WO2007034401A1 - Amino acid and its uses - Google Patents

Amino acid and its uses Download PDF

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Publication number
WO2007034401A1
WO2007034401A1 PCT/IB2006/053353 IB2006053353W WO2007034401A1 WO 2007034401 A1 WO2007034401 A1 WO 2007034401A1 IB 2006053353 W IB2006053353 W IB 2006053353W WO 2007034401 A1 WO2007034401 A1 WO 2007034401A1
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WO
WIPO (PCT)
Prior art keywords
free
proline
organism
supplement
effective amount
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/IB2006/053353
Other languages
French (fr)
Inventor
Andre Vosloo
Leon Van Rensburg
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.)
North West University
Original Assignee
North West University
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 North West University filed Critical North West University
Priority to AU2006293520A priority Critical patent/AU2006293520A1/en
Priority to EP06809330A priority patent/EP1931333A1/en
Priority to US11/992,178 priority patent/US20100099734A1/en
Publication of WO2007034401A1 publication Critical patent/WO2007034401A1/en
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
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/401—Proline; Derivatives thereof, e.g. captopril
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K20/00—Accessory food factors for animal feeding-stuffs
    • A23K20/10—Organic substances
    • A23K20/142—Amino acids; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/17—Amino acids, peptides or proteins
    • A23L33/175—Amino acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/12—Drugs for disorders of the metabolism for electrolyte homeostasis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • 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

  • This invention relates to an amino acid and its uses. This invention further relates to compositions and methods for treating humans and animals and the use of such an amino acid.
  • Water is an essential molecule for sustaining life and an animal's ability to cope with changes in its internal water content is paramount for its survival.
  • Osmosis usually occurs in a saline environment, such as sea water, or by extracellular freezing, or from diseases such as diabetes or hyperglycemia, causing osmotic imbalances.
  • Taurine is a sulfur-based, non-protein amino acid and is known to act as an osmolyte in cases of dehydration. Taurine is also said to be cytoprotective by acting as an antioxidant, a calcium modulator, a synaptic neuromodulator and a membrane stabilizer. For this reason, it is known to include taurine in energy drinks for human consumption.
  • L-proline has thus far not been recognized as an antioxidant or free radical scavenger.
  • L-proline concentration increases when freshwater and brackish water animals are exposed to hyperosmotic stress. It is also known that L-profine is released from cells of Australian Abalone (Haliotis roei) to maintain cell volume at low saiinities. L-proline is therefore generally considered as an intracellular osmolyte of animal cells, but to date, most studies were focused on the intracellular production and secretion of L- proline in cases where the organism is placed under hyperosmotic stress.
  • EP 1 514 554 A1 discloses a composition based on natural substances, useful in the maintenance of the correct skin hydration and in the prevention and/or the treatment of the effects of skin ageing, in particular wrinkles, characterized in that it comprises in combination ceramides in the form of extract of Oryza sativa; fish cartilage hydrolysate; and one or more amino acids selected from L-proline, L-!eusine 7 L-valine and L-cysteine.
  • This composition comprises between 20 to 200 mg, preferably 40 mg per day of these amino acids.
  • a disadvantage of this composition is that the levels of L- proline that are suggested are insufficient to elevate the concentration of cellular free L-proline to the extent that it restricts dehydration and reduction in free radical concentration in the user, when exposed to water and heat stress.
  • a first aspect of the invention there is provided use of an effective amount of free L-proline in the preparation of a supplement for supplementing the concentration of free cellular L-proline in an organism, for restricting dehydration of such an organism.
  • the supplement may be prepared by providing between 20 mg and 1000 mg free L-proiine per kilogram body mass of the organism to benefit from the use thereof, in an oral administration form.
  • the supplement may be prepared by mixing 100 mg free L-proline per kilogram body mass of the organism to benefit from the use thereof, with a drink suitable for human consumption.
  • an effective amount of free L-proline as a supplement for supplementing the concentration of free cellular L-proline in an organism, for restricting dehydration of such an organism.
  • the supplement may comprise between 20 mg and 1000 mg free L-proftne per kilogram body mass of the organism to benefit from the use thereof, in an oral administration form.
  • the supplement may comprise 100 mg free L-proline per kilogram body mass of the organism to benefit from the use thereof, mixed with a drink suitable for human consumption.
  • a supplement for suppiement ⁇ ng the concentration of free cellular L-proline in an organism, for restricting dehydration of such an organism comprising an effective amount of free L-proline.
  • the above supplement may be effective in reducing the levels of free radicals in organisms experiencing water stress.
  • the effective amount of L-proline may comprise between 20 mg and 1000 mg free L-proline per kilogram body mass of the organism to benefit from the use thereof, in an oral administration.
  • the effective amount of L-proiine may comprise 100 mg free L-proline per kilogram body mass of the organism to benefit from the use thereof, mixed with a drink suitable for human consumption.
  • a method of treating dehydration in humans and animals including the step of administering to an individual in need thereof an effective amount of a supplement according to the third aspect of the invention
  • the organism is a human and the free L-proline concentration is supplemented through oral administration of effective amounts of free L-proline to counter dehydration of such human. It will be appreciated that such supplementation would be particularly required and effective in cases where the human to whom the supplement is administered experience water stress owing to exercise, heat or lack of water intake, it will be appreciated further that the supplement would be effective in increasing free L-proline concentration and water levels in such a human, where the supplement is taken prophylacticaily.
  • a method of supplementing the concentration of free cellular L-proline in an organism, for restricting dehydration of such an organism including the step of administering to such organism an effective amount of free L-proline.
  • An effective amount of free L-proline may be between 20 mg and 1000 mg, preferably 100 mg free L-proline per kilogram body mass of the organism, three times a day.
  • An effective amount of a suppfement according to a preferred embodiment of the invention for restricting dehydration and for reducing the cellular concentration of free radicals in humans was prepared by mixing 100 mg free L-proiine per kilogram body mass of the human with any conventional off-the-shelf energy or cold drink.
  • the supplement was prepared by mixing 8 g of free L-proline with 500 ml energy drink.
  • the supplement was taken orally by a adult male three times a day.
  • the supplement according to the invention could find wide application in the field of preventing and treating dehydration in humans and animals such as the use in the prevention of dehydration in extreme athletes; the use as supplement to hydration drips in human patients (including pediatric appiication); the use to enhance feeds for ornamental fish prior to international shipment; and the use enhancing feeds of sheep, cattle, poultry, fish and other animals prior to slaughtering and freezing.

