sound medical practice, delivers the calcium and/or magnesium hydroxy-3 -methylbutyrates used in this invention to the subject to be treated in such a manner so as to be effective in the treatment or prevention of calcium or magnesium deficiency pathologies.
- the calcium and magnesium hydroxy-3 -methylbutyrates of this invention may be used to replace or supplement other dietary sources of calcium for Irumans or other animals.
- the supplements may be used to assure adequate intake of calcium and magnesium for metabolic needs, or to prevent or treat certain disorders arising from a deficiency of these elements.
- Calcium and magnesium hydroxy-3 -methylbutyrates may be added to foods or beverages in amounts that increase mineral absorption but that do not adversely affect the flavor or texture of the food.
- the calcium and magnesium salts can be synthesized and isolated separately and subsequently blended to produce a composition with the desired ratio of calcium to magnesium.
- the precursor calcium and magnesium compounds i.e. calcium and magnesium carbonates or calcium and magnesium oxides or hydroxides
- the precursor calcium and magnesium compounds can be mixed in the desired ratio in a preliminary step and co-dissolved in an aqueous solution of 3-hydroxy- 3-methylbutyric acid to form a mixture of the calcium and magnesium hydroxy-3 - methylbutyrates of this invention.
- calcium and magnesium are present at molar ratios of from about 2: 1 to about 20: 1 (Ca:Mg).
- Example 1 74.1 grams (1.0 moles) of calcium hydroxide is added to approximately 400 ml of water with vigorous agitation, forming a sluny. 224 grams of 3-methyl-3-hydroxy-3- methylbutyric acid (1.90 moles) is introduced slowly. Following the addition of the acid, the mixture is heated to 70 degrees C. and stfrred for 90 minutes, then allowed to cool to room temperature. Insoluble particles of excess lime are removed by filtration on a uechner funnel through Whatman #4 (20 micron) filter paper.
- the filtrate a clear, non- turbid liquid, is evaporated to dryness, producing crystalline calcium 3 -hydroxy-3 -methylbu-tyrate monohydrate in virtually quantitative yield.
- a separate vessel 20.15 grams (0.50 moles) of magnesium oxide is added to approximately 200 ml of water with vigorous agitation, forming a sluny.
- 112 grams of 3- methyl-3-hydroxy-3-methylbutyric acid (0.95 moles) is introduced slowly. Following the addition of the acid, the mixture is heated to 70 degrees C. and stined for three hours, then allowed to cool to room temperature. Insoluble particles of excess magnesium oxide are removed by filtration on a Buechner funnel through Whatman #4 (20 micron) .filter paper.
- the filtrate a clear, non-turbid liquid, is evaporated to dryness, producing crystalline magnesium 3 -hydroxy-3 -methylbutyrate in virtually quantitative yield.
- the calcium and magnesium salts are ground together in a mortar and pestle to produce a mixture with a bulk density of 0.60 grams per cubic centimeter.
- Example 2 74.1 grams (1.0 moles) of calcium hydroxide and 20.15 grams (0.50 moles) of magnesium oxide are added to 500 ml of water with vigorous agitation, formiixg a sluny. 336 grams of 3-methyl-3-hydroxy-3-methylbutyric acid (2.85 moles) is introduced slowly. Following the addition of the acid, the mixture is heated to 70 degrees C. and stined for 90 minutes, then allowed to cool to room temperature. Insoluble particles of excess lime and magnesia are removed by filtration on a Buechner funnel through Whatman #4- (20 micron) filter paper.
- Example 3 The present example provides two physiological studies in -which varying amounts of calcium hydroxymethlbutyrate was administered orally in the form of capsules to volunteers, all of whom were healthy adults characterized as "physiologically normal.” Venous blood samples were drawn just before (Control) and two hours following ingestion of the capsules. (Experimental). Levels of serum calcium in the venous blood samples were measured just before (Control) and two hours after (Experimental) administration, expressed in units of milligrams per deciliter (mg/dL). In the study represented in Table 1, nine of ten subjects exhibited significantly elevated levels of serum calcium two hours after ingesting 1,000 milligrams of calcium hydroxymethylbutyrate, thereby demonstrating absorption and metabolic availability of calcium.
