CN102293736A - Preparation process of taxol-polymer medicine-carrying micelles - Google Patents
Preparation process of taxol-polymer medicine-carrying micelles Download PDFInfo
- Publication number
- CN102293736A CN102293736A CN2011102558678A CN201110255867A CN102293736A CN 102293736 A CN102293736 A CN 102293736A CN 2011102558678 A CN2011102558678 A CN 2011102558678A CN 201110255867 A CN201110255867 A CN 201110255867A CN 102293736 A CN102293736 A CN 102293736A
- Authority
- CN
- China
- Prior art keywords
- dspe
- paclitaxel
- micelle
- peg
- taxol
- 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)
- Medicinal Preparation (AREA)
Abstract
The invention relates to a preparation process of taxol-polymer medicine-carrying micelles and belongs to the technical field of preparation of medicines. The preparation process comprises the following steps of: 1) preparing mixed solution of taxol and a carrier material; 2) preparing a dry lipid film and removing the residual organic solvent; 3) adding a proper amount of 0.9 percent sodium chloride solution into warm water bath, placing into a constant-temperature water bath oscillator to oscillate at constant temperature for 0.5 to 5 hours, wherein the frequency is 50 to 250 times per minute; and 4) cooling material solution obtained in the step 3) and performing membrane filtration to prepare the taxol-polymer medicine-carrying micelles, wherein the carrier material is polyethylene glycol 2000-distearoyl phosphatidyl ethanolamine (PEG2000-DSPE) or a mixture of the PEG2000-DSPE and DSPE. By the process of the invention, a new hydration method is provided, so that the properties of the micelles can be improved or remain unchanged. The PEG2000-DSPE is replaced by the cheap DSPE with considerable quantity (such as 70 percent), so the measured average grain size is still far less than the minimum average grain size of the taxol PEG2000-DSPE polymer micelle particles prepared by the traditional method.
Description
Technical field
The present invention relates to a kind of paclitaxel-polymer drug-carried micelle preparation technology, belong to the medicament preparing technical field.
Background technology
As a kind of important natural anti-cancer drugs, paclitaxel possesses drug effects such as the formation of the differentiation that suppresses tumor cell, neovascularity and neoplasm metastasis, multiple cancer is had fairly obvious therapeutical effect.Yet, being subjected to the influence of the no target function of traditional formulation for paclitaxel, patient tends to cause very strong toxic and side effects after using.For the therapeutic effect of bringing into play this medicine and reduce its toxic and side effects, develop out the hot subject that the novel drug-supplying system with target function is current medicament field.Accompany with it, pharmaceutical preparation also progressively develops to direction efficient, quick-acting, long-acting, that taking dose is little, toxic and side effects is little.Wherein, the development of the novel drug-supplying system of this class has entered the stage of nanometer system.In recent years, have amphipathic polymer micelle and particularly be subjected to people's attention.Polymer micelle originates from the 90's of 20th century as the developmental research of pharmaceutical carrier, and it is by amphipathic nature polyalcohol spontaneous a kind of self-assembled structures that forms in aqueous solution.Its hydrophilic fragment (as Polyethylene Glycol) forms shell, hydrophobicity fragment (as DSPE) forms kernel, and the nucleocapsid structure of the uniqueness of Gou Chenging can be stated from the insoluble drug bag in the kernel thus.That is in the developmental research of the drug-supplying system of current this medicine, the main a kind of amphiphilic block copolymers PEG that adopts
2000-DSPE, but self assembly forms the nano-micelle system of spherical nucleocapsid structure in aqueous solution, and wherein hydrophobic block formation kernel bag carries paclitaxel, greatly increases the water solublity of paclitaxel, evade the supervision layer by layer of vivo immuning system simultaneously, thereby prolonged the time of medicine in blood circulation.Because the polymer micelle particle diameter is generally less than 100 nm, characteristics such as drug loading height, medicine carrying scope are wide so its drug-supplying system has, the holdup time is long in the good stability, body, medicine stability and bioavailability have effectively been improved, alleviated untoward reaction, also can connect targeted molecular on the surface simultaneously, realize initiatively target administration with specific recognition function.
