CN114224957A - Composition with effect of inhibiting uric acid generation and preparation method thereof - Google Patents

Composition with effect of inhibiting uric acid generation and preparation method thereof Download PDF

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CN114224957A
CN114224957A CN202111646938.7A CN202111646938A CN114224957A CN 114224957 A CN114224957 A CN 114224957A CN 202111646938 A CN202111646938 A CN 202111646938A CN 114224957 A CN114224957 A CN 114224957A
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uric acid
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周启蒙
洪泳渺
徐捍山
陈朋
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Sirio Pharma Co Ltd
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Abstract

The invention discloses a uric acid-reducing composition, which comprises 1.5-2.5 parts by weight of vine tea extract and 0.5-1.5 parts by weight of cordyceps militaris extract, wherein the vine tea extract contains 30-90% by weight of dihydromyricetin, the cordyceps militaris extract contains 0.1-0.5% by weight of cordycepin, the% by weight and the parts by weight are calculated by dry weight, and the extract is obtained by taking water as an extraction solvent.

Description

Composition with effect of inhibiting uric acid generation and preparation method thereof
Technical Field
The invention relates to the technical field of medicines and foods, in particular to a composition for reducing uric acid.
Background
Hyperuricemia (HUA) is a metabolic disease caused by increased uric acid production and/or decreased uric acid excretion due to disturbance of purine metabolism in the body. The diagnosis of hyperuricemia is internationally defined as: under normal purine diet state, the fasting blood uric acid level is not 2 times on the same day, male is more than 420 mu mol/L, female is more than 360 mu mol/L. The latest edition of Chinese guidelines for diagnosis and treatment of hyperuricemia and gout (2019) defines: blood uric acid levels in excess of 420 μmol/L2 times a day are known as hyperuricemia, whether in men or women.
Ampelopsis grossedentata (Hand-Mazz) W.T.Wang) tender leaves, originally recorded in tea Jing, are perennial woody vine plants of the genus Ampelopsis of the family Vitaceae. The vine tea can be used as a medicine or an edible tea, and the use of the tender stem leaves of the vine tea in tea has been known for hundreds of years. According to the records of the literature such as Chinese herbal medicine compilation, the vine tea has the efficacy of clearing heat and removing toxicity when used as a medicine, and can treat cold, wind heat, sore throat and the like. Modern researches show that the vine tea and the extractive thereof contain abundant flavonoid compounds, particularly have the highest content of dihydromyricetin, and have various pharmacological activities of resisting inflammation, resisting bacteria, resisting oxidation, reducing blood sugar, reducing blood fat, reducing blood pressure and the like.
The cordyceps sinensis is a rare Chinese herbal medicine and has high medicinal value, but the natural resource of the cordyceps sinensis is scarce, the price is high, and the cordyceps sinensis is difficult to cultivate. Cordyceps militaris (Cordyceps militaris), also known as Cordyceps militaris, belongs to Ascomycota, Hypocreales, Clavicipitaceae. The cordyceps militaris and the cordyceps sinensis belong to the same genus and different species, artificial culture and scale production are realized, and researches show that the bioactive components of the cordyceps militaris and the cordyceps sinensis are similar, so that the cordyceps militaris can be used as an effective substitute product of the cordyceps sinensis. Research shows that the cordyceps militaris is rich in various nutritional ingredients such as cordycepin, cordyceps polysaccharide, cordycepic acid, amino acid and the like, and has pharmacological activities such as tumor resistance, immunoregulation, inflammation resistance, oxidation resistance and the like.
Rosa roxburghii Tratt, also known as reeling silk flower, Senchun angelica, and Tibet fruit, is perennial deciduous shrub of Rosa of Rosaceae, and is mainly produced in southwest region of China. Roxburgh rose leaf is recorded in the herbal and wood formula for treating scabies, carbuncles and incised sores. Rosa roxburghii contains flavone, vitamin C, superoxide dismutase (SOD), polysaccharide, polyphenol, triterpenes and other components, wherein each 100 g of Rosa roxburghii contains 920 mg of flavone, 1300-3500 mg of vitamin C and 13000 units of SOD on average, and is known as 'fruit king'. Pharmacological research shows that the roxburgh rose preparation has pharmacological activities of resisting oxidation, resisting tumors, resisting atherosclerosis, reducing blood sugar and the like.
