Imidazole dipeptide compositions with renal protective effects and uses thereof

Abstract

A renal-protective imidazole dipeptide composition and its use. The renal-protective imidazole dipeptide composition contains anserine and carnosine, and the anserine content is 10%-99% and the carnosine content is 1%-90%, assuming that the total weight of anserine and carnosine is 100%. Experiments with mice showed that mice with hyperuricemia and renal damage after continuous administration of the imidazole dipeptide composition for a certain period of time showed significantly less renal damage than the control group, demonstrating that the imidazole dipeptide composition has a good renal-protective effect.

Description

[Technical Field]

[0001] The present invention relates to imidazole dipeptide compositions and uses thereof, in particular to imidazole dipeptide compositions having renal protective effects and the use of such compositions in the manufacture of related products having renal protective effects (e.g., pharmaceuticals or specific medical foods, etc.). [Background technology]

[0002] The kidney is an important organ in the human body, and its main function is to remove metabolic products, waste products, and toxic substances from the body by forming urine, and to retain water and other useful substances through reabsorption.Irregular eating habits can lead to the production of high uric acid, and long-term high uric acid can induce various complications such as gout, diabetes, metabolic syndrome, oxidative stress, inflammation, hypertension, and endothelial dysfunction, and also place a heavy burden on the kidney, leading to kidney damage.

[0003] Creatinine and urea nitrogen are normal biochemical indicators of renal function. Creatinine is a waste product produced by human muscles. It is mostly excreted by the kidneys and is not easily affected by food, so it relatively objectively reflects renal function. An increase in blood creatinine concentration indicates a decrease in the kidney's ability to remove waste. Urea nitrogen is a metabolic product of protein breakdown during digestion and is converted in the liver through the urea cycle. When renal function is impaired, the ability to excrete urea naturally decreases, urea accumulates in the blood, and the blood urea nitrogen level increases.

[0004] CN113616688A discloses a composition for repairing kidney damage and its use. The active ingredients of the composition consist of anserine (β-alanyl-1-methyl-L-histidine, Ans) dry powder, Astragalus membranaceus extract, and Sophora Root extract. The mass ratio of the anserine dry powder, Astragalus membranaceus extract, and Sophora Root extract in the composition is 80-90:3-10:5-15. Experiments have shown that the composition consisting of anserine dry powder, Astragalus membranaceus extract, and Sophora Root extract can repair kidney damage to some extent, but anserine alone has poor kidney damage repair effects. Furthermore, the herbal flavors of the Astragalus membranaceus extract and Sophora Root extract used in this composition are generally unpleasant. Summary of the Invention

[0005] One object of the present invention is to provide a composition that has renal protective effects.

[0006] Another object of the present invention is to provide uses of said composition.

[0007] The present invention provides the following technical solutions:

[0008] Technical Solution 1: A composition containing anserine and carnosine, in which the total weight of anserine and carnosine is 100%, the anserine content is 10%-99%, and the carnosine content is 1%-90%, and the renal protective effect is achieved by imidazole dipeptide composition.

[0009] Technical Scheme 2: The imidazole dipeptide composition according to Technical Scheme 1, in which the anserine content is 91% and the carnosine content is 9%, based on the total weight of anserine and carnosine being 100%.

[0010] According to some specific embodiments of the present invention, in the imidazole dipeptide composition of the present invention, the sum of the weights of anserine and carnosine accounts for 50% or more, preferably 60% or more, more preferably 70% or more, 80% or more, 85% or more, 90% or more, 95% or more, or 100% of the total weight of the composition.

[0011] Technical Scheme 3: The imidazole dipeptide composition according to Technical Scheme 1 or 2, which consists of anserine and carnosine.

[0012] Technical Scheme 4: The imidazole dipeptide composition according to Technical Scheme 1 or 2, further comprising other substances with renal protective effects. According to some specific embodiments of the present invention, the amount of the other substances with renal protective effects accounts for 50% or less of the total weight of the imidazole dipeptide composition of the present invention.

[0013] Technical Scheme 5: The imidazole dipeptide composition according to Technical Scheme 4, wherein the other substance having renal protective effects includes histidine and / or histidine derivatives. The histidine derivatives include, but are not limited to, oligopeptides containing histidine residues, such as oligopeptides consisting of multiple histidines or histidine and other amino acids, and may be dipeptides, tripeptides, etc., preferably dipeptides. The histidine and histidine derivatives may be derived from animals and / or plants, such as chicken, fish, or other animal muscles.

