WO2020263229A1 - STABILITÉ DE LA VITAMINE D DANS DU β-HYDROXY-β-MÉTHYLBUTYRATE (HMB) - Google Patents

STABILITÉ DE LA VITAMINE D DANS DU β-HYDROXY-β-MÉTHYLBUTYRATE (HMB) Download PDF

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Publication number
WO2020263229A1
WO2020263229A1 PCT/US2019/038948 US2019038948W WO2020263229A1 WO 2020263229 A1 WO2020263229 A1 WO 2020263229A1 US 2019038948 W US2019038948 W US 2019038948W WO 2020263229 A1 WO2020263229 A1 WO 2020263229A1
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WO
WIPO (PCT)
Prior art keywords
vitamin
hmb
formulation
hmbfa
composition
Prior art date
Application number
PCT/US2019/038948
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English (en)
Inventor
John Rathmacher
Martin PUPURA
Original Assignee
Metabolic Technologies, Inc.
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 Metabolic Technologies, Inc. filed Critical Metabolic Technologies, Inc.
Priority to BR112020026621-3A priority Critical patent/BR112020026621A2/pt
Priority to CA3105039A priority patent/CA3105039A1/fr
Priority to AU2019453386A priority patent/AU2019453386A1/en
Priority to EP19935709.6A priority patent/EP3836803A4/fr
Priority to PCT/US2019/038948 priority patent/WO2020263229A1/fr
Priority to KR1020217010076A priority patent/KR20220050082A/ko
Priority to JP2020572417A priority patent/JP7520731B2/ja
Priority to CN201980057166.8A priority patent/CN113056206A/zh
Priority to SG11202012984YA priority patent/SG11202012984YA/en
Publication of WO2020263229A1 publication Critical patent/WO2020263229A1/fr
Priority to CONC2021/0000763A priority patent/CO2021000763A2/es

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Classifications

    • 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
    • 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
    • A23L33/15—Vitamins
    • A23L33/155—Vitamins A or D
    • 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
    • A61K31/59—Compounds containing 9, 10- seco- cyclopenta[a]hydrophenanthrene ring systems
    • 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
    • A61K31/59—Compounds containing 9, 10- seco- cyclopenta[a]hydrophenanthrene ring systems
    • A61K31/593—9,10-Secocholestane derivatives, e.g. cholecalciferol, i.e. vitamin D3
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/12—Carboxylic acids; Salts or anhydrides thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
    • A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
    • A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/46—Ingredients of undetermined constitution or reaction products thereof, e.g. skin, bone, milk, cotton fibre, eggshell, oxgall or plant extracts
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4841—Filling excipients; Inactive ingredients
    • A61K9/4858—Organic compounds
    • 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

