CN113398144B - Application of nucleotide mixture in preparation of preparation for preventing or relieving sarcopenia of old people - Google Patents

Application of nucleotide mixture in preparation of preparation for preventing or relieving sarcopenia of old people Download PDF

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CN113398144B
CN113398144B CN202110851468.1A CN202110851468A CN113398144B CN 113398144 B CN113398144 B CN 113398144B CN 202110851468 A CN202110851468 A CN 202110851468A CN 113398144 B CN113398144 B CN 113398144B
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CN113398144A (en
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李勇
武欣
陈玉松
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Chen Yusong
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/706Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
    • A61K31/7064Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
    • A61K31/7076Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines containing purines, e.g. adenosine, adenylic acid
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/706Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/706Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
    • A61K31/7064Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
    • A61K31/7068Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
    • A61K31/7072Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/706Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
    • A61K31/7064Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
    • A61K31/7076Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines containing purines, e.g. adenosine, adenylic acid
    • A61K31/708Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines containing purines, e.g. adenosine, adenylic acid having oxo groups directly attached to the purine ring system, e.g. guanosine, guanylic acid
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00Drugs for disorders of the muscular or neuromuscular system

Abstract

The invention discloses an application of a nucleotide mixture in preparing a preparation for preventing or relieving sarcopenia of old people, belonging to the field of medicine and health care. The nucleotide mixture consists of five types of 5' -mononucleotides or sodium salt forms thereof, and the mass ratio of various nucleotides in the synthesis of CMP, AMP, UMP, GMP and IMP acid type is respectively as follows: CMP 23-78%, AMP 6-44%, UMP 7-40%, GMP 7-51%, IMP 0, or greater than 0 and not greater than 2.5%. The nucleotide has small molecular weight, can be absorbed by human body quickly, and has high bioavailability. The invention discovers that the ingestion of nucleotide can improve the function of skeletal muscle of the old organism and increase the muscle mass by improving the function disorder of mitochondria and reducing the oxidative stress, thereby playing the role of preventing and treating sarcopenia. Provides a new way for preparing the medicine or the functional food for preventing and treating sarcopenia.

Description

Application of nucleotide mixture in preparation of preparation for preventing or relieving sarcopenia of old people
Technical Field
The invention belongs to the field of medicine health care, relates to a nucleotide product and new application thereof, and particularly relates to application of a nucleotide mixture produced by taking ribonucleic acid as a raw material and degrading the ribonucleic acid by an enzyme method in preparation of a preparation for preventing or relieving sarcopenia of old people.
Background
In today's society, the increasing life expectancy of everyone is leading to a rapid aging of the global population with a significant decline in fertility rates. According to data issued by the national statistical bureau, the population of the aged 60 years old and over in China reaches 2.54 hundred million by 18.1 percent of the total population at the end of 2019, and the population of the aged 65 years old and over reaches 1.76 million by 12.6 percent of the total population. Reports predict that china will enter the aging society from the aging society in about 2022, at which time 65 years and older will account for over 14% of the total population.
The aging of the population brings great challenges to public health in China and even the world. With the continuous development of the aging population of China, sarcopenia, a syndrome closely related to the elderly, is more concerned. Sarcopenia is an age-related clinical syndrome of decreased skeletal muscle mass, strength and/or associated loss of body function. Sarcopenia has become a global health problem. Muscle mass declines 1-2% per year in people over the age of 50, while muscle strength declines 1.5% per year between the ages of 50 and 60, with 3% decline in older people over the age of 60. With the increase of age, the incidence of sarcopenia is rapidly increased, the incidence of sarcopenia of the old people in China is higher, and according to the previous research, the incidence of sarcopenia of people over 60 years in China is 18.6%, wherein the incidence of sarcopenia of people over 80 years in China is 52%. Sarcopenia leads to an increased risk of falls and fractures in the elderly, a decline in the ability to live daily, and is associated with heart disease, respiratory disease and cognitive disorders. Can cause the patients to have motor dysfunction, the life quality is reduced, the independent living ability is lost, or the patients need to be attended by others for a long time, and the death risk is increased. Sarcopenia increases hospitalization risks, increases the care costs during hospitalization, and increases hospitalization costs. It has been found that hospitalization of sarcopenia in elderly patients is 5 times more expensive than non-sarcopenia patients. In 2000, sarcopenia caused an estimated direct medical cost of about $ 185 billion per year in the united states, accounting for 1.5% of the total cost of direct healthcare. It has been found that if the prevalence of sarcopenia is reduced by 10%, U.S. medical expenses can be saved by $ 11 billion per year. In China, with the arrival of aging society, sarcopenia brings great economic and social burden to individuals and society if no intervention is added.
