A fermented small molecule peptide mixture with uric acid lowering effect, and its preparation method and application

Abstract

The present invention relates to the field of extraction of small molecule peptide mixtures, and in particular to a fermentable small molecule peptide mixture with a uric acid-lowering effect, and its preparation method and application. The present invention provides a method for preparing a fermentable small molecule peptide mixture with a uric acid-lowering effect, comprising the following steps: mixing Cordyceps militaris with water to obtain a bacterial solution; mixing a composite raw material with the bacterial solution, fermenting the composite probiotic powder, enzymolysis and filtering to obtain a fermentable small molecule peptide mixture. The small molecule peptide mixture of the present invention has a significant uric acid-lowering effect and few side effects, and can be used to prepare uric acid-lowering drugs.

Description

Technical Field

[0001] The present invention relates to the field of extraction of small molecule peptide mixtures, and in particular to a fermented small molecule peptide mixture with uric acid lowering effect, and a preparation method and application thereof. Background Art

[0002] As China's economy booms and people's living standards continue to improve, a shift in diets high in calories, fat, and sugar has led to an increasing number of people suffering from gout.

[0003] Gout is a group of diseases caused by impaired purine metabolism and decreased uric acid excretion. Clinically, it is characterized by hyperuricemia, recurrent acute monoarthritis, the formation of tophi as a result of sodium urate deposition, and chronic tophi-induced arthritis, often ultimately progressing to gouty nephropathy. Therefore, maintaining a healthy uric acid level is crucial.

[0004] Currently, gout is primarily treated with Western medicine, including colchicine, nonsteroidal anti-inflammatory drugs, and allopurinol. While these medications can temporarily alleviate the symptoms of hyperuricemia and lower blood uric acid, their limited effectiveness makes them difficult to fundamentally treat gout. Furthermore, long-term use of these medications can have significant side effects on the human body. Therefore, selecting high-performance, low-side-effect, and broad-spectrum raw materials for food or pharmaceutical processing, while achieving significant benefits for the human body and uric acid-lowering effects, remains a major challenge in the field of traditional Chinese medicine ingredient extraction and preparation technology. Summary of the Invention

[0005] In order to solve the above problems, the present invention provides a fermented small molecule peptide mixture with uric acid lowering effect, and its preparation method and application. The small molecule peptide mixture has obvious uric acid lowering effect, small side effects and a wide range of effects.

[0006] In order to achieve the above object, the present invention provides the following technical solutions:

[0007] The present invention provides a method for preparing a fermentable small molecule peptide mixture having a uric acid-lowering effect, comprising the following steps:

[0008] Mixing Cordyceps militaris and water in a mass ratio of (15-20):(150-200) to obtain a bacterial solution;

[0009] The composite raw material and the bacterial solution are mixed and then fermented with composite probiotic powder, and the obtained fermentation solution is sequentially enzymatically hydrolyzed and ultrafiltered to retain small peptides with a molecular weight of 300 to 2000 Da, thereby obtaining a fermentable small molecule peptide mixture; the composite raw material comprises Poria cocos, chicory, white back Panax notoginseng, Job's tears rice bran, Sophora japonica flower, Gardenia jasminoides, lotus and sunflower disc; the mass ratio of the composite raw material to the bacterial solution is (90 to 150):(150 to 200);

[0010] The enzymatic hydrolysis comprises a first enzymatic hydrolysis using cellulase, a second enzymatic hydrolysis using pectinase and a third enzymatic hydrolysis using papain.

[0011] Preferably, the mass ratio of Poria cocos, chicory, white back Panax notoginseng, Job's tears rice bran, Sophora japonica flower, Gardenia jasminoides, lotus and sunflower disc in the composite raw material is (10-15):(15-20):(10-20):(10-20):(10-15):(10-20):(10-15):(15-25).

[0012] Preferably, the pH of the first enzymatic hydrolysis is 4.5-5.6, the temperature is 45-55°C, and the time is 0.5-2h;

[0013] The first enzymatic hydrolysis solution obtained after the first enzymatic hydrolysis is mixed with pectinase to perform a second enzymatic hydrolysis; the pH of the second enzymatic hydrolysis is 3 to 6, the temperature is 15 to 55° C., and the time is 0.5 to 2 hours;

[0014] The second enzymatic hydrolysis solution obtained after the second enzymatic hydrolysis is mixed with papain to perform a third enzymatic hydrolysis; the pH of the third enzymatic hydrolysis is 6-7, the temperature is 55-65° C., and the time is 0.5-2 hours.