At existing paclitaxel PEG
2000In the preparation process of-DSPE medicine carrying system of polymer micelle, its aquation treatment process adopts mechanical agitation or vortex method to carry out, and the minimum grain size that can prepare is near 50nm, and distributed areas reach
, this makes its micelle administration system possess certain targeting.We know, are the targeting that grain refine and the uniformity (promptly reducing the particle size distribution interval) that improves particle size distribution all can improve drug-supplying system by the particle diameter that reduces polymer micelle.Therefore, at paclitaxel PEG
2000Under the enough little situation of the particle diameter of-DSPE polymer micelle, how further reducing its grain diameter is a new problem that runs in the present Study on Preparation.Along with further reducing of micelle particle diameter, will promote the lifting of this class drug delivery system performance, especially aspect targeting.Secondly, because PEG
2000The costing an arm and a leg of-DSPE also restricting this novel drug-supplying system and entering clinical practice.How to seek the effectively cheap encapsulating material replacement PEG that substitutes
2000-DSPE, preparation is for the present suitable paclitaxel PEG of performance
2000-DSPE polymer micelle also is the problem that this research at present runs into.
Summary of the invention
The technical problem to be solved in the present invention is to overcome existing paclitaxel PEG
2000Big, the pockety defective of-DSPE polymer micelle preparation technology's cost height, particle diameter provides a kind of novel aquation technology, and its product cut size that obtains is little, be more evenly distributed.
At this drug-supplying system, technology of the present invention is at first launched the research of the further refinement of granule, after preparation technology having been proposed a kind of new aquation method and improving, has confirmed the prepared paclitaxel PEG that goes out
2000-DSPE polymer micelle performance obtains to promote or remain unchanged, thereby has confirmed the effectiveness and the reliability of this new method.At last, by cheap DSPE is substituted PEG with sizable amount
2000-DSPE(is as reaching 70%), for having prepared new paclitaxel polymer micelle administration system under new preparation process, measured mean diameter is still much smaller than not containing DSPE prepared paclitaxel PEG under traditional method
2000-DSPE polymer micelle granule minimum average particle diameters.
Particularly, the invention provides following technical scheme:
Paclitaxel-polymer drug-carried micelle preparation technology comprises the steps 1) mixed liquor of preparation paclitaxel and carrier material; 2) make dried lipid thin film and remove residual organic solvent; 3) in the tepidarium, add an amount of 0.9% sodium chloride solution, constant temperature vibration 0.5-5h, frequency is per minute 50-250 time; 4) with the cooling of step 3) gained feed liquid, membrane filtration promptly makes paclitaxel-polymer drug-carried micelle; Described carrier material is PEG
2000-DSPE or PEG
2000The mixture of-DSPE and DSPE.
In the described step 3), constant temperature vibration 1h, frequency is per minute 150 times.
Described PEG
2000In the mixture of-DSPE and DSPE, the mass ratio of DSPE is 10-30%.
The beneficial effect of technology of the present invention is: (1) is at paclitaxel-PEG
2000The preparation of-DSPE carrier micelle, will have that traditional mechanical in the preparation method stirs or the aquation method of vortex change into implement constant temperature oscillation treatment new process by the water bath with thermostatic control shaker after, prepared micelle mean diameter is reduced to present mean diameter 16.1nm by the existing about 51nm of method minimum average particle diameters, thereby has realized the refinement of micelle particle diameter; Meanwhile, also developed the new purposes (this instrument was mainly used in extracorporeal releasing experiment in the past) of water bath with thermostatic control shaker thus; (2) the prepared paclitaxel-PEG of new method
2000The envelop rate of-DSPE carrier micelle has improved about 5%, has promptly surpassed 90%; Its drug loading then result with traditional method is suitable, promptly reaches 4.32%; (3) during the discussion that reduces cost at this medicine-carried system was studied, this technology was by partly substituting PEG with DSPE
2000Adopt the carrier micelle result who is prepared under the new technology of being advised to show behind-the DSPE: along with the increase of replacement amount, its micelle particle diameter meansigma methods and distributed area all increase to some extent, and micellar stability also obviously promotes.Promptly reach at 70% o'clock in the replacement amount, mean diameter is 30.2nm, and this is still much smaller than the present mean diameter of the 51nm of other method; And its particle size distribution interval does not still surpass
, micelle stability can extend to by about 3 days that do not contain the DSPE situation and contain 70% o'clock more than 5 days.
