CN101856332A - Method for preparing 8, 9-single-epoxy brevifolin PLGA microspheres - Google Patents
Method for preparing 8, 9-single-epoxy brevifolin PLGA microspheres Download PDFInfo
- Publication number
- CN101856332A CN101856332A CN201010208729A CN201010208729A CN101856332A CN 101856332 A CN101856332 A CN 101856332A CN 201010208729 A CN201010208729 A CN 201010208729A CN 201010208729 A CN201010208729 A CN 201010208729A CN 101856332 A CN101856332 A CN 101856332A
- Authority
- CN
- China
- Prior art keywords
- plga
- solution
- colostrum
- microsphere
- concentration
- 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
Images
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a method for preparing 8, 9-single-epoxy brevifolin PLGA microspheres, which comprises the following steps of: adding PLGA into CH2Cl2 to obtain PLGA solution, dissolving 8, 9-single-epoxy brevifolin into PBS to obtain medicinal solution, precisely measuring a certain amount of medicinal solution and adding the medicinal solution into a proper amount of PLGA solution, ultrasonically emulsifying the solution to obtain foremilk, adding the foremilk into PVA aqueous solution, stirring the solution by a magnetic stirrer, evaporating the CH2Cl2, and solidifying microspheres to obtain the 8, 9-single-epoxy brevifolin PLGA microspheres. The 8, 9-single-epoxy brevifolin PLGA microspheres prepared according to the preparation method of the invention can increase the dissolubility and stability of the 8, 9-single-epoxy brevifolin, and more important, has targeting property so as to reduce the dose, reduce the toxic or side effect and improve the bioavailability.
Description
Technical field
The present invention relates to a kind of preparation method of medicine, be specifically related to a kind of preparation method of 8,9 single-epoxy brevifolin phenol PLGA microspheres.
Background technology
Euphorbiaceae Leafflower (Phyllanthus) plant the whole world have 600 surplus kind, have the hepatitis B virus of killing activity from discovery Herba Scopariae (Phyllanthus niruri L.) such as nineteen eighty-two India scholar Thyagarjan external.Phyllanthus plant has 33 kinds in China, Shaanxi Province's phyllanthus plant has two kinds, be Cacumen Securinegae Suffruticosae (Phyllanthus urinaria L) and Phyllanthus simplex Retz (P.simplex Retz.), mainly be distributed in Shan Nan, Phyllanthus simplex Retz claim again Herba Phyllanthi Urinariae, Margarita etc., record the earliest in " the SHENGCAO property of medicine is wanted fully ", have the effect of suppressing the hyperactive liver, heat clearing away, diuretic, detoxifcation, be used for the treatment of enteritis, hepatitis, urinary tract infection, nameless gall etc.People have isolated tens chemical compounds from Phyllanthus simplex Retz at present, and these chemical compounds have been carried out the screening of structure evaluation and antivirus action, and the result shows that its 8,9 contained single-epoxy brevifolin phenol have good antiviral effect.
Polylactic acid-glycolic guanidine-acetic acid copolymer (PLGA) is commonly used for the degradable material in the slow control delivery, it is a kind of degradable functional high molecule material, have good encystation, thermoplasticity, biocompatibility and good degradation property, its degradation rate changes along with the difference of two kinds of chemical compound proportion of composing, can be prepared into microball preparation according to the polylactic acid-glycolic guanidine-acetic acid that the character and the purposes of medicine select different proportion to form with given efficacy, therefore, PLGA is widely used in the preparation and the production of microsphere as a kind of the most frequently used polymeric material.Prepared PLGA microsphere, its particle diameter does not wait from several microns to the hundreds of micron, can be used for injection and oral.These microball preparations of making have general formulation can not and advantage: can cover bad smell, reduce the not compliance in patient's medication process; Improve the availability of medicine when reducing dosage; Can regulate the size of particle diameter, slowly realize target administration in the release; Medicine is stable in vivo to be discharged constantly, effectively avoids drug level " peak valley " phenomenon that fluctuation caused in vivo.
