CN104116753A - Application of aucubin to preparation of medicines for treating idiopathic pulmonary fibrosis - Google Patents
Application of aucubin to preparation of medicines for treating idiopathic pulmonary fibrosis Download PDFInfo
- Publication number
- CN104116753A CN104116753A CN201410377002.2A CN201410377002A CN104116753A CN 104116753 A CN104116753 A CN 104116753A CN 201410377002 A CN201410377002 A CN 201410377002A CN 104116753 A CN104116753 A CN 104116753A
- Authority
- CN
- China
- Prior art keywords
- aucubin
- ethyl acetate
- defat
- application according
- time
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Landscapes
- Medicines Containing Plant Substances (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to the field of applications of traditional Chinese medicine extracts and in particular provides an application of aucubin to preparation of medicines for treating idiopathic pulmonary fibrosis. Aucubin is preferably the eucommia ulmoides samara extract, wherein the purity of aucubin is above 98%.
Description
Technical field
The invention belongs to Chinese medicine extract purposes field, be specifically related to the new purposes of aucubin.
Background technology
Idiopathic pulmonary fibrosis (Idiopathic Pulmonary Fibrosis, IPF) is a kind of specific type of chronic fibrosis interstitial pneumonia, and pathogenic factor is still not clear.The potential paathogenic factor of generally acknowledging at present comprises smoking, the exposure of environment occupational factor, infected by microbes, gastroesophageal reflux and inherited genetic factors etc.Idiopathic pulmonary fibrosis is the development of a kind of chronic progressive external, irreversible pathological change substantially, and pathological changes is confined to pulmonary, and histopathology and high-resolution ct are shown as plain edition interstitial pneumonia type feature.Idiopathic pulmonary fibrosis often occurs in old people, yet each age level is all visible clinically, and its sickness rate presents the trend of increase with advancing age.The poor prognosis of idiopathic pulmonary fibrosis, makes a definite diagnosis only 3-5 of rear median survival interval, and within 5 years, survival rate is less than 50%.Clinical trial medicine for idiopathic pulmonary fibrosis comprises glucocorticoid, colchicine, ciclosporin A, acetyl cysteine, anticoagulant, pirfenidone, sldenafil and imatinib etc. at present, but idiopathic pulmonary fibrosis is generally poor to the therapeutic response of hormone and various medicines, there is no at present the medicine of the final prognosis of effective patient of improvement.The state of an illness unique effective treatment in late period is just lung transplantation.Therefore studying the mechanism of idiopathic pulmonary fibrosis and inquire into new effective means of prevention is the focus of current basis and clinical concern.
Aucubin (aucubin, AU) belongs to iridoid glycosides, and molecular formula is C
15h
22o
9, molecular weight 346.33,181 ℃ of fusing points, soluble in water, methanol and ethanol isopolarity solvent, be dissolved in the weak polar solvents such as chloroform, ether and petroleum ether hardly.This compound is mainly present in Cortex Eucommiae Eucommia ulmoides Oliver, Cornaceae plant peach jaurel belongs in the plants such as (Aucubachinensis), Plantaginaceae plant Plantago (Plantago), be one of medium-height grass the effective elements of the medicines such as the Cortex Eucommiae, Herba Plantaginis, Radix Rehmanniae, have that protecting liver and detoxication, antiinflammatory, antioxidation, promotion collagen are synthetic, numerous pharmacologically actives such as osteoporosis and trophic nerve unit cell.Aucubin structural formula is as follows:
The Cortex Eucommiae is the dry bark of the Eucommiaceae plant Cortex Eucommiae, is Chinese famous and precious tonic herb.Tool invigorating the liver and kidney, bone and muscle strengthening, blood pressure lowering, many effects such as antiabortive, it is Chinese peculiar medical material, its medicinal history is long, clinical, has a wide range of applications.Eucommia is the side-product of Cortex Eucommiae industry, contains gutta-percha, oils and fats, protein, iridoid etc., and wherein aucubin (aucubin, AU) content is up to 7%-11%.Aucubin has the pharmacologically actives such as antiinflammatory, antioxidation, removing toxic substances protect the liver, anti-bacteria and anti-virus, osteoporosis, because its character is active, biological activity obviously but be difficult for obtaining, be called as " star molecule ", have exploitation and be worth.Be showed no at present the report of aucubin to idiopathic pulmonary fibrosis effect both at home and abroad.