Description of drawings
Accompanying drawing is used to provide further understanding of the present invention, and constitutes the part of description, is used from explanation the present invention with embodiments of the invention one, is not construed as limiting the invention.In the accompanying drawings:
Fig. 1 is that the present invention adopts the paclitaxel-PEG for preparing after the constant temperature oscillation treatment new technology
2000The particle size distribution figure of-DSPE polymer micelle;
Fig. 2 adopts the RP-HPLC method to measure the standard curve that this inventive method prepares micellar content of taxol.
The specific embodiment
Below in conjunction with accompanying drawing the preferred embodiments of the present invention are described, should be appreciated that preferred embodiment described herein only is used for description and interpretation the present invention, and be not used in qualification the present invention.
Embodiment 1
1, paclitaxel-PEG
2000The preparation method of-DSPE carrier micelle
At room temperature precision takes by weighing a certain amount of paclitaxel (0.35mg) and carrier material PEG
2000-DSPE(10mg) after, they are placed eggplant-shape bottle, add the chloroform (1ml) and the acetonitrile (3ml) of an amount of volume, and vortex 5min, medicine and carrier material are dissolved fully and mix homogeneously.40 ℃ with 60r/min decompression rotary evaporation, make the dried lipid thin film.After reducing to room temperature, remove residual organic solvent through vacuum drying.In 37 ℃ of water-baths, add an amount of 0.9% sodium chloride solution (2ml), the constant temperature vibration is cooled to room temperature, adopts 0.22 μ m membrane filtration, thereby has prepared paclitaxel-PEG
2000-DSPE carrier micelle.
Constant temperature duration of oscillation and frequency are as shown in table 1.
Table 1 paclitaxel-PEG
2000Constant temperature vibration and frequency meter in-the DSPE carrier micelle grain preparation process
| ? | Duration of oscillation (h) | Frequency of oscillation (inferior/minute) |
| Method 1 | 0.5 | 250 |
| Method 2 | 1 | 150 |
| Method 3 | 3 | 100 |
| Method 4 | 5 | 50 |
2, the quality determining method and the result of the product of the method 2 of table 1
), micelle is to the embedding of medicine
Recording paclitaxel by uv-spectrophotometric instrument (being the UV method) has absworption peak at 267nm and 332nm place, and after paclitaxel was aggregated the embedding of thing micelle, the absworption peak at the 332nm place weakened greatly, and this shows that paclitaxel is by the obvious embedding of micelle.
2), the particle size distribution of polymer micelle
With the above-mentioned paclitaxel-PEG that makes
2000-DSPE polymer micelle solution is put into the particle diameter pipe, adopts the micellar particle size distribution of particle size analyzer determination.Experimental result is found, the preparation-obtained paclitaxel-PEG of the present invention
2000The particle size distribution of-DSPE polymer micelle is between 12-20nm, and mean diameter is 16.1nm, sees shown in Figure 1.This result and the similar micellar particle size distribution result of other existing method gained can find after relatively, the size of mean diameter only have only other method gained minimum average particle diameters 1/3rd, and its distributed area and the narrowest result are quite (promptly
), thereby be expected to improve effectively the Targeting Performance of drug-supplying system.Relatively find that the variation of its particle size distribution is very small in the back through the polymer micelle that the inventive method is made with corresponding blank micellar result.These results show, constant temperature oscillation treatment new technology of the present invention is prepared to be gone out polymer micelle and not only have the good particle size distribution characteristic that improves the drug targeting performance, and has stable particle size distribution characteristic.
), drug loading and entrapment efficiency determination
(1) use RP-HPLC method (external standard method) to measure the chromatographic condition of content of taxol
Chromatographic column: Dikma RP-C
18Post (4.6mm * 200mm, 5 μ m); Mobile phase is acetonitrile-water (55:45), and flow velocity is 1ml/min; The detection wavelength is 227nm, sample size 20 μ l; Column temperature: 25 ℃.
