CN103705470B - Methylprednisolone-loading nanoparticles as well as preparation method and application thereof - Google Patents
Methylprednisolone-loading nanoparticles as well as preparation method and application thereof Download PDFInfo
- Publication number
- CN103705470B CN103705470B CN201410003889.9A CN201410003889A CN103705470B CN 103705470 B CN103705470 B CN 103705470B CN 201410003889 A CN201410003889 A CN 201410003889A CN 103705470 B CN103705470 B CN 103705470B
- Authority
- CN
- China
- Prior art keywords
- prednisolone
- load
- ibuprofen
- nano microsphere
- inulin
- 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.)
- Expired - Fee Related
Links
Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses methylprednisolone-loading nanoparticles which consist of methylprednisolone and a carrier at a weight ratio of 1:(2-20), wherein the carrier is ibuprofen-modified ibuprofen and the grain size of the methylprednisolone-loading nanoparticles is 70-400nm. The invention further discloses a preparation method and application of the nanoparticles. The methylprednisolone-loading nanoparticles disclosed by the invention can be used for effectively transferring methylprednisolone to the injured part in a targeting manner, and have a very strong methylprednisolone slow-release function, so that side effects caused by high dosage and toxicity of methylprednisolone are avoided.
Description
Technical field
The present invention relates to carrying medicament Nano microsphere preparation field, be specifically related to Nano microsphere of a kind of load prednisolone and its preparation method and application.
Background technology
The central nervous system injury caused by vehicle accident, violence strike or commercial production accident etc. is very common clinically.Neuronal death, disintegrate and disappearance can be caused after central nervous system injury; And then inflammatory cell invades, glial cell and connective tissue proliferation, thus cause permanent motion, sensory function sexual disorders brings very large difficulty to the life of people.Although a lot of effort that had a lot of scholar to do in this respect, effective therapeutic modality still be there is no for central nervous system injury.Up to the present, prednisolone is unique medication of the listing for the treatment of acute spinal cord injury, and large bolus injection prednisolone can cause delayed ischemic neurological deficits usually.Although current cure mechanism is not very clear, cure mechanism main after it is believed that central nervous system injury may be relevant with the lipid oxidation that prednisolone suppresses and inflammatory reaction.Although heavy dose of prednisolone administration can have certain repair to function of nervous system in acute CNS injuries, often cause very serious side effect, comprise gastrorrhagia, septicemia, pneumonia, acute corticosteroid myopathy and wound infection.The side effect of prednisolone may be because the high dose of itself and toxicity cause.Therefore efficient targeting transmits the prednisolone arrival damage location of wide clinical application is research direction main at present.
Nano medication loaded particle based on nanotechnology (utilizes nanotechnology using biomaterial as carrier due to its distinctive subcellular structure, medicine is disperseed, parcel, is adsorbed in the nano-carrier within the scope of 1 ~ 1000nm), can be relatively easy to go deep into organization internal and blood vessel depths.Natural polymer, especially compound of polysaccharide have distinctive biodegradability and biocompatibility, are therefore widely used in load anti-inflammatory medicaments, antibiotic, protein, the carriers such as gene.Suitable chemical modification effectively can improve the character of natural polysaccharide, such as: the hydrophilicity of the polysaccharide of hydrophobic modification can change.
Summary of the invention
The object of this invention is to provide a kind of Nano microsphere of load prednisolone, to solve in prior art, prednisolone can not efficient targeting be delivered to damage location and the high dose of prednisolone own, toxicity causes the defects such as side effect.The present invention also provides its preparation method and application.
For addressing the aforementioned drawbacks, the present invention by the following technical solutions:
A Nano microsphere for load prednisolone, is made up of 1:2 ~ 20 in mass ratio prednisolone and carrier, and described carrier is ibuprofen modification inulin; The particle diameter of the Nano microsphere of described load prednisolone is 70 ~ 400nm.
The preparation method of the Nano microsphere of above-mentioned load prednisolone, comprises the steps:
Step one, under agitation, by N, N '-carbonyl dimidazoles and ibuprofen in molar ratio 1 ~ 1.3:1 be added in dimethylsulfoxide solvent, stirred at ambient temperature reaction 1 ~ 3h;
Step 2, inulin is joined in the reactant liquor of step one, at 60 ~ 100 DEG C, react 12 ~ 48h; Wherein, described in inulin unit and step one, the molar ratio of ibuprofen is 1 ~ 10:2;
Step 3, to be poured into by the reactant liquor of step 2 in cold water and separate out precipitation, washing, drying obtain ibuprofen modification inulin;
Under step 4, stirring condition, ibuprofen modification inulin prednisolone and step 3 prepared in mass ratio 1:2 ~ 20 dissolves in organic solvent, being added drop-wise to volume is again in the hot water of organic solvent 4 ~ 20 times, remove organic solvent afterwards, lyophilization, obtains the Nano microsphere of described load prednisolone.
