CN115005447A - Application of oligoguluronic acid in preparation of anti-fatigue product - Google Patents

Application of oligoguluronic acid in preparation of anti-fatigue product Download PDF

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CN115005447A
CN115005447A CN202210680622.8A CN202210680622A CN115005447A CN 115005447 A CN115005447 A CN 115005447A CN 202210680622 A CN202210680622 A CN 202210680622A CN 115005447 A CN115005447 A CN 115005447A
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fatigue
acid
product
products
oligoguluronic
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CN115005447B (en
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王璐
姜英辉
张涛
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Qingdao Customs Technology Center
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    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23LFOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/125Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives containing carbohydrate syrups; containing sugars; containing sugar alcohols; containing starch hydrolysates
    • 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
    • A61K31/702Oligosaccharides, i.e. having three to five saccharide radicals attached to each other by glycosidic linkages
    • 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
    • A61K31/715Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A61K31/734Alginic acid
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P39/00General protective or antinoxious agents
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23VINDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00Food compositions, function of food ingredients or processes for food or foodstuffs

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Abstract

The invention relates to an application of oligoguluronic acid in preparing an anti-fatigue product, wherein the product comprises the following components in parts by weight: (1) products that increase exercise tolerance of skeletal muscle; (2) a product for accelerating the fatigue recovery of the organism; (3) an anti-fatigue product; (4) products for reducing the content of lactic acid and urea in serum after exercise; or (5) products that increase the body's liver glycogen and muscle glycogen stores.