(2) standard curve of drug loading
Precision takes by weighing paclitaxel reference substance 32mg, and with acetonitrile dissolving and be settled to 50ml, being mixed with concentration is 640 μ g/ml solution, puts 4 ℃ of refrigerators and preserves.With acetonitrile the paclitaxel standard solution is mixed with the solution that concentration is 64,32,16,8,4,2,1 μ g/ml respectively, by above-mentioned chromatographic condition operation, at the 227nm place, adopt the RP-HPLC method to measure the peak area of paclitaxel respectively, the point that 7 groups of measured results are plotted among Fig. 2 illustrates.As seen from Figure 2, these points have good linear distribution characteristics, and we adopt equation of linear regression to obtain the standard curve of its drug loading like this.Note records the paclitaxel peak area and is
YBe designated as with respective concentration
XAfter, then the equation that obtains of match is as follows
The correlation coefficient of its match
This result shows that in the concentration range of being measured, the peak area of paclitaxel and the drug loading standard curve between the concentration present good line relationship, and then adopts high performance liquid chromatography to determine that the method for paclitaxel concentration is accurately and reliably.
(3) method response rate experiment
At blank PEG
2000Add the accurate an amount of paclitaxel that takes by weighing in-DSPE the micelle, be mixed with the sample that theoretical concentration is respectively 64,8,1 μ g/ml with acetonitrile, adopt the RP-HPLC method to measure their peak area respectively, it (is working sample value M that reuse gained standard curve equation (1) obtains the drug level value
Paclitaxel-PEG2000-DSPE micelle); Then separately to blank PEG
2000-DSPE micelle is done same concentration determination (being blank value).So the formula of the computational methods response rate is
The response rate (%)=(working sample value-blank value)/addition * 100% (2)
Here addition is theoretical sample concentration.For the paclitaxel of variable concentrations, the method response rate that records the results are shown in Table 2.Show as seen thus, the end value that the paclitaxel method response rate that the inventive method obtains and existing method record is suitable, remains on same index level.Therefore, the mensuration that the present invention carried out is reliable.
The method response rate of table 2 paclitaxel
| Paclitaxel concentration (μ g/ml) | The method response rate (
  |
 |
 |
 |
 |
 |
 |
(4) mensuration of drug loading
Be dissolved in the methanol of certain volume taking by weighing the paclitaxel polymer micelle that a certain amount of present embodiment makes, survey peak area with the RP-HPLC method, calculate concentration by standard curve again, the concentration that itself and the aforementioned micelle that contains DSPE is measured compares, and the drug loading calculating formula that just obtains the latter is as follows
Drug loading (%)=(M
Paclitaxel)/(M
Paclitaxel-PEG2000-DSPE micelle) * 100% (3)
M wherein
PaclitaxelBe dissolved in the drug level that records in the methanol for the paclitaxel polymer micelle.The measured drug loading of micelle that the inventive method is made is 4.32%, and this result is suitable with the existing methods drug loading.
(5) mensuration of envelop rate
At the micelle that is generated with 5ml dissolve with methanol the inventive method, obtain deposit through centrifugalize with after filtering, reuse RP-HPLC method is surveyed its peak area, utilizes the standard curve of paclitaxel to obtain its drug level M
The paclitaxel dosageAfter, adopt as shown in the formula just obtaining corresponding micellar envelop rate, promptly
Envelop rate (%)=(M
Paclitaxel)/(M
The paclitaxel dosage) * 100% (4)
For paclitaxel-PEG that the inventive method generated
2000-DSPE polymer micelle, measured envelop rate are 90.1%, and this similar micellar result than existing other method preparation has improved about 5%.
Embodiment 2
1, the chimeric preparation that the paclitaxel polymer micelle of DSPE is arranged
Consider the dissolubility of DSPE,, prepare different carrier micelles by choosing the different proportion material composition.Promptly under the paclitaxel situation of same amount, by choosing not commensurability carrier material PEG
2000-DSPE(9mg, 7mg, 3mg), with chloroform (3ml) dissolving of an amount of volume; Each carrier material quality all remains 10mg, and correspondence is chosen DSPE amount (1mg, 3mg, 7mg) and added the 1ml chloroform so respectively, stirs DSPE is dissolved fully in 65 ℃ of oil baths.Adopt 1 the preparation method of embodiment 1 then, obtained the carrier micelle of three kinds of different formulated components.As a comparison, under the paclitaxel situation of same amount, dissolve with the chloroform of 3ml; After the 10mg carrier material is all selected DSPE for use,, obtained control sample through same dissolution mechanism and preparation process.