[0014] Technical Scheme 6: Use of the imidazole dipeptide composition according to any one of Technical Schemes 1 to 5 in the manufacture of a composition having renal protective effects.

[0015] In the present invention, the term "renal protection" means having a protective effect on the kidney, and includes supplementary protection of the kidney and contribution to kidney health.

[0016] According to some specific embodiments of the present invention, the renal protective effect includes alleviating renal damage caused by hyperuric acid.

[0017] According to some specific embodiments of the invention, the nephroprotective effect comprises lowering uric acid levels, serum creatinine and / or urea nitrogen levels in individuals with hyperuricemic nephropathy.

[0018] According to some specific embodiments of the present invention, the renal protective effect includes improving renal tissue damage caused by hyperuricemia and alleviating inflammatory cell infiltration in renal tissue.

[0019] According to some specific embodiments of the invention, the renal protective effect comprises reducing the levels of pro-inflammatory factors such as TNF-α, IL-1β, IL-6, etc. in renal impaired individuals.

[0020] According to some specific embodiments of the present invention, the nephroprotective effect comprises increasing glutathione levels in serum and / or kidney tissue of hyperuricemia individuals.

[0021] According to some specific embodiments of the present invention, the renal protective effect comprises increasing SOD levels in serum and / or kidney tissue of hyperuricemia individuals and mitigating oxidative damage.

[0022] According to some specific embodiments of the invention, the nephroprotective effect comprises reducing malondialdehyde levels in serum and / or kidney tissue of hyperuricemia individuals.

[0023] The present invention further provides a method for renal protection, comprising administering an effective amount of the imidazole dipeptide composition described in any one of technical solutions 1 to 5 of the present invention to an individual in need thereof.

[0024] According to some specific embodiments of the invention, the individual is a mammal or a human.

[0025] Technical Scheme 7: The use according to Technical Scheme 6, wherein the composition is for producing a medicine.

[0026] Technical Solution 8: The use according to Technical Solution 7, wherein the pharmaceutical contains an effective amount of the imidazole dipeptide composition.

[0027] Technical Scheme 9: The use according to Technical Scheme 7 or 8, wherein the dosage of the imidazole dipeptide composition in the pharmaceutical is 1 mg-200 mg / day, preferably 1 mg-100 mg / day, more preferably 5 mg-50 mg / day.

[0028] Technical Solution 10: The use according to any one of Technical Solutions 7 to 9, wherein the pharmaceutical further comprises auxiliary materials, preferably including one or a combination of two or more of sorbitol, maltodextrin, and magnesium stearate.

[0029] Technical Scheme 11: The use according to any one of Technical Schemes 7 to 10, wherein the pharmaceutical is a tablet, capsule, powder or granule.

[0030] Technical Scheme 12: The use according to Technical Scheme 6, wherein the composition is for producing food. The food may be, for example, a functional food, a supplement, etc. The functional food may be, for example, a health food, a specific medical food, a therapeutic diet, etc.

[0031] Technical Scheme 13: The use according to Technical Scheme 12, wherein the amount of the imidazole dipeptide composition in the food may be 1 mg-200 mg / day, preferably 1 mg-100 mg / day, more preferably 5 mg-50 mg / day, in terms of adult intake.

[0032] The present invention has demonstrated through experiments that the imidazole dipeptide composition according to the present invention has a good protective effect on the kidneys of mice and can effectively alleviate kidney damage caused by hyperuric acid.