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  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Polymers & Plastics (AREA)
  • Engineering & Computer Science (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Food Science & Technology (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Mycology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Animal Husbandry (AREA)
  • Zoology (AREA)
  • Nutrition Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Obesity (AREA)
  • Hematology (AREA)
  • Diabetes (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

This invention relates to a supplement, the use thereof and method for supplementing the concentration of free cellular L-proline in an organism, for restricting dehydration of such an organism, the supplement comprising an effective amount of free L-proline. The supplement is effective in reducing the levels of free radicals in organisms experiencing water stress. This invention further relates to a method of treating dehydration in humans and animals including the step of administering to an individual in need thereof an effective amount of a supplement according to the third aspect of the invention. An effective amount of free L-proline is typically between 20 and 1000 mg, preferably 100 mg free L-proline per kilogram body mass of the organism, three times a day.

Description

AMINO ACID AND ITS USES
INTRODUCTION AND BACKGROUND
This invention relates to an amino acid and its uses. This invention further relates to compositions and methods for treating humans and animals and the use of such an amino acid.
Water is an essential molecule for sustaining life and an animal's ability to cope with changes in its internal water content is paramount for its survival.
Loss of internal water is a threat common to all animals. Such losses could occur through evaporation, waste excretion, or osmosis. Osmosis usually occurs in a saline environment, such as sea water, or by extracellular freezing, or from diseases such as diabetes or hyperglycemia, causing osmotic imbalances.
In humans, loss of water occurs through breathing, sweating, urinating and other processes. This loss of water is exacerbated during exercise, high temperature and dry environmental conditions. As a result of water loss and oxidative stress, levels of intracellular free radicals increase, causing damage to the cells, and if this process is not curbed, it is most often fatal. Taurine is a sulfur-based, non-protein amino acid and is known to act as an osmolyte in cases of dehydration. Taurine is also said to be cytoprotective by acting as an antioxidant, a calcium modulator, a synaptic neuromodulator and a membrane stabilizer. For this reason, it is known to include taurine in energy drinks for human consumption.
It is known to use L-proline orally in addition to other compositions such as ceramtdes and fish cartilage hydrolysate in the maintenance of the correct skin hydration as disclosed in EP 1 514 554 A1. However, L-proline has thus far not been recognized as an antioxidant or free radical scavenger.
It has been shown that L-proline concentration increases when freshwater and brackish water animals are exposed to hyperosmotic stress. It is also known that L-profine is released from cells of Australian Abalone (Haliotis roei) to maintain cell volume at low saiinities. L-proline is therefore generally considered as an intracellular osmolyte of animal cells, but to date, most studies were focused on the intracellular production and secretion of L- proline in cases where the organism is placed under hyperosmotic stress. However, a disadvantage of the prior art is that none of the published prior art studies is directed at the use of free L-proline supplementation in the prevention and/or treatment of dehydration and increase in free radicals In organisms placed under hyperosmotic stress. EP 1 514 554 A1 discloses a composition based on natural substances, useful in the maintenance of the correct skin hydration and in the prevention and/or the treatment of the effects of skin ageing, in particular wrinkles, characterized in that it comprises in combination ceramides in the form of extract of Oryza sativa; fish cartilage hydrolysate; and one or more amino acids selected from L-proline, L-!eusine7 L-valine and L-cysteine. This composition comprises between 20 to 200 mg, preferably 40 mg per day of these amino acids. A disadvantage of this composition is that the levels of L- proline that are suggested are insufficient to elevate the concentration of cellular free L-proline to the extent that it restricts dehydration and reduction in free radical concentration in the user, when exposed to water and heat stress.
OBJECTS OF THE PRESENT INVENTION
it is accordingly an object of the present invention to provide a supplement and method with which the aforesaid disadvantages could be alleviated and to provide new uses of L-proline.