2, particle size determination result
For the paclitaxel polymer micelle of above-mentioned 1 prepared chimeric DSPE, owing to contain more rigid radical in the structure of DSPE, experiment shows can't form polymer micelle with DSPE merely.That is be entirely DSPE when carrier material, when adopting thin film aquation legal system of the present invention to be equipped with, the film of formation is insoluble in 0.9% sodium chloride solution, thereby can't form transparent micellar solution.
Work as PEG
2000After-DSPE part was substituted by DSPE, the inventive method can prepare the paclitaxel polymer micelle of the chimeric DSPE of output, and then the cost of this type of drug-supplying system is reduced.And in the paclitaxel polymer micelle carrier material of this chimeric DSPE, contain a certain amount of PEG
2000During-DSPE, all can obtain micellar solution by preparation method of the present invention.Along with the adding of DSPE and the minimizing of PEG-DSPE, the particle diameter of preparation-obtained paclitaxel polymer micelle increases to some extent, and concrete measurement result is listed in the table 3.Meanwhile, experimental result shows that also the micellar stability of gained also also increases with this changes of contents.Promptly be increased at 70% o'clock at substitute, the time of micelle stability has surpassed 5 days, the less than 3 days that does not contain the substitute situation that surpasses far away.
The experiment value of the chimeric DSPE paclitaxel of table 3 polymer micelle particle diameter
| DSPE and PEG 2000-DSPE mass ratio | The mean diameter of experiment measuring |
 |
 |
 |
|
 |
Embodiment 1,2 used instrument and equipments:
1100 type high performance liquid chromatographs (U.S. Agilent company); Nicomp
TM380ZLS type particle size analyzer (U.S. PSS company); RE-52A type rotary evaporator (going up Industrial Co., Ltd. of Nereid section); SHZ-III type circulating vacuum pump (going up Industrial Co., Ltd. of Nereid section); W201B type thermostat water bath (going up Industrial Co., Ltd. of Nereid section); DZF-6050 type vacuum drying oven (going up Industrial Co., Ltd. of Nereid section); SHZ-B type constant temperature water bath agitator; BP1245 type electronic balance.
：
Paclitaxel (Shanghai Sunve Pharmaceutical Co., Ltd., content 98.6%); PEG
2000-DSPE (German Lipoid company); DSPE (DSPE, German Lipoid company); The paclitaxel reference substance; Chloroform: analytical pure, Chemical Reagent Co., Ltd., Sinopharm Group; Acetonitrile: chromatographically pure, U.S. TEDIA; 0.9% sodium chloride solution (autogamy).
It should be noted that at last: the above only is the preferred embodiments of the present invention, be not limited to the present invention, although the present invention is had been described in detail with reference to previous embodiment, for a person skilled in the art, it still can be made amendment to the technical scheme that aforementioned each embodiment put down in writing, and perhaps part technical characterictic wherein is equal to replacement.Within the spirit and principles in the present invention all, any modification of being done, be equal to replacement, improvement etc., all should be included within protection scope of the present invention.
Claims (3)
1. paclitaxel-polymer drug-carried micelle preparation technology is characterized in that: comprise the steps 1) mixed liquor of preparation paclitaxel and carrier material; 2) make dried lipid thin film and remove residual organic solvent; 3) in the tepidarium, add an amount of 0.9% sodium chloride solution, place water bath with thermostatic control shaker constant temperature vibration 0.5-5h, frequency is per minute 50-250 time; 4) with the cooling of step 3) gained feed liquid, membrane filtration promptly makes paclitaxel-polymer drug-carried micelle; Described carrier material is PEG
2000-DSPE or PEG
2000The mixture of-DSPE and DSPE.
2. paclitaxel according to claim 1-polymer drug-carried micelle preparation technology is characterized in that: in the described step 3), and constant temperature vibration 1h, frequency is per minute 150 times.
