CN112546052A - Composition containing marine oligosaccharide for preventing and treating gout - Google Patents
Composition containing marine oligosaccharide for preventing and treating gout Download PDFInfo
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- CN112546052A CN112546052A CN202011575821.XA CN202011575821A CN112546052A CN 112546052 A CN112546052 A CN 112546052A CN 202011575821 A CN202011575821 A CN 202011575821A CN 112546052 A CN112546052 A CN 112546052A
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- oligosaccharide
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/702—Oligosaccharides, i.e. having three to five saccharide radicals attached to each other by glycosidic linkages
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
- A23L2/00—Non-alcoholic beverages; Dry compositions or concentrates therefor; Preparation or treatment thereof
- A23L2/52—Adding ingredients
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/125—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives containing carbohydrate syrups; containing sugars; containing sugar alcohols; containing starch hydrolysates
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/716—Glucans
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- A—HUMAN NECESSITIES
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/06—Antigout agents, e.g. antihyperuricemic or uricosuric agents
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- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
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Abstract
The invention discloses a composition containing marine oligosaccharide for preventing and treating gout, which is prepared by taking the marine oligosaccharide as a main active ingredient. The marine oligosaccharide is a micromolecular sugar chain obtained by degrading marine animal polysaccharide, algae polysaccharide and microbial polysaccharide through chemical and biological enzyme methods, and mainly comprises chitosan oligosaccharide, mannuronic acid oligosaccharide, guluronic acid oligosaccharide, agar oligosaccharide, new agar oligosaccharide, carrageenan oligosaccharide and the like. The test result shows that the marine oligosaccharide can inhibit the action of mouse liver xanthine oxidase XOD, reduce the in vivo generation of uric acid, reduce the deposition of urate substances in the kidney, accelerate uric acid metabolism and relieve sodium urate induced gout arthritis. In addition, the marine oligosaccharide can reduce inflammatory reaction, improve organism immunity, play a certain role in analgesia, be used for preparing medicines or health products for preventing and treating gout, and provide a natural or natural-like medicine for preventing and treating gout, thereby reducing adverse reactions caused by using the gout medicines.
Description
Technical Field
The invention discloses a composition containing marine oligosaccharide for preventing and treating gout, and particularly belongs to the technical field of marine organisms.
Background
Gout is a disease in which urate is deposited in tissues due to disorder of voice metabolism, increased blood uric acid levels and/or decreased uric acid excretion. Gout is clinically characterized by hyperuricemia and is manifested by recurrent arthritis, tophus formation and joint deformity, and severe cases can cause joint movement disorder and chronic interstitial nephritis and uric acid nephrolithiasis when kidney is affected. Hyperuricemia is the biochemical basis of gout, which is necessarily accompanied by hyperuricemia. In recent years, the incidence of gout and hyperuricemia is on the rise, the onset age is on the low age, and the disease is closely related to the occurrence of hypertension, hyperlipidemia, atherosclerosis and obesity insulin resistance, and becomes an early marker for identifying metabolic syndrome. Therefore, the study of the pathogenesis and treatment of gout is attracting attention.
Uric acid is a weak acid with low solubility, and the highest solubility in body fluid is 381--1. Uric acid produced by daily biuret metabolism is 2/3-3/4 discharged from the body by urine, and the rest 1/4-1/3 are discharged into the intestinal cavity by liver and gall, and degraded by decomposing bacteria in the intestinal cavity into ammonia and carbon dioxide, and rarely degraded into allantoin and carbon dioxide by leukocyte myeloperoxidase. The content of uric acid pool in normal human body is 120--1The stability of the medicine depends on the balance between uric acid generation and uric acid excretion, once the balance is broken, the uric acid content of the body is obviously increased, and the uric acid in body fluid exceeds the saturated concentration of the uric acid to separate out crystals to deposit on soft tissues to form gout.
