CN101312718A - Nutraceutical composition for the treatment of muscle wasting - Google Patents
Nutraceutical composition for the treatment of muscle wasting Download PDFInfo
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- CN101312718A CN101312718A CNA2006800383106A CN200680038310A CN101312718A CN 101312718 A CN101312718 A CN 101312718A CN A2006800383106 A CNA2006800383106 A CN A2006800383106A CN 200680038310 A CN200680038310 A CN 200680038310A CN 101312718 A CN101312718 A CN 101312718A
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- resveratrol
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Abstract
The use of at least one component selected from the group consisting of EGCG, hydroxytyrosol, resveratrol and derivatives, metabolites or analogues thereof in the manufacture of a nutraceutical composition for the prevention and treatment of muscle wasting leading to muscle loss, atrophy and other associated muscle disorders in animals, in particular mammals including humans.
Description
The present invention relates to the novel use of nutraceutical (nutraceutical) compositions, described compositions comprises the component of at least a EGCG of being selected from, hydroxytyrosol, resveratrol and derivant thereof, metabolite or analog as active component.
Compositions of the present invention is specially adapted to particularly comprise in the human mammal wasting (causing muscle loss, amyotrophy) and other related muscles deficiency disorder in prevention and the treatment animal.
The effectiveness in field of nutrition and drug world application represented in term used herein " nutraceutical ".Therefore, the nutraceutical composition of described novelty can be used as the supplement of F﹠B, dietary supplement and be used for through application intestinal or parenteral as pharmaceutical preparation, described preparation can be a solid preparation, for example capsule or tablet, or liquid preparation, for example solution or suspension.Civilization shows as can be known in the past, and term " nutraceutical composition " also comprises the F﹠B that contains above-mentioned active component.
Term used herein " resveratrol and derivant thereof, metabolite or analog " comprises the chemical compound that following general formula is contained
Wherein, A represents carbon-carbon single bond or two key, and described pair of key can be trans or cis, and R1, R2, R3, R4, R5 and R6 represent hydrogen, hydroxyl independently of one another, through the hydroxyl of etherificate or through the hydroxyl of esterification.Preferably A is two key (Compound I CH=CH-).
Through etherificate or can be derived from straight or branched alkyl unsubstituted or substituted, that have 1 to 26 carbon atom through the hydroxyl of esterification, or derived from straight or branched aliphatic series, araliphatic or aromatic carboxylic acid unsubstituted or substituted, that have 1 to 26 carbon atom.Hydroxyl through etherificate further can be the glycosides base, further can be glucosiduronic acid or sulfate group through the hydroxyl of esterification.Wherein A is resveratrol (R1, R3 and R5=hydrogen, R2, R4 and a R6=hydroxyl) for the example of the formula I chemical compound of-CH=CH-; PiceameyeriRehd. Et Wils. tan phenol (piceatannol) (R3 and R5=hydrogen, R1, R2, R4 and R6=hydroxyl) and rhapontigenin (R5=hydrogen, R1, R3, R4 and R6=hydroxyl and R2=methoxyl group).Wherein A is dihydro resveratrol (R1, R3 and R5=hydrogen, R2, R4 and a R6=hydroxyl) for the example of the formula I chemical compound of-CH2-CH2-; Dihydro PiceameyeriRehd. Et Wils. tan phenol (R3 and R5=hydrogen, R1, R2, R4 and R6=hydroxyl) and tristin (R3 and R5=hydrogen; R2, R4 and R6=hydroxyl and R1=methoxyl group).These chemical compounds are known, commercially available and can obtain according to approach well known.