The PLGA microsphere has hydrophobic interaction and easily is gathered in liver by cytophagous phagocytosis, therefore, the treating hepatitis medicine is made the PLGA microsphere, has both played slow releasing function, has reached the effect of passive liver target again, has increased curative effect when reducing dosage.
Summary of the invention
The object of the present invention is to provide a kind of preparation method of 8,9 single-epoxy brevifolin phenol PLGA microspheres.
For achieving the above object, the technical solution used in the present invention is: at first get PLGA and join dichloromethane (CH
2Cl
2) in, making concentration is 25～35mgmL
-1PLGA solution, with 8,9-single-epoxy brevifolin phenol is dissolved in PBS solution, makes 10～15mgmL
-1Drug solution; Measure a certain amount of drug solution according to 1: 5～10 ratio precision then and join in an amount of PLGA solution, ultrasonic emulsification makes colostrum; This colostrum is joined in 1～3%PVA aqueous solution of 8～12 times of amounts, magnetic stirring apparatus 1500r stirred after 2～4 hours, 500rmin again
-1Stirring at low speed 1.5～2.5 hours is with dichloromethane (CH
2Cl
2) volatilize, microsphere is solidified, promptly.
8, the 9 single-epoxy brevifolin phenol PLGA microspheres that obtain according to preparation method of the present invention can not only increase dissolubility, the stability of 8,9 single-epoxy brevifolin phenol, and the more important thing is to have targeting, thereby the minimizing dosage reduces toxic and side effects, improves bioavailability.
Description of drawings
Fig. 1 is the influence of PLGA kind to microsphere envelop rate and drug loading;
Fig. 2 is the influence of PVA concentration to microsphere envelop rate and drug loading;
Fig. 3 is the influences of different colostrum ratios to microsphere envelop rate and drug loading;
Fig. 4 is the influence of PLGA concentration to microsphere envelop rate and drug loading;
Fig. 5 is the microspherulite diameter scattergram
The specific embodiment
The present invention is described in detail below in conjunction with embodiment.
One, microsphere preparation technology's research
The preparation of microsphere is subjected to influence of various factors, these factors are restricting the quality of prepared microsphere jointly, therefore, by selecting very representative investigation index-envelop rate and drug loading, reference index as the microspheres quality evaluation, prepared PLGA microsphere is carried out influence factor's investigation, have very important significance.
1.PLGA kind is to the influence of microsphere envelop rate and drug loading
The condition of choosing ratio, colostrum and the PVA ratio of PLGA concentration, PVA concentration, medicine and PLGA solution and preparing colostrum is investigated the influence of the PLGA of three kinds of different proportion of composing to microsphere envelop rate and drug loading as fixed factor.Each factor and level see Table 1.
Table 4-1 investigates each factor and the level of PLGA kind
| Factor | Level |
| PLGA kind/LA: GA | ??65∶35；75∶25；85∶15 |
| PLGA concentration/mgmL -1 | ??30 |
[0025]
| PVA concentration/% | ??2 |
| The colostrum proportion of composing | ??1∶7 |
| The ratio of colostrum and PVA aqueous solution | ??1∶10 |
| The condition of preparation colostrum | Ultrasonic emulsification 2min (ultrasonic 10s, 10s at interval) |
The PLGA kind the results are shown in Table 2, Fig. 1 to the investigation of microspheres quality influence.
Table 2 PLGA kind is to the influence of microsphere envelop rate and drug loading
| The PLGA proportion of composing | Concentration/the mgmL of concentrated solution -1 | Envelop rate/% | Drug loading/% | Outward appearance |
| ??75∶25 | ??0.017 | ??92.20 | ??5.50 | The stable homogeneous white emulsion has small amount of precipitate |
| ??85∶15 | ??0.029 | ??86.09 | ??5.06 | Faint yellow inhomogeneous suspension has a large amount of precipitations |
| ??65∶35 | ??0.02 | ??90.45 | ??5.22 | Faint yellow than homogeneous latex emulsion, small amount of precipitate is arranged |
(poly (lactic-co-glycolic acid) PLGA) is a kind of degradable functional high molecule material to polylactic acid-glycolic guanidine-acetic acid copolymer, and is nontoxic because of having excellent biological compatibility, is widely used in preparing microball preparation.It is to be polymerized at random by two kinds of monomer-lactic acid and hydroxyacetic acid, and different monomer ratio can be prepared dissimilar PLGA, its physical state, and chemical property and palliating degradation degree be the difference along with the difference of compositing monomer ratio all.