Aucubin has the preparation method of multiple maturation in the prior art, but at present, the process research of extracting aucubin from Eucommia is less.Chinese patent 201010297478.7, " a kind of process of extracting aucubin from Cortex Eucommiae fruit " disclosed, mainly comprise flash or supersound extraction, macroporous resin adsorption purification, but this technique obtains aucubin purity only 50%, and reagent consumption is large, complex operation, industrialization produce that the production cycle is long, cost is high, is unfavorable for suitability for industrialized production and the exploitation of aucubin monomer.Chinese patent 201310028642.8 discloses " a kind of method of rapidly and efficiently preparing aucubin monomer from the Cortex Eucommiae ", and the method can make aucubin through extraction-crystallization two steps, but yield is lower, serious waste of resources.Chinese patent CN 101863938 A disclose " a kind of method of preparing high-purity aucubin ", the method is carried out the separated aucubin that obtains with polymer carrier immobile phase chromatographic column, silica gel column chromatography, recrystallization, and step is many, product yield is lower, the production cycle is longer.
Summary of the invention
Object of the present invention aims to provide a kind of new purposes of aucubin.We study and find that aucubin has preventive and therapeutic effect to idiopathic pulmonary fibrosis, can be used for the medicine of preparation treatment idiopathic pulmonary fibrosis.
For achieving the above object, technical scheme of the present invention is:
The application of aucubin in preparation treatment idiopathic pulmonary fibrosis medicine.
Described aucubin is preferably Eucommia extract, and wherein aucubin purity is more than 98%.
Described aucubin further preferably be take Eucommia as raw material, by Eucommia, shells, and kernel is pulverized, and through defat with petroleum ether, ethanol extraction, adds acetone crystallisation by cooling, then through silicagel column purification, obtains aucubin monomer.
Further preferred, described aucubin is to obtain by following preparation method, comprises the following steps:
1. defat: by the dry Cortex Eucommiae kernel that really shells to obtain, kernel is pulverized, and defat with petroleum ether, obtains defat coarse fodder; Described petroleum ether consumption is that the 6-10 of Cortex Eucommiae fruit kernel quality doubly measures, and defat number of times is 2-4 time, and degreasing time is 1.5-4 hour;
2. extract: add ethanol to extract described defat coarse fodder, filter, merge extractive liquid,, 40 ℃ of-60 ℃ of 1/5-1/12 that are concentrated into extracting liquid volume, obtain concentrated extracting solution; Described ethanol consumption is that the 6-12 of Cortex Eucommiae fruit quality doubly measures, and extraction time is 3-5 time, and each extraction time is 2-5 hour;
3. crystallization: described concentrated extracting solution is added to the saturated dissolving of acetone, and crystallisation by cooling, obtains aucubin coarse crystal;
4. silica gel column chromatography: described aucubin coarse crystal is added to the saturated dissolving of ethyl acetate, add again silica gel column chromatography, wherein silica gel for chromatography and aucubin roughly the mass ratio of crystal be 6:1-11:1, the solution then forming with ethyl acetate and methanol is eluting successively, collects eluent; In the solution that during described eluting successively, ethyl acetate used and methanol form, the concentration of ethyl acetate reduces from high to low gradually;
5. concentrate drying: by described eluent 40 ℃-60 ℃ concentrated, lyophilization, obtains aucubin monomer product.Preferred version: be 40-50 order after suddenly pulverizing described in 1..
Preferred version: step 1. PetroChina Company Limited.'s ether consumption is that the 8-9 of Cortex Eucommiae fruit kernel doubly measures, and defat number of times is 3-4 time, and degreasing time is 2-3 hour.
