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WO2009079775A1 - Compositions et procédés pour supporter une fonction de protéine de choc thermique - Google Patents

Compositions et procédés pour supporter une fonction de protéine de choc thermique Download PDF

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Publication number
WO2009079775A1
WO2009079775A1 PCT/CA2008/002238 CA2008002238W WO2009079775A1 WO 2009079775 A1 WO2009079775 A1 WO 2009079775A1 CA 2008002238 W CA2008002238 W CA 2008002238W WO 2009079775 A1 WO2009079775 A1 WO 2009079775A1
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WIPO (PCT)
Prior art keywords
heat shock
composition
glutamine
proteins
creatine
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.)
Ceased
Application number
PCT/CA2008/002238
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English (en)
Other versions
WO2009079775A9 (fr
Inventor
Marvin A. Heuer
Ken Clement
Michele Molino
Joseph Macdougall
Philip Apong
Jason Peters
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Northern Innovations and Formulations Corp
Original Assignee
Northern Innovations and Formulations Corp
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
Priority claimed from US11/962,963 external-priority patent/US20090162458A1/en
Priority claimed from US11/962,948 external-priority patent/US20090163573A1/en
Application filed by Northern Innovations and Formulations Corp filed Critical Northern Innovations and Formulations Corp
Priority to CA2709343A priority Critical patent/CA2709343A1/fr
Publication of WO2009079775A1 publication Critical patent/WO2009079775A1/fr
Publication of WO2009079775A9 publication Critical patent/WO2009079775A9/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/65—Paeoniaceae (Peony family), e.g. Chinese peony
    • 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
    • A61K31/12—Ketones
    • A61K31/121—Ketones acyclic
    • 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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
    • A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
    • A61K31/385—Heterocyclic compounds having sulfur as a ring hetero atom having two or more sulfur atoms in the same ring
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/79—Schisandraceae (Schisandra family)