[0015] Preferably, the mass of the cellulose, pectinase and papain is 0.1% to 0.3% of the mass of the fermentation liquid obtained by fermentation.

[0016] Preferably, the fermentation temperature is 26-28° C., the fermentation time is 18-24 hours, and the humidity is below 70 wt.%.

[0017] Preferably, the particle size of the composite raw material is 20 to 60 meshes.

[0018] Preferably, when the composite probiotic powder is fermented, the composite probiotics include Bifidobacterium adolescentis, Bifidobacterium lactis, Bifidobacterium longum, Lactobacillus acidophilus, Lactobacillus casei and Lactobacillus rhamnosus; the inoculation amount of the composite probiotics is 1% of the mass of the fermentation liquid.

[0019] The present invention uses the above-mentioned preparation method to prepare a fermentation-type small molecule peptide mixed solution.

[0020] The present invention provides the use of the fermented small molecule peptide mixture in the preparation of uric acid-lowering drugs.

[0021] The present invention provides a uric acid-lowering drug, wherein the active ingredient of the drug comprises a fermented small molecule peptide mixture prepared by the above-mentioned preparation method.

[0022] Beneficial Effects: The present invention provides a method for preparing a fermentable small-molecule peptide mixture with a uric acid-lowering effect, comprising the following steps: mixing Cordyceps militaris with water to obtain a bacterial solution; mixing a composite raw material with the bacterial solution, fermenting the composite probiotics, and sequentially enzymatically hydrolyzing and filtering the fermented solution to obtain a fermentable small-molecule peptide mixture. The small-molecule peptide mixture prepared by the preparation method of the present invention has a significant uric acid-lowering effect, few side effects, and a wide range of effects. Experimental results show that the fermentable small-molecule peptide mixture prepared by the method of the present invention has a very significant clinical effect. For example, it is prepared as an oral liquid and administered to gout patients of different ages. 100 ml is taken on an empty stomach every morning for half a month as a course of treatment. After three courses of treatment, there is a certain degree of improvement. After six courses of treatment, uric acid is basically maintained within the normal range. The older the patient, the more courses of treatment are required. The uric acid-lowering efficiency reaches 90%, and the patient's mental state and gastrointestinal function are greatly improved.

[0023] In addition, the present invention has selected the raw materials with wide sources, low raw material cost, safe ingredients, wider market circulation and no toxic side effects, and the raw materials are prepared into the fermentation type small molecule peptide mixed solution comprising each bioactive factor (oligosaccharide, saponin and flavonoid) hydrolyzate, and multiple bioactive factors play a synergistic role, and the body is adjusted in many directions, and overall, so as to reach the optimal effect of reducing uric acid, and insist on taking not only to promote uric acid excretion, but also to the system such as human digestion and endocrine system, and the effect of regulating improvement is also arranged. The method of the present invention improves the utilization rate of the raw materials of medicine and food, reduces the cost of reducing uric acid body medication, and greatly increases the bioavailability of human body and the biological activity of reducing uric acid. It can be seen that the preparation method of the present invention has low cost, and the small molecule peptide mixed solution obtained by preparation also has the advantage that market circulation quality is easy to control.

[0024] Moreover, the preparation method of the present invention has the advantages of short preparation cycle, simple preparation process and repeatable operation, so the preparation method of the present invention can be applied to industrial production. DETAILED DESCRIPTION

[0025] Unless otherwise specified, the materials used in the present invention can be purchased by those skilled in the art.