Organic solvent described in step 4 is acetone, one or more in dimethyl sulfoxine or dimethyl formamide; The temperature of described hot water is 40 ~ 80 DEG C; The method of described removing organic solvent is for volatilization or remove under reduced pressure.
The application of the Nano microsphere of above-mentioned load prednisolone pivot nerve injury or the slow releasing preparation as prednisolone in the treatment.
Beneficial effect of the present invention:
1, the Nano microsphere of load prednisolone of the present invention is using ibuprofen modification inulin as carrier, prednisolone efficient targeting can be delivered to damage location.Ibuprofen modification inulin compares inulin as carrier, effectively can extend the half-life of prednisolone medicine, and may play the collaborative effect promoting central nervous system injury with ibuprofen.
2, the Nano microsphere of load prednisolone of the present invention has very strong prednisolone slow-release function, by the form of slow release, effectively can extend the drug half-life of prednisolone, avoid the high dose of prednisolone own, side effect that toxicity causes, have good curative effect to the treatment of central nervous system injury.
3, the Nano microsphere good biocompatibility of load prednisolone of the present invention, biochemical property is stablized.
4, the Nano microsphere particle diameter that preparation method of the present invention is obtained is more homogeneous, good dispersion.
Detailed description of the invention
Below in conjunction with embodiment the present invention done and further explain.The following example only for illustration of the present invention, but is not used for limiting practical range of the present invention.
A preparation method for the Nano microsphere of load prednisolone, using ibuprofen modification inulin as carrier, ibuprofen modification inulin is made up of biocompatible inulin and anti-inflammatory agent ibuprofen, and concrete preparation comprises the steps:
Step one, under agitation, by N, N '-carbonyl dimidazoles and ibuprofen in molar ratio 1 ~ 1.3:1 be added in dimethylsulfoxide solvent, stirred at ambient temperature reaction 1 ~ 3h;
Step 2, inulin is joined in the reactant liquor of step one, at 60 ~ 100 DEG C, react 12 ~ 48h; Wherein, described in inulin unit and step one, the molar ratio of ibuprofen is 1 ~ 10:2;
Step 3, to be poured into by the reactant liquor of step 2 in cold water and separate out precipitation, washing, drying obtain ibuprofen modification inulin.Ibuprofen modification inulin preparation process is as follows:
Under step 4, stirring condition, ibuprofen modification inulin prednisolone and step 3 prepared in mass ratio 1:2 ~ 20 dissolves in organic solvent, being added drop-wise to volume is again in 40 ~ 80 DEG C of hot water of organic solvent 4 ~ 20 times, afterwards by dialysing or removing organic solvent under reduced pressure, lyophilization, obtains the Nano microsphere of described load prednisolone.Described organic solvent is acetone, one or more in dimethyl sulfoxine or dimethyl formamide.
The Nano microsphere particle diameter of the load prednisolone of above-mentioned preparation is more homogeneous, and particle size range is 70 ~ 400nm, good dispersion.
The Nano microsphere of the load prednisolone of above-mentioned preparation can pivot nerve injury or the slow releasing preparation as prednisolone be applied in the treatment, during use, the Nano microsphere of load prednisolone is scattered in water by the means such as ultrasonic, form the aqueous dispersions that concentration is the Nano microsphere of the load prednisolone of 1 ~ 50mg/ml, by intravenous injection or CNS trauma regional administration.
Following examples inulin is provided by Shanghai Aladdin Reagent Company; Prednisolone is provided by Yueyang Huanyu Pharmaceutical Co., Ltd..
Embodiment 1
The preparation of ibuprofen modification inulin
Under agitation, 0.43g N, N '-carbonyl dimidazoles (2.65mmol) and 0.5g ibuprofen (2.42mmol) are joined in 5mL dimethylsulfoxide solvent, continue stirring at room temperature reaction 1h.0.5g inulin (3.08mmol) joins in above-mentioned reactant liquor, stirring reaction 24h at 80 DEG C.Poured into by above-mentioned reactant liquor in 100mL cold water, sucking filtration, washing, drying obtain ibuprofen modification inulin.
Load prednisolone the preparation of Nano microsphere
Under agitation, 5mg ibuprofen modification inulin and 1mg prednisolone are dissolved in 1mL acetone, dropwise join in 10mL50 DEG C of hot water.Above-mentioned solution stirred overnight volatilized or removes acetone under reduced pressure, lyophilization, obtaining the Nano microsphere of load prednisolone.The particle size range of Nano microsphere prepared by the present embodiment is 120 ~ 160nm.
