Composition and application thereof in preparation of products for reducing uric acid and / or preventing and treating hyperuricemia

Abstract

The invention discloses a composition and application thereof in preparation of a product for reducing uric acid and / or preventing and treating hyperuricemia. The composition is prepared from the following components in parts by weight: 0.04 to 0.18 part of SOD (superoxide dismutase), 1 to 10 parts of trehalose, 17 to 34 parts of green wheat seedling powder and 55 to 81 parts of milk. The composition can safely and effectively reduce uric acid in serum of an animal body, plays a role in treating hyperuricemia, and has the advantage of good palatability.

Description

Technical Field

[0001] The present invention belongs to the technical field of pharmaceutical chemistry. More specifically, it relates to a composition and its application in the preparation of products for reducing uric acid and / or preventing and treating hyperuricemia. Background Art

[0002] In the field of chemical medicine, uric acid is the final metabolite of purine compounds in humans. Endogenous and exogenous purines in the human body are ultimately metabolized to uric acid by xanthine oxidase in the liver. Due to the evolutionary deletion of uricase, primates and humans are unable to metabolize uric acid to allantoin, so the serum uric acid level in humans is five to six times higher than that in other mammals.

[0003] Hyperuricemia (HUA) refers to the situation where, in adults under normal purine diet, regardless of gender, the fasting serum uric acid level exceeds 420 μmol / L on two non-consecutive days. Hyperuricemia is caused by the imbalance between uric acid synthesis and excretion. A large amount of urate deposition in the body easily induces joint and tissue damage, resulting in an inflammatory response, and then triggers metabolic diseases such as gout, cardiovascular diseases, and diabetes.

[0004] Generally, simply being in the state of hyperuricemia has no conscious symptoms. However, if in this state for a long time, urate in the blood will crystallize and deposit in joints, subcutaneous tissues, kidneys and other parts, and then a series of clinical manifestations such as gout and gout complications will occur.

[0005] Hyperuricemia is the pathophysiological basis of gout. For the treatment of gout, it is mainly divided into drug treatment and non-drug treatment. Different from the various adverse reactions such as liver and kidney damage caused by drug treatment, non-drug treatment shows significant advantages in terms of safety and patient compliance. Introducing the concept of homologous medicated food and using food as medicine into the prevention and treatment of hyperuricemia and gout ensures the wide availability of food raw materials, and there are no side effects after long-term consumption, which provides users with a safe and reliable health option and plays a great advantage in the long treatment cycle of hyperuricemia and gout. Generally speaking, the treatment prospects of foods and / or health products for hyperuricemia and gout are broad. How to discover more foods and / or health products that can be used to reduce uric acid or prevent and treat hyperuricemia has become a technical problem that needs to be solved urgently. Summary of the Invention

[0006] Aiming at the above-mentioned problems in the prior art, the primary object of the present invention is to provide a composition. The composition has the advantages of good palatability, can effectively reduce the uric acid in the serum of animals, can play a role in treating hyperuricemia, and has no obvious side effects.

[0007] The second object of the present invention is to provide a preparation method of the composition.

[0008] The third object of the present invention is to provide use of the composition in the preparation of uric acid-lowering products.

[0009] The fourth object of the present invention is to provide a composition for use in preparing a product for preventing and / or treating hyperuricemia or gout, gout complications or renal damage caused by hyperuricemia.

[0010] The above-mentioned object of the present invention is achieved by the following technical solutions:

[0011] The present invention claims protection for a composition, which consists of the following components by weight: 0.04-0.18 parts of superoxide dismutase (SOD), 1-10 parts of trehalose, 17-34 parts of green wheatgrass powder, and 56-81 parts of milk.

[0012] The inventor constructed a white-feathered pigeon model with chronic hyperuricemia by feeding a high-purine, high-fat diet, and experimentally detected the blood uric acid levels of different groups on the 0th, 7th and 14th days, and weighed and recorded the remaining feed amount to compare the palatability of the feeds of different groups. The inventor found through research that the composition of SOD, trehalose, green wheatgrass powder and milk has a significant uric acid-lowering effect, can play a role in treating hyperuricemia, and has no obvious side effects. In addition, the above combination also improves palatability, so that the composition or a product containing such a composition has the advantage of good palatability.