The sarcopenia has high prevalence rate and great health hazard, and brings great economic burden to individuals and society, but no specific medicine aiming at the sarcopenia exists at present. Nutritional intervention and physical exercise are currently recommended preventive and therapeutic strategies for sarcopenia. Exercise intervention is an effective therapeutic strategy, and can improve muscle quality and strength, increase muscle protein synthesis rate, enhance mitochondrial function, increase skeletal muscle satellite cell content, and the like. However, resistance to resistance training may occur, thereby reducing its promoting effect on skeletal muscle protein synthesis. In addition, exercise is sometimes difficult to achieve in elderly people with reduced physical function. Research shows that sarcopenia is closely related to nutritional deficiency, and nutritional intervention is one of the important means for treating sarcopenia. Compared with medicine, the nutritional composition has more natural components and less side effects. Therefore, it is clearly important to explore a nutritional composition that is effective in preventing and alleviating sarcopenia, based on a better understanding of the underlying mechanisms of this disease.
Nucleotides are composed of pentoses, bases and phosphoric acid, and are basic constituent units of nucleic acids. The nucleotide can be derived from endogenous synthesis of human body and exogenous synthesis by biological enzymolysis technology and the like. In recent years, research finds that exogenous nucleotides are indispensable nutrient components under specific physiological conditions, and the exogenous nucleotides can be absorbed and utilized by tissues under the conditions of tissues and organs with vigorous metabolism or when organisms are stressed, challenged by immunity, damaged by liver, starved and rapidly grown, so that the consumption of de novo synthesis or salvage synthesis of the organisms is saved, and the functions of the tissues can be optimized. In addition, after the nucleic acid is degraded into the nucleotide in vitro by an enzymolysis mode, the in vivo decomposition process can be omitted, and the nucleic acid is easier to digest and absorb by the human body. At present, no report is found on the research of the effect of exogenous nucleotide obtained by enzymolysis technology on the prevention and the relief of sarcopenia.
Disclosure of Invention
According to the research, the ingestion of nucleotide improves the skeletal muscle function and increases the muscle mass of the aged SAMP8 mice by improving the function disorder of mitochondria and reducing the oxidative stress. At present, in the aspect of treating sarcopenia, nucleotide and other non-protein nitrogen nutritional supplements are not seen in the market, and novel products for preventing and relieving sarcopenia can be provided for the middle-aged and the elderly through innovative research and development, and if the technology is applied to the health industry, the health care and medical treatment requirements of sarcopenia patients can be fully met.
The invention aims to provide application of a nucleotide mixture preparation with lower molecular weight and quick absorption in preparing a preparation for preventing and delaying sarcopenia, and provides a new way for preventing and treating sarcopenia through a dietary supplement. Meanwhile, a stable, effective and repeatable experimental animal model method is established.
In order to realize the purpose, the invention adopts the following technical scheme:
the invention provides application of a nucleotide mixture in preparing a preparation for preventing or relieving sarcopenia of old people, wherein the nucleotide mixture is a 5' -monophosphate nucleotide mixture.
The nucleotide mixture consists of five types of 5' -mononucleotides or sodium salt forms thereof, wherein the mass ratio of various nucleotides in the synthesis of CMP, AMP, UMP, GMP and IMP acid type is respectively as follows: CMP 23-78%, AMP 6-44%, UMP 7-40%, GMP 7-51%, IMP 0, or greater than 0 and not greater than 2.5%.
Further, the mass ratio of each nucleotide in the nucleotide mixture to be converted into CMP, AMP, UMP, GMP and IMP acid type is respectively as follows: CMP 43%, AMP 17%, UMP 21%, GMP 18%, and IMP are 1%.
Further, the preparation is powder, tablets, soft and hard capsules, beverage or oral liquid.
Furthermore, the 5' -monophosphate nucleotide mixture can improve the skeletal muscle function of the elderly organism, increase the muscle mass and delay the occurrence and development of sarcopenia by improving mitochondrial dysfunction and reducing oxidative stress.
The invention discovers that the existing substance, namely the 5' -monophosphate nucleotide mixture has the function of preventing and delaying sarcopenia of an aged SAMP8 mouse, and discovers the application of the mixture in preparing medicines or functional foods for preventing and treating sarcopenia and other diseases. Animal experiments prove that the ingested nucleotide can reduce the oxidative stress level in mice, improve mitochondrial dysfunction, enhance the muscle function of old mice and increase the muscle mass. The nucleotide mixture is shown to have remarkable effects of preventing and treating sarcopenia.
