CN105999217B

CN105999217B - Composition for preventing and treating hyperuricemia and preparation method and application thereof

Info

Publication number: CN105999217B
Application number: CN201610457583.XA
Authority: CN
Inventors: 梁少瑜; 曾永长; 吴正治; 曹美群; 李仲秋
Original assignee: Shenzhen Institute of Gerontology
Current assignee: Shenzhen Institute of Gerontology
Priority date: 2016-06-22
Filing date: 2016-06-22
Publication date: 2020-02-21
Anticipated expiration: 2036-06-22
Also published as: CN105999217A

Abstract

The invention provides a composition for preventing and treating hyperuricemia, which comprises a traditional Chinese medicine extract and functional factors, wherein the traditional Chinese medicine extract comprises the following raw materials in parts by weight: 3-30 parts of astragalus membranaceus, 3-30 parts of semen coicis, 3-30 parts of plantain herb, 1-9 parts of rhizoma atractylodis, 1-12 parts of radix achyranthis bidentatae and 2-9 parts of pawpaw, wherein the functional factor comprises 0.1-5 parts of bonito peptides. The invention also provides a preparation method of the composition. The composition for preventing and treating hyperuricemia disclosed by the invention is prepared by combining traditional Chinese medicines such as astragalus membranaceus, coix seeds, plantain herbs, rhizoma atractylodis, radix achyranthis bidentatae and pawpaw and bonito peptide, and combining the traditional Chinese medicines with conditioning and functional factors to inhibit the generation of uric acid and promote excretion via synergistic effects, so that the effect of reducing uric acid is greatly enhanced.

Description

Composition for preventing and treating hyperuricemia and preparation method and application thereof

Technical Field

The invention belongs to the field of traditional Chinese medicines, and particularly relates to a composition for preventing and treating hyperuricemia, and a preparation method and application thereof.

Background

With the changes in modern lifestyles, including fat-rich, high purine diets and fructosylated beverages, the proportion of people with elevated blood uric acid levels on physical examination is increasing. Epidemiological studies have shown that changes in uric acid levels and the prevalence of hyperuricemia have a similar prevalence with hypertension, obesity, diabetes, and kidney disease over the last 100 years. The HUA prevalence rate in nearly 10 years in China is increased by about 10 times on average. Hyperuricemia, as a disease with involvement of multiple systems, can directly cause gout, hyperuricemia nephropathy, aggravation of atherosclerosis, pancreatic islet resistance and the like, and the harm is not negligible.

At present, the western medicine for treating hyperuricemia mainly comprises two categories of generation of uric acid and promotion of uric acid excretion, wherein probenecid, fensultone, benzbromarone and the like are commonly used, and the application of the medicines is often accompanied with serious liver and kidney function damage. Hyperuricemia belongs to the dominant disease category of traditional Chinese medicine treatment, and early intervention can obviously reduce the morbidity of gout, hyperuricemia nephropathy and cardiovascular and cerebrovascular diseases caused by hyperuricemia.

The traditional Chinese medicine considers that the hyperuricemia is the syndrome of principal deficiency and secondary excess, and the occurrence of the hyperuricemia is mainly caused by congenital deficiency, or caused by external pathogenic wind, cold, dampness and heat soaking human body channels and collaterals, or fatigue, or imbalance of chills and fever, or eating disorder (alcoholism, food damage and the like) causes the dysfunction of liver-spleen-kidney and tri-jiao gasification, and metabolic disorder of water essence, and causes the internal reversion of the water essence and the change of the water essence due to reversion. The spleen failing to transport and transform due to liver and kidney deficiency is the disease origin, and the symptoms of wind-cold-damp-heat, phlegm turbidity and blood stasis blocking the meridians are the targets. Hyperuricemia is mainly treated by eliminating dampness, and is also treated by clearing heat, removing blood stasis and tonifying qi. The astragalus root is used for tonifying spleen and lung qi, inducing diuresis and reducing edema, the coix seed is used for tonifying spleen and promoting diuresis, relaxing muscles and tendons and removing maladies, the plantain is used for clearing heat and promoting diuresis, the atractylodes rhizome is used for drying dampness and tonifying spleen, the achyranthes root is used for promoting blood circulation, removing blood stasis and dredging collaterals, the pawpaw is used for removing dampness and harmonizing stomach, and the effects of clearing heat and promoting diuresis, removing blood stasis and stimulating the menstrual; the functional factor bonito peptide can effectively inhibit XOD enzyme activity, reduce the generation of uric acid, improve uric acid transport protein of renal epithelial cells and strengthen the excretion of uric acid. The Chinese herbal medicines and the functional factors are compounded to jointly influence the generation and excretion ways of uric acid, so that the uric acid is restored to a normal level, the effect is mild, and the symptoms of brutal discharge and rough analgesia are avoided.

