CN101278931A - New medicinal application of myricetin - Google Patents
New medicinal application of myricetin Download PDFInfo
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- CN101278931A CN101278931A CNA2008100507472A CN200810050747A CN101278931A CN 101278931 A CN101278931 A CN 101278931A CN A2008100507472 A CNA2008100507472 A CN A2008100507472A CN 200810050747 A CN200810050747 A CN 200810050747A CN 101278931 A CN101278931 A CN 101278931A
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- ampelopsin
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Abstract
The invention discloses an inhibitor when myricetin is used for xanthine oxidase and is taken as a target. The invention can be used as the anti-gout medicine for the use of prevention and treatment. The medicine can be separately made of the myricetin. The medicine also can be made of myricetin composition. The inhibitor can be prepared into tablet, capsule, granule, injection and suspension.
Description
Technical field
The present invention relates to Chinese medicine extraction single component ampelopsin, have new medical usage through the pharmacological evaluation proof.Ampelopsin is inhibited to xanthine oxidase specifically, can reduce uricopoiesis, has the effect of prevention and treatment gout.Belong to the field of Chinese medicines.
Background technology
Gout is the commonly encountered diseases that a kind of purine metabolic disturbance causes uric acid to form, and is classified as one of big pertinacious disease of 21 centurys 20 by the United Nations.Up-to-date epidemiological study shows that China's gout sickness rate rises year by year, surpasses the world average level, and traditional anti-gout drugs-uricosureic agent (as probenecid, benzbromarone etc.) often is attended by side effect such as erythra, heating, kidney damage.Xanthine oxidase inhibitor can reduce stress or the injury to organizing that free radical causes, and also can reduce the formation of uric acid in the human body.Discover with the xanthine oxidase to be that the inhibitor of action target spot has good gout effect, be the important drugs of treatment gout and can reduce some fatal gout complication.
Xanthine oxidase inhibitor is as anti-gout drugs, it mainly is the allopurinol of the listing sixties in last century, still it has a lot of side effect though use till today always, use the back patient heating, allergic rash, stomachache, diarrhoea, leukocyte and thrombocytopenia can be arranged, even side effect (progress of xanthine oxidase inhibitor, foreign medical science pharmacy fascicle, 2006 such as liver dysfunction are arranged, 33 (5), 351-353).Therefore, the new xanthine oxidase inhibitor of research has crucial meaning.We find new xanthine oxidase inhibitor-ampelopsin be extraction from the Chinese medicine Caulis seu folium ampelopsis brevipedunculatae (Caulis Ampelopsis Brevipedunculae), separation, purification and single component (patent, a kind of preparation method of ampelopsin and new medical use), ampelopsin (myricetin) is a kind of flavone compound, the pharmacological action of having reported has anticoagulant, ampelopsin that the inductive rabbit platelet of collagen, arachidonic acid and PAF is assembled inhibitory action is arranged, having anti-PAF effect, is a new paf receptor antagonists.The tool antithrombotic, resist myocardial ischemia, microcirculation improvement, blood sugar lowering, antioxidation, hepatoprotective, separate multiple pharmacologically actives such as light ethylism, antitumor, antiinflammatory, mutation, caries prevention, we retrieve the patent (application of ampelopsin in the preparation medicament for restraining uric acid transportor URAT 1, Kong Lingdong etc.) be to promote urate excretion, action target spot is the sub-URAT1 of the transhipment of Reabsorption in the urate excretion process.Up to the present, find to suppress as yet uricopoiesis, be the report of the inhibitor of action target spot with the xanthine oxidase.Produce good gout effect thereby have very strong xanthine oxidase inhibitory action and suppress uricopoiesis, and take for a long time and do not have toxic and side effects, have bright development prospect and economic benefit through pharmacological evaluation proof ampelopsin.
The structure of ampelopsin (myricetin)
Summary of the invention
One of purpose of the present invention is exactly to find the xanthine oxidase inhibitor of the inhibition uricopoiesis of strong (ampelopsin single component) of a kind of effect from natural plants.Reported the extract (progress of the xanthine oxidase inhibitor of resources of Chinese medicinal herb of Caulis seu folium ampelopsis brevipedunculatae (Caulis Ampelopsis Brevipedunculae) stem and leaf, Chinese crude drug, 2006,29 (12), 1386-1389) has the effect of stronger inhibition xanthine oxidase, main component is the mixture based on dihydromyricetin in this extract, do not have clear and definite effective monomer component, according to the structure activity relationship of xanthine oxidase inhibitor: flavanone, flavanone and flavonol do not have the activity of inhibition xanthine oxidase owing to lack the two keys between the C2-C3; So dihydromyricetin does not have this activity, main active component is an ampelopsin, so we are converted into ampelopsin through new extracting method with dihydromyricetin, has carried out deep activity research then.