Term used herein " EGCG " comprise (-)-epigallocatechin gallate (EGCG) (epigallocatechin gallate, EGCG) and/or one or more plant its derivant (through esterified form, glucoside, sulfuric ester).EGCG is the main catechin that is found in the green tea.Green tea is mainly derived from catechin to the beneficial effect of health.In rat, the level that green tea catechins can reduce weightening finish after the meal, visceral fat mass and reduce triglyceride, blood plasma leptin and glucose.Also known tea catechol is used for increasing the energy expenditure of mice.Shown that the tea catechol is used to lose weight in the mankind, visceral fat mass and reduction plasma cholesterol, insulin and glucose level.Shown that green tea extract significantly increases energy expenditure and the fat oxidation in the healthy male.And, shown that in the brown adipose tissue of rat EGCG stimulates metabolic activity and oxygen expenditure.In addition, to studies show that several animals carry out, catechin suppresses the absorption of cholesterol, reduces the level of plasma cholesterol.Equally, epicatechin promotes the drainage of cholesterol and total lipid.Therefore, EGCG stimulates themogenesis and/or changes fat absorption, thereby has antiobesity action.
Term used herein " hydroxytyrosol " comprises that hydroxytyrosol and/or one or more plant its derivant (through esterified form, join saccharide, sulfate), such as oleuropein.A kind of in hydroxytyrosol or derivatives thereof or the analog is single compound form or is the form of purified plant extract (particularly Fructus Canrii Albi extract).Hydroxytyrosol is the main polyphenol that is found in the Fructus Canarii albi.It is said that hydroxytyrosol is a kind of antioxidant of high radical scavenging activity that has, its removing ability is the twice of quercetin, is more than three times of epicatechin.In the waste water that the course of processing of Fructus Canarii albi produces, contain the great amount of hydroxy group butyl alcohol, can reclaim hydroxytyrosol, thereby generate the butyl alcohol extract by this waste water.Hydroxytyrosol has and the identical health promotion effect of other many alcohol: suppress arteriosclerosis, promote intestinal and respiratory health and prophylaxis of cancer.Hydroxytyrosol has also reduced by the caused oxidative stress of smoking.
Used term " derivant, metabolite and analog thereof " has been contained by resveratrol, EGCG and hydroxytyrosol by chemical reaction institute derived compounds among the present invention, or has unusual similar structures and show the chemical compound of identical or similar pharmacologically active in animal.
Wasting is characterised in that, progressive loss of muscle mass, and muscle (particularly skeletal muscle or voluntary muscle and cardiac muscle) dies down and degenerates.
The process that atrophy and hypertrophy take place is guarded between each mammalian species.Multiple studies show that, between the rodent and the mankind, the basic molecule, cell and the physiological process that are taken place during the atrophy process are identical.Therefore, the rodent model of skeletal muscle atrophy successfully is used to understand the atrophy responses with predict human.
Wasting causes by multiple reason, and with various pathology and disease association.These comprise, but be not limited to, by the caused duchenne muscular dystrophy of genetic disorder disease, such as DuchenneShi duchenne muscular dystrophy, progressive muscular dystrophy, Becker type duchenne muscular dystrophy, Dejerine-Landouzy duchenne muscular dystrophy, ErbShi duchenne muscular dystrophy and child neuraxon duchenne muscular dystrophy without hesitation.Wasting also can come from chronic disease and age.With advancing age, skeletal muscle has been increased by the ratio of fibrous tissue replacement.Therefore, the normal aging among the mankind is relevant with the reduction gradually of skeletal muscle mass and intensity, and this disease is called as muscle and reduces disease, and it is owing to weak and run down.
And, the deficiency disorder relevant with the age, such as hypertension, glucose intolerance and diabetes, obesity, dyslipidemia, medicated porridge sample arteriosclerosis and cardiovascular disease, also the reduction with muscle quality is relevant.
In addition, other disease, such as cancer, autoimmune disease, infectious disease, HIV infection, AIDS, chronic inflammatory disease, arthritis, malnutrition, nephropathy, chronic obstructive nephropathy (COPD), emphysema, osteomalacia, chronic low back pain, peripheral nerve is impaired, spinal cord is impaired, chemistry is impaired, (CNS) is impaired for nervus centralis, relevantly with wasting maybe can cause wasting.At last, cause the disease of wasting uselessly to cause, such as long-term immobilization (because disease or such as the deformity that is subject on the wheelchair), long-term bed, fracture or wound by following with sexually transmitted disease (STD) disease.The skeletal muscle loss that causes of postoperative bed is about 10% weekly according to estimates.