Hyperuricemia and gout are diseases caused by the sustained increase of uric acid in vivo beyond its physiologically tolerable range, even at saturated concentrations, and therefore the drug treatment strategy for this disease is mainly to reduce elevated uric acid in blood and extracellular fluids. While blood and extracellular uric acid concentrations depend on the balance between the rate of uric acid production and renal excretion, therapeutic measures are to restore the balance between the two, i.e., to promote uric acid excretion and/or to reduce uric acid production, and to control the development of symptoms and complications. The clinical treatment aims are four: firstly, terminating the attack of acute arthritis as soon as possible; ② preventing the relapse of arthritis; correcting hyperuricemia and preventing the complication that urate is deposited on kidney, joints and the like; and fourthly, preventing uric acid kidney stone from forming.
At present, western medicines are mainly used for the conventional treatment of gout and hyperuricemia, modern medicine treatment methods for gout mainly comprise inflammation diminishing, pain relieving, urate excretion promoting and blood uric acid reducing, and western medicines for treating gout mainly comprise the following two main types: anti-inflammatory agents: including colchicine, non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, adrenocorticoids, glucosamine, IL-1 inhibitors, etc.; uric acid lowering drugs: has the medicine of benzbromarone for promoting uric acid excretion, allopurinol for inhibiting uric acid production and febuxostat. The medicines achieve the purpose of relieving or treating gout and hyperuricemia through different action links, but more and more clinical observations show that the medicines all have certain toxic and side effects. Therefore, the search for highly effective and low-toxicity anti-hyperuricemia and anti-gout substances or methods is a research hotspot of the medical community at present.
Disclosure of Invention
In order to overcome the defects in the prior art, the invention provides a composition containing marine oligosaccharide for preventing and treating gout and a preparation method thereof, and provides a slight solution for reducing the concentration of uric acid in blood and treating gout by the functional activity of the marine oligosaccharide and the synergistic interaction among different oligosaccharides.
In order to achieve the purpose, the invention is realized by the following technical scheme:
the composition containing marine oligosaccharide for preventing and treating gout is a preparation prepared by taking marine oligosaccharide as a main active ingredient, adding a proper amount of health food or a pharmaceutically acceptable carrier or auxiliary ingredients and performing a conventional preparation process.
The marine oligosaccharide is a micromolecular sugar chain obtained by degrading marine animal polysaccharide, algae polysaccharide and microbial polysaccharide through chemical and biological enzyme methods, and mainly comprises chitosan oligosaccharide, mannuronic acid oligosaccharide, guluronic acid oligosaccharide, agar oligosaccharide, new agar oligosaccharide, carrageenan oligosaccharide and the like.
Preferably, the marine oligosaccharide mainly comprises chitosan oligosaccharide and mannuronic acid oligosaccharide, and accounts for 20-80% of the active ingredients.
Further preferably, the ratio of chitosan oligosaccharide to mannuronic acid oligosaccharide in the marine oligosaccharide is 5: 1-1: 5.
Further preferably, the ratio of chitosan oligosaccharide to mannuronic acid oligosaccharide in the marine oligosaccharide is 2: 1.
Further preferably, the polymerization degree of the chitosan oligosaccharide in the marine oligosaccharide is 2-8, and the deacetylation degree is more than 90%.
Further preferably, the polymerization degree of mannuronic acid oligosaccharide in the marine oligosaccharide is in the range of 2-8.
The chitosan oligosaccharide is obtained by degrading chitosan which is a product of deacetylation of chitin, is oligosaccharide formed by connecting 2-20 glucosamine through glycosidic bonds, is also the only alkaline amino polysaccharide with positive charges in natural polysaccharide, has good water solubility, and is easy to be absorbed by organisms. The research shows that the chitosan oligosaccharide has the inhibition effect on the activity of the yellow hebelt oxidase of the chronic hyperuricemia and reduces the blood uric acid value. Meanwhile, the chitosan oligosaccharide has alkaline amino, so that blood can be alkalized after entering the blood, the solubility of uric acid is increased, and the dissolution of uric acid stones is accelerated. In addition, the chitosan oligosaccharide has a plurality of physiological functions of promoting joint repair, protecting myocardial tissues and cells, protecting liver, regulating blood fat, resisting oxidation, reducing blood sugar and the like, and has a certain protection effect on kidney.
