CN104000878A - Composition for treating hyperuricemia and application thereof - Google Patents
Composition for treating hyperuricemia and application thereof Download PDFInfo
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- CN104000878A CN104000878A CN201410238113.5A CN201410238113A CN104000878A CN 104000878 A CN104000878 A CN 104000878A CN 201410238113 A CN201410238113 A CN 201410238113A CN 104000878 A CN104000878 A CN 104000878A
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Abstract
The invention belongs to the technical field of medicine preparation, and particularly relates to a composition for treating hyperuricemia and an application thereof. The composition for treating hyperuricemia is characterized by comprising a sky-fruit extractive. The composition comprises 10-20 parts of dark plum, 50-70 parts of polygonum cuspidatum, 12-35 parts of rhizoma atractylodis, 100-120 parts of sky fruit, 26-40 parts of purple grapes, 55-80 parts of waxgourd seeds and 10-20 parts of kelp sprout. The composition is suitable for treatment of hyperuricemia or gout or uric acid nephropathy, particularly treatment of gout and hyperuricemia. The composition for treating hyperuricemia has the beneficial effects that 1. experiments prove that the composition has a relatively good uric acid reduction effect; and 2. by adopting compatibility of traditional Chinese medicines, the composition is capable of improving immunity of organisms while treating the hyperuricemia and has no toxic or side effects.
Description
Technical field
The invention belongs to pharmaceutical technology field, in particular to a kind of compositions and application thereof for the treatment of hyperuricemia.
Background technology
Xiang Tianguo (formal name used at school Fructus Swietenia Macrophylla), belongs to Meliaceae plant, has another name called Fructus Fici Beecheyanae, Solomon Islands, the South Pacific Ocean is originated in source, to high approximately 30 meters to 40 meters of sky fruit tree, because its fruit is gained the name to sky growth, must be through the harvest of 15 years growth ability results; Be described as to sky fruit " after plant ", owing to lacking scientific research and the refine of modern science, the value containing to sky fruit for many years is not all developed and is extensively utilized unfortunately.
Contribute to regulate the homeostasis between the each organ of human body to sky fruit; ensure the normal activity of each cell; promote the blood flow of microcirculqtory system; improve human body immunity; guarantee that the operation of human organ function of organization is sound; can promote blood circulation and prevent from angiemphraxis from can helping prevention of cardiac and apoplexy.To treatment diabetes, hypertension, anaphylactic disease, endocrine disturbance etc. have effect of highly significant;
Gout is the metabolic disease that long-term purine metabolism obstacle, hyperuricemia cause; Hyperuricemia is the important biochemical basis of gout, also become the risk factor of numerous disease simultaneously, as hyperuricemia not only can be brought out gouty arthritis, urinary calculus, urate nephropathy, and also the disease such as serum uric acid level rising and abnormalities of sugar/lipid metabolism, obesity is closely related.
In recent years along with the change of people life style, the prevalence of hyperuricemia and gout is ascendant trend gradually, is mainly in male, and has the tendency of rejuvenation, has become city crowd's a kind of commonly encountered diseases, frequently-occurring disease.Hyperuricemia and gout usually with other metabolic diseases as the diseases such as hypertension, coronary heart disease, diabetes occur simultaneously, bring serious harm to human health.Studies show that, hyperuricemia is atherosclerotic risk factor, and the occur together case fatality rate of Patients with Hyperuricemia of cardiovascular and cerebrovascular disease is in rising trend.
On clinical treatment, reduce absorbing again of uric acid, increase the excretion of urine uric acid, be one of effective ways that effectively reduce in gout and hyperuricemia therapeutic process serum Uric Acid Concentration.In people's kidney, the heavy absorption process of uric acid mainly depends on the special transport protein on film, i.e. uric acid transporter body 1 (Urate Transporter 1, URAT1).URAT1 is a kind of uric acid-anion exchanger, is responsible for the heavily absorption of glomerular filtration 90% uric acid in proximal convoluted tubule.
