CN116139231A - Compositions for specific dissolution of urate crystals in joints - Google Patents
Compositions for specific dissolution of urate crystals in joints Download PDFInfo
- Publication number
- CN116139231A CN116139231A CN202211679380.7A CN202211679380A CN116139231A CN 116139231 A CN116139231 A CN 116139231A CN 202211679380 A CN202211679380 A CN 202211679380A CN 116139231 A CN116139231 A CN 116139231A
- Authority
- CN
- China
- Prior art keywords
- composition
- uric acid
- extract
- urate crystals
- joints
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
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Abstract
The invention provides a composition for specifically dissolving urate crystals in joints, which is at least selected from at least two of betaine, yam extract and chinaroot greenbrier extract, can obviously inhibit the XOD activity of liver and intestinal tracts, inhibit the kidney from reabsorption uric acid transporter URAT1, promote the expression of intestinal secretion uric acid transporter ABCG2, enhance the activity of Na+ -K+ pumps and have the effect of promoting the dissolution of urate crystals deposited in joints. The composition can be used in combination with uric acid lowering agent to accelerate blood uric acid lowering to normal range, and reduce acute gout attack risk in blood uric acid lowering process.
Description
Technical Field
The invention relates to the technical field of gout treatment, in particular to a composition capable of specifically dissolving urate crystals in joints and reducing the clinical dosage of a gout treatment medicine.
Background
The gout attack process is as follows: the initiation is that the urinary acid salt crystals are precipitated in the joint to induce joint inflammation, the activity of inflammatory small NLRP3 in the joint and the expression, maturation and secretion of inflammatory factors IL-1 beta are rapidly increased, and a large amount of neutrophils are recruited to joint synovial fluid to amplify joint inflammation cascade. Meanwhile, urate crystals can induce oxidative stress under the mediation of NADPH and Myeloperoxidase (MPO), so that severe edema and pain nerve stimulation are caused, and severe pain and edema symptoms of joints of people are caused.
The patients progress from hyperuricemia to acute gout, chronic gouty arthritis and tophus, and the root cause is that urate crystals are crystallized and separated out in joints to induce joint inflammation. Whether gout and the pain level at the onset of gout are induced depends not only on the blood uric acid level, but also on the number and rate of urate crystals deposited at the joint: the more the deposition amount of the uric acid salt is, the faster the deposition speed is, the easier the gout is to be in attack, and the more serious the pain is when the gout is in attack; the smaller the deposition amount of the urate crystals, the slower the deposition speed, the less easy the gout is to be easy to attack, and the less intense the pain feeling is when the gout is to be attack. The crystallization of the urinary acid salt crystals in other tissues and organs can lead to injury of tissues and organs and induce complications.
Through follow-up of blood uric acid change of gout patients in conventional uric acid reduction treatment and sodium urate crystals deposited at joints (dual-energy CT quantitative determination of the volume and density of the sodium urate crystals deposited at joints), researchers such as Chui CSK and the like formulate a dissolution model of the gout patients, and find that: when blood uric acid is more than 430 mu moL/L, the dissolution time of sodium urate crystals deposited at joints is close to infinite length; the time for the sodium urate crystals deposited at the joints to begin to dissolve significantly at blood uric acid=240 μmol/L is 10-19 months, and still 4-8 months are required for the sodium urate crystals deposited at the joints to begin to dissolve when blood uric acid approaches 0. This indicates that: conventional uric acid lowering drugs have limited efficacy in alleviating and treating gout.
In addition, studies have shown that: the dissolution of urate crystals in joint bursa solution is mainly achieved by reducing sodium ions/increasing potassium ion concentration of bursa solution, increasing ABCG2 activity and expression (promoting uric acid transfer from bursa solution to blood) and the like. Therefore, according to the above-mentioned target thought, there is a need to develop a drug that specifically promotes dissolution of urate crystals in joints.
Disclosure of Invention
Based on this, there is a need to provide compositions that specifically solubilize urate crystals in the joint and reduce the clinical dose of gout therapeutic agents.