Algin is a safe food additive, which is a water-soluble compound consisting of mannuronic acid and guluronic acid, contains carboxyl and hydroxyl functional groups in the molecule, can interact with various proteins, lipids and various metal ions, is a biological molecule with health care effect, and has been found to have various biological activities. The mannuronic acid oligosaccharide is a special structural unit in algin molecules, and is prepared into low-molecular weight mannuronic acid through directional degradation and fractional classification. Research shows that the mannuronic acid oligosaccharide can obviously reduce the expression level of cyclooxygenase (COX-2) gene and the activity of cyclooxygenase (COX-1/COX-2), reduce inflammatory reaction and inhibit the growth of osteoclasts, and can also directly promote the proliferation of hematopoietic progenitor cells and the recovery of hematopoietic function, promote the proliferation of bone marrow stromal cells forming microenvironment, promote the secretion of positive hematopoietic factors and improve the hematopoietic function of organisms.
The marine oligosaccharide is used for preventing and treating gout, and is a carrier or auxiliary component compound preparation of marine oligosaccharide which is given to patients by 0.5 g-5 g of active components every day.
The preparation of the composition containing the marine oligosaccharide is various different formulations which can be used clinically, such as tablets, capsules, granules, pills, paste, tinctures and oral liquids; or conventional health food such as tablet, capsule, granule, beverage, etc.
The invention has the following beneficial effects:
1. animal experiments prove that the marine oligosaccharide can indeed inhibit the action of mouse liver xanthine oxidase XOD, reduce the in vivo generation of uric acid, reduce the deposition of urate substances in the kidney, accelerate uric acid metabolism and relieve gout arthritis induced by sodium urate. In addition, the marine oligosaccharide can reduce inflammatory reaction, improve organism immunity, play a certain role in analgesia, be used for preparing medicines or health products for preventing and treating gout, and provide a natural or natural-like medicine for preventing and treating gout, so that adverse reactions caused by using the gout medicines are reduced;
2. the marine oligosaccharide of the present invention is derived from natural active ingredients, and therefore, is safe and easily available, and thus can be widely used in industries related to hyperuricemia or metabolic disorders related to hyperuricemia.
Drawings
FIG. 1 is a schematic diagram showing the effect of marine oligosaccharides on the kidney of a mouse with hyperuricemia.
Detailed Description
The present invention is further illustrated by the following examples, which are intended to be illustrative, not limiting and are not intended to limit the scope of the invention.
Example 1
A composition containing marine oligosaccharide for preventing and treating gout comprises chitosan oligosaccharide and mannuronic acid oligosaccharide, wherein the specific gravity of the chitosan oligosaccharide and the mannuronic acid oligosaccharide is 5: 1.
Example 2
A composition containing marine oligosaccharide for preventing and treating gout comprises chitosan oligosaccharide and mannuronic acid oligosaccharide, wherein the specific gravity of the chitosan oligosaccharide and the mannuronic acid oligosaccharide is 2: 1.
Example 3
A composition containing marine oligosaccharide for preventing and treating gout comprises chitosan oligosaccharide and mannuronic acid oligosaccharide, wherein the specific gravity of the chitosan oligosaccharide and the mannuronic acid oligosaccharide is 1: 1.
Example 4
A composition containing marine oligosaccharide for preventing and treating gout comprises chitosan oligosaccharide and mannuronic acid oligosaccharide, wherein the specific gravity of the chitosan oligosaccharide and the mannuronic acid oligosaccharide is 1: 2.