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Abstract
Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
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EP04719787A EP1750527A1 (fr) | 2004-03-11 | 2004-03-11 | Composition et procede d'amelioration de la biodisponibilite du calcium et du magnesium dans des complements alimentaires et des additifs alimentaires |
PCT/US2004/007452 WO2005096846A1 (fr) | 2004-03-11 | 2004-03-11 | Composition et procede d'amelioration de la biodisponibilite du calcium et du magnesium dans des complements alimentaires et des additifs alimentaires |
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PCT/US2004/007452 WO2005096846A1 (fr) | 2004-03-11 | 2004-03-11 | Composition et procede d'amelioration de la biodisponibilite du calcium et du magnesium dans des complements alimentaires et des additifs alimentaires |
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WO2005096846A1 true WO2005096846A1 (fr) | 2005-10-20 |
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PCT/US2004/007452 WO2005096846A1 (fr) | 2004-03-11 | 2004-03-11 | Composition et procede d'amelioration de la biodisponibilite du calcium et du magnesium dans des complements alimentaires et des additifs alimentaires |
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EP (1) | EP1750527A1 (fr) |
WO (1) | WO2005096846A1 (fr) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20120053240A1 (en) * | 2009-12-18 | 2012-03-01 | Metabolic Technologies, Inc. | Method of Administering beta-hydroxy-beta-methylbutyrate (HMB) |
JP2013528060A (ja) * | 2010-06-10 | 2013-07-08 | アボット・ラボラトリーズ | カルシウムhmbおよび可溶性タンパク質を含む実質的に清澄な栄養液体 |
CN108129294A (zh) * | 2018-01-24 | 2018-06-08 | 穆云 | 一种HMB-Ca生产工艺方法 |
Citations (4)
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US4992470A (en) * | 1990-02-08 | 1991-02-12 | Iowa State University Research Foundation, Inc. | Method of enhancing immune response of mammals |
WO1994017678A1 (fr) * | 1993-02-11 | 1994-08-18 | Iowa State University Research Foundation, Inc. | Procede d'augmentation de la valeur nutritive du colostrum et du premier lait de femelles porteuses de mammiferes |
US5360613A (en) * | 1992-09-16 | 1994-11-01 | Iowa State University Research Foundation, Inc. | Method of reducing blood levels of total cholesterol and low-density lipoprotein cholesterol |
US20030139354A1 (en) * | 2000-06-02 | 2003-07-24 | Herwig Buccholz | Composition for the treatment and/or the prevention of osteoporosis and/or inflammatory joint diseases |
-
2004
- 2004-03-11 EP EP04719787A patent/EP1750527A1/fr not_active Withdrawn
- 2004-03-11 WO PCT/US2004/007452 patent/WO2005096846A1/fr active Application Filing
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4992470A (en) * | 1990-02-08 | 1991-02-12 | Iowa State University Research Foundation, Inc. | Method of enhancing immune response of mammals |
US5360613A (en) * | 1992-09-16 | 1994-11-01 | Iowa State University Research Foundation, Inc. | Method of reducing blood levels of total cholesterol and low-density lipoprotein cholesterol |
WO1994017678A1 (fr) * | 1993-02-11 | 1994-08-18 | Iowa State University Research Foundation, Inc. | Procede d'augmentation de la valeur nutritive du colostrum et du premier lait de femelles porteuses de mammiferes |
US20030139354A1 (en) * | 2000-06-02 | 2003-07-24 | Herwig Buccholz | Composition for the treatment and/or the prevention of osteoporosis and/or inflammatory joint diseases |
Non-Patent Citations (1)
Title |
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KREIDER; FERREIRA; WILSON; ALMADA, INTERNATIONAL JOURNAL OF SPORTS MEDICINE, vol. 20, no. 8, 1999, GERMANY, pages 503 - 509, XP008037671 * |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20120053240A1 (en) * | 2009-12-18 | 2012-03-01 | Metabolic Technologies, Inc. | Method of Administering beta-hydroxy-beta-methylbutyrate (HMB) |
JP2013528060A (ja) * | 2010-06-10 | 2013-07-08 | アボット・ラボラトリーズ | カルシウムhmbおよび可溶性タンパク質を含む実質的に清澄な栄養液体 |
CN108129294A (zh) * | 2018-01-24 | 2018-06-08 | 穆云 | 一种HMB-Ca生产工艺方法 |
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EP1750527A1 (fr) | 2007-02-14 |
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