Download EP 1253830 B1 - European Patent Office

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EP 1 253 830 B1
EUROPEAN PATENT SPECIFICATION
(12)
(45) Date of publication and mention
(51) Int Cl.:
A23L 1/305 (2006.01)
A61K 35/20 (2006.01)
of the grant of the patent:
11.11.2009 Bulletin 2009/46
A23L 1/302 (2006.01)
(86) International application number:
(21) Application number: 01910231.8
PCT/NL2001/000112
(22) Date of filing: 12.02.2001
(87) International publication number:
WO 2001/058284 (16.08.2001 Gazette 2001/33)
(54) PHARMACEUTICAL COMPOSITION FOR MUSCULAR ANABOLISM
PHARMAZEUTISCHE ZUSAMMENSETZUNG FÜR MUSKELANABOLISMUS
COMPOSITION PHARMACEUTIQUE DESTINEE A L’ANABOLISME MUSUCULAIRE
(84) Designated Contracting States:
AT BE CH CY DE DK ES FI FR GB GR IE IT LI LU
MC NL PT SE TR
• HAGEMAN, Robert, Johan, Joseph
NL-6705 CT Wageningen (NL)
(74) Representative: van Westenbrugge, Andries et al
(30) Priority: 10.02.2000 US 500802
Nederlandsch Octrooibureau
Postbus 29720
2502 LS Den Haag (NL)
(43) Date of publication of application:
06.11.2002 Bulletin 2002/45
(56) References cited:
(73) Proprietor: N.V. Nutricia
EP-A- 0 875 155
WO-A-99/56758
US-A- 5 726 146
2700 MA Zoetermeer (NL)
WO-A-98/43617
WO-A-99/64022
(72) Inventors:
EP 1 253 830 B1
• SMEETS, Rudolf, Leonardus, Lodewijk
NL-5912 TD Venlo (NL)
Note: Within nine months of the publication of the mention of the grant of the European patent in the European Patent
Bulletin, any person may give notice to the European Patent Office of opposition to that patent, in accordance with the
Implementing Regulations. Notice of opposition shall not be deemed to have been filed until the opposition fee has been
paid. (Art. 99(1) European Patent Convention).
Printed by Jouve, 75001 PARIS (FR)
EP 1 253 830 B1
Description
Field of the invention
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[0001] The invention is concerned with pharmaceutical or nutritional compositions suitable for increasing muscular
mass ("lean body mass"), e.g. for athletes, and for preventing loss of lean body mass that may occur in periods of rest
and during recovery from disease.
Background
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[0002] Products intended for increasing muscle mass are commercially available, such as the product Phosphagain.
A review of nutritional supplements for increasing muscle mass has been presented by Clarkson and Rawson in Crit.
Rev. Food Sci. Nutr. 39 (1999) 317-328. They conclude that many claims of this effect are unsupported, and that the
weight gain following of creatine ingestion is most likely water retention but that it could also be due to some new muscle
protein. From this review, we learn that very little evidence exists that ergogenic components indeed improve athletic
performance.
[0003] According to US 5,726,146, lean body mass can be increased without increase body fat by administration of
a supplement containing creatine, taurine, and ribonucleic acid, optionally with carbohydrate for enhancing cellular
uptake of these ingredients.
[0004] WO 98/43617 discloses a dietary supplement comprising L-carnitine, coenzyme Q10 and taurine useful in the
correction of the abnormality in mitochondrial energetics occurring in cardiac failure and certain other diseases. It further
discloses a high protein, high calorie nutritional feeding supplement comprising these three nutrients together with
cysteine, vitamin E, vitamin C, selenium, and thiamine. The protein fraction can comprise of normal (i.e. denatured)
whey proteins, 1:1 with casein.
[0005] WO 95/10192 discloses a nutritional drink containing colostrum, for the purpose of improving physical performance and recovery. The colostrum is defatted and de-caseinated, and sterilised by filtration.
[0006] WO 99/56758 describes a food composition for use in changing body composition (increased lean tissue)
and/or physical work capacity, which contains undenatured colostrum, in particular colostrum derived growth factors
and colostrum-derived casein. The composition may further contain vitamins minerals, amino acids, and carbohydrates.
[0007] EP 875 155 discloses a composition for enteral peri-operative use comprising glutamine and other amino acids
selected from arginine, lysine ornithine and histidine.
[0008] WO 99/64022 describes a nutritive composition comprising colostrum in combination with glutamine among
other ingredients.