The invention adopts the following technical scheme:
the invention provides a composition for specifically dissolving urate crystals in joints, which is at least selected from at least two of betaine, yam extract and chinaroot greenbrier extract.
Preferably, the weight ratio of betaine to yam extract in the composition is (1-5): 1-5.
Preferably, the weight ratio of betaine to smilax extract in the composition is (1-6): 1-6.
Preferably, the weight ratio of the yam extract to the chinaroot greenbrier extract in the composition is (1-10): 1-10.
Preferably, the composition further comprises lily extract.
Preferably, the composition further comprises tributyrin.
Preferably, the composition further comprises at least one of EGCG, vitamin C, taurine.
Preferably, the composition further comprises uric acid lowering agents and/or adjuvants. The uric acid reducing medicine is at least one selected from allopurinol, febuxostat, benzbromarone and probenecid. The auxiliary material can be microcrystalline cellulose and the like.
The invention provides a composition for specifically dissolving urate crystals in joints, which comprises the following components in parts by weight: 0.1 to 15 parts of betaine, 0.1 to 10 parts of yam extract, 0.1 to 10 parts of chinaroot greenbrier extract, 0.3 to 8 parts of lily extract, 0.1 to 15 parts of tributyrin, 0.1 to 8 parts of EGCG, 0.25 to 12 parts of vitamin C and 0.5 to 12 parts of taurine; the betaine is chemically synthesized or extracted by natural organisms, wherein the purity of the natural organism extraction is more than 50 percent, and the purity of the chemically synthesized betaine is more than 95 percent; the main component of the yam extract is dioscin, and the content is more than 30%; the main component of the chinaroot greenbrier extract is astilbin, and the content is more than 40%; the main component of the lily extract is alkaloid, and the content is more than 5%.
The invention also provides a preparation for specifically dissolving the urate crystals in the joint, which is prepared from the composition for specifically dissolving the urate crystals in the joint. The dosage form may be selected from: solutions, suspensions, emulsions, powders, lozenges, pills, syrups, troches, tablets, chewing gums, slurries, capsules and the like.
Compared with the prior art, the invention has the beneficial effects that:
1) According to the invention, a large number of screening tests show that at least two of betaine, yam extract and chinaroot greenbrier extract can obviously inhibit the XOD activity of liver and intestinal tract, inhibit the kidney from reabsorption uric acid transporter URAT1, promote the expression of intestinal secretion uric acid transporter ABCG2, reduce the synthesis of uric acid, increase the intestinal and renal excretion capacity of uric acid and reduce blood uric acid.
2) A large number of screening experiments show that the composition containing at least two of betaine, yam extract and chinaroot greenbrier extract can improve the expression of the bursa uric acid transporter ABCG2 and enhance the activity of Na+ -K+ pump, and has the effect of promoting the dissolution of urate crystals deposited in joints.
3) The composition containing betaine, rhizoma Dioscoreae extract, rhizoma Smilacis chinensis extract, tributyrin, etc. can be used in combination with uric acid lowering agent to accelerate blood uric acid lowering to normal range, and reduce acute gout attack risk during blood uric acid lowering process.
Drawings
FIG. 1 is a statistical chart showing the results of the hyperuricemia change in the model test of hyperuricemia mice in example 4.
FIG. 2 is a statistical chart showing the results of the relative expression amounts of the intestinal ABCG2 in the hyperuricemia mouse model test in example 4.
FIG. 3 is a statistical chart showing the results of the relative expression amounts of the bursa ABCG2 in the hyperuricemia mouse model test in example 4.
FIG. 4 is a statistical graph of the relative activity of the bursa Na-K pump tested in the hyperuricemia mouse model of example 4.
FIG. 5 is a statistical graph of the results of the intestinal and liver XOD activity of the hyperuricemia mouse model test of example 4.
FIG. 6 is a statistical chart showing the results of the relative expression amounts of URAT1 in kidney in the hyperuricemia mouse model test of example 4.
FIG. 7 is a statistical plot of changes in footpad thickness and inflammatory factor IL-1β for the acute gout rat model of example 5.
Fig. 8 is a three-dimensional reconstructed picture of dual-energy CT of intra-articular crystals before and after intervention by a subject.