There remains a need for compositions having improved effects in lowering blood uric acid in hyperuricemia subjects.
In addition, when the natural medicine extract is used as a liquid preparation or a solid beverage for brewing, a large amount of foam is easy to appear, the aesthetic degree of the product is influenced, and the mouthfeel of the finished product is seriously influenced.
It is desirable to provide a composition having an improved effect of lowering blood uric acid in a hyperuricemic subject and having reduced foaming when used for brewing as a liquid formulation or as a solid beverage.
Disclosure of Invention
The purpose of the present invention is to provide a composition having an improved effect of reducing blood uric acid in a hyperuricemia subject.
It is a further object of the present invention to provide a composition having an improved effect of lowering blood uric acid in a hyperuricemia subject, and having reduced foam when used as a liquid formulation or as a solid beverage for brewing.
The invention relates to a uric acid-reducing composition, which comprises 1.5-2.5 parts by weight of vine tea extract and 0.5-1.5 parts by weight of cordyceps militaris extract, wherein the vine tea extract contains 30-90% by weight of dihydromyricetin, the cordyceps militaris extract contains 0.1-0.5% by weight of cordycepin, the% by weight and the parts by weight are calculated by dry weight, and the extract is obtained by taking water as an extraction solvent.
Preferably, the composition of the invention may be in the form of a liquid formulation or a solid beverage for brewing and the composition comprises a thickening agent, for example, the thickening agent may be selected from one or more of gellan gum, xanthan gum, guar gum or carrageenan, preferably gellan gum.
The invention also relates to the use of the composition in the preparation of a medicament or food product for reducing blood uric acid in a hyperuricemic subject.
The composition has an improved effect of reducing the blood uric acid of a hyperuricemia subject compared with a single ampelopsis grossedentata extract with the same dose. When the composition is used as a liquid preparation or a solid beverage for brewing, the foam is reduced, and the finished product is more attractive and more convenient to take.
Drawings
FIG. 1 is a graph showing xanthine oxidase inhibitory effect in vitro of Ampelopsis grossedentata extract;
FIG. 2 is a graph comparing the uric acid lowering effect of Ampelopsis grossedentata extract and Ampelopsis grossedentata composition on hyperuricemia population;
FIG. 3 is a graph comparing the amount of foam formed in the composition with and without the addition of a thickening agent at the same material combination ratios.
Detailed Description
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. In case of conflict, the present document, including definitions, will control. Preferred methods and materials are described below, but methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention. The materials, methods, and examples disclosed herein are illustrative only and not intended to be limiting.
All numerical ranges recited in this disclosure are to be understood to disclose all specific values within that range, as well as any two numerical subranges within that range. For example, with respect to 1-20, it is understood that specific values of 1, 2, 3, 3.5, 4.5, 10, 12, 15, 20, etc., and sub-ranges of 1-5, 2-6, 3.5-7.5, 15-20, etc., are disclosed.
In one aspect, the invention relates to a uric acid-reducing composition, which comprises 1.5-2.5 parts by weight of ampelopsis grossedentata extract and 0.5-1.5 parts by weight of cordyceps militaris extract, wherein the ampelopsis grossedentata extract contains 30-90% by weight of dihydromyricetin, the cordyceps militaris extract contains 0.1-0.5% by weight of cordycepin, and the extracts are obtained by using water as an extraction solvent based on dry weight.
In one aspect, the uric acid lowering composition comprises 1.8-2.2 parts by weight of ampelopsis grossedentata extract and 0.8-1.2 parts by weight of cordyceps militaris extract, wherein the ampelopsis grossedentata extract comprises 30-90% by weight of dihydromyricetin, and the cordyceps militaris extract comprises 0.1-0.5% by weight of cordycepin.
In one aspect, the uric acid-lowering composition comprises 2 parts by weight of ampelopsis grossedentata extract and 1 part by weight of cordyceps militaris extract, wherein the ampelopsis grossedentata extract comprises 30-90% by weight of dihydromyricetin, and the cordyceps militaris extract comprises 0.1-0.5% by weight of cordycepin.