Preferred version: the step 8-10 that 2. middle ethanol consumption is raw material doubly measures, and extraction time is 3-4 time, and each extraction time is 3-4 hour.
Preferred version: step 3. in after the saturated dissolving of ethyl acetate, by lysate be placed in 4-10 ℃ cooling, crystallization 12-72 hour.
Preferred version: step 4. in silica gel for chromatography and aucubin roughly the mass ratio of crystal be 8:1-10:1.
Preferred version: step in 4. with the solution of ethyl acetate and the methanol composition successively order of eluting is: routine ethyl acetate is the order eluting of 1:0,10:1,6:1,4:1 than methanol in mass ratio successively, and consumption is respectively 3-5BV, 3-6BV, 4-6BV, 3-5BV.
Below the present invention is further explained and is illustrated.
Aucubin of the present invention is preferably Eucommia extract, can be selected from pulverizing by employing, squeezes, calcines, grinds, sieves, percolation, extraction, water extraction, alcohol extraction, water precipitating, precipitate with ethanol, ester are carried, the method such as ketone is carried, chromatography, filtration obtains.Take this extract can be made into pharmaceutical preparation as active substance, and described extract can be the material of extractum form, can be that dry extract can be also fluid extract, can be powdered substance, according to the difference of preparation, need to make different states.
The present invention also mentions that aucubin is through the pharmaceutical preparation of applicable any unit dosage form of taking of processing preparation, these pharmaceutical preparatioies are selected from following dosage form: tablet, sugar coated tablet, film coated tablet, enteric coated tablet, capsule, hard capsule, soft capsule, oral liquid, suck agent, granule, electuary, pill, powder, unguentum, sublimed preparation, suspensoid, powder, solution, suppository, ointment, plaster, cream, spray, drop, patch, while needing, can make slow releasing preparation, enteric coated preparation.
Aucubin of the present invention, when being prepared into pharmaceutical preparation, can add medicine acceptable carrier, described medicine acceptable carrier is selected from: antioxidant, intercalating agent surfactant filler disintegrating agent wetting agent dispersant lubricant solvent slow release material enteric material pH adjusting agent, correctives, pigment etc., conventional carrier is as mannitol, dextran, lactose, glucose, sorbitol, mannitol, xylitol, sodium chloride, silicon derivative, cellulose and cellulose derivative, sodium sulfite, sodium pyrosulfite, alginate, gelatin, polyvinylpyrrolidone, glycerol, Tween 80, agar, calcium carbonate, calcium bicarbonate, Polyethylene Glycol, cyclodextrin, beta-schardinger dextrin-, phospholipid material, Kaolin, Pulvis Talci, calcium stearate, magnesium stearate etc.
The pharmaceutical preparation of aucubin of the present invention is by Eucommia being processed through extraction or other modes, being made pharmaceutically active substance, subsequently, take this active substance as raw material, while needing, add medicine acceptable carrier, according to the routine techniques of galenic pharmacy, make pharmaceutical preparation.
The specific embodiment
Below by embodiment, the present invention will be further explained, and percentage composition described in embodiment is quality percentage composition.
The preparation of embodiment 1 Eucommia extract aucubin
By Eucommia shelling, kernel powder is broken to 40 orders, gets 10kg and drops into extraction pot, adds 60L defat with petroleum ether, defat 2 times, and each 3 hours, leaching medicinal residues was defat coarse fodder.Add 80L ethanol to defat coarse fodder supersound extraction 2 hours, extract merge extractive liquid, 3 times.40 ℃ of extracting solution be evaporated to original volume 1/8 and reclaim ethanol.Concentrated solution adds the saturated dissolving of acetone, 7 ℃ of crystallizations 48 hours, and coarse crystal adds the saturated dissolving of ethyl acetate.Get 10L silica gel dress post, saturated solution is added to silicagel column, (quality is than ethyl acetate: methanol=1:0) to use successively 3BV ethyl acetate, (quality is than ethyl acetate: methanol=10:1) for 4BV10:1 ethyl acetate/methanol, (quality is than ethyl acetate: methanol=6:1) for 5BV6:1 ethyl acetate/methanol, (quality is than ethyl acetate: methanol=4:1) for 4BV4:1 ethyl acetate/methanol eluant solution, by thin layer chromatography, detect simultaneously, collect aucubin flow point, merge eluent, 40 ℃ of concentrating under reduced pressure, lyophilization, obtain aucubin monomer 410g, through HPLC method, measure, its content reaches 98.7%.