At present, in clinical conventional gout treatment medicine, benzbromarone is best to the inhibition of URAT1, but because its side effect is more, numerous external pharmacy corporations are attached great importance to and are found new URAT1 inhibitor and dropped into a large amount of manpower and materials, wish therefrom to find better effects if side effect new hyperuricemia medicine still less.
Therefore,, in the urgent need to the combination of a kind of plant amedica, under the prerequisite of insulting physiological function not, can effectively treat the symptom such as hyperuricemia and gout.
Summary of the invention
For solving the problems of the technologies described above, the invention provides a kind of compositions and application thereof for the treatment of hyperuricemia.
A compositions for the treatment of hyperuricemia, is characterized in that, comprises to sky berry extract.
Wherein, described compositions is by Fructus Mume, Rhizoma Polygoni Cuspidati, Rhizoma Atractylodis, Xiang Tianguo, purple grape, Semen Benincasae, Thallus Laminariae (Thallus Eckloniae) bud composition, wherein, described Fructus Mume is 10-20 part, and Rhizoma Polygoni Cuspidati is 50-70 part, and Rhizoma Atractylodis are 12-35 part, Xiang Tianguo is 100-120 part, purple grape is 26-40 part, and Semen Benincasae is 55-80 part, and Thallus Laminariae (Thallus Eckloniae) bud is 10-20 part.
Wherein, described Fructus Mume is 15-18 part, and Rhizoma Polygoni Cuspidati is 60-68 part, and Rhizoma Atractylodis are 15-32 part, and Xiang Tianguo is 110-118 part, and purple grape is 30-38 part, and Semen Benincasae is 65-77 part, and Thallus Laminariae (Thallus Eckloniae) bud is 15-18 part.
Wherein, comprise pharmaceutically acceptable carrier composition.
Wherein, it is characterized in that oral formulations can be tablet, capsule, pill, granule, drop pill, soft capsule, suspension, solution, syrup, nano-emulsion, liposome.
Of the present inventionly be applicable to hyperuricemia or gout or urate nephropathy to sky berry extract, be specially adapted to treat gout and hyperuricemia.
Pharmaceutical composition of the present invention is applicable to hyperuricemia or gout or urate nephropathy, is specially adapted to treat gout and hyperuricemia.
Process for preparing medicine of the present invention is: to sky berry extract preparation method: will pulverize to sky fruits, cross 20 mesh sieves, add the water of 10 times of quality, be to extract 3-5 hour between 60-70 DEG C in temperature, obtain extracting solution centrifugal, after remove impurity, below temperature 70 C, be concentrated into and the quality such as raw material, obtain to sky berry extract.
The preparation method of compositions: aforesaid raw material is mixed by corresponding weight proportion, first clean remove impurity with clear water, the warm water soaking 1-3h of 30-50 DEG C of quality such as then used, then, add raw material weight 3-5 water doubly, extract 3-5 time at 75-90 DEG C, after cold filtration, 65 DEG C of following concentrated becoming and the flowing soaking paste of the quality such as raw material, shake up sealing, preserve as for shady and cool ventilation place.Above-mentioned extractum can directly be done medicinal, also can be used for as animal uric acid resisting model test.
A kind of compositions for the treatment of hyperuricemia of the present invention is a pure plant extracts of developing for hyperuricemia and gout crowd, include the multiple natural alkaline soil plants such as Fructus Mume, Semen Benincasae, green Sargassum, Thallus Laminariae (Thallus Eckloniae) bud, purple grape, after edible, its concentrated plant essence including can generate alkaloid in body metabolism, improve the uric acid metabolism in human body fluid, by urinating and the metabolism such as defecation excretes harmful substance, make that you are dynamic, health is more healthy.