Definitions

  • the present invention relates to a composition comprising b - h ydro x y- b - met h y 1 b u t y at c (HMB) and vitamin D.
  • the present invention relates to compositions containing HMB and vitamin D and methods of stabilizing vitamin D when vitamin D is combined with acidic compositions.
  • Vitamin D has classically been associated with calcium and phosphorous metabolism and bone strength. Until recently, an adequate vitamin D level has been defined using the vitamin D deficiency disease rickets. In recent years vitamin D has been found to have more widespread effects on metabolism other than on calcium and bone structure. Low vitamin D status has been associated with the following: osteoporosis, falls, Type I diabetes, cancer, autoimmune disease, hypertension, periodontal disease, multiple sclerosis, susceptibility/poor response to infection 1 .
  • Vitamin D deficiency is a problem worldwide, as sun exposure has decreased and the use of sunscreen has increased the problem has only been exacerbated. Diet and health can also be mitigating factors on vitamin D levels. Subjects with fat malabsorption syndromes, chronic diseases, on certain medications, or obesity have a higher risk for vitamin D deficiency 2 . Skin tone can also have an effect, as the darker the skin tone, the more time required to produce the same amount of vitamin D. Therefore supplementation is the best way to increase vitamin D and decrease deficiency 2 . Cholecalciferol (Vitamin D3) can be synthesized by humans thru irradiation of 7-dehydrochloesterol in the skin or extracted from lanolin.
  • Vitamin D is only contained in few foods and often in small amounts, fortification of foods or the supplementation through dietary supplements is necessary. Since the 1930, food and beverage manufactures started fortify foods such as, milk, bread, hot dogs, sodas and even beer. Vitamin D is also available in dietary supplements.
  • Vitamin D3 is a large and hydrophobic sterol molecule with poor water solubility that is easily degraded by light and oxygen.
  • the stability of vitamin D is excellent in the absence of water, light, acidity, and at low temperatures 3 .
  • the 5,6-trans-isomer and isotachysterol can form when exposed to acid and light 4 .
  • Vitamin is less susceptible to oxidation than vitamin A but oxidation of Vitamin D can be the predominant route for decomposition at the conjugated double bond system at 5,6 and 7,8 position of the secosteroid structure 3 .
  • Vitamin D is quite stable in processes used for fluid milk production or in the production of non-fat dry milk 4 . No significant loss were observed with steam injected at 95°C 5 . More recently, Vitamin D has been found to be stable in orange juice which has a pH of approximately 4 6 . The bioavailability was equally available as when consumed in capsule forms. However, long-term stability of Vitamin D3 at pH of 4 and lower had not been determined.
  • HMB Alpha-ketoisocaproate is the first major and active metabolite of leucine.
  • a minor product of KIC metabolism is b- ⁇ tg ⁇ ocg-b- methyl butyrate (HMB).
  • HMB has been found to be useful within the context of a variety of applications. Specifically, in U.S. Patent No. 5,360,613 (Nissen), HMB is described as useful for reducing blood levels of total cholesterol and low- density lipoprotein cholesterol. In U.S. Patent No. 5,348,979 (Nissen et al.), HMB is described as useful for promoting nitrogen retention in humans. U.S. Patent No. 5,028,440 (Nissen) discusses the usefulness of HMB to increase lean tissue development in animals.
  • HMB is described as effective in enhancing the immune response of mammals.
  • U.S. Patent No. 6,031,000 (Nissen et al.) describes use of HMB and at least one amino acid to treat disease-associated wasting.
  • HMB a-ketoisocaproate
  • KIC a-ketoisocaproate
  • HMB is superior to leucine in enhancing muscle mass and strength.
  • the optimal effects of HMB can be achieved at 3.0 grams per day when given as calcium salt of HMB, or 0.038g/kg of body weight per day, while those of leucine require over 30.0 grams per day.
  • HMB Once produced or ingested, HMB appears to have two fates.
  • the first fate is simple excretion in urine. After HMB is fed, urine concentrations increase, resulting in an approximate 20-50% loss of HMB to urine.