Detailed Description
The present invention will be described in further detail with reference to specific examples so as to more clearly understand the present invention by those skilled in the art.
The following examples are given for illustration of the invention only and are not intended to limit the scope of the invention. All other embodiments obtained by those skilled in the art without creative efforts are within the protection scope of the present invention based on the specific embodiments of the present invention.
In the examples of the present invention, all raw material components are commercially available products well known to those skilled in the art unless specified otherwise; in the embodiments of the present invention, unless specifically indicated, all technical means used are conventional means well known to those skilled in the art.
Part of raw material source description:
rhizoma Dioscoreae extract: the dioscin content was 40% and was purchased from western amp, brio biotechnology limited.
Chinaroot greenbrier extract: astilbin content 70%, purchased from western amp, biotech limited.
Lily extract: the aqueous extract is purchased from Shaanxi, he Biotechnology Limited.
Betaine: purity 95%, purchased from the company xianbaite biotechnology limited.
EGCG: epigallocatechin gallate, 95% pure, was purchased from western amp, biotech limited.
Tributyrin: purity 99%, purchased from Shandong national chemical Co.
Vitamin C: purity 99%, purchased from Shanghai Seiyaka Biotechnology Co.
Taurine: purity 99%, purchased from Shanghai Seiyaka Biotechnology Co.
Microcrystalline cellulose: purity 97%, purchased from Shanghai Seiyaka Biotechnology Co.
Example 1
The present example provides a variety of compositions, the specific dosage ratios are given in the following table:
| composition and method for producing the same | Betaine (betaine) | Chinese yam extract | Smilax china extract | Lily extract | Microcrystalline cellulose | Total of parts by weight |
| Composition 1 | 25 | 75 | 100 | |||
| Composition 2 | 25 | 75 | 100 | |||
| Composition 3 | 25 | 75 | 100 | |||
| Composition 4 | 25 | 25 | 50 | 100 | ||
| Composition 5 | 25 | 25 | 50 | 100 | ||
| Composition 6 | 25 | 25 | 50 | 100 | ||
| Composition 7 | 25 | 25 | 25 | 25 | 100 | |
| Composition 8 | 25 | 25 | 25 | 25 | 100 |
Example 2
This example provides a composition (9) comprising tributyrin, EGCG, vitamin C and taurine in a weight ratio of 30:20:20:30.
Example 3
The embodiment provides a composition (10) which comprises the following components in parts by weight: 12.5 parts of betaine, 12.5 parts of yam extract, 12.5 parts of chinaroot greenbrier extract, 12.5 parts of lily extract, 15 parts of tributyrin, 10 parts of EGCG, 10 parts of vitamin C and 15 parts of taurine.
Example 4 hyperuricemia mouse model verification
65 male Balb/c mice with the weight of 20-25 g are selected, each 5 male Balb/c mice are divided into 13 groups randomly: 1 healthy control group, 1 hyperuricemia model group, 1 drug-taking control group (allopurinol), and 13 composition experimental groups (for effect test of 10 compositions in examples 1 to 3).
The construction method of the mouse model comprises the following steps: after 7 days of adaptive feeding, molding is started. The 5 Balb/c mice in the blank group normally drink water and are filled with 100 mu L of physiological saline; the other groups were fed with normal diet and drinking water, 300 mg/(kg/d) of potassium oxyzinate and 200 mg/(kg/d) of adenine were fed with normal diet and drinking water each day, after molding for 1 hour, the healthy control group and the hyperuricemia model group were fed with normal saline, the drug control group was fed with normal allopurinol 20mg/kg/d, and the 10 experimental groups were fed with composition 1 to composition 10 (preparation method of the drug: dissolving composition with normal saline in an amount of 40 mg/kg/d), and the administration was continued for 7 days.
Mice were sacrificed 1h after dosing on day 7 to remove blood, liver, kidneys, intestines and joints. Serum uric acid, XOD activity, ABCG2 expression level, URAT1 expression level, na+ -k+ pumping activity were detected.