The preparation of embodiment 2 Eucommia extract aucubins
By Eucommia shelling, kernel powder is broken to 50 orders, gets 10kg and drops into extraction pot, adds 80L defat with petroleum ether, defat 3 times, and each 4 hours, leaching medicinal residues was defat coarse fodder.Add 100L ethanol to defat coarse fodder supersound extraction 4 hours, extract merge extractive liquid, 5 times.40 ℃ of extracting solution be evaporated to original volume 1/10 and reclaim ethanol.Concentrated solution adds the saturated dissolving of acetone, 4 ℃ of crystallizations 72 hours, and coarse crystal adds the saturated dissolving of ethyl acetate.Get 10L silica gel dress post, saturated solution is added to silicagel column, (quality is than ethyl acetate: methanol=1:0) to use successively 3BV ethyl acetate, (quality is than ethyl acetate: methanol=10:1) for 4BV10:1 ethyl acetate/methanol, (quality is than ethyl acetate: methanol=6:1) for 5BV6:1 ethyl acetate/methanol, (quality is than ethyl acetate: methanol=4:1) for 4BV4:1 ethyl acetate/methanol eluant solution, , by thin layer chromatography, detect simultaneously, collect aucubin flow point, merge eluent, 40 ℃ of concentrating under reduced pressure, lyophilization, obtain aucubin monomer 480g, through HPLC method, measure, its content reaches 99.2%.
Embodiment 3
The research of the Protection to idiopathic pulmonary fibrosis by embodiment 1 and the resulting aucubin of embodiment 2 and commercially available aucubin (being purchased from Yuan Ye bio tech ltd, Shanghai) for embodiment 3.
1. experimental technique
1.1 dosage design and groupings
Experiment is divided into Normal group, model group, aucubin low dose group (1mg/kg), middle dosage group (5mg/kg), high dose group (10mg/kg), commercially available aucubin (10mg/kg) and pirfenidone positive controls (10mg/kg).
Table 1 test grouping and dosage design
1.2 experimental procedure
Healthy 70 of male SD rats (body weight 250～300g), be divided at random 7 groups: as Normal group (A group), bleomycin group (B group), the basic, normal, high dosage group of aucubin (C, D, E group), commercially available aucubin group (F group), pirfenidone positive controls (G group).B organizes rats by intraperitoneal injection 3% pentobarbital sodium (30mg/kg), after anesthesia, lie on the back and be fixed on Mus platform, routine disinfection drape after cervical region preserved skin, cut after skin successively blunt separation and expose trachea, with the syringe diagonal of 1mL, thrust in trachea, to fast injection bleomycin solution 0.2-0.3ml in lung, hold up immediately Mus plate, roll 2 minutes, medicinal liquid is evenly distributed in two lungs, after the skin of again sterilizing, close wound.The normal saline of A group injection same volume.C, D, E, F, G group rat molding method, with B group, start to give aucubin and the pirfenidone solution of the basic, normal, high dosage of lumbar injection every day in trachea injection bleomycin second day.By aucubin for distilled water, Fluorofenidone with 0.5% Carboxymethyl cellulose sodium be according to dosage mixed with respective concentration before experiment every day, now with the current, by 10mL/kg gastric infusion.A group and B group start to give isopyknic distilled water at operation second day.Experimental session rat freely drinks water, feed (standard diet).Measure weekly rat body weight once.In experiment, start the rat of putting to death for the 4th week after administration.Adopt femoral artery depletion method, after pentobarbital sodium anesthesia, rat is lain on the back and is fixed on Mus platform, open breast and appear cardiopulmonary, after taking off lungs, with normal saline, repeatedly clean, electronic balance weighing body weight and lung weight, calculate lung coefficient (lungs weight/body weight * 100%).4% formaldehyde is right upper lung, lower-left lung fixedly, and conventional dehydration embedding, makes the thick paraffin section of 5 μ m, in order to HE dyeing.
