CN104116752B - The application of aucubin in preparation treatment kidney region fibrosis medicine - Google Patents
The application of aucubin in preparation treatment kidney region fibrosis medicine Download PDFInfo
- Publication number
- CN104116752B CN104116752B CN201410376559.4A CN201410376559A CN104116752B CN 104116752 B CN104116752 B CN 104116752B CN 201410376559 A CN201410376559 A CN 201410376559A CN 104116752 B CN104116752 B CN 104116752B
- Authority
- CN
- China
- Prior art keywords
- aucubin
- ethyl acetate
- defat
- apply 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.)
- Active
Links
Landscapes
- Medicines Containing Plant Substances (AREA)
Abstract
The present invention relates to Chinese medicine extract purposes field, specifically provide the application of aucubin in preparation treatment kidney region fibrosis medicine.Described aucubin is preferably Eucommia extract, and wherein aucubin purity is more than 98%.
Description
Technical field
The invention belongs to Chinese medicine extract purposes field, be specifically related to the novelty teabag of aucubin.
Background technology
Renal fibrosis is a kind of pathophysiological change, be kidney function by health to damage, then to damage, until the progressive process of afunction.The consequently irreversible infringement of renal function Progressive symmetric erythrokeratodermia, brings huge threat to human health.Kidney region fibrosis is the common pathological characters that kidney disease caused by a variety of causes advances to End-stage renal failure.A large amount of clinical and pathological data shows, the order of severity of the Chronic Renal Injury that a variety of causes causes and kidney region fibrosis comparatively glomerulopathy changes to closely.Therefore, in order to slow down and reverse the process of chronic renal disease, improve renal function, find and find the active drug for the treatment of renal fibrosis for guiding clinical treatment, to improve nephrotic's quality of life significant.
Aucubin (aucubin, AU) belongs to iridoid glycosides, and molecular formula is C
15h
22o
9, molecular weight 346.33, fusing point 181 DEG C, soluble in water, methanol and ethanol polar solvent, be dissolved in the weak polar solvents such as chloroform, ether and petroleum ether hardly.This compound is mainly present in Cortex Eucommiae EucommiaulmoidesOliver, Cornaceae plant peach jaurel belongs in the plant 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, there is numerous pharmacologically actives such as protecting liver and detoxication, antiinflammatory, antioxidation, promotion collage synthesis, 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, and its medicinal history is long, has a wide range of applications clinical.Eucommia is the side-product of Cortex Eucommiae industry, and containing gutta-percha, oils and fats, protein, iridoid etc., wherein aucubin (aucubin, AU) content is up to 7%-11%.Aucubin has antiinflammatory, antioxidation, removing toxic substances protect the liver, the pharmacologically active such as anti-bacteria and anti-virus, osteoporosis, because its character is active, biological activity obviously but not easily obtain, be called as " star molecule ", have Development volue.Be showed no the report of aucubin to kidney region fibrosis effect both at home and abroad at present.
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, disclose " a kind of from Cortex Eucommiae fruit, extract the process of aucubin ", 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 rapidly and efficiently preparing aucubin monomer from the Cortex Eucommiae ", and the method can obtain aucubin through extraction-crystallization two step, but yield is lower, serious waste of resources.Chinese patent CN101863938A discloses " a kind of method preparing high-purity aucubin ", the method is separated obtains aucubin 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 novelty teabag of aucubin.We study and find that aucubin has preventive and therapeutic effect to kidney region fibrosis, can be used for the medicine preparing treatment kidney region fibrosis.
For achieving the above object, technical scheme of the present invention is:
The application of aucubin in preparation treatment kidney region fibrosis medicine.
Described aucubin is preferably Eucommia extract, and wherein aucubin purity is more than 98%.
It is raw material that described aucubin is preferably further with Eucommia, is shelled by Eucommia, and kernel is pulverized, and through defat with petroleum ether, ethanol extraction, adds acetone crystallisation by cooling, then through silica column purification, obtains aucubin monomer.