SUMMARY OF THE INVENTION
According to a first aspect of the invention there is provided use of an effective amount of free L-proline in the preparation of a supplement for supplementing the concentration of free cellular L-proline in an organism, for restricting dehydration of such an organism.
The supplement may be prepared by providing between 20 mg and 1000 mg free L-proiine per kilogram body mass of the organism to benefit from the use thereof, in an oral administration form.
The supplement may be prepared by mixing 100 mg free L-proline per kilogram body mass of the organism to benefit from the use thereof, with a drink suitable for human consumption.
According to a second aspect of the invention there is provided use of an effective amount of free L-proline as a supplement for supplementing the concentration of free cellular L-proline in an organism, for restricting dehydration of such an organism.
The supplement may comprise between 20 mg and 1000 mg free L-proftne per kilogram body mass of the organism to benefit from the use thereof, in an oral administration form. The supplement may comprise 100 mg free L-proline per kilogram body mass of the organism to benefit from the use thereof, mixed with a drink suitable for human consumption.
According to a third aspect of the invention there is provided a supplement for suppiementϊng the concentration of free cellular L-proline in an organism, for restricting dehydration of such an organism, the supplement comprising an effective amount of free L-proline.
The above supplement may be effective in reducing the levels of free radicals in organisms experiencing water stress.
The effective amount of L-proline may comprise between 20 mg and 1000 mg free L-proline per kilogram body mass of the organism to benefit from the use thereof, in an oral administration.
The effective amount of L-proiine may comprise 100 mg free L-proline per kilogram body mass of the organism to benefit from the use thereof, mixed with a drink suitable for human consumption.
According to a fourth aspect of the invention there is provided a method of treating dehydration in humans and animals including the step of administering to an individual in need thereof an effective amount of a supplement according to the third aspect of the invention,
In one embodiment the organism is a human and the free L-proline concentration is supplemented through oral administration of effective amounts of free L-proline to counter dehydration of such human. It will be appreciated that such supplementation would be particularly required and effective in cases where the human to whom the supplement is administered experience water stress owing to exercise, heat or lack of water intake, it will be appreciated further that the supplement would be effective in increasing free L-proline concentration and water levels in such a human, where the supplement is taken prophylacticaily.
According to a fifth aspect of the invention there is provided a method of supplementing the concentration of free cellular L-proline in an organism, for restricting dehydration of such an organism including the step of administering to such organism an effective amount of free L-proline.
An effective amount of free L-proline may be between 20 mg and 1000 mg, preferably 100 mg free L-proline per kilogram body mass of the organism, three times a day. EXAMPLE
An effective amount of a suppfement according to a preferred embodiment of the invention for restricting dehydration and for reducing the cellular concentration of free radicals in humans, was prepared by mixing 100 mg free L-proiine per kilogram body mass of the human with any conventional off-the-shelf energy or cold drink.
Therefore, for an adult male with a mass of 80 kg, the supplement was prepared by mixing 8 g of free L-proline with 500 ml energy drink. The supplement was taken orally by a adult male three times a day.
It was found that use of the supplement lead to an increase in cellular concentration of free L-proline in the user and the elevated concentration was so maintained.
It was surprisingly further found that the supplement substantially reduced water loss and dehydration of the user, particularly when exposed to heat and water stress and during exercising.
It is foreseen that the supplement according to the invention could find wide application in the field of preventing and treating dehydration in humans and animals such as the use in the prevention of dehydration in extreme athletes; the use as supplement to hydration drips in human patients (including pediatric appiication); the use to enhance feeds for ornamental fish prior to international shipment; and the use enhancing feeds of sheep, cattle, poultry, fish and other animals prior to slaughtering and freezing.
It wiif be appreciated that variations in detail are possible with the invention without departing from the scope of the appended ciaims.