1.3 detect index
Pulmonary morphology is observed: getting respectively lungs, to be placed in 4% formaldehyde fixing, conventional dehydration, embedding, section, HE dyeing.The method providing according to Szapiel etc., determines alveolitis and pulmonary fibrosis degree, carries out pathology semi-quantitative analysis.
Alveolitis classification:
0 grade: without alveolitis;
1 grade: slight alveolitis, extent of disease is confined to full lung below 20%;
2 grades: moderate alveolitis, extent of disease accounts for full lung 20%-50%;
3 grades: Diffuse alveolar is scorching, and extent of disease is greater than 50%.
Interstitial pulmonary fibrosis classification:
0 grade: without interstitial pulmonary fibrosis;
1 grade: slight interstitial pulmonary fibrosis, extent of disease is confined to full lung below 20%;
2 grades: moderate interstitial pulmonary fibrosis, extent of disease accounts for full lung 20%-50%;
3 grades: severe interstitial pulmonary fibrosis, extent of disease is greater than 50%, and alveolar merges, pulmonary parenchyma structure disturbance.
Utilize microimage analysing system, pathological section carried out to alveolitis and fibrosis is measured automatically, lung tissue HE dyeing pathological section is divided into following three regions and analyzes:
(1) Wu Ran district: be alveolar space area occupied.
(2) engrain district: be nucleus area occupied.
(3) understain district: be interstitial lung fibrous connective tissue area occupied.
The degree of alveolitis and pulmonary fibrosis can be determined by the difference of above three region area occupied.During alveolitis, interstitial lung inflammatory cell infiltration increases, and shows as engrain district area change, and during fibrosis, alveolar mostly subsides or disappears, and a large amount of collagen fiber appear in interstitial, show as the area minimizing of Wu Ran district, understain district area change.With engrain district, represent nucleus area occupied, i.e. alveolar inflammation area, understain district represents fibrous connective tissue and collagen fiber area occupied, Wu Ran district represents alveolar space area.Pathological section is placed under image analyzer microscope, and under the 10x visual field, every section, by left-to-right, chosen successively from top to bottom 10 visuals field and is carried out graphical analysis, measures the area value (pixel/visual field) in corresponding each district, and is converted into (um
2/ the visual field), average.
1.4 statistical method:
Adopt SPSS16.0 to carry out statistical analysis, the level set of statistical significance is P<0.05.Adopt mean ± standard deviation
by Leven ' s test method check normality and homogeneity of variance.If meet normality and homogeneity of variance, with one factor analysis of variance (One-way ANOVA) and post Hoc LSD, carry out statistical analysis; If do not meet normality and heterogeneity of variance, check with Kruskal-Wallis.If Kruskal-Wallis check has statistical significance (P<0.05), use Dunnett ' s Test (nonparametric technique) to compare analysis.During evaluation, consider significant difference and biological significance.
2 experimental results
The impact of aucubin on pathologic
With Normal group comparison, model group rat presents severe alveolitis, and there is more hemorrhagic focus part, alveolar septum broadening, and inflammatory cell infiltration, macrophage activation is obvious: volume increases, and cell contains a large amount of granules, and most of macrophage is foam sample and changes; The fibroblast that lamellar is assembled activation is closely adjacent, and alveolar septum and areas of inflammation are shown in the collagen fiber of lamellar hypertrophy, and fibrosis obviously increases.From the statistical result of average pathology integration, can find out, model group pathology integration is significantly higher than sham operated rats, prompting renal fibrosis model modeling success.After administration 15 days, aucubin high dose group and Fluorofenidone positive controls, commercially available aucubin are compared and are all occurred significant difference with model group, and there is a change for the better for kidney region fibrosis.