Disclosure of Invention

The invention aims to provide a composition for preventing and treating hyperuricemia and application thereof, wherein the aims of reducing the uric acid and even recovering the uric acid to be normal are achieved by compounding Chinese herbal medicines and functional factors, particularly compounding the Chinese herbal medicines and bonito peptide.

The invention provides a composition for preventing and treating hyperuricemia, which comprises a traditional Chinese medicine extract and a functional factor, wherein the functional factor comprises 0.1-5 parts of bonito peptide by weight, and the traditional Chinese medicine extract comprises the following raw materials: 3-30 parts of astragalus, such as 5 parts, 8 parts, 12 parts, 15 parts, 20 parts, 22 parts, 25 parts, 28 parts and the like; 3-30 parts of coix seeds, such as 5 parts, 8 parts, 12 parts, 15 parts, 20 parts, 22 parts, 25 parts, 28 parts and the like; 3-30 parts of plantain herb, such as 5 parts, 8 parts, 12 parts, 15 parts, 20 parts, 22 parts, 25 parts, 28 parts and the like; 1-9 parts of rhizoma atractylodis, such as 2 parts, 3 parts, 4 parts, 5 parts, 6 parts, 7 parts, 8 parts and the like; 1-12 parts of achyranthes bidentata, such as 3 parts, 5 parts, 8 parts, 10 parts, 11 parts and the like; and 2-9 parts of pawpaw, such as 3 parts, 4 parts, 5 parts, 6 parts, 7 parts, 8 parts and the like.

Wherein the traditional Chinese medicine extract is water extract, alcohol extract or the mixture of the water extract and the alcohol extract.

Preferably, the composition further comprises 1-9 parts of volatile oil of atractylodes rhizome.

Preferably, the traditional Chinese medicine extract comprises the following raw materials in parts by weight: 6-20 parts of astragalus membranaceus, 6-20 parts of semen coicis, 6-20 parts of plantain herb, 2-6 parts of rhizoma atractylodis, 3-8 parts of radix achyranthis bidentatae and 4-6 parts of pawpaw, wherein the functional factor comprises 0.3-2 parts of bonito peptides.

Preferably, the traditional Chinese medicine extract comprises the following raw materials in parts by weight: 9 parts of astragalus membranaceus, 6 parts of semen coicis, 9 parts of plantain herb, 3 parts of rhizoma atractylodis, 4 parts of radix achyranthis bidentatae and 5 parts of pawpaw, wherein the functional factor comprises 1 part of bonito peptides.

In a second aspect of the invention, there is provided a process for the preparation of any of the compositions according to the first aspect of the invention, comprising the steps of:

step 1, taking raw materials of a traditional Chinese medicine extract, and extracting to obtain the traditional Chinese medicine extract;

and 2, mixing the traditional Chinese medicine extract with the functional factors to obtain the traditional Chinese medicine composition.

Wherein, the extraction in the step 1 can adopt: water extraction; alcohol extraction; extracting with water, extracting with ethanol, and mixing the extracts; extracting with ethanol, extracting with water, and mixing the extracts; or the raw materials are divided into two parts, water extraction and alcohol extraction are carried out respectively, and then extracts are combined for extraction by a plurality of extraction methods.

