CN103599123B - A kind of medicine for the treatment of purine metabolic disorder disease - Google Patents
A kind of medicine for the treatment of purine metabolic disorder disease Download PDFInfo
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Abstract
The present invention relates to a kind of medicine for the treatment of purine metabolic disorder disease, flavone compound and modified derivative thereof shown in formula (I) are provided, for suppressing xanthine oxidase activity and promoting the active purposes of urate excretion, wherein: R
1, R
2, R
3be-H or monosaccharide residue independently of one another; R
4for-H or-OH.Particularly, be used for the treatment of purine metabolic disorder disease, may be used for treatment hyperuricemia and relevant disease, reduction individual serum UA level; Be used for the treatment of hyperuricemia; Be used for the treatment of relevant disease comprise the gout, the arthritis that are used for the treatment of metabolic arthritis and cause and be used for the treatment of the chronic interstitial nephritis, renal calculus etc. that metabolic arthritis causes.Have native chemical structure, safety, low toxicity, curative effect fast, the advantage of few side effects;
Description
Technical field
The present invention relates to technical field of pharmaceuticals, specifically, relate to the application of a kind of flavone compound and modified derivative thereof and be used for the treatment of the medicine of purine metabolic disorder disease.
Background technology
From the epidemic data of European and American developed countries and China, the morbidity of hyperuricemia (HUA) is in the trend risen year by year.Along with the raising of people's living standard, dietary structure tends to high fat, high protein aspect changes.In China, not only there is the situation improved with living standard raising in the morbidity of hyperuricemia, and the morbidity of hyperuricemia is in the trend of becoming younger.
Hyperuricemia refers to that the generation of the serum uric acid (UA) that human body causes due to purine metabolic disturbance increases and (or) drains a kind of disease reduced.Under normal purine diet state, non-twice horizontal male of Diagnostic Value of Fasting Serum UA is higher than 420mmol/L on the same day, and women, higher than 360mmol/L, is namely called hyperuricemia.UA depends on the formation speed of UA and the equilibrium relation of drainage rate in the concentration of extracellular fluid.Though UA generates to increase or drain to reduce or drain not subtract but generate exceed excretion, UA all can be made to accumulate and occur hyperuricemia.Gout is the crystal dependency arthrosis caused by a kind of monosodium urate salt (MSU) deposition, with purine metabolic disturbance and (or) to drain the hyperuricemia caused by reducing directly related for UA, belongs to metabolic rheumatic disorder category.It is the most important biochemical basis of gout generation and the most direct risk factor that serum UA raises.
Hyperuricemia is not only the important biochemical basis causing gout, and closely related with the generation of hypertension, hyperlipemia, atherosclerosis, obesity, insulin resistant.
When Patients with Hyperuricemia is in high UA state for a long time, UA salt-pepper noise will in tissue and organ deposition.The gouty arthritis recurrent exerbation that its clinical manifestation is hyperuricemia and causes therefrom, tophaceous deposition, tophus chronic arthritis and joint deformity, kidney urate calculus and (or) gouty excess of the kidney matter pathological changes, and above-mentioned pathological changes can exist alone or in combination.But hyperuricemia can not be equal to gout, the two is not only had any different but also be related, two different phases regarded as with hyperuricemia and gout in disease progression, strict boundary can be there is no between the two.
From clinical drug treatment requirement, the major requirement of control primary disease reaches following object: stop acute arthritis outbreak as early as possible; Prevent arthritis from recurring; Correct hyperuricemia, the disease that control UA mineralization is caused in kidney, joint etc.; Prevent uric acid kidney stones from being formed.Make a general survey of both at home and abroad, the medicine of current clinical treatment has Western medicine and Chinese medicine.Western medicine mainly contains the medicine such as colchicine, Tai Song or crovaril, indometacin, ibuprofen, piroxicam, naproxen, prednisone, benemid, sulphinpyrazone, benzbromarone, allopurinol, but all with more side effect.Chinese medicine aspect mainly contains gout relaxing tablet, gout stator, pain relieving rheumatism ball, TONGFENGDING capsule etc., but from ingredient, substantially all arranged in pairs or groups by medical herbs crude extract such as Semen Coicis, Cortex Phellodendri, Radix Achyranthis Bidentatae, Rhizoma Atractylodis, Rhizoma Smilacis Glabrae, Rhizoma Dioscoreae Septemlobae, Radix Stephaniae Tetrandrae, Semen Plantaginis, Rhizoma Alismatis, Caulis Lonicerae, Radix Paeoniae Rubra, Radix Clematidis, Radix Angelicae Sinensis, Radix Gentianae Macrophyllae, Poria, Pheretima, Fructus Chaenomelis, Radix Glycyrrhizaes and form.From curative effect, Chinese Herbs do not have Western medicine curative effect fast, the course for the treatment of is longer.