In prescription, organic acid and the volatile oil such as Fructus Mume contains citric acid, malic acid, can help to clean blood, makes blood flow momentum normalization, gets rid of excessive acid element; Rhizoma Polygoni Cuspidati, containing anthraquinone analog compound, has and dispels the wind, dampness removing, removing blood stasis with potent drugs, the effect of stimulating the menstrual flow.Rhizoma Atractylodis have drying damp and strengthening spleen, and effect of wind-damp dispelling, protects the liver capable of regulating gastrointestinal motility function, antiulcer.Main effective ingredient is the volatile oil taking sagittol and hinesol as representative.Contain saponin, contain the necessary nutrition of the human bodies such as flavone, isoflavone and multiple native protein, vitamin A, B1, B3, B6, D, E and folic acid, ferrum, potassium to sky fruit to sky fruit, and ratio is suitable, there is the blood circulation of improvement, purify the blood, adjust and mend and promote the effects such as immunity.The flavonoid containing in purple grape is a kind of powerful antioxidant, can remove interior free yl, can anhydrate swollen, and tonneau urine; Semen Benincasae is the seed of Vegetables Fructus Benincasae, is rich in natural plant grease and mineral, and the material such as Saponin, has good diuresis, and modern pharmacology proves that Semen Benincasae can also enhancing human body immunity power; Thallus Laminariae (Thallus Eckloniae) bud Thallus Laminariae (Thallus Eckloniae) bud contains a large amount of mineral, vitamin, cellulose, calcium, potassium, iodine, and the alginic acid containing can excrete in conjunction with sodium unnecessary in small intestinal, helps the hypertension of releiving; Containing in addition fucosterol can excrete unnecessary cholesterol.
Beneficial effect of the present invention is: 1, checking by experiment, and compositions has good uric acid resisting effect; 2, adopt the method for drug matching, make, in treatment hyperuricemia, to improve the immunity of body, have no side effect.
Detailed description of the invention
Below in conjunction with specific embodiment, the present invention is described in further detail, the embodiment providing is only in order to illustrate the present invention, instead of in order to limit the scope of the invention.
Experimental technique in following embodiment, if no special instructions, is conventional method.Test material used in following embodiment, if no special instructions, is and purchases available from routine biochemistry reagent shop.
embodiment 1:
In the present embodiment, proved by experiment aspect treatment hyperuricemia, to there is good effect to sky berry extract.
materials and methods
1.1 test compounds
Title: to sky berry extract
1.2 preparations to sky berry extract solution
To sky berry extract preparation method: will pulverize to sky fruits 500g, and cross 20 mesh sieves, and add the water of 10 times of quality, be between 65 DEG C, to extract 4 hours in temperature, obtain extracting solution centrifugal, after remove impurity, below temperature 70 C, be concentrated into and the quality such as raw material, obtain to sky berry extract.
First, will be dissolved in 4055 μ L DPBS to sky berry extract 81.1mg, vortex 1min, ultrasonic 10min, the centrifugal 5min of 10000rpm, obtains the mother solution that concentration is 20mg/mL.Then dilute mother solution with DPBS, contain 0.06,0.2 to ultimate density respectively, 0.6,2,6,20 mg/mL to sky berry extract solution.
detection system
1.3.1 material
A. people's transport of drug body URAT1 stable gene is expressed HEK293 cell: Human Embryonic Kidney 293 cells(HEK293 cells) be the specific cells system that comes from the human embryonic kidney cell who grows in tissue culture.Express this cell of pcDNA3.1 carrier transfection to have inserted the mammal of people's transport of drug body URAT1 gene, and with geneticin screening patience cell, and then acquisition surface of cell membrane uric acid transporter body is stablized the cell strain of high expressed.
B. culture medium
The DMEM in high glucose culture medium (Lot No.NYM1045, Hyclone) that contains 10% hyclone (Lot No.1227693, Invitrogen ' s Gibco) is for the cell culture of this research.
C. pancreatin
0.25%?Trypsin-EDTA（1×）（Lot?No.1155732,?Invitrogen’s?Gibco）
D. radiolabeled probe's substrate
Uric?acid,?[8-14C]-?(Lot?No.?742-107-0578-B-20121130-SBA,?Moravek)
Glucose?D,?[14C（U）]-?(Lot?No.?120319,?ARC)
E. buffer solution
Dulbecco’s?Phosphate?Buffered?Saline,?DPBS(Lot?No.?070M8306,?Sigma-Aldrich)
1.3.2 experimental procedure
A. HEK293 monolayer cell culture
After trypsinization, transport of drug body URAT1 gene expression cell and transport of drug body SGLT2 gene expression cell are inoculated in the coated 24 hole culture plates (Lot No. 20130801, CHI SCIENTIFIC) of lysine, and cell inoculum density is 10
5cells/well cultivates 2 days in 37 DEG C, the incubator of 5% CO2, saturated humidity.