Preferably, in the case that the composition contains the volatile oil of atractylodes, the atractylodes used for extracting the volatile oil can be atractylodes in the raw materials of traditional Chinese medicine extracts, and then the step 1 is as follows: extracting raw materials of a traditional Chinese medicine extract to obtain the traditional Chinese medicine extract and rhizoma atractylodis volatile oil; or the rhizoma atractylodis used for extracting the volatile oil does not adopt the rhizoma atractylodis in the raw materials of the traditional Chinese medicine extract, and the step 1 is as follows: extracting volatile oil from rhizoma Atractylodis; extracting the raw materials of the traditional Chinese medicine extract to obtain the traditional Chinese medicine extract.

Wherein the volatile oil extracted from rhizoma Atractylodis can be extracted by conventional volatile oil extraction method, preferably steam distillation and/or supercritical CO2 extraction method.

The composition according to the first aspect of the present invention or the composition prepared by the preparation method according to the second aspect of the present invention can be used alone as an active ingredient for preventing and treating hyperuricemia, and can also be used in combination with other existing active ingredients for preventing and treating hyperuricemia. Therefore, in a third aspect of the present invention, there is provided a preparation for preventing and treating hyperuricemia, wherein the active ingredients comprise any of the compositions according to the first aspect of the present invention, or any of the compositions prepared by any of the preparation methods according to the second aspect of the present invention.

Wherein, the preparation can also comprise other active ingredients for preventing and treating hyperuricemia.

Wherein the preparation can be oral liquid, soft extract, syrup, granule, capsule, tablet, pill, powder or transdermal preparation, etc.

The preparation can also comprise pharmaceutically acceptable auxiliary materials according to the dosage form requirement of the preparation.

The fourth aspect of the present invention provides the use of any composition described in the first aspect of the present invention, or any composition prepared by any preparation method described in the second aspect of the present invention, or any preparation described in the third aspect of the present invention in the preparation of a preparation for preventing and treating hyperuricemia (e.g., a health product, a medicine, a food, etc.).

The composition for preventing and treating hyperuricemia disclosed by the invention is prepared by combining traditional Chinese medicines such as astragalus membranaceus, coix seeds, plantain herbs, rhizoma atractylodis, radix achyranthis bidentatae and pawpaw and bonito peptide, and combining the traditional Chinese medicines with conditioning and functional factors to inhibit the generation of uric acid and promote excretion via synergistic effects, so that the effect of reducing uric acid is greatly enhanced.

Drawings

FIG. 1 shows the effect of relative expression levels of URAT1, GLUT9, OAT1 proteins in rat kidney tissues after feeding 28 days in pharmacodynamic studies.

Detailed Description

The invention will be better understood by reference to the following examples.

Example 1

The preparation is mainly prepared from the following components in parts by weight:

9 parts of astragalus, 6 parts of coix seed, 9 parts of plantain herb, 3 parts of rhizoma atractylodis, 4 parts of achyranthes root, 5 parts of pawpaw and 1 part of bonito peptide.

The raw materials, rhizoma Atractylodis coarse powder, adopt SFE-CO₂The method has the extraction pressure of 30MPa, the extraction temperature of 50 ℃ and CO₂Flow 25kg h^-1Extracting for 2h to obtain rhizoma atractylodis volatile oil. Mixing rhizoma Atractylodis residue with radix astragali, Coicis semen, herba plantaginis, Achyranthis radix, and fructus Chaenomelis, extracting with water for 2 times, adding 12 times (by weight) of water for the first time, soaking for 0.5 hr, boiling for 1.5 hr, adding 8 times (by weight) of water for the second time, boiling for 1 hr, and mixing the two extractive solutions; the extract is filtered and the filtrate is filtered,concentrating under reduced pressure at 65-85 deg.C under-0.03 to-0.08 MPa to 1.2 g/mL; spray drying, wherein the injection inlet temperature is 160-; adding skipjack peptide and related adjuvants, granulating, and spraying rhizoma Atractylodis volatile oil to obtain granule.