The impact of table 2 aucubin on each group induced lung coefficient
Note: with Normal group comparison,
++p<0.01, with model group comparison,
*p<0.05.
3 experiment brief summaries
The above results shows, aucubin high dose group, commercially available aucubin group can significantly be improved the symptoms such as the alveolitis of idiopathic pulmonary fibrosis model, the change of macrophage foam cell formation sample, fibrocyte activation and collagen fiber hypertrophy, and idiopathic pulmonary fibrosis is had some improvement.
Claims (10)
1. the application of aucubin in preparation treatment idiopathic pulmonary fibrosis medicine.
2. application according to claim 1, is characterized in that, described aucubin is Eucommia extract, and wherein aucubin purity is more than 98%.
3. according to application described in claim 1 or 2, it is characterized in that, described aucubin is to take Eucommia as raw material, by Eucommia, shells, kernel is pulverized, through defat with petroleum ether, and ethanol extraction, add acetone crystallisation by cooling, then through silicagel column purification, obtain aucubin monomer.
4. application according to claim 3, is characterized in that, the preparation method of described aucubin comprises the following steps:
1. defat: by the dry Cortex Eucommiae kernel that really shells to obtain, kernel is pulverized, and defat with petroleum ether, obtains defat coarse fodder; Described petroleum ether consumption is that the 6-10 of Cortex Eucommiae fruit kernel quality doubly measures, and defat number of times is 2-4 time, and degreasing time is 1.5-4 hour;
2. extract: add ethanol to extract described defat coarse fodder, filter, merge extractive liquid,, 40 ℃ of-60 ℃ of 1/5-1/12 that are concentrated into extracting liquid volume, obtain concentrated extracting solution; Described ethanol consumption is that the 6-12 of Cortex Eucommiae fruit quality doubly measures, and extraction time is 3-5 time, and each extraction time is 2-5 hour;
3. crystallization: described concentrated extracting solution is added to the saturated dissolving of acetone, and crystallisation by cooling, obtains aucubin coarse crystal;
4. silica gel column chromatography: described aucubin coarse crystal is added to the saturated dissolving of ethyl acetate, add again silica gel column chromatography, wherein silica gel for chromatography and aucubin roughly the mass ratio of crystal be 6:1-11:1, the solution then forming with ethyl acetate and methanol is eluting successively, collects eluent; In the solution that during described eluting successively, ethyl acetate used and methanol form, the concentration of ethyl acetate reduces from high to low gradually;
5. concentrate drying: by described eluent 40 ℃-60 ℃ concentrated, lyophilization, obtains aucubin monomer product.
5. application according to claim 4, is characterized in that, step is 40-50 order after pulverizing described in 1..
6. application according to claim 4, is characterized in that, step 1. PetroChina Company Limited.'s ether consumption is that the 8-9 of Cortex Eucommiae fruit kernel doubly measures, and defat number of times is 3-4 time, and degreasing time is 2-3 hour.
7. application according to claim 4, is characterized in that, the step 8-10 that 2. middle ethanol consumption is raw material doubly measures, and extraction time is 3-4 time, and each extraction time is 3-4 hour.
8. application according to claim 4, is characterized in that, step 3. in after the saturated dissolving of ethyl acetate, by lysate be placed in 4-10 ℃ cooling, crystallization 12-72 hour.
9. application according to claim 4, is characterized in that, step 4. in silica gel for chromatography and aucubin roughly the mass ratio of crystal be 8:1-10:1.