[0026] The present invention provides a method for preparing a fermentable small molecule peptide mixture having a uric acid-lowering effect, comprising the following steps:

[0027] Mixing Cordyceps militaris and water in a mass ratio of (15-20):(150-200) to obtain a bacterial solution;

[0028] The composite raw material and the bacterial solution are mixed and then fermented with composite probiotics, and the obtained fermentation solution is sequentially enzymatically hydrolyzed and ultrafiltered to retain molecular peptides with a molecular weight of 300 to 2000 Da, thereby obtaining a fermentable small molecule peptide mixture; the composite raw material comprises Poria cocos, chicory, white back Panax notoginseng, Job's tears rice bran, Sophora japonica flower, Gardenia jasminoides, lotus and sunflower disc; the mass ratio of the composite raw material to the bacterial solution is (90 to 150):(150 to 200);

[0029] The enzymatic hydrolysis comprises a first enzymatic hydrolysis using cellulase, a second enzymatic hydrolysis using pectinase and a third enzymatic hydrolysis using papain.

[0030] The present invention mixes Cordyceps militaris with water in a mass ratio of (15-20): (150-200) to obtain a bacterial liquid. In the present invention, the Cordyceps militaris is preferably crushed Cordyceps militaris obtained after being crushed; the particle size of the crushed Cordyceps militaris is preferably 0.5-2 cm, more preferably 0.6-1.8 cm, and most preferably 0.7-1.5 cm. The present invention does not have any limitation on the mixing method, and a method well known to those skilled in the art can be used.

[0031] In the present invention, the Cordyceps militaris and water are preferably mixed in a mass ratio of (16-19):(160-190), more preferably (17-18):(170-180), to obtain a bacterial liquid.

[0032] The invention mixes the composite raw material with the bacterial liquid, performs composite probiotic fermentation, and sequentially enzymatically hydrolyzes and ultrafilters the obtained fermentation liquid to retain small peptides with a molecular weight of 300 to 2000 Da, thereby obtaining a fermentable small molecule peptide mixture.

[0033] In the present invention, the composite raw material comprises poria cocos, chicory, Gynura divaricata, coix bran, sophora japonica flower, gardenia jasminoides, lotus flower and sunflower disc. In the present invention, the particle size of the composite raw material is preferably 20-60 mesh, more preferably 25-55 mesh, and most preferably 30-50 mesh; the mass ratio of poria cocos, chicory, Gynura divaricata, coix bran, sophora japonica flower, gardenia jasminoides, lotus flower and sunflower disc in the composite raw material is preferably (10-15):(15-20):(10-20):(10-20):(10-15):(10-20):(10-15):(15-25), more preferably (11-14):(16-19):(11-19):(11-19):(11-14):(11-19):(11-14):(16-24), and most preferably (12-13):(17-18):(12-18):(12-18):(12-13):(12-18):(12-13):(17-23). The present invention uses a variety of drugs and foods with the same origin as the raw materials for preparation, including poria cocos, coix bran, Gynura divaricata, chicory, sophora japonica flower, gardenia jasminoides, lotus leaf, sunflower disc and cordyceps militaris; the poria cocos has the effects of promoting diuresis and excreting dampness, strengthening the spleen and calming the mind. It is used for edema with scanty urine, phlegm retention with dizziness and palpitation, poor appetite due to spleen deficiency, loose stools and diarrhea, restlessness of the mind, palpitation and insomnia; coix bran is rich in fatty acids, polysaccharides, vitamins, etc., and has various functions such as anti-cancer, anti-virus, anti-inflammatory, blood pressure lowering, blood sugar lowering, improving the body's immunity, antioxidant, etc.; Gynura divaricata has the effects of lowering blood sugar, clearing heat and cooling blood, promoting blood circulation and relieving pain, and stopping bleeding. It is used for cough; bronchitis, pulmonary tuberculosis; ulcers; carbuncles; burns; traumatic injuries; rheumatic pain; metrorrhagia; traumatic bleeding. Soothing muscles and dispelling stasis. Treating pertussis, fractures, traumatic bleeding, carbuncles and furuncles; chicory, belonging to the spleen, liver, bladder and gallbladder meridians. Clearing the liver and gallbladder, promoting digestion and strengthening the stomach, diuretic and detumescent; sophora japonica flower has the effects of lowering blood pressure, dilating the coronary artery, etc. The flavonoids extracted from sophora japonica flower have antioxidant activity. It also has antibacterial and hemostatic effects; gardenia jasminoides, belonging to the heart, lung and triple energizer meridians. Removing vexation by purging fire, clearing heat and promoting diuresis, cooling blood and detoxifying; externally, it reduces swelling and relieves pain; lotus leaf has the effects of losing weight and reducing fat, antioxidant, anti-convulsion, protecting the liver, anti-liver fibrosis, etc.; sunflower disc has the effects of clearing heat, calming the liver, relieving pain, stopping bleeding, etc.; cordyceps militaris has the functions of enhancing the human immune function, anti-cancer, antibacterial, anti-fatigue, anti-aging, anti-convulsion, etc.; gout belongs to the category of arthralgia syndrome in traditional Chinese medicine, belonging to the category of damp-heat arthralgia. It is mostly caused by the struggle between dampness and heat, which condenses in the meridians. Therefore, the clinical treatment mostly focuses on clearing heat and promoting diuresis; in the present invention, poria cocos and coix bran strengthen the spleen and remove dampness, Gynura divaricata, chicory, sophora japonica flower and gardenia jasminoides are the ministers to clear the damp-heat in the meridians, lotus leaf is the assistant to cooperate with poria cocos and coix seed to remove dampness without harming the healthy qi, cordyceps militaris is the envoy, tonifying the kidney and warming yang, which can warm and dredge the meridians, making the meridians unobstructed and not stagnant. All the prescriptions work together to achieve the effects of clearing heat and promoting diuresis, dredging collaterals and relieving pain.