This paper selects LA for use: GA=75: 25, LA: GA=85: 15 and LA: GA=65: the PLGA of 35 3 kinds of different proportion of composing is as research material, investigate by envelop rate and drug loading its obtained microsphere, the proportion of composing of discovery PLGA has very big influence to the quality of microsphere, along with the difference of ratio, the outward appearance of microsphere, drug loading and envelop rate all present bigger difference.Discover by experiment as LA: GA=75: in the time of 25, the prepared microsphere of PLGA has higher entrapment and drug loading, and therefore, it is LA: GA=75 that the PLGA proportion of composing is selected in this experiment for use: 25 crystallization is as the host material of parcel microsphere.
2.PVA concentration is to the influence of microsphere envelop rate and drug loading
Choosing the ratio of ratio, colostrum and PVA aqueous solution of PLGA kind, PLGA concentration, medicine and PLGA solution and the condition of preparation colostrum is fixed factor, investigates the influence of the PVA of three kinds of variable concentrations to microsphere envelop rate and drug loading.Each factor and level see Table 3.
Table 3 is investigated each factor and the level of PVA concentration
| Factor | Level |
| PVA concentration/% | ??1；2；3 |
| PLGA kind/LA: GA | ??75∶25 |
| PLGA concentration/mgmL -1 | ??30 |
| The colostrum proportion of composing | ??1∶7 |
| The ratio of colostrum and PVA aqueous solution | ??1∶10 |
| The condition of preparation colostrum | Ultrasonic emulsification 2min (ultrasonic 10s, 10s at interval) |
PVA concentration sees Table 4, Fig. 2 to the measurement result that influences of microsphere envelop rate and drug loading.
Table 4 PVA concentration is to the influence of microsphere envelop rate and drug loading
| PVA concentration/% | Envelop rate/% | Drug loading/% | Outward appearance |
| ??1 | ??64.63 | ??4.04 | Yellow homogeneous emulsion |
| ??2 | ??92.20 | ??5.50 | White homogeneous emulsion has a small amount of white precipitate |
| ??3 | ??80.16 | ??5.01 | Faint yellow suspension has a large amount of white precipitates |
(polyvinyl alcohol is a kind of white or yellow-white powdery granule PVA) to polyvinyl alcohol, is the crystalline polymer material that is formed through alcoholysis by polyvinyl acetate, and is different with alcoholysis degree according to its degree of polymerization, and different character and specification are arranged.The PVA of domestic employing has specifications such as 05-88 and 17-88, and two kinds of filmogens all can be water-soluble.Because the polyvinyl alcohol non-activity does not decompose stable in properties, be absorbed hardly in digestive tract after the oral administration, 80% polyvinyl alcohol was discharged with stool in 48 hours, therefore, prepare in the process of microsphere at multi-emulsion method, usually be used as a kind of material relatively more commonly used and be applied to outer aqueous phase.
Outer water is important influence in the process for preparing microsphere with multi-emulsion method, and it is directly connected to the envelop rate and the drug loading of microsphere.This experiment adds the concentration of polyvinyl alcohol only continuous phase concentration is selected in the influence of microsphere envelop rate and drug loading by investigating.The concentration that Fig. 2 reflects PVA all has bigger influence to the envelop rate and the drug loading of microsphere.By selected above three kinds of PVA concentration are compared discovery, when PVA concentration was 2%, the envelop rate and the drug loading of PLGA microsphere all peaked, and therefore, the PVA aqueous solution of selection 2% is as the outer water of preparation microsphere.
3. different colostrum proportion of composing are to the influence of microsphere envelop rate and drug loading
Choosing the ratio of PLGA kind, PLGA concentration, PVA concentration, colostrum and PVA aqueous solution and the condition of preparation colostrum is fixed factor, investigates the influence of different colostrum ratios to microsphere envelop rate and drug loading.Each factor and level see Table 5.