So, it is active and promote the flavone compound of uric acid (UA) Excretion and the application of modified derivative thereof that research has suppression xanthine oxidase (XOD), and exploitation have natural exist structure, safety, low toxicity, curative effect fast, the medicine of the treatment hyperuricemia of few side effects is significant.
Summary of the invention
The object of the invention is for the problems referred to above, provide a kind of have suppress xanthine oxidase activity and promote the flavone compound of urate excretion effect and the application of modified derivative thereof and have native chemical structure, safety, low toxicity, curative effect fast, the medicine being used for the treatment of purine metabolic disorder disease of few side effects.
The present invention, provides and has the flavone compound shown in structural formula (I) and modified derivative thereof and be used at suppression xanthine oxidase activity and promote the active purposes of urate excretion;
（I）
Wherein: R
1, R
2, R
3be-H or monosaccharide residue independently of one another; R
4for-H or-OH; Dotted line represents have or do not have double bond.
The present invention, provides and has the flavone compound shown in structural formula (I-a) and modified derivative thereof and be used at suppression xanthine oxidase activity and promote the active purposes of urate excretion; It is singly-bound between C2-C3; Described R
1for-H or rhamnose (Rha) residue, R
2, R
3be-H, R independently of one another
4for-H or-OH;
（I-a）；
More specifically, select the astilbin of following structural formula (I-1), the naringenin of following structural formula (I-2):
（I-1），
（I-2）。
The present invention, provides and has the flavone compound shown in structural formula (I-b) and modified derivative thereof and be used at suppression xanthine oxidase activity and promote the active purposes of urate excretion; It is double bond between C2-C3; Described R
1, R
4be-H, R independently of one another
2for glucose (Glc) residue, R
3for-H or xylose (Xyl) residue;
（I-b）；
More specifically, select the Schaftoside of following structural formula (I-3), the Saponaretin of following structural formula (I-4):
（I-3），
（I-4）。
The present invention, the pharmaceutical composition of the activated structural formula of tool (I) and modified derivative thereof, has one or more reactive compounds and pharmaceutically acceptable carrier, is used for the treatment of purine metabolic disorder disease.Particularly, may be used for treatment hyperuricemia and relevant disease, reduction individual serum UA level.Be used for the treatment of hyperuricemia; Be used for the treatment of relevant disease comprise the gout, the arthritis that are used for the treatment of metabolic arthritis and cause and be used for the treatment of the chronic interstitial nephritis, renal calculus etc. that metabolic arthritis causes.
The present invention, treat hyperuricemia and comprise idiopathic hyperuricemia and insecondary hyperuricemia.
The present invention, treat that antihyperuricemic disease includes but not limited to that hyperuricemia causes that gouty acute arthritis recurrent exerbation, tophus are formed, tophaceous arthritis and joint deformity, involve kidney and cause chronic interstitial nephritis and uric acid kidney stones to be formed.
The present invention, when medicine and pharmacology use, can become pharmaceutical composition containing one or more compounds meeting structural formula flavone compound shown in (I) and modified derivative thereof with pharmaceutically acceptable vehicle group; Namely aforementioned pharmaceutical compositions preparation includes but not limited to the preparation that the new technique such as the preparations such as tablet, injection, capsule, pill, syrup, granule, tincture, oral suspensions, Orally taken emulsion, powder and controlled release, liposome, microemulsion, microsphere microcapsule carrier, nanoparticle, Echogenic Microbubbles, microelectron-mechanical drug administration carrier, self-emulsifying drug transmission, mucosal drug delivery, percutaneous dosing, target administration is made.
The preparation that the pharmaceutical composition that the present invention is formed is made may be used for the aspect such as medicine and health product.
The flavone compound shown in structural formula (I) and the modified derivative thereof of meeting provided by the present invention can extract and obtain from natural herbs (as Rhizoma Smilacis Glabrae, Herba Desmodii Styracifolii, Herba Lysimachiae, Rhizoma Alismatis etc.), and suitably semi-synthetic or synthetic method also can be used to obtain.
The present invention, is proved by lot of experiments, and medicine of the present invention is the medicine for the treatment of hyperuricemia with safety, low toxicity.And medicament sources is enriched, low price, not by region, season etc. natural conditions restriction.The preparation no matter preparation is oral administration or drug administration by injection made by medicine of the present invention, has very significant curative effect to treatment hyperuricemia and relevant intercurrent disease, reduction individual serum UA level.