[0013] In order to observe the safety and effectiveness of the composition in mice, the inventors fed C57 mice with No. 2 feed, which has good activity on white-feathered pigeons, for 3 months, and recorded the weight, fasting blood sugar and uric acid of mice in different groups on the 0th, 15th, 30th, 45th, 60th, 75th and 90th days through experimental detection. On the 80th day, potassium oxonate (50mg / mL) was intraperitoneally injected, and the dose was 0.1mL / 10g, which uniformly improved the overall uric acid level of mice, and facilitated the detection of uric acid test strips and biochemical analyzers. On the 90th day, the weight of liver and kidney was recorded by dissection, and the liver function indicators represented by alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and the renal function indicators represented by blood urea nitrogen and blood creatinine were detected by biochemical analyzer to evaluate the safety of the above-mentioned product composition, and the feed intake was recorded to evaluate the palatability of each group of feed.

[0014] The inventors found through research that after continuous feeding for 3 months, the uric acid levels in mice did not reach the detectable level of >180 μmol / L by uric acid test strips. However, after intraperitoneal injection of potassium oxonate to increase blood uric acid on the 80th day, compared with the model group, the uric acid levels in mice fed with the composition of SOD, trehalose, green wheat seedling powder and milk, and those in the positive control group treated with allopurinol were significantly decreased, showing good uric acid-lowering effects. In terms of safety, after continuous feeding for 3 months, the mice fed with the combination of SOD, trehalose, green wheat seedling powder and milk were active, with normal diet, body weight, shiny hair, and no abnormalities in urine and feces. The fasting blood glucose levels detected at different time intervals were within the normal range, while the blood glucose in the model group was significantly increased. After dissection on the 90th day of feeding, the liver and kidneys of the mice fed with the product composition were ruddy and shiny, and there were no abnormalities in the biochemical indexes of liver and kidney functions, while the allopurinol group showed an obvious trend of kidney injury. It was preliminarily clarified that the product composition had no obvious toxic and side effects on experimental mice and had good safety.

[0015] Preferably, by weight, the composition consists of the following components: 0.08 - 0.16 parts of SOD, 2 - 6 parts of trehalose, 24 - 32 parts of green wheat seedling powder, and 60 - 76 parts of milk.

[0016] Preferably, by weight, the composition consists of the following components: 0.1 - 0.14 parts of SOD, 3 - 5 parts of trehalose, 26 - 30 parts of green wheat seedling powder, and 65 - 75 parts of milk.

[0017] Preferably, by weight, the composition consists of the following components: 0.14 - 0.18 parts of SOD, 1 - 3 parts of trehalose, 17 - 24 parts of green wheat seedling powder, and 78 - 81 parts of milk.

[0018] Specifically, the milk is whole milk powder or skim milk powder. More specifically, in actual applications, commercial whole milk powder or skim milk powder can be selected.

[0019] Specifically, the green wheat seedling powder is a product made by grinding commercial barley wheat seedlings.

[0020] Specifically, the SOD is SOD powder complexed with metals such as manganese extracted and purified after fermentation of yeast engineering bacteria, or yeast powder containing SOD, or commercial edible SOD powder.

[0021] Furthermore, the present invention claims a method for preparing a composition, which is obtained by mixing SOD, trehalose, green wheat seedling powder, milk and the excipients contained therein.

[0022] Furthermore, the above composition further contains an excipient composition added for shaping and palatability.

[0023] Further, the above composition can also be prepared into a dosage form that is more conducive to consumption, such as tablets (such as milk tablets), granules, powders, capsules, etc.

[0024] Further, the present invention claims the application of the above composition in the preparation of products for reducing uric acid.

[0025] Further, the present invention claims the application of the above composition in the preparation of products for preventing and / or treating hyperuricemia or gout, gout complications or kidney damage caused thereby.

[0026] Specifically, the treatment of hyperuricemia refers to reducing blood uric acid, regulating the intestinal environment, and scavenging free radicals by improving the diet structure to alleviate the oxidative stress and inflammatory response caused by hyperuricemia. More specifically, the improvement of the diet structure refers to the proportion of the intake of the composition in various foods.

[0027] Specifically, the regulation of the intestinal environment is mainly manifested as the homeostasis of the intestinal flora. Among them, trehalose is a proliferation factor for Bifidobacterium, and oligosaccharides are hardly digested and absorbed by the human body, and do not cause fluctuations in blood glucose and insulin levels in the body after ingestion, so they can be eaten by diabetics. In addition, trehalose can stabilize the uricase produced by intestinal bacteria and increase the activity of uricase, maintaining the degradation ability of uricase in the intestine to uric acid from food sources or produced by bacteria, and reducing the generation of intestinal uric acid.

[0028] Among them, superoxide dismutase (SOD) is an antioxidant enzyme, and its main function is to catalyze the disproportionation of superoxide radicals (O 2- ) to generate hydrogen peroxide (H 2 O 2 ) and oxygen (O 2 ). Among them, manganese-complexed SOD is not degraded by digestive enzymes in the stomach and is not absorbed or rarely absorbed by the digestive tract after entering the intestine. It can scavenge free radicals in the intestine to protect intestinal epithelial cells from damage caused by oxidation and inflammation, protect the intestinal barrier function, reduce the increase in blood uric acid caused by intestinal leakage, and has a positive effect on reversing hyperuricemia.