Embodiment 2
The preparation of ibuprofen modification inulin
Under agitation, 0.43g N, N '-carbonyl dimidazoles (2.65mmol) and 0.5g ibuprofen (2.42mmol) are joined in 5mL dimethylsulfoxide solvent, continue stirring at room temperature reaction 1h.0.39g inulin (2.42mmol) joins in above-mentioned reactant liquor, stirring reaction 24h at 80 DEG C.Poured into by above-mentioned reactant liquor in 100mL cold water, sucking filtration, washing, drying obtain ibuprofen modification inulin.
Load prednisolone the preparation of Nano microsphere
Under agitation, 5mg ibuprofen modification inulin and 1mg prednisolone are dissolved in 1mL acetone, dropwise join in 10mL50 DEG C of hot water.Above-mentioned solution stirred overnight volatilization or decompression are divided exactly acetone, lyophilization, obtains the Nano microsphere of load prednisolone.The particle size range of Nano microsphere prepared by the present embodiment is 120 ~ 360nm.
Embodiment 3
The preparation of ibuprofen modification inulin
Under agitation, 0.39g N, N '-carbonyl dimidazoles (2.42mmol) and 0.5g ibuprofen (2.42mmol) are joined in 5mL dimethylsulfoxide solvent, continue stirring at room temperature reaction 1h.1.96g inulin (12.1mmol) joins in above-mentioned reactant liquor, stirring reaction 24h at 80 DEG C.Poured into by above-mentioned reactant liquor in 100mL cold water, sucking filtration, washing, drying obtain ibuprofen modification inulin.
Load prednisolone the preparation of Nano microsphere
Under agitation, 5mg ibuprofen modification inulin and 1mg prednisolone are dissolved in 1mL acetone, dropwise join in 10mL50 DEG C of hot water.Above-mentioned solution stirred overnight volatilization or decompression are divided exactly acetone, lyophilization, obtains the Nano microsphere of load prednisolone.The particle size range of Nano microsphere prepared by the present embodiment is 70 ~ 130nm.
Embodiment 4
At 37 DEG C, the Nano microsphere of 6g load prednisolone embodiment 1 prepared and 1g do not have loaded prednisolone to put into 10mL phosphate buffered solution (0.01M respectively, pH=7.4) dialyse, sample every half an hour, utilize high performance liquid chromatography (HPLC, C-18 post, mobile phase is acetonitrile V: water V=34:66, flow velocity is 1mL/h, and determined wavelength is 243nm.) measuring the concentration of prednisolone, experimental result shows, does not have the drug half-life of loaded prednisolone to be 4h, and the Nano microsphere of load prednisolone prepared by embodiment 1 can extend the drug half-life of prednisolone effectively to 8.5h.
Claims (5)
1. a Nano microsphere for load prednisolone, is characterized in that, is made up of 1:2 ~ 20 in mass ratio prednisolone and carrier, and described carrier is ibuprofen modification inulin; The particle diameter of the Nano microsphere of described load prednisolone is 70 ~ 400nm.
2. the preparation method of the Nano microsphere of load prednisolone according to claim 1, is characterized in that, comprise the steps:
Step one, under agitation, by N, N '-carbonyl dimidazoles and ibuprofen in molar ratio 1 ~ 1.3:1 be added in dimethylsulfoxide solvent, stirred at ambient temperature reaction 1 ~ 3h;
Step 2, inulin is joined in the reactant liquor of step one, at 60 ~ 100 DEG C, react 12 ~ 48h; Wherein, described in inulin unit and step one, the molar ratio of ibuprofen is 1 ~ 10:2;
Step 3, to be poured into by the reactant liquor of step 2 in cold water and separate out precipitation, washing, drying obtain ibuprofen modification inulin;
Under step 4, stirring condition, ibuprofen modification inulin prednisolone and step 3 prepared in mass ratio 1:2 ~ 20 dissolves in organic solvent, being added drop-wise to volume is again in 40 ~ 80 DEG C of hot water of organic solvent 4 ~ 20 times, remove organic solvent afterwards, lyophilization, obtains the Nano microsphere of described load prednisolone.
3. the preparation method of the Nano microsphere of load prednisolone according to claim 2, is characterized in that, organic solvent described in step 4 is acetone, one or more in dimethyl sulfoxine or dimethyl formamide.
4. the preparation method of the Nano microsphere of load prednisolone according to claim 2, is characterized in that, removes the method for organic solvent for volatilization in step 4.