Goal of the invention two with single component ampelopsin preparation become good effect, toxicity is little, can prevent and treat the medicine of gout, and be provided for clinical preparation.
The invention provides the pharmaceutical preparation of ampelopsin, comprising tablet, capsule, granule, oral liquid, injection, drop pill etc.
But its spy is preferably contained ampelopsin and the pharmaceutical excipient of 99%-1% or the medicine of other prescription of 1%-99%.But preferably contain ampelopsin and the pharmaceutical excipient of 70%-20% or the medicine of other prescription of 30%-80%, but preferably select ampelopsin and the excipient of 40%-30% or the medicine of other prescription that contains 60%-70% for use.The medicine that other compatibility in the medicine is used, the ampelopsin that refers to effective dose is certain medicine material, again compatibility other allowed the Chinese medicine or the chemical drugs that share.
Wherein pharmaceutical excipient comprises filler, disintegrating agent etc.Described filler is selected from starch, lactose, microcrystalline Cellulose, dextrin etc.; Described disintegrating agent is selected from carboxymethyl starch sodium, hyprolose, polyvinylpolypyrrolidone; Optional adhesive, wetting agent and the lubricant of adding.
Ampelopsin and pharmaceutical preparation thereof have the effect of diseases such as prevention and treatment gout, and its pharmacological action is confirmed by following pharmacodynamics test example.
1, acute toxicity testing research
Select 20 of white mice for use, 18～20g, male and female half and half.Ampelopsin is mixed with 50% concentration, the oral administration gavage administration, dosage is each 2.0ml/20g, every day 1 time, this irritates stomach amount is maximum volume under the Cmax that can accept of white mice, observes 7d continuously.The result shows that white mice diet, drinking-water and activity etc. are all normal, do not see toxicity, also none mice dying, repeated experiments 1 time. obtain identical result.Anxious poison experiment dose is equivalent to 2000 times of clinical consumption, tentative confirmation this medicine safety non-toxic.
2, long term toxicity test research
Select 80 of healthy white rats for use, be born for 6 weeks, male and female half and half are equally divided into 4 groups, 20 every group.Wherein 3 groups of oral administration gavages give ampelopsin, and dosage is respectively 2,1,0.5g/kg, and every day 1 time, continuous 3 months, another group gave suitable distilled water by above-mentioned heavy dose and compares, and observes every day such as its active situation and behavior variation etc., weighs weekly 1 time; After 3 months, every group is stayed 4 rats (after 1 week of drug withdrawal, remake following alkali and look into), and all the other are put to death entirely, gets blood and send alkali numeration of leukocyte, hemoglobinometry regulating liver-QI kidney function test, and its each internal organs naked eyes of anatomic observation and histology change.Experimental result shows that ampelopsin does not have obvious influence to rat activity and behavior; Rat body weight, surrounding hemogram and hepatic and renal function all there is not obviously influence yet.The result of histopathologic examination shows that no pathology change.Do not see obvious malicious secondary answering so take for a long time, further confirmed the safety non-toxic of this medicine.
3, ampelopsin is to the influence of mice blood uric acid
Get 60 male mices, be divided into 6 groups (normal control group, model group, the high, medium and low dosage group of ampelopsin, allopurinol groups) at random, 10 every group.All irritate stomach by 0.1mL10g every day.Behind the 6d, except that the normal control group, other 5 groups of mices are lumbar injection 10% xanthine 0.1mL10g respectively, gets blood behind the 30min and surveys the hematuria acid number.
Table 1 ampelopsin is to the influence of mice blood uric acid (equal n=10, X ± S)
Compare in twos through variance analysis, model group compares with blank group: △ P＜0.01; Ampelopsin group, allopurinol group and model group compare: ampelopsin group height, middle dosage, allopurinol group * P＜0.05.
Model group blood uric acid content is significantly higher than the normal control group, difference significance (P＜0.01), and medication group and model group be blood uric acid content difference highly significant relatively, all is lower than model group (P＜0.01 or P＜0.05); Significantly reduce with the normal control group, and there were significant differences.The mechanism that further specifies ampelopsin reduction blood uric acid content is the same with allopurinol, is to reduce uricopoiesis.Alleviate its infringement, thereby effectively control the gout outbreak tissue.