[0033] According to a specific embodiment of the present invention, treatment with an imidazole dipeptide composition had a significant uric acid-lowering effect on mice with hyperuricemia-related kidney damage. Serum creatinine and urea nitrogen levels in the treatment group were significantly reduced to normal levels, demonstrating that treatment with imidazole dipeptide alleviated hyperuricemia-related kidney damage. Histopathological sections of the mouse kidneys showed that treatment with the imidazole dipeptide composition significantly improved hyperuricemia-related kidney tissue damage and alleviated inflammatory cell infiltration in kidney tissue. Furthermore, the levels of three pro-inflammatory factors, TNF-α, IL-1β, and IL-6, were significantly reduced in the treatment with the imidazole dipeptide composition. Furthermore, detection of glutathione in serum and kidney tissue homogenate indicated that treatment with the imidazole dipeptide composition improved glutathione levels in the serum and kidney tissue of hyperuricemia-related mice and alleviated oxidative damage caused by uric acid production. The results of superoxide dismutase detection in serum and kidney tissue homogenate showed that the imidazole dipeptide composition treatment improved SOD levels in the serum and kidney tissue of hyperuric acid model mice and alleviated oxidative damage caused by uric acid generation. The results of glutathione peroxidase detection in serum and kidney tissue homogenate showed that the imidazole dipeptide composition treatment improved glutathione peroxidase levels in the serum and kidney tissue of hyperuric acid model mice and alleviated oxidative damage caused by uric acid generation. The results of malondialdehyde detection in serum and kidney tissue homogenate showed that the imidazole dipeptide composition treatment significantly reduced malondialdehyde levels in the serum and kidney tissue of hyperuric acid model mice, and the malondialdehyde levels in all intervention groups were not significantly different from those in the control group, demonstrating that all treatments can alleviate oxidative damage caused by uric acid generation.

[0034] The imidazole dipeptide composition provided by the present invention has a renal protective effect. In a mouse experiment, mice with high uric acid kidney damage were given the imidazole dipeptide composition of the present invention for a certain period of time, and the mice showed significantly less kidney damage than the control group, demonstrating a good renal protective effect. [Brief explanation of the drawings]

[0035] [Figure 1] Figure 1 is a flow chart of the animal experiments. [Figure 2] Figure 2 shows the effect of different interventions on serum uric acid in mice. [Figure 3] Figure 3 shows the effect of different interventions on serum creatinine levels in mice. [Figure 4] Figure 4 shows the effect of different interventions on serum urea nitrogen levels in mice. [Figure 5] Figure 5 shows the pathological analysis of the effects of different interventions on the kidneys of mice. [Figure 6] FIG. 6 shows kidney inflammatory factor levels (TNF-α) in mice. [Figure 7] FIG. 7 shows kidney inflammatory factor levels (IL-1β) in mice. [Figure 8] FIG. 8 shows kidney inflammatory factor levels (IL-6) in mice. [Figure 9] FIG. 9 shows kidney inflammatory factor levels (IL-10) in mice. [Figure 10] FIG. 10 shows serum lipopolysaccharide levels in mice. [Figure 11] FIG. 11 shows serum lactate dehydrogenase levels in mice. [Figure 12] FIG. 12 shows serum glutathione levels in mice. [Figure 13] FIG. 13 shows kidney tissue glutathione levels in mice. [Figure 14] FIG. 14 shows serum superoxide dismutase levels in mice. [Figure 15] FIG. 15 shows kidney tissue superoxide dismutase levels in mice. [Figure 16] FIG. 16 shows serum glutathione peroxidase levels in mice. [Figure 17] FIG. 17 shows kidney tissue glutathione peroxidase levels in mice. [Figure 18] FIG. 18 shows serum malondialdehyde levels in mice. [Figure 19] FIG. 19 shows kidney tissue malondialdehyde levels in mice.

[0036] In the figure, data are expressed as mean ± standard deviation. Letters such as a, b, and c indicate the significance analysis results (p<0.05) of data from the same column. When the accompanying letters are the same, there is no significant difference between the accompanying values. DETAILED DESCRIPTION OF THE INVENTION

[0037] In order to make the technical features, objectives and beneficial effects of the present invention more clearly understood, the technical solutions of the present invention are described in detail below, but should not be understood as limiting the scope of the present invention. [Example]

[0038] Example 1 This example provided an imidazole dipeptide composition having the following composition, by weight: anserine 91 parts, carnosine 9 parts.

[0039] Anserine and carnosine were collected in the above ratio and mixed uniformly to obtain the physiologically active peptide of this example, which was an imidazole dipeptide composition.

[0040] Example 2 This example provides a pharmaceutical product comprising the composition provided by Example 1.

[0041] Example 3 This example provided a food product containing the composition provided by Example 1.