The wasting deficiency disorder can cause serious health consequences without treatment.
The change that occurs in the wasting process can cause that condition dies down, thereby causes physical function variation and health status to worsen.
Thus, amyotrophy can seriously limit the patient and recovers from stationary state.Because the wasting that chronic disease causes can cause the activeness premature loss, and has increased the sickness rate of disease.In the old people who suffers from the defective muscle function and quality aspect relevant with the age, with the caused wasting of a property especially serious problem, it can cause permanent paralysis and premature dead, and fracture rates increases by useless.Although the clinical value of this disease is very big, exist Therapeutic Method seldom to be used to prevent this disease or this disease is recovered.
Be surprised to find now, contain be selected from following at least a component as composition of active components can be used for the prevention and the treatment animal in, particularly comprise in the human mammal, cause the wasting and the related muscles deficiency disorder of muscle loss and atrophy, described component is selected from: EGCG, hydroxytyrosol, resveratrol and its derivant, metabolite or analog.
In the specific embodiment of the present invention, nutraceutical composition except above-mentioned defined active component, also comprises at least a following carotenoid that is selected from: beta-carotene, phylloxanthin, cryptoxanthin, lycopene and beta-cryptoxanthin.
Except the mammal and the mankind, the special animal of being concerned about of the present invention is for for example, and domestic animal or house pet are such as horse, dromedary camel (camels dromedaries), Canis familiaris L., cat and bird and zoo captive animal.Domestic animal, house pet and zoo animal are preferably taken in active component via food (for example pet food comprises its drinking water).
And, have been found that compositions of the present invention works to various different critical paths involved in the muscle loss process.Compositions of the present invention increases muscle quality and the muscular strength in the animal model.
Therefore, the invention provides a kind of compositions that is used for the treatment of the wasting deficiency disorder, described deficiency disorder for example comprises duchenne muscular dystrophy and reduces disease, long-term bed, the spinal cord pain of injury, apoplexy, the caused wasting of fracture by cancer, AIDS, rheumatic arthritis, renal failure, uremia, chronic heart failure, the muscle relevant with the age.The present invention also provides a kind of method that is used for the treatment of Metabolic disorder disease, and described deficiency disorder comprises obesity, diabetes, hyperlipemia and bone loss (boneloss).
In preferred implementation of the present invention, described compositions comprises the combination of combination, EGCG and beta-cryptoxanthin of combination, EGCG and lycopene of combination, hydroxytyrosol and resveratrol of EGCG and resveratrol or the combination of hydroxytyrosol and lycopene.And, multivitamin and mineral supplement can be added in the nutraceutical composition of the present invention, to obtain the necessary nutrition of in some meals, losing of appropriate amount.Multivitamin and mineral supplement also can be used for the prevention of disease and prevent because nutrition leak and the deficiency that life style causes.
In other embodiments, nutraceutical composition of the present invention comprises resveratrol and derivant, metabolite or analog, and at least a following additional component: EGCG, hydroxytyrosol and derivant thereof, metabolite or analog, particularly resveratrol and the EGCG of being selected from.The content of above-mentioned resveratrol chemical compound (particularly resveratrol) is enough to provide about 0.5mg/ days to about 2000mg/ days, preferably about 5mg/ days to about 500mg/ days dosage for adult (the about 70kg of body weight) in the compositions.Therefore, if nutraceutical composition is food or beverage, the amount of then wherein contained resveratrol chemical compound (particularly resveratrol) suitably is that about 0.2mg is to every part of about 500mg.If nutraceutical composition is a medicament preparation, then this preparation can comprise about 0.5mg to the every solid dosage unit of about 500mg (for example every capsule or every tablet of tablet), or can be about 0.5mg daily dose about 2000mg daily dose extremely for liquid formulations.Preferably, the working concentration of EGCG makes that adult's (the about 70kg of body weight) day's expenditure is 10mg/ days to 2000mg/ days.Every portion of food or beverage are suitable for comprising the EGCG of about 2mg to about 500mg.If nutraceutical composition is a medicament preparation, then in this preparation the content of EGCG for about 5mg to the every dosage unit of about 500mg (for example every capsule or every tablet of tablet), or be extremely about 2000mg daily dose of about 10mg daily dose for liquid formulations content.