Table 5 is investigated each factor and the level of colostrum ratio
| Factor | Level |
| The colostrum ratio | ??1∶5；1∶7；1∶10 |
| PLGA kind/LA: GA | ??75∶25 |
| PLGA concentration/mgmL -1 | ??30 |
| PVA concentration/% | ??2 |
| The ratio of colostrum and PVA aqueous solution | ??1∶10 |
| The condition of preparation colostrum | Ultrasonic emulsification 2min (ultrasonic 10s, 10s at interval) |
Different colostrum proportion of composing see Table 6, Fig. 3 to the influence of microsphere envelop rate and drug loading.
The different colostrum ratios of table 6 are to the influence of microsphere envelop rate and drug loading
| The colostrum ratio | Envelop rate/% | Drug loading/% | Outward appearance |
| ??1∶5 | ??60.09 | ??5.01 | Yellow emulsion has a large amount of precipitations |
| ??1∶7 | ??92.95 | ??5.81 | White homogeneous emulsion has a small amount of white precipitate |
| ??1∶10 | ??79.52 | ??3.30 | Faint yellow heterogeneity suspension has precipitation |
The amount of the medicine that the size of colostrum proportion of composing directly has influence on pharmaceutical carrier and comprised, thereby can be directly reflected into the envelop rate of prepared microsphere and the size of drug loading is come up, as seen from Figure 3, envelop rate and drug loading all present along with the increase of colostrum proportion of composing and increase earlier the trend that afterwards reduces, when the ratio of drug solution that forms colostrum and PLGA solution is 1: 7, envelop rate and drug loading all reach maximum, be respectively 92.95%, 5.81%, therefore, select 1: 7 as the ratio that forms colostrum.
4.PLGA concentration is to the influence of microsphere envelop rate and drug loading
With the ratio of PLGA kind, PVA concentration, colostrum proportion of composing, colostrum and PVA aqueous solution and the condition of preparation colostrum is fixed factor, investigates the influence of different PLGA concentration to microsphere envelop rate and drug loading.Each factor and level see Table 7.
Table 7 is investigated each factor and the level of PLGA concentration
| Factor | Level |
| PLGA concentration/mgmL -1 | ??10；30；50 |
| PLGA kind/LA: GA | ??75∶25 |
| PVA concentration/% | ??2 |
| The colostrum proportion of composing | ??1∶7 |
| The ratio of colostrum and PVA aqueous solution | ??1∶10 |
| The condition of preparation colostrum | Ultrasonic emulsification 2min (ultrasonic 10s, 10s at interval) |
PLGA concentration sees Table 8 to the influence of microsphere envelop rate and drug loading, Fig. 4.
Table 8 PLGA concentration is to the influence of microsphere envelop rate and drug loading
| PLGA concentration/mgmL -1 | Envelop rate/% | Drug loading/% | Outward appearance |
| ??10 | ??41.70 | ??7.45 | White homogeneous emulsion |
| ??30 | ??92.20 | ??5.50 | White has a small amount of white precipitate than the homogeneous emulsion |
| ??50 | ??74.38 | ??2.65 | Faint yellow heterogeneity suspension |
Fig. 4 reflects that more intuitively PLGA concentration all has remarkable influence to the envelop rate and the drug loading of microsphere, and along with the increase of PLGA concentration, the drug loading of microsphere presents falling tendency, takes the lead in reducing after the increase and seal, as PLGA concentration 30mgmL
-1The time, the envelop rate of microsphere reaches 92.20%, and its drug loading also reaches 5.50%, takes all factors into consideration its influence to envelop rate and drug loading, selects 30mgmL
-1PLGA is as the optimum concentration of this microsphere of preparation.
5. the colostrum preparation method is to the influence of microsphere envelop rate, drug loading and outward appearance
As fixed factor, each factor and level see Table 9 with the ratio of PLGA kind, PLGA concentration, PVA concentration, colostrum proportion of composing and colostrum and PVA aqueous solution.