[0034] In the present invention, the mass ratio of the composite raw material and the bacterial solution is (90-150):(150-200), preferably (100-140):(170-200).

[0035] The present invention preferably mixes the composite raw material with the bacterial liquid and then performs composite probiotic fermentation. The obtained fermentation liquid is sequentially enzymatically hydrolyzed and ultrafiltered to retain small peptides with a molecular weight of 300 to 2000 Da, more preferably 1500 Da, and most preferably 1000 Da, to obtain a fermentable small molecule peptide mixture.

[0036] In the present invention, the mass ratio of the bacterial liquid to the fermentation-type small molecule peptide mixture is preferably (150-200): (25-31), and more preferably (170-200): (28-31).

[0037] In the present invention, the compound probiotic fermentation is preferably carried out in a fermentation tank; the temperature of the compound probiotic fermentation is preferably 26-28°C, more preferably 27°C; the time of the compound probiotic fermentation is 18-24h, more preferably 1-2.5h; the humidity of the compound probiotic fermentation is 70wt.% or less, more preferably> 60wt.%; when the present invention carries out compound probiotic fermentation, the compound probiotic preferably includes Bifidobacterium adolescentis, Bifidobacterium lactis, Bifidobacterium longum, Lactobacillus acidophilus, Lactobacillus casei and Lactobacillus rhamnosus; the inoculum amount of the compound probiotic is 1% of the mass of the fermentation liquid. The present invention has no particular limitation on the source of the compound probiotic, and is preferably purchased from Shandong Junle Biotechnology Co., Ltd. The present invention uses fermentation technology and utilizes Cordyceps militaris bacterial liquid to ferment various substances. The material is simple and the effect is obvious. Cordyceps militaris bacterial liquid is easy to prepare and fermentation is easy to succeed.

[0038] The present invention performs enzymatic hydrolysis on the fermented broth after fermentation, wherein the enzymatic hydrolysis includes a first enzymatic hydrolysis using cellulase, a second enzymatic hydrolysis using pectinase, and a third enzymatic hydrolysis using papain. In the present invention, cellulase and pectinase can break down the cell wall for enzymatic hydrolysis, while papain hydrolyzes macromolecular proteins into a small molecule peptide mixture. The present invention uses multiple proteolytic enzymes for step-by-step enzymatic hydrolysis to obtain enzymatic hydrolyses of different components, and can also avoid interaction between the hydrolytic enzymes, thereby ensuring a more effective fermentable small molecule peptide mixture.