Wherein, 1) the method for detecting serum uric acid comprises the following steps:
measuring blood uric acid by using Uric Acid (UA) colorimetric test boxes (purchased from Wuhan Yilai Rui biotechnology Co., ltd., product number E-BC-K016-M), taking 25 mu L of standard substances with different concentrations, and adding the standard substances into corresponding standard tubes; 25. Mu.L of the sample to be measured was taken and added to the corresponding measuring tube. 250 μl of reagent II was added to each well, vortexed and mixed for 3s, left stand for 5min, centrifuged for 5min with 2000g, and the supernatant was taken. 160. Mu.L of the supernatant was placed in the wells of the corresponding enzyme-labeled plate, and 50. Mu.L of the third reagent and 50. Mu.L of the fourth reagent were sequentially added to each well. And (3) vibrating the plate for 10 seconds by using an enzyme label instrument, standing for 15 minutes at room temperature, and measuring the OD value of each hole at 690nm of the enzyme label instrument.
2) The method for detecting the XOD activity comprises the following steps:
blood and liver XOD xanthine oxidase activity was detected using a Xanthine Oxidase (XOD) activity detection kit (available from beijing solebao technologies, inc., cat No. BC 1095), liver sample treatment protocol: weighing about 0.1g liver, adding 1ml of reagent I, homogenizing in ice bath, centrifuging at 4deg.C for 10min at 8000g, collecting supernatant, and placing on ice to be tested; plasma sample processing mode: and (5) directly detecting. Preheating a spectrophotometer or an enzyme-labeled instrument for more than 30min, adjusting the wavelength to 530nm, and zeroing the spectrophotometer by distilled water. Dilution of standard solution: the standard solution was diluted with distilled water to 0.25. Mu. MoL/mL (25. Mu.L, 10. Mu. MoL/mL sodium nitrite and 975. Mu.L distilled water may be pipetted and mixed). The procedure is as described in the kit and the absorbance at 530nm is determined.
3) The method for detecting the expression quantity of the ABCG2 and the URAT1 comprises the following steps:
extracting total RNA of a tissue sample, measuring the concentration and purity of the total RNA by adopting an ultra-micro ultraviolet/visible spectrophotometer, and adopting an OD260/OD280 as an assessment method of RNA purity, wherein the purity of the sample RNA is kept between 1.8 and 2.0. Reverse transcription to cDNA, adding 60 μL dH2O to dilute cDNA for standby. The reaction system is as follows: the mass of 2. Mu.L 5X PrimeScript RT master mix,RNA was kept at 5 to 10ng, and 10. Mu.L was supplemented with ddH 2O. Reaction conditions: 37 ℃ for 30min;85 ℃ for 5min;4 ℃ for 30min. Real-time fluorescent quantitative polymerase chain reaction (RT-PCR) detects the expression level of ABCG2 and URAT1 and the expression level of housekeeping gene GAPDH. The RT-PCR test was repeated 3 times for each sample, and the average value was taken as the expression level of the sample gene. The ratio of ABCG2/GAPDH and URAT1/GAPDH was used as the relative expression level of the sample genes.
4) The method for detecting Na+ -K+ pump activity comprises the following steps:
the bursa was rinsed with pre-chilled PBS (10 mm, ph=7.4) to remove residual blood. The bursa and PBS were added to a glass homogenizer and thoroughly ground on ice. For further tissue cell lysis, the homogenate may be sonicated, or repeatedly freeze-thawed, and finally centrifuged at 5000g for 5-10 min, and the supernatant is taken for detection. Taking out the required strips from the aluminum foil bags after balancing at room temperature for 20min, and sealing the rest strips by using a self-sealing bag and returning to 4 ℃. Setting a standard substance hole and a sample hole, wherein 50 mu L of standard substances with different concentrations are respectively added into the standard substance hole, 50 mu L of samples to be detected are added into the sample hole, and blank holes are not added. In addition to the blank wells, 100. Mu.L of horseradish peroxidase (HRP) -labeled detection antibody was added to each of the standard wells and sample wells, and the reaction wells were sealed by a sealing plate and incubated for 60min in a 37℃water bath or incubator. Removing liquid, beating to dry on absorbent paper, filling washing liquid (350 mu L) in each hole, standing for 1min, throwing off the washing liquid, beating to dry on absorbent paper, and repeating the plate washing for 5 times. Substrate A, B was added 50. Mu.L each to each well and incubated at 37℃for 15min in the absence of light. The OD of each well was measured at a wavelength of 450nm by adding 50. Mu.L of stop solution to each well for 15min.