Drawings
FIG. 1 is a graph showing the effect of nucleotide mixtures on SOD in muscle tissue of aged SAMP8 mice.
FIG. 2 is a graph showing the effect of nucleotide mixtures on SDH enzyme activity in muscle tissue of aged SAMP8 mice.
FIG. 3 is a graph showing the effect of nucleotide mixtures on ATP content in muscle tissue of aged SAMP8 mice.
FIG. 4 is a graph of the effect of nucleotide mixtures on mitochondria in aged SAMP8 murine soleus.
FIG. 5 shows the effect of nucleotide mixtures and single species of nucleotides on ATP content in muscle tissue of aged SAMP8 mice.
Detailed Description
The following non-limiting examples will allow one of ordinary skill in the art to more fully understand the present invention, but are not intended to limit the invention in any way.
Example 1
1. The nucleotide mixture of this example is prepared from five 5' -mononucleotides or their sodium salts in the form of: CMP43 wt%, AMP17 wt%, UMP21 wt%, GMP18 wt%, IMP 1 wt% ratio.
2. The preparation method comprises the following steps:
(1) the five 5' -mononucleotides or their sodium salts are detected separately and qualified for use.
(2) Five 5' -mononucleotides or their sodium salts qualified in quality inspection are sieved with a 60-mesh sieve for later use.
(3) Weighing the required mononucleotide samples according to the proportion, adding all the mononucleotide samples, and mixing for not less than 40 minutes. The obtained sample is preserved at normal temperature.
Example 2
The nucleotide mixture of this example is prepared from five 5' -mononucleotides or their sodium salts in the form of: CMP 78 wt%, AMP6 wt%, UMP 8 wt%, GMP7 wt%, IMP 1 wt% ratio. The preparation method is the same as example 1.
Example 3
The nucleotide mixture of this example is prepared from five 5' -mononucleotides or their sodium salts in the form of: CMP23 wt%, AMP 44 wt%, UMP 25 wt%, GMP7 wt%, IMP 1 wt% ratio. The preparation method is the same as example 1.
Example 4
The nucleotide mixture is prepared from five types of 5' -mononucleotides or sodium salts thereof according to the following forms: CMP23 wt%, AMP17 wt%, UMP 40 wt%, GMP 19 wt%, IMP 1 wt% ratio. The preparation method is the same as example 1.
Example 5
The nucleotide mixture is prepared from five types of 5' -mononucleotides or sodium salts thereof according to the following forms: CMP 24 wt%, AMP17 wt%, UMP7 wt%, GMP 51 wt%, IMP 1 wt% ratio. The preparation method is the same as example 1.
Example 6
Materials and methods
1. Sample preparation: the nucleotide mixture samples obtained in examples 1 to 5 above.
2. Experimental animals: the experimental animals selected rapidly aged model mice SAMP8 and control group SAMR1 mice, SF-class male mice, 10-12 weeks old, 78 mice, purchased from the department of laboratory animal sciences of Beijing university, 1 mouse per cage, and had free food and water intake. The temperature range of the animal room is 25 +/-1 ℃, the relative humidity is 50-60 percent, and the indoor illumination is controlled in the light-dark period rhythm of 12h/12 h.
3. Experimental groups and doses: one week after adaptive feeding of mice, the mice were divided into 6 groups (n-12): a non-nucleotide group, a normal control group (basal feed, SAMP8-age control), a SAMR1 model control group (basal feed), a nucleotide low dose intervention group (0.3g/kg + basal feed), a nucleotide medium dose intervention group (0.6g/kg + basal feed), and a nucleotide high dose intervention group (1.2g/kg + basal feed). The nucleotides were incorporated into basal feeds at different doses for intervention. Another 6-month-old SAMP8 mice were used as young control groups (SAMP8-yong control) at the experimental nodes.
4. The experimental method comprises the following steps:
4.1 grip measurement
It was found that the SAMP8 mice had the highest muscle mass at the age of 7 months, entered the prophase of sarcopenia from the age of 8 months, and entered the period of sarcopenia at the age of 10 months, and therefore, the mice were selected and subjected to the three-time gripping force test at the age of 7 months, 9 months, and 11 months, and the measurement was repeated 5 times at each time to take the maximum value.
4.2 measurement of body composition of mouse
Body composition (lean muscle and fat content) of the mice was measured using an MRI imaging system.
4.3 detection of antioxidant enzyme Activity
The kit is used for detecting the enzyme activities of SOD, Succinate Dehydrogenase (SDH) and the like in the tibialis anterior muscle.