  • Another fate relates to the activation of HMB to HMB-CoA.
  • HMB-CoA Once converted to HMB-CoA, further metabolism may occur, either dehydration of HMB-CoA to MC-CoA, or a direct conversion of HMB-CoA to HMG-CoA, which provides substrates for intracellular cholesterol synthesis.
  • HMB is incorporated into the cholesterol synthetic pathway and could be a source for new cell membranes that are used for the regeneration of damaged cell membranes.
  • Human studies have shown that muscle damage following intense exercise, measured by elevated plasma CPK (creatine phosphokinase), is reduced with HMB supplementation within the first 48 hrs. The protective effect of HMB lasts up to three weeks with continued daily use.
  • HMB human levothyroxine
  • CaHMB calcium HMB
  • HMBFA HMB free acid
  • HMB has been shown to be effective for increasing muscle mass, increasing strength, and improving muscle function. These effects are most significant when vitamin D levels in the blood are sufficient, which has been further defined to be around at least 25 ng/ml or higher.
  • HMBFA free acid form
  • Vitamin D levels in compositions the solely comprise HMBFA and Vitamin D degrade significantly over time.
  • HMBFA may be a more effective delivery form of HMB in terms of effect on muscle
  • Vitamin D it is desirable to combine HMBFA with Vitamin D in order to maximize the efficacy of HMB.
  • Vitamin D is stabilized against degradation in acidic formulations, including formulations containing HMB with the inclusion of at least one stabilization excipient.
  • One object of the present invention is to provide a composition containing HMBFA and vitamin D that is stable.
  • Another object of the present invention is to provide a composition containing HMBFA and vitamin D, wherein the vitamin D does not decrease significantly over time.
  • the present invention intends to overcome the difficulties encountered heretofore. To that end, a composition comprising HMBFA and vitamin D is provided.
  • Figure 1 depicts the stability of Vitamin D in Formula 7.
  • Figure 2 depicts the stability of Vitamin D in Formula 10.
  • Figure 3 depicts the stability of Vitamin D in Formula 11.
  • formulations for improving the stability of Vitamin D when Vitamin D is combined with HMB improves the stability of Vitamin D.
  • additional components that act as a stabilizing excipient in formulations of HMB and Vitamin D improves the stability of Vitamin D.
  • the stabilizing excipients include but are not limited to EDTA, butylated hydroxytoluene (BHT), carnitine, rosemary extract, camosolic acid, and/or sorbic acid.
  • BHT butylated hydroxytoluene
  • the inclusion of at least one of these additives in formulations containing HMB and Vitamin D results in minimal loss of Vitamin D in the formulation over time.
  • the addition of an additive to a formulation containing Vitamin D combined with an acidic components such as HMB FA), stabilizes the Vitamin D against degradation over time.
  • Vitamin D is intended to include vitamins D2, D3, and D4 and related analogs.
  • Stabilizing excipients that are encompassed by this invention include EDTA or antioxidants including BHT, BHA, ascorbyl palmitate, propyl gallate, vitamin E, ascorbic acid, cysteine, methionine, monothiogylcerol, sodium thiosulphate, or sulfites.
  • Vitamin D has been found to degrade significantly over time when Vitamin D is included in acidic formulations. As it is desirable to combine Vitamin D with HMBFA in low pH, acidic formulations, the need exists for stable formulations of HMB and Vitamin D. It was
  • a stabilizing excipient such as EDTA, BHT, carnitine, rosemary extract, camosolic acid, and/or sorbic acid results in a formulation in which Vitamin D is stabilized against degradation over time.
  • HMB utilized in clinical studies and marketed as an ergogenic aid has been in the calcium salt form.
  • HMB in the free acid form (HMBFA) has been developed, which was shown to be more rapidly absorbed than CaHMB, resulting in quicker and higher peak serum HMB levels and improved serum clearance to the tissues.
  • the pH of HMBFA is ⁇ 3.
  • HMB free acid may therefore be a more efficacious method of administering HMB than the calcium salt form, particularly when administered directly preceding intense exercise.
  • HMB in any form.
