CN101810715A - New application of fructus evodiae and extracts and compounds thereof - Google Patents
New application of fructus evodiae and extracts and compounds thereof Download PDFInfo
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Abstract
The invention provides a new application of fructus evodiae and extracts and compounds thereof to prepare a medicament for treating hyperuricemia or/and gout. The invention also provides a medicinal composition prepared from effective dose of the fructus evodiae or extracts thereof as active components. The medicament comprises a fructus evodiae raw medicinal material, a solvent extract, total alkaloids of the fructus evodiae, single alkaloid of the fructus evodiae or a compound preparation containing the components, has the functions of blood uric acid reduction, anti-inflammation and analgesic activity, can be used for treating hyperuricemia and/or gout, has definite medicinal effect and high safety and provides a new medicine application selection for the clinics.
Description
Technical field
The present invention relates to the new purposes of Fructus Evodiae and extract thereof, particularly, is the purposes in the medicine of preparation treatment hyperuricemia and/or gout.Belong to field of medicaments.
Background technology
Gout belongs to the metabolic rheumatism, be that purine metabolic disturbance and/or urate excretion reduce caused a kind of crystal induced arthritis, clinical manifestation is that characteristic acute arthritis, the tophus due to hyperuricemia and the urate crystal deposition forms, the tophus chronic arthritis, and urate nephropathy, uric acid lithangiuria etc. can take place, severe patient can occur that disable in the joint, renal insufficiency.Above-mentioned performance can be different combinations, has embodied the heterogeneity of primary disease.Gout normal and central obesity, hyperlipemia, diabetes, hypertension and cardiovascular and cerebrovascular disease occur together.The prerequisite of gout morbidity is a hyperuricemia, and therefore, hyperuricemia is the most important biochemical basis of gout, secondly is that urate deposition causes inflammatory reaction.Over nearly 20 years, along with the change of dietary structure (take in to increase, high purine food increase), ethanol especially the absorption increase of beer class beverage and the minimizing of muscular labor momentum as heat, cause the sickness rate of hyperuricemia and primary gout to be ascendant trend year by year, and age of onset present and become younger.According to related data, the U.S.'s gout sickness rate eighties to the nineties in 20th century is 0.275%～1.000%, and gout sickness rate in 2003 is 2.7%; The European and American areas is 2%～18%.There is New Development patients up to a million every year in China at present, and report China hyperuricemia sickness rate such as Fang Qi were 1.4% in 1980; Du Hui in 1998 etc. show that in the Shanghai investigation hyperuricemia sickness rate is 10.1%, and the gout sickness rate reaches 0.34%; The investigation of the red grade of Shao Ji in Nanjing in 2003 shows that the hyperuricemia sickness rate has reached 13.3%, and the gout sickness rate reaches 1.33%.This shows that the epidemiologic feature of gout is quietly changing, gout becomes the commonly encountered diseases that threatens China and people of the world's health just day by day.
Treatment hyperuricemia and/or gout mostly are oral drugs at present, and the western medicine drug main will divide three classes according to the disease situation: 1. the treatment of acute stage: colchicine, nonsteroidal antiinflammatory drug, glucocorticoid; 2. the treatment of intermission: suppress uricopoiesis and promote the urate excretion medicine, as allopurinol, probenecid and sulfinpyrazone etc.3. the treatment of chronic phase: Diet Therapy and said medicine.But have side effect such as gastrointestinal reaction, skin allergy, renal damage, hepatic injury, leukopenia because of such medicine, patient's compliance is relatively poor.