Table 9 is investigated the factor and the level of colostrum preparation method
| Factor | Level |
| PLGA kind/LA: GA | ??75∶25 |
| PLGA concentration/mgmL -1 | ??30 |
| PVA concentration/% | ??2 |
| The colostrum proportion of composing | ??1∶7 |
| The ratio of colostrum and PVA aqueous solution | ??1∶10 |
By above fixed factor is set, investigate of the influence of different colostrum preparation methoies to microsphere envelop rate, drug loading and outward appearance, colostrum preparation method and condition see Table 10.
Table 10 colostrum preparation method and condition
| The colostrum preparation method | Condition |
| Ultrasonic | 2min (ultrasonic 10s, 10s at interval) |
| High-speed stirred | ??10000r·min -1 |
The colostrum preparation method sees Table 11 to the influence of microsphere envelop rate, drug loading and outward appearance.
Table 11 colostrum preparation method is to the influence of microsphere envelop rate, drug loading and outward appearance
| The colostrum preparation method | Envelop rate/% | Drug loading/% | Outward appearance |
| Ultrasonic | ??92.20 | ??5.50 | White has a small amount of white precipitate than the homogeneous emulsion |
| High-speed stirred | ??92.95 | ??5.81 | Clarification, homogeneous be fluorescence liquid slightly |
The form of the different prepared microspheres of preparation method presents bigger difference, the bigger and big or small heterogeneity of ultrasonic method microspheres prepared particle diameter, and the visible larger particles of naked eyes presents the suspension state, and by high speed homogenizer 10000rmin
-1Stir prepared microsphere and present more uniform pellucidity.By the envelop rate and the drug loading of two kinds of obtained microspheres of method of comparison, the microsphere that discovery obtains by high-speed stirred, its envelop rate and drug loading all are higher than the envelop rate and the drug loading of the prepared microsphere of ultrasonic method.
Brief summary: comprehensive above analysis and investigation to each factor, select the prescription of optimum condition as the microsphere preparation: 30mgmL
-1PLGA (LA: GA=75: 25); Drug solution and PLGA solution proportion 1: 7; 10000rmin
-1High-speed stirred prepares colostrum; In the aqueous solution of dispersion and 2%PVA, magnetic agitation.
Two, the preparation of best prescription technology microsphere and quality analysis
By single factor analysis, select 8 of the best, 9-single-epoxy brevifolin phenol microsphere preparation technology prepares 6 batches of microspheres, and preparation technology is as follows:
Precision is measured a certain amount of 12.5mgmL
-18,9-single-epoxy brevifolin phenol PBS solution, joining concentration according to 1: 7 ratio is 30mgmL
-1PLGA solution in, 10000rmin
-1High-speed stirred makes colostrum, this colostrum is joined in the 2%PVA aqueous solution of 10 times of amounts, and magnetic stirrer is used 1500rmin earlier
-1Stirred 3 hours fast, again magnetic stirring apparatus is transferred to 500rmin
-1, stirring at low speed 2 hours is treated dichloromethane (CH
2Cl
2) volatilize, can obtain solidified microsphere.6 batches of microspheres of preparation under the same condition.
Get according to optimised process make 8, each 1mL of 9-single-epoxy brevifolin phenol PLGA microsphere supernatant liquid filtering liquid, join the upper end of 0.5g sephadex column, carry out eluting, by observing change in color in the gel column with tri-distilled water, collect 5～10mL eluent, concentrate, sample introduction, with high effective liquid chromatography for measuring be not wrapped 8,9-single-epoxy brevifolin phenol, the envelop rate of calculating microsphere.8, the computing formula of 9-single-epoxy brevifolin phenol PLGA microsphere envelop rate is as follows:
In the formula: M
1---the quality of the single-epoxy brevifolin phenol of adding
M
2---the quality of free single-epoxy brevifolin phenol
M
3---the quality of the PLGA of adding
Prepared 6 batches of microspheres present stable homogeneous than pellucidity, its envelop rate and drug loading see Table 12.