  • HMB in any form may be incorporated into the delivery and/or administration form in a fashion so as to result in a typical dosage range of about 0.5 grams HMB to about 30 grams HMB.
  • Any suitable dose of HMB can be used within the context of the present invention.
  • the composition When the composition is administered orally in an edible form, the composition is preferably in the form of a dietary supplement, foodstuff or pharmaceutical medium, more preferably in the form of a dietary supplement or foodstuff.
  • a dietary supplement or foodstuff comprising the composition can be utilized within the context of the present invention.
  • the composition regardless of the form (such as a dietary supplement, foodstuff or a pharmaceutical medium), may include amino acids, vitamins, proteins, peptides, carbohydrates, fats, sugars, minerals and/or trace elements.
  • the composition will normally be combined or mixed in such a way that the composition is substantially uniformly distributed in the dietary supplement or foodstuff.
  • the composition can be dissolved in a liquid, such as water.
  • composition of the dietary supplement may be a powder, a gel, a liquid or may be tabulated or encapsulated, for instance in a softgel formulation.
  • the following examples examined the stability of Vitamin D when combined with HMB in a softgel or capsule delivery form.
  • the invention is not limited to any particular delivery form, and can include combinations of HMB and Vitamin D in liquid formulations, gels and foodstuffs.
  • composition is combined with a suitable pharmaceutical carrier, such as dextrose or sucrose.
  • composition of the pharmaceutical medium can be intravenously administered in any suitable manner.
  • administration via intravenous infusion the administration via intravenous infusion
  • composition is preferably in a water-soluble non-toxic form.
  • Intravenous administration is particularly suitable for hospitalized patients that are undergoing intravenous (IV) therapy.
  • the composition can be dissolved in an IV solution (e.g., a saline or glucose solution) being administered to the patient.
  • IV solution e.g., a saline or glucose solution
  • the composition can be added to nutritional IV solutions, which may include amino acids, glucose, peptides, proteins and/or lipids.
  • the amounts of the composition to be administered intravenously can be similar to levels used in oral administration. Intravenous infusion may be more controlled and accurate than oral administration.
  • Methods of calculating the frequency by which the composition is administered are well- known in the art and any suitable frequency of administration can be used within the context of the present invention (e.g., one 6 g dose per day or two 3 g doses per day) and over any suitable time period (e.g., a single dose can be administered over a five minute time period or over a one hour time period, or, alternatively, multiple doses can be administered over an extended time period).
  • the composition can be administered over an extended period of time, such as weeks, months or years.
  • Any suitable dose of HMB and vitamin D can be used within the context of the present invention. Methods of calculating proper doses are well known in the art.
  • administering or administration includes providing a composition to a mammal, consuming the composition and combinations thereof.
  • Vitamin D3 (100 HP, BASF, Denmark) in HMB FA plus Choline Chloride (Acros Organics)
  • Vitamin D 3 (100 HP, BASF, Denmark) in HMB FA plus Betaine (Sigma-Aldrich)
  • Vitamin D3 was measured by HPLC by Heartland assays.
  • FIGs 1, 2, and 3 illustrate the stability of Vitamin D3 in formula 7, 10, and 11, respectively.
  • HMBFA TSI lot 12111036
  • K2CO3 potassium carbonate
  • a stir bar was added and the mixture was stirred for 60 h.
  • the resulting pH was approximately 4.5.
  • the reaction may be accelerated by mixing water (35 g) with potassium carbonate (37) g and then adding HMBFA (400 g).
  • the EDTA used in formula 7 and formula 8 was Dow’s disodiumEDTA (VerseneTM NA Chelating Agent, Dow Chemical, Midland, MI.
  • disodium EDTA was replaced with the preservative BHT.
  • formula 11 also contained the antioxidant NovaSol rosemary extract which is high in camosolic acid and the preservative NovaSol DS/4 (sorbic acid).