10. application according to claim 4, it is characterized in that, step in 4. with the solution of ethyl acetate and the methanol composition successively order of eluting is: routine ethyl acetate is the order eluting of 1:0,10:1,6:1,4:1 than methanol in mass ratio successively, and consumption is respectively 3-5BV, 3-6BV, 4-6BV, 3-5BV.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410377002.2A CN104116753B (en) | 2014-08-01 | 2014-08-01 | The application of aucubin in preparation treatment idiopathic pulmonary fibrosis medicine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410377002.2A CN104116753B (en) | 2014-08-01 | 2014-08-01 | The application of aucubin in preparation treatment idiopathic pulmonary fibrosis medicine |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104116753A true CN104116753A (en) | 2014-10-29 |
| CN104116753B CN104116753B (en) | 2015-09-09 |
Family
ID=51762533
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410377002.2A Active CN104116753B (en) | 2014-08-01 | 2014-08-01 | The application of aucubin in preparation treatment idiopathic pulmonary fibrosis medicine |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104116753B (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110664829A (en) * | 2019-11-04 | 2020-01-10 | 昆明医科大学 | Application of geniposide in preparation of anti-pulmonary fibrosis drugs |
| CN115671124A (en) * | 2022-08-25 | 2023-02-03 | 海南医学院第一附属医院 | Application of aucubin in preparation of hypoxic pulmonary hypertension vascular remodeling drug |
| CN118978556A (en) * | 2024-10-22 | 2024-11-19 | 江西中医药大学 | A guaiacyl sesquiterpenoid compound and its preparation method and application |
-
2014
- 2014-08-01 CN CN201410377002.2A patent/CN104116753B/en active Active
Non-Patent Citations (2)
| Title |
|---|
| 康桢等: "桃叶珊瑚苷及其苷元的药理研究进展", 《中国中药杂志》, vol. 32, no. 24, 31 December 2007 (2007-12-31), pages 2585 - 2587 * |
| 裴旭: "特发性肺纤维化的治疗进展", 《国际内科学杂志》, vol. 35, no. 5, 31 May 2008 (2008-05-31), pages 280 - 283 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110664829A (en) * | 2019-11-04 | 2020-01-10 | 昆明医科大学 | Application of geniposide in preparation of anti-pulmonary fibrosis drugs |
| CN115671124A (en) * | 2022-08-25 | 2023-02-03 | 海南医学院第一附属医院 | Application of aucubin in preparation of hypoxic pulmonary hypertension vascular remodeling drug |
| CN115671124B (en) * | 2022-08-25 | 2023-07-04 | 海南医学院第一附属医院 | Application of aucubin in preparation of anoxic pulmonary arterial high pressure vascular remodeling drugs |
| CN118978556A (en) * | 2024-10-22 | 2024-11-19 | 江西中医药大学 | A guaiacyl sesquiterpenoid compound and its preparation method and application |
Also Published As
| Publication number | Publication date |
|---|---|
| CN104116753B (en) | 2015-09-09 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5675839B2 (en) | Pharmaceutical composition comprising sunflower extract, method for its preparation and use | |
| WO2018058261A1 (en) | Traditional chinese medicine composition for treating psoriasis and preparation method thereof | |
| WO2005051404A1 (en) | Pharmaceutical composition for the treatment of cardiovascular and cerebrovascular diseases | |
| CN102600219A (en) | Total flavone extract of abelmoschus manihot and preparing method of total flavone extract | |
| CN102068535A (en) | Citrus aurantium or Fructus aurantii total flavonoids extract extracted by ethanol reflux and use thereof | |
| CN104116753B (en) | The application of aucubin in preparation treatment idiopathic pulmonary fibrosis medicine | |
| CN105687441A (en) | Application of litchi rind polyphenol in medicines for treating hyperglycemia and insulin resistance | |
| CN101450127A (en) | Pawpaw total phenolic acid extract and use thereof | |
| CN105031468B (en) | Fructus Alpinae Oxyphyllae extract with treatment chronic kidney disease effect and its application | |
| CN101322734B (en) | Total Codonopsis saponins with anti-inflammatory and immune effects and preparation method thereof | |
| CN104116752B (en) | The application of aucubin in preparation treatment kidney region fibrosis medicine | |
| CN102225095B (en) | Effective fraction of plantain seeds as well as preparation method and application thereof | |
| CN102370901A (en) | Pharmaceutical composition for treating nephrosis and preparing process thereof | |