[0029] Among them, the main component of green wheat seedling powder is insoluble fiber, which is not digested and absorbed by the normal intestine, but can be degraded by intestinal bacteria into short-chain fatty acids such as acetic acid, propionic acid, and butyric acid. These short-chain fatty acids can inhibit the reabsorption of uric acid in the intestine and kidney, playing a role in reducing uric acid. At the same time, short-chain fatty acids can also change the intestinal flora and increase the content of probiotics, which is beneficial to reversing hyperuricemia.

[0030] Among them, milk or dairy products have a low purine content. A large number of studies have shown that there is a strong negative correlation between milk intake and the incidence of hyperuricemia and gout. First, orotic acid in milk promotes the renal excretion of uric acid; second, milk contains casein and lactalbumin, both of which have been proven to reduce blood uric acid levels through diuretic effects; third, the 64-amino acid carboxyl-terminal fragment of casein - glycomacropeptide reduces gout attacks by inhibiting the inflammatory response caused by monosodium urate crystals in joints; fourth, milk is rich in vitamin D, and the level of 1,25-(OH)2-vitamin D3 in patients with severe hyperuricemia or gout is significantly reduced; finally, milk and dairy products are rich in calcium and lactose. Both calcium and lactose show a significant negative correlation with uric acid. For every 1 g increase in lactose intake, the uric acid concentration decreases by 0.5 mmol / dL; for every 1 mg increase in calcium intake, the plasma uric acid concentration decreases by 0.02 mmol / dL.

[0031] Specifically, the hyperuricemia is chronic hyperuricemia caused by high-purine and high-fat diets.

[0032] Preferably, the gout complications are one or more of gouty arthritis, urinary calculi, or cardiovascular diseases. More specifically, gout can be acute gout or chronic gout; the cardiovascular diseases include, but are not limited to, cardiovascular lesions caused by hypertension, thrombosis, atherosclerosis, chronic heart failure, diabetes, etc.

[0033] Preferably, the product can be food, health products, dairy products, fermented products, food additives, etc.

[0034] Compared with the prior art, the present invention has the following beneficial effects:

[0035] The present invention discovers that the combination of SOD, trehalose, green wheat seedling powder, and milk has a significant uric acid-lowering effect, can play a role in treating hyperuricemia, and has no obvious side effects; the composition exerts an obvious synergistic uric acid-lowering effect through multiple targets such as the intestine and kidney. For example, there is a literature report that an adult needs to drink 800 ml (equivalent to 80 g of protein) of milk to show an obvious uric acid-lowering effect. In the present invention, after milk is combined with SOD, trehalose, and green wheat seedling powder, the amount of milk powder equivalent to an adult's intake per day only needs to be 5 - 10 g, which greatly facilitates dietary behavior and reduces digestive tract symptoms such as abdominal pain and diarrhea caused by excessive drinking of milk. In addition, the composition has good palatability, making the composition or products containing such a composition have the advantage of good palatability. Finally, the composition has no toxic and side effects on the kidneys and liver, and long-term consumption will not cause an increase in blood sugar, and has good safety. BRIEF DESCRIPTION OF THE DRAWINGS

[0036] Figure 1 Schematic diagram of the influence on the fluctuations of uric acid levels on day 0, day 7, and day 14 in white - feather meat pigeons with chronic hyperuricemia models of different groups. Among them, the red broken line represents the changes in blood uric acid levels in white - feather meat pigeons in the hyperuricemia group fed with Feed No. 1 from day 0 to day 14; the three green broken lines respectively represent the changes in blood uric acid levels in white - feather meat pigeons in the composition group provided by the present invention fed with Feed No. 2, Feed No. 4, and Feed No. 5 from day 0 to day 14; the yellow broken line represents the changes in blood uric acid levels in white - feather meat pigeons in the allopurinol group fed with Feed No. 3 from day 0 to day 14. The data are mean ± standard deviation; n = 5 / group, *P < 0.05, **P < 0.01, ***P < 0.001, compared with the hyperuricemia model group.

