KR20140106772A - Composition for inhibition of gout comprising extracts of chrysanthemum indicum L. - Google Patents
Composition for inhibition of gout comprising extracts of chrysanthemum indicum L. Download PDFInfo
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- KR20140106772A KR20140106772A KR1020130019836A KR20130019836A KR20140106772A KR 20140106772 A KR20140106772 A KR 20140106772A KR 1020130019836 A KR1020130019836 A KR 1020130019836A KR 20130019836 A KR20130019836 A KR 20130019836A KR 20140106772 A KR20140106772 A KR 20140106772A
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- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000002834 transmittance Methods 0.000 description 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
- 239000003383 uricosuric agent Substances 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 238000003809 water extraction Methods 0.000 description 1
- 230000004584 weight gain Effects 0.000 description 1
- 235000019786 weight gain Nutrition 0.000 description 1
- 229940075420 xanthine Drugs 0.000 description 1
- 239000003064 xanthine oxidase inhibitor Substances 0.000 description 1
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Abstract
Description
The present invention relates to a composition for inhibiting airflow, and more specifically gamguk (Chrysanthemum indicum L.) extract.
Gout is a disease caused by an inflammatory reaction to monosodium urate monohydrate crystals (MSU) secondary to hyperuricemia, a recent study found that rheumatoid arthritis overtook rheumatoid arthritis, the most common inflammatory arthritis in men over 40 years of age . The causes of increased gouty arthritis include westernization of diet, increased obesity, aging of the population, increased prevalence of renal disease and hypertension, increased use of diuretics and low-dose aspirin such as Thiazide . Gout is also the most common inflammatory arthritis in men. It has been reported that the prevalence rate is about 1 ~ 2% in Western countries, and the incidence is low in Asians compared to Westerners. However, it is reported that prevalence rates are increasing in western and Asian countries due to westernized eating habits and lifestyle. In Korea, 9.3% of adults (14.3% of men, 2.2% of women) are found to have hyperuricemia. Gout is a type of adult disease that occurs in obese men. Increased uric acid in the blood is deposited in the form of monosodium urate cystal (MSU) in the joints or surrounding tissues to induce inflammation, resulting in pain, edema, and severe deformity of the joints. The course of the illness increases the uric acid level in the blood, but acute intermittent arthritis occurs from the point of no symptoms to chronic gouty arthritis with deformation of the joints.
Gout is known to be a clear and successful treatment of the disease, but it is often accompanied by other diseases such as hypertension and chronic renal failure, so drug side effects should be carefully considered, Patient efforts are essential for prognosis in long-term treatment.
Gout and hyperuricemia are not included in the diagnostic criteria for metabolic syndrome, which is a complex disorder with hypertension, hyperlipidemia, hyperglycemia, abdominal obesity, and clinical manifestations that increase the risk of adult diseases such as arteriosclerotic heart disease and
In the chronic phase of gout, uric acid is lowered in the blood, and the uric acid lowering agent is classified into xanthine oxidase (XO) inhibitor and uricosuric agent according to the mechanism. Allopurinol and febuxostat, which was recently developed as a new drug. Allopurinol is a xanthine oxidase (XO) inhibitor that can be effectively used regardless of the cause of hyperuricemia, but the most serious side effect of allopurinol is hypersensitivity syndrome, Eosinophilia, hepatitis, kidney failure, etc., are known to be at risk of death. Febuxostat, also known as xanthine oxidase inhibitor or allopurinol, is a nonpurine selective blocking agent that is metabolized mainly in the liver to form glucuronide. Most of the gout is chronic, and even if there is no symptoms, it is treated prophylactically to lower the anti-inflammatory and uric acid levels. These preventive treatments should be used after the disease has been maintained for a period of time in a calm state, otherwise the ventilation will recur more severely. However, there is a lot of controversy about the proper period of the illness, and it is also difficult to prevent the acute onset of the gout which recurrently intermittently recurrent. The Gout induction enzyme Inhibition of xanthin oxidase has not been specialized and popularized yet. Gout is used chronically, so the side effects caused by cholchine and allopurinol become serious problems. Therefore, there is no need for prophylactic use for a long period of time, and a natural product preparation which can relieve inflammation is needed.