Definitions

  • compositions and methods for supporting heat shock protein function are provided.
  • the present invention relates to a composition and method for supporting heat shock protein function in cells.
  • the present invention relates to a composition and method comprising a combination of at least one substance for activating or supporting heat shock protein function and glutamine, which act substantially simultaneously via differing mechanisms to increase heat shock protein function in cells, particularly heat shock protein 72 (HSP72) in skeletal muscle, to facilitate increased hypertrophy as a result of exercise.
  • HSP72 heat shock protein 72
  • HSP heat shock proteins
  • HSPs are a highly conserved family of stress proteins present in all organisms from bacteria to humans.
  • Heat shock proteins function as molecular chaperones to prevent protein aggregation and facilitate the folding of nascent proteins, particularly new peptides emerging from ribosomes, not only in conditions of stress but also under normal physiological conditions.
  • Molecular chaperones recognize nascent proteins, predominantly via exposed hydrophobic residues, and bind selectively to those proteins to form relatively stable complexes. In these complexes, the protein is protected and able to fold into its functional form.
  • HSPs are categorized into families based on molecular weight. Among the many families of heat shock proteins, HSP72, the stress-inducible protein of the HSP70 family, is one of the best known endogenous factors protecting cells against tissue injury. Research of exercise-induced stress response has shown that exercise results in increased expression of HSP72 mRNA and subsequently in HSP72 protein.
  • the present invention relates to a composition and method for promoting or maintaining protein accretion in cells, particularly in skeletal muscle cells, by supporting heat shock protein function.
  • the present invention is directed towards a composition and method of promoting or maintaining protein accretion in cells, particularly in skeletal muscle cells, by supporting heat shock protein function.
  • Compositions and methods are presented that support heat shock protein function through multiple, non-mutually exclusive biological mechanisms.
  • the term 'subject' refers to mammals and non-mammals.
  • Mammals refers to any member of the Mammalia class including, but not limited to, humans; non-human primates such as chimpanzees and other apes and monkey species; farm animals such as cattle, horses, sheep, goats, and swine; domestic animals such as rabbits, dogs, and cats; laboratory animals including rodents, such as rats, mice, and guinea pigs; and the like.
  • non- mammals include, but are not limited to, birds, and the like.
  • compositions according to the present invention may be included in foods, dietary supplements, nutraceuticals, medical foods, botanical drugs, homeopathic remedies, over-the-counter drugs, prescription drugs, and compounded drugs.
  • the compositions of the present invention are provided as nutritional compositions.
  • the acceptable routes of administration compatible with the various embodiments of the present invention include those well-known in the art and include: oral, rectal, and parenteral.
  • parenteral refers to methods of administration to that region outside of the digestive tract.
  • parenteral routes of administration include, but are not limited to, subcutaneous, intramuscular or intravenous injection, and nasopharyngeal, mucosal or transdermal absorption.
  • the preferred route is administration is oral and includes acceptable oral dosage forms commonly known in the art.
  • the term 'acceptable oral dosage form' would be known by one of skill in the art to include, for example, powder beverage mixes, liquid beverages, ready-to-eat bars, hard and soft capsules, tablets, caplets, and dietary gels.
  • the dosage forms of the present invention may be provided in accordance with customary processing techniques for any of the forms mentioned above.
  • the compositions set forth in the example embodiments herein may contain any appropriate number and type of excipients, as is well known in the art.
  • Material of the present disclosure that is of plant origin may be in the form of an extract.
  • An extract as used herein, is most simply a preparation derived from a plant source. Extracts suitable for use in the present invention may be produced by extraction methods as are known and accepted in the art such as alcoholic extraction, aqueous extractions, carbon dioxide extractions, for example. Extracts may be concentrated, removing most of the solvent and/or water. Such extracts are typically liquid but may subsequently be provided as a dry powder. Plant extracts may be standardized to a known compound present in the extract.
  • a plant extract may be made from the entire plant or any part thereof.
  • Plant parts include leaves, stems, flowers, inflorescences, shoots, cotyledons, etc.
  • the various parts may be dehydrated or used fresh. Often, the plant parts are washed before processing.
  • forms of unprocessed, or raw, plants may be used in embodiments of the present invention. Such forms may be whole or part and may be fresh or dried.
  • plant extracts are used.
  • promoting or maintaining protein accretion refers to any act, process, or intervention which through any mechanism will act towards maintaining or increasing protein, particularly in skeletal muscle cells.
  • skeletal muscle protein breakdown catabolism
  • skeletal muscle protein buildup anabolism