Modern clinical and pharmacological research shows that Chinese medicine has certain curative effect in treatment hyperuricemia and/or gout prescription mask.According to the Yin Lian statistics, in 45 pieces of clinical reports, four wonderful Tonga flavor treatment acute gouty arthritises are treated nearly 1500 routine acute gout patients, and total effective rate reaches more than 90%, and uric acid recovers normal or obviously reduces, and relapse rate all reduces.Wan Yujun etc. treat gouty arthritis with Collettii melon side, and Collettii melon side group hematuria acid number descends obviously.Reports such as Jin Chenyu, particle for eliminating turbidity and treating arthralgia can significantly reduce acute gout model synovium of joint PGE
2With the 6-k-PGF1 alpha levels, IL-1, IL-6 level also there is obvious downward modulation effect.Reports such as WANG WENJUAN, Radix Angelicae Sinensis are picked up the level that the pain ball can reduce blood uric acid and xanthine oxidase in the experimental hyperuricemia rat blood serum.
Fructus Evodiae is a tcm clinical practice Chinese medicine commonly used, and the beginning is stated from Shennong's Herbal, its bitter in the mouth suffering, heat warm in nature, slightly poisonous.Energy warming spleen and stomach for dispelling cold, dispersing the depressed liver-QI for alleviating pain.Be used for diseases such as headache due to JUE YIN disorder, abdomen gastral cavity cold type of pain, vomiting are had loose bowels, dysmenorrhea, hypertension.Chemistry, pharmacological research to Fructus Evodiae shows that its chemical constituent is mainly multiple alkaloid, volatile oil, bitter principle etc. at present.Main effective ingredient is an alkaloid, has antiinflammatory, heart tonifying, blood pressure lowering and pharmacological actions such as antitumor, antithrombotic.About Fructus Evodiae treatment gout, the report that compound preparation is arranged, as application number: 200510021790.2, denomination of invention: a kind of medicine for the treatment of gout, this disclosure of the Invention a kind of medicine for the treatment of gout, it is made up of the following crude drug of clinical effective: Semen Arecae, Herba Epimedii, Rhizoma Atractylodis, Semen Coicis, silkworm excrement, Pericarpium Citri Reticulatae, Radix Platycodonis, Rhizoma Curcumae Longae, Folium Perillae, Fructus Evodiae, Fructus Chaenomelis, Rhizoma Zingiberis Recens.This Drug therapy gout curative effect is better, and side effect is little, and safety is good.
Though Chinese medicine has shown good prospect and definite curative effect in treatment hyperuricemia and/or gout, some relevant listing medicines are also arranged, but be compound preparation, do not see about having independent use Fructus Evodiae and alkaloids composition thereof to fall blood uric acid, be used for the treatment of the report of hyperuricemia and/or gout.
Summary of the invention
In order to solve the problems of the technologies described above, the invention provides a kind of new purposes of single medicine Fructus Evodiae, another technical scheme of the present invention has provided a kind of pharmaceutical composition for the treatment of hyperuricemia and/or gout.
The invention provides Fructus Evodiae and extract thereof the purposes in the medicine of preparation treatment hyperuricemia and/or gout.
Wherein, described Fructus Evodiae extract is a Fructus Evodiae total alkaloids.
Wherein, described Fructus Evodiae extract is the Fructus Evodiae ethanol extraction.Further, described concentration of alcohol is a 50%-95% ethanol.Still more preferably, described concentration of alcohol is 70% ethanol.
Described medicine is to have the medicine that falls blood uric acid, antiinflammatory, analgesic activity.
The present invention also provides the purposes of rutaecarpin or derivatives thereof in the medicine of preparation treatment hyperuricemia and/or gout.
Wherein, described rutaecarpin derivant comprises rutaecarpine, dehydroevodiamine, Hydroxyevodiamine, nor-Fructus Evodiae amide.Described medicine is to have the medicine that falls blood uric acid, antiinflammatory, analgesic activity.
Wherein, rutaecarpin (Evodiamine): chemical name: 8,13,13b, 14-tetrahydro-14-methyindolo[2 ' 3 '; 3,4] pyrido[2,1-b] quinazolin-5 (7H)-one, molecular formula: C
19H
17N
3O, molecular weight: 303.36.
Physicochemical property: yellow flat crystal, be positive with the bismuth potassium iodide reaction that improves, the reaction of silicon ursolic acid is positive.