Recently, febuxostat (febuxostat), developed by Teijin Pharmaceuticals in Japan, has only recently been developed in the United States for new gout medicines that are licensed as new gout medications in the United States in 40 years. Takeda, a pharmaceutical company that sells febuxostat in the United States, is one of the largest pharmaceutical companies in Asia and is taking up the US pharmaceutical company URL Parma, which is spurring the development of more and more gout pills.
Treatment of gout has a long tradition that spans the history of medicine, but recent changes in dietary therapy have led to the development of new uric acid-lowering drugs that can be used in patients with resistance to conventional drugs. In addition to these developments, it would be possible to develop a product with the concept of edible vaccine if it can induce uric acid degradation by using natural products using medicinal crops in Gyeongbuk province. Natural products contain many anti-inflammatory substances. It is thought that it is possible to isolate substances inhibiting inflammation caused by monosodium urate by using germination, and they can be developed as food materials that can prevent the acute onset of gout.
In order to facilitate accessibility of consumers and also to extinguish a variety of tastes, it is necessary to develop materials with preventive power against gout using natural materials. It is expected that this will have a very positive effect not only in domestic but also in the international market where the efficacy of herbal medicine and medicinal plants as an agent for treating or preventing adult diseases is not well recognized. Since the products currently on the market are developed mainly as medicines, the width of choice according to individual taste is very narrow. Therefore, it is possible to expand the scope of application by developing it into encapsulation, powdering and direct addition to food in the form of functional food, not medicine.
Functional ingredients effective on the joints and bones recognized by Korea Food & Drug Administration include complex extracts such as gossy auris, complex extracts such as glucosamine, rosehip powder, fatty acid complex, and hepatic extract, complex extracts such as chrysanthemum extract, green lipped mussel extract oil, Extracts, N-acetylglucosamine, dimethylsulfone (MSM), black yeast culture powder and soy isoflavones. Among them, effective against inflammation are complexes such as green lipped mussel extract oil, hop extract and golden extract, fatty acid complex And others are functional ingredients that help bone formation and cartilage formation. In order to be effective in acute and chronic gout, there should be an inflammation-inhibiting action, and a small number of functional ingredients with inflammation-inhibiting action are currently registered.
The inventors of the present invention have conducted intensive researches to overcome the problems of the prior arts, and as a result, it has been confirmed that Chrysanthemum indicum L. extract is effective in inhibiting gout in cell and gout animal models, thereby completing the present invention .
Therefore, the main object of the present invention to provide a vent for inhibiting composition containing gamguk (Chrysanthemum indicum L.) extract have the effect to inhibit ventilation.
Another object of the invention is the gamguk (Chrysanthemum indicum L.) extract of the present invention.
According to one aspect of the invention there is provided gamguk (Chrysanthemum indicum L.) extract.
Chrysanthemum indicum Linne ( Chrysanthemum indicum Linne) is a perennial herb that belongs to the Compositae family. It is a wild chrysanthemum widely distributed in the mountainous areas of central and southern Korea. In oriental medicine, antimicrobial, anti-cancer, anti-inflammatory, immunomodulatory and antioxidative activities are known through various studies. However, to date, there is no known literature showing the correlation between excretion and gout suppression.
In the present invention, the extract can be extracted with any extraction solvent known in the art, and preferably, it is extracted with water, ethanol or a mixed solvent thereof. methanol, aceton, n-butanol, ethylacetate and the like can be used. In the present invention, the product is extracted with ethanol designated as a solvent to be used for extracting plants from the Korea Food & Drug Administration.
In the case of the water extract of the present invention, the extract is subjected to hot water extraction at 100 ° C for 1 to 5 hours by mixing 5 to 20 times of water (v / w) with the sample, and in the case of the ethanol extract, 5 to 20 times Of 60% ethanol and homogenizing the mixture at 10,000 to 30,000 rpm for 1 to 5 minutes with a homogenizer, followed by stirring and extraction for 24 to 48 hours.
In the present invention, the extract may inhibit xanthine oxidase. Xanthin oxidase, which is involved in purine metabolism in vivo, is an enzyme that produces urate that increases urate in the plasma and accumulates in the fracture and causes pain. As shown in Table 2, the water extracts and ethanol extracts from hamsters exhibit lower uric acid production and higher inhibitory activity of xanthin oxidase than the control. This indicates that the mungbean extract inhibits xanthin oxidase, an enzyme that causes gout, to reduce uric acid in plasma and prevent accumulation in fracture, thereby preventing pain and suppressing gout.