B. radiolabeled probe's concentration of substrate
Preparation concentration is the Uric acid of 60 μ M, [8-
14c]-, then mix with testing compound equal-volume, making its ultimate density is 30 μ M.
Preparation concentration is the Glucose D of 60 μ M, [
14c(U)], then mix with testing compound equal-volume, making its ultimate density is 30 μ M.
C. nonlabelled compound concentration
Various testing samples (2 × final concentration), and with 60 μ M radioactive label Uric acid, [8-
14c]-and the Glucose D of 60 μ M, [
14c(U)] equal-volume mixes.To the ultimate density of sky berry extract be 0.03,0.1,0.3,1,3,10mg/mL.
D. cellular uptake test
First remove culture fluid in culture plate, DPBS for cultured cell is cleaned to twice, and temperature is bathed 10min in 37 ° of C DPBS buffer, then start containing radiolabeled probe substrate solution displacement DPBS with 500 μ L to take in the cell of medicine; After 2min, by ice bath DPBS buffer cessation reaction, and clean 3 times; Then 500 μ l 0.1mol/L NaOH cell lysis are added in each hole; Extract lysate in scintillation vial, add the scintillation solution (Aquasol-2) of 3mL, and by the radioactive intensity in Tri-Carb 2910TR liquid scintillation instrument (PerkinElmer, Waltham, USA) working sample.In cellular uptake test, each concentration repeats 3 times (n=3).
interpretation of result
1.4.1 inhibitory action
Will be not defined as 100%(control containing the absorption activity of nonradioactive labeling's probe substrate and the radiolabeled probe substrate of testing compound thing), as the percent absorption under the various compound existence conditions of criterion calculation.
statistical method
Microsoft Excel 2010 computed in software for Mean ± standard error (SD).Each numerical value represents the meansigma methods of two measured values of an experiment.GraphPad Prism 5.0 softwares are used for drawing nonlinear regression curve chart, and the IC of computerized compound on the impact of transport of drug body transport activity
50.
result
To sky berry extract, uric acid transporter body (hURAT1) is mediated
14the impact of C-URIC ACID transport activity, in table 1, is not added under inhibitor condition hURAT1 couple
14the absorption ratio of C-URIC ACID is defined as 100%(control).Variable concentrations, to the interpolation of sky berry extract, mediates hURAT1
14c-URIC ACID takes in ratio and obviously declines with the increase of concentration, and has significant significant difference.
To sky berry extract, uric acid transporter body (hURAT1) is mediated
14c-URIC ACID transport activity affects nonlinear regression curve.Transverse axis is the logarithm of drug level, and the longitudinal axis is that control takes in active percentage ratio.Each concentration point and curve are good dependency (R
2=0.9827), calculate A2 to uric acid transporter body (hURAT1) mediation by each concentration point
14the inhibitory action IC of C-URIC ACID
50=2.50mg/mL.
conclusion
Result of the test shows, to sky berry extract, the transport activity of hURAT1 is had to good inhibitory action, IC
50value is 2.50mg/mL.
table 1. mediates uric acid transporter body to sky berry extract
14
the impact (n=3) of C-URIC ACID transport activity
embodiment 2:
In the present embodiment, proved that by experiment compositions has good effect aspect treatment hyperuricemia.
The preparation method of compositions: raw material mixes by following weight proportion, and Fructus Mume is 15 grams, and Rhizoma Polygoni Cuspidati is 68 grams, and Rhizoma Atractylodis are 32 grams, and Xiang Tianguo is 118 grams, and purple grape is 30 grams, and Semen Benincasae is 65 grams, and Thallus Laminariae (Thallus Eckloniae) bud is 18 grams.