Example 5
A composition containing marine oligosaccharide for preventing and treating gout comprises chitosan oligosaccharide and mannuronic acid oligosaccharide, wherein the specific gravity of the chitosan oligosaccharide and the mannuronic acid oligosaccharide is 1: 5.
Example 6 pharmacological experiment of reducing uric acid with marine oligosaccharide
1. The test method comprises the following steps:
(1) taking 180 male SPF Kunming mice (24 +/-2 g), and randomly dividing into a normal control group and a hyperuricemia model group;
the model group was gavaged with adenine (ademine) at a dose of 200 mg/kg/d, and the normal control group was gavaged with distilled water at the same dose 2 times a day with 4h intervals in between. And (3) blood is taken from the mice on the 7 th day of the experiment to measure the content of the serum SCr, the BUN and the UA, and the significant difference of the serum SCr, the BUN and the UA content of the model group and the normal control group is taken as a successful mark for making the model. After the hyperuricemia animal model is successfully established, randomly dividing the model group into a model control group and a marine oligosaccharide group (a chitosan oligosaccharide group, a mannosyloligosaccharide group, a chitosan oligosaccharide and mannosylaldehyde mixture test group (wherein examples 1-5 are respectively test groups 1-5), wherein the model control group and the marine oligosaccharide group continue to be gavaged every day to maintain a 200 mg/kg/d adenine solution, in addition, the marine oligosaccharide group (the chitosan oligosaccharide group, the mannosyloligosaccharide group, the chitosan oligosaccharide and mannosylaldehyde mixture test group (test groups 1-5) continues to be gavaged every day with a 300mg/kg/d marine oligosaccharide solution corresponding to the group name, and the normal control group and the hyperuricemia model control group are gavaged with pure water with the same volume for 7 days continuously, and mice are weighed and recorded on days 1, 4 and 7;
(2) after 1 hour of intragastric administration on day 7, blood was sacrificed and blood samples obtained by centrifugation at 3500r/min for 10min using a centrifuge were separated to obtain serum stored at-20 ℃. Removing the liver and kidney of the mouse and washing with a physiological saline solution;
(3) measuring the urea nitrogen, creatinine and uric acid levels of the serum obtained in the step (2);
(4) taking the organs obtained in (2) to calculate a kidney coefficient by dividing the weight of the individual mouse by the weight of each organ of the individual mouse, excising liver and kidney tissues, weighing and homogenizing the liver with cold physiological saline (0.9%), and centrifuging at 2000rpm for 10 minutes at 4 ℃, leaving the supernatant for xanthine oxidase activity analysis;
2. statistical analysis of results
The experimental data are expressed as mean ± standard deviation (X ± SD). Analyzing and processing by using SPSS16.0 statistical software, wherein the total difference between groups is detected by t, the average comparison between groups is analyzed by variance, and the pairwise comparison between groups is detected by Q;
3. results
TABLE 1 Effect on uric acid levels in hyperuricemia mice
As can be seen from the data in Table 1, the serum uric acid level in the group of adenine-induced hyperuricemia model group was increased as compared with that in the normal mice, demonstrating successful modeling. Different marine oligosaccharide experimental groups can obviously reduce the serum uric acid content of the mouse with high uric acid, and the marine oligosaccharide is proved to have good effect of reducing uric acid; and compared with the single use of the chitosan oligosaccharide and the mannuronic acid oligosaccharide, the combined use of the chitosan oligosaccharide and the mannuronic acid oligosaccharide has better effect of reducing uric acid, wherein the effect of reducing uric acid is the best in the test group 2.
TABLE 2 Effect of Marine oligosaccharides on liver xanthine oxidase Activity in hyperuricemia mice
The data in table 2 show that all the marine oligosaccharide experimental groups can significantly reduce the xanthine oxidase activity of the liver of a mouse with high uric acid content, which indicates that the uric acid reducing effect of the marine oligosaccharide can be realized by inhibiting the xanthine oxidase activity, and the chitosan oligosaccharide and the mannuronic acid oligosaccharide have more obvious effect in combination use compared with the single use of the chitosan oligosaccharide and the mannuronic acid oligosaccharide, and indicates that the marine oligosaccharide has a certain promotion effect of reducing the xanthine oxidase activity of the liver of the mouse.