The detection statistics of the relevant indexes are shown in fig. 1 to 6, and it can be seen that:
a) The betaine and the yam extract, the betaine and the chinaroot greenbrier extract, and the yam extract and the chinaroot greenbrier extract can mutually enhance the uric acid reducing capability between the two extracts, namely, the uric acid reducing capability of the combination of the betaine, the yam extract and the chinaroot greenbrier extract is stronger than the superposition effect of the uric acid reducing effects of any one component. The compositions 4-8 mainly inhibit the XOD activity of liver and intestinal canal, inhibit the kidney from reabsorption uric acid transporter URAT1, promote the expression of intestinal canal secretion uric acid transporter ABCG2, reduce the synthesis of uric acid, increase the intestinal canal and kidney excretion capacity of uric acid, and further reduce blood uric acid.
b) The blood uric acid reduction amounts of the composition 7 and the composition 8 are not significantly different, which indicates that the lily extract does not significantly enhance the uric acid reduction effect of the combination of betaine, yam extract and smilax extract.
c) Composition 9 has significant uric acid lowering effect.
d) Composition 10 has an efficacy of uric acid lowering that is superior to compositions 8 and 9.
e) The composition can improve the expression of the bursa uric acid transporter ABCG2 and enhance the activity of Na+ -K+ pump to different degrees, and has the potential of promoting the dissolution of urate crystals deposited in joints.
Example 5 acute gout rat model validation
100 male SD rats with the age of 5 weeks and weight of 90-110 g are selected, wherein each 5 male SD rats are divided into 13 groups randomly: 1 healthy control group, 1 gout model group, 1 drug administration control group (diclofenac sodium), 10 composition experimental groups (for performing effect test on 10 compositions in examples 1 to 3).
The method of the rat model comprises the following steps: after 7 days of adaptive feeding, molding was started. The health control group and the gout model group are respectively irrigated with 100 mu L of stomach, the drug control group is irrigated with 100 mu L of 120mg/mL of diclofenac sodium, and the composition experimental group is respectively irrigated with 1-10 compositions (the preparation method of the drug comprises the steps of dissolving the composition with physiological saline with the dosage of 40 mg/kg/d), and the pretreatment is carried out continuously for 3 days. After 1h of treatment on day 3, 100. Mu.L of physiological saline was injected into the joints of the footpads of the healthy control group, and 100. Mu.L of monosodium urate crystals (MSU) of 40mg/mL were injected into the footpads of the gout model group, the drug control group, and the composition experimental groups 1 to 17. After 2 days, the footpad thickness was measured, rats were sacrificed and the expression level of the inflammatory factor IL-1 beta was determined.
Statistics of the test results of the thickness of the foot pad and the expression level of the inflammatory factor IL-1 beta are shown in FIG. 7, and can be seen:
a) The test results for compositions 1-7 showed that: betaine, yam extract and chinaroot greenbrier extract and combinations thereof have certain effects of relieving gouty arthritis, but are poor in effect.
b) The test results for composition 8 showed that: the thickness of the rat model foot pad with acute gout shows a remarkable difference after the intervention of the composition 7 and the composition 8, which shows that the lily extract cooperates with the three to show remarkable effect of relieving acute gout, and the main molecular mechanism reduces the expression and secretion of inflammatory factor IL-1 beta.
c) The test results for composition 9 showed that: has obvious effect of relieving acute gout.
d) The test results for composition 10 showed that: composition 10 has a significant effect of alleviating acute gout and is superior to compositions 8 and 9.