[0042] Experimental study of the renal protective effect of imidazole dipeptides The present inventors have verified the renal protective effect of the imidazole dipeptide of the present invention through animal experiments.

[0043] 1. Test samples and test animals Test sample: the physiologically active peptide of Example 1 (i.e., an imidazole dipeptide consisting of 91 parts of anserine and 9 parts of carnosine). Test animals: Five-week-old male ICR mice were purchased from Shanghai JSJ Laboratory Animal Co., Ltd. and were SPF grade.

[0044] 2. Grouping and treatment of experimental animals All mice were housed at 24 ± 2°C under a 12-h light / 12-h dark cycle with free access to food and water. After 1 week of adaptation, mice were randomly assigned to groups (7 mice per group): normal control, model, positive control, low-dose imidazole dipeptide (IDP-L), and high-dose imidazole dipeptide (IDP-H). The model construction cycle was 2 weeks, and the intervention cycle was 4 weeks. During the model construction period, except for the normal control group, each group received daily intragastric administration of 300 mg / kg potassium oxonate and hypoxanthine (prepared as a suspension in 0.5% CMC-Na solution) to construct the hyperuricemia model. During the intervention period, except for the normal control group, each group was administered 300 mg / kg of potassium oxonate and hypoxanthine intragastrically every day to maintain model construction. After 2 hours of model construction, the mice in each group were administered the doses shown in Figure 1. The administration samples for each group were dissolved in saline, and the normal group and model group were intragastrically administered with the same amount of saline.

[0045] 3. Sampling and processing of detection samples During the model construction period, blood samples were collected weekly by tail snip to monitor changes in serum uric acid. On the final two days of the experiment, fresh feces were collected from each group of mice and stored in a -20°C refrigerator. Before sacrifice, mice were fasted for 12 hours and then subjected to the final model construction. After 1 hour of model construction, blood samples were collected and then sacrificed and dissected. Whole blood from mice was stored at 4°C for 2 hours, then centrifuged at 3000 rpm for 10 minutes. Serum was aliquoted and stored in a -80°C refrigerator. Livers and kidneys were removed from the mice. One kidney was preserved in 4% paraformaldehyde for pathological analysis. The other tissue samples were immediately snap-frozen in liquid nitrogen, aliquoted, and stored at -80°C.

[0046] 4. Detection method Uric acid, creatinine, urea nitrogen, lactate dehydrogenase, xanthine oxidase (XOD), lipopolysaccharide (LPS), oxidative stress levels (glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA)), inflammatory factors (TNF-alpha, IL-1β, IL-6, IL-10), and hypoxanthine phosphoribosyltransferase 1 (HPRT1) levels were detected according to the methods described in the reagent cassette. Mice were weighed twice weekly. Urine pH was measured weekly using pH test paper. Pathological analysis of kidney tissue was completed in collaboration with Wuhan Servicebio Technology Co., Ltd. Western blot analysis of kidney urate transporters was performed according to the laboratory's routine procedures.

[0047] 5. Data processing methods Statistical analysis was performed using SPSS22.0 software based on the Tukey method, and differences were considered statistically significant when p<0.05. Drawings, correlation analysis, and bioinformatics analysis were performed using GraphPadPrism8 and Rstudio.

[0048] 6. Experimental results and conclusions 6.1 Model building results After one week of model construction using potassium oxonate and hypoxanthine, the mice were tail-cut and blood samples were collected to measure serum uric acid levels. After one week of model construction, serum uric acid levels in some mice were significantly elevated, but in most mice, serum uric acid levels were not significantly elevated. Therefore, a secondary model construction was performed on the mice (maintaining the model construction for one week). After two weeks of model construction, the mice were tail-cut and blood samples were collected to measure serum uric acid levels. After two weeks of model construction, serum uric acid levels in all mice, except for the normal group, were significantly elevated compared to the normal group, with the increase being approximately two-fold higher. This demonstrated that the construction of the hyperuricemia model was highly successful. Therefore, starting from the third week of model construction, intragastric administration of imidazole dipeptide or probiotic intervention was performed during model construction.

[0049] 6.2 Changes in mouse body weight and urine pH during intragastric administration Although the body weight of some mice in the six-week intragastric administration intervention fluctuated, the body weight of most groups did not change significantly or only slightly. During the six-week period, the urinary pH between different groups at the same time and between different times in the same group both fluctuated, but the fluctuations were not large and irregular.