3. paclitaxel according to claim 1-polymer drug-carried micelle preparation technology is characterized in that: described PEG
2000In the mixture of-DSPE and DSPE, the mass ratio of DSPE is 10-30%.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201110255867 CN102293736B (en) | 2011-08-31 | 2011-08-31 | Preparation process of taxol-polymer medicine-carrying micelles |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201110255867 CN102293736B (en) | 2011-08-31 | 2011-08-31 | Preparation process of taxol-polymer medicine-carrying micelles |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102293736A true CN102293736A (en) | 2011-12-28 |
| CN102293736B CN102293736B (en) | 2013-06-05 |
Family
ID=45354577
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 201110255867 Expired - Fee Related CN102293736B (en) | 2011-08-31 | 2011-08-31 | Preparation process of taxol-polymer medicine-carrying micelles |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102293736B (en) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104174036A (en) * | 2014-08-29 | 2014-12-03 | 国家纳米科学中心 | Nano-micelle capable of realizing integration of diagnosis and treatment, as well as preparation method and application of nano-micelle |
| CN105636583A (en) * | 2013-09-13 | 2016-06-01 | 板井昭子 | Aqueous solution formulation, and manufacturing method for same |
| CN107365284A (en) * | 2017-08-16 | 2017-11-21 | 桂林茗兴生物科技有限公司 | A kind of method that taxol is extracted from Chinese yew |
| CN111450055A (en) * | 2020-03-31 | 2020-07-28 | 天津大学 | Synthesis method of antitoxic immunizing agent for hepatitis B |
| CN111743877A (en) * | 2019-03-28 | 2020-10-09 | 复旦大学 | Paclitaxel lapatinib compound nanocrystal and preparation method thereof |
| CN117482044A (en) * | 2023-11-13 | 2024-02-02 | 湛江中心人民医院 | Preparation of polymer nano drug-loaded micelle loaded with PD-1/PD-L1 inhibitor and application of polymer nano drug-loaded micelle after vascular injury |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20060251710A1 (en) * | 2005-04-12 | 2006-11-09 | Kwon Glen S | Micelle composition of polymer and passenger drug |
| CN101439032A (en) * | 2007-11-22 | 2009-05-27 | 沈阳沃森药物研究所 | Paclitaxel lipid complexes and micelle composition thereof for injection |
| CN102133172A (en) * | 2011-01-24 | 2011-07-27 | 北京大学 | Paclitaxel nano micelle and application thereof |
-
2011
- 2011-08-31 CN CN 201110255867 patent/CN102293736B/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20060251710A1 (en) * | 2005-04-12 | 2006-11-09 | Kwon Glen S | Micelle composition of polymer and passenger drug |
| CN101439032A (en) * | 2007-11-22 | 2009-05-27 | 沈阳沃森药物研究所 | Paclitaxel lipid complexes and micelle composition thereof for injection |
| CN102133172A (en) * | 2011-01-24 | 2011-07-27 | 北京大学 | Paclitaxel nano micelle and application thereof |
Non-Patent Citations (2)
| Title |
|---|
| APARNA KRISHNADAS ET AL: "Sterically Stabilized Phospholipid Mixed Micelles: In Vitro Evaluation as a Novel Carrier for Water-Insoluble Drugs", 《PHARMACEUTICAL RESEARCH》 * |
| 褚洪雨 等: "紫杉醇聚合物胶束载药体系的研究进展", 《化工时刊》 * |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105636583A (en) * | 2013-09-13 | 2016-06-01 | 板井昭子 | Aqueous solution formulation, and manufacturing method for same |
| CN105636583B (en) * | 2013-09-13 | 2019-08-20 | 板井昭子 | Aqueous solution preparation and its manufacturing method |
| CN104174036A (en) * | 2014-08-29 | 2014-12-03 | 国家纳米科学中心 | Nano-micelle capable of realizing integration of diagnosis and treatment, as well as preparation method and application of nano-micelle |
| CN104174036B (en) * | 2014-08-29 | 2018-03-13 | 国家纳米科学中心 | A kind of nano-micelle for realizing diagnosis and treatment integration and its preparation method and application |
| CN107365284A (en) * | 2017-08-16 | 2017-11-21 | 桂林茗兴生物科技有限公司 | A kind of method that taxol is extracted from Chinese yew |