4.4 measurement of ATP content in muscle tissue
ATP content in muscle tissue was measured using an ATP content test kit.
4.5 Observation of mitochondrial morphological Structure
And observing indexes such as the number and the form of mitochondria and the integrity of a membrane structure by adopting a transmission electron microscope.
5. The statistical method comprises the following steps: all results are expressed as means ± sd, and statistical tests were performed using SPSS18.0 software for one-way anova with p <0.05 as the difference being statistically significant.
Second, example 1 Experimental results
1. Effect of nucleotide mixtures on mouse grip
As can be seen from the results in table 1, the results of the grip test in 7-month-old mice show: compared with a normal control group, the holding power of the mice in the nucleotide high dose group and the SAMR1 group is obviously enhanced (P < 0.05). The results of the grip test of 9-month-old mice show that: compared with the non-nucleotide group and the normal control group, the mice in the low, medium and high nucleotide dose groups and the SAMR1 group have obviously enhanced holding power. The results of the grip test on 9-month-old mice also show: compared with the non-nucleotide group and the normal control group, the grip strength of mice in the nucleotide low, medium and high dose groups, the young control group and the SAMR1 group is obviously enhanced. The nucleotide intervention is shown to improve the muscle function of the aged SAMP8 mice and enhance the holding power of the mice.
TABLE 1 Effect of the nucleotide mixture described in example 1 on mouse grip
Figure BDA0003182660720000071
n=12)
Figure BDA0003182660720000072
Note:#indicates that the difference is statistically significant (P < 0.05) compared with the nucleotide-free group;*this indicates that the difference was statistically significant (P < 0.05) compared to the normal control group.
Third, example 1 Experimental results
As can be seen from table 2, the body composition results showed that the muscle mass was significantly increased in the nucleotide medium dose group, the high dose group, the young control group and the SAMR1 group, compared with the no nucleotide group and the normal control group. Compared with the nucleotide-free group, the normal control group and the nucleotide low-dose group, the difference of the young control group has statistical significance, but compared with the nucleotide medium-dose group and the nucleotide high-dose group, the difference has no significance, and the nucleotide mixture can obviously increase the muscle mass of the aged mice. And the results of percentage of muscle in the weight also show that the percentage of muscle in the nucleotide high dose group is obviously higher than that in the normal control group and the young control group (P < 0.05). The fat content and the percentage of fat in weight of the mice in the nucleotide high-dose group are obviously lower than those of the young control group, but no statistical difference is obvious among other groups. The results show that the nucleotide mixture has better effect of treating sarcopenia of the elderly.
Table 2 effect of the nucleotide mixture described in example 1 on body composition of mice (n ═ 6)
Figure BDA0003182660720000081
Note:#indicates that the difference is statistically significant compared to the nucleotide-free group;*indicating that the difference is statistically significant compared to the normal control group;aindicating that the difference is statistically significant compared to young controls.
As can be seen from FIG. 1, the SOD enzyme activities of the nucleotide high dose group, the young control group and the SAMR1 group were significantly increased as compared with the non-nucleotide group and the normal control group,the nucleotide mixture has better antioxidant effect. In the context of figure 1 of the drawings,#indicates that the difference is statistically significant compared to the nucleotide-free group;*indicating that the difference was statistically significant compared to the normal control group.
As can be seen from FIG. 2, compared with the nucleotide-free group and the normal control group, the SDH enzyme activity in the nucleotide medium and high dose groups is obviously increased, the SDH is used as one of the marker enzymes reflecting the mitochondrial function, and the intervention of the nucleotide mixture enhances the increase of the SDH enzyme activity in the muscle of the aged mouse, which indicates that the nucleotide mixture can help to improve the mitochondrial dysfunction of the muscle of the aged mouse. In the context of figure 2, it is shown,#indicates that the difference is statistically significant compared to the nucleotide-free group;*indicating that the difference was statistically significant compared to the normal control group.
As can be seen from FIG. 3, ATP levels were significantly increased in each of the other groups as compared with the nucleotide-free group. Compared with a normal control group, the ATP content of the nucleotide high-dose group is obviously increased. The nucleotide intervention is shown to have a remarkable effect on increasing the ATP content in the muscle of the mice. In the context of figure 3, it is shown,#indicates that the difference is statistically significant compared to the nucleotide-free group;*indicating that the difference was statistically significant compared to the normal control group.