5. the preparation method of the Nano microsphere of load prednisolone according to claim 2, is characterized in that, removes the method for organic solvent for removing under reduced pressure in step 4.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410003889.9A CN103705470B (en) | 2014-01-06 | 2014-01-06 | Methylprednisolone-loading nanoparticles as well as preparation method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410003889.9A CN103705470B (en) | 2014-01-06 | 2014-01-06 | Methylprednisolone-loading nanoparticles as well as preparation method and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103705470A CN103705470A (en) | 2014-04-09 |
| CN103705470B true CN103705470B (en) | 2015-06-17 |
Family
ID=50399066
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410003889.9A Expired - Fee Related CN103705470B (en) | 2014-01-06 | 2014-01-06 | Methylprednisolone-loading nanoparticles as well as preparation method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103705470B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105012238A (en) * | 2015-06-16 | 2015-11-04 | 上海市肺科医院 | Methylprednisolone immune nanoliposome having active lung targeting property, and preparation method thereof |
| CN105727306B (en) * | 2016-03-01 | 2019-01-29 | 南通大学附属医院 | A kind of nanoscopic drug carriers and preparation method thereof loading methylprednisolone |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002040029A2 (en) * | 2000-11-17 | 2002-05-23 | Pharma Biotech Limited | Corticosteroids adducts with natural polysaccharide polymers |
| CN103491950A (en) * | 2011-02-24 | 2014-01-01 | 普渡研究基金会 | Nanomedicines for early nerve repair |
-
2014
- 2014-01-06 CN CN201410003889.9A patent/CN103705470B/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002040029A2 (en) * | 2000-11-17 | 2002-05-23 | Pharma Biotech Limited | Corticosteroids adducts with natural polysaccharide polymers |
| CN103491950A (en) * | 2011-02-24 | 2014-01-01 | 普渡研究基金会 | Nanomedicines for early nerve repair |
Non-Patent Citations (1)
| Title |
|---|
| USE OF IBUPROFEN AND METHYLPREDNISOLONE FOR THE PREVENTION OF PAIN AND SWELLING AFTER REMOVAL OF IMPACTED THIRD MOLARS;S.SCHULTZE-MOSGAU ET.AL;《J ORAL MAXILLOFAC SURG》;19951231;第53卷;第2-7页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN103705470A (en) | 2014-04-09 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Wang et al. | Progress of electrospun nanofibrous carriers for modifications to drug release profiles | |
| Allawadhi et al. | Biomedical applications of polysaccharide nanoparticles for chronic inflammatory disorders: Focus on rheumatoid arthritis, diabetes and organ fibrosis | |
| Panos et al. | New drug delivery systems based on chitosan | |
| CN102871966B (en) | Nano drug carrier particles for improving bioavailability of rapamycin and preparation method thereof | |
| KR20110036704A (en) | Method of forming non-immunogenic hydrophobic protein nanoparticles and uses therefor | |
| Huang et al. | Surface modified titania nanotubes containing anti-bacterial drugs for controlled delivery nanosystems with high bioactivity | |
| Zheng et al. | Novel iron–polysaccharide multilayered microcapsules for controlled insulin release | |
| Lou et al. | Functional PVA/VB2/TiO2 nanofiber webs for controlled drug delivery | |
| CN102688195A (en) | Preparation method for doxorubicin hydrochloride-entrapped chitosan carboxymethyl chitosan nanometer controlled-release particle with pH sensibility | |
| CN103705470B (en) | Methylprednisolone-loading nanoparticles as well as preparation method and application thereof | |
| Huang et al. | Pharmacokinetics, efficacy, and safety evaluation of docetaxel/hydroxypropyl-sulfobutyl-β-cyclodextrin inclusion complex | |
| CN103316352A (en) | Graphene oxide nano-drug carrier and anti-tumor drug as well as preparation method of anti-tumor drug | |
| CN105343870B (en) | A kind of keratin nanoparticle and preparation method thereof | |
| CN104887630A (en) | A lipidosome-covered dehydrogenated silibinin phospholipid complex and a preparing method thereof | |
| Hua et al. | Polymer nanoparticles prepared by supercritical carbon dioxide for in vivo anti-cancer drug delivery | |
| CN101317832B (en) | Oral administration nano-drug administration system of resveratrol | |
| Sabra et al. | Gastrointestinal delivery of APIs from chitosan nanoparticles | |
| CN103877593B (en) | Based on the kidney targeting supermolecule and preparation method thereof of catechol beautify chitosan | |
| CN110960512A (en) | Amino acid-chitosan nano drug-loading system, preparation method and application thereof | |
| CN103495177B (en) | The preparation of albumin compound thermo-sensitive macromolecule micro-capsule and the application as pharmaceutical carrier | |
| CN114522150B (en) | Preparation method and application of pH-sensitive plant microcapsule nano extruder | |
| CN105727306A (en) | Novel nanometer drug carrier loaded with methyllprednisolone and preparation method of novel nanometer drug carrier | |
| CN1198100A (en) | Chitosan drug delivery system | |
| CN105726481A (en) | Preparation and application of targeted mitochondrion nano particles on the basis of composite porcelain body | |
| Oliveira et al. | Microparticles as a strategy for low-molecular-weight heparin delivery |
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: 20150617 Termination date: 20170106 |