In one aspect, the uric acid reducing composition further comprises 0.1-1.5 parts by weight of a roxburgh rose preparation and 0-0.5 parts by weight of a sour cherry preparation, wherein the roxburgh rose preparation comprises 5-30% by weight of vitamin C, the sour cherry preparation comprises 0.5-30% by weight of vitamin C, the% by weight and the parts by weight are calculated by dry weight, the roxburgh rose preparation is obtained by drying roxburgh rose juice, and the sour cherry preparation is obtained by drying whole sour cherry fruits.
In one aspect, the uric acid lowering composition further comprises 0.8-1.2 parts by weight of a roxburgh rose preparation and 0.1-0.2 parts by weight of a tart cherry preparation, wherein the roxburgh rose preparation comprises 5-30% by weight of vitamin C, and the tart cherry preparation comprises 5-30% by weight of vitamin C.
In one aspect, the uric acid lowering composition further comprises 1 part by weight of a roxburgh rose preparation and 0.1 part by weight of a tart cherry preparation, wherein the roxburgh rose preparation comprises 5-30% by weight of vitamin C, and the tart cherry preparation comprises 0.5-30% by weight of vitamin C.
In one aspect, the composition is in the form of a liquid formulation or a solid beverage for brewing, and the composition comprises a thickening agent.
In one aspect, the liquid formulation is an oral liquid or a liquid beverage, and the solid beverage is an effervescent tablet, a dispersible tablet, a granule or a powder.
In one aspect, the thickening agent is selected from one or more of gellan gum, xanthan gum, guar gum or carrageenan, preferably gellan gum.
In one aspect, the composition may further comprise adjuvants such as maltitol, sodium bicarbonate, sodium carbonate, sorbitol, citric acid, flavorants, juices, thickeners, and the like.
In one aspect, the composition comprises ampelopsis grossedentata extract (5-15%), cordyceps militaris extract (3-6%), rosa roxburghii preparation (1-6%), sour cherry preparation (0-3%), maltitol (5-15%), sodium bicarbonate (10-20%), sodium carbonate (2-10%), sorbitol (20-30%), citric acid (20-30%), sweetener (0-1%), edible essence (0-2%), fruit juice (0-5%) and thickener (0-5%). The composition can be prepared by the main processes of crushing, sieving, weighing, granulating, drying, mixing, tabletting and the like of the raw materials.
In one aspect, the invention relates to the use of the uric acid lowering composition of the invention in the preparation of a medicament or food for lowering blood uric acid in a hyperuricemic subject.
In one aspect, the composition is administered once daily.
In one aspect, the Ampelopsis grossedentata extract is an extract obtained using water as an extraction solvent. For example, Ampelopsis grossedentata is prepared by extracting, filtering, concentrating, drying, and sieving to obtain Ampelopsis grossedentata extract.
In one aspect, the cordyceps militaris extract is an extract obtained by using water as an extraction solvent. For example, the extract of Cordyceps militaris is prepared by extracting Cordyceps militaris with water, filtering, concentrating, drying, and sieving.
In one aspect, the Rosa roxburghii preparation is a preparation dried from Rosa roxburghii juice. For example, Rosa roxburghii can be concentrated, dried, and sieved to make Rosa roxburghii preparation.
In one aspect, the sour cherry preparation is obtained by drying and screening whole sour cherries. For example, the whole sour cherry is mixed, dried and sieved to prepare the sour cherry preparation.
In one aspect, the composition is prepared by blending the Ampelopsis grossedentata extract, the Cordyceps militaris extract, the optional Rosa roxburghii preparation, and the optional tart cherry preparation.
Examples
Example 1 in vitro xanthine oxidase inhibitory Activity of Ampelopsis grossedentata
Take XOD activity inhibition assay as an example. The in vitro XOD inhibitory activity of Ampelopsis grossedentata extract was measured as half the Inhibitory Concentration (IC)50) The specific operation is as follows:
reagent and apparatus
Reagent: the Ampelopsis grossedentata extract is prepared by extracting Ampelopsis grossedentata, filtering, concentrating, drying and sieving; xanthine oxidase (X902417-500U, 50U/mg); xanthine (X820565-25 g, not less than 99.5%, molecular weight 152); allopurinol (A800424-25 g, 98%, molecular weight 136); PBS buffer (pH7.5); hydrochloric acid solution (6 mol/L); DMSO, and the like.