  • the term 'heat shock proteins' is understood to encompass the mRNA species corresponding to expressly labeled heat shock proteins as well as other stress proteins, which are known to be translated into proteins. Still furthermore to be included within the term 'heat shock proteins' are factors that are known to regulate the expression or function of heat shock proteins such as heat shock transcription factor 1 (HSF1 ), a member of a family of transcription factors. When only either constitutive or inducible heat shock proteins are herein intended, they will be explicitly identified as such by reference as either constitutive or inducible.
  • HSF1 heat shock transcription factor 1
  • the phrase "supporting heat shock protein function” refers to any mechanism by which the biological role of heat shock proteins, as herein defined, is promoted, maintained, increased, enhanced, or in any way encouraged.
  • the biological mechanisms to be promoted, maintained, increased, enhance, or in any way encouraged may include, but are not limited to: transcription of DNA encoding heat shock proteins, post-transcriptional modifications, translation of RNA encoding heat shock proteins into proteins, post- translational modifications serving to activate inactive heat shock proteins, and the transport of heat shock proteins, or components, thereof, to a location of activity. Also included are any like-biological mechanism affecting known regulators of heat shock proteins such as transcriptional regulators of heat shock proteins such as heat shock factor 1 (HSF1 ), for example.
  • HSF1 heat shock factor 1
  • heat shock response facilitator refers to any act, process, or intervention which through any mechanism will act towards maintaining or increasing inducible heat shock responses.
  • a “heat shock response facilitator” will support heat shock protein function as defined above for "supporting heat shock protein function”.
  • HSP72 is the preferred mechanism through which heat shock response facilitators of the present invention act.
  • Glutamine is the most abundant amino acid found in the body and has important functions as a precursor for the synthesis of other amino acids.
  • glutamine' refers to glutamine derivatives such as esters, amides, and salts, as well as other derivatives, including derivatives having pharmacoproperties upon metabolism to an active form.
  • Glutamine derivatives herein also include molecules, which at some time post- ingestion, yield glutamine.
  • Glutamine derivatives are, for example, glutamic acid or glutamate, L-glutamine-ketoisocaproate, L-glutamine-alpha-ketoglutarate, and N-acetyl-L-glutamine.
  • Glutamine as used herein, although the present invention is not to be limited by any theoretical explanation, is herein understood to include peptides, particularly di- and tri- peptides, containing at least one glutamine residue.
  • the preferred glutamine peptide is the dipeptide alanyl- glutamine.
  • glutamine in a composition, will act to increase the production heat shock proteins, act as a coactivator, and modulate transcriptional regulatory machinery in the promoter region of the gene.
  • Enhanced expression of heat shock proteins will act to increase protein accretion via increased stabilization of nascent proteins.
  • the increased expression of chaperone proteins in working muscle stabilizes the large number of new proteins being synthesized by working muscle. This in turn leads to increased accumulation of contractile protein, i.e. muscle hypertrophy.
  • a serving of the present composition comprises from about 1 mg to about 1.5 g of glutamine. More preferably, a serving of the present composition comprises from about 1 mg to about 1 .0 g of glutamine. A serving of the present composition most preferably comprises from about 1 mg to about 750 mg of glutamine.
  • the preferred derivative of glutamine is the dipeptide alanyl- glutamine.
  • Schisandrin B is a dibenzocyclooctadiene compound that is isolated from Schisandrae chinensis. Schisandrin B has been used to enhance the detoxification of xenobiotics in the liver and assist in liver regeneration. Recent studies have shown that schisandrin B can protect various organs from free- radical induced damage. [0029] In a study using mice, administration of schisandrin B was shown to increase the production of HSP70. Treatment with schisandrin B produces oxidants via cytochrome p-450 metabolism, which act as mild stressors to induce HSP70 production.
  • HSP72 schisandrin B
  • Enhanced expression of HSP72 will act to increase protein accretion via increased stabilization of nascent proteins.
  • the increased expression of chaperone proteins, i.e. HSP72, in working muscle is important in order to stabilize the large number of new proteins being synthesized by working muscle, leading to increased accumulation of contractile protein, i.e. muscle hypertrophy.
  • a serving of the present composition comprises Schisandrae chinensis supplying schisandrin B.
  • the Schisandrae chinensis is in the form of an extract in the amount of from about 1 mg to about 500 mg. More preferably, a serving of the present composition comprises from about 10 mg to about 250 mg of Schisandrae chinensis.
  • a serving of the present composition most preferably comprises from about 50 mg to about 150 mg of Schisandrae chinensis.
  • the amount of schisandrin B in a serving to the present invention is from about 0.001 mg to about 5 mg.
  • Paeoniflorin is a major constituent of peony plants, such as Paeonia lactoflora, P. suffruticosa, P. obovata, and P. veitchii.
  • the roots of peony plants have commonly been used in Chinese medicine to reduce fever and pain, stop bleeding, prevent infection, and as an antispasmodic.
  • 'paeoniflorin' refers to paeoniflorin derivatives such as esters, amides, and salts, as well as other derivatives, including derivatives having pharmacoproperties upon metabolism to an active form.
  • Paeoniflorin derivatives herein also include molecules, which at some time post- ingestion, yield paeoniflorin.