So the present invention, has outstanding substantive distinguishing features and significant good effect.
The present invention, the flavone compound shown in formula (I) and modified derivative thereof have and suppress xanthine oxidase activity and promote urate excretion effect, medicine have native chemical structure, safety, low toxicity, curative effect fast, the advantage of few side effects.
The present invention is further illustrated for embodiment below.
Detailed description of the invention
Be that embodiment is described in further detail content of the present invention with astilbin:
（I-1）。
Embodiment 1: each solvent site of Rhizoma Smilacis Glabrae suppresses the situation of XOD activity
Cleaning Principle: XOD catalysis xanthine generates UA, UA and NBT(NBT) react raw empurpled first and (formazan), after the activity of XOD is suppressed, the UA amount generated reduces, the first of purple and generating also just reduces thereupon, by measure under 560nm generation purple first and absorbance detect the size of inhibit activities.
The preparation of sample: get rhizoma smilacis glabrae medicinal material 100g, coarse crushing, crosses 40 mesh sieves, and with 15 times amount, 10 times amount, 5 times amount 50% ethanol percolate extraction 3 times, merging percolate, is recycled to without alcohol taste, is settled to 250ml with distilled water, be Rhizoma Smilacis Glabrae sample solution.Measure Rhizoma Smilacis Glabrae sample 25ml and be placed in separatory funnel, use petroleum ether, chloroform, ethyl acetate and n-butanol extraction successively, respectively evaporate to dryness, with dmso solution and standardize solution to 25ml, obtain petroleum ether part, chloroform extract, ethyl acetate extract, n-butanol portion and water position sample.
Blank XOD determination of activity: draw in 50mmol/L phosphate buffer 3ml to 10ml volumetric flask, then add 3ml xanthine solution (2.0mmol/L) and 0.4mlNBT(1.8mg/L) respectively, shake up, be XOD determination of activity blank solution.Add 2.5mlXOD solution (0.08U/ml) toward this blank solution again to shake up, be XOD determination of activity solution.Add beginning timing with XOD solution, after 25 DEG C of reaction 30min, be contrast with blank solution under 560nm wavelength, measure XOD absorbance A
0.
Each sample solution measures the inhibitory action of XOD activity: accurate absorption in " preparation of sample " item respectively extracts position Solutions Solution 0.5ml to be measured, respectively be placed in 10ml volumetric flask, obtain sample XOD inhibit activities mensuration blank solution and sample XOD inhibit activities mensuration XOD solution respectively by operation under " blank XOD determination of activity " item.Add beginning timing with XOD solution, after 25 DEG C of reaction 30min, be contrast with blank solution under 560nm wavelength, measure XOD absorbance A
x.
The each solvent site of table 1 Rhizoma Smilacis Glabrae suppresses XOD determination of activity result
The suppression measurement result of XOD activity is as shown in table 1, and suppression order in each position is ethyl acetate extract solution suppression ratio > Rhizoma Smilacis Glabrae sample solution suppression ratio > > water position solution suppression ratio ≈ petroleum ether part solution suppression ratio ≈ n-butanol portion solution suppression ratio ≈ chloroform extract solution suppression ratio.Wherein Rhizoma Smilacis Glabrae sample has stronger inhibitory action to activity, and in each extraction position, ethyl acetate extract is the strongest to the inhibitory action of activity, and exceedes Rhizoma Smilacis Glabrae sample.Ethyl acetate extract suppresses the effect of XOD activity to be better than crude drug, shows to suppress the material base of XOD activity mainly to concentrate in ethyl acetate extract in rhizoma smilacis glabrae medicinal material.Show through flavones content analysis, Rhizoma Smilacis Glabrae flavones ingredient is the effective site suppressing XOD activity.Through mass spectrum and contrast liquid phase analysis, confirm in flavone position the highest containing astilbin, also have a small amount of naringenin, 2-(3,4-hydroxy phenyl in addition) flavone compound such as-3,4-dihydro-2H-1-.alpha.-5:6-benzopyran-3,5,7-triols.