The instrument comprises the following steps: a micropipette (10-100. mu.L, 100-; centrifuge tubes (1.5 mL, 15mL, 50 mL); volumetric flask (25 mL); a vortex oscillator; a constant temperature gas bath oscillator; ultraviolet spectrophotometer, etc.
Experimental methods
Solution preparation:
PBS buffer: solution A: 0.2M KH2PO 4. Precisely weighing 2.72g of the extract, and dissolving the extract in 100mL of distilled water; and B, liquid B: 0.2M Na2HPO 4. Precisely weighing 11.36g of the extract, and dissolving the extract in 400mL of distilled water; and (3) mixing the solution A: the liquid B is prepared according to the following steps of 16: 84 (56: 294) to obtain 0.2M phosphate buffer solution with pH7.5, and diluting the mixture with distilled water 2.857 times to obtain 70mM phosphate buffer solution with pH 7.5.
Xanthine oxidase solution (0.1U/mL): a40. mu.L solution of xanthine oxidase (250U/mL) at a given concentration was diluted with PBS to 10 mL, and mixed well as denoted by B (1U/mL, 10 mL), and 9 mL of PBS was added to 1mL of B and mixed well as denoted by C (0.1U/mL, 10 mL) for use.
Xanthine solution (150. mu. mol/L): accurately weighing 11.4 mg xanthine, diluting to 25mL with PBS buffer solution, performing ultrasonic treatment for 15 min, diluting 1.5mL xanthine to 30 mL, and performing ultrasonic treatment for 5 min for later use.
Hydrochloric acid solution (1 mol/L): adding a certain amount of distilled water into a high-concentration hydrochloric acid solution (6 mol/L), and diluting to 1 mol/L for later use.
Sample solutions of different concentrations: a certain amount of sample is precisely weighed, dissolved in 2% DMSO, and diluted to a corresponding concentration by PBS buffer solution for later use.
Inhibition of XOD activity assay:
negative group: 1.7 mL of LPBS buffer, 0.6 mL of xanthine oxidase solution.
Negative blank group: 2.3 mLPBS buffer.
Sample group: 1mL of sample solution, 0.7 mL of buffer solution of LPBS, and 0.6 mL of xanthine oxidase solution.
Sample blank group: 1mL of sample solution, 1.3 mL of PBS buffer.
All groups were incubated at 25 ℃ for 15 min, and 1.2 mL of xanthine solution was added and reacted at 25 ℃ for 30 min. The reaction was terminated by adding 0.5 mL of hydrochloric acid solution, and the absorbance was measured at 290 nm.
Data processing:
the XOD activity inhibition rate is calculated by the following formula:
inhibition (%) = [ ((a negative-a minus empty) - (a sample-a-like empty))/(a negative-a minus empty) ], 100%
In the formula, A negative and A negative blank are the absorbances of a negative group and a negative blank group respectively, and A sample blank are the absorbances of a sample group and a sample blank group respectively. Calculating IC according to the inhibition rate of samples with different concentrations50
Results of the experiment
Ampelopsis grossedentata extract IC50=395.4 μ g/mL. Has a certain xanthine oxidase in vitro inhibition effect. The results are shown in FIG. 1.
Example 2 comparison of in vitro xanthine oxidase inhibitory Activity of vine tea composition compared to pure vine tea extract
The reagents, instruments and experimental methods were the same as in example 1, except that the sample combination ratios were different.
Wherein the Cordyceps militaris extract is prepared by extracting with water, filtering, concentrating, drying, and sieving; the fructus Rosae Normalis preparation is prepared by concentrating fruit juice, drying, and sieving; the sour cherry preparation is prepared by mixing, drying and screening whole sour cherries.