Further preferred, described aucubin is obtained by following preparation method, comprises the following steps:
1. defat: shell the Cortex Eucommiae of drying fruit to obtain kernel, and kernel is pulverized, and defat with petroleum ether, obtains defat coarse fodder; Described petroleum ether consumption is the 6-10 times amount of Cortex Eucommiae fruit kernel quality, and defat number of times is 2-4 time, and degreasing time is 1.5-4 hour;
2. extract: described defat coarse fodder is added ethanol and extracts, filter, merge extractive liquid, 40 DEG C-60 DEG C 1/5-1/12 being concentrated into extracting liquid volume, obtain concentrated extracting solution; Described ethanol consumption is the 6-12 times amount of Cortex Eucommiae fruit quality, and extraction time is 3-5 time, and each extraction time is 2-5 hour;
3. crystallization: described concentrated extracting solution is added the saturated dissolving of acetone, crystallisation by cooling, obtain aucubin coarse crystal;
4. silica gel column chromatography: described aucubin coarse crystal is added the saturated dissolving of ethyl acetate, add silica gel column chromatography again, wherein the mass ratio of silica gel for chromatography and aucubin coarse crystal is 6:1-11:1, then with the solution eluting successively that ethyl acetate and methanol form, 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: concentrated at 40 DEG C-60 DEG C by described eluent, lyophilization, obtains aucubin monomer product.
Preferred version: rapid 1. described in pulverize after be 40-50 order.
Preferred version: step 1. PetroChina Company Limited.'s ether consumption is the 8-9 times amount of Cortex Eucommiae fruit kernel, and defat number of times is 3-4 time, and degreasing time is 2-3 hour.
Preferred version: step 2. middle ethanol consumption is the 8-10 times amount of raw material, 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, lysate is placed in 4-10 DEG C of cooling, crystallization 12-72 hour.
Preferred version: step 4. in the mass ratio of silica gel for chromatography and aucubin coarse crystal be 8:1-10:1.
Preferred version: the order of the step 4. solution eluting successively of middle ethyl acetate and methanol composition 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 be further explained and illustrate.
Aucubin of the present invention is preferably Eucommia extract, can be selected from pulverizing, squeeze, calcine, grind, sieve, percolation, extraction, water extraction, alcohol extraction, water precipitating, precipitate with ethanol, ester are carried, the method such as ketone is carried, chromatography, filtration obtains by employing.With this extract for active substance can be made into pharmaceutical preparation, described extract can be the material of extractum form, can be dry extract also can be fluid extract, can be powdered substance, need to make different states according to the difference of preparation.
The present invention also mentions the pharmaceutical preparation of aucubin through the applicable any unit dosage form taken 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, can make slow releasing preparation, enteric coated preparation when needing.
Aucubin of the present invention, medicine acceptable carrier can be added when being prepared into pharmaceutical preparation, 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 being processed through extraction or other modes by Eucommia, making pharmaceutically active substance, subsequently, with this active substance for raw material, when needing, add medicine acceptable carrier, make pharmaceutical preparation according to the routine techniques of galenic pharmacy.
Detailed description of the invention
Below by embodiment, the present invention will be further explained, and described in embodiment, percentage composition is mass percentage.
The preparation of embodiment 1 Eucommia extract aucubin
Shelled by Eucommia, kernel powder is broken to 40 orders, and get 10kg and drop into extraction pot, add 60L defat with petroleum ether, defat 2 times, each 3 hours, leaching medicinal residues is defat coarse fodder.Add 80L ethanol to defat coarse fodder supersound extraction 2 hours, extract 3 times, merge extractive liquid.Extracting solution 40 DEG C is evaporated to 1/8 of original volume and reclaims ethanol.Concentrated solution adds the saturated dissolving of acetone, and 7 DEG C of crystallizations 48 hours, coarse crystal adds the saturated dissolving of ethyl acetate.Get 10L silica gel dress post, saturated solution is added silicagel column, use 3BV ethyl acetate (quality is than ethyl acetate: methanol=1:0) successively, 4BV10:1 ethyl acetate/methanol (quality is than ethyl acetate: methanol=10:1), 5BV6:1 ethyl acetate/methanol (quality is than ethyl acetate: methanol=6:1), 4BV4:1 ethyl acetate/methanol eluant solution (quality is than ethyl acetate: methanol=4:1), detect by thin layer chromatography simultaneously, collect aucubin flow point, merge eluent, 40 DEG C of concentrating under reduced pressure, lyophilization, obtain aucubin monomer 410g, measure through HPLC method, its content reaches 98.7%.