Example 2

10 parts of astragalus, 15 parts of coix seed, 9 parts of plantain, 6 parts of rhizoma atractylodis, 8 parts of achyranthes, 2 parts of pawpaw and 1.6 parts of bonito peptide.

Extracting the raw materials, rhizoma atractylodis coarse powder, for 6 hours by adopting a steam distillation method to prepare the rhizoma atractylodis volatile oil. Mixing radix astragali, Coicis semen, herba plantaginis, Achyranthis radix, and fructus Chaenomelis, extracting with 60% ethanol for 2 times, soaking in 10 times (by weight) of 60% ethanol for 0.5 hr, reflux-extracting for 1.5 hr, adding 6 times (by weight) of 60% ethanol for the second time, reflux-extracting for 1 hr, and mixing the two extractive solutions; filtering the extractive solution, concentrating under reduced pressure at 55-80 deg.C under-0.03 to-0.08 Mpa until no alcohol smell exists; mixing the concentrated solution with the rhizoma atractylodis mother solution, and spray-drying at the injection inlet temperature of 160-; adding skipjack peptide and related adjuvants, granulating, spraying rhizoma Atractylodis volatile oil, and tabletting to obtain tablet.

Example 3

20 parts of astragalus membranaceus, 20 parts of semen coicis, 15 parts of plantain herb, 2 parts of rhizoma atractylodis, 5 parts of radix achyranthis bidentatae, 2 parts of pawpaw and 1.0 part of bonito peptide.

Mixing rhizoma Atractylodis, radix astragali, Coicis semen, herba plantaginis, Achyranthis radix, and fructus Chaenomelis, extracting with 80% ethanol at low temperature for 2 times, adding 10 times (by weight) of 80% ethanol for the first time, soaking for 0.5 hr, extracting at 60 deg.C for 2.0 hr, adding 8 times (by weight) of 80% ethanol for the second time, extracting at 60 deg.C for 1.5 hr, and mixing the two extractive solutions. Concentrating under reduced pressure at 55-70 deg.C under-0.03-0.08 Mpa until no alcohol smell; adding skipjack peptide and related adjuvants, dissolving in distilled water, mixing with the concentrated solution of Chinese medicinal materials, and adding water to desired volume to obtain oral liquid.

Example 4

5 parts of astragalus, 20 parts of coix seed, 15 parts of plantain, 3 parts of rhizoma atractylodis, 4 parts of achyranthes root, 4 parts of pawpaw and 0.5 part of bonito peptide.

Extracting the raw materials with 85 percent ethanol of rhizoma atractylodis at low temperature for 2 times, adding 12 times of 85 percent ethanol for the first time, soaking for 0.5h, extracting for 1.5 h at 55 ℃, adding 10 times of 85 percent ethanol for the second time, extracting for 1.0 h at 60 ℃, combining the two extracting solutions, concentrating at low temperature and reduced pressure at 55-65 ℃, and concentrating under the vacuum degree of-0.02-0.08 Mpa until no alcohol smell exists. Mixing radix astragali, Coicis semen, herba plantaginis, Achyranthis radix, and fructus Chaenomelis, adding water, extracting for 2 times, adding 20 times of water for the first time, soaking for 0.5 hr, boiling for 1.5 hr, adding 15 times of water for the second time, boiling for 1.5 hr, mixing the two extractive solutions, concentrating under reduced pressure at 65 deg.C-85 deg.C under-0.03 to-0.08 MPa, and concentrating to 1.2 g/mL. Mixing the rhizoma Atractylodis concentrated solution and other Chinese medicinal material concentrated solutions, adding bonito peptide and related adjuvants, dissolving, and metering to desired volume to obtain oral liquid.

Example 5

30 parts of astragalus, 10 parts of coix seed, 25 parts of plantain, 8 parts of rhizoma atractylodis, 10 parts of achyranthes root, 5 parts of pawpaw and 0.8 part of bonito peptide.

