CN103169695B - Application of alpha-lipoic acid, acetyl-L-carnitine, coenzyme Q10 and hydroxytyrosol composition for preventing and treating amyotrophy - Google Patents
Application of alpha-lipoic acid, acetyl-L-carnitine, coenzyme Q10 and hydroxytyrosol composition for preventing and treating amyotrophy Download PDFInfo
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- CN103169695B CN103169695B CN201210451911.7A CN201210451911A CN103169695B CN 103169695 B CN103169695 B CN 103169695B CN 201210451911 A CN201210451911 A CN 201210451911A CN 103169695 B CN103169695 B CN 103169695B
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- amyotrophy
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- carnitine
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Abstract
The invention relates to an application of an alpha-lipoic acid, acetyl-L-carnitine, coenzyme Q10 and hydroxytyrosol composition for preventing and treating amyotrophy, wherein the alpha-lipoic acid, the acetyl-L-carnitine, the coenzyme Q10 and the hydroxytyrosol are composited in appropriate proportion, so that the generation of mitochondria in muscle can be promoted; the loss of the mitochondria can be inhibited; and the muscle function can be improved. Therefore, the atrophy of muscle fibers during the generation process of the amyotrophy is inhibited effectively; and the growth of the muscle fibers during the recuperation process of the amyotrophy is promoted. In addition, the motion function decline caused by the amyotrophy is lightened effectively; and the improvement in the motion function during the recuperation process of the amyotrophy is promoted.
Description
Technical field
The present invention relates to biology and medicine and pharmacology field, particularly alpha-lipoic acid, acetyl-L-carnitine, ubiquinone
10and hydroxytyrosol compatibility is in the application preventing and treating in amyotrophy generation.
Background technology
Skeletal muscle atrophy refers to that the pathologic such as quality minimizing or afunction that skeletal muscle occurs changes, and mainly comprises by muscle and uses and reduce the muscular atrophy of disuse causing and the neurogenic muscular atrophy being caused by the nerve damage that participates in muscle control.Amyotrophy main manifestations is that muscle protein content reduces, and diameter of muscle fiber diminishes, the lower degradation of muscle strength and fatigue resistance.
Amyotrophic control causes the amyotrophic constitutional cause of disease except removing, main by suitable training at present, gives muscle load, delays amyotrophy and occurs.But based on individual pathological state and condition restriction (as space flight), training scheme often can not get effectively carrying out.Therefore, adopt appropriate nutrition or pharmaceutical intervention occur or promote amyotrophic rehabilitation course to become one of amyotrophic Critical policies of control to alleviate amyotrophy.But, have not yet to see and can effectively prevent and treat amyotrophic nutritional intervention measure or medicine.
Existing research discovery, the nutrient effect of most of single components is limited even invalid, comprises acetyl-L-carnitine and ubiquinone
10deng.Wherein acetyl-L-carnitine can promote muscle Mitochondria to generate the expression of related gene, increase quantity (the list of references 1:Cassano of I fiber type in musculus soleus, P.et al.Acetyl-L-carnitine feeding to unloaded rats triggers in soleus muscle the coordinated expression of genes involved in mitochondrial biogenesis.Biochimica et Biophysica A cta (BBA)-Bioenergetics1757, 1421-1428 (2006)), but and have no the amyotrophic effect of obvious inhibition (list of references 2:Cassano, P.et al.Muscle unloading potentiates the effects of acetyl ?L ?canitine on the slow oxidative muscle phenotype.BioFactors36, 70-77 (2010)).In the time of supplementary coenzyme Q10 and other antioxidants, can not reach the effect that suppresses amyotrophy and improve muscle function.(list of references 2:Koesterer, T., Dodd, S.L. & Powers, S.Increased antioxidant capacity does not attenuate muscle atrophy caused by unweighting.Journal of Applied Physiology93,1959 (2002)) limitation of the nutrient of prompting single component in antagonist atrophy process.
Summary of the invention
The deficiency existing in order to overcome prior art treatment amyotrophy method, the object of the invention is to propose new drug target---the mitochondrion that amyotrophy occurs of preventing and treating, in earlier stage the Mitochondrially targeted nutrient theory of setting up and proving according to us, adopt alpha-lipoic acid, acetyl-L-carnitine, ubiquinone
10and hydroxytyrosol, form compatibility with appropriate ratio, work in coordination with and improve mitochondrial function, in the situation by normal diet, take in effective natural nutrient-alpha-lipoic acid, acetyl-L-carnitine, ubiquinone
10and hydroxytyrosol compatibility, improve muscle function, reach the object that suppresses amyotrophy symptom and promote amyotrophy symptom rehabilitation course.