In the present invention, the above-mentioned extract provides a composition for suppressing hyaluronidase, which inhibits hyaluronidase. As shown in Table 3, inhibition of the hyaluronidase activity of the water extract of hamyang was low, but the inhibition of the activity of hyaluronidase was higher than that of the water extract of hamyang in the 60% ethanol extract of hamyook. This shows that the 60% ethanol extract of hamjuk suppresses hyaluronidase activity and has anti-inflammatory effect.
In the present invention, the above-described extract does not cause acute toxicity and chronic toxicity.
In the present invention, the acute toxicity and chronic toxicity are safe from the survival rate, body weight, dietary intake, organ weight and hepatotoxicity.
According to the present invention, as shown in Examples 5 and 6, the acacia extract did not cause acute toxicity and chronic toxicity (Figs. 4 to 12), thereby confirming that the acacia extract was a highly safe substance .
In the present invention, the composition for suppressing airflow is characterized in that the composition for suppressing airflow reduces edema and inflammatory cytokine expression.
In the present invention, the inflammatory cytokine is an inducible nitric oxide synthase (iNOS), interleukin 1-beta (IL-1?), Tumor necrosis factor-alpha .
According to the present invention, the expression of inflammatory cytokines was increased in the feet of a ventilated mouse model prepared by injecting MSU into the feet (FIG. 14). These results confirmed that the ventilated mouse model was constructed properly. In the ventilated mouse model of the ventilated mouse model, the low concentration (1 g / kg) of the roots suppressed the inflammatory cytokine, but did not reduce the swelling of the feet. The high concentration (2 g / kg ) Treatment showed an effect of suppressing edema of the foot together with reduction of inflammatory cytokine (Fig. 15 to Fig. 17). This result suggests that the germinated extract may reduce airway edema while reducing inflammatory cytokines.
In the present invention, the extract may be added to a health food for the purpose of inhibiting the gout, and is preferably used in the form of beverage, circle, tablet, capsule, powder, Wherein the composition is contained in any one selected from the group consisting of:
When the cuttlefish extract is used as a food additive, it can be added as it is or can be used together with other food or food ingredients, and can be suitably used according to a conventional method. The amount of the active ingredient to be mixed can be suitably determined according to the intended use (prevention, health or therapeutic treatment).
As described above, according to the present invention, the mung bean extract inhibits xanthine oxidase, which is a gout inducing enzyme, and exhibits an enhanced gout inhibitory effect even in a gout model mouse. In addition, the extract of Chojungguk showed safety in both acute and chronic toxicity. Therefore, the extract of the mung bean gum according to the present invention can be used in a functional health food composition useful for the gout suppressing effect.
Fig. 1 is a digital caliper which is a measuring part and a measuring part of the back foot of a mouse.
Fig. 2 shows the effect of ethanol concentration on the elution of phenol compounds from Ganoderma lucidum extract.
FIG. 3 shows the effect of extraction time on phenol compound elution from Ganoderma lucidum extract.
Fig. 4 shows the results of the acute toxic effect of red ginseng root.
FIG. 5 shows the effect of oral administration of red ginseng on body weight for 13 weeks.
Fig. 6 shows the effect of oral administration of red ginseng on body weight change for 13 weeks.
FIG. 7 shows the effect of 13 weeks of transdermal administration on the dietary intake.
FIG. 8 shows the effect of 13 weeks of intestinal tract administration on the average dietary intake.
FIG. 9 shows the effect of oral administration of red ginseng on water intake for 13 weeks.
Fig. 10 shows the effect of 13 weeks of intestinal tract administration on the average water intake.
Fig. 11 shows the effect of oral administration of red ginseng on the organ weight for 13 weeks.
FIG. 12 shows the effect of oral administration of red ginseng on plasma GOT and GPT for 13 weeks.
FIG. 13 shows the result of comparison with a control foot injected with physiological saline after 24 hours and 72 hours after injecting monosodium urate crystal (MSU) into the foot joint (right foot: test group, left foot: control group).
FIG. 14 shows the results of measurement of the expression level of inflammatory cytokines with time after injection of monosodium urate crystal (MSU).