Chemical structural formula:
Rutaecarpine (Rutaecarpin): chemical name: 8,13-dihydroindolo[2 ', 3 '; 3,4] pyrido[2,1-b] quinazolin-5 (7H)-one, molecular formula: C
18H
13N
3O, molecular weight: 287.31, physicochemical property: colourless crystallization, be positive with the bismuth potassium iodide reaction that improves, the reaction of silicon ursolic acid is positive.
Chemical structural formula:
Dehydroevodiamine (Dehydroevodiamine): molecular formula: C
19H
15N
3O, molecular weight: 301.353, physicochemical property: yellow flaky crystal, the bismuth potassium iodide colour developing is for orange red.
Chemical structural formula:
The present invention also provides a kind of pharmaceutical composition for the treatment of hyperuricemia and/or gout, and it is to be active component by the Fructus Evodiae of effective dose or its extract, adds the medicament that acceptable accessories or complementary composition are prepared from.
Wherein, described Fructus Evodiae extract is a Fructus Evodiae total alkaloids.
Wherein, described medicament is an oral formulations.
The present invention also provides the purposes of this pharmaceutical composition in the medicine of preparation treatment hyperuricemia and/or gout.
Medicine of the present invention comprises Fructus Evodiae primary crude drug, Fructus Evodiae total alkaloids, rutaecarpin or contains the compound preparation of Fructus Evodiae bases component, have the blood uric acid of falling, antiinflammatory, analgesic activity, can be used for treating hyperuricemia and/or gout, drug effect is clear and definite, safe, provide a kind of new medication to select for clinical.
The specific embodiment
The preparation of embodiment 1 medicine of the present invention
It is an amount of to take by weighing Fructus Evodiae coarse powder (crossing sieve No. two), adds 70% alcohol reflux twice, adds 8 times of amount solvents at every turn, extract 1.5h, merging filtrate, reclaim under reduced pressure is not to there being the alcohol flavor, and it is 1.25-1.35 that extracting solution is concentrated into relative density, add appropriate amount of starch, in 60-70 ℃ of oven dry, pulverize, sieve, encapsulated, promptly get Fructus Evodiae total alkali capsule.
The preparation of embodiment 2 medicines of the present invention
One, the preparation of Fructus Evodiae extract:
(1) Fructus Evodiae water extract: take by weighing Fructus Evodiae coarse powder (crossing sieve No. two) and in right amount, add 8 times of water, decoct 2 times, each 1h is concentrated into an amount of.Facing the time spent becomes every 1ml to contain the medicinal liquid of 1.0g crude drug with the 0.5%CMC solution dilution, is for experiment.
(2) Fructus Evodiae total alkaloids: take by weighing Fructus Evodiae coarse powder (crossing sieve No. two) in right amount, add 70% alcohol reflux twice, add 8 times of amount solvents at every turn, extract 1.5h, merging filtrate, reclaim under reduced pressure adds the dense HCl of 1ml during to 500ml, continues to reclaim ethanol to 125ml, alkalize to PH=9, chloroform extraction is to closely colourless, and the reclaim under reduced pressure chloroform is to doing, and adds tween, 10% ethanol water is an amount of.Facing the time spent becomes every 1ml to contain the medicinal liquid of 1.0g crude drug with the 0.5%CMC solution dilution, for pharmacological testing with (adopting high-efficient liquid phase technique to measure rutaecarpin content 0.247mg/ml, rutaecarpine content 1.64mg/ml).
Except can adopting 70% ethanol extraction, also can select the ethanol extraction of other concentration, as 50%-95% ethanol.Because ethanol extraction mainly contains the alkaloids composition, the Different concentrations of alcohol extract all has the treatment hyperuricemia or/and the drug effect of gout.