The alpha-lipoic acid that human body is taken in is mainly derived from vegetable and the fruit in food; Acetyl-L-carnitine is to be mainly derived from meat; Coenzyme Q10 is mainly derived from pluck and beef etc.Hydroxytyrosol is a kind of native compound that derives from Fructus Canrii Albi extract.Existing studies have shown that, alpha-lipoic acid, coenzyme Q10 and hydroxytyrosol all have remarkable antioxidation.Acetyl-L-carnitine and alpha-lipoic acid have good protective effect to muscle and brain; hydroxytyrosol is to the facilitation such as bone growth and development and cardiovascular function, simultaneously the effect to cancer promotion treatment as good in pulmonary carcinoma, breast carcinoma, uterus carcinoma and carcinoma of prostate etc. have.Therefore, these compounds all belong to the higher medicine of safety.
In order to achieve the above object, the technical solution adopted in the present invention is:
Alpha-lipoic acid, acetyl-L-carnitine, ubiquinone
10and hydroxytyrosol compatibility is in the application preventing and treating in amyotrophy generation, it is characterized in that, using mitochondrion as the Main Function target spot of preventing and treating amyotrophy generation, provides alpha-lipoic acid, acetyl-L-carnitine, ubiquinone
10and the application of hydroxytyrosol compatibility in the medicine of preventing and treating amyotrophy generation, alpha-lipoic acid, acetyl-L-carnitine, ubiquinone
10and the Mitochondrially targeted nutrient such as hydroxytyrosol, act on respectively multiple Metabolism of Mitochondria approach, the collaborative mitochondrial injury of repairing, to alleviate and lose the amyotrophic generation that load etc. causes, can significantly promote its rehabilitation course for the amyotrophy pathological symptom having occurred simultaneously. described alpha-lipoic acid structural formula is
acetyl-L-carnitine structural formula is
ubiquinone
10structural formula is
hydroxytyrosol structural formula is
Alpha-lipoic acid, acetyl-L-carnitine, ubiquinone
10and hydroxytyrosol compatibility dosage is 10:20:1:2.
Alpha-lipoic acid, acetyl-L-carnitine, ubiquinone
10and hydroxytyrosol compatibility can effectively promote the increase of muscle quality in amyotrophy rehabilitation course.
Alpha-lipoic acid, acetyl-L-carnitine, ubiquinone
10and hydroxytyrosol compatibility can effectively suppress myofibrillar dwindling in amyotrophy process, and promote myofibrillar growth in amyotrophy rehabilitation course.
Alpha-lipoic acid, acetyl-L-carnitine, ubiquinone
10and hydroxytyrosol compatibility can effectively improve the improvement that the motor function being caused by amyotrophy declines and promotes motor function in amyotrophy rehabilitation course.
Alpha-lipoic acid, acetyl-L-carnitine, ubiquinone
10and hydroxytyrosol compatibility can suppress the minimizing of amyotrophy process Mitochondria and promote the increase of amyotrophic rehabilitation course process Mitochondria.
Alpha-lipoic acid, acetyl-L-carnitine, ubiquinone
10and hydroxytyrosol compatibility can significantly suppress the generation increase that amyotrophy process Mitochondria generates reduction and promotes amyotrophic rehabilitation course process Mitochondria.
Alpha-lipoic acid, acetyl-L-carnitine, ubiquinone
10and hydroxytyrosol is chondriosome nutrient, wherein intracellular main target spot is mitochondrion.
It is the amyotrophic active drug action target spot of control that the present invention proposes mitochondrion first, applies Mitochondrially targeted nutrient, is prevent and treat amyotrophic New Policy, has initiative.The Mitochondrially targeted nutrient adopting comprises alpha-lipoic acid, acetyl-L-carnitine, ubiquinone
10and hydroxytyrosol.The formula that the appropriate proportioning of these compositions forms has remarkable synergism, can effectively alleviate amyotrophy, promotes amyotrophic rehabilitation course.
Advantage of the present invention: one, intervention target spot is clear and definite.For the disorder of amyotrophy Mitochondria metabolic pathway, select Mitochondrially targeted nutrient to act on correlation molecule path.
Two, good safety.Alpha-lipoic acid, acetyl-L-carnitine, ubiquinone
10and hydroxytyrosol is all the natural nutrients that derive from food, wherein alpha-lipoic acid is mainly derived from vegetable and fruit, and acetyl-L-carnitine is mainly derived from meat, ubiquinone
10be mainly derived from pluck, hydroxytyrosol derives from Fructus Canarii albi.They have no side effect to health, have good safety.