The preparation method disclosed by the embodiment of the invention comprises the steps of adding conventional auxiliary materials into commercially available extracts, and preparing capsules through a preparation process, wherein the capsules have a remarkable uric acid reducing effect.

Example 6

The invention is mainly prepared from the following components in parts by weight:

6 parts of astragalus membranaceus, 18 parts of coix seeds, 20 parts of plantain herbs, 9 parts of rhizoma atractylodis, 2 parts of radix achyranthis bidentatae, 8 parts of pawpaw and 4 parts of bonito peptides.

In the above examples, the components are commercially available, and may be made into various pharmaceutically acceptable dosage forms, such as oral liquid, capsules, tablets, powders or granules, by conventional preparation processes (such as steam distillation, supercritical carbon dioxide extraction, water extraction or ethanol extraction with different mass fractions), without limitation.

Pharmacodynamic study of composition for preventing and treating hyperuricemia

1 materials of the experiment

Potassium oteroxide (Shandong Jinhui Shuangdao chemical Co., Ltd.) is prepared by the following steps: accurately weighing 15g of distilled water each time to prepare 15% of suspension emulsion;

adenine (ziyun biotechnology limited, guangzhou);

uric acid kit (shanghai fenghui medical science and technology ltd);

urea nitrogen (shanghai kowa bioengineering, ltd);

creatinine (CR) detection kit (japan hydrops medical corporation);

cholesterol (national drug group chemical agents limited);

bile salts (national drug group chemical agents limited);

a xanthine oxidase detection test kit and a xanthine dehydrogenase kit (Nanjing institute of bioengineering);

superoxide dismutase kit (Nanjing institute of bioengineering);

malondialdehyde kit (Shanghai enzyme-linked Biotech, Inc.);

allopurinol (Periplaneta Calif.) is prepared into 2.7 mg/ml suspension with 0.1% CMC-Na, 3 days for each time, and stored at 4 deg.C for use.

Preparation of herbal extracts, reference example 1: 540g of astragalus root, 360g of coix seed, 540g of plantain herb, 180g of rhizoma atractylodis, 240g of achyranthes and 300g of pawpaw, the raw materials and the rhizoma atractylodis are crushed and SFE-CO is adopted₂The method has the extraction pressure of 30MPa, the extraction temperature of 50 ℃ and CO₂Flow 25kg h^-1Extracting for 2h to obtain rhizoma atractylodis volatile oil. Mixing rhizoma Atractylodis residue with radix astragali, Coicis semen, herba plantaginis, Achyranthis radix, and fructus Chaenomelis, extracting with water for 2 times, adding 12 times of water for the first time, soaking for 0.5 hr, boiling for 1.5 hr, adding 8 times of water for the second time, boiling and extractingCombining the two extracting solutions for 1 hour; filtering the extracting solution, concentrating under reduced pressure at 65-85 deg.C under-0.03 to-0.08 Mpa to 1.2 g/mL; spray drying, wherein the injection inlet temperature is 160-; spraying dry powder, granulating, and spraying rhizoma Atractylodis volatile oil to obtain Chinese medicinal extract.

2 laboratory animals

SPF male SD rat (Experimental animal center of Zhongshan university, the license number of the experimental animal production: SCXK (Guangdong) 2011-.

3 Experimental methods

3.1 model preparation, grouping and dose setting:

with adenine (100 mg kg)^-1·d^-1Ig) + Potassium Oxocyanate (1.5 g kg)^-1·d^-1Ig) preparation of a hyperuricemic rat model. SD male rats were adaptively bred for 5 days, and animals were randomly divided by body weight into a normal control group, a model control group, an allopurinol group, an example 1 (L) group, an example 1 (M) group, an example 1 (H) group, a herbal extract group and a bonito peptide group, each of which was 10 animals. The corresponding drugs are administered according to the grouping situation.