  • paeoniflorin in a composition, will act to increase the expression of heat shock proteins, particularly HSP72, via directly activating HSF1.
  • Paeoniflorin or derivatives of paeoniflorin will enhance the expression of heat shock proteins by increasing the phosphorylation and DNA-binding ability of HSF1 thereby facilitating the induction of heat shock proteins.
  • Enhanced expression of heat shock proteins, particularly HSP72 will act to increase protein accretion via increased stabilization of nascent proteins.
  • the increased expression of chaperone proteins, i.e. HSP72, in working muscle is important in order to stabilize the large number of new proteins being synthesized by working muscle, leading to increased accumulation of contractile protein, i.e. muscle hypertrophy.
  • a serving of the present composition comprises Paeonia species plant containing paeoniflorin.
  • the Paeonia species plant is in the form of an extract, the extract preferably comprising from about 1 mg to about 300 mg of paeoniflorin. More preferably, a serving of the present composition comprises from about 1 mg to about 150 mg of paeoniflorin. A serving of the present composition most preferably comprises from about 1 mg to about 75 mg of paeoniflorin.
  • Geranylgeranylacetone is an acyclic polyisoprenoid that has been used to protect gastric mucosa. Geranylgeranylacetone has been shown to activate transcription factors, particularly heat shock transcription factor HSF1 , which are able to bind to DNA and induce transcription. HSF1 is normally suppressed since it is typically bound to the C-domain of constitutively active HSP70. Geranylgeranylacetone is able to bind to the C-domain of the HSP70 thereby causing HSF1 to dissociate. HSF1 is now able to undergo trimerization and be translocated to the nucleus, where it binds to the heat shock-responsive element in the promoter region of inducible HSP70 (i.e. HSP72) genes.
  • HSF1 heat shock transcription factor
  • Non-differentiated myoblasts are a small population of quiescent muscle precursor cells that occupy a "satellite" position immediately outside of muscle fibers. They are normally maintained in a quiescent state and become activated to fulfill roles of routine maintenance, repair and hypertrophy. Satellite cells are thought to be muscle-specific stem cells which are capable of producing large numbers of differentiated progeny as well as being capable of self-renewal. Such that satellite cells can fulfill their biological role, they must become activated, proliferate, differentiate and fuse to existing muscle cells. In this way, multinucleate muscle fibers are maintained or increased in size in response to stimuli.
  • 'geranylgeranylacetone refers to geranylgeranylacetone derivatives such as esters, amides, and salts, as well as other derivatives, including derivatives having pharmacoproperties upon metabolism to an active form.
  • Geranylgeranylacetone derivatives herein also include molecules, which at some time post-ingestion, yield geranylgeranylacetone.
  • a serving of the present composition comprises from about 1 mg to about 300 mg of geranylgeranylacetone. More preferably, a serving of the present composition comprises from about 25 mg to about 150 mg of geranylgeranylacetone. A serving of the present composition most preferably comprises from about 25 mg to about 75 mg of geranylgeranylacetone.
  • Alpha lipoic acid is a co-enzyme found in the cellular energy-producing structures, the mitochondria. Moreover, alpha lipoic acid works in synergy with vitamins C and E as an antioxidant in both water- and fat- soluble environments. As used herein, derivatives of alpha lipoic acid also includes derivatives of alpha lipoic acid such as esters, and amides, as well as other derivatives, including derivatives that become active upon metabolism.
  • alpha lipoic acid has been demonstrated to have efficacy as a protective against diabetic neuropathy; a benefit mediated by stimulating a heat shock response including HSF1 and HSP72.
  • alpha lipoic acid' refers to alpha lipoic acid derivatives such as esters, amides, and salts, as well as other derivatives, including derivatives having pharmacoproperties upon metabolism to an active form.
  • Alpha lipoic acid derivatives herein also include molecules, which at some time post-ingestion, yield alpha lipoic acid.
  • Alpha lipoic acid derivatives are, for example, calcium alpha lipoic acid, sodium alpha lipoic acid, and alpha lipoic acid tromethamine.
  • alpha lipoic acid or derivatives of alpha lipoic acid in a composition will act to increase the expression of heat shock proteins, particularly HSF1 and HSP72.
  • Enhanced expression of heat shock proteins, particularly HSP72 will act to increase protein accretion via increased stabilization of nascent proteins.
  • the increased expression of chaperone proteins, i.e. HSP72, in working muscle is important in order to stabilize the large number of new proteins being synthesized by working muscle, leading to increased accumulation of contractile protein, i.e. muscle hypertrophy.
  • a serving of the present composition comprises from about 1 mg to about 250 mg of alpha lipoic acid or derivatives of alpha lipoic acid. More preferably, a serving of the present composition comprises from about 1 mg to about 100 mg of alpha lipoic acid or derivatives of alpha lipoic acid. A serving of the present composition most preferably comprises from about 10 mg to about 50 mg of alpha lipoic acid or derivatives of alpha lipoic acid.
  • Creatine is a naturally occurring amino acid derived from the amino acids glycine, arginine, and methionine. Although it is found in meat and fish, it is also synthesized by humans. Creatine is predominantly used as a fuel source in muscle. About 65% of creatine is stored in muscle as phosphocreatine (creatine bound to a Phosphate molecule). Muscular contractions are fueled by the dephosphorylation of adenosine triphosphate (ATP) to produce adenosine diphosphate (ADP) and without a mechanism to replenish ATP stores, the supply of ATP would be rapidly consumed.