Replace EGCG or except EGCG, compositions can comprise hydroxytyrosol.The content of hydroxytyrosol can provide the daily dose of about 0.01mg/kg body weight to about 60mg/kg body weight for waiting the object of study of taking it in the said composition.Every portion of food or beverage are suitable for comprising the hydroxytyrosol of about 0.3mg to about 1250mg.If nutraceutical composition is a medicament preparation, then in this preparation the content of hydroxytyrosol for about 1mg to the every dosage unit of about 4000mg (for example every capsule or every tablet of tablet), or be extremely about 4000mg daily dose of about 1mg daily dose for liquid formulations content.
Be selected from carotenoid under the situation of beta-carotene, phylloxanthin, cryptoxanthin, lycopene and beta-cryptoxanthin, preferably, the working concentration of this carotenoid is feasible to comprise that the day's expenditure of people's (the about 70kg of body weight) animal is 0.05mg/ days to 50mg/ days (being equivalent to about 0.0007 daily dose to about 0.7mg/kg body weight), more preferably 0.5mg/ days to 30mg/ days.Every part of nutraceutical composition preferably comprises the carotenoid of 0.05mg to about 50mg.If said composition is a medicament preparation, then in the said composition content of carotenoid preferably can for about 0.5mg to every dosage unit of about 50mg (for example every capsule or every tablet of tablet) or liquid formulations unit.
Term used herein " part " refers to be grown up in the amount of a meal common food that absorbs or beverage in the time, for example can be in about 100g refers to the scope of about 500g.
The active component of above-mentioned defined compositions has the different mechanism of action, thereby has synergism in the process of the related muscles deficiency disorder in prevention muscle loss, atrophy and mammal (particularly human).
Following examples further specify the present invention.
Embodiment 1
Fed C57BLKS/J db/db mice (n=20/ group) resveratrol, EGCG and this two kinds of combination of compounds 3 months, and measured its effect muscle quality.C57BLKS/J db/db mice is because the shortage of leptin receptor suffers from serious Metabolic disorder disease, and owing to agingly suffers from loss muscle mass.Wasting is relevant with chronic metabolism disorder.And rodent and human in the two, the wasting by generation that various means are induced causes similar variation in muscle anatomy, cross section, function, fibrous type conversion, contractile protein expression and histology.In addition, proved that several agents can be used for regulating rodent and human skeletal muscle atrophy disease in the two.These reagent comprise anabolic steroid, growth hormone, insulin-like growth factor 1 and receptor, agonist.Therefore, rodent model can be used for assessing the effect of the inhibition wasting of chemical compound.
Male db/db mice from Jackson Laboratory (Bar Harbor, ME, USA).Big adult mice of 8 weeks is used in this experiment.Be housed in the plastics cage that has straw mattress mice is single, and allow it freely to obtain standard rodent and tap water.Temperature (24 ℃), humidity (55%) and the illumination of control animal house (bright-dark circulation in 12 hours).Animal is divided into four groups at random.To bestow resveratrol and EGCG with the blended form of feedstuff.Semen Maydis cellulose (meals 1%) is used as placebo as the supporting agent of resveratrol and EGCG and when using separately.Take in placebo for the 1st group; Take in the meals that contain 0.08 resveratrol for the 2nd group; Take in the meals that contain 0.08%EGCG for the 3rd group; Take in the meals that contain 0.08 resveratrol and 0.08%EGCG for the 4th group.In whole research process, measure body weight and food intake.After treating March, measure the muscle gross mass by nuclear magnetic resonance, NMR (NMR).During whole research, the food intake between each group is obviously difference not.
The body weight of each treatment group and muscular tissue weight are listed in the table 1.
Table 1:Treat the body weight (BW), muscle quality of db/db mice after 3 months and with respect to the variation of baseline.