EXAMPLE 6 clinical Effect of reducing blood uric acid
40 cases of chronic gouty arthritis patients (the disease history of gout is 3-15 years, the attack frequency is more than or equal to 8 times/year) are collected as subjects (the assigned city people hospitals), the subjects are randomly divided into 4 groups, each group comprises 10 persons, and the intervention modes are as follows: the blood uric acid levels were measured on day 15, 30, 45 before and after the intervention, with the statistics shown in the following table:
dry expected subject blood uric acid changes (mean ± standard deviation)
| Group of | Day 0 (front clothes) | For 15 days | For 30 days | 45 days |
| Control group | 734±47 | 733±33 | 717±45 | 729±38 |
| Composition 8 | 726±28 | 609±42 | 456±52 | 394±29 |
| Composition 9 | 729±45 | 627±34 | 489±29 | 421±52 |
| Composition 10 | 724±34 | 596±33 | 414±19 | 359±24 |
The results show that: composition 8, composition 9 and composition 10 all significantly reduced uric acid, with composition 10 having the strongest uric acid reducing capacity, indicating that there is a potential interaction between the components of composition 8 and composition 9 to enhance uric acid reducing capacity, consistent with animal experimental data. In the above 3 composition intervention groups, the number of patients with blood uric acid below 420. Mu. Mol/L after 45 days of intervention was 9 (90%), 7 (70%), 10 (100%), respectively. Namely: the clinical test results show that the uric acid lowering effect of the composition 10 is optimal.
Meanwhile, the embodiment further collects the gout attack times, the joint pain eliminating time after attack and the joint swelling eliminating time in the dry expectation of the subject, and the statistical results are shown in the following table:
seizure frequency and pain sensation of the subject during intervention, and time to swelling elimination (mean ± standard deviation)
| Group of | Number of gout attacks | Pain sensation eliminating time/h | Swelling elimination time/h |
| ControlGroup of | 2.3±0.7 | 63±13 | 117±15 |
| Composition 8 | 0.8±0.4 | 9±3.6 | 26±7 |
| Composition 9 | 0.1±0.1 | 2±1.3 | 9±2.8 |
| Composition 10 | 0 | 0 | 0 |
The results show that: compared with the control group, the compositions 8, 9 and 10 had significantly improved prognosis, gout flares, joint pain elimination time and joint swelling elimination time. Of these, composition 10 works best, with no symptoms of redness, warmth, swelling of the joints and acute gout flares occurring in the patient during the intervention. It also shows that the components of the composition 8 and the composition 9 have potential mutual enhancement effect of relieving acute gout.
In addition, the present example further extended the clinical intervention time to 120 days for the subjects, and the double-energy CT was used to determine the volume of the joint urate crystals before and after the intervention for 120 days, and the dissolution effect of the urate crystals before and after the intervention was evaluated. Fig. 8 shows a three-dimensional reconstructed picture of dual-energy CT of intra-articular crystals before and after intervention in a portion of a subject.
The results of the changes in volume of urate crystals deposited before and after intervention are statistically shown in the following table:
changes in volume of urate crystals deposited before and after intervention
| Patient(s) | Before intervention (cm) 3 ) | Prognosis of dry (cm) 3 ) | Variation value (cm) 3 ) |
| Control group | 3.78±0.62 | 3.97±0.74 | 0.19±0.23 |
| Composition 8 | 3.67±0.23 | 3.19±0.31 | -0.48±0.28 |
| Composition 9 | 3.84±0.58 | 3.14±0.81 | -0.70±0.21 |
| Composition 10 | 3.96±0.42 | 2.65±0.37 | -1.31±0.41 |
The results show that: dissolution of urate crystals deposited in the joints of 0 (0%) in the non-intervention group subjects, dissolution of urate crystals in the joints of 4 (40%) in the intervention group subjects, dissolution of urate crystals in the joints of 6 (60%) in the intervention group subjects, and dissolution of urate crystals in the joints of 9 (90%) in the intervention group subjects were performed in composition 10.