First clean remove impurity with clear water, the warm water soaking 2h of 40 DEG C of quality such as then used, then, add the water of 4 times of raw material weights, extract 4 times at 82 DEG C, after cold filtration, 65 DEG C of following concentrated becoming and the flowing soaking paste of the quality such as raw material, shake up sealing, the hyperuricemia that obtains medical treatment compositions is preserved as for shady and cool ventilation place.
materials and methods
1.1 test compounds
Title: treatment hyperuricemia compositions
1.2 fall the preparation of urea composition solution
Treatment hyperuricemia compositions extractum is configured to respectively to the solution of ultimate density 10,15,20 mg/mL with distilled water, for administration.
detection system
1.3.1 material
Uric acid detection kit, Bioengineering Research Institute's product is built up in Nanjing, lot number 20130516.
Kunming mouse, SPF, buys in Beijing Vital River Experimental Animals Technology Co., Ltd., credit number SCXK(capital) 2012-0001.
experimental procedure
A, uric acid impact on normal mouse
After mice overnight fasting, by body weight random packet.The clear water and high, normal, basic three the dosage groups for the treatment of hyperuricemia compositions that give various dose, by the compound recipe of different proportioning compositions, administration volume is 20mL/kg.6h after administration, plucks eyeball and gets blood 0.5mL, and room temperature leaves standstill after 1h, and the centrifugal serum of preparing of 3000rpm, gets serum kit measurement uric acid level, adopts the compound recipe of the more different proportionings of method of analysis of variance whether to have synergism.
B, uric acid impact on hyperuricemia model mice
After mice overnight fasting, by body weight random packet.Give the treatment hyperuricemia compositions of various dose.3h after administration, gavage gives hypoxanthine 1000mg/kg, and while subcutaneous injection Oteracil Potassium 300mg/kg, cause hyperuricemia model, after 3h, eyeball is got blood 0.5mL, room temperature leaves standstill after 1h, the centrifugal serum of preparing of 3000rpm, gets serum kit measurement uric acid level, adopts the compound recipe of the more different proportionings of method of analysis of variance whether to have synergism.
interpretation of result
1.4.1 the uric acid impact on normal mouse
Normal mouse gavage is treated hyperuricemia compositions, between administration concentration 10 ~ 20mg/kg, produces obvious anti-uric acid effect, and suppression ratio is up to 58.27%, and three groups of administration groups all have significant difference, the results are shown in Table 2.
table 2. is treated the uric acid impact of hyperuricemia compositions on normal mouse
1.4.2 the uric acid impact on hyperuricemia model mice
Hyperuricemia model mouse stomach is treated to hyperuricemia compositions, between administration concentration 10 ~ 20mg/kg, produce obvious anti-uric acid effect, suppression ratio is up to 56.86%, and three groups of administration groups all have significant difference, the results are shown in Table 3.
table 3. is treated the uric acid impact of hyperuricemia compositions on hyperuricemia model mice
2 results
Treatment hyperuricemia compositions all has significant reducing effect to the uric acid level of normal mouse and hyperuricemia model mice, and the effect suppressing has significant dose relationship, and has significant significant difference.
conclusion
Result of the test shows, treatment hyperuricemia compositions has obvious reducing effect to the uric acid level in animal body, has broad prospects preparing on uric acid resisting medicine.
embodiment 3:
In the present embodiment, prove by experiment to fall urea composition and there is good effect aspect treatment hyperuricemia.
Only be with the difference of embodiment 2:
The preparation method of compositions: raw material mixes by following weight proportion, and Fructus Mume is 10 grams, and Rhizoma Polygoni Cuspidati is 50 grams, and Rhizoma Atractylodis are 35 grams, and Xiang Tianguo is 100 grams, and purple grape is 26 grams, and Semen Benincasae is 80 grams, and Thallus Laminariae (Thallus Eckloniae) bud is 10 grams.