The dose settings for each sample are shown in table 1. The samples of each dosage group are dissolved, diluted and subjected to constant volume to be in a proper intragastric administration volume.

TABLE 1 dosage in terms of body weight

The dosage of allopurinol in the allopurinol group is 27mg kg calculated by weight dosage conversion^-1·d^-1In the example 1 (L) group, the dose was 0.82 g.kg^-1·d^-1The dose in the group (M) of example 1 was 1.64 g.kg^-1·d^-1The dose in the group (H) of example 1 was 3.28 g.kg^-1·d^-1The dosage of the Chinese herbal medicine extract group is 1.44 g.kg^-1·d^-1The dosage of skipjack peptide group was 0.2 g/kg^-1·d^-1And continues for 28 d.

3.2 detection of indicators

3.2.1 measurement of serum metabolism index and xanthine oxidase

Before modeling, 14d of administration is carried out, and after 1h of the last administration, blood is collected from orbital venous plexus; after administration for 28 days, 1 hour after the last administration, pentobarbital sodium (45 mg. kg-1) was intraperitoneally injected for anesthesia, blood was taken from the abdominal aorta of the rat, and serum was isolated to determine the levels of Uric Acid (UA), Creatinine (CR), urea nitrogen (BUN), total Cholesterol (CHO), Triglyceride (TG), and Xanthine Oxidase (XOD).

3.2.2 Change in the Activity of Xanthine Oxidase (XOD) and Xanthine Dehydrogenase (XDH) in liver tissue

Administering 28d, i.e. 1h after the last administration, i.e. injecting pentobarbital sodium (45 mg. kg)^-1) Anaesthetizing, collecting blood from abdominal aorta, collecting liver tissue mass, and preparing into 100 g.L with pre-cooled physiological saline^-1The liver was homogenized and examined within 36 hours. The activity of XOD and XDH in the liver homogenate was measured according to the kit instructions.

3.2.3 determination of renal cortex GLUT9, OAT1, URAT1 protein expression

Cutting kidney tissue, grinding with liquid nitrogen to single cell state, adding 200ul RIPA lysate (containing PMSF1 mM) per 10mg tissue, cracking on ice for 30min, centrifuging at 4 deg.C 12000rpm for 15min, collecting supernatant, and storing in refrigerator at-80 deg.C. Coomassie brilliant blue G250 was used to measure the OD value of the protein solution, and the concentration of the sample protein was adjusted to the same level (4-8. mu.g. mu.l)^-1). The extracted protein is separated by electrophoresis of 10% SDS-PAGE gel, and 40-60 mu g of total protein is loaded in each hole. Transferring for 70min under the condition of 70v, transferring the protein onto a PVDF membrane, and rinsing the protein membrane in TBST for 1-2 min; adding 5% skimmed milk powder sealing solution, and sealing for 1 hr. The primary antibody was diluted in a ratio of 1:1000 (GLUT 9), 1:500 (OAT 1, GAPDH, URAT 1) according to the protein Marker instructions, with reference to the primary antibody specification; the PVDF membrane was placed in the primary antibody solution and incubated overnight at 4 ℃. TBST wash 3 times. Horseradish peroxidase (HRP) -labeled secondary antibodies were diluted at a 1:2500 ratio, with reference to secondary antibody instructions. Incubating the PVDF membrane and the secondary antibody for 1h at room temperature; washing with TBST for 3 times. Using BeyoECLPlus chemiluminescence reagent, developing color in dark, tabletting with X-ray, and developingDeveloping with a developer and a fixer.

3.2.4 data processing and statistics

All experimental data are expressed. SPSS was used for one-way anova, and the difference between the two mean values was examined by t.

3.3 results

3.3.1 changes in serum UA, CR, BUN, TG, CHO, XOD levels in rats before and after 14, 28d of model creation are shown in tables 2-4, respectively.

As can be seen from Table 2, the serum UA, CR, BUN, TG, CHO, XOD levels of the rats in each group before the model building are basically similar, and no obvious difference (p > 0.05) between the groups is found.