[0037] Figure 2 Changes in the body weight levels of C57 mice with chronic hyperuricemia models of different groups from day 0 to day 90. The body weight of the mice was measured every 15 days. Among them, the red broken line represents the changes in body weight of the mice in the hyperuricemia group fed with the same Feed No. 1 as that for white - feather meat pigeons (model group) from day 0 to day 90; the green broken line represents the changes in body weight of the mice in the composition group provided by the present invention fed with the same Feed No. 2 as that for white - feather meat pigeons from day 0 to day 90; the yellow broken line represents the changes in body weight of the mice in the allopurinol group fed with the same Feed No. 3 as that for white - feather meat pigeons from day 0 to day 90. The data are mean ± standard deviation; n = 8 / group, *P < 0.05, **P < 0.01, ***P < 0.001, compared with the hyperuricemia model group.

[0038] Figure 3 Changes in the fasting blood glucose levels of C57 mice with chronic hyperuricemia models of different groups from day 0 to day 90. The fasting blood glucose level of the mice was measured every 15 days. Among them, the red broken line represents the changes in fasting blood glucose levels of the mice in the hyperuricemia group fed with Feed No. 1 from day 0 to day 90; the green broken line represents the changes in fasting blood glucose levels of the mice in the composition group provided by the present invention fed with Feed No. 2 from day 0 to day 90; the yellow broken line represents the changes in fasting blood glucose levels of the mice in the allopurinol group fed with Feed No. 3 from day 0 to day 90. The data are mean ± standard deviation; n = 8 / group, *P < 0.05, **P < 0.01, ***P < 0.001, compared with the hyperuricemia model group.

[0039] Figure 4For the changes in serum uric acid levels of C57 mice with chronic hyperuricemia models in different groups from day 0 to day 90, the serum uric acid levels of mice were measured every 15 days. As of day 75, the serum uric acid levels of mice in each group were still below the detection threshold of the uric acid meter, but the fasting blood glucose levels in each group had shown differences. Therefore, on day 80, potassium oxonate at a concentration of 50 mg / mL was intraperitoneally injected into mice in each group at a dose of 0.1 mL / 10 g to overall increase the serum uric acid levels of mice in each group, and dissection and sample collection were performed on day 90. Among them, the red broken line represents the changes in serum uric acid levels of mice in the hyperuricemia group fed with diet No. 1 from day 0 to day 90; the green broken line represents the changes in serum uric acid levels of mice in the composition group provided by the present invention fed with diet No. 2 from day 0 to day 90; the yellow broken line represents the changes in serum uric acid levels of mice in the allopurinol group fed with diet No. 3 from day 0 to day 90. The data are mean ± standard deviation; n = 8 / group, *P < 0.05, **P < 0.01, ***P < 0.001, compared with the hyperuricemia model group.

[0040] Figure 5 On day 90, orbital venous plexus blood was collected from C57 mice with chronic hyperuricemia models in different groups, and the blood urea nitrogen level ( Figure 5 C) and creatinine level ( Figure 5 D) in the blood were detected by a biochemical analyzer to indicate kidney function. At the same time, the kidneys were dissected and taken out for photographing ( Figure 5 A), and the weights of both kidneys were recorded to obtain the kidney-body ratio ( Figure 5 B). The data are mean ± standard deviation; n = 8 / group, *P < 0.05, **P < 0.01, ***P < 0.001, compared with the hyperuricemia model group.

[0041] Figure 6 On day 90, orbital venous plexus blood was collected from C57 mice with chronic hyperuricemia models in different groups, and alanine aminotransferase (ALT) ( Figure 6 C), aspartate aminotransferase (AST) ( Figure 6 D), albumin (ALB) ( Figure 6 E), alkaline phosphatase (ALP) ( Figure 6 F), total bile acid (TBA) ( Figure 6 G), and total bilirubin (T.BIL-V) ( Figure 6 H) in the blood were detected by a biochemical analyzer to indicate liver function. At the same time, the livers were dissected and taken out for photographing ( Figure 6 A), and the liver weights were recorded to obtain the liver-body ratio ( Figure 6 B). The data are mean ± standard deviation; n = 8 / group, *P < 0.05, **P < 0.01, ***P < 0.001, compared with the hyperuricemia model group. Detailed implementation methods

[0042] The following examples illustrate the method of the present invention but do not limit it. Other modifications and adaptive changes of various conditions and parameters that are obvious to those skilled in the art are included in the essence and scope of the present invention.

[0043] Description of the examples: (1) Commonly used model animals for hyperuricemia are mice and rats. Since these animals have uricase activity, there has been no report of acute and chronic hyperuricemia mouse and rat animal models caused by long-term feeding of pure food (including high-purine foods such as yeast powder). Instead, it is necessary to add uricase inhibitors such as potassium oxonate to successfully establish the model. The present invention selects white - feather meat pigeons. These animals, like humans, do not have uricase activity. By feeding the same pure food feed rich in purines, without adding uricase inhibitors, a hyperuricemia and gout model can be successfully established in a very short time (such as 1 - 2 weeks), and the uric acid level can even exceed 1000 μmol / L.