[0009] There is a need for nutritional and/or pharmaceutical preparation that indeed helps to increase muscle strength
during training. During periods when training efforts have to be stopped, e.g. because of injuries or holidays, it is frequently
observed that muscle mass that was built up during exercise rapidly decreases, and a lot of time is normally required
to regain the level that was previously present. Losses in lean body mass are also observed frequently in persons that
have to be inactive for quite a while, e.g. because they have to stay in bed due to injury, disease or other disorders.
Thus, there is also a need for effective formulations, and especially nutritional formulations, that help prevent losses of
body mass during these periods.
[0010] Muscle consists of proteins, like myosine and actin, lipids and carbohydrates. Skeletal muscle tissue is continuously broken off and replaced in a dynamic process that depends on mechanical damage, exercise and feeding
status at a particular point in time.
Description of the invention
[0011]
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It has now been found that the simultaneous or sequential administration of
1- component that triggers anabolism (initiators),
2- components that provide building blocks (substrates) for biosynthesis of muscle tissue, and
3- components that facilitate biosynthetic processes (facilitators) increases, for a certain period of time, lean body
mass and/or can prevent catabolism in periods of rest.
[0012] Sequential use means that the different components can be administered separately during the day, but they
must be consumed during the same day. In this way, for example a product with one or more facilitators is consumed
first, followed by consumption, e.g. 2 hours after consumption of the first product, of an effective amount of substrate
and initiator in the same product. However, preferably all three types of components are consumed simultaneously in
one product.
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[0013] The invention pertains to pharmaceutical and/or nutritional compositions suitable for enhancing muscular anabolism, i.e. production of muscle tissue or reduction of loss of muscle tissue. The compositions according to the invention
comprise an initiator for muscular tissue production, a facilitator for biosynthesis, and a substrate. They furthermore
comprise a facilitator, including creatine or a functional equivalent, and optionally further components facilitating tissue
production, and also a substrate comprising e.g. carbohydrates, amino acids etc.
[0014] The products can have a powdered structure, packed in sachets or cans or similar reservoirs. Other dry forms
that are equally suitable are cereals and bars. The product can also have the form of a drink, e.g. based on a dairy drink
(milk, whey) or fruit juice (orange, apple, grape). For liquid products it is advantageous to let it have a pH below 4.2 in
order to stabilize some of the active components. The product can also have the form of a paste or spread or sauce.
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Initiators
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[0015] The initiators (also referred to as triggering substances or triggers) to be used in the compositions of the
invention are components that start up the anabolic processes. Examples are anabolic growth factors like Insulin-Like
Growth Factor (IGF-1). These must be present as part of an extract of a protein-rich food ingredient, in particular in an
extract from a proteinaceous material of animal origin, like milk, blood or egg. Undenatured whey and especially undenatured colostrum in particular bovine colostrum comprises a variety of anabolic trigger substances. The high effectivity
of whey and colostrum that was found may also be explained by the presence of components that increase the bioavailability of the initiator components. In case of anabolic growth factors, such components are binding proteins.
[0016] Specific extracts of animal origin may be used as a source of triggers for anabolism, providing that the extraction
procedures do not affect the trigger components. The F0 value, defined in the Manual of Common Methods, defines
decimal reductions of germs as a result of heat treatment of food products. Thus an F0 value of 3.0 defines a thousandfold reduction of germs and is achieved by treatment at 121°C with a Z value of 10. A heat treatment above F0 = 3.0
normally destroys most of these trigger components. Thus the extracts should not have been subjected to a heat treatment
with an F0 of 3.0 or higher, and preferably any heat treatment should have an F0 of less than 2.4. Most preferably, a
heat treatment, if any, should not have an F0 of more than 0.2.
[0017] Suitable methods for obtaining such products avoiding substantial heat treatment are described in the art and
include filtration and centrifugal techniques. The amount of extract can be as low as 5 mg per daily dose, if a high degree
of purification of the triggering substances from the proteinaceous material is obtained. However, when bovine colostrum
is used as sole source for triggering substances, at least 5 g of the product, that is obtained by using the method disclosed
in WO 97/16977, should be included in a daily dose according to the invention.
[0018] The inclusion of insulinotrophic components like digestible carbohydrates and arginine and lysine can further
enhance the triggering activity of extracts of animal proteins. Arginine and lysine should be included in amounts of more
than 1.0 g and preferably more than 1.5 g per daily dose. Carbohydrates are preferably glucose polymers like maltodextrins
and should be present in an amount of more than 4 g and preferably more than 8 g.