Three, the compatibility mechanism based on chondriosome nutrient theory.Alpha-lipoic acid, acetyl-L-carnitine, ubiquinone
10and the principle of hydroxytyrosol compatibility is: 1, acetyl-L-carnitine, ubiquinone
10promote the biological oxidation of mitochondrion fatty acid, promote mitochondrion energy supply ability; 2, for the generation of excessive active oxygen in amyotrophy generation Mitochondria, alpha-lipoic acid, ubiquinone
10and hydroxytyrosol can work in coordination with and remove intramuscular active oxygen, maintain mitochondrial oxidation reduction balance; 3, mitochondrion loss is the important pathological characters that amyotrophy occurs, and we adopt alpha-lipoic acid, and acetyl-L-carnitine and hydroxytyrosol compatibility can significantly promote mitochondrial generation, maintain mitochondria number; 4,, for the decline of mitochondria activity, select alpha-lipoic acid and ubiquinone
10deng coenzyme/prothetic group and the electron transport body of key enzyme in mitochondrion, effectively improve mitochondrial function.
So adopt alpha-lipoic acid in our invention, acetyl-L-carnitine, ubiquinone
10and the compatibility of four kinds of nutrients of hydroxytyrosol, wherein compatibility dosage is 10:20:1:2.This compatibility program action target spot is clear and definite, and nutrient synergistic mechanism is remarkable, has the market prospect of extensive use in amyotrophy control application, can open up a new medical approach for amyotrophic prevention and treatment.
Brief description of the drawings
Fig. 1 is alpha-lipoic acid, acetyl-L-carnitine, ubiquinone
10and the impact of hydroxytyrosol compatibility on muscle quality.
Fig. 2 is alpha-lipoic acid, acetyl-L-carnitine, ubiquinone
10and hydroxytyrosol compatibility is to myofibrillar inhibitory action of dwindling in amyotrophy process, and facilitation to Growth of Muscle Fiber in amyotrophy rehabilitation course.
Fig. 3 is alpha-lipoic acid, acetyl-L-carnitine, ubiquinone
10and the affect coordinate diagram of hydroxytyrosol compatibility on rat motor function, wherein: abscissa is grouping, not nutrient adding compatibility of three groups, left side, three groups, right side nutrient adding compatibility.Vertical coordinate is the lasting time of rat motor.
Fig. 4 is alpha-lipoic acid, acetyl-L-carnitine, ubiquinone
10and the affect coordinate diagram of hydroxytyrosol compatibility on rat soleus muscle Mitochondria DNA copy number, wherein: abscissa is grouping, not nutrient adding compatibility of three groups, left side, three groups, right side nutrient adding compatibility.Vertical coordinate is rat order fish flesh Mitochondria DNA copy number.
Fig. 5 is alpha-lipoic acid, acetyl-L-carnitine, ubiquinone
10and hydroxytyrosol compatibility generates the coordinate diagram that affects of regulatory factor PGC-1 α on rat soleus muscle Mitochondria, wherein: abscissa is grouping, not nutrient adding compatibility of three groups, left side, three groups, right side nutrient adding compatibility.Vertical coordinate is the level that rat soleus muscle Mitochondria generates regulatory factor PGC-1 α.
Detailed description of the invention
1. animal feeding
Sprague Dawley male rat is to buy from Shanghai Si Laike animal Co., Ltd.Rat feeding is in the room of controllable temperature (22 degree are to 28 degree) and humidity (60%), and the light in room maintains in the circulation at 12 hour daytime, 12 hour night, and carrying out middle rat in experiment can ad lib and water inlet.
2. hind leg loses the foundation of load model
Experimental rat one is divided into six groups, 10 every group.Six groups are respectively: (1) Normal group; (2) hind leg loses 3 weeks groups of load; (3) hind leg loses to load to add for 3 weeks and adds nutrient compatibility group every day 1 week group (4) normal control while of rehabilitation.(5) hind leg loses and adds nutrient compatibility group every day 3 weeks whiles of load.(4) hind leg loses to load to add for 3 weeks and adds nutrient compatibility group every day 1 week while of rehabilitation.Be 4 weeks experimental period.Nutrient compatibility is: alpha-lipoic acid every day (50mg/kg), acetyl-L-carnitine (100mg/kg), ubiquinone
10(5mg/kg) and hydroxytyrosol (10mg/kg).
3. correlated results
(1) alpha-lipoic acid, acetyl-L-carnitine, ubiquinone
10and hydroxytyrosol compatibility loses the amyotrophic inhibitory action of load induction to hind leg and to applying the facilitation of amyotrophy rehabilitation course after load.