The preparation of embodiment 2 Eucommia extract aucubin
Shelled by Eucommia, kernel powder is broken to 50 orders, and get 10kg and drop into extraction pot, add 80L defat with petroleum ether, defat 3 times, each 4 hours, leaching medicinal residues is defat coarse fodder.Add 100L ethanol to defat coarse fodder supersound extraction 4 hours, extract 5 times, merge extractive liquid.Extracting solution 40 DEG C is evaporated to 1/10 of original volume and reclaims ethanol.Concentrated solution adds the saturated dissolving of acetone, and 4 DEG C of crystallizations 72 hours, coarse crystal adds the saturated dissolving of ethyl acetate.Get 10L silica gel dress post, saturated solution is added silicagel column, use 3BV ethyl acetate (quality is than ethyl acetate: methanol=1:0) successively, 4BV10:1 ethyl acetate/methanol (quality is than ethyl acetate: methanol=10:1), 5BV6:1 ethyl acetate/methanol (quality is than ethyl acetate: methanol=6:1), 4BV4:1 ethyl acetate/methanol eluant solution (quality is than ethyl acetate: methanol=4:1), , detect by thin layer chromatography simultaneously, collect aucubin flow point, merge eluent, 40 DEG C of concentrating under reduced pressure, lyophilization, obtain aucubin monomer 480g, measure through HPLC method, its content reaches 99.2%.
Embodiment 3
The aucubin obtain embodiment 1 and embodiment 2 and commercially available aucubin (being purchased from Yuan Ye bio tech ltd, Shanghai) are studied for the Protection to kidney region fibrosis of embodiment 3.
1. experimental technique
1.1 dose design and grouping
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 Fluorofenidone positive controls (10mg/kg).
Table 1 tests grouping and dose design
1.2 experimental procedure
Healthy male SD rat 70 (body weight 250 ~ 300g), randomly draws 60 for experimental group, lumbar injection streptozotocin (STZ, 55mg/kg, be dissolved in the aseptic citrate buffer solution of 0.1mol/L, and concentration is 2%, and pH value is 4.5).Remain the citrate buffer solution that 10 are Normal group, lumbar injection same volume.72 hours and the 7th day tail venous blood sampling survey random blood sugar after administration, glucose in urine biochemical indicator.Twice blood glucose all >=16.7mmol/L, glucose in urine +++ ~ ++++be defined as diabetes rat model.60 diabetes rats of mould will be specified to, be divided into model group (B group) at random, the basic, normal, high dosage group of aucubin (C, D, E group), commercially available aucubin group (F group), Fluorofenidone positive controls (G group).Aucubin distilled water, Fluorofenidone 0.5% Carboxymethyl cellulose sodium are according to dosage mixed with respective concentration before experiment by every day, now with the current, by 10mL/kg gastric infusion, and 1 times/day, continuous 15 days.A group and B group give isopyknic distilled water.Experimental session rat freely drinks water, and feed (standard diet), does not use insulin and other hypoglycemic medicine.The 8th weekend after experiment starts administration puts to death rat.Slaughter the previous day and collect twenty-four-hour urine liquid with single metabolic cage, survey urine volume, 3000rpm leaves and takes supernatant in-20 DEG C of preservations after centrifugal 5 minutes, for the mensuration of 24h microdose urine protein.Weigh before execution, rat is put to death by femoral artery blood-letting, leaves and takes blood specimen, and it is frozen in-20 DEG C that 3000rpm gets serum after centrifugal 5 minutes, the biochemical indicators such as blood glucose to be measured, blood urea nitrogen (BUN), serum creatinine (Scr).Cut rapidly two kidney after opening abdominal cavity, remove after two kidney tunicle filter paper blots bloodstain and weigh; Left kidney is placed in 4% paraformaldehyde and fixes, and treats light Microscopic observation renal pathology morphological change
1.3 Testing index
Kidney morphologic observation: get rat kidney respectively and be placed in 4% paraformaldehyde and fix, conventional dehydration, embedding, section, HE dyeing, carry out histopathologic examination.Pathology ranking criterion: tubulointerstitial injury is marked, each specimen Stochastic choice does not repeat 10 visuals field, comprises cortex, medullary substance, skin marrow intersection, comprises 6 specific targets: (1) tubular ectasia; (2) renal tubules atrophy; (3) renal cells cavity is formed; (4) renal cells cavity is formed; (5) kidney region fibrosis; (6) renal interstitial inflammatory cell infiltration, namely the focal type cell infiltration of renal interstitial is mild damage; The inflammatory cell infiltration that diffusivity is dispersed in is moderate infringement; The intensive inflammatory cell infiltration of diffusivity is severe infringement.According to the degree of pathological lesion, 0 point is divided into each project: normal; 1 point: mild damage's (pathological changes is less than 20%); 2 points: moderate infringement (pathological changes 20% ~ 40%); 3 points: severe infringement (pathological changes is greater than 40%).