Description

Application of oligoguluronic acid in preparation of anti-fatigue product
Technical Field
The invention belongs to the technical field of biology, and particularly relates to application of oligoguluronic acid in preparation of an anti-fatigue product.
Background
Fatigue is a complex physiological and biochemical change process of an organism, and refers to a normal physiological phenomenon which is necessarily caused when mental or physical strength reaches a certain stage. It marks a temporary decline in the body's original working capacity and may be a precursor to the body's development of a disease state. The occurrence of fatigue can cause reduced exercise capacity, reduced work efficiency, and increased error accidents. If the fatigue can not be recovered in time after the occurrence of fatigue, the fatigue can be gradually accumulated, so that endocrine disturbance and immunity decline of the organism can be caused, even organic diseases can be caused, and the health of human beings can be threatened.
The fatigue of the body can be eliminated by rest, sleep and physical methods, and the anti-fatigue effect can be realized by supplementing nutrient substances and medication. Some Branched Chain Amino Acids (BCAA) including leucine and isoleucine are decomposed and metabolized in muscles, are easily oxidized to provide energy for organisms, and have important effects on maintaining normal activities of human brains and delaying and eliminating exercise-induced fatigue. In addition, creatine, B vitamins, vitamin C, vitamin E, vitamin A, carotene, trace elements of selenium, copper, zinc, metallothionein and the like can also improve the metabolism of the organism and delay the occurrence of fatigue. In recent years, fatigue has attracted more and more attention as a sub-health symptom, and anti-fatigue, i.e., delaying the generation of fatigue and/or promoting the elimination of fatigue, has become a hot issue of research in sports medicine.
The Guluronic acid oligosaccharide is intercellular polysaccharide extracted from marine brown algae, and is a linear compound formed by connecting L-Guluronic acid (L-Guluronic acid, G) through alpha-1, 4-glycosidic bond. At present, the polyguluronic acid has a plurality of biological activities such as oxidation resistance, immunoregulation and mucosal protein function regulation reported in domestic and foreign documents, but no report is found about the research and application of the polyguluronic acid in the aspect of fatigue resistance.
Disclosure of Invention
The invention firstly relates to the use of oligoguluronic acids or salts thereof for producing:
(1) products that increase exercise tolerance of skeletal muscle;
(2) a product for accelerating the fatigue recovery of the organism;
(3) an anti-fatigue product;
(4) products for reducing the content of lactic acid and urea in serum after exercise;
(5) products that increase the body's liver glycogen and muscle glycogen stores;
the product is a food or a medicine,
the structure of the oligoguluronic acid or the salt thereof is shown as the following formula, the molecular skeleton is a linear oligosaccharide compound formed by connecting L-guluronic acid (G) through alpha- (1,4) -glycosidic bonds, and the weight average molecular weight range is 0.3 kD-15 kD;
Figure BDA0003698233730000011
wherein, R is H or Li, Na, K, Ca, Mg, n is less than or equal to 60.
The food or the medicine is an oral dosage form, including but not limited to tablets, granules and oral liquid;
the food or the medicine comprises an effective amount of the oligoguluronic acid or the salt thereof and necessary auxiliary materials.
The beneficial effect of the invention is that,
(1) the invention demonstrates that the oligoguluronic acid can better increase the exercise tolerance of skeletal muscle, accelerate the recovery of tired organism and has good anti-fatigue effect.
(2) The guluronic acid oligosaccharide compound provided by the invention has the advantages of low molecular weight acid oligosaccharide, is strong in water solubility, easy to absorb, rich in source, unique in action mechanism and wide in industrial development and application prospect.
Drawings
FIG. 1, chemical structure of low molecular weight guluronic acid (LG) (salt).
Detailed Description
Experiments show that the low molecular weight guluronic acid can effectively prolong the swimming time of the exhausted mouse, obviously reduce the levels of blood lactic acid and serum urea nitrogen, and obviously improve the contents of liver glycogen and muscle glycogen of the exhausted mouse for the first time; therefore, it can be used for preventing or improving fatigue symptoms.
The low molecular weight guluronic acid in the invention can be obtained by grading and degrading algin extracted from kelp, sea oak, Ascophyllum nodosum, kelp or brown algae related to Chordannia, or by chemical synthesis.
The sugar residues of the low molecular weight guluronic acid (LG) are all composed of alpha-1, 4-D-mannuronic acid, and the structural formula is as follows:
Figure BDA0003698233730000021
wherein R is H or metal cations such as Li, Na, K, Ca, Mg and the like, n is less than or equal to 80, and preferably 25 to 50;
the weight average molecular weight of the low molecular weight guluronic acid is in the range of 0.3kD to 15kD, preferably 5kD to 10 kD.
Example 1: effect of oligoguluronic acid (LG) on exhaustion of mouse swimming time
The duration of the mouse from continuous movement to exhaustion can be measured to reflect the endurance of the body.
The experimental steps of the mouse swimming exhaustion model are as follows:
(1) the mice were continuously gavage for 2 weeks, and the gavage drugs and the doses were as follows: the positive drug is octacosanol (10mg/kg), the oligoguluronate is a low dose group (25mg/kg), a medium dose group (50mg/kg) and a high dose group (100 mg/kg); gavage is performed 1 time per day; the salt form of LG is sodium salt or magnesium salt, and the weight average molecular weight is 8 kD.
(2) After half an hour of the last treatment, the lead wires with the weight of 3 percent loaded on the tail of the mouse are placed in a swimming pool with the water temperature of 30 +/-1 ℃ and the swimming time of the mouse, namely the swimming exhaustion time of the mouse, from the beginning of swimming to the time when the mouse sinks 8 seconds below the water surface without power and can not float out of the water surface, is recorded.