After experiment finishes, weigh and put to death rat, get shank musculus soleus and weigh, the ratio that calculates muscle and body weight with this, acquired results as shown in Figure 1, can obviously find out that hind leg loses load and causes that the ratio of muscle and body weight obviously declines, in rehabilitation course process, this ratio gos up; Alpha-lipoic acid, acetyl-L-carnitine, ubiquinone
10and hydroxytyrosol compatibility can significantly promote the rising of this ratio in rehabilitation course.
Fig. 2 shows simultaneously, and in amyotrophy process, muscle fiber cross sectional area significantly reduces, and rehabilitation course can make cross sectional area increase; Alpha-lipoic acid, acetyl-L-carnitine, ubiquinone
10and hydroxytyrosol compatibility can partly suppress cross sectional area losing reducing in load process, can promote the increase of muscle fiber area of section in amyotrophy rehabilitation course simultaneously.
In addition, Fig. 3 shows in amyotrophy process, rat motor function reduction, also corresponding rising of motor function in amyotrophy rehabilitation course; Alpha-lipoic acid, acetyl-L-carnitine, ubiquinone
10and hydroxytyrosol compatibility can suppress motor function losing the decline in load process and promote its lifting in rehabilitation course process.
Result represents with Mean ± S.E.M form, and statistical result represents the statistical result of 10 rats; Data analysis uses Two Way-ANOVA analytical method, comprise " losing load/rehabilitation " effect and " nutrient compatibility " effect, significantly statistical significance is * p<0.05, * p<0.01, * * * p<0.01 hind leg loses load group Vs. Normal group; #p<0.05, ##p<0.01, ###p<0.01 rehabilitation course group Vs. hind leg loses load group; ! P<0.05,! ! P<0.01,! ! ! P<0.01 is without nutrient compatibility group Vs. nutrient compatibility group.
(2) alpha-lipoic acid, acetyl-L-carnitine, ubiquinone
10and hydroxytyrosol compatibility can effectively suppress the inhibition of hind leg mistake load Mitochondria generation and the minimizing of mitochondria number; Can effectively promote the activation of rehabilitation course Mitochondria generation and increasing of mitochondria number simultaneously.
Mitochondrion is as one of most important organelle in muscle, for metabolism and the contraction of muscle provide energy---and ATP, has occurred that in amyotrophy process the inhibition of mitochondrion generation and the minimizing of mitochondria number are as Fig. 4, shown in 5.Alpha-lipoic acid, acetyl-L-carnitine, ubiquinone
10and hydroxytyrosol compatibility can effectively suppress the reduction of topmost regulatory factor PGC-1 α in the generation of hind leg mistake load Mitochondria and the minimizing of mitochondria DNA copy number; Can effectively promote the rising of PGC-1 α in rehabilitation course and increasing of mitochondria DNA copy number simultaneously.These all point out alpha-lipoic acid, acetyl-L-carnitine, ubiquinone
10and the function of hydroxytyrosol compatibility aspect the generation of promotion mitochondrion and protection mitochondria number.
(2) disorder of mitochondrial function is the amyotrophic new drug target of reply, and chondriosome nutrient can be reached and be suppressed amyotrophic object by protective wire mitochondria function.
By above the results show alpha-lipoic acid, acetyl-L-carnitine, ubiquinone
10and hydroxytyrosol compatibility can effectively suppress amyotrophy and mitochondrion generation inhibition and the decreased number of the induction of hind leg mistake load; Can promote in rehabilitation course amyotrophic improvement and mitochondrion generates and the improvement of number simultaneously.
Alpha-lipoic acid, acetyl-L-carnitine, ubiquinone
10and hydroxytyrosol is the natural component in daily food, its useful effect concentration is low, and safety is without any side effects.Long-term taking has remarkable effect to clinical treatment and prevention amyotrophy, is the effective ways that effect a permanent cure, and has the market prospect of extensive use.This is alpha-lipoic acid, acetyl-L-carnitine, ubiquinone
10and hydroxytyrosol compatibility has been opened up a new medical approach in clinical extensive use.