[0044] (2) In order to compare the safety and effectiveness of the selected product composition during long - term feeding, the present invention selects the second - group feed with good activity for white - feather meat pigeons to feed C57 mice for 3 months. Body weight, fasting blood glucose, and uric acid are detected on the 15th day, 30th day, 45th day, 60th day, 75th day, and 90th day respectively. It is found that there is no significant difference in body weight and uric acid among the groups of mice. The fasting blood glucose of the mice fed with feed 2 product composition (the composition group containing SOD, trehalose, green wheat seedling powder, and whole milk) is lower than that of feed 1 (model group), and this difference change is statistically significant on the 45th day, 60th day, 75th day, and 90th day. In order to facilitate the detection of changes in the uric acid levels of each group of mice, potassium oxonate is intraperitoneally injected on the 80th day to increase the whole - body blood uric acid level and achieve homogenization of each group. It is found that the blood uric acid levels of the mice in the product composition (the composition group containing SOD, trehalose, green wheat seedling powder, and whole milk) and the allopurinol group are slightly lower than those in the model group, preliminarily indicating that the product composition and the positive drug allopurinol have the effect of reducing uric acid. On the 90th day, orbital venous plexus blood is collected for detection of liver function indexes represented by alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and kidney function indexes represented by blood urea nitrogen and serum creatinine. At the same time, the liver and kidneys are dissected out for weighing and photographing. It is found that there is no significant difference in the relevant biochemical indexes of the liver and kidneys of each group of mice, and the appearance color of the liver and kidneys is ruddy without lesions. Combining with indexes such as the body weight, fasting blood glucose, and uric acid of the mice, it is found that the composition or the product containing this composition has no obvious side effects. At the same time, the remaining feed amount is weighed and detected every 15 days, and the feed intake is calculated by the difference between the initial amount and the final remaining amount of the feed, so as to calculate the average value of the feed intake (g / cage / day).

[0045] (3) The palatability of food or feed is mainly reflected by the feed intake of animals. The results show that the white - feather meat pigeons have a relatively large intake of the combined feed containing SOD, trehalose, green wheat seedling powder and milk. The intake of mice increases slightly.

[0046] (4) Among the feed ingredients, except for the food composition SOD, trehalose, green wheat seedling powder and milk added in the present invention, and the uric - acid - lowering drug allopurinol used as a positive control, other ingredients such as sucrose, corn flour, maltodextrin, lard, brewer's yeast (high - purine food), choline chloride, methionine, vitamin A, and mineral A are normal feed or modeling feed (such as high - fat, brewer's yeast).

[0047] More specifically, in the present invention, by weight, composition 1 includes: 0.14 parts of SOD, 3.57 parts of trehalose, 24.96 parts of green wheat seedling powder, and 71.33 parts of milk.

[0048] By weight, composition 2 includes: 0.04 parts of SOD, 10 parts of trehalose, 34 parts of green wheat seedling powder, and 55.96 parts of milk.

[0049] By weight, composition 3 includes: 0.18 parts of SOD, 1 part of trehalose, 17.87 parts of green wheat seedling powder, and 80.95 parts of milk.

[0050] (5) To ensure that the weight ratio of each group of feed formulas is 100%, compared with the model group, after adding the products for research purposes such as SOD, trehalose, green wheat seedling powder and milk and the drug allopurinol in the control group, the extra weight is made up by reducing the amount of corn flour and lard. Because reducing the amount of corn flour has the least impact on the experimental results, and although reducing the amount of lard may cause deviations in the experimental results, the added whole - milk powder also contains lipids, and its impact can be minimized. Moreover, compared with the positive control group (the lard content in the two groups of feed is the same), the effect of the product combination group can be effectively evaluated.

[0051] Experiment on the uric - acid - lowering activity of the composition in Example 1 for white - feather meat pigeons

[0052] (1) Grouping of experimental animals

[0053] Adult male white - feathered meat pigeons were selected and raised under standard conditions. The experimental pigeons were placed in special cages (2 pigeons / cage), with free access to water and food, and kept in a temperature - controlled room (temperature 26°C; relative humidity 45% - 60%; lighting, 24 hours, 10 Lux). The white - feathered meat pigeons were grouped according to their initial uric acid levels to ensure the homogenization of the initial serum uric acid levels in each group. They were divided into 5 groups, with 5 pigeons in each group, namely the hyperuricemia model group (HUA group), 3 groups of composition groups containing different proportions of SOD, trehalose, green wheat seedlings powder and whole milk, and the positive drug allopurinol group (AP group). Each group of pigeons was given the corresponding feed and sufficient water for 7 days. After anesthesia, wing - root venous blood was taken to measure the uric acid levels in the blood of pigeons in different groups, and then they were sacrificed by exsanguination from the posterior cervical vein.