Substrates
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[0019] In order to allow an adequate rate of biosynthesis of muscle tissue, the presence of sufficient amounts of
substrate in the form of a variety of amino acids is required. It appears that requirements for protein in athletes are higher
than in non-athletes. Daily requirements in strength athletes are above 120g protein and in endurance athletes above
100g protein. Though it appeared that some amino acids become rate-limiting earlier in biosynthesis of muscle tissue
than other ones, a mixture of all amino acids, including the essential amino acids is preferably provided according to the
invention. These amino acids should be provided as protein or hydrolysate thereof; it is especially preferred to use intact
protein for taste reasons and because the amino acids will then be released more slowly. The latter ensures a constant
but sufficient provision of the substrate amino acids to the tissues and where the amino acids are insulinotrophic, a
longer increase of plasma insulin levels.
[0020] In order to provide sufficient amounts of amino acids, typically more than 5g protein and especially more than
10 or even more than 20g protein is included in the formulations. Suitable proteins are all proteins that comprise high
amounts of essential amino acids, especially leucine, lysine and methionine, such as casein, soy, pea, potato, egg and
whey proteins. However, when undenatured proteins of animal origin like colostrum or whey from mammal milk, blood
or eggs are used, these ingredients also comprise triggering components for anabolism.
[0021] Proteins and amino acids can be expressed as protein equivalents (PE). One PE can be calculated by multiplying
the Kjeldahl nitrogen content of the substrate by the factor 6.25.
[0022] In order to increase the amount of the amino acids that are most critical to muscle building, methionine, lysine
and leucine, additional amounts of these amino acids can be included. This can be done by including peptides, or amino
acid complexes or free amino acids in the formula. Preferably free amino acids are used, especially those in the L-form.
The amounts of methionine that are included per daily serving should exceed 0.2 g (9.4% N: 0.12 g PE) and preferably
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exceed 0.5 g; the preferred range is 1-6 g Met. Preferably the amount of methionine is more than 2.8 g per 100 g protein
equivalents and in particular in the range 3.0-5.0. The amount of lysine per daily serving should be more than 1.0 g
(19.6% N: 1.3 g PE) and preferably more than 2.0 g, e.g. 2.5 - 15.0 g. Calculated per 100g protein equivalents, the
amount of lysine should be more than 8.3 g, and in particular in the range 8.5-11. The amount of leucine per daily serving
should be more than 2.0 g (10.4% N: 1.3 g PE) and preferably more than 3.0 g, e.g. 3.5 - 20 g.
[0023] Sleeping disorders are often experienced, especially in those persons that consume large amounts of branched
chain amino acids (BCAA: valine, isoleucine, leucine). This is especially undesirable when one wants to maintain anabolism during a longer period of time. For this reason it is important that the ratio of L-IeucineBCAA is relatively high. This
ratio should be higher than 0.46 and in particular be in the range 0.5-3.0.
[0024] In addition the amount of L-tryptophan should be relatively high. The ratio Trp/BCAA should be higher than
0.055, preferably in the range of 0.06-0.2 and in particular be in the range of 0.07-0.13. Also persons that suffer from
disease frequently appear to experience problems with maintaining nitrogen balance. By consuming the above-mentioned
types and amounts of substrates their capacity to synthesise muscle tissue is maximally supported.
Facilitator
[0025] According to the invention, lean body tissue can only be synthesised when sufficient energy is available and
sufficient amounts of cofactors are available as facilitator of the anabolic biochemical processes. Intracellular energy
should be available in the form of adenosine tri-phosphate (ATP). Creatine phosphate (CP) is able to provide "energised
phosphate" to ADP, which restores ATP levels once they have been used for labour or biochemical processes. It is
therefore especially advantageous to include in the formulation a source of both energy, in the form of digestible carbohydrates, and creatine. Instead of creatine, Krebs cyc le intermediates such as citrate and Krebs cycle precursors, such
as pyruvate, glutamate, glutamine, can be used.
[0026] The amount of digestible carbohydrates should be above 4 g per daily dose and preferably more than 10 g per
day. That of creatine should be above 1.0 g per daily dose and preferably more than 2.0 g, for example 8 g. Suitable
carbohydrates are maltodextrins, e.g. the one having DE = 19, lactose, ribose, sucrose or mixtures thereof. Creatine
can be the salt creatine, creatine phosphate, or functional and stable equivalents thereof, including acid addition salts,
metal and ammonium salts, hydrolysable esters etc.