| CN109091602A (en) | Semen allii tuberosi effective component, extracting method and its application in terms of liver injury medicament is protected in preparation | |
| CN100584358C (en) | Traditional Chinese medicine composition for treating cardio cerebrovasculer disease and its preparations and preparation method | |
| CN102670711A (en) | White flower salviae miltiorrhizae extract for curing angiitis, preparation method and application | |
| CN102048874A (en) | Fructus Aurantii Fructus or Fructus Fructus Total Flavonoids Extract Extracted by Water Decoction and Application thereof | |
| CN101926848B (en) | Medicinal composition for treating heart cerebrovascular diseases and preparation thereof | |
| CN105796637A (en) | Anti-breast cancer traditional Chinese medicine composition as well as preparation method and application thereof | |
| CN100509009C (en) | A Chinese medicinal preparation for treating cardiovascular and cerebrovascular diseases and ischemic apoplexy, and its preparation method | |
| CN105362259B (en) | A kind of Hickory Leaves extract pinostrobin with anti-trioxypurine effect and its preparation method and application | |
| CN103989752A (en) | Pharmaceutical composition used for preventing and treating diabetes mellitus combined with hypertension | |
| CN104042678B (en) | A kind of treat hyperlipemia pharmaceutical composition and preparation method and purposes | |
| CN104116751B (en) | The application of aucubin in preparation treatment hepatic fibrosis medicines | |
| CN107693576A (en) | A kind of Chinese medicine composition for being used to treat coronary heart disease |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20161220 Address after: 411000 Hunan province Changsha high tech Development Zone, Lu Tin Road No. 28, No. 601, C8-C10 building science and Technology Park Lugu Patentee after: Changsha are biological technology Co., Ltd. Address before: 410078 Hunan province Changsha Kaifu District, Xiangya Road No. 110 clinical pharmacology research institute of Central South University Patentee before: Ouyang Dongsheng |
|
| TR01 | Transfer of patent right | ||
| PE01 | Entry into force of the registration of the contract for pledge of patent right | ||
| PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: Application of aucubin to preparation of medicines for treating idiopathic pulmonary fibrosis Effective date of registration: 20190516 Granted publication date: 20150909 Pledgee: Bank of Changsha Limited by Share Ltd science and Technology Branch Pledgor: Changsha are biological technology Co., Ltd. Registration number: 2019430000039 |
|
| CP03 | Change of name, title or address |
Address after: Room 601, building c8-c10, jinruilugu science and Technology Park, No.28 Lutian Road, high tech Development Zone, Changsha City, Hunan Province, 410000 Patentee after: Changsha Duzheng Biotechnology Co., Ltd Address before: 411000 Hunan province Changsha high tech Development Zone, Lu Tin Road No. 28, No. 601, C8-C10 building science and Technology Park Lugu Patentee before: CHANGSHA DUXACT BIOTECH Co.,Ltd. |
|
| CP03 | Change of name, title or address | ||
| PC01 | Cancellation of the registration of the contract for pledge of patent right |
Date of cancellation: 20200922 Granted publication date: 20150909 Pledgee: Bank of Changsha Limited by Share Ltd. science and Technology Branch Pledgor: CHANGSHA DUXACT BIOTECH Co.,Ltd. Registration number: 2019430000039 |
|
| PC01 | Cancellation of the registration of the contract for pledge of patent right | ||
| PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: Application of aucubin in the preparation of drugs for idiopathic pulmonary fibrosis Effective date of registration: 20200928 Granted publication date: 20150909 Pledgee: Bank of Changsha Limited by Share Ltd. science and Technology Branch Pledgor: Changsha Duzheng Biotechnology Co., Ltd Registration number: Y2020430000014 |
|
| PE01 | Entry into force of the registration of the contract for pledge of patent right | ||
| PC01 | Cancellation of the registration of the contract for pledge of patent right |
Date of cancellation: 20211202 Granted publication date: 20150909 Pledgee: Bank of Changsha Limited by Share Ltd. science and Technology Branch Pledgor: Changsha Duzheng Biotechnology Co., Ltd Registration number: Y2020430000014 |
|
| PC01 | Cancellation of the registration of the contract for pledge of patent right |