Two, the preparation of rutaecarpin
Rutaecarpin (Evodiamine): chemical name: 8,13,13b, 14-tetrahydro-14-methyindolo[2 ' 3 '; 3,4] pyrido[2,1-b] quinazolin-5 (7H)-one, molecular formula: C
19H
17N
3O, molecular weight: 303.36; Physicochemical property: yellow flat crystal, be positive with the bismuth potassium iodide reaction that improves, the reaction of silicon ursolic acid is positive.
But rutaecarpin reference literature preparation, also can directly buy the commercially available prod, as: the rutaecarpin of purity 〉=98%, lot number: GY20070603, Xi'an hat space biotechnology Co., Ltd provides, and faces the time spent to add ethanol and make the medicinal liquid of 0.257mg/ml concentration and use for pharmacological evaluation.
The rutaecarpin chemical structural formula:
Below prove beneficial effect of the present invention by concrete pharmacodynamics test.
Experiment material:
Animal: Kunming mouse, male and female have concurrently, body weight 18-23g, plant of Sichuan Province's laboratory animal special commission provides, regular grade animal, licence: SCXK (river) 2008-14.
Reagent reagent: rutaecarpin: purity 〉=98%, lot number CY20070603, Xi'an hat space Bioisystech Co., Ltd produces.Dimethylbenzene (chemical reagent two factories in Zhengzhou produce for analytical pure, lot number 990819); Glacial acetic acid (chemical plant, Xinning, Shantou, Guangdong produces for analytical pure, lot number 210819).Hypoxanthine: purity 〉=99%, lot number 037K06854, Sigma-Aldrich company provides.Aspirin Enteric-coated Tablets: the 25mg/ sheet, lot number 090603, Shijiazhuang City Condar pharmaceutical factory produces, the accurate word H13023679 of traditional Chinese medicines.Indometacin enteric-coated tablet: the 25mg/ sheet, lot number 0812010, Jiangsu Yabang Aipusen Pharmaceutical Co., Ltd. produces, the accurate word H32021431 of traditional Chinese medicines.Allopurinol tablet: the 0.1g/ sheet, lot number 090901, Qingyang, Chongqing pharmaceutcal corporation, Ltd produces, the accurate word H50021422 of traditional Chinese medicines.The testing uric acid test kit: lot number 1009091, Maike Tech Co., Ltd., Sichuan Prov. produces.
Experimental apparatus: BP-211D Sai Duolisi electronic balance, Germany.T-1000 type electronic balance, two outstanding brother's (group) company limiteies of the U.S..BASIC 70VB 0370 type semi-automatic biochemical analyzer, French Hickman (SECOMAM) company.LXJ-II type centrifugal precipitation mechanism, Shanghai medical analytical instrument factory.
Test example 1 Fructus Evodiae medical material different component is to the influence of mice blood uric acid
50 of male mices, body weight 18--22g is divided into 5 groups at random, and 10 every group, press the listed dosage gastric infusion of table 1, the administration capacity is 0.2mL10g
-1, blank group and model group are irritated the 0.5%CMC-Na solution that stomach waits capacity, and each organizes administration every day 1 time, gives 6d continuously, and 30min after the last administration removes blank group (intraperitoneal injection of saline 10mLkg
-1) outside, all the other mices are with 10% hypoxanthine 1000mgkg
-1The lumbar injection modeling, every Mus is got blood by the eye socket venous plexus behind the 1h, and separation of serum is pressed the uricase end-point method and is measured the serum uric acid value, the results are shown in Table 1.Adopt t check carrying out group difference significance relatively.
Table 1 Fructus Evodiae different component is to the influence of mice blood uric acid
Compare with the blank group: ▲ ▲ ▲ P＜0.001, compare with model group: * P＜0.05, * * * P＜0.001
Result of the test: compare with model group, the Fructus Evodiae total alkaloids group has utmost point significant difference, Fructus Evodiae water extract group zero difference to reducing the mice blood uric acid.Illustrate that Fructus Evodiae total alkaloids has the effect of obvious reduction mice blood uric acid.