[0027] Because of the high amounts of protein that are digested, consumption of extra amounts of minerals and
vitamins in the diet is desirable. Especially vitamin B6 should be fortified to ensure a consumption of at least 1.8 mg vit.
B6 per 100g protein that is consumed. The high volume of protein that is normally consumed by body builders ensures
a load of methionine that should be handled appropriately in order to have only moderate increases in plasma levels of
homocysteine. It is therefore recommended to include folic acid, vitamin B12, vitamin B6, zinc and magnesium in the
formula, because deficiencies of one or more of these components frequently occur, while they are mandatory for
homeostasis of homocysteine loads. The levels should be at least 1 mg vitamin B6, 200 Pg folic acid, 1 Pg cyanocobalamine, 40 mg magnesium and 5 mg zinc or the functional equivalents of these components per daily serving. The
prior art discloses which forms of these components can be advantageously used for nutritional purposes. Vitamin B6
can e.g. have the form of pyridoxine or pyridoxal; folic acid can be in the monoglutamate form; zinc can be administered
as salt, e.g. as zinc carbonate; magnesium can have the form of an inorganic salt like magnesium carbonate.
[0028] A further improvement of the product can be obtained by including in the product one of the metabolites of
leucine, especially beta-hydroxy-beta-methylbutyrate (HMB). The latter compound can be included in an amount of 1-20
g per daily serving, in particular in the range 2-5 g per day. The component can be included as pure substance or as
inorganic salt such as the calcium salt, or any other functional equivalent. Other components like yeast, carnitine,
pyruvate, dihydroxyacetone, glutamine, ubiquinone (especially CoQ10) and other vitamins and minerals can be included
as well. It is especially preferred to include melatonin, which supports the anabolic function of the composition.
[0029] Table 1 shows the scope of the products according to the invention.
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Table 1: Components according to the invention
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Initiators
Substrates
Facilitators
Undenatured extracts from proteinacous
material of animal origin
+
optionally extra:
insulinotrophic components like:
digestible carbohydrates
L-Arginine
L-Lysine
and/or
HMB
Proteins
and/or
L-leucine
L-methionine
L-lysine
Creatine and/or Krebs cycle intermediates or
precursors thereof
+ optionally
digestible carbohydrates
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optionally extra:
vitamin B6, folic acid,
vitamin B12
magnesium, zinc melatonin
Examples
Example 1. Bar for body building purposes
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[0030] An extract for isolating anabolic components from colostrum is prepared by applying the centrifugation process
as described in WO 97/16977. The liquid phase is consequently purified by elution over a strong anionic exchanger.
The liquid is then freeze-dried. The bar is prepared by using methods that are known in the art that ensure that per bar
of 30g weight is present:
100 mg of colostrum powder produced as given above,
5 g soy protein
2 g L-leucine
1.5 g L-lysine
0.6 g L-methionine
2.0 g creatine
13.6 g glucose syrup
2.0 mg vitamin B6
0.2g L-tryptophan
Example 2. Powdered formula in can of 900 g. Twenty grams of powder are dissolved in 200 ml milk.
[0031]
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Per 100g powder the formula contains:
50 g undenatured colostrum powder
40 g maltodextrin DE 19
10 g creatine
Per day about 40-100 g of the powder is consumed.
Example 3. Powder packed as in example 2, consisting per 100g formula of:
[0032]
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33 g undenatured egg white powder
50 g maltodextrin DE 25
12 g creatine
2 g melatonine
5 g of a mineral/vitamin premix that comprises 1250 ug folic acid, 10 mg pyridoxine, 7.5 ug cyanocobalamine, 75
mg zinc, 10 mg copper and 400 mg magnesium
Per day about 25 g of powder is consumed e.g. suspended in 200 ml orange juice.
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Example 4. Powdered product for body building, that consists per 100 g formula of
[0033]
72 g undenatured whey protein powder, providing 43 g protein and 21 g lactose
5 g sucrose
8 g creatine
1 g L-methionine
1 g L-tryptophan
1 g melatonine
6 g of the mineral/vitamin premix described in example 3
4gHMB
4 g L-leucine
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Per day about 50 g formula is consumed, e.g. by dissolving this amount of powder in milk together with the breakfast cereal.
Example 5. Liquid product obtained by preblending the powder of example 3 in orange juice.