[0039] In the present invention, the pH of the first enzymatic hydrolysis is preferably 4.5-5.6, more preferably 4.6-5.5, more preferably 4.7-5.4; the temperature of the first enzymatic hydrolysis is preferably 45-55°C, more preferably 46-54°C, and most preferably 47-53°C; the time of the first enzymatic hydrolysis is preferably 0.5-2h, more preferably 1h. In the present invention, the first enzymatic hydrolysis solution obtained after the first enzymatic hydrolysis is preferably mixed with pectinase for the second enzymatic hydrolysis; the pH of the second enzymatic hydrolysis is preferably 3-6, more preferably 3.5-5.5, more preferably 4-5; the temperature of the second enzymatic hydrolysis is preferably 15-55°C, more preferably 20-55°C, and most preferably 25-50°C; the time of the second enzymatic hydrolysis is preferably 0.5-2h, more preferably 1h. The present invention preferably mixes the second enzymatic hydrolysis solution obtained after the second enzymatic hydrolysis with papain for a third enzymatic hydrolysis; the pH of the third enzymatic hydrolysis is preferably 6-7, more preferably 6.1-6.9, and most preferably 6.3-6.7; the temperature of the third enzymatic hydrolysis is preferably 55-65°C, more preferably 56-64°C, and most preferably 57-63°C; the time of the third enzymatic hydrolysis is preferably 0.5-2 hours, more preferably 1 hour. Under the enzymatic hydrolysis temperature, time, and pH conditions of the present invention, sufficient reaction between the enzyme and the substrate can be ensured.

[0040] In the present invention, the mass of the cellulose, pectinase and papain is preferably 0.1% to 0.3% of the mass of the fermentation broth obtained by fermentation; the mass of the cellulose is more preferably 0.2% of the mass of the fermentation broth obtained by fermentation.

[0041] In the present invention, the composite material is preferably cleaned before being mixed with the bacterial solution. The present invention does not limit the cleaning method, and any method known to those skilled in the art can be used.

[0042] In the present invention, the fermentable small molecule peptide mixture preferably includes oligosaccharides, saponins and flavonoids. The synergistic effect of the bioactive factors such as oligosaccharides, saponins and flavonoids of the present invention has a very significant effect, among which flavonoids has multi-faceted efficacy. It is a very strong antioxidant that can effectively remove oxygen free radicals in the body. This antioxidant effect can prevent cell degeneration and aging, and can also prevent the occurrence of cancer. Flavonoids can also improve blood circulation, lower cholesterol, and improve the symptoms of cardiovascular and cerebrovascular diseases; oligosaccharides have the effect of improving the microecological environment in the human body, regulating gastrointestinal function, preventing and treating constipation, and improving the immune function of the human body. In addition, oligosaccharides are similar to water-soluble plant fibers, which can improve blood lipid metabolism and reduce the content of cholesterol and triglycerides in the blood.

[0043] The fermented small molecule peptide mixture of the present invention also contains multiple biologically active factors such as oligosaccharides, saponins and flavonoids, and has no toxic side effects. Regular use of the mixture can not only promote uric acid excretion, but also regulate and improve the human digestive and endocrine systems. It not only improves the utilization rate of medicinal and edible raw materials and reduces the cost of uric acid-lowering medication, but also greatly increases the bioavailability and uric acid-lowering biological activity of the human body. Therefore, the fermented small molecule peptide mixture of the present invention can be used for lowering uric acid.

[0044] The present invention provides the use of the fermented small molecule peptide mixture in the preparation of a uric acid-lowering drug. The fermented small molecule peptide mixture of the present invention can significantly reduce the blood uric acid level in hyperuricemia model mice.

[0045] The present invention provides a uric acid-lowering drug, wherein the active ingredient of the drug comprises a fermented small molecule peptide mixture prepared by the above-mentioned preparation method. In the present invention, the dosage form of the drug preferably includes a solid dosage form and a liquid dosage form.

[0046] To further illustrate the present invention, the following detailed description of a fermented small molecule peptide mixture with uric acid-lowering effect provided by the present invention, its preparation method and application is provided in conjunction with the examples, but they should not be understood as limiting the scope of protection of the present invention.