| CN111743877A (en) * | 2019-03-28 | 2020-10-09 | 复旦大学 | Paclitaxel lapatinib compound nanocrystal and preparation method thereof |
| CN111450055A (en) * | 2020-03-31 | 2020-07-28 | 天津大学 | Synthesis method of antitoxic immunizing agent for hepatitis B |
| CN117482044A (en) * | 2023-11-13 | 2024-02-02 | 湛江中心人民医院 | Preparation of polymer nano drug-loaded micelle loaded with PD-1/PD-L1 inhibitor and application of polymer nano drug-loaded micelle after vascular injury |
| CN117482044B (en) * | 2023-11-13 | 2024-09-20 | 湛江中心人民医院 | Preparation of polymer nano drug-loaded micelle loaded with PD-1/PD-L1 inhibitor and application of polymer nano drug-loaded micelle after vascular injury |
Also Published As
| Publication number | Publication date |
|---|---|
| CN102293736B (en) | 2013-06-05 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102293736B (en) | Preparation process of taxol-polymer medicine-carrying micelles | |
| CN106265510B (en) | The multistage target polymer micella and preparation method thereof of pH trigger-type drug release in a kind of tumour cell | |
| CN105997880B (en) | A kind of anti-tumor nano drug and preparation method thereof based on crosslinked bio degradable polymer vesica | |
| Li et al. | Folate-targeting annonaceous acetogenins nanosuspensions: significantly enhanced antitumor efficacy in HeLa tumor-bearing mice | |
| CN108144067B (en) | Tetravalent platinum compound-bicyclic double-bond amphiphilic polymer prodrug, nano micelle, preparation method and application thereof | |
| CN112274656B (en) | Preparation method and application of macrocyclic amphiphilic self-assembled nanoparticles capable of delivering combined medicaments to tumor tissues in proportion | |
| Elzeny et al. | Polyphosphoester nanoparticles as biodegradable platform for delivery of multiple drugs and siRNA | |
| CN111718465B (en) | Poly-dithioacetal and preparation method and application thereof | |
| Zeng et al. | Construction of a cancer-targeted nanosystem as a payload of iron complexes to reverse cancer multidrug resistance | |
| WO2014079377A1 (en) | Antitumor prodrugs with function of p-glycoprotein inhibition | |
| CN103342788A (en) | Triblock polycation, and preparation method and application thereof | |
| CN105106176A (en) | Degradable organic silicon nanocapsule drug carrier as well as preparation method and application thereof | |
| Wei et al. | Hepatocyte-targeted delivery using oleanolic acid-loaded liposomes for enhanced hepatocellular carcinoma therapy | |
| CN105859990A (en) | Polymer with side chains containing lipoyl, preparation method of polymer, polymer vesica prepared from polymer and application of polymer vesica | |
| CN107266384A (en) | N carboxyl inner-acid anhydride monomers and polyaminoacid based on 2 aminohexadecanoic acids and preparation method thereof | |
| CN109481404A (en) | A kind of preparation method of pH sensitivity imidazoles liposome | |
| WO2017049821A1 (en) | Water-soluble docetaxel anticancer drug compound and preparation method and use thereof | |
| CN109369625A (en) | A kind of ortho esters 5 FU 5 fluorouracil prodrugs, preparation method and its acid-sensitive nanoparticle and application | |
| CN106361724A (en) | 20(R)-ginsenoside Rg3 slow release nanometer microsphere composition, and preparation method thereof | |
| CN108324686B (en) | Ellagic acid self-microemulsion and preparation method thereof | |
| CN104473873B (en) | A kind of Cabazitaxel long circulating liposome injection and preparation method thereof | |
| CN102600190A (en) | Adriamycin lipid pharmaceutical composition | |
| CN102604083B (en) | Polymer modified lipid material and application thereof | |
| CN111330019B (en) | Flumazenil clathrate compound and preparation method and application thereof | |
| CN107674196B (en) | Docetaxel prodrug with anti-tumor effect 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 | ||
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20130605 Termination date: 20180831 |