As shown in Table 3, the serum UA, BUN, CR and XOD levels of the model-making rats were significantly increased (p < 0.01) and the levels of TG and CHO were slightly increased but were not statistically different (p > 0.05) when 14d was administered compared with the normal control group. Compared with the model control group, the levels of the Chinese herbal medicine group BUN, the serum UA and XOD of the allopurinol group, the BUN and XOD levels of the example 1 (M) group and the UA, BUN and XOD levels of the example 1 (H) group are all obviously reduced (p is less than 0.05), and the changes of the other index levels are not statistically different (p is more than 0.05). The results show that the oteracil potassium + adenine modeling is 14d, the hyperuricemia rat model is successful, and meanwhile, the increase of the uric acid level causes the kidney injury to cause the reduction of the glomerular filtration function and the increase of the creatinine and the uric acid nitrogen level. Administration of 14d, allopurinol and group (H) of example 1 showed good effects of lowering serum UA levels and inhibiting XOD activity. The effect of reducing uric acid by 14d administered in the two dose groups of example 1 (L) and (M) was not significant, but the group of example 1 (M) exhibited good XOD inhibitory activity. In example 1, the BUN levels in the (M) and (H) groups and the Chinese herbal medicine group are reduced, suggesting that the BUN has the function of protecting the kidney function.

As can be seen from Table 4, the serum UA, BUN, CR and XOD levels of the rats in the model control group were significantly increased (p < 0.01) compared with those in the normal control group when 28d was administered. Compared with the model control group, the serum UA and XOD levels of allopurinol group, UA, BUN, CR and XOD levels of example 1 (L), (M) and (H) and Chinese herbal medicines, and UA and XOD levels of bonito peptide are significantly reduced (p is less than 0.05). The result shows that when the allopurinol is administered for 28 days, the allopurinol has good effects of reducing serum uric acid level and inhibiting XOD activity, but has no reversal effect on renal function damage caused by hyperuricemia. In example 1, the (L), (M), and (H) groups, the Chinese herbal medicine group, and the bonito peptide group all exhibited excellent effects of lowering serum uric acid level, inhibiting XOD activity, and protecting kidney function.

Interaction property analysis, namely analyzing the dose group, the Chinese herbal medicine group and the skipjack peptide group in the example 1, wherein the Chinese herbal medicine and the skipjack peptide are used together, so that the UA and XOD levels are reduced, the renal injury is reversed, the CR and BUN levels are reduced, the effect is better than that of the two single use, and the two have synergistic effect (E in the dose group in the example 1, E Chinese herbal medicine + E skipjack peptide).

TABLE 2 rat serum UA, CR, BUN, TG, CHO, XOD levels before modelling (n = 10)

Table 3 administration of serum UA, CR, BUN, TG, CHO, XOD levels (n = 10) in 14d rats

Note: comparison with normal control group:^#p<0.01; comparison with model control group:^*p<0.05。

table 4 serum UA, CR, BUN, TG, CHO, XOD levels in 28d dosed rats (n = 10)

3.3.2 Change in hepatic tissue XOD and XDH Activity in 28d rats administered

Xanthine Oxidase (XOD) and Xanthine Dehydrogenase (XDH) are two tautomeric forms of xanthine oxidase dehydrogenases, a member of the flavoprotein family. Both forms of enzymes are involved in purine metabolism and are key enzymes in purine metabolism and uric acid synthesis. Inhibiting the activity of purine metabolism key enzyme, and effectively reducing the serum uric acid level. As shown in table 5, the XOD and XDH activities of the model control group were significantly increased (p < 0.05) compared to the normal control group; compared with the model group, the allopurinol group, example 1 (L) (M), and (H) groups XOD and XDH activities were significantly reduced (p < 0.05), and the example 1 (H) group was not significantly different from the allopurinol group in XOD activity (p > 0.05). It is suggested that example 1 exerts a uric acid lowering effect by inhibiting XOD, XDH activity, and the strength of inhibition of XOD activity is comparable to allopurinol.