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
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  • Polymers & Plastics (AREA)
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  • Food Science & Technology (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
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  • Bioinformatics & Cheminformatics (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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  • Diabetes (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Coloring Foods And Improving Nutritive Qualities (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne une composition comprenant une formulation acide contenant du β-hydroxy-β-méthylbutyrate (HMB), de préférence sous la forme d'acide libre, de la vitamine D et un excipient de stabilisation, la vitamine D étant stabilisée contre la dégradation.
PCT/US2019/038948 2018-06-25 2019-06-25 STABILITÉ DE LA VITAMINE D DANS DU β-HYDROXY-β-MÉTHYLBUTYRATE (HMB) WO2020263229A1 (fr)

Priority Applications (10)

Application Number Priority Date Filing Date Title
BR112020026621-3A BR112020026621A2 (pt) 2018-06-25 2019-06-25 Formulação estável, e, métodos para estabilizar vitamina d em uma formulação acídica e para minimizar a degradação de vitamina d em uma formulação acídica.
CA3105039A CA3105039A1 (fr) 2019-06-25 2019-06-25 Stabilite de la vitamine d dans .beta.-hydroxy .beta.-methylbutyrate (hmb)
AU2019453386A AU2019453386A1 (en) 2018-06-25 2019-06-25 Stability of vitamin D in beta-hydroxy- beta-methylbutyrate (HMB)
EP19935709.6A EP3836803A4 (fr) 2018-06-25 2019-06-25 Stabilité de la vitamine d dans du beta-hydroxy-beta-méthylbutyrate (hmb)
PCT/US2019/038948 WO2020263229A1 (fr) 2019-06-25 2019-06-25 STABILITÉ DE LA VITAMINE D DANS DU β-HYDROXY-β-MÉTHYLBUTYRATE (HMB)
KR1020217010076A KR20220050082A (ko) 2019-06-25 2019-06-25 β-하이드록시-β메틸부티레이트(HMB)에서의 비타민 D의 안정성
JP2020572417A JP7520731B2 (ja) 2019-06-25 2019-06-25 β－ヒドロキシ－β－メチルブチレート（ＨＭＢ）中のビタミンＤの安定性
CN201980057166.8A CN113056206A (zh) 2019-06-25 2019-06-25 维生素D在β-羟基-β-甲基丁酸(HMB)中的稳定性
SG11202012984YA SG11202012984YA (en) 2019-06-25 2019-06-25 STABILITY OF VITAMIN D IN ß-HYDROXY- ß-METHYLBUTYRATE (HMB)
CONC2021/0000763A CO2021000763A2 (es) 2018-06-25 2021-01-25 Estabilidad de la vitamina d en b-hidroxi- b-metilbutirato(hmb)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/US2019/038948 WO2020263229A1 (fr) 2019-06-25 2019-06-25 STABILITÉ DE LA VITAMINE D DANS DU β-HYDROXY-β-MÉTHYLBUTYRATE (HMB)

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WO2020263229A1 true WO2020263229A1 (fr) 2020-12-30

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PCT/US2019/038948 WO2020263229A1 (fr) 2018-06-25 2019-06-25 STABILITÉ DE LA VITAMINE D DANS DU β-HYDROXY-β-MÉTHYLBUTYRATE (HMB)

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JP (1) JP7520731B2 (fr)
KR (1) KR20220050082A (fr)
CN (1) CN113056206A (fr)
AU (1) AU2019453386A1 (fr)
CA (1) CA3105039A1 (fr)
SG (1) SG11202012984YA (fr)
WO (1) WO2020263229A1 (fr)

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060019933A1 (en) * 2004-07-22 2006-01-26 David Boardman Process for preparing stabilized vitamin D
US20140037797A1 (en) * 2011-02-07 2014-02-06 Abbott Laboratories Nutritional products comprising beta-hydroxy-beta-methylbutyrate

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6849613B2 (en) * 2001-08-29 2005-02-01 Kedar N. Prasad Multiple antioxidant micronutrients
US20100178369A1 (en) * 2009-01-15 2010-07-15 Nicole Lee Arledge Antioxidant-stabilized concentrated fish oil
CN102512655B (zh) * 2011-11-30 2013-10-30 北京康比特体育科技股份有限公司 左旋肉碱组合物和制剂，及其制备方法和应用
WO2015137965A1 (fr) * 2014-03-14 2015-09-17 Metabolic Technologies, Inc. Liquides et produits alimentaires contenant du bêta-hydroxy-bêta-méthylbutyrate (hmb) sous forme d'acide libre
US11918679B2 (en) * 2016-03-30 2024-03-05 Symrise Ag Active mixure

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060019933A1 (en) * 2004-07-22 2006-01-26 David Boardman Process for preparing stabilized vitamin D
US20140037797A1 (en) * 2011-02-07 2014-02-06 Abbott Laboratories Nutritional products comprising beta-hydroxy-beta-methylbutyrate

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CN113056206A (zh) 2021-06-29
AU2019453386A1 (en) 2021-02-18
JP7520731B2 (ja) 2024-07-23
CA3105039A1 (fr) 2020-12-30
SG11202012984YA (en) 2021-01-28
KR20220050082A (ko) 2022-04-22
JP2022545299A (ja) 2022-10-27

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