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 ' stest method inspection normality and homogeneity of variance.If meet normality and homogeneity of variance, carry out statistical analysis with one factor analysis of variance (One-wayANOVA) and postHocLSD; If do not meet normality and heterogeneity of variance, then check with Kruskal-Wallis.If Kruskal-Wallis inspection has statistical significance (P<0.05), then Dunnett ' sTest (nonparametric technique) is used to compare analysis.Significant difference and biological significance is considered during evaluation.
2 experimental results
Aucubin is on the impact of Renal Paphology
Comparing with Normal group, there is tubular ectasia, atrophy in model group rats kidney, and renal cells is downright bad, kidney region fibrosis and the intensive inflammatory cell infiltration of diffusivity.As can be seen from the statistical result of average pathology integration, model group pathology integration is significantly higher than Normal group, prompting renal fibrosis model modeling success.Administration is after 15 days, and aucubin high dose group, commercially available aucubin and Fluorofenidone positive controls all occur significant difference compared with model group, and there is a change for the better for kidney region fibrosis.
Table 2 aucubin is on the pathological impact of kidney region fibrosis
Note: compare with Normal group,
++p<0.01, compares with model group,
*p<0.05.
3 experiment brief summaries
The above results shows, aucubin high dose group, commercially available aucubin group significantly can improve tubular ectasia, the atrophy of kidney region fibrosis model, and the symptoms such as renal interstitial inflammatory cell infiltration, have some improvement to kidney region fibrosis.
Claims (10)
1. the application of aucubin in preparation treatment kidney region fibrosis medicine.
2. apply according to claim 1, it is characterized in that, described aucubin is Eucommia extract, and wherein aucubin purity is more than 98%.
3. apply according to claim 1 or 2, it is characterized in that, described aucubin is raw material with Eucommia, shelled by Eucommia, kernel is pulverized, through defat with petroleum ether, and ethanol extraction, add acetone crystallisation by cooling, then through silica column purification, obtain aucubin monomer.
4. apply according to claim 3, it is characterized in that, the preparation method of described aucubin comprises the following steps:
1. defat: shell the Cortex Eucommiae of drying fruit to obtain kernel, and kernel is pulverized, and defat with petroleum ether, obtains defat coarse fodder; Described petroleum ether consumption is the 6-10 times amount of Cortex Eucommiae fruit kernel quality, and defat number of times is 2-4 time, and degreasing time is 1.5-4 hour;
2. extract: described defat coarse fodder is added ethanol and extracts, filter, merge extractive liquid, 40 DEG C-60 DEG C 1/5-1/12 being concentrated into extracting liquid volume, obtain concentrated extracting solution; Described ethanol consumption is the 6-12 times amount of Cortex Eucommiae fruit quality, and extraction time is 3-5 time, and each extraction time is 2-5 hour;
3. crystallization: described concentrated extracting solution is added the saturated dissolving of acetone, crystallisation by cooling, obtain aucubin coarse crystal;
4. silica gel column chromatography: described aucubin coarse crystal is added the saturated dissolving of ethyl acetate, add silica gel column chromatography again, wherein the mass ratio of silica gel for chromatography and aucubin coarse crystal is 6:1-11:1, then with the solution eluting successively that ethyl acetate and methanol form, 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: concentrated at 40 DEG C-60 DEG C by described eluent, lyophilization, obtains aucubin monomer product.
5. apply according to claim 4, it is characterized in that, step 1. described in pulverize after be 40-50 order.
6. apply according to claim 4, it is characterized in that, step 1. PetroChina Company Limited.'s ether consumption is the 8-9 times amount of Cortex Eucommiae fruit kernel, and defat number of times is 3-4 time, and degreasing time is 2-3 hour.
7. apply according to claim 4, it is characterized in that, step 2. middle ethanol consumption is the 8-10 times amount of raw material, and extraction time is 3-4 time, and each extraction time is 3-4 hour.
8. apply according to claim 4, it is characterized in that, step 3. in after the saturated dissolving of ethyl acetate, lysate is placed in 4-10 DEG C of cooling, crystallization 12-72 hour.
9. apply according to claim 4, it is characterized in that, step 4. in the mass ratio of silica gel for chromatography and aucubin coarse crystal be 8:1-10:1.