[0050] 6.3 Effects of different interventions on three renal functions in mice Serum uric acid levels are the most important indicator for directly assessing hyperuricemia. Creatinine is formed in muscles through spontaneous and irreversible conversion from creatine phosphate. Unless muscle mass changes significantly, the amount of creatinine formed is generally constant. Because the amount of circulating free creatinine is entirely dependent on its excretion rate, measuring creatinine levels in serum or plasma can be used to evaluate glomerular filtration efficiency and identify renal function status. Blood urea nitrogen originates in the liver and is excreted from the body via the kidneys with urine. Renal failure, nephritis, urethral obstruction, etc. can increase blood urea nitrogen levels. As can be seen, serum creatinine and urea nitrogen are two indicators for assessing renal function. The results of the three renal function tests are shown in Figures 2, 3, and 4. The uric acid levels in the model group were significantly higher than those in all other groups. After four weeks of treatment, uric acid levels in all intervention groups were significantly reduced, demonstrating that all interventions with different formulations had a favorable uric acid-lowering effect. Among these, uric acid levels in the positive control group and the high and low dose imidazole dipeptide groups were reduced to normal levels (no significant difference compared to the normal group), while uric acid levels in the other intervention groups were slightly higher than the normal group but significantly lower than the model group. As uric acid concentrations increased in the model group, serum creatinine and urea nitrogen levels were significantly elevated compared to the normal group, consistent with literature findings that hyperuricemia is associated with renal dysfunction in mice. With the exception of the positive control group, serum creatinine and urea nitrogen levels in all other intervention groups were reduced to normal levels (no significant difference compared to the normal group, but significant difference compared to the model group), demonstrating that imidazole dipeptide treatment can alleviate renal damage caused by hyperuricemia. The creatinine and urea nitrogen levels of the mice in the positive control group were elevated, indicating that allopurinol can reduce the uric acid levels of mice with hyperuricemia, but has strong nephrotoxicity to mice.

[0051] 6.4 Protective effects of different interventions on the kidneys of mice Clinically, alterations in renal tissue structure and inflammatory cell infiltration are prominent pathological features of hyperuricemia. Figure 5 shows histopathological sections of the kidneys of mice from each group. In the normal group, the glomerular matrix was uniform, the tubular epithelial cells were round and swollen, and the connective tissue between the tubules was the renal interstitium, with no obvious interstitial proliferation. No obvious inflammatory changes were observed. In the model group, the field of view showed a small amount of lymphocytic infiltration (black arrows) around the blood vessels and granulocytes (red arrows) within the glomeruli. A relatively large number of tubular epithelial cells showed aqueous degeneration, swelling, sparse cytoplasm, and weak staining (green arrows). The tubules were dilated, flattened, and had enlarged lumens (blue arrows). The lumens were filled with eosinophilic flocs (purple arrows). A few exfoliated epithelial-like cells (yellow arrows) were also observed within the tubules. In the positive group, the field of view showed atrophy of the renal tubules, weak eosinophilicity of the epithelial cells, narrow lumina, unclear structure (white arrow), proliferation of a small amount of surrounding connective tissue (orange arrow), accompanied by a small amount of lymphocytes (black arrow) and granulocyte infiltration (red arrow). A large amount of renal tubule epithelial cells showed aqueous degeneration, swelling of the cells, sparse cytoplasm, and weak staining (green arrow). A small amount of renal tubules showed dilation, flattening of the renal tubule epithelial cells, and enlarged lumina. A few granulocytes (blue arrow) were seen in the lumina, and a small amount of eosinophilic material (purple arrow) was seen in the lumina of the renal tubules. Renal tissue damage in mice in other groups was significantly improved compared to the model group. Visual field observations revealed a small number of tubular epithelial cells with aqueous degeneration, swelling, sparse cytoplasm, and light staining (green arrows). A small amount of eosinophilic material (purple arrows) was observed within the tubules. Using potassium oxonate and hypoxanthine to model hyperuricemia, mice exhibited significant inflammation and tissue structural damage in their kidneys. Tubular reabsorption and glomerular filtration efficiency significantly affected uric acid levels. Tubular damage and glomerular filtration dysfunction further increased uric acid concentrations and led to the deposition of uric acid crystals. Allopurinol treatment reduced uric acid levels in hyperuricemia mice, but also resulted in severe kidney damage.With the exception of the positive control group, all other intervention groups significantly improved renal tissue damage caused by hyperuricemia and alleviated inflammatory cell infiltration in renal tissue. The results of pathological evaluation based on the pathological change diagnostic criteria (Table 1) are shown in Table 2.