Six batches 8 in table 12, the envelop rate and the drug loading of 9-single-epoxy brevifolin phenol PLGA microsphere
| Batch | Envelop rate/% | Drug loading/% |
| ??1 | ??92.75 | ??5.51 |
| ??2 | ??92.66 | ??5.52 |
| ??3 | ??92.32 | ??5.50 |
| ??4 | ??93.04 | ??5.54 |
| ??5 | ??92.27 | ??5.49 |
| ??6 | ??93.28 | ??5.55 |
| Average | ??92.72 | ??5.52 |
| ??RSD/％ | ??0.43 | ??0.42 |
To prepared 8,9-single-epoxy brevifolin phenol PLGA microsphere is measured its mean diameter by laser particle size analyzer.Particle size distribution is seen Fig. 5.
Six batches of microspheres that make according to optimised process all have higher drug loading and envelop rate, and microspherulite diameter is little and even, observe down in optical microscope to be complete sphere, good reproducibility, placed seven days under the room temperature, the basic no change of color, a little white powder appears in the cillin bottle bottom.
Claims (1)
1. the preparation method of a single-epoxy brevifolin phenol PLGA microsphere is characterized in that:
1) at first, get PLGA and join in the dichloromethane, making concentration is 25～35mgmL
-1PLGA solution, then with 8,9-single-epoxy brevifolin phenol is dissolved in PBS solution, makes 10～15mgmL
-1Drug solution;
2) secondly, the volume ratio according to 1: 5～10 joins drug solution in the PLGA solution, and ultrasonic emulsification makes colostrum;
3) last, being 1～3% PVA aqueous solution with this colostrum and mass concentration joins colostrum in the PVA aqueous solution by 1: 8～12 volume ratio, with the 1500r/min magnetic agitation after 2～4 hours, stirred 1.5～2.5 hours with 500r/min again, dichloromethane is volatilized, make microsphere solidify 8,9 single-epoxy brevifolin phenol PLGA microspheres.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201010208729XA CN101856332B (en) | 2010-06-25 | 2010-06-25 | Method for preparing 8, 9-single-epoxy brevifolin PLGA microspheres |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201010208729XA CN101856332B (en) | 2010-06-25 | 2010-06-25 | Method for preparing 8, 9-single-epoxy brevifolin PLGA microspheres |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101856332A true CN101856332A (en) | 2010-10-13 |
| CN101856332B CN101856332B (en) | 2012-03-28 |
Family
ID=42942638
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201010208729XA Expired - Fee Related CN101856332B (en) | 2010-06-25 | 2010-06-25 | Method for preparing 8, 9-single-epoxy brevifolin PLGA microspheres |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101856332B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106046339A (en) * | 2016-06-07 | 2016-10-26 | 西安交通大学 | Synthesis method of PLGA (poly(lactic-co-glycolic acid)) chemically modified material and method for preparing nanoparticles from material |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6447796B1 (en) * | 1994-05-16 | 2002-09-10 | The United States Of America As Represented By The Secretary Of The Army | Sustained release hydrophobic bioactive PLGA microspheres |
| CN1714861A (en) * | 2004-06-28 | 2006-01-04 | 中国医学科学院药物研究所 | Thymus penta peptide slow releasing micro ball and preparation method thereof |
| CN101298450A (en) * | 2008-04-25 | 2008-11-05 | 西安交通大学 | Extraction and separation method of effective ingredients brevifolin and 8,9-single-epoxy brevifolin in phyllanthus simplex |
| CN101278897B (en) * | 2008-04-25 | 2010-06-09 | 西安交通大学 | Process for preparing brevifolin solid lipid nano particle |
-
2010
- 2010-06-25 CN CN201010208729XA patent/CN101856332B/en not_active Expired - Fee Related
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6447796B1 (en) * | 1994-05-16 | 2002-09-10 | The United States Of America As Represented By The Secretary Of The Army | Sustained release hydrophobic bioactive PLGA microspheres |
| CN1714861A (en) * | 2004-06-28 | 2006-01-04 | 中国医学科学院药物研究所 | Thymus penta peptide slow releasing micro ball and preparation method thereof |
| CN101298450A (en) * | 2008-04-25 | 2008-11-05 | 西安交通大学 | Extraction and separation method of effective ingredients brevifolin and 8,9-single-epoxy brevifolin in phyllanthus simplex |
| CN101278897B (en) * | 2008-04-25 | 2010-06-09 | 西安交通大学 | Process for preparing brevifolin solid lipid nano particle |