Test example 2 Fructus Evodiae different components are to the influence of mouse corrosion disease effect
Adopt the scorching method of Mice Auricle caused by dimethylbenzene xylene.40 of male mices, body weight 19--23g is divided into 4 groups, every group 10 at random, presses the listed dosage gastric infusion of table 2, and the administration capacity is 0.2mL10g
-1, blank group is irritated the 0.5%CMC-Na solution that stomach waits capacity, administration every day 1 time, give 3d continuously, 30min after the last administration, outside coating dimethylbenzene 0.02mL/ only causes inflammation in every mouse right ear exterior feature, left side ear in contrast, cause scorching back 20min and take off cervical vertebra execution mice, lay auricle respectively at left and right ear same area, put on the electronic balance and weigh with diameter 7mm card punch, with left and right auricle weight difference value representation swelling degree, calculate and respectively organize the ear swelling degree, calculate suppression ratio, the results are shown in Table 2.Adopt t check carrying out group difference significance relatively.
The influence of table 2 Fructus Evodiae different component xylol induced mice ear swelling
Compare with the blank group: * P＜0.05, * * * P＜0.001
Result of the test: compare with the blank group, Fructus Evodiae water extract group xylol induced mice ear swelling has obvious inhibitory action, and the Fructus Evodiae total alkaloids group has antiinflammatory trend, no significant difference.Illustrate that Fructus Evodiae water extract has tangible antiinflammatory action.
Test example 3 Fructus Evodiae different components are to the influence of mice analgesic activity
Adopt mouse writhing method.40 of mices, male and female half and half, body weight 18-22g is divided into 4 groups at random, and 10 every group, press the listed dosage gastric infusion of table 3, the administration capacity is 0.2mL10g
-1, blank group is irritated the 0.5%CMC-Na solution that stomach waits capacity.Administration every day 1 time, successive administration 3d.30min after the last administration in every Mus lumbar injection 0.7% glacial acetic acid solution 0.2mL, observes and each Mus in the 15min given behind the glacial acetic acid in record turns round the body number of times, calculates the analgesia rate, the results are shown in Table 3.Adopt t check carrying out group difference significance relatively.
Table 3 Fructus Evodiae different component is to the influence of writhing response number of times due to the mouse peritoneal injection glacial acetic acid
Compare with the blank group: * * * P＜0.001
Result of the test: compare with the blank group, Fructus Evodiae water extract, Fructus Evodiae total alkaloids all have utmost point significant difference to the pain reaction that mouse peritoneal injection acetic acid causes.Show that Fructus Evodiae water extract, Fructus Evodiae total alkaloids all have significant analgesia role.
Test example 4 rutaecarpins are to the influence of mice blood uric acid
60 of male mices, body weight 18-22g is divided into 5 groups at random, 10 every group.Press the listed dosage gastric infusion of table 4, the administration capacity is 0.2mL10g
-1, blank group and model group wait the 0.5%CMC-Na solution of capacity with method, and each organizes administration every day 1 time, give 6 days continuously, after the last administration 30 minutes, except that the blank group 0.5%CMC-Na solution of capacity (lumbar injection etc.), all the other mices were with 10% hypoxanthine 1000mgkg
-1The lumbar injection modeling, 1 hour every Mus is got blood by the eye socket venous plexus after the modeling, and separation of serum is pressed the uricase end-point method and is measured the serum uric acid value, the results are shown in Table 4.Adopt t check carrying out group difference significance relatively.
Table 4 rutaecarpin is to the influence of mice blood uric acid
Compare with the blank group: ▲ ▲ ▲ P＜0.001, compare with model group: * P＜0.05, * * * P＜0.001
Result of the test: compare with model group, the high, medium and low dosage group of rutaecarpin all has notable difference, no significant difference between the high, medium and low dosage group of rutaecarpin to reducing the mice blood uric acid.Illustrate that rutaecarpin has the effect of obvious reduction mice blood uric acid.