Embodiment 2: the extraction and purification of astilbin in Rhizoma Smilacis Glabrae
Get rhizoma smilacis glabrae medicinal material 100g, coarse crushing, cross 40 mesh sieves, with 15 times amount, 10 times amount, 5 times amount 50% ethanol percolate extraction 3 times, merge percolate, concentrated (30 DEG C, d=1.15-1.20), add 2 times amount 95% ethanol that concentrated liquid is long-pending, stir after producing flocculent deposit and leave standstill 12h in 4 DEG C of refrigerators, centrifugal 30min under 4000r/min condition afterwards.Get supernatant, rotary evaporation removing ethanol.Clean 2 times with appropriate petroleum ether again, dry, add 50% ethanol 500ml and dissolve, adopt polyamide purification via adsorption-based process.Be eluent with water, 10% ethanol, 50% ethanol respectively, collect 50% ethanol elution, concentrated evaporate to dryness, obtains faint yellow material.Through NMR, SM, IR and UV spectrum analysis, this thing is astilbin (3
, , 4
, , 5,7-kaempferol-3-rhamnoside).
Embodiment 3: the impact that hyperuricemia rat blood serum UA and XOD activity is suppressed.
Testing all rats is SD rat, wherein female male half and half.Totally 80, body weight 200-240g.Get rat 80, be divided at random blank group, model group, medicine group and colchicine group totally 4 groups, often organize 20.Except blank group, all the other each group with the modeling of adenine 100mg/kg gavage, continuous one week.5d starts respectively to medicine group and colchicine group gastric infusion astilbin 40mg/kg and colchicine 40mg/kg, continuous 5d.Blank group and the model group isopyknic distilled water of gavage respectively, respectively organizes all by 0.25ml/25g body weight gavage.At experiment 10d, 1h after administration, each treated animal is plucked eyeball and is got blood, measures the activity of UA and XOD in rat blood serum.
Test data with mean standard deviation (
± s) represent, adopt the analysis of SPSS11.5 statistical package, compare between group and use one factor analysis of variance method, significance level is with P < 0.05 and P < 0.01 standard.Following examples adopt identical analytic process.
The impact of table 2 hyperuricemia rat model UA and XOD activity
As can be seen from Table 2, compared with blank group, in model group rats serum, UA level and XOD activity all have and significantly increase (P < 0.01).By contrast model group, the UA level that medicine group and colchicine group are respectively organized and XOD activity all have decline (P < 0.05) in various degree, and the Amplitude Ratio colchicine group of medicine group reduction is large.Above analytic explanation medicine group is conducive to suppressing the activity of XOD and reducing UA level, has positive effect to the treatment of hyperuricemia.
Embodiment 4: to the diuresis of large mouse with renal calculs
Testing all rats is SD rat, wherein female male half and half.Totally 60, body weight 200-240g.60 rats are divided into 3 groups at random: blank group, medicine group and frusemide group, often organize 20.Test is carried out through 1 month modeling Cheng Shihou.After water 12h is can't help in animal fasting, each group rat all presses 30ml/kg lumbar injection with normal saline.Respectively to medicine group and frusemide group gavage astilbin 40mg/kg and frusemide 50mg/kg immediately, administration volume is 20ml/kg, and blank group gives equal-volume distilled water.Compeling rat hypogastric region with hand makes all the other urine drain.Immediately single rat is put in people's metabolic cage.3rd, 6, give the warm water of 50ml/kg25-30 DEG C after 9h respectively again to every rat at every turn.Collect each animal 0-15h urine and voided volume is determined in side.
The different group of table 3 is to the diuresis (unit: ml) of rat Water l oad
As can be seen from Table 3, and blank group compares, and medicine group and matched group all significantly can increase the voided volume (P < 0.05) of rat, be beneficial to the discharge of lithangiuria, and medicine group are more remarkable.
embodiment 5: on the impact of hyperuricemia rat blood serum cholesterol, creatinine, urea nitrogen levels, triglyceride (TG) content.
Testing all rats is SD rat, wherein female male half and half.Totally 80, body weight 200-240g.Get rat 80, be divided at random blank group, model group, medicine group, colchicine group totally 4 groups, often organize 20.Except blank group, all the other each group with the modeling of adenine 100mg/kg gavage, continuous one week.5d starts respectively to medicine group and colchicine group gastric infusion astilbin 40mg/kg and colchicine 40mg/kg, continuous 5d.Blank group and the model group isopyknic distilled water of gavage respectively, respectively organizes all by 0.25ml/25g body weight gavage.At experiment 10d, 1h after administration, each treated animal is plucked eyeball and is got blood, measures rat blood serum cholesterol, creatinine, urea nitrogen levels, content of triglyceride.