[0047] Example 1

[0048] Crush 30g of Cordyceps militaris and mix with 300ml of water, then measure out 300ml of bacterial solution; the particle size of the crushed Cordyceps militaris is 1cm;

[0049] 10 parts by mass of Poria (20 g), 15 parts by mass of Chicory (30 g), 10 parts by mass of Panax notoginseng (20 g), 10 parts by mass of Coix seed rice bran (20 g), 10 parts by mass of Sophora japonica (20 g), 10 parts by mass of Gardenia jasminoides (20 g), 10 parts by mass of Lotus leaf (20 g) and 15 parts by mass of Sunflower disk (30 g) were mixed with 150 parts by mass (300 ml) of bacterial liquid, and then the composite probiotic powder (the composite probiotic powder is Bifidobacterium adolescentis, Bifidobacterium lactis, Bifidobacterium longum, Lactobacillus acidophilus, Lactobacillus casei and Lactobacillus rhamnosus, purchased from Shandong Junle Biotechnology Co., Ltd.) was fermented for 24 h at room temperature of 27 ° C and humidity of less than 70 wt.% to obtain a fermentation liquid, the inoculum amount of the composite probiotic powder is 1% of the mass of the fermentation liquid, and the fermentation liquid is enzymolyzed with cellulase under the conditions of pH 5 and temperature of 50 ° C for 1 h to obtain a first enzymolyzate, and the first enzymolyzate is obtained at pH 5. 4. The first hydrolyzate is enzymatically hydrolyzed with pectinase at a temperature of 50°C for 1 hour to obtain a second hydrolyzate, and the fermentation broth is enzymatically hydrolyzed with papain at a pH of 6.5 and 60°C for 1 hour to obtain a third hydrolyzate; wherein the amount of cellulose is 0.2% by mass of the fermentation broth; and the amounts of pectinase and papain are 0.1% by mass of the fermentation broth.

[0050] The obtained enzymatic hydrolysate was ultrafiltered through an ultrafiltration membrane with a molecular weight cutoff of 2000 Da to obtain 25 parts by mass of a fermentation-type small molecule peptide mixture (50 ml).

[0051] Thirty SPF-grade Kunming male mice weighing (25 ± 5) g were selected (Liaoning Changsheng Biotechnology Co., Ltd.). After acclimation for 3 days, the mice were subjected to modeling. Modeling was performed using oral gavage with yeast extract (successful modeling was indicated if the serum uric acid level in the mice was significantly higher than that in the blank group after modeling). The mice were divided into a blank group, a model group, and a treatment group, with 10 mice in each group. Blood uric acid levels were measured one week after modeling.

[0052] During the modeling period, mice maintained a normal diet. The blank group received an equal volume of distilled water by gavage daily, while the model and drug-treated groups received 20 g / kg / day of yeast extract by gavage. On the morning of day 8 after modeling, blood samples were collected for testing. Starting on day 9, the blank group continued to receive an equal volume of distilled water by gavage, while the model group continued to receive yeast extract by gavage. The drug-treated group received yeast extract by gavage in the morning and drug-treated in the afternoon. At the end of day 15, serum uric acid levels were measured. The results are shown in Table 1.

[0053] Table 1 Survey data of blood uric acid (μmol / L)

[0054] Before modeling After modeling After administration Blank group 172.86±22.51 176.22±20.66 184.20±21.95 Model Group 174.41±20.65 384.19±25.88 374.08±26.18 Drug administration group 184.00±16.30 394.06±13.82 230.09±13.69*

[0055] Compared with the model group, *P<0.01

[0056] It can be seen from the experimental data recorded in Table 1 that the fermented small molecule peptide mixture of the present invention can significantly reduce the blood uric acid of the mice with successful modeling.

[0057] Example 2

[0058] The experimental procedures are the same as those in Example 1, except that 170 parts by mass of Cordyceps militaris liquid (340 ml), 12 parts by mass of Poria cocos (24 g), 16 parts by mass of chicory (32 g), 13 parts by mass of Panax notoginseng (26 g), 14 parts by mass of Job's tears rice bran (28 g), 15 parts by mass of Sophora japonica (30 g), 13 parts by mass of Gardenia jasminoides (26 g), 11 parts by mass of lotus leaves (22 g) and 19 parts by mass of sunflower discs (19 g) are added to obtain 28 parts by mass of fermented small molecule peptide mixture (56 ml).

[0059] After the 15th day, the blood uric acid levels were measured and the results are shown in Table 2.

[0060] Table 2 Survey data of blood uric acid (μmol / L)

[0061] Before modeling After modeling After administration Blank group 174.28±17.21 176.60±13.31 180.60±11.60 Model Group 183.21±11.19 389.00±12.18 374.74±12.38 Drug administration group 180.68±11.31 393.59±17.01 197.87±16.11*

[0062] Compared with the model group, *P<0.01

[0063] It can be seen from the experimental data recorded in Table 2 that the fermented small molecule peptide mixture of the present invention can significantly reduce the blood uric acid of the mice with successful modeling.