Test example 5 rutaecarpins are to the antiinflammatory action of mice
Adopt mice caused by dimethylbenzene xylene ear swelling method.Get 60 of male mices, body weight 18-22g is divided into 5 groups at random, 12 every group.Press the listed dosage gastric infusion of table 5, the administration capacity is 0.2mL10g
-1, blank is organized the 0.5%CMC-Na solution that waits capacity with method, administration every day 1 time, give 3 days continuously, after the last administration 30 minutes, outside coating dimethylbenzene 0.02mL/ only caused inflammation in every mouse right ear exterior feature, compare with left ear, cause scorching back 20min and take off cervical vertebra execution mice, lay auricle respectively at left and right ear same area, put on the electronic balance and weigh with diameter 7mm card punch, with left and right auricle weight difference value representation swelling degree, calculate and respectively organize the ear swelling degree, calculate suppression ratio, the results are shown in Table 5.Adopt t check carrying out group difference significance relatively.
The influence of table 5 rutaecarpin xylol induced mice ear swelling (x ± S)
Compare with the blank group: * P＜0.05, * * P＜0.01, * * * P＜0.001
Result of the test: the high, medium and low dosage group of rutaecarpin xylol induced mice ear swelling all has inhibitory action.With the blank group relatively, high dose group has utmost point significance inhibitory action (P＜0.001), in, low dose group has obvious inhibitory action (P＜0.05, P＜0.05).Show that rutaecarpin has tangible antiinflammatory action.
Test example 6 rutaecarpins are to the mice analgesic test
Adopt mouse writhing method.Get 60 of mices, male and female half and half, body weight 18-22g is divided into 5 groups at random, and 12 every group.Press the listed dosage gastric infusion of table 6, the administration capacity is 0.2mL10g
-1, the blank 0.5%CMC-Na solution that waits capacity with method of organizing, administration every day 1 time gives 3 days continuously.After the last administration 30 minutes, every mouse peritoneal was injected 0.7% glacial acetic acid solution 0.2mL.Observe and each Mus in the 15min given behind the glacial acetic acid in record turns round the body number of times, calculate the analgesia rate, the results are shown in Table 6.Adopt t check carrying out group difference significance relatively.
Table 6 rutaecarpin is to the influence of writhing response number of times due to the mouse peritoneal injection glacial acetic acid (x ± S)
Compare with the blank group: * P＜0.05, * * * P＜0.001
Result of the test: the high, medium and low dosage group of rutaecarpin all has the obvious suppression effect to the pain reaction that mouse peritoneal injection glacial acetic acid causes.Compare with the blank group, low dose group has utmost point significance inhibitory action (P＜0.001), and high, middle dosage group has obvious inhibitory action (P＜0.05, P＜0.05).Show that rutaecarpin has significant analgesia role.
The 7 rutaecarpin acute toxicity tests of test example
Get 40 of mices, body weight 18～22g, fasting 12h before the experiment is divided into 2 groups at random, and 20 every group, male and female half and half.Press the listed dosage gastric infusion of table 7, the administration capacity is 0.2mL10g
-1, blank group waits the 0.5%CMC-Na solution of capacity with method.Single administration is observed 14d continuously, and two groups of situations such as mice behavioral activity, state, diet, stool, urine, hair color, secretions and death of itemized record the results are shown in Table 7.
The acute toxicity test of table 7 rutaecarpin (x ± SD)
Result of the test: 14d after the mice administration, the behavior of mice, diet, feces no abnormality seen, none is only dead, and 14d mice weight average increasing value is 11.8 ± 3.9g, blank group is 12.8 ± 3.7g, and the body weight gain of administration treated animal and matched group be there was no significant difference (P＞0.05) relatively.Put to death mice behind the 14d, internal organs such as the perusal heart, liver, spleen, lung, kidney, intestinal, no abnormal variation.