Example 6. Supplement
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[0034]
The following components were combined an the amounts indicated for a daily dose:
30 g bovine colostrum
120 g carbohydrates
5 g creatine
6 g of essential L-amino acids (Lys, Leu, Val, Phe, Thr. His, Ile, Met) methionine module: Zn, Vit. B6, folic acid
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Example 7. Supplement
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[0035]
The following components were combined an the amounts indicated for a daily dose:
30 g bovine colostrum
36 g carbohydrates
5 g creatine
6 g of essential L-amino acids (Lys, Leu, Val, Phe, Thr. His, Ile, Met) methionine module: Zn, Vit. B6, folic acid
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Example 8. Supplement
[0036]
The following components were combined an the amounts indicated for a daily dose:
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30 g bovine colostrum
6 g carbohydrates
5 g creatine
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Claims
1.
A pharmaceutical composition containing, per daily dose,
- at least 5 mg of anabolic growth factors,
- at least 0.12 g of protein equivalents as anabolic substrates, the protein equivalents comprising a weight ratio
of leucine to branched-chain amino acids between 0.5 and 3.0, and
- at least 3 g of anabolic facilitators selected from creatine, citrate, pyruvate, glutamate and glutamine, comprising
at least 1 g of creatine or its functional equivalent.
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2.
The pharmaceutical composition of claim 1, wherein the anabolic growth factors comprise at least 5 g of a nondenatured animal protein, non-denatured being defined as having an F0 of less than 3.0.
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3.
- at least 5 g of non-denatured animal protein selected from milk protein, egg protein and blood protein, nondenatured being defined as having an F0 of less than 3.0,
- at least 0.12 g of protein equivalents as anabolic substrates, the protein equivalents comprising a weight ratio
of leucine to branched-chain amino acids between 0.5 and 3.0, and
- at least 3 g of anabolic facilitators selected from creatine, citrate, pyruvate, glutamate and glutamine, comprising
at least 1 g of creatine or its functional equivalent.
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A pharmaceutical composition containing, per daily dose,
4.
The pharmaceutical composition of claim 2 or 3, wherein the animal protein comprises colostrum.
5.
The pharmaceutical composition of any one of claims 1-4, comprising digestible carbohydrates at a level of at least
4 g per daily dose.
6.
The pharmaceutical composition of claim 5, comprising digestible carbohydrates at a level of at least 8 g per daily
dose.
7.
The pharmaceutical composition of any one of claims 1-6, comprising total proteins at a level of more than 10 g per
daily dose.
8.
The pharmaceutical composition of any one of claims 1-7, comprising one or more of the following per daily dose:
more than 0.2 g methionine, more than 1.0 g lysine, more than 2.0 g leucine, and more than 0.2 g tryptophan.
9.
The pharmaceutical composition of any one of claims 1-8, in which the weight ratio of leucine to branched-chain
amino acids is between 0.5 and 0.8 and the weight ratio of tryptophan to branched-chain amino acids is between
0.055 and 0.2.
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10. The pharmaceutical composition of any one of claims 1-9, further comprising at least one component selected from
the group consisting of vitamin B6, vitamin B12, folic acid, magnesium and zinc.
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11. The pharmaceutical composition of any one of claims 1-10, further comprising 1-20 g of β-hydroxy-β-methylbutyrate
and/or 0.5-10 g melatonine per daily dose.
12. The pharmaceutical composition of any one of claims 1-11, which is a supplement.
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13. Use of at least 1 g of biosynthesis facilitators selected from creatine, citrate, pyruvate, glutamate and glutamine,
and at least 5 g non-denatured animal protein, non-denatured being defined as having an F0 of less than 3.0, the
protein comprising a weight ratio of leucine to branched-chain amino acids between 0.5 and 3.0, per daily dose for
preparing a pharmaceutical or nutritional composition for improving muscular anabolism.
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14. Use of at least 1 g of biosynthesis facilitators selected from creatine, citrate, pyruvate, glutamate and glutamine,
and at least 5 g of non-denatured animal protein, non-denatured being defined as having an F0 of less than 3.0, the
protein comprising a weight ratio of tryptophan to branched-chain amino acids between 0.07 and 0.2, per daily dose
for preparing a pharmaceutical or nutritional composition for improving muscular anabolism.
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15. Use of at least 1 g of biosynthesis facilitators selected from creatine, citrate, pyruvate, glutamate and glutamine,
and at least 5 g of non-denatured animal protein, non-denatured being defined as having an F0 of less than 3.0, the
protein comprising a weight ratio of methionine to total protein equivalents between 3.0 and 5.0 per 100, per daily
dose for preparing a pharmaceutical or nutritional composition for improving muscular anabolism.