Example 8 composition 10 reduces the clinical dosage of uric acid lowering drugs and reduces the risk of side effects
There are 4 uric acid lowering drugs that have been marketed in China: allopurinol, febuxostat, benzbromarone, probenecid, which has severe renal toxicity, has been basically marketed today. The clinical application rate is ranked from high to low: febuxostat (about 69-70%) > benzbromarone (about 21-22%) > allopurinol (about 8-10%). Hyperuricemia and gout are chronic metabolic diseases, and need to be taken for a long time or even for a lifetime, and if the patients are treated by only uric acid lowering drugs, the patients can have side effects with different degrees, such as gastrointestinal tract loss, liver and kidney injury, increased death risk and the like.
In the embodiment, the mode that the febuxostat and the benzbromarone which are low-dose uric acid reducing medicines are singly used or respectively combined with the composition 10 is adopted to verify whether the composition 10 can reduce the dosage of the uric acid reducing medicines.
40 cases of chronic gouty arthritis patients (the disease history of gout is 3-15 years, the attack frequency is more than or equal to 8 times/year) are recruited as subjects (entrusted to the civilian hospitals of the Weifang), and the subjects are randomly divided into 4 groups of 10 persons each, wherein the subjects are respectively: 40mg febuxostat intervention group, 50mg benzbromarone intervention group, 20mg febuxostat+10 g composition 10 intervention group and 25mg benzbromarone+10 g composition 10 intervention group. The intervention period was 30 days and changes in blood uric acid during the intervention were observed.
The results are shown in the following table:
clinical effects of small doses of drug alone or in combination with composition 10
The results show that: after 15 days and 30 days of intervention, the clinical uric acid reducing effects of the 20mg febuxostat+10 g composition 10 intervention group and the 25mg benzbromarone+10 g composition 10 intervention group are respectively stronger than those of 40mg febuxostat and 50mg benzbromarone, namely the composition 10 can obviously reduce the clinical dosage of uric acid reducing medicines.
Moreover, during clinical intervention, the number of people who had developed symptoms of acute gout flares or joint redness, swelling, in the 40mg febuxostat intervention group, the 50mg benzbromarone intervention group, the 20mg febuxostat+10 g composition 10 intervention group and the 25mg benzbromarone+10 g composition 10 intervention group were 4 people (40%), 3 people (30%), 0 people (0%), respectively, i.e., composition 10 could reduce the risk of gout flares during drug uric acid lowering treatment.
It should be noted that the above examples are only for further illustrating and describing the technical solution of the present invention, and are not intended to limit the technical solution of the present invention, and the method of the present invention is only a preferred embodiment and is not intended to limit the scope of the present invention. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (10)
1. A composition for specifically dissolving urate crystals in joints, wherein the composition is at least two selected from betaine, yam extract and chinaroot greenbrier extract.
2. The composition for specifically dissolving urate crystals in joints according to claim 1, wherein the weight ratio of betaine to yam extract in the composition is (1-5): 1-5.
3. A composition for the specific dissolution of crystals of urate in a joint according to claim 1, wherein the weight ratio of betaine to smilax extract in the composition is (1-6): 1-6.
4. A composition for specifically dissolving intra-articular urate crystals according to claim 1, wherein the weight ratio of the yam extract to the chinaroot greenbrier extract in the composition is (1-10): 1-10.
5. The composition for specifically dissolving intra-articular urate crystals according to claim 1, wherein the composition further comprises a lily extract.
6. A composition for specifically dissolving intra-articular urate crystals according to anyone of claims 1 to 5, characterized in that it further comprises tributyrin.
7. The composition for specifically dissolving intra-articular urate crystals according to claim 6, wherein the composition further comprises at least one of EGCG, vitamin C, taurine.
8. A composition for specifically dissolving intra-articular urate crystals according to anyone of claims 1 to 5, characterized in that it further comprises uric acid lowering agents and/or adjuvants.
9. The composition for specifically dissolving intra-articular urate crystals according to anyone of claims 1 to 5, wherein the uric acid lowering drug is selected from at least one of allopurinol, febuxostat, benzbromarone, probenecid.
10. A preparation for specifically dissolving intra-articular urate crystals, characterized in that it is prepared using the composition for specifically dissolving intra-articular urate crystals according to anyone of claims 1 to 9.
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