CN103006563A - Preparation method of long-circulating nanoparticles - Google Patents
Preparation method of long-circulating nanoparticles Download PDFInfo
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- CN103006563A CN103006563A CN 201110284572 CN201110284572A CN103006563A CN 103006563 A CN103006563 A CN 103006563A CN 201110284572 CN201110284572 CN 201110284572 CN 201110284572 A CN201110284572 A CN 201110284572A CN 103006563 A CN103006563 A CN 103006563A
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Abstract
The invention relates to a preparation method of long-circulating nanoparticles and belongs to the field of drug processing. The preparation method can be operated simply and can produce the long-circulating nanoparticles having good targeting performances and external release properties. The preparation method comprises the following steps of dissolving 5-Fu, PEG-PHDCA and phospholipid in a mixed organic solvent of tetrahydrofuran and ethanol to obtain an organic phase, slowly and dropwisely adding the organic phase into a water phase of a surfactant with magnetic stirring, then persistently stirring for 1 hour so that the organic phase is dispersed fully, carrying out reduced pressure evaporation to remove the mixed organic solvent and to obtain a nanoparticle colloidal suspension liquid having blue opalescence, carrying out overspeed centrifugal separation precipitation and washing of nanoparticles, carrying out ultrasonic dispersion by a mannitol solution having the content of 4%, and carrying out freeze drying.
Description
Technical field:
The invention belongs to the medicine manufacture field, in particular, relate to a kind of preparation method of long-circulating nanoparticles.
Background technology:
As everyone knows, the defense function of human body is very strong, and it is very strong to the identification ability of external foreign body that its powerful RE is engulfed system.Many researchs are found, behind the quiet notes of nanoparticle, mainly concentrate in mononuclear phagocyte (MPS) abundant organ, especially liver, spleen, the bone marrow, for the medicine of these organs of targeting, that yes is desirable for this, but for other medicines, nanoparticle is concentrated in these organs, so that the circulation time of medicine in blood is very short, do not arrive target organ, can not produce the long-acting slow-release effect.For addressing the above problem, developed long-circulating nanoparticles.
Long-circulating nanoparticles mainly is the surface nature that changes microgranule by finishing, to reach long circulating effect.By improve the nanoparticle surface hydrophilicity, increase sterically hindered, reduce Zeta potential, control particle diameter can reduce or avoid within the specific limits MPS to the identification of nanoparticle and combination subsequently, engulf, thereby reach macrocyclic purpose.
Long-circulating nanoparticles can be used for sustained-release preparation, and clinical angiographic diagnosis is for the nanoparticle of PEG coating, can connect albumen, antibody, gene etc. by proper method, be used for the targeting specified tissue, gene therapy, with its outstanding advantage and widely range of application day by day be subject to the attention of Producer.
5-fluorouracil can be alone or drug combination treat various types of malignant tumor, but major defect is fat-soluble little, oral absorption not exclusively and be difficult to prediction; Behind vein or the artery administration, drug half-life short (only being 10min in vivo) is unfavorable for continuous chemotherapy, and has the toxicity such as local excitation reaction, gastrointestinal reaction and bone marrow depression of dose dependent; Synthetic Fluorouracil derivative anti-tumor activity is not high, and these deficiencies have limited 5-Fu application clinically to a certain extent.
Summary of the invention:
The present invention is exactly for the problems referred to above, provides a kind of simple to operate, product to have the preparation method of the long-circulating nanoparticles of better targeting, release in vitro.
In order to realize above-mentioned purpose of the present invention, preparation process of the present invention is: get 5-Fu, PEG-PHDCA and phospholipid are dissolved in it in mixed organic solvents of oxolane and ethanol, consist of organic facies, under magnetic agitation, this organic facies slowly is added drop-wise to the aqueous phase of surfactant, after dropwising, continue to stir 1h, organic facies is fully spread, and then reduction vaporization is removed organic solvent, obtains the nanoparticle colloidal state suspension of blueing color opalescence, this nanoparticle through the ultracentrifugation precipitation separation, is washed; With 4% mannitol solution ultra-sonic dispersion, lyophilization.
The specific embodiment:
Preparation process of the present invention is: get 5-Fu, PEG-PHDCA and phospholipid are dissolved in it in mixed organic solvents of oxolane and ethanol, consist of organic facies, under magnetic agitation, this organic facies slowly is added drop-wise to the aqueous phase of surfactant, after dropwising, continue to stir 1h, organic facies is fully spread, then reduction vaporization is removed organic solvent, obtain the nanoparticle colloidal state suspension of blueing color opalescence, this nanoparticle through the ultracentrifugation precipitation separation, is washed; With 4% mannitol solution ultra-sonic dispersion, lyophilization.
The present invention selects mixing speed, preparation temperature, V
Water: V
Organic, the phospholipid consumption is as the influence factor of nanoparticle quality, can see Table 1, table 2, table 3, table 4.
Table 1 mixing speed is on the impact of nanoparticle quality
| Rotating speed/rmin -1 | Particle diameter/nm | Envelop rate/% |
| 200 | 605 | 38.36 |
| 500 | 321 | 35.18 |
| 800 | 143 | 33.34 |
| 1200 | 87 | 23.21 |
Table 2V
Water: V
OrganicImpact on the nanoparticle quality
| V Water∶V Organic | Particle diameter/nm | Envelop rate/% |
| 1.5∶1 | 246 | 35.03 |
| 2.5∶1 | 131 | 33.45 |
| 3.5∶1 | 125 | 27.76 |
| 5.5∶1 | 103 | 20.20 |
Table 3 preparation temperature is on the impact of nanoparticle quality
| Preparation temperature/℃ | 20 | 25 | 30 | 40 | 50 |
| Envelop rate/% | 32.68 | 35.84 | 35.53 | 34.51 | 29.35 |
Table 4 phospholipid consumption is on the impact of nanoparticle quality
| Phospholipid consumption/mg | Particle diameter/nm | Envelop rate/% |
| 0 | 145 | 30.31 |
| 10 | 126 | 37.89 |
| 20 | 134 | 39.37 |
| 40 | 295 | 40.56 |
| 80 | 441 | 41.54 |
As a kind of preferred version, preparation process of the present invention is: mixing speed 200rmin
-1, 25 ℃ of preparation temperatures, V
Water: V
OrganicBe that 1.5: 1, phospholipid consumption are 80mg