[0054] (2) Establishment of the hyperuricemia model in white - feathered meat pigeons and administration of drugs

[0055] The hyperuricemia model group was given Feed No. 1, the composition groups with different proportions were given Feed No. 2, No. 4, and No. 5, and the positive drug allopurinol group was given Feed No. 3. Each group of pigeons was given the corresponding feed and sufficient water for a total of 14 days. Table 1 lists the ingredient ratios of Feed No. 1 - 5. In Table 1, Feed 2 uses Food Composition 1, Feed 1 is the model group, and Feed 3 is the positive control group. Replacing Composition 1 in Feed 2 with Composition 2 or Food Composition 3 forms Feed 4 and Feed 5 respectively. Feeding white - feathered meat pigeons with Feed 4 and Feed 5 can also play a role in treating hyperuricemia.

[0056] Table 1 Feed ingredient table (content %, wt / wt)

[0057]

[0058]

[0059] (4) Evaluation of the palatability of different feeds

[0060] The feed intake was calculated by finding the difference between the initial amount and the remaining amount at the end of the feed, and then the average feed intake (grams / cage / week) was calculated to compare the palatability differences of the feeds in each group. Table 2 lists the average feed intakes of the feeds in each group.

[0061] Table 2 Average feed intake of white - feathered meat pigeons (grams / cage / week)

[0062]

[0063] As can be seen from Table 2 above, compared with the model group (Feed 1 group), the average intakes of Feed 2, Feed 4, and Feed 5 in two weeks were higher than that of Feed 1, and the average total intakes in two weeks increased by 16.09%, 16.00%, and 19.52% respectively. The intake of Feed 3 in the positive control group also increased to varying degrees. This shows that the palatability of the feed containing the composition is relatively excellent.

[0064] (5) Euthanasia of animals and detection of biochemical indicators

[0065] On the 7th day and 14th day after feeding the corresponding feed to each group of white - feathered meat pigeons, after anesthesia, wing - root venous blood was taken. After centrifuging the blood samples, the supernatant was taken, and the blood uric acid level was measured using a uric acid test strip.

[0066] Figure 1 It is a schematic diagram showing the effects of different groups on the fluctuations of uric acid levels in white - feathered meat pigeons with chronic hyperuricemia on the 0th day, 7th day, and 14th day. Among them, it shows the effects of the composition containing SOD, trehalose, green wheat seedling powder, and whole - milk powder on the fluctuations of uric acid levels in white - feathered meat pigeons with chronic hyperuricemia. Compared with the initial serum uric acid of white - feathered meat pigeons, the serum uric acid of white - feathered meat pigeons in the HUA group showed an upward trend, and the average serum uric acid level was higher than that of other groups. This shows that the plan of constructing a hyperuricemia model by externally supplementing high - purine to white - feathered meat pigeons with Feed 1 is feasible.

[0067] The three compositions (Feed 2, Feed 4, and Feed 5) provided by the present invention were continuously fed to white - feathered meat pigeons for 14 days, and the serum uric acid level was significantly lower than that of the HUA group. Among them, Feed 2 had a better uric - acid - lowering effect. It is thus speculated that the composition containing SOD, trehalose, green wheat seedling powder, and whole - milk powder has a good effect on reducing serum uric acid.

[0068] In the AP group, the serum uric acid of white - feathered meat pigeons showed a trend of first rising and then falling, indicating that the combination of trehalose and SOD with green wheat seedling powder and milk has a faster effect on reducing the serum uric acid of white - feathered meat pigeons than the combination of AP with green wheat seedling powder and milk.

[0069] Safety experiment of the composition in Example 2 on C57 mice

[0070] (1) Grouping of experimental animals

[0071] Male C57 mice weighing about 18 ± 2 g were selected and housed under standard conditions in a controlled room at a temperature of 25 ± 1 °C and a humidity of 50 ± 10%. A 12-hour light / dark cycle was maintained. All animals were allowed free access to laboratory diet and water. The C57 mice were grouped according to their initial body weight and blood glucose levels to ensure the homogenization of the initial body weight and blood glucose levels of each group of mice; they were divided into 3 groups, with 8 mice in each group, namely the chronic hyperuricemia model group (HUA group), the composition 1 group containing SOD, trehalose, green wheat seedlings powder and whole milk (i.e., the feed 2 group of white pigeons), and the positive drug allopurinol group (AP group). Each group of mice and white pigeons were given the corresponding same feed and sufficient water, and fed for 90 days. Body weight, fasting blood glucose, uric acid and remaining feed amount were measured every 15 days. After anesthesia, orbital venous plexus blood was taken to measure the uric acid level in the blood of mice in different groups. The liver and kidneys were dissected, weighed, photographed and recorded, and then the mice were sacrificed by cervical dislocation.