Different combinations of experimental samples are shown in table 1:
TABLE 1 Experimental sample combination weight ratios
Figure DEST_PATH_IMAGE001
The results are shown in Table 2:
TABLE 2 results of in vitro xanthine oxidase inhibitory Activity in different ratio combinations
Figure 583004DEST_PATH_IMAGE002
Comparative example:
TABLE 3 results of in vitro xanthine oxidase inhibitory Activity in various ratio combinations
Figure DEST_PATH_IMAGE003
TABLE 4 results of in vitro xanthine oxidase inhibitory Activity in different ratio combinations
Figure 437828DEST_PATH_IMAGE004
Example 3 comparison of the uric acid lowering Effect of Ampelopsis grossedentata composition in comparison with the hyperuricemia population of simply Ampelopsis grossedentata extract
The effect of taking the vine tea extract, the cordyceps militaris extract and the roxburgh rose preparation composition is compared with the effect of taking the vine tea extract alone in the hyperuricemia population. The specific information is as follows:
reagents and instrumentation:
baijie (BeneCheck) PD-G001-3-P household uric acid tester and matched test paper; roche (ROCHE) Accu-CHEK softclin household blood sampling pens. The rest of the extract or preparation sources are the same as example 2, and other common filling auxiliary materials are from commercial common raw material suppliers.
Test samples:
vine tea extract group: ampelopsis grossedentata extract and other common filling auxiliary materials
Vine tea composition group: the composition is equal to the vine tea extract in the vine tea extract group, and comprises the vine tea extract, the cordyceps militaris extract and the roxburgh rose preparation (the dry weight and the mass ratio of the three are 2: 1: 1.2)
The test population:
age: adults (18-80 years old);
quantity: ampelopsis grossedentata group (3 persons); composition set (6 persons)
Inclusion criteria were: the concentration of the fingertip blood uric acid is more than 420 mu mol/L;
evaluation indexes are as follows: blood uric acid concentration of fingertip in empty stomach state
The taking method comprises the following steps: taken after lunch
The research period is as follows: 5 weeks
Subject exclusion criteria:
1. subjects took azathioprine, aspirin (> 325 mg), atorvastatin, fenofibrate, losartan, thiazines, systemic corticosteroids, estrogens, oral contraceptives 2 weeks prior to or during the trial
2. Serum creatinine > 3.0 mg/dL
3. GPT > 100 mg/dL
4. Pregnant or lactating women
5. People who consider cancer chemotherapy or radiotherapy or other researchers to be unsuitable for taking part in test
Test procedure
Alcohol is used for disinfecting a finger area to be detected of a subject, a subsequent blood sampling point is kept to be the same finger, a blood sampling pen is penetrated by 3 grades of force, the first drop of blood is discarded, subsequent fingertip blood is taken, and the corresponding uric acid test paper is used for detecting the concentration of the fingertip blood uric acid. 8 parts per week earlier: blood was collected on an empty stomach for 5 weeks.
Results of the experiment
Subjects had a reduction in self baseline blood uric acid levels after 5 weeks of administration of the vine tea composition versus an equivalent amount of vine tea extract, as shown in table 3:
TABLE 3
Figure DEST_PATH_IMAGE005
After the subjects took the composition for 5 weeks, the fingertip blood uric acid level was significantly reduced compared to the initial state, while the ampelopsis grossedentata extract group had no significant change compared to the initial uric acid level. And the composition group was more significantly reduced than the ampelopsis grossedentata extract from the baseline level.
Conclusion of the experiment
The composition is more effective in reducing uric acid levels in a subject than the extract of Ampelopsis grossedentata alone. The results are shown in FIG. 2.
EXAMPLE 4 Effect of thickeners on improving foam in compositions
Apparatus and materials
The material is Ampelopsis grossedentata extract (5-15%), Cordyceps militaris extract (3-6%), Rosa roxburghii preparation (3-6%), sour cherry preparation (0-3%), maltitol (5-15%), sodium bicarbonate (10-20%), sodium carbonate (2-10%), sorbitol (20-30%), citric acid (20-30%), sweetening agent (0-1%), edible essence (0-2%) and fruit juice (0-5%). The difference between different groups is whether the thickening agent is added or not and the type of the thickening agent.
Then the solid beverage (containing effervescent tablets) is prepared by the main processes of crushing, sieving, weighing, granulating, drying, mixing, tabletting and the like of the raw materials.
Measuring cylinder, pipettor (1000 ml), constant temperature water bath, ruler.
Experimental methods
Preparing effervescent tablets added with various thickening agents of 1 percent and no thickening agent, taking 250ml of dry beakers, precisely adding 200ml of distilled water into the dry beakers respectively, keeping the water temperature at 37 ℃ for heating in a water bath, adding one piece of each beaker, measuring and recording the highest position where foam rises from the top of the liquid level, recording the height difference between the top of the liquid level and the highest position where the foam can reach, namely measuring the foaming amount, and evaluating the foaming amount through the height of the foam.