In sum, by the different influence experiment, the mice blood uric acid influence experiments that influence writhing response number of times due to experiment, the mouse peritoneal injection glacial acetic acid of extracting component xylol induced mice ear swelling of Fructus Evodiae, reach rutaecarpin antiinflammatory, analgesia, the mice blood uric acid is influenced test, the effective site that draws anti-hyperuricemia of Fructus Evodiae and/or gout is the Fructus Evodiae alkaloid, and this active component of Fructus Evodiae can be used for the treatment of hyperuricemia and/or gout.The present invention provides new purposes for the application of Chinese medicine Fructus Evodiae medical material, total alkaloids, single creature alkali cpd, also provides new, available resources widely for the drug research and development of treatment hyperuricemia and/or gout.
Claims (10)
1. Fructus Evodiae and extract thereof the purposes in the medicine of preparation treatment hyperuricemia and/or gout.
2. purposes according to claim 1 is characterized in that: described Fructus Evodiae extract is a Fructus Evodiae total alkaloids.
3. purposes according to claim 1 is characterized in that: described Fructus Evodiae extract is the Fructus Evodiae ethanol extraction.
4. according to any described purposes of claim 1-3, it is characterized in that: described medicine is to have the medicine that falls blood uric acid, antiinflammatory, analgesic activity.
5. the purposes of rutaecarpin or derivatives thereof in the medicine of preparation treatment hyperuricemia and/or gout.
6. purposes according to claim 5 is characterized in that: described rutaecarpin derivant comprises rutaecarpine, dehydroevodiamine, Hydroxyevodiamine, nor-Fructus Evodiae amide.
7. according to claim 5 or 6 described purposes, it is characterized in that: described medicine is to have the medicine that falls blood uric acid, antiinflammatory, analgesic activity.
8. pharmaceutical composition for the treatment of hyperuricemia and/or gout, it is by the Fructus Evodiae of effective dose or its extract, or rutaecarpin and derivant thereof be active component, adds the medicament that acceptable accessories or complementary composition are prepared from.
9. pharmaceutical composition according to claim 8 is characterized in that: described Fructus Evodiae extract is a Fructus Evodiae total alkaloids.
10. will show 8 or 9 described pharmaceutical compositions according to right, it is characterized in that: described medicament is an oral formulations.
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| CN102399221A (en) * | 2011-09-23 | 2012-04-04 | 江苏省中国科学院植物研究所 | Application of diindoloquinazoline alkaloid in preparation of antitumor drugs and antifungal drugs |
| CN102399221B (en) * | 2011-09-23 | 2016-05-25 | 江苏省中国科学院植物研究所 | The application of two indole quinazoline Alkaloids in antitumor, the antifungal drug of preparation |
| CN102727454A (en) * | 2012-05-25 | 2012-10-17 | 成都中医药大学附属医院 | Evodiamine dispersion tablets and preparation method thereof |
| CN102775413A (en) * | 2012-08-23 | 2012-11-14 | 中山大学 | Amino-substituted rutaecarpin analog, and synthesis method and application thereof in preparation of anti-obesity medicaments |
| WO2014029360A1 (en) * | 2012-08-23 | 2014-02-27 | 中山大学 | Amino-substituted rutaecarpin analog and synthesis method and use thereof in preparation of anti-obesity drug |
| CN103288827A (en) * | 2013-04-17 | 2013-09-11 | 江苏省中国科学院植物研究所 | Preparation method and activity of novel indole quinazoline alkaloid |
| CN103288827B (en) * | 2013-04-17 | 2016-05-25 | 江苏省中国科学院植物研究所 | A kind of preparation method and activity of new indole quinazoline Alkaloid |
| CN104586857A (en) * | 2014-12-30 | 2015-05-06 | 新昌县大成生物科技有限公司 | Application of Criofolinine in preparation of medicines for treating gout |
| CN106214807A (en) * | 2016-08-04 | 2016-12-14 | 余庆县黔龙民族药业有限责任公司 | The processing technique of Fructus Evodiae |
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