In untreated animal (contrast), muscle quality has reduced by 2%.On the contrary, in hundred veratryl alcohols, EGCG and resveratrol+EGCG group, muscle quality has increased by 6%, 3% and 9% respectively.Therefore, bestow resveratrol, EGCG and the combination of these two and prevented the muscle loss in the mice.The combination of resveratrol and EGCG obviously increases muscle quality, and is more effective than any one unification compound of independent use.
Embodiment 2: pharmaceutical composition (adopting following composition to prepare by conventional process for preparation)
Soft gelatin capsule
Adopt following composition to prepare soft gelatin capsule by conventional process for preparation:
Active component: resveratrol 10mg, vitamin E 50mg;
Other composition: glycerol, water, gelatin, vegetable oil.
Hard gelatine capsule
Adopt following composition to prepare soft gelatin capsule by conventional process for preparation:
Active component: resveratrol 5mg, EGCG 100mg, genistein 5mg, vitamin E 50mg, vitamin K 1mg;
Other composition: filler: lactose or cellulose or cellulose derivative, lubricant (if desired): magnesium stearate (0.5%)
Tablet
Adopt following composition to prepare tablet by conventional process for preparation:
Active component: resveratrol 5mg, EGCG 50mg, vitamin E 20mg;
Other composition: microcrystalline Cellulose, silicon dioxide (SiO2), magnesium stearate, cross-linking sodium carboxymethyl cellulose (cross carmellose sodium).
Embodiment 3 adopts following composition to prepare food by conventional process:
The soft drink that contains resveratrol, EGCG and hydroxytyrosol can be prepared as follows:
1.1 concentration of juices liquid and can water-soluble flavouring agent[g]
The orange concentrated solution
60.3 ° Brix, 5.15% acidity 657.99
The Fructus Citri Limoniae concentrated solution
43.5 ° Brix, 32.7% acidity 95.96
The orange flavouring agent can water-soluble 3.43
The Fructus Pruni flavouring agent can water-soluble 6.71
Water 26.46
1.2 pigment
Beta-carotene 10%CWS 0.89
Water 67.65
1.3 acid and antioxidant
Ascorbic acid 4.11
Anhydrous citric acid 0.69
Water 43.18
1.4 stabilizing agent
Pectin 0.20
Sodium benzoate 2.74
Water 65.60
1.5 can oily molten flavouring agent
The orange flavouring agent can oil molten 0.34
Distillatory orange oil 0.34
1.6 active component
The consumption of resveratrol, EGCG and hydroxytyrosol is, 5mg resveratrol/every part, and every part of 10mgEGCG/ and 5mg hydroxytyrosol/every part
With concentration of juices liquid and can mixing by water-soluble flavouring agent, and do not mix air.Pigment is dissolved in the deionized water.Ascorbic acid and citric acid is soluble in water.Sodium benzoate is soluble in water.In whipping process, add pectin, and make its dissolving simultaneously ebullient.With this solution cooling.With orange oil and can oily molten flavouring agent premix.Active component involved in 1.6 stirred add in the concentration of juices mixture (1.1).
In order to prepare soft drink, all are together partially mixed with 1.1 to 1.6, utilize Turrax and high pressure homogenize instrument (P then
1=200bar, p
2=50bar) homogenize.
Claims (9)
1. be selected from the purposes of at least a component in making nutraceutical composition of EGCG, hydroxytyrosol, resveratrol and derivant thereof, metabolite or analog, described compositions is used for prevention and treatment animal, particularly comprise in the human mammal, cause muscle loss, amyotrophic wasting and other related muscles deficiency disorder.
2. the purposes of resveratrol as claimed in claim 1 and derivant, metabolite or analog, described resveratrol and derivant thereof, metabolite or analog and be selected from least a additional component combination of EGCG, hydroxytyrosol and derivant thereof, metabolite or analog.
3. as claim 1 or the described purposes of claim 2, wherein, described nutrient composite comprises at least a carotenoid that is selected from beta-carotene, phylloxanthin, cryptoxanthin, lycopene and beta-cryptoxanthin in addition.