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16. Use of at least 1 g of biosynthesis facilitators selected from creatine, citrate, pyruvate, glutamate and glutamine,
and at least 5 g of non-denatured animal protein, non-denatured being defined as having an F0 of less than 3.0,
and 1-20 g of β-hydroxy-β-methylbutyrate and/or 0.5-10 g melatonine per daily dose for preparing a pharmaceutical
or nutritional composition for improving muscular anabolism.
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Patentansprüche
1.
Pharmazeutische Zusammensetzung enthaltend, pro Tagesdosis,
- wenigstens 5 mg anabole Wachstumsfaktoren,
- wenigstens 0,12 g Proteinäquivalente als anabole Substrate, wobei die Proteinäquivalente ein Gewichtsverhältnis von Leucin zu verzweigtkettigen Aminosäuren zwischen 0,5 und 3,0 umfassen, und
- wenigstens 3 g anabole Hilfsmittel ausgewählt aus Kreatin, Citrat, Pyruvat, Glutamat und Glutamin, umfassend
wenigstens 1 g Kreatin oder sein funktionelles Äquivalent.
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2.
Pharmazeutische Zusammensetzung nach Anspruch 1, wobei die anabolen Wachstumsfaktoren wenigstens 5 g
eines nicht denaturierten tierischen Proteins umfassen, wobei nicht denaturiert so definiert ist, dass es ein F0 von
weniger als 3,0 aufweist.
3.
Pharmazeutische Zusammensetzung enthaltend, pro Tagesdosis,
- wenigstens 5 g nicht denaturiertes tierisches Protein, ausgewählt aus Milchprotein, Eiprotein und Blutprotein,
wobei nicht denaturiert so definiert ist, dass es ein F0 von weniger als 3,0 aufweist,
- wenigstens 0,12 g Proteinäquivalente als anabole Substrate, wobei die Proteinäquivalente ein Gewichtsverhältnis von Leucin zu verzweigtkettigen Aminosäuren zwischen 0,5 und 3,0 aufweisen, und
- wenigstens 3 g anabole Hilfsmittel ausgewählt aus Kreatin, Citrat, Pyruvat, Glutamat und Glutamin, umfassend
wenigstens 1 g Kreatin oder sein funktionelles Äquivalent.
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4.
Pharmazeutische Zusammensetzung nach Anspruch 2 oder 3, wobei das tierische Protein Kolostrum umfasst.
5.
Pharmazeutische Zusammensetzung nach einem der Ansprüche 1-4, umfassend abbaubare Kohlenhydrate in einem Anteil von wenigstens 4 g pro Tagesdosis.
6.
Pharmazeutische Zusammensetzung nach Anspruch 5, umfassend abbaubare Kohlenhydrate in einem Anteil von
wenigstens 8 g pro Tagesdosis.
7.
Pharmazeutische Zusammensetzung nach einem der Ansprüche 1-6, umfassend Gesamtproteine in einem Anteil
von mehr als 10 g pro Tagesdosis.
8.
Pharmazeutische Zusammensetzung nach einem der Ansprüche 1-7, umfassend eines oder mehrere der folgenden
pro Tagesdosis: mehr als 0,2 g Methionin, mehr als 1,0 g Lysin, mehr als 2,0 g Leucin und mehr als 0,2 g Tryptophan.
9.
Pharmazeutische Zusammensetzung nach einem der Ansprüche 1-8, in welcher das Gewichtsverhältnis von Leucin
zu verzweigtkettigen Aminosäuren zwischen 0,5 und 0,8 liegt und das Gewichtsverhältnis von Tryptophan zu verzweigtkettigen Aminosäuren zwischen 0,055 und 0,2 liegt.
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10. Pharmazeutische Zusammensetzung nach einem der Ansprüche 1-9, außerdem umfassend wenigstens eine Komponente, ausgewählt aus der Gruppe bestehend aus Vitamin B6, Vitamin B12, Folsäure, Magnesium und Zink.
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11. Pharmazeutische Zusammensetzung nach einem der Ansprüche 1-10, außerdem umfassend 1-20 g β-Hydroxy-βmethylbutyrat und/oder 0,5-10 g Melatonin pro Tagesdosis.