Fig. 15 shows the effect on the edema of the foot caused by the monosodium urate crystal (MSU).
16 shows the effect of pre-treatment (low concentration) on the edema of the foot caused by uric acid crystals (Monosodium urate crystal; MSU).
Figure 17 shows the effect of pre-treatment (high concentration) on the inflammatory cytokine of the liver by monosodium urate crystal (MSU).
Hereinafter, the present invention will be described in more detail with reference to Examples. These embodiments are only for illustrating the present invention, and thus the scope of the present invention is not construed as being limited by these embodiments.
Example One : Exclusion Preparation of extract
In the case of the extract of water as a solvent, the sample was mixed with 10 times of water (v / w), and the sample was used at 100 ° C for 2 The ethanol extracts were homogenized in a homogenizer at 20,000 rpm for 10 minutes and then stirred for 24 hours. The extract was filtered through a filter paper (whatman No. 1 filter paper ), And concentrated as needed in a rotary vacuum evaporator (yela NE, Japan) to be used as a sample.
Example 2 : Phenolic Compound quantitation
In order to investigate the effects of ethanol concentration and extraction time on the elution of phenolic compounds, the optimum extraction concentration of the samples was measured according to the ethanol concentration. As a result, as shown in FIG. 2, the content of EtOH was continuously increased from 3.63 mg / g in 10% EtOH, 5.78 mg / g in 30% EtOH and 6.23 mg / g in 60% EtOH. mg / g, respectively. Therefore, it was confirmed that the optimum concentration of ethanol for solvent extraction was 70%.
The optimum extraction concentration of the samples was measured with ethanol concentration of 70%. As a result, as shown in FIG. 3, the extraction yield was the highest at 6.8 mg / g when extracted for about 6 hours, and remained at a similar value after 6 hours. Therefore, it was found that the optimum conditions for the elution of the useful components of hamjuk consisted of 6 hours of extraction using 70% ethanol.
240 μL of a 5% sodium carbonate (
Sample
Example 3: Ventilation inhibition ( Xanthin oxidase [ XOase ] inhibition ) Effect measurement
XOase activity inhibition assay was performed according to the method of Stirpe and Corte. That is, 0.1 mL of the enzyme solution and 0.3 mL of the extraction solution were added to 3 mL of the substrate solution in which 2 mM of xanthine was dissolved in 0.1 M potassium phosphate buffer (pH 7.5), 0.3 mL of distilled water was added to the control solution After incubation at 37 ° C for 30 minutes, the reaction was terminated by adding 1 ml of 20% trichloroacetic acid, followed by centrifugation to remove the protein. Uric acid produced in the reaction solution was measured at 292 nm, . The results are shown in Table 2 below.
[Formula 1]
(μg / mL)
(%)
(μg / mL)
(%)
Xanthine oxidase, which is involved in purine metabolism in vivo, is an enzyme that causes urine to build up urate (urate) in the plasma to accumulate in the fracture and cause pain. In order to find a natural substance which inhibits these enzymes, the inhibitory effect of this enzyme was measured by extracting phenol substance from water and 60% ethanol. As a result, as shown in Table 2, the inhibition rate of water extract was 67.53% and that of 60% ethanol extract was 83.45%.
Example 4: Inflammation inhibition ( Hyaluronidase Inhibition) activity measurement
Hyaluronidase (HAase) inhibitory activity was measured according to the Ovine test. That is, 0.5 mL of the extraction solution was mixed with 0.5 mL of HAase (100 U / mL) dissolved in 2 mM sodium phosphate buffer (pH 6.9), reacted at 38 ° C. for 5 minutes, and incubated in a 0.3 M phosphate buffer Hyaluronic acid (HA) was prepared at a concentration of 4 mg / mL as a substrate and reacted at 38 ° C for 45 minutes. Then, 5 mL of the albumin solution dissolved in 0.24 M acetate buffer (pH 3.75) And the transmittance was measured at 600 nm.
[Formula 2]
As a result, as shown in Table 3, the water extract showed a low inhibition rate of 6.76%, while the 60% ethanol extract showed 30.2% inhibition activity.