Results of the experiment
Compared with the group without the thickening agent, the foam of the group added with the thickening agent is obviously reduced, and the appearance and the taste of the product are greatly improved. The results are shown in table 4 and fig. 3.
TABLE 4 foam height Change with thickener addition
Figure 217565DEST_PATH_IMAGE006
While certain features of the invention have been illustrated and described herein, many modifications, substitutions, changes, and equivalents will now occur to those skilled in the art. It is, therefore, to be understood that the appended claims are intended to cover all such modifications and changes as fall within the true spirit of the invention.

Claims (10)

1. A composition for reducing uric acid comprises 1.5-2.5 parts by weight of Ampelopsis grossedentata extract and 0.5-1.5 parts by weight of Cordyceps militaris extract, wherein the Ampelopsis grossedentata extract contains 30-90% by weight of dihydromyricetin, the Cordyceps militaris extract contains 0.1-0.5% by weight of cordycepin, the% by weight and the parts by weight are based on dry weight, and the extract is obtained by using water as an extraction solvent.
2. Uric acid lowering composition according to claim 1, wherein the uric acid lowering composition comprises 1.8-2.2 parts by weight of Ampelopsis grossedentata extract comprising 30-90% by weight of dihydromyricetin and 0.8-1.2 parts by weight of Cordyceps militaris extract comprising 0.1-0.5% by weight of cordycepin.
3. Uric acid lowering composition according to claim 1, wherein the uric acid lowering composition comprises 2 parts by weight of Ampelopsis grossedentata extract comprising 30-90% by weight of dihydromyricetin and 1 part by weight of Cordyceps militaris extract comprising 0.1-0.5% by weight of cordycepin.
4. Uric acid reducing composition according to claim 1, further comprising 0.1-1.5 parts by weight of a Rosa roxburghii preparation comprising 5-30% by weight of vitamin C and 0-0.5 parts by weight of a tart cherry preparation comprising 0.5-30% by weight of vitamin C, the% by weight and parts by weight being based on dry weight, the Rosa roxburghii preparation being obtained by drying with Rosa roxburghii juice and the tart cherry preparation being obtained by drying with whole tart cherry fruits.
5. Uric acid lowering composition according to claim 1, further comprising 0.8-1.2 parts by weight of a Rosa roxburghii preparation comprising 5-30% by weight of vitamin C and 0.1-0.2 parts by weight of a tart cherry preparation comprising 0.5-30% by weight of vitamin C.
6. Uric acid lowering composition according to claim 1, further comprising 1 part by weight of a Rosa roxburghii preparation comprising 5-30% by weight of vitamin C and 0.1 part by weight of a tart cherry preparation comprising 0.5-30% by weight of vitamin C.
7. Uric acid lowering composition according to any one of claims 1 to 6, wherein the composition is in the form of a liquid formulation or a solid beverage for brewing and comprises a thickener.
8. Uric acid lowering composition according to claim 7, wherein the liquid preparation is oral liquid or liquid beverage and the solid beverage is effervescent tablet, dispersible tablet, granule or powder.
9. Uric acid lowering composition according to claim 7, wherein the thickener is selected from one or more of gellan gum, xanthan gum, guar gum or carrageenan, preferably gellan gum.
10. Use of a uric acid lowering composition according to any one of claims 1-9 in the preparation of a medicament or food product for lowering blood uric acid in a hyperuricemic subject.
CN202111646938.7A 2021-12-30 2021-12-30 Composition with effect of inhibiting uric acid generation and preparation method thereof Pending CN114224957A (en)

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CN104473977A (en) * 2014-11-18 2015-04-01 广东省微生物研究所 Cordyceps militaris water extract as well as preparation method and application thereof
CN105901230A (en) * 2016-04-27 2016-08-31 济南舒美生物科技有限公司 Compound health tea with efficacy of hyperuricemia inhibition

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Publication number Priority date Publication date Assignee Title
CN104473977A (en) * 2014-11-18 2015-04-01 广东省微生物研究所 Cordyceps militaris water extract as well as preparation method and application thereof
CN105901230A (en) * 2016-04-27 2016-08-31 济南舒美生物科技有限公司 Compound health tea with efficacy of hyperuricemia inhibition

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