The results are shown in table 1: the exhaustive swimming time and the LG have a linear dose effect relationship, the exhaustive swimming time of the high-dose group is increased by 63.5 percent, the exhaustive swimming time of the medium-dose group is increased by 39.2 percent and the exhaustive swimming time of the octacosanol group is increased by 67.5 percent relative to the blank group, which shows that the movement endurance of mice can be improved by the LG high-dose group and the LG medium-dose group, so that the magnesium salt has an anti-fatigue effect, and the magnesium salt has a more ideal effect compared with the sodium salt.
TABLE 1 Effect of LG on mouse weight bearing swimming time
Figure BDA0003698233730000022
Figure BDA0003698233730000031
P <0.01 (compared to model group) and p <0.05 (compared to model group).
Example 2: effect of oligoguluronic acid (LG) on depleting mouse Blood Lactic Acid (BLA) and serum urea nitrogen (BUN)
The appearance and progression of fatigue can be observed, usually by measuring biochemical indicators that cause fatigue. When the mouse body can not obtain enough energy through sugar and fat catabolism for a long time, protein and amino acid catabolism is strengthened, nucleotide metabolism is accelerated, and the final products of the metabolic pathway generate urea. The less production of haematurin, the stronger the body endurance of the mouse and the more capable it is to bear the exercise load.
Blood lactic acid is a product of glycolysis under an anoxic condition, and along with the acceleration of glycolysis speed, the content of lactic acid in muscles is continuously accumulated, so that the pH value of cells is reduced, a series of biochemical changes are generated, and further fatigue is caused. The more lactic acid accumulates in the muscle, the more severe the fatigue manifests itself.
The experimental steps of the mouse swimming exhaustion model are as follows:
(1) after 2 weeks of continuous gavage, the positive drug is octacosanol (10mg/kg), the oligoguluronate is in a low dose group (25mg/kg), a medium dose group (50mg/kg) and a high dose group (100 mg/kg); gavage is performed 1 time per day; the salt type of LG is magnesium salt, and the weight average molecular weight is 8 kD.
(2) After half an hour of the last treatment, taking blood from tail veins, measuring the content of Blood Urea Nitrogen (BUN) and Blood Lactic Acid (BLA) before swimming, putting lead wires with 3 percent of weight of mouse tail into a 50 x 40 swimming pool for swimming, keeping the water temperature at 30 +/-1 ℃, taking out the mouse after swimming for 1 hour, and removing the weight;
(3) blood is collected from eyeball 15min after resting, and Blood Urea Nitrogen (BUN) and Blood Lactic Acid (BLA) content of mouse are determined.
The results are shown in table 2, and it can be seen that,
(1) before swimming, the difference of the serum urea nitrogen of each group is not obvious, and after swimming, the serum urea nitrogen content of each group is obviously increased. After swimming, the mid-and high-dose groups of LG and the octacosanol group serum urea nitrogen were significantly lower than the model group, suggesting that LG reduces serum urea nitrogen accumulation in sports mice.
(2) The blood lactic acid content difference of each group before swimming is not obvious, and the blood lactic acid content of each group after swimming is obviously increased. And the blood lactic acid content of the model group is obviously higher than that of the high-dose group and octacosanol group of LG, which shows that LG can reduce blood lactic acid accumulation in a mouse body after exercise and accelerate the recovery of the body.
TABLE 2 Effect of LG on mouse serum Urea Nitrogen (BUN) and Blood Lactic Acid (BLA)
Figure BDA0003698233730000032
P <0.05 (compared to model group).
Example 3: effect of oligoguluronic acid (LG) on liver glycogen and myoglycogen in depleted mice
Glycogen stores in organisms are positively correlated with exercise tolerance. When the exercise time is increased, a large amount of muscle glycogen is consumed, the exercise capacity of the organism is reduced, fatigue occurs, the intake amount of blood sugar is increased, and when the intake rate is higher than the decomposition rate of liver glycogen, the blood sugar level is reduced. Because blood glucose supplies the central nervous system, a decrease in blood glucose can cause an under-motivation of the central nervous system, resulting in systemic fatigue.
The experimental steps of the mouse swimming exhaustion model are as follows:
(1) after 2 weeks of continuous gavage of the mice, the positive drug is octacosanol (10mg/kg), the oligoguluronate is a low dose group (25mg/kg), a medium dose group (50mg/kg) and a high dose group (100 mg/kg); gavage is performed 1 time per day; the salt form of LG is magnesium salt, and the weight average molecular weight is 8 kD.
(2) After half an hour of the last treatment, putting the lead wire with the weight of 3 percent loaded at the tail of the mouse into a swimming pool of 50 multiplied by 40 for swimming, wherein the water temperature is 30 +/-1 ℃, taking out the mouse after 1 hour of swimming, and removing the load;
(3) after blood was taken from the eyeball, the eyeball was immediately sacrificed, and the liver and hind leg muscles were taken out and the liver glycogen and muscle glycogen content were measured, respectively.
The results are shown in Table 3 and show that: the liver glycogen and muscle glycogen of the medium-high dose group and the octacosanol group are obviously higher than those of the blank group, and the LG of the medium-high dose group can increase the liver glycogen and muscle glycogen content, and the glycogen can be directly decomposed into glucose to enter blood to be utilized by other tissues through blood circulation. Therefore, LG in the medium and high dose groups can delay and resist the onset of fatigue.
TABLE 3 Effect of LG on mouse liver glycogen and muscle glycogen
Figure BDA0003698233730000041
P <0.05 (compared to model group), p <0.01 (compared to model group); # p <0.05 (compared to positive drug).
The experimental results show that the oligoguluronic acid can better increase the exercise tolerance of skeletal muscle and accelerate the recovery and anti-fatigue effects of a fatigue organism. The oligoguluronic acid can be used as a natural health product or medicine for preventing and treating fatigue. The product is derived from marine algae, has the advantages of abundant resources, easy industrialization, high safety and the like, and has wide market and application prospects in the aspect of fatigue resistance. The invention provides reference meaning and inspiration for high-value utilization of marine algae.
Finally, it should be noted that the above embodiments are only used to help those skilled in the art understand the essence of the present invention, and are not used to limit the protection scope of the present invention.