4, ampelopsin is to the influence of mice chondrus ocellatus Holmes colloidality foot swelling
Get 50 of mices, be divided into 5 groups by body weight, press gastric infusion every day of dosage shown in the table 4 once, administration is 7 days altogether, 30min after the last administration, only inject 1% carrageenin 0.03ml/ down in the right back vola aponeurosis (aponeuroses) of mice, behind the 6h dislocation of mice cervical vertebra is put to death behind the Yu Zhiyan, cut the bilateral metapedes, weigh respectively, ask the poor of left and right heavy sensation in the foot amount, be the swelling degree.The result shows: ampelopsin can obviously suppress the mice foot swelling that carrageenin causes, and high, there were significant differences for middle dosage group.See Table 2.
Table 2 ampelopsin is to the influence of mice chondrus ocellatus Holmes colloidality foot swelling
Compare * P＜0.05 with matched group; * * P＜0.001.
5, the influence of ampelopsin xylol induced mice auricle edema
Get 50 of mices, be divided into 5 groups by body weight, press gastric infusion every day of dosage shown in the table 5 once, administration is 7 days altogether, and 2h after the last administration drips dimethylbenzene 0.05ml in mouse right ear, and left ear is a normal control.Behind the 4h dislocation of mice cervical vertebra is put to death, cut two ears, lay round auricle at the same position of left and right ear respectively, weigh, ask the poor of left and right auricle weight, be the swelling degree with the card punch of diameter 9mm along the auricle baseline.The result shows: ampelopsin can obviously suppress the mice auricle swelling that dimethylbenzene causes, and has significant difference.See Table 3.
The influence of table 3 ampelopsin xylol induced mice auricle edema
Compare * P＜0.05 with matched group; * P＜0.01; * * P＜0.001.
6, to the bullate influence of rat granuloma
Get 50 of rats, under ether light anaesthesia aseptic condition, the cotton balls (10mg) of will sterilizing is implanted each subcutaneous both sides of Mus axillary fossa, next day after the operation, is divided into five groups at random, 10 every group.Press the gastric infusion of dosage shown in the table 2, every day 1 time, continuous 7 days, 1h after the last administration with the rat sacrificed by decapitation, peeled off and takes out the cotton balls granulation tissue, weighed and deducted cotton balls weight, and it is clean to put in the normal saline rinsing, dries in 80 ℃ of baking boxs, weighs.The results are shown in Table 4.
Table 4 ampelopsin is to the bullate influence of rat granuloma
Compare * P＜0.05 with matched group; * P＜0.01
The result shows that each dosage group of ampelopsin can obviously suppress the hypertrophy of granulation tissue, makes the weight saving of granulation cotton balls.Compare significant difference with matched group.
From above toxicity and pharmacodynamic experiment as can be known, ampelopsin has the effect of treatment and prevention gout, and therapeutic effect is remarkable, takes for a long time and is free from side effects.
The ampelopsin plant origin is abundant, and low price is not seen toxic and side effects, preparation simple (preparation method of ampelopsin, pharmaceutical preparation and new medical use thereof), and can make oral formulations, taking convenience.
The specific embodiment
In conjunction with the embodiments the present invention is further described, but the present invention is not subjected to any restriction of embodiment.
Embodiment 1 (capsule)
Prescription: ampelopsin: 150g
Starch 30g
Carboxymethyl starch sodium 20g
3% hydroxyl weapon base cellulose aqueous solution is an amount of
Ampelopsin raw material, starch, carboxymethyl starch sodium, mix homogeneously is granulated with 3% hydroxypropyl methylcellulose aqueous solution, drying, granulate, the capsule of packing into No. 1 is made 1000, promptly.Every contains ampelopsin 150mg.Each 2.Every day 2 times.
Embodiment 2 (tablet)
Prescription: ampelopsin: 150g
Lactose 30g
Carboxymethyl starch sodium 20g
3% hydroxypropyl methylcellulose aqueous solution is an amount of
Pulvis Talci 2.5g
Ampelopsin raw material, microcrystalline Cellulose, carboxymethyl starch sodium, mix homogeneously is granulated with 3% hydroxypropyl methylcellulose aqueous solution, drying, granulate adds the Pulvis Talci mixing, and tabletting is made 1000, promptly.Every contains ampelopsin 150mg.Each 2.Every day 2 times.