As can be seen from Table 4, compared with blank group, no matter model group is cholesterolemia and serum creatinine, or blood urea nitrogen and blood triglyceride, has remarkable increase (P < 0.01); Compared by model group and medicine group, cholesterolemia in medicine group, serum creatinine and blood triglyceride all slightly reduce, and blood urea nitrogen significantly decreases, and also lower than the blood urea nitrogen of blank group, illustrate that medicine causes various Developmental and Metabolic Disorder all to have protective effect to uric acid disease; Can also learn from table 4, colchicine group creatinine numerical value, triglyceride numerical value and blood urea nitrogen numerical value are higher than model group numerical value all in various degree, thus when display takes colchicine for hyperuricemia, relatively large to the damage of renal function.
The impact of table 4 hyperuricemia rat model cholesterol, creatinine, urea nitrogen levels, content of triglyceride
Be that embodiment is described in further detail content of the present invention above with astilbin, but this should be interpreted as that the scope of the above-mentioned theme of the present invention is only limitted to following example.All technology realized based on foregoing of the present invention all belong to scope of the present invention.
Those skilled in the art can use for reference present disclosure, and suitable improving technique parameter realizes.Special needs to be pointed out is, all similar replacements and change are easy to do for a person skilled in the art, and they are all deemed to be included in the present invention.Product of the present invention and application are described by preferred embodiment, related personnel obviously can not depart from content of the present invention, spirit and scope methods and applications as herein described are changed or suitably change with combination, realize and apply the technology of the present invention.
Claims (5)
1. flavone compound and modified derivative thereof are used at suppression xanthine oxidase activity and promote the active purposes of urate excretion; Described flavone compound and modified derivative thereof have the structural formula being selected from lower group:
（I-3），（I-4）。
2. comprise the application in preparation treatment purine metabolic disorder disease of the pharmaceutical composition with structural formula described in claim 1, described pharmaceutical composition by structural formula described in one or both claim 1 composition and pharmaceutically acceptable carrier form.
3. application according to claim 2, described in be applied as and be used for the treatment of hyperuricemia.
4. application according to claim 2, described in be applied as the gout, the arthritis that are used for the treatment of metabolic arthritis and cause.
5. application according to claim 2, described in be applied as the chronic interstitial nephritis, the renal calculus that are used for the treatment of metabolic arthritis and cause.
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| EP3834627A4 (en) * | 2018-08-10 | 2022-05-04 | Suntory Holdings Limited | Composition for promoting uric acid excretion, composition for inhibiting urat1 and composition for lowering blood uric acid level |
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| CN105311011A (en) * | 2014-06-09 | 2016-02-10 | 苏州凯祥生物科技有限公司 | Novel application of benzopyran derivative in preparation of drug for treating hyperuricaemia |
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| CN108404004A (en) * | 2018-04-17 | 2018-08-17 | 江西中医药大学 | A kind of Rhizoma Smilacis Glabrae extract and its preparation method and application |
| CN108619120A (en) * | 2018-07-09 | 2018-10-09 | 广东省微生物研究所（广东省微生物分析检测中心） | Purposes of 2`, the 5`- resacetophenone in the drug for preparing anti-trioxypurine relevant disease |
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| CN115707464A (en) * | 2021-08-19 | 2023-02-21 | 北京大学 | Inhibition of schaftoside on novel coronavirus main protease and medicinal application thereof |
| CN116549537B (en) * | 2023-06-08 | 2024-02-27 | 北京罗诺强施医药技术研发中心有限公司 | Stable compositions and uses thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101804064A (en) * | 2010-04-08 | 2010-08-18 | 成都军区昆明总医院 | Application of dihydroquercetin and glucoside compounds to preparing drug-resistance bacteria medicine |
| CN101879264A (en) * | 2009-05-05 | 2010-11-10 | 戴永青 | Chinese medicinal composition for reducing blood uric acid |
-
2013
- 2013-12-03 CN CN201310645221.XA patent/CN103599123B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101879264A (en) * | 2009-05-05 | 2010-11-10 | 戴永青 | Chinese medicinal composition for reducing blood uric acid |
| CN101804064A (en) * | 2010-04-08 | 2010-08-18 | 成都军区昆明总医院 | Application of dihydroquercetin and glucoside compounds to preparing drug-resistance bacteria medicine |
Non-Patent Citations (1)
| Title |
|---|
| 土茯苓抑制黄嘌呤氧化酶活性的物质基础研究;徐婷婷 等;《中药材》;20120430;第35卷(第4期);582-585 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3834627A4 (en) * | 2018-08-10 | 2022-05-04 | Suntory Holdings Limited | Composition for promoting uric acid excretion, composition for inhibiting urat1 and composition for lowering blood uric acid level |
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