First clean remove impurity with clear water, the warm water soaking 1h of 50 DEG C of quality such as then used, then, add the water of 3 times of raw material weights, extract 5 times at 75 DEG C, after cold filtration, 65 DEG C of following concentrated becoming and the flowing soaking paste of the quality such as raw material, shake up sealing, the hyperuricemia that obtains medical treatment compositions is preserved as for shady and cool ventilation place.
embodiment 4:
In the present embodiment, prove by experiment to fall urea composition and there is good effect aspect treatment hyperuricemia.
Only be with the difference of embodiment 2:
The preparation method of compositions: raw material mixes by following weight proportion, and Fructus Mume is 20 grams, and Rhizoma Polygoni Cuspidati is 70 grams, and Rhizoma Atractylodis are 12 grams, and Xiang Tianguo is 120 grams, and purple grape is 40 grams, and Semen Benincasae is 55 grams, and Thallus Laminariae (Thallus Eckloniae) bud is 20 grams.
First clean remove impurity with clear water, the warm water soaking 3h of 30 DEG C of quality such as then used, then, add the water of 5 times of raw material weights, extract 3 times at 90 DEG C, after cold filtration, 65 DEG C of following concentrated becoming and the flowing soaking paste of the quality such as raw material, shake up sealing, the hyperuricemia that obtains medical treatment compositions is preserved as for shady and cool ventilation place.
Claims (7)
1. a compositions for the treatment of hyperuricemia, is characterized in that, comprises to sky berry extract.
2. the compositions for the treatment of hyperuricemia according to claim 1, is characterized in that, described compositions is by Fructus Mume, Rhizoma Polygoni Cuspidati, Rhizoma Atractylodis, Xiang Tianguo, purple grape, Semen Benincasae, Thallus Laminariae (Thallus Eckloniae) bud composition, wherein, described Fructus Mume is 10-20 part, and Rhizoma Polygoni Cuspidati is 50-70 part, Rhizoma Atractylodis are 12-35 part, and Xiang Tianguo is 100-120 part, and purple grape is 26-40 part, Semen Benincasae is 55-80 part, and Thallus Laminariae (Thallus Eckloniae) bud is 10-20 part.
3. a kind of uric acid resisting compositions according to claim 2, is characterized in that, described Fructus Mume is 15-18 part, Rhizoma Polygoni Cuspidati is 60-68 part, and Rhizoma Atractylodis are 15-32 part, and Xiang Tianguo is 110-118 part, purple grape is 30-38 part, and Semen Benincasae is 65-77 part, and Thallus Laminariae (Thallus Eckloniae) bud is 15-18 part.
4. the compositions for the treatment of hyperuricemia according to claim 2, is characterized in that, comprises pharmaceutically acceptable carrier composition.
5. according to the uric acid resisting compositions described in claim 1-4 any one, it is characterized in that oral formulations can be tablet, capsule, pill, granule, drop pill, soft capsule, suspension, solution, syrup, nano-emulsion, liposome.
A pharmaceutical composition as claimed in claim 1 as effective ingredient the purposes in treatment hyperuricemia or ventilation or urate nephropathy.
A pharmaceutical composition as claimed in claim 2 as effective ingredient the purposes in treatment hyperuricemia or ventilation or urate nephropathy.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105267576A (en) * | 2015-10-09 | 2016-01-27 | 刘谦 | Traditional Chinese medicine composition for treating urate nephropathy |
-
2014
- 2014-05-30 CN CN201410238113.5A patent/CN104000878A/en active Pending
Non-Patent Citations (3)
| Title |
|---|
| GREENTROPICALS: "《http://greentropicals.wordpress.com/2013/06/15/sky-fruit-fructuse-swietenia-macrophylla/》", 15 June 2013 * |
| 刘湘源主编: "《图表式临床风湿病学》", 31 July 2013, 中国医药科技出版社 * |
| 朱成全等主编: "《防治"四高"药膳大全》", 28 February 2014, 中国医药科技出版社 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105267576A (en) * | 2015-10-09 | 2016-01-27 | 刘谦 | Traditional Chinese medicine composition for treating urate nephropathy |
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