[0072] (2) Establishment and administration of hyperuricemia model mice

[0073] The chronic hyperuricemia model group was given Feed No. 1, the composition group was given Feed No. 2, and the positive drug allopurinol group was given Feed No. 3. Each group of mice was given the corresponding feed and sufficient water for a total of 90 days. On the 80th day, potassium oxonate was injected intraperitoneally to achieve the purpose of synchronous elevation of uric acid levels and facilitate detection. The feed formula is shown in Table 1.

[0074] (3) Evaluation of palatability of different feeds

[0075] The feed intake was calculated by the difference between the initial amount and the final remaining amount of the feed, and then the average feed intake (g / cage / day) was calculated to compare the palatability differences among different groups of feeds.

[0076] Table 3 Average daily feed intake of C57 mice (g / cage / day)

[0077] Date / Average Feed Intake (g) Feed 1 Feed 2 Feed 3 Average Feed Intake from 11.30 to 12.01 (g) 11.53±1.24 12.85±0.42 12.08±0.95 Average Feed Intake from 12.13 to 12.14 (g) 14.90±0.00 14.30±1.41 15.75±4.03 Average Feed Intake from 12.29 to 12.30 (g) 12.16±0.06 12.84±0.73 12.61±1.30 Average Feed Intake from 01.13 to 01.14 (g) 11.65±0.35 12.65±0.78 12.55±1.34 Average Feed Intake from 01.29 to 01.30 (g) 11.15±0.49 11.90±0.99 10.95±1.20 Average Feed Intake from 02.15 to 02.16 (g) 10.70±0.57 11.55±0.92 11.95±1.06 Total Average (g) 12.01±1.50 12.68±1.14 12.64±2.13

[0078] As can be seen from Table 3 above, the average daily intake of Feed No. 2 and Feed No. 3 was slightly higher than that of Feed No. 1 in the model group, and the average intake increased by 5.3% and 5.0% respectively. Although the increase ratio was not high, it at least indicated that the addition of the composition was no less palatable to C57 mice than the control group.

[0079] (4) Evaluation of safety of different feeds

[0080] After feeding the corresponding feed to the mice for 90 days, the activity status, diet status, hair color, urine and feces conditions of the mice were evaluated every 15 days, and the body weight, fasting blood glucose, uric acid and average feed intake of the mice were measured. The results are shown in Appendix Figure 2 、Appendix Figure 3 、Appendix Figure 4and Table 3. On the 90th day, after anesthesia, blood was collected from the orbital venous plexus for biochemical detection. The liver and kidneys were dissected for photographing records. The results are shown in Appendix Figure 5 and Appendix Figure 6 .

[0081] (5) Animal euthanasia and detection of biochemical indicators

[0082] After feeding the corresponding diets to each group of mice for 90 days, blood was collected from the orbital venous plexus after anesthesia. After centrifuging the blood samples, the supernatant was taken, and relevant biochemical indicators were measured using a biochemical analyzer. The liver and kidneys were dissected for photographing, and the liver weight and kidney weight were recorded, and then quickly frozen in liquid nitrogen for subsequent experimental detection.

[0083] Figure 2 Shows the changes in body weight levels of C57 mice with chronic hyperuricemia models in different groups from day 0 to day 90. The body weight of mice was measured every 15 days. The trends of body weight levels of the three groups of mice were the same, with no significant differences, indicating that there were no significant differences in the effects of Diet 1, Diet 2, and Diet 3 on the body weight of mice.

[0084] Figure 3 Shows the changes in fasting blood glucose levels of C57 mice with chronic hyperuricemia models in different groups from day 0 to day 90. The fasting blood glucose level of mice was measured every 15 days. Among them, Diet 1 is rich in oil and purine. In the hyperuricemia group of mice fed with Diet 1, the fasting blood glucose level was higher than the other two groups since the 45th day, and there were statistical differences. In contrast, the composition group and allopurinol group had no significant effect on the fasting blood glucose of mice, indicating that long-term consumption of this composition would not cause an increase in blood glucose and has good safety.