As can be seen in FIG. 4, the transmission electron micrograph of the mouse soleus muscle shows that the mitochondrial membrane structure of the nucleotide-free group of mice is severely damaged and the mitochondrial cristae disappears. Mitochondria in the muscle of the normal control mice also developed different degrees of destruction, vacuoles were present in the mitochondria, and the membrane structure was incomplete. Compared with the mice of the non-nucleotide group and the normal control group, the mice of the low, medium and high dose groups have less muscle and mitochondrial damage, the mitochondrial membrane structure is relatively complete, and the mitochondrial cristae can be seen. Indicating that the intervention of the nucleotide mixture is capable of improving mitochondrial dysfunction in muscle.
Fourth, Effect of the nucleotide mixtures described in examples 2-5 on body composition of mice
The effect of the nucleotide mixtures of examples 2 to 5 on body composition of mice was tested with reference to the experiment on the effect of the nucleotide mixtures of example 1 on body composition of mice, and the results are shown in Table 3.
TABLE 3 Effect of the nucleotide mixtures described in examples 2 to 5 on body composition of mice
Figure BDA0003182660720000091
Note:#indicates that the difference is statistically significant compared to the nucleotide-free group;*indicating that the difference is statistically significant compared to the normal control group;aindicating that the difference is statistically significant compared to young controls.
Fifth, conclusion of experiment
The research discusses the effects of preventing and treating sarcopenia of the elderly by setting a normal control group without nucleotide group as a control group. Animal experiment results show that the nucleotide can improve the skeletal muscle function of an aged SAMP8 mouse by improving mitochondrial dysfunction and reducing oxidative stress, and can increase the muscle mass, thereby playing roles in preventing and treating sarcopenia. The experimental result shows that the nucleotide mixture has obvious effect of treating sarcopenia and has the potential of being used as a novel medicament for treating sarcopenia.
Example 7
The nucleotide mixture was prepared as described in example 1.
Animal model: the experimental animals selected from model mice SAMP8 and control group SAMR1 mice with rapid aging, SF-class male mice, 10-12 weeks old, and 1 mouse per cage, and had free food and water. The temperature range of the animal room is 25 +/-1 ℃, the relative humidity is 50-60 percent, and the indoor illumination is controlled in the light-dark period rhythm of 12h/12 h.
Grouping experiments: one week after adaptive feeding of mice, the mice were divided into 5 groups (n ═ 10): a no nucleotide group, a SAMP8 normal control group (basal diet), a SAMR1 model control group (basal diet), a nucleotide mix group (1.2g/kg nucleotide mix + basal diet), a nucleotide mix + amino acid group (1.2g/kg nucleotide mix + amino acid + basal diet). Mice were fed different groups of feed for intervention.
Determination of ATP content in muscle tissue: ATP content in muscle tissue was measured using an ATP content test kit.
As a result, as shown in FIG. 5, the ATP content was significantly increased in each of the other groups as compared with the nucleotide-free group. The addition of amino acids to the nucleotide mixture had little effect on the increase in ATP levels in the muscle of the mice, demonstrating that amino acids have little or no effect therein. In the context of figure 5, it is shown,#indicates that the difference is statistically significant compared to the nucleotide-free group;*indicating that the difference was statistically significant compared to the normal control group.
It will be apparent to those skilled in the art from this disclosure that many changes and modifications can be made, or equivalents modified, in the embodiments of the invention without departing from the scope of the invention. Therefore, any simple modification, equivalent change and modification made to the above embodiments according to the technical essence of the present invention shall still fall within the protection scope of the technical solution of the present invention, unless the contents of the technical solution of the present invention are departed.

Claims (4)

1. The application of the nucleotide mixture in preparing the preparation for preventing or relieving sarcopenia of the elderly is characterized in that the nucleotide mixture consists of five 5' -mononucleotides or sodium salt forms thereof, and the mass ratios of various nucleotides in the acid form of CMP, AMP, UMP, GMP and IMP are respectively as follows: CMP 23-78%, AMP 6-44%, UMP 7-40%, GMP 7-51%, IMP is greater than 0 and not greater than 2.5%.
2. The use according to claim 1, wherein the mass ratio of each nucleotide in the nucleotide mixture to be converted into CMP, AMP, UMP, GMP and IMP acid type is: CMP 43%, AMP 17%, UMP 21%, GMP 18%, and IMP are 1%.
3. The use according to claim 1, wherein the formulation is a powder, tablet, soft or hard capsule, beverage or oral liquid.
4. The use of claim 1, wherein the 5' -monophosphate nucleotide mixture is capable of improving skeletal muscle function, increasing muscle mass and delaying the occurrence and development of sarcopenia in the elderly by improving mitochondrial dysfunction and reducing oxidative stress.
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