[0064] Example 3

[0065] The experimental procedures are the same as those in Example 1, except that 200 parts by mass of Cordyceps militaris liquid (400 ml), 14 parts by mass of Poria cocos (28 g), 19 parts by mass of chicory (38 g), 16 parts by mass of Panax notoginseng (32 g), 15 parts by mass of Job's tears rice bran (30 g), 14 parts by mass of Sophora japonica (28 g), 14 parts by mass of Gardenia jasminoides (28 g), 12 parts by mass of lotus leaves (24 g) and 23 parts by mass of sunflower discs (46 g) are added to obtain 31 parts by mass of fermented small molecule peptide mixture (62 ml).

[0066] After the 15th day, the blood uric acid levels were measured. The results are shown in Table 3.

[0067] Table 3 Survey data of blood uric acid (μmol / L)

[0068] Before modeling After modeling After administration Blank group 179.72±12.13 183.41±10.70 181.09±12.20 Model Group 177.07±11.69 392.83±15.46 380.09±14.28 Drug administration group 182.66±11.51 390.14±15.22 164.71±13.31*

[0069] Compared with the model group, *P<0.01

[0070] It can be seen from the experimental data recorded in Table 2 that the fermented small molecule peptide mixture of the present invention can significantly reduce the blood uric acid of the mice with successful modeling.

[0071] Comparative Example 1

[0072] The preparation method is the same as that of Example 3, except that no enzymatic hydrolysis is performed in this comparative example. The test results are shown in 4.

[0073] Table 4 Blood uric acid survey data of Example 3 and Comparative Example 1 (μmol / L)

[0074]

[0075]

[0076] It can be seen from the experimental data recorded in Table 4 that the fermentable small molecule peptide mixture prepared by the method of the present invention, that is, the fermentable small molecule peptide mixture obtained after enzymatic hydrolysis, can significantly reduce the blood uric acid of the successfully modeled mice.

[0077] Application Example 1

[0078] Eighty male patients aged 30 to 50 years with hyperuricemia were selected and divided into two groups, each with 40 participants: one aged 30 to 40 years and the other aged 41 to 50 years. Each participant took 100 ml of the small molecule peptide mixture extract prepared in Example 3 on an empty stomach every morning. Changes in blood uric acid levels were recorded before, after three courses of treatment, and after six courses of treatment, as shown in Table 5.

[0079] Table 5 Survey data of blood uric acid (μmol / L)

[0080]

[0081] As shown in the experimental data in Table 5, the clinical experimental effect of the fermented small molecule peptide mixture of the present invention is very significant. It is prepared in the form of an oral liquid and taken once a day on an empty stomach in the morning by gout patients of different ages. A half-month course of treatment is a course of treatment. After three courses of treatment, there is a certain degree of improvement. After six courses of treatment, uric acid is basically maintained within the normal range (210-420 μmol / mL). The older the age, the more courses of treatment are required. In addition, the mental state and gastrointestinal function of the patients taking it are greatly improved, and the uric acid-lowering efficiency is 90%.

[0082] Although the present invention has been disclosed above with reference to preferred embodiments, it is not intended to limit the present invention. Anyone familiar with this technology can make various changes and modifications without departing from the spirit and scope of the present invention. Therefore, the scope of protection of the present invention should be based on the definition of the claims.