4. the purposes of resveratrol as claimed in claim 1 and derivant, metabolite or analog, described resveratrol and derivant thereof, metabolite or analog and be selected from EGCG and the combination of at least a additional component of hydroxytyrosol.
5. the purposes of resveratrol as claimed in claim 1, described resveratrol and EGCG combination.
6. as any described purposes in the claim 1 to 5, wherein, the consumption of described resveratrol is enough to for waiting that the object of study of taking it provides the daily dose of 0.03mg/kg body weight to about 10mg/kg body weight; The consumption of described EGCG is enough to for waiting that the object of study of taking it provides the daily dose of about 0.1mg/kg body weight to about 20mg/kg body weight; The consumption of described hydroxytyrosol is enough to for waiting that the object of study of taking it provides the daily dose of about 0.03mg/kg body weight to about 10mg/kg body weight.
7. purposes as claimed in claim 3, the consumption of wherein said carotenoid are enough to for waiting that the object of study of taking it provides the daily dose of about 0.0007mg/kg body weight to about 0.7mg/kg body weight.
8. as any described purposes in the claim 1 to 7, wherein, described nutraceutical composition is food or beverage or the supplement composition that is used for Foods or drinks.
9. as any described purposes in the claim 1 to 7, wherein, described nutraceutical composition is a pharmaceutical composition.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP05022414 | 2005-10-14 | ||
| EP05022414.6 | 2005-10-14 | ||
| EP06009943.9 | 2006-05-15 |
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| CN2010105185792A Division CN101978958A (en) | 2005-10-14 | 2006-10-11 | Nutraceutical composition for the treatment of muscle wasting |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103169695A (en) * | 2013-02-05 | 2013-06-26 | 西安交通大学 | Application of alpha-lipoic acid, acetyl-L-carnitine, coenzyme Q10 and hydroxytyrosol composition for preventing and treating amyotrophy |
| CN104837369A (en) * | 2012-10-04 | 2015-08-12 | 雅培制药有限公司 | Methods for enhancing the effect of EGCg on mitigating skeletal muscle loss |
| CN105451728A (en) * | 2013-08-09 | 2016-03-30 | 三得利控股株式会社 | Agent for promoting in vivo absorption of hydroxytyrosol and derivatives thereof and use of same |
| CN106061291A (en) * | 2013-12-18 | 2016-10-26 | 雅培公司 | Methods for increasing skeletal muscle protein synthesis using green tea extract |
| CN115245201A (en) * | 2021-04-28 | 2022-10-28 | 益达生医股份有限公司 | Nutritional composition for improving sarcopenia and application thereof |
| WO2022226828A1 (en) * | 2021-04-28 | 2022-11-03 | 益达生医股份有限公司 | Nutritional composition for improving sarcopenia and use thereof |
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2006
- 2006-10-11 CN CNA2006800383106A patent/CN101312718A/en active Pending
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104837369A (en) * | 2012-10-04 | 2015-08-12 | 雅培制药有限公司 | Methods for enhancing the effect of EGCg on mitigating skeletal muscle loss |
| CN103169695A (en) * | 2013-02-05 | 2013-06-26 | 西安交通大学 | Application of alpha-lipoic acid, acetyl-L-carnitine, coenzyme Q10 and hydroxytyrosol composition for preventing and treating amyotrophy |
| CN105451728A (en) * | 2013-08-09 | 2016-03-30 | 三得利控股株式会社 | Agent for promoting in vivo absorption of hydroxytyrosol and derivatives thereof and use of same |
| CN106061291A (en) * | 2013-12-18 | 2016-10-26 | 雅培公司 | Methods for increasing skeletal muscle protein synthesis using green tea extract |
| CN115245201A (en) * | 2021-04-28 | 2022-10-28 | 益达生医股份有限公司 | Nutritional composition for improving sarcopenia and application thereof |
| WO2022226828A1 (en) * | 2021-04-28 | 2022-11-03 | 益达生医股份有限公司 | Nutritional composition for improving sarcopenia and use thereof |
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