TABLE 3 influence of Marine oligosaccharides on serum Biochemical indices of hyperuricemia mouse model
Compared with a normal control group, the serum urea nitrogen and the creatinine of the model group are obviously increased; both serum urea nitrogen and creatinine were significantly reduced in the marine oligosaccharide group compared to the model group, with test group 2 being closer to the normal control group in the marine oligosaccharide group. This indicates that marine oligosaccharides have a protective effect on renal function.
The effect of marine oligosaccharides on the kidney of hyperuricemia mice is shown in figure 1. As can be seen from the results in FIG. 1, the kidney coefficient of the model group is obviously higher than that of the blank group, which indicates that the kidney of the mouse is obviously damaged in the process of feeding the mouse with adenine, and the difference of the marine oligosaccharide and the model group is obvious, which indicates that the marine oligosaccharide can reduce the damage to the kidney.
The results show that the marine oligosaccharide can obviously reduce the serum uric acid level of the hyperuricemia mouse to be close to the normal group level, has an inhibiting effect on xanthine oxidase activity, reduces the generation of precursors such as uric acid and the like, further reduces the generation of SCr, BUN and UA in the mouse, reduces the values of the indexes in the serum, and can be used for preparing medicines, foods, health care products or auxiliary medicaments for reducing uric acid and improving gout.
The above embodiments are only used for illustrating the technical solution of the present invention, and not for limiting the same; although the invention has been described in detail with reference to the foregoing embodiments, it will be apparent to those skilled in the art that various changes may be made and equivalents may be substituted for elements thereof; such modifications and substitutions do not depart from the spirit and scope of the present invention as set forth in the appended claims.
Claims (7)
1. A composition containing marine oligosaccharide for preventing and treating gout is characterized in that the composition is a preparation prepared by taking marine oligosaccharide as a main active ingredient, adding a proper amount of health food or a pharmaceutically acceptable carrier or auxiliary ingredients and performing a conventional preparation process.
2. The composition for preventing and treating gout using marine oligosaccharides according to claim 1, wherein the marine oligosaccharides are small-molecule sugar chains obtained by degrading marine animal polysaccharides, algal polysaccharides, and microbial polysaccharides by chemical and biological enzymatic methods, and mainly comprise chitosan oligosaccharides, mannuronic acid oligosaccharides, guluronic acid oligosaccharides, agaro oligosaccharides, neoagaro oligosaccharides, and carrageenan oligosaccharides.
3. The composition containing marine oligosaccharides for preventing and treating gout according to claim 1, wherein the marine oligosaccharides are mainly chitosan oligosaccharides and mannuronic acid oligosaccharides, and account for 20-80% of active ingredients.
4. The composition containing marine oligosaccharides for preventing and treating gout according to claim 1, wherein the ratio of chitosan oligosaccharides to mannuronic acid oligosaccharides in the marine oligosaccharides is 5: 1-1: 5.
5. The composition containing marine oligosaccharides for preventing and treating gout according to claim 1, wherein the ratio of chitosan oligosaccharides to mannuronic acid oligosaccharides in the marine oligosaccharides is 2: 1.
6. The composition containing marine oligosaccharides for preventing and treating gout according to claim 1, wherein the degree of polymerization of chitosan oligosaccharides in the marine oligosaccharides is in the range of 2 to 8, and the degree of deacetylation is 90% or more.
7. The composition containing marine oligosaccharides for preventing and treating gout according to claim 1, wherein the degree of polymerization of mannuronic acid oligosaccharides in the marine oligosaccharides ranges from 2 to 8.
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