Claims

1. Use of an effective amount of free L-proline in the preparation of a supplement for supplementing the concentration of free cellular L- proline in an organism, for restricting dehydration of such an organism.
2. Use according to claim 1 wherein the supplement is prepared by providing between 20 mg and 1000 mg free L-proiine per kilogram body mass of the organism to benefit from the use thereof, in an oral administration form.
3. Use according to claim 2 wherein the supplement is prepared by mixing 100 mg free L-proline per kilogram body mass of the organism to benefit from the use thereof, with a drink suitable for human consumption.
4. Use of an effective amount of free L-proiine as a supplement for supplementing the concentration of free cellular L-proline in an organism, for restricting dehydration of such an organism.
5. Use according to claim 4 wherein the supplement comprises between 20 mg and 1000 mg free L-proline per kilogram body mass of the organism to benefit from the use thereof, in an oral administration form.
6. Use according to claim 5 wherein the supplement comprises 100 mg free L-proline per kilogram body mass of the organism to benefit from the use thereof, mixed with a drink suitable for human consumption.
7. A supplement for supplementing the concentration of free celiular L- proline in an organism, for restricting dehydration of such an organism, the supplement comprising an effective amount of free L-proline.
8. A supplement according to claim 7 effective in reducing the levels of free radicals in organisms experiencing water stress.
9. A supplement according to claim 7 or claim 8 wherein the effective amount of L-proline comprises between 20 mg and 1000 mg free L- proline per kilogram body mass of the organism to benefit from the use thereof, in an oral administration form.
10. A supplement according to claim 7 or claim 8 wherein the effective amount of L-proline comprises 100 mg free L-proiine per kilogram body mass of the organism to benefit from the use thereof, mixed with a drink suitable for human consumption.
11. A method of treating dehydration in humans and animals including the step of administering to an individual in need thereof an effective amount of a supplement according to any one of claims 7 to 10.
12.A method according to claim 11 wherein the organism is a human and the free L-pro!ine concentration is supplemented through oral administration of effective amounts of free L-proline to counter dehydration of such human.
13. A method according to claim 12 wherein the human to whom the supplement is administered experiences water stress owing to exercise, heat or lack of water intake.
14. A method according to claim 11 or claim 12 wherein the supplement is taken prophylacticaliy and is effective in increasing free L-proline concentration and water levels in the human.
15. A method of supplementing the concentration of free cellular L-proline in an organism, for restricting dehydration of such an organism including the step of administering to such organism an effective amount of free L-proline.
16. A method according to claim 9 wherein the effective amount of free L- proline is between 20 mg and 1000 mg, per kilogram body mass of the organism to benefit therefrom, three times a day.
17. A method according to claim 10 wherein the effective amount of free
L-proiine is 100 mg free L-proline per kilogram body mass of the organism, three times a day.
18. Use of free L-proline in the preparation of a supplement substantially as herein described and exemplified.
19. Use of free L-proline as a supplement substantially as herein described and exemplified.
20. A supplement substantially as herein described and exemplified.
21. A method of treating dehydration substantially as herein described and exemplified.
22.A method of supplementing the concentration of free cellular L-proline in an organism substantially as herein described and exemplified.
PCT/IB2006/053353 2005-09-20 2006-09-19 Amino acid and its uses Ceased WO2007034401A1 (en)