[0052] [Table 1]

[0053] [Table 2]

[0054] After pathological analysis of the kidneys, the present invention further investigated the effects of hypoxanthine and potassium oxonate-induced hyperuricemia on the levels of various cytokines in the kidney tissue of mice. As shown in Figures 6-9, after 6 weeks of model construction, the kidney pro-inflammatory factor levels (TNF-α, IL-1β, IL-6) of the mice in the model group were significantly elevated compared to the normal group, and the anti-inflammatory factor IL-10 level was significantly reduced, indicating that the model construction induced a significant inflammatory response in the mouse kidney. After various interventions, the levels of the three pro-inflammatory factors were significantly reduced in all intervention groups, with no significant difference in TNF-α in the high-dose imidazole dipeptide group compared to the normal group.

[0055] Lipopolysaccharides are components of the outer cell wall of Gram-negative bacteria and are composed of lipids and polysaccharides (glycolipids). Lipopolysaccharides are endotoxins that exhibit multiple biological activities when acting on other living cells, such as human or animal cells. Lipopolysaccharides are toxic to the host, and endotoxins are called endotoxins because they are released after bacteria die, lyse, or are artificially destroyed. Literature has reported that high uric acid affects intestinal permeability and that serum lipopolysaccharide levels increase with systemic inflammation. In this experiment, there were no significant differences between serum lipopolysaccharide levels in all experimental groups (Figure 10), indicating that renal inflammation is not severe enough to cause enteritis.

[0056] Lactate dehydrogenase (LDH), a carbohydrate-degrading enzyme, plays a key role in bioenergy metabolism by catalyzing the oxidation of lactate to pyruvate. Lactate dehydrogenase activity is primarily assessed in myocardial and hepatocellular injury. When various tissues and organs in the body are damaged, changes in LDH in the tissues and organs themselves result in changes in LDH in the blood. Urinary LDH levels in patients with chronic glomerular nephritis, diabetic cirrhosis, and renal malignancies are generally 3-6 times higher than in healthy individuals, but urinary urea and small peptides can inhibit enzyme activity. Serum LDH levels in patients with chronic kidney disease and uremia are generally normal. In this study, there were no significant differences between lactate dehydrogenase levels in all experimental groups (Figure 11).

[0057] 6.5 Amelioration of oxidative stress in mice by different interventions When xanthine oxidase catalyzes the conversion of purines to uric acid, it generates large amounts of superoxide anions and H2O2, leading to increased levels of oxidative stress throughout the body. Glutathione is an important endogenous antioxidant and can neutralize reactive oxygen species in the body. Superoxide dismutase, the body's most important antioxidant enzyme, catalyzes the dismutation of superoxide anions to produce hydrogen peroxide and oxygen. Glutathione peroxidase can catalyze the conversion of hydrogen peroxide and many organic peroxides to water or organic alcohols using reduced glutathione. It can remove peroxides from living cells and play an important role in protecting cells from radicals. Intracellular lipids readily react with radicals to produce lipid peroxides. Glutathione peroxidase can eliminate the toxic effects of radicals by reducing lipid peroxides using reduced glutathione. Glutathione peroxidase is distributed in most tissues. In some pathological conditions, the activity of glutathione peroxidase is significantly up-regulated or down-regulated. Malondialdehyde is a natural product of the oxidation of biological lipids. When oxidative stress occurs in animal or plant cells, lipids are oxidized, and the level of propionaldehyde can reflect the level of oxidative stress in the body.

[0058] The results of glutathione detection in serum and kidney tissue homogenate (Figures 12 and 13) show that the glutathione concentrations in the model group mice were significantly lower than those in the normal group. All treatments improved glutathione levels in the serum and kidney tissue of hyperuricemia model mice and alleviated oxidative damage caused by uric acid production. The change trends of glutathione concentrations in serum and kidney tissue homogenate of different experimental groups were almost consistent. In all intervention groups, the glutathione concentrations in serum and kidney tissue homogenate of the allopurinol group and low-dose imidazole dipeptide group were significantly higher than those of the model group, and the levels were not significantly different from those of the normal group.