Embodiment 3 (granule)
Prescription: ampelopsin 150g
Icing Sugar: 350g
Ampelopsin raw material, Icing Sugar, mix homogeneously is used an amount of alcohol granulation, and drying, granulate, packing are made 250 bags, promptly.Each 1 bag.Every day 2 times
Embodiment 4 (drop pill)
Prescription: ampelopsin 15g
Polyethylene glycol 6000 25g
Macrogol 4000 10g
Take by weighing the 25g polyethylene glycol 6000, the 10g Macrogol 4000 melts in water-bath, add ampelopsin raw material 15g, stir, in the impouring insulating tube, regulate thermostat, in the liquid paraffin (12-14 ℃) that medicinal liquid is splashed into cooled off, after dripping off, will blot paraffin oil on the pill impouring filter paper under 80-90 ℃, make 1000, promptly.
Claims (6)
1, the application of a kind of xanthine oxidase inhibitor-ampelopsin in prevention and treatment gout medicine.
2, application according to claim 1 is characterized in that: contain the ampelopsin of dose therapeutically effective and one or more pharmaceutically acceptable pharmaceutical excipients, or the preparation that can make with the other medicines of ampelopsin prescription.
3, pharmaceutical preparation according to claim 2, but it is characterized in that preferably containing ampelopsin and the pharmaceutical excipient of 99%-1% or the medicine of other prescription of 1%-99%.But preferably contain ampelopsin and the pharmaceutical excipient of 70%-20% or the medicine of other prescription of 30%-80%, but preferably select ampelopsin and the excipient of 40%-30% or the medicine of other prescription that contains 60%-70% for use.
4, pharmaceutical preparation according to claim 2 is characterized in that said medicine is the dosage form of oral formulations.
5, pharmaceutical preparation according to claim 4 is characterized in that said oral formulations is selected from any in the middle of the tablet, pill, capsule, soft capsule, granule, suspensoid, drop pill, oral liquid.
6, the described pharmaceutical excipient of claim 2 comprises filler, disintegrating agent etc., and filler is selected from starch, lactose, microcrystalline Cellulose, dextrin, calcium phosphate etc.; Disintegrating agent is selected from carboxymethyl starch sodium, hyprolose, polyvinylpolypyrrolidone; Also optional adhesive, wetting agent and the lubricant of adding.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2008100507472A CN101278931A (en) | 2008-05-27 | 2008-05-27 | New medicinal application of myricetin |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2008100507472A CN101278931A (en) | 2008-05-27 | 2008-05-27 | New medicinal application of myricetin |
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| CN101278931A true CN101278931A (en) | 2008-10-08 |
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| CNA2008100507472A Pending CN101278931A (en) | 2008-05-27 | 2008-05-27 | New medicinal application of myricetin |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104274624A (en) * | 2014-09-29 | 2015-01-14 | 覃宇 | Traditional Chinese medicinal composition for treating gout |
| CN114028584A (en) * | 2021-11-18 | 2022-02-11 | 辽宁万嘉医药科技有限公司 | Polyphenol multi-element cyclodextrin inclusion compound for reducing uric acid and preparation method thereof |
| CN116210900A (en) * | 2022-12-29 | 2023-06-06 | 抱朴生命科技(广州)有限公司 | Plant polyphenol sustained-release composition for regulating xanthine oxidase activity and accurate nutrient and preparation method thereof |
-
2008
- 2008-05-27 CN CNA2008100507472A patent/CN101278931A/en active Pending
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104274624A (en) * | 2014-09-29 | 2015-01-14 | 覃宇 | Traditional Chinese medicinal composition for treating gout |
| CN114028584A (en) * | 2021-11-18 | 2022-02-11 | 辽宁万嘉医药科技有限公司 | Polyphenol multi-element cyclodextrin inclusion compound for reducing uric acid and preparation method thereof |
| CN114028584B (en) * | 2021-11-18 | 2023-09-05 | 辽宁万嘉医药科技有限公司 | Uric acid-reducing polyphenol-containing multi-cyclodextrin inclusion compound and preparation method thereof |
| CN116210900A (en) * | 2022-12-29 | 2023-06-06 | 抱朴生命科技(广州)有限公司 | Plant polyphenol sustained-release composition for regulating xanthine oxidase activity and accurate nutrient and preparation method thereof |
| CN116210900B (en) * | 2022-12-29 | 2024-01-30 | 抱朴生命科技(广州)有限公司 | Plant polyphenol sustained-release composition for regulating xanthine oxidase activity and accurate nutrient and preparation method thereof |
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Open date: 20081008 |