Exclusion To test the safety of extracts and to test for inhibition of gout In vivo test
For the in vivo test for the safety and the inhibition of gout inhibitory effect, 7 - week - old C57BL / 6J male rats were used in this study. They were purchased from Sam Taco (Seoul) and raised in an animal breeding clean room. Breeding conditions ranged from 7:00 am to 7:00 pm for 12 hours with a light bulb and 12 hours afterwards. Diet and water were allowed to eat freely, and dietary and water intakes were measured.
Example 5: Acute toxicity Measure
Mice were divided into 6 groups of 10 rats per group, and the rats were diluted in distilled water to prepare concentrations (0, 0.5, 1, 2.5, 5, and 10 g / kg) and then oral gavage The behavior of posterior mice was observed and the survival rate was measured. After one week, anesthetics were injected into the peritoneal cavity (tiletamine and zolezepam: 25 mg / kg; zylazine: 10 mg / kg) and the rats were sacrificed and blood was collected. Plasma was isolated and stored at -80 ° C until analysis. Liver and kidney were weighed and stored at -80 ° C until analysis. Glutamate oxaloacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT) were measured for liver toxicity. As a result, one mouse did not die for one week as shown in Fig. 4, and no specific behavior pattern was observed in mice. Dietary intake and body weight did not differ between groups. There was no difference in renal and hepatic weights between the groups, and plasma GOT and GPT were not different.
Example 6: Chronic Toxicity Measure
The gonads were diluted with water (0, 0.25, 0.5, 1, 2 g / kg) in the water ingested by the mice and were freely taken for 13 weeks. Changes in body weight, dietary intake, water intake, and behavior during the period were observed. One mouse did not die after 13 weeks and no specific behavior was observed. In chronic toxicity studies, rats were sacrificed and blood and liver and kidney weights were measured as in the acute toxicity test. Liver and plasma were stored at -80 ° C until analysis. GOT and GPT were measured for hepatotoxicity.
1. Weight change
The mice were diluted with water to a concentration of 0, 0.25, 0.5, 1, and 2 g / kg, respectively. Mice were divided into five groups of 10 mice, and each group was fed with water diluted with 0, 0.25, 0.5, 1, 2 g / kg for 13 weeks. As a result, the body weights measured every week as shown in FIGS. 5 and 6 were not different between the groups, and there was no difference between the groups in the final weight gain for 13 weeks.
2. Dietary intake
The average daily dietary intake was also measured weekly for 13 weeks. As a result, there was no difference between the groups in any of the measured states as shown in Figs. There was also no difference in the daily dietary intake of 13 weeks.
3. Water intake
Water was changed twice a week, and average daily water intake was measured and expressed as a weekly average. As a result, as shown in FIGS. 9 and 10, the water intake was significantly higher in the intestinal tract intake group and the water intakes were higher in all the intestinal tract intake groups when the daily average water intakes of the 13 weeks were combined.
4. Long term weight
There was no difference in weight, height, liver, spleen, and heart weight of the organs measured for 13 weeks (FIG. 11).
5. Hepatotoxicity
GOT and GPT were measured in plasma to measure hepatotoxicity. The measurement kit was measured using a transaminase kit from Asan Pharmaceutical (Seoul). Plasma tumor necrosis factor (TNF) -α was measured by enzyme-linked immunosorbent assay (Invitrogen, Camarillo, CA, USA). As a result, plasma GOT and GPT did not differ between the groups (FIG. 12).
Example 7: Production of ventilation model
Monosodium urate cystal (MSU) was prepared and injected as follows. First, 4 g uric acid is dissolved in 800 ml of 0.5 M NaOH while heating (
Example 8: for cytokine expression measurement real - time PCR
Gene expression of foot tissue was analyzed by real-time PCR. To summarize the process of extracting RNA first, hypothalamic tissue was placed in a 1 ml TRI-reagent (Sigma Chemical Co, MO, USA) and homogenized using ultrasonic waves. 200 μl of chloroform was added thereto, and the mixture was vigorously shaken for 15 seconds, followed by reaction at room temperature for 5 minutes, followed by centrifugation at 4 ° C and 13,200 rpm for 15 minutes. The same volume of isoprophanol was added to the separated supernatant, which was reacted at room temperature for 10 minutes, and then centrifuged at 4 ° C and 13,200 rpm for 10 minutes to precipitate RNA. The precipitated RNA was washed with 1 ml of cold 75% ethanol, centrifuged for 5 minutes at 4 ° C, 13,200 rpm, and the precipitate was dried at room temperature. Finally, the remaining RNA was dissolved in 30 μl of Rnase-free water and stored at? 70 ° C. RNA concentrations were measured at 260 and 280 nm using a Nano-drop (Thermo, Wilmington, USA). In order to amplify the RNA, 1 μg of the separated RNA was prepared with cDNA using High-Capacity cDNA Reverse Transcription Kit (Applied Biosystems, Foster City, CA, USA) and real-time PCR was performed. Real time PCR was performed using Real-Time PCR 7500 System and Power SYBR Green PCR Master Mix (Applied Biosystems). The process was pre-reacted at 95 DEG C for 10 minutes and then repeated 45 times for denaturation (95 DEG C, 15 seconds), annealing (55 DEG C, 20 seconds), and extension (72 DEG C, 35 seconds) . Β-actin was used as an internal standard and the primer sequences are shown in Table 4.