12. Pharmazeutische Zusammensetzung nach einem der Ansprüche 1-11, welche ein Ergänzungsmittel ist.
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13. Verwendung von wenigstens 1 g Biosynthesehilfsmitteln, ausgewählt aus Kreatin, Citrat, Pyruvat, Glutamat und
Glutamin, und wenigstens 5 g nicht denaturiertem tierischen Protein, wobei nicht denaturiert so definiert ist, dass
es ein F0 von weniger als 3,0 aufweist, wobei das Protein ein Gewichtsverhältnis von Leucin zu verzweigtkettigen
Aminosäuren zwischen 0,5 und 3,0 aufweist, pro Tagesdosis zum Herstellen einer pharmazeutischen Zusammensetzung oder Nahrungszusammensetzung zum Verbessern des Muskelaufbaus.
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14. Verwendung von wenigstens 1 g Biosynthesehilfsmitteln, ausgewählt aus Kreatin, Citrat, Pyruvat, Glutamat und
Glutamin, und wenigstens 5 g nicht denaturiertem tierischen Protein, wobei nicht denaturiert so definiert ist, dass
es ein F0 von weniger als 3,0 aufweist, wobei das Protein ein Gewichtsverhältnis von Tryptophan zu verzweigtkettigen
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Aminosäuren zwischen 0,07 und 0,2 umfasst, pro Tagesdosis zum Herstellen einer pharmazeutischen Zusammensetzung oder Nahrungszusammensetzung zum Verbessern des Muskelaufbaus.
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15. Verwendung von wenigstens 1 g Biosynthesehilfsmitteln, ausgewählt aus Kreatin, Citrat, Pyruvat, Glutamat und
Glutamin, und wenigstens 5 g nicht denaturiertem tierischen Protein, wobei nicht denaturiert so definiert ist, dass
es ein F0 von weniger als 3,0 aufweist, wobei das Protein ein Gewichtsverhältnis von Methionin zu Gesamtproteinäquivalenten zwischen 3,0 und 5,0 pro 100 aufweist, pro Tagesdosis zum Herstellen einer pharmazeutischen Zusammensetzung oder Nahrungszusammensetzung zum Verbessern des Muskelaufbaus.
16. Verwendung von wenigstens 1 g Biosynthesehilfsmitteln, ausgewählt aus Kreatin, Citrat, Pyruvat, Glutamat und
Glutamin, und wenigstens 5 g nicht denaturiertem tierischen Protein, wobei nicht denaturiert so definiert ist, dass
es ein F0 von weniger als 3,0 aufweist, und 1-20 g β-Hydroxy-β-methylbutyrat und/oder 0,5-10 g Melatonin pro
Tagesdosis zum Herstellen einer pharmazeutischen Zusammensetzung oder Nahrungszusammensetzung zum
Verbessern des Muskelaufbaus.
15
Revendications
1.
Composition pharmaceutique contenant, par dose journalière:
20
- au moins 5 mg de facteurs de croissance anaboliques,
- au moins 0,12 g d’équivalents de protéines en tant que substrats anaboliques, les équivalents de protéines
comprenant un rapport pondéral de la leucine aux aminoacides ramifiés entre 0,5 et 3,0, et
- au moins 3 g de facilitateurs anaboliques choisis parmi la créatine, un citrate, un pyruvate, un glutamate et la
glutamine, comprenant au moins 1 g de créatine ou de son équivalent fonctionnel.
25
2.
Composition pharmaceutique selon la revendication 1, dans laquelle les facteurs de croissance anaboliques comprennent au moins 5 g d’une protéine animale non dénaturée, non dénaturé étant défini comme ayant un F0 inférieur
à 3,0.
3.
Composition pharmaceutique contenant, par dose journalière,
30
- au moins 5 g d’une protéine animale non dénaturée choisie parmi une protéine de lait, une protéine d’oeuf et
une protéine du sang, non dénaturé étant défini comme ayant un F0 inférieur à 3,0,
- au moins 0,12 g d’équivalents de protéines en tant que substrats anaboliques, les équivalents de protéines
comprenant un rapport pondéral de la leucine aux aminoacides ramifiés entre 0,5 et 3,0, et
- au moins 3 g de facilitateurs anaboliques choisis parmi la créatine, un citrate, un pyruvate, un glutamate et la
glutamine, comprenant au moins 1 g de créatine ou de son équivalent fonctionnel.
35
40
45
4.
Composition pharmaceutique selon la revendication 2 ou 3, dans laquelle la protéine animale comprend du colostrum.
5.
Composition pharmaceutique selon l’une quelconque des revendications 1-4, comprenant des hydrates de carbone
digestibles à un niveau d’au moins 4 g par dose journalière.
6.
Composition pharmaceutique selon la revendication 5, comprenant des hydrates de carbone digestibles à un niveau
d’au moins 8 g par dose journalière.