Claims

1. Use of a fermented small molecule peptide mixture with uric acid lowering effect in the preparation of a uric acid lowering drug, characterized in that: The steps of preparing the fermentable small molecule peptide mixture are as follows: Mixing Cordyceps militaris and water in a mass ratio of (15-20):(150-200) to obtain a bacterial solution; The composite raw material is mixed with the bacterial solution and then the composite probiotic powder is fermented. The obtained fermentation solution is sequentially enzymatically hydrolyzed and ultrafiltered to retain small peptides with a molecular weight of 300 to 2000 Da, thereby obtaining a fermentable small molecule peptide mixture; the composite raw material comprises Poria cocos, chicory, white back Panax notoginseng, Job's rice bran, Sophora japonica, Gardenia jasminoides, lotus leaves and sunflower discs; the mass ratio of the composite raw material to the bacterial solution is (90 to 150): (150 to 200); ... The mass ratio of lotus seeds, lotus leaves and sunflower discs is (10-15):(15-20):(10-20):(10-20):(10-15):(10-20):(10-15):(15-25); the fermentation temperature is 26-28°C and the time is 18-24 hours; the composite probiotic powder is Bifidobacterium adolescentis, Bifidobacterium lactis, Bifidobacterium longum, Lactobacillus acidophilus, Lactobacillus casei and Lactobacillus rhamnosus; the inoculation amount of the composite probiotic powder is 1% of the mass of the fermentation liquid; The enzymatic hydrolysis comprises the following steps: performing a first enzymatic hydrolysis using cellulase, performing a second enzymatic hydrolysis using pectinase, and performing a third enzymatic hydrolysis using papain; the pH of the first enzymatic hydrolysis is 4.5-5.6, the temperature is 45-55° C., and the time is 0.5-2 h; mixing the first enzymatic hydrolysis solution obtained after the first enzymatic hydrolysis with pectinase for a second enzymatic hydrolysis; the pH of the second enzymatic hydrolysis is 3-6, the temperature is 15-55° C., and the time is 0.5-2 h; mixing the second enzymatic hydrolysis solution obtained after the second enzymatic hydrolysis with papain for a third enzymatic hydrolysis; the pH of the third enzymatic hydrolysis is 6-7, the temperature is 55-65° C., and the time is 0.5-2 h; and the masses of the cellulose, pectinase, and papain are all 0.1%-0.3% of the mass of the fermentation liquid obtained by fermentation.

2. The application according to claim 1, characterized in that The fermentation humidity is below 70 wt.%.

3. The application according to claim 1, characterized in that The particle size of the composite raw material is 20 to 60 meshes.

4. A uric acid-lowering drug, characterized in that: The active ingredient of the drug includes a fermentable small molecule peptide mixture; the preparation method of the fermentable small molecule peptide mixture comprises the following steps: Mixing Cordyceps militaris and water in a mass ratio of (15-20):(150-200) to obtain a bacterial solution; The composite raw material is mixed with the bacterial solution and then the composite probiotic powder is fermented. The obtained fermentation solution is sequentially enzymatically hydrolyzed and ultrafiltered to retain small peptides with a molecular weight of 300 to 2000 Da, thereby obtaining a fermentable small molecule peptide mixture; the composite raw material comprises Poria cocos, chicory, white back Panax notoginseng, Job's rice bran, Sophora japonica, Gardenia jasminoides, lotus leaves and sunflower discs; the mass ratio of the composite raw material to the bacterial solution is (90 to 150): (150 to 200); ... The mass ratio of lotus seeds, lotus leaves and sunflower discs is (10-15):(15-20):(10-20):(10-20):(10-15):(10-20):(10-15):(15-25); the fermentation temperature is 26-28°C and the time is 18-24 hours; the composite probiotic powder is Bifidobacterium adolescentis, Bifidobacterium lactis, Bifidobacterium longum, Lactobacillus acidophilus, Lactobacillus casei and Lactobacillus rhamnosus; the inoculation amount of the composite probiotic powder is 1% of the mass of the fermentation liquid; The enzymatic hydrolysis comprises the following steps: performing a first enzymatic hydrolysis using cellulase, performing a second enzymatic hydrolysis using pectinase, and performing a third enzymatic hydrolysis using papain; the pH of the first enzymatic hydrolysis is 4.5-5.6, the temperature is 45-55° C., and the time is 0.5-2 h; mixing the first enzymatic hydrolysis solution obtained after the first enzymatic hydrolysis with pectinase for a second enzymatic hydrolysis; the pH of the second enzymatic hydrolysis is 3-6, the temperature is 15-55° C., and the time is 0.5-2 h; mixing the second enzymatic hydrolysis solution obtained after the second enzymatic hydrolysis with papain for a third enzymatic hydrolysis; the pH of the third enzymatic hydrolysis is 6-7, the temperature is 55-65° C., and the time is 0.5-2 h; and the masses of the cellulose, pectinase, and papain are all 0.1%-0.3% of the mass of the fermentation liquid obtained by fermentation.

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