IL-1β: interleukin-1β iNOS: inducible nitric oxide synthase
Example 9: Exorcism Measurement of ventilation inhibition effect
In order to measure the gout inhibition effect, the mice were divided into the control group injected with physiological saline solution and the group injected with MSU. The MSU injection group was further diluted with water to obtain 0, 0.25, 0.5, 1, 2, 4 and 10 g / kg And then injected into the mice. The extracts were administered orally for 7 days. On the 6th day, MSU 4mg / 50μl was injected into both hind paws, and oral gavage was administered on the morning of the 7th day, and the mice were sacrificed after the anesthetic administration in the afternoon. Blood was centrifuged to separate plasma and plasma and liver were stored at -80 ° C. The degree of foot edema was measured with digital calipers.
As a result, there was a statistically significant increase in foot edema compared to the control group injected with saline in the MSU injection group. At low concentrations of 0.25, 0.5 and 1 g / kg, the expression of inflammatory cytokines tended to decrease, but the effect on the edema was not significant. kg / kg, the number of paws was decreased compared to the group without paws, and the number of paws was decreased most in the group receiving 10 g / kg. Expression of iNOS, IL-1β, and TNF-α was significantly increased in the MSU group compared to the control group. iNOS was significantly decreased in all groups compared with the control group, and decreased most in the 10 g / kg group. IL-1β decreased in proportion to the concentration at 2 and 4 g / kg, but increased in the 10 g / kg group rather than 2 and 4 g / kg. TNF-α was reduced in the 2 and 4 g / kg groups but not in 10 g / kg (FIGS. 15 and 16).
There was no statistically significant difference in the expression of inflammatory cytokines in the liver between the MUS and control groups and between the immunized group and the untreated group. There was no statistically significant difference in the concentration of TNF-α in the blood between the groups (FIG. 17).
Claims (10)
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| JP2018501245A (en) * | 2014-12-23 | 2018-01-18 | コリア インスティテュート オブ オリエンタル メディシン | Gout control composition containing sweet chrysanthemum and cinnamon bark extract as an active ingredient |
| US10098921B2 (en) | 2014-12-23 | 2018-10-16 | Korea Institute Of Oriental Medicine | Method for treating gout and gout-induced arthritis using composition containing mixed extract of Chrysanthemum indicum and Cinnamomum cassia |
| KR20160130624A (en) | 2015-05-04 | 2016-11-14 | 재단법인 경기과학기술진흥원 | A Pharmaceutical Composition Comprising Extract or Fraction of Salvia plebeia R. Br. for Preventing or Treating Gout |
| CN104815030A (en) * | 2015-05-23 | 2015-08-05 | 陈泽林 | Traditional Chinese medicine preparation for treating gout and preparation method of traditional Chinese medicine preparation |
| CN105288301A (en) * | 2015-11-27 | 2016-02-03 | 青岛海之源智能技术有限公司 | Tincture for treating epinephelus akaara ulcer disease and preparation method thereof |
| KR102187877B1 (en) * | 2020-03-25 | 2020-12-07 | 주식회사 프롬바이오 | Composition for ameliorating, preventing or treating hyperuricemia or gout comprising extract of Chrysanthemum indicum L. and Cornus officinalis |
| CN113100443A (en) * | 2021-05-17 | 2021-07-13 | 卢静 | Composition and soft capsule for relieving gout and preparation method thereof |
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