10. apply according to claim 4, it is characterized in that, the order of the step 4. solution eluting successively of middle ethyl acetate and methanol composition 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 |
|---|---|---|---|
| CN201410376559.4A CN104116752B (en) | 2014-08-01 | 2014-08-01 | The application of aucubin in preparation treatment kidney region fibrosis medicine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410376559.4A CN104116752B (en) | 2014-08-01 | 2014-08-01 | The application of aucubin in preparation treatment kidney region fibrosis medicine |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104116752A CN104116752A (en) | 2014-10-29 |
| CN104116752B true CN104116752B (en) | 2015-11-18 |
Family
ID=51762532
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410376559.4A Active CN104116752B (en) | 2014-08-01 | 2014-08-01 | The application of aucubin in preparation treatment kidney region fibrosis medicine |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104116752B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107198696B (en) * | 2017-06-22 | 2020-05-29 | 南方医科大学 | Application of asperuloside in preparation of medicine for treating renal fibrosis |
| CN110538189A (en) * | 2019-09-22 | 2019-12-06 | 江西普正制药股份有限公司 | Eucommia ulmoides extract composition for treating renal fibrosis and application thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102911222A (en) * | 2012-10-30 | 2013-02-06 | 薛宏宇 | Extraction method of aucubin and application of aucubin |
-
2014
- 2014-08-01 CN CN201410376559.4A patent/CN104116752B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102911222A (en) * | 2012-10-30 | 2013-02-06 | 薛宏宇 | Extraction method of aucubin and application of aucubin |
Non-Patent Citations (1)
| Title |
|---|
| 糖对人肾成纤维细胞增殖及纤维连结蛋白分泌的影响;王伟铭等;《上海医学》;19980531;第21卷(第5期);第253-255页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN104116752A (en) | 2014-10-29 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN100475243C (en) | Hypoglycemic, antilipenic and hemopathy-treating glutinous rehmannia extract and preparing method thereof | |
| CN101062165B (en) | Citrus aurantium total flavone extract and the preparing method thereof | |
| CN102600219B (en) | Total flavone extract of abelmoschus manihot and preparing method of total flavone extract | |
| WO2018058261A1 (en) | Traditional chinese medicine composition for treating psoriasis and preparation method thereof | |
| CN101062128A (en) | Extract of total glucosides of paeony and the preparing method thereof | |
| CN102138966A (en) | Tibetan capillaris extract and preparation method, pharmaceutical composition and use thereof | |
| CN102068535A (en) | Immature bitter orange or bitter orange total flavonoids extract prepared by ethanol reflux and extraction and application thereof | |
| CN104116752B (en) | The application of aucubin in preparation treatment kidney region fibrosis medicine | |
| CN107349244B (en) | Extraction method of malonyl ginsenoside | |
| CN105982970A (en) | Traditional Chinese medicinal composition for treating psoriasis and preparation method of traditional Chinese medicinal composition | |
| CN103479711B (en) | Application of eucommia ulmoides lignans extracts in preparation of medicine treating renal interstitial fibrosis | |
| CN104116753B (en) | The application of aucubin in preparation treatment idiopathic pulmonary fibrosis medicine | |
| CN104224867B (en) | A kind of desmodium sugar-free particle and preparation method thereof | |
| CN101978982A (en) | Application of Japanese ginseng or extract thereof to preparation of medicament for resisting gout and repairing hyperuricemic kidney injury | |
| CN109248188A (en) | A kind of preparation method and applications of goldspink root extract | |
| CN102641342B (en) | A kind of Chinese medicine extract and preparation method for the treatment of nephropathy | |
| CN100584358C (en) | Traditional Chinese medicine composition for treating cardio cerebrovasculer disease and its preparations and preparation method | |
| CN104116751B (en) | The application of aucubin in preparation treatment hepatic fibrosis medicines | |
| CN101926848B (en) | Medicinal composition for treating heart cerebrovascular diseases and preparation thereof | |
| CN107693576A (en) | A kind of Chinese medicine composition for being used to treat coronary heart disease | |
| CN108210651A (en) | It is a kind of to be used to treat natural drug composition of diabetic nephropathy and preparation method thereof | |
| CN103989966B (en) | Medicine composition for preventing and treating migraine disease and preparation method and application thereof | |
| CN1977887B (en) | Medicinal composition for treating hepatitis | |
| CN102652791A (en) | Medicinal composition with hepatic fibrosis resistance and preparation method | |
| CN112717061B (en) | Pretreatment extract of heat-clearing eight-ingredient capsule and preparation method thereof |
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 | ||
| 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 |