7.
Composition pharmaceutique selon l’une quelconque des revendications 1-6, comprenant des protéines totales à
un niveau supérieur à 10 g par dose journalière.
8.
Composition pharmaceutique selon l’une quelconque des revendications 1-7, comprenant une ou plusieurs des
substances suivantes par dose journalière: plus de 0,2 g de méthionine, plus de 1,0 g de lysine, plus de 2,0 g de
leucine et plus de 0,2 g de tryptophane.
9.
Composition pharmaceutique selon l’une quelconque des revendications 1-8, dans laquelle le rapport pondéral de
la leucine aux aminoacides ramifiés se situe entre 0,5 et 0,8 et le rapport pondéral du tryptophane aux aminoacides
ramifiés se situe entre 0,055 et 0,2.
50
55
9
EP 1 253 830 B1
10. Composition pharmaceutique selon l’une quelconque des revendications 1-9, comprenant en outre au moins un
constituant choisi dans le groupe constitué par la vitamine B6, la vitamine B12, l’acide folique, le magnésium et le zinc.
5
11. Composition pharmaceutique selon l’une quelconque des revendications 1-10, comprenant en outre 1-20 g de βhydroxy-β-méthylbutyrate et/ou 0,5-10 g de mélatonine par dose journalière.
12. Composition pharmaceutique selon l’une quelconque des revendications 1-11, qui est un supplément.
10
15
13. Utilisation d’au moins 1 g de facilitateurs de biosynthèse choisis parmi la créatine, un citrate, un pyruvate, un
glutamate et la glutamine, et d’au moins 5 g de protéine animale non dénaturée, non dénaturé étant défini comme
ayant un F0 inférieur à 3,0, la protéine comprenant un rapport pondéral de la leucine aux aminoacides ramifiés entre
0,5 et 3,0, par dose journalière, pour la préparation d’une composition pharmaceutique ou nutritive destinée à
améliorer l’anabolisme musculaire.
14. Utilisation d’au moins 1 g de facilitateurs de biosynthèse choisis parmi la créatine, un citrate, un pyruvate, un
glutamate et la glutamine, et d’au moins 5 g de protéine animale non dénaturée, non dénaturé étant défini comme
ayant un F0 inférieur à 3,0, la protéine comprenant un rapport pondéral du tryptophane aux aminoacides ramifiés
entre 0,07 et 0,2, par dose journalière, pour la préparation d’une composition pharmaceutique ou nutritive destinée
à améliorer l’anabolisme musculaire.
20
25
30
15. Utilisation d’au moins 1 g de facilitateurs de biosynthèse choisis parmi la créatine, un citrate, un pyruvate, un
glutamate et la glutamine, et d’au moins 5 g de protéine animale non dénaturée, non dénaturé étant défini comme
ayant un F0 inférieur à 3,0, la protéine comprenant un rapport en masse de la méthionine aux équivalents de
protéines totaux d’entre 3,0 et 5,0 pour 100, par dose journalière, pour la préparation d’une composition pharmaceutique ou nutritive destinée à améliorer l’anabolisme musculaire.
16. Utilisation d’au moins 1 g de facilitateurs de biosynthèse choisis parmi la créatine, un citrate, un pyruvate, un
glutamate et la glutamine, et d’au moins 5 g de protéine animale non dénaturée, non dénaturé étant défini comme
ayant un F0 inférieur à 3,0, et de 1-20 g de β-hydroxy-β-méthylbutyrate et/ou de 0,5-10 g de mélatonine par dose
journalière pour la préparation d’une composition pharmaceutique ou nutritive destinée à améliorer l’anabolisme
musculaire.
35
40
45
50
55
10
EP 1 253 830 B1
REFERENCES CITED IN THE DESCRIPTION
This list of references cited by the applicant is for the reader’s convenience only. It does not form part of the European
patent document. Even though great care has been taken in compiling the references, errors or omissions cannot be
excluded and the EPO disclaims all liability in this regard.
Patent documents cited in the description
•
•
•
•
US 5726146 A [0003]
WO 9843617 A [0004]
WO 9510192 A [0005]
WO 9956758 A [0006]
•
•
•
Non-patent literature cited in the description
•
Clarkson ; Rawson. Crit. Rev. Food Sci. Nutr.,
1999, vol. 39, 317-328 [0002]
11
EP 875155 A [0007]
WO 9964022 A [0008]
WO 9716977 A [0017] [0030]