In amyotrophy process, there is the inhibition of mitochondrion generation and the minimizing of mitochondria number, in the present invention, taking Metabolism of Mitochondria approach as target spot, adopt targetedly chondriosome nutrient compatibility can effectively promote mitochondrion generate and improve mitochondrial function, thereby alleviate amyotrophic generation, promote amyotrophic rehabilitation.Chondriosome nutrient is that a class targeting is in mitochondrial natural product, by promoting mitochondrion to generate or improving the effect that mitochondrial function reaches prevention or treats disease.They or itself be exactly coenzyme or the prothetic group of various enzymes in mitochondrion, as thioctic acid (lipoi c acid) and ubiquinone
10(coenzyme Q
10)), or can alleviate Cellular Oxidation damage, as thioctic acid, coenzyme Q10, vitamin C and vitamin E etc., or can promote mitochondrion to generate or improve mitochondrial function, as resveratrol (resveratrol), hydroxytyrosol (hydroxytyrosol), epigallocatechin gallate (EGCG) (epigallocatechin gallate, EGCG) etc.In the present invention, recently the Metabolism of Mitochondria defect Mechanism during the amyotrophy of finding based on research team occurs, proposing first mitochondrion is the active drug target spot in amyotrophy control, select chondriosome nutrient by specific aim, design nutrients formula, can effectively alleviate the multiple mitochondria dysfunction that amyotrophy causes, thus prevention and treatment amyotrophy.
Claims (8)
1. alpha-lipoic acid, acetyl-L-carnitine, ubiquinone
10and hydroxytyrosol compatibility prevents and treats the application in amyotrophy medicine in preparation, it is characterized in that, using mitochondrion as the action target spot of preventing and treating amyotrophy and occurring, provide alpha-lipoic acid, acetyl-L-carnitine, ubiquinone
10and hydroxytyrosol compatibility is prevented and treated amyotrophic generation, alpha-lipoic acid, acetyl-L-carnitine, ubiquinone
10and hydroxytyrosol is as Mitochondrially targeted nutrient, act on respectively multiple Metabolism of Mitochondria approach, the collaborative mitochondrial injury of repairing, alleviates and loses the amyotrophic generation that load causes, promote its rehabilitation for the amyotrophy pathological symptom having occurred, described alpha-lipoic acid structural formula is simultaneously
acetyl-L-carnitine structural formula is
ubiquinone
10structural formula is
hydroxytyrosol structural formula is
2. application according to claim 1, is characterized in that, alpha-lipoic acid, acetyl-L-carnitine, ubiquinone
10and hydroxytyrosol compatibility dosage is 10:20:1:2.
3. application according to claim 1 and 2, is characterized in that, alpha-lipoic acid, acetyl-L-carnitine, ubiquinone
10and hydroxytyrosol compatibility promotes the increase of muscle quality in amyotrophy rehabilitation course.
4. application according to claim 1 and 2, is characterized in that, alpha-lipoic acid, acetyl-L-carnitine, ubiquinone
10and myofibrillar dwindling in hydroxytyrosol compatibility inhibition amyotrophy process, and promote myofibrillar growth in amyotrophy rehabilitation course.
5. application according to claim 1 and 2, is characterized in that, alpha-lipoic acid, acetyl-L-carnitine, ubiquinone
10and hydroxytyrosol compatibility improves the improvement that the motor function being caused by amyotrophy declines and promotes motor function in amyotrophy rehabilitation course.
6. application according to claim 1 and 2, is characterized in that, alpha-lipoic acid, acetyl-L-carnitine, ubiquinone
10and hydroxytyrosol compatibility suppresses the generation increase that amyotrophy process Mitochondria generates reduction and promotes amyotrophic rehabilitation course Mitochondria.
7. application according to claim 1 and 2, is characterized in that, alpha-lipoic acid, acetyl-L-carnitine, ubiquinone
10and hydroxytyrosol compatibility suppresses the minimizing of amyotrophy process Mitochondria and promotes the increase of amyotrophic rehabilitation course Mitochondria.
8. application according to claim 1 and 2, is characterized in that, mitochondrion is as the drug target in amyotrophy, and described four kinds of nutrient compatibilities improve mitochondrial function, prevent and treat amyotrophy.
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| IT202200006080A1 (en) * | 2022-03-28 | 2023-09-28 | Laboratorio Della Farm S P A | Oral solid composition for the management of neuropathic, osteo-articular, gynecological, post-surgical pain and mitochondrial trophism |
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| CN101003501B (en) * | 2006-01-20 | 2010-04-21 | 北京英力科技发展有限公司 | Method for synthesizing coenzyme Q10 in high efficiency |
| ES2670836T3 (en) * | 2010-06-16 | 2018-06-01 | Alfasigma S.P.A. | Acetyl-carnitine for use in a method to increase neurogenesis in neuronal tissue |
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| IT202200006080A1 (en) * | 2022-03-28 | 2023-09-28 | Laboratorio Della Farm S P A | Oral solid composition for the management of neuropathic, osteo-articular, gynecological, post-surgical pain and mitochondrial trophism |
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