Priority Applications (3)

Application Number Priority Date Filing Date Title
AU2006293520A AU2006293520A1 (en) 2005-09-20 2006-09-19 Amino acid and its uses
EP06809330A EP1931333A1 (en) 2005-09-20 2006-09-19 Amino acid and its uses
US11/992,178 US20100099734A1 (en) 2005-09-20 2006-09-19 Amino acid and its uses

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
ZA200507602 2005-09-20
ZA2005/07602 2005-09-20

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WO2007034401A1 true WO2007034401A1 (en) 2007-03-29

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Country Status (6)

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US (1) US20100099734A1 (en)
EP (1) EP1931333A1 (en)
CN (1) CN101267817A (en)
AU (1) AU2006293520A1 (en)
WO (1) WO2007034401A1 (en)
ZA (1) ZA200801664B (en)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP6154322B2 (en) * 2011-06-07 2017-06-28 味の素株式会社 Amino acid composition

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1991014435A1 (en) * 1990-03-19 1991-10-03 Brigham And Women's Hospital Treatment of osmotic disturbance with organic osmolytes
WO1993000806A1 (en) * 1991-07-01 1993-01-21 Quadrant Holdings Cambridge Limited Dried blood cells and method of preparation
EP0715850A1 (en) * 1994-12-07 1996-06-12 Research Development Corporation Of Japan Use of proline and/or derivatives as an antihepatitis agent
WO2003075903A2 (en) * 2002-03-08 2003-09-18 Universiteit Leiden Use proline and its functional equivalentsfor quenching ros and/ or radicals
EP1514554A1 (en) * 2003-09-03 2005-03-16 Medestea Internazionale S.r.l. Oral composition based on natural substances useful in the maintenance of the correct hydration of the skin

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1991014435A1 (en) * 1990-03-19 1991-10-03 Brigham And Women's Hospital Treatment of osmotic disturbance with organic osmolytes
WO1993000806A1 (en) * 1991-07-01 1993-01-21 Quadrant Holdings Cambridge Limited Dried blood cells and method of preparation
EP0715850A1 (en) * 1994-12-07 1996-06-12 Research Development Corporation Of Japan Use of proline and/or derivatives as an antihepatitis agent
WO2003075903A2 (en) * 2002-03-08 2003-09-18 Universiteit Leiden Use proline and its functional equivalentsfor quenching ros and/ or radicals
EP1514554A1 (en) * 2003-09-03 2005-03-16 Medestea Internazionale S.r.l. Oral composition based on natural substances useful in the maintenance of the correct hydration of the skin

Also Published As

Publication number Publication date
EP1931333A1 (en) 2008-06-18
ZA200801664B (en) 2008-12-31
US20100099734A1 (en) 2010-04-22
CN101267817A (en) 2008-09-17
AU2006293520A1 (en) 2007-03-29

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