[0059] The results of superoxide dismutase detection in serum and kidney tissue homogenate (Figures 14 and 15) showed that superoxide dismutase enzyme activity in the model group mice was significantly lower than that in the normal group. All treatments improved SOD levels in the serum and kidney tissue of high uric acid model mice and alleviated oxidative damage caused by uric acid production. The change trends in SOD enzyme activity in serum and kidney tissue homogenate of different experimental groups were nearly consistent. In all intervention groups, SOD enzyme activity in serum and kidney tissue homogenate of the allopurinol group and high-dose imidazole dipeptide group was significantly higher than that of the model group. The results of glutathione peroxidase detection in serum and kidney tissue homogenate (Figures 16 and 17) showed that glutathione peroxidase enzyme activity in the model group mice was significantly lower than that of the normal group. All treatments improved glutathione peroxidase levels in the serum and kidney tissue of hyperuricemia model mice, alleviating oxidative damage caused by uric acid production. The change trends in glutathione peroxidase enzyme activity in the serum and kidney tissue homogenate of different experimental groups were nearly consistent. Among all intervention groups, the glutathione peroxidase enzyme activity in the serum and kidney tissue homogenate of the allopurinol group and the high and low dose imidazole dipeptide groups was significantly higher than that of the model group. Malondialdehyde detection results in the serum and kidney tissue homogenate (Figures 18 and 19) showed that the malondialdehyde concentrations in the model mice were significantly higher than those in the normal group. All of the therapeutic methods were able to significantly improve the malondialdehyde levels in the serum and kidney tissue of the hyperuricemia model mice, and the malondialdehyde levels in all intervention groups were not significantly different from those in the normal group, indicating that all of the therapeutic methods could alleviate the oxidative damage caused by the generation of uric acid.

[0060] As is clear from the above experiments, the imidazole dipeptide composition of the present invention has a renal protective effect.

Claims

1. A composition containing anserine and carnosine, wherein the total weight of anserine and carnosine is 100%, and the content of carnosine is 10%-99% and 1%-90%, respectively, of the imidazole dipeptide composition having kidney-protecting effects.

2. 2. The imidazole dipeptide composition according to claim 1, wherein the anserine content is 91% and the carnosine content is 9%, with the total weight of anserine and carnosine being 100%.

3. 3. The imidazole dipeptide composition according to claim 1, comprising anserine and carnosine.

4. 3. The imidazole dipeptide composition according to claim 1 or 2, further comprising other substances having renal protective effects.

5. The other substance having a renal protective effect includes histidine and / or histidine derivatives, preferably, the histidine derivatives include, but are not limited to, oligopeptides containing histidine residues, more preferably dipeptides or tripeptides; 5. The imidazole dipeptide composition according to claim 4, wherein the histidine, histidine derivative is preferably of animal and / or plant origin, for example from chicken, fish or other animal muscle.

6. Use of the imidazole dipeptide composition according to any one of claims 1 to 5 in the manufacture of a composition having a renal protective effect.

7. The use according to claim 6, wherein the composition is for the manufacture of a medicament.

8. 8. The use of claim 7, wherein the medicament comprises an effective amount of the imidazole dipeptide composition.

9. 9. The use according to claim 7 or 8, wherein the dosage of the imidazole dipeptide composition in the medicament is 1 mg-200 mg / day, preferably 1 mg-100 mg / day, more preferably 5 mg-50 mg / day.

10. The use according to any one of claims 7 to 9, wherein the pharmaceutical product further comprises secondary materials, preferably comprising one or a combination of two or more of sorbitol, maltodextrin, magnesium stearate.

11. The use according to any one of claims 7 to 10, wherein the pharmaceutical is a tablet, capsule, powder or granule.

12. 7. The use according to claim 6, wherein the composition is for producing a food product.

13. 13. The use according to claim 12, wherein the amount of the imidazole dipeptide composition in the food is 1 mg-200 mg / day, preferably 1 mg-100 mg / day, more preferably 5 mg-50 mg / day.

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