Table 5 change in liver tissue XOD, XDH activity in 28d dosed rats (n = 10)

Note: comparison with normal control group:^#p<0.05; comparison with model control group: p<0.05。

3.3.3 Effect of rat Kidney tissue URAT1, GLUT9, OAT1 protein relative expression levels after 28 days of feeding

The results are shown in fig. 1, URAT1, GLUT9 and OAT1 are important uric acid transporters of kidney responsible for uric acid reabsorption and secretion. As can be seen from fig. 1, compared with the normal control group, the expression level of uric acid transporter URAT1 and GLUT9 proteins responsible for uric acid reabsorption in the model control group is increased, and the expression level of uric acid transporter OAT1 responsible for uric acid secretion in the model control group is decreased; compared with a model control group, allopurinol, example 1 (L), (M) and (H) have the effects of reducing the expression levels of URAT1 and GLUT9 proteins and increasing the expression level of OAT1 protein.

The pharmacodynamic study is carried out by adopting the composition prepared in the embodiment 2-6, and the result is the same as that of the embodiment 1, when the traditional Chinese medicine extract is used together with the bonito peptide, the UA, XOD and XDH levels can be obviously reduced, the URAT1 and GLUT9 protein expression levels can be reduced, the kidney injury can be reversed, the CR and BUN levels can be reduced, the OAT1 protein expression can be increased, the effect is superior to that of the two single use, and the synergistic effect is generated.

The embodiments of the present invention have been described in detail, but the embodiments are merely examples, and the present invention is not limited to the embodiments described above. Any equivalent modifications and substitutions to those skilled in the art are also within the scope of the present invention. Accordingly, equivalent changes and modifications made without departing from the spirit and scope of the present invention should be covered by the present invention.

Claims

1. The composition for preventing and treating hyperuricemia is characterized by comprising a traditional Chinese medicine extract and functional factors, wherein the traditional Chinese medicine extract comprises the following raw materials in parts by weight: 3-30 parts of astragalus membranaceus, 3-30 parts of semen coicis, 3-30 parts of plantain herb, 1-9 parts of rhizoma atractylodis, 1-12 parts of radix achyranthis bidentatae and 2-9 parts of pawpaw, wherein the functional factor is 0.1-5 parts of bonito peptides.

2. The composition of claim 1, wherein the herbal extract comprises: an aqueous extract and/or an alcoholic extract of astragalus membranaceus, an aqueous extract and/or an alcoholic extract of coix seed, an aqueous extract and/or an alcoholic extract of plantain herb, an aqueous extract and/or an alcoholic extract of atractylodes lancea, an aqueous extract and/or an alcoholic extract of achyranthes bidentata, and an aqueous extract and/or an alcoholic extract of papaya.

3. The composition according to any one of claims 1-2, wherein the raw materials of the traditional Chinese medicine extract comprise the following components in parts by weight: 6-20 parts of astragalus membranaceus, 6-20 parts of semen coicis, 6-20 parts of plantain herb, 2-6 parts of rhizoma atractylodis, 3-8 parts of radix achyranthis bidentatae and 4-6 parts of pawpaw, wherein the functional factor is 0.3-2 parts of bonito peptides.

4. The composition as claimed in claim 3, wherein the raw materials of the traditional Chinese medicine extract comprise the following components in parts by weight: 9 parts of astragalus membranaceus, 6 parts of semen coicis, 9 parts of plantain herb, 3 parts of rhizoma atractylodis, 4 parts of radix achyranthis bidentatae and 5 parts of pawpaw, wherein the functional factor is 1 part of bonito peptides.

5. A process for the preparation of a composition according to any one of claims 1 to 4, comprising the steps of:

6. A preparation for preventing and treating hyperuricemia, characterized in that the active ingredient thereof comprises the composition according to any one of claims 1 to 4.

7. Use of a composition according to any one of claims 1 to 4, or a formulation according to claim 6, for the preparation of a preparation for the control of hyperuricemia.