Claims (4)

1. Use of oligoguluronic acid or a salt thereof for the preparation of:
(1) products that increase exercise tolerance of skeletal muscle;
(2) a product for accelerating the fatigue recovery of the organism;
(3) an anti-fatigue product;
(4) products for reducing the content of lactic acid and urea in serum after exercise;
(5) products that increase the body's liver glycogen and muscle glycogen stores;
the product is food or medicine.
2. The use according to claim 1, wherein the oligoguluronic acid or the salt thereof has a structure represented by the following formula, wherein the molecular skeleton is a linear oligosaccharide compound formed by connecting L-guluronic acid (G) through an alpha- (1,4) -glycosidic bond, and the weight average molecular weight is 0.3-15 kD; preferably 5-10 kD;
Figure FDA0003698233720000011
in the formula, R is H or Li, Na, K, Ca and Mg, preferably Mg, and n is less than or equal to 75, preferably 25-50.
3. The use according to claim 1 or 2, wherein the food or pharmaceutical product is in an oral dosage form, including but not limited to tablets, granules, oral liquid.
4. Use according to claim 1 or 2, characterized in that said food or pharmaceutical product comprises an effective amount of said oligoguluronic acid or a salt thereof, and the necessary excipients.
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Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20020137723A1 (en) * 2000-02-03 2002-09-26 Byon Jae Hyong Low molecular weight polymannuronate
CN1518897A (en) * 2003-09-01 2004-08-11 中国海洋大学 Combined holoside as well as preparation method and application
CN101325973A (en) * 2005-10-06 2008-12-17 Ntnu技术转让公司 Use of oligouronates for treating mucus hyperviscosity
US20110177132A1 (en) * 2008-05-23 2011-07-21 Aliza Apple Allon Compositions and Methods for Generating Musculoskeletal Tissue
CN103948611A (en) * 2014-03-31 2014-07-30 青岛海洋生物医药研究院股份有限公司 Application of oligomeric guluronic acid salts in preparation of Parkinson's disease prevention and treatment drugs or products
CN104666327A (en) * 2015-01-14 2015-06-03 中国海洋大学 Application of low-polymer mannuronic acid and derivative thereof in preparation of medicines and health products for resisting fatigue and amyotrophia
CN105395563A (en) * 2015-12-11 2016-03-16 青岛海洋生物医药研究院股份有限公司 Application of oligoguluronic acid and derivative thereof in preparation of drugs and health products used for preventing and treating hyperlipidemia and complications thereof
CN110652517A (en) * 2018-06-29 2020-01-07 上海绿谷制药有限公司 Algin oligosacchride diacid composition

Patent Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20020137723A1 (en) * 2000-02-03 2002-09-26 Byon Jae Hyong Low molecular weight polymannuronate
CN1518897A (en) * 2003-09-01 2004-08-11 中国海洋大学 Combined holoside as well as preparation method and application
CN101325973A (en) * 2005-10-06 2008-12-17 Ntnu技术转让公司 Use of oligouronates for treating mucus hyperviscosity
US20110177132A1 (en) * 2008-05-23 2011-07-21 Aliza Apple Allon Compositions and Methods for Generating Musculoskeletal Tissue
CN103948611A (en) * 2014-03-31 2014-07-30 青岛海洋生物医药研究院股份有限公司 Application of oligomeric guluronic acid salts in preparation of Parkinson's disease prevention and treatment drugs or products
CN104666327A (en) * 2015-01-14 2015-06-03 中国海洋大学 Application of low-polymer mannuronic acid and derivative thereof in preparation of medicines and health products for resisting fatigue and amyotrophia
CN105395563A (en) * 2015-12-11 2016-03-16 青岛海洋生物医药研究院股份有限公司 Application of oligoguluronic acid and derivative thereof in preparation of drugs and health products used for preventing and treating hyperlipidemia and complications thereof
CN110652517A (en) * 2018-06-29 2020-01-07 上海绿谷制药有限公司 Algin oligosacchride diacid composition
US20210260085A1 (en) * 2018-06-29 2021-08-26 Shanghai Green Valley Pharmaceutical Co., Ltd. Composition of alginic oligosaccharic diacids

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