[0085] Figure 4 Shows the changes in serum uric acid levels of C57 mice with chronic hyperuricemia models in different groups from day 0 to day 90. The serum uric acid level of mice was measured every 15 days. As of the 75th day, the serum uric acid levels of each group of mice were still below the detection threshold of the uric acid meter, but the fasting blood glucose levels of each group had shown differences. Therefore, on the 80th day, potassium oxonate at a concentration of 50 mg / mL was intraperitoneally injected into each group of mice at a dose of 0.1 mL / 10 g to overall increase the serum uric acid levels of each group of mice, and anatomical specimens were taken on the 90th day. Among them, as of the 75th day, the three groups of mice fed with different diets had no significant effect on the fluctuation of uric acid levels in the body. On the 80th day, after intraperitoneal injection of potassium oxonate, the uric acid levels in the composition group and allopurinol group were lower than those in the hyperuricemia group, preliminarily indicating that this composition and allopurinol have the effect of reducing uric acid. On the 90th day, compared with the hyperuricemia group of mice, the composition group and allopurinol group reduced the serum uric acid levels of mice to varying degrees, further verifying the uric acid-lowering efficacy of this composition.

[0086] Figure 5On the 90th day, orbital venous plexus blood was collected from C57 mice with chronic hyperuricemia models in different groups, and the blood urea nitrogen level ( Figure 5 C) and creatinine level ( Figure 5 D) in the blood were detected by a biochemical analyzer to indicate kidney function. At the same time, the kidneys were dissected out, photographed ( Figure 5 A), and the weights of both kidneys were recorded to obtain the kidney-body ratio ( Figure 5 B). Among them, the kidneys of the mice fed with the three groups of feeds had a ruddy, plump appearance, there was no obvious difference in the kidney-body ratio, and there was also no statistical difference in the blood urea nitrogen and blood creatinine levels. Therefore, it shows that the composition has no toxic and side effects on the kidneys and has good safety.

[0087] Figure 6 On the 90th day, orbital venous plexus blood was collected from C57 mice with chronic hyperuricemia models in different groups, and alanine aminotransferase (ALT) ( Figure 6 C), aspartate aminotransferase (AST) ( Figure 6 D), albumin (ALB) ( Figure 6 E), alkaline phosphatase (ALP) ( Figure 6 F), total bile acid (TBA) ( Figure 6 G), total bilirubin (T.BIL-V) ( Figure 6 H) in the blood were detected by a biochemical analyzer to indicate liver function. At the same time, the livers were dissected out, photographed ( Figure 6 A), and the liver weights were recorded to obtain the liver-body ratio ( Figure 6 B). Among them, the livers of the mice fed with the three groups of feeds had a ruddy appearance, no lesions, no obvious difference in the liver-body ratio, and there was also no statistical difference in the biochemical indexes related to liver function. Further, it shows that the composition has no toxic and side effects on the liver and has good safety for the liver and kidneys.

[0088] Based on the above experiments and their results, the present invention proves that the composition containing SOD, trehalose, green wheat seedling powder and whole milk can safely and effectively reduce the uric acid in the serum of experimental animals, and thus play a role in treating hyperuricemia.

[0089] The above embodiments are the preferred embodiments of the present invention, but the embodiments of the present invention are not limited by the above embodiments. Any other changes, modifications, substitutions, combinations, and simplifications made without departing from the spirit and principle of the present invention shall be equivalent replacement methods and are all included in the protection scope of the present invention.

Claims

1. A composition, characterized in that The composition consists of the following components by weight: 0.04-0.18 parts of SOD, 1-10 parts of trehalose, 17-34 parts of green wheatgrass powder, and 55-81 parts of milk.

2. The composition according to claim 1, characterized in that The composition consists of the following components by weight: 0.08-0.16 parts of SOD, 2-6 parts of trehalose, 24-32 parts of green wheatgrass powder, and 60-76 parts of milk.

3. The composition according to claim 1, characterized in that The composition consists of the following components by weight: 0.1-0.14 parts of SOD, 3-5 parts of trehalose, 24-30 parts of green wheatgrass powder, and 65-75 parts of milk.

4. The composition according to any one of claims 1 to 3 further comprises an auxiliary material composition added for excipient and palatability.

5. The composition according to any one of claims 1 to 4 is prepared into tablets, granules, powders or capsules.

6. Use of the composition according to any one of claims 1 to 4 in the preparation of a product for lowering uric acid.

7. Use of the composition according to any one of claims 1 to 4 in the preparation of a product for preventing and / or treating hyperuricemia or gout, gout complications or renal damage caused by it.

8. The use according to claim 7, characterized in that: The gout complications are one or more of gouty arthritis, urinary tract stones or cardiovascular disease.

9. The use according to claim 7, characterized in that: The products are food, health products, dairy products, fermented products, and food additives.

10. A method for preparing the composition according to any one of claims 1 to 3, characterized in that: The composition is obtained by mixing SOD, trehalose, green barley grass powder and milk.

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