  • ATP adenosine triphosphate
  • ADP adenosine diphosphate
  • Phosphocreatine which is generated from the phosphorylation of creatine by the enzyme creatine kinase, serves as a major source of phosphate from which ADP is regenerated to ATP.
  • HSP70 family member HSC70 is present in an inactive polymerized form that upon stimulation de-polymerized into predominantly more active monomeric form.
  • Creatine Kinase or phosphocreatine contributes to the conversion of polymerized HSC70 to monomeric HSC70.
  • Creatine' refers to derivatives of creatine such as esters, amides, and salts, as well as other derivatives, including derivatives having pharmacoproperties upon metabolism to an active form. Creatine derivatives herein also include molecules, which at some time post-ingestion, yield creatine. Creatine derivatives are, for example, creatine ethyl ester, creatine alpha ketoglutarate creatine pyroglutamate, creatine pyruvate, and creatine taurinate.
  • a serving of the present composition comprises from about 0.5 g to about 5 g of creatine or derivative of creatine. More preferably, a serving of the present composition comprises from about 1 g to about 3.5 g of creatine or derivative of creatine. A serving of the present composition most preferably comprises from about 1 .5 g to about 3 g of creatine or derivative of creatine.
  • the composition of the present invention may be administered in a dosage form having controlled release characteristics, e.g. time-release.
  • the controlled release may be in forms such as a delayed release of active constituents, gradual release of active constituents, or prolonged release of active constituents.
  • active constituents release strategies extend the period of bioavailability or target a specific time window for optimal bioavailability.
  • the composition may be administered in the form of a multicompartment capsule which combines both immediate release and time-release characteristics. Individual components of the composition may be contained in differential compartments of such a capsule such that the specific components may be released rapidly while others are time-dependently released. Alternatively, a uniform mixture of the various components of the present invention may be divided into both immediate release and time-release compartments to provide a multi-phasic release profile.
  • the composition may be consumed in any form.
  • the dosage form of the composition may be provided as, e.g., a powder beverage mix, a liquid beverage, a ready-to-eat bar or drink product, a capsule, a liquid capsule, a soft-gel capsule, a tablet, a caplet, or as a dietary gel.
  • the preferred dosage form of the present invention is as a caplet.
  • compositions may be provided in accordance with customary processing techniques for herbal and compositions in any of the forms mentioned above.
  • compositions set forth in the example embodiment herein may contain any appropriate number and type of excipients, as is well known in the art.
  • compositions or those similarly envisioned by one of skill in the art may be utilized in methods to promote or maintain protein accretion in cells, particularly in skeletal muscle cells, by supporting heat shock protein function, thereby increasing hypertrophy as a result of exercise.
  • the present invention provides for compositions and methods for promoting or maintaining protein accretion in cells, particularly in skeletal muscle cells, by supporting heat shock protein function, particularly inducible heat shock proteins.
  • Components of compositions and methods provided in accordance with this embodiment are directed towards inducible heat shock proteins which are modulated, in part, by HSF1.
  • HSF1 inducible heat shock proteins
  • glutamine or derivative of glutamine which act via mechanism independent of HSF1 , together with at least one additional component known to support inducible heat shock protein function via HSF1 , will act to promote or maintain protein accretion in cells, particularly in skeletal muscle cells via synergistic and distinct mechanisms.
  • the present invention provides for compositions and methods for promoting or maintaining protein accretion in cells, particularly in skeletal muscle cells, by supporting both inducible and constitutive heat shock protein function.
  • creatine or a derivative of creatine is included to support the activity of constitutive heat shock proteins.
  • compositions of the present invention include formulations further comprising additional active ingredients and/or inactive ingredients, including solvents, diluents, suspension aids, thickening or emulsifying agents, sweeteners, flavorings, preservatives, solid binders, lubricants and the like, as suited to the particular dosage form desired.
  • additional active ingredients and/or inactive ingredients including solvents, diluents, suspension aids, thickening or emulsifying agents, sweeteners, flavorings, preservatives, solid binders, lubricants and the like.
  • a composition comprising the following ingredients per serving are prepared for consumption as four caplets, to be taken twice daily:
  • a composition comprising the following ingredients per serving are prepared for consumption as five caplets, to be taken twice daily:
  • a composition comprising the following ingredients per serving are prepared for consumption as six caplets, to be taken twice daily with one serving being taken prior to exercise:
  • a composition comprising the following ingredients per serving are prepared for consumption as three caplets, to be taken twice daily with one serving being taken prior to exercise:

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Abstract

L'invention porte sur des compositions et des procédés pour favoriser ou maintenir l'accrétion de protéines dans des cellules, en particulier dans des cellules du muscle squelettique, par support d'une fonction de protéine de choc thermique. Les compositions comprennent de la glutamine et des composants supplémentaires dirigés pour améliorer l'activité de protéines de choc thermique.
PCT/CA2008/002238 2007-12-21 2008-12-18 Compositions et procédés pour supporter une fonction de protéine de choc thermique Ceased WO2009079775A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CA2709343A CA2709343A1 (fr) 2007-12-21 2008-12-18 Compositions et procedes pour supporter une fonction de proteine de chocthermique

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US11/962,963 US20090162458A1 (en) 2007-12-21 2007-12-21 Compositions and methods for inducing the expression of heat shock proteins
US11/962,948 2007-12-21
US11/962,963 2007-12-21
US11/962,948 US20090163573A1 (en) 2007-12-21 2007-12-21 Compositions and methods for enhancing protein accretion in skeletal muscle

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WO2009079775A1 true WO2009079775A1 (fr) 2009-07-02
WO2009079775A9 WO2009079775A9 (fr) 2009-08-20

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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007005394A1 (fr) * 2005-07-05 2007-01-11 Mitralign, Inc. Ancrage de tissu, systeme et procedes d'ancrage l'utilisant
WO2007009395A1 (fr) * 2005-07-22 2007-01-25 The Hong Kong University Of Science And Technology Preparation de schisandrine b

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007005394A1 (fr) * 2005-07-05 2007-01-11 Mitralign, Inc. Ancrage de tissu, systeme et procedes d'ancrage l'utilisant
WO2007009395A1 (fr) * 2005-07-22 2007-01-25 The Hong Kong University Of Science And Technology Preparation de schisandrine b

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
CURI R. ET AL.: "Molecular mechanisms of glutamine action", JOURNAL OF CELLULAR PHYSIOLOGY, vol. 204, 2005, pages 392 - 401 *
LEHMKUHL M. ET AL.: "The effects of 8 weeks of creatine monohydrate and glutamine supplementation on body composition and performance measures.", JOURNAL OF STRENGTH AND CONDITIONING RESEARCH, vol. 17, no. 3, 2003, pages 425 - 438 *
WISCHMEYER P. E.: "Glutamine: the first clinically relevant pharmacological regulator of heat shock protein expression?", CURRENT OPINION IN CLINICAL NUTRITION AND METABOLIC CARE, vol. 9, 2006, pages 201 - 206 *
YAN D. ET AL.: "Paeoniflorin, a novel heat shock protein-inducing compound", CELL STRESS AND CHAPERONES, vol. 9, no. 4, 2004, pages 378 - 389 *

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WO2009079775A9 (fr) 2009-08-20

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