Non-Patent Citations (2)
| Title |
|---|
| 《Phytochemistry》 19911231 HUGO E.GOTTLIEB等 Ethyl brevifolin carboxylate from Flueggea microcarpa 2435-2438 1 第30卷, 第7期 2 * |
| 《中国中药杂志》 20060930 牛晓峰等 黄珠子草有效成分短叶苏木酚及8,9-单环氧短叶苏木酚对大鼠肝损伤的保护作用 1529-1532 1 第31卷, 第18期 2 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106046339A (en) * | 2016-06-07 | 2016-10-26 | 西安交通大学 | Synthesis method of PLGA (poly(lactic-co-glycolic acid)) chemically modified material and method for preparing nanoparticles from material |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101856332B (en) | 2012-03-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Oliveira et al. | Spray-dried chitosan microspheres cross-linked with d, l-glyceraldehyde as a potential drug delivery system: preparation and characterization | |
| CN1104891C (en) | Controlled release preparation containing a salt of morphine | |
| CN101053553B (en) | Biodegradable fluorourcacil polyester medicine-carried nanospheres and its preparation method | |
| CN1923303A (en) | Temperature sensing nano gel system for blood vessel embolism material | |
| CN101045064A (en) | Gitamycin slow-release micro-ball preparation and its preparing process | |
| CN103623430A (en) | Preparation method and application of targeted co-supported drug delivery system nano-particles based on polylactic-co-glycolic acid | |
| CN103585113B (en) | Apigenin polylactic acid sustained release microsphere and preparation method thereof | |
| CN101856332B (en) | Method for preparing 8, 9-single-epoxy brevifolin PLGA microspheres | |
| CN107625768A (en) | A kind of Sorafenib albumin nano preparation of high oral administration biaavailability and preparation method thereof | |
| CN103356491A (en) | Preparation method of syringopicroside (SYR) poly(lactide-co-glycolide) (PLGA) nanoparticles | |
| CN104721140B (en) | The preparation method that amphiphilic ions type drug holding theca with the controllable drug release of targeting and embolism effect steeps | |
| CN112386584B (en) | Bacterial-responsive enrofloxacin composite nano system for livestock and preparation method thereof | |
| CN101623255B (en) | Artesunate nanoemulsion drug composition and preparation method thereof | |
| CN108542893A (en) | A kind of nano particle and preparation method thereof with excellent blood stability energy | |
| CN105126102A (en) | Hypocrellin B nanoparticle and preparation method thereof | |
| CN101756909B (en) | Lung-targeting ceftiofur microsphere and preparation method thereof | |
| CN105078924B (en) | A kind of sodium alginate base pH response type drug microcapsules and preparation method thereof | |
| CN101305985B (en) | Preparation method of coffee acid polylactic acid copolymer nanometer microsphere | |
| CN101292961A (en) | Method for preparing ferulic acid polylactic acid-hydroxide acetic acid copolymer microsphere | |
| CN101700230B (en) | Monosialote rahexosylganglioside microsphere and preparing method thereof | |
| CN110302153A (en) | A kind of preparation method of Sorafenib nano-micelle | |
| CN112190567B (en) | Preparation method and application of ivermectin sustained-release microspheres | |
| CN109044991A (en) | Macrophage carrying medicine and preparation method thereof | |
| CN107982214A (en) | Enrofloxacin solid lipid nano suspension for animals and preparation method thereof | |
| CN106265513A (en) | A kind of effect of nano-paclitaxel 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 | ||
| EE01 | Entry into force of recordation of patent licensing contract |
Application publication date: 20101013 Assignee: Xi'an will Xinrong Kang Pharmaceutical Co. Ltd. Assignor: Xi'an Jiaotong University Contract record no.: 2014610000010 Denomination of invention: Improved preparation process of 8-chlorotheophylline Granted publication date: 20120328 License type: Exclusive License Record date: 20140311 |
|
| LICC | Enforcement, change and cancellation of record of contracts on the licence for exploitation of a patent or utility model | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20120328 Termination date: 20140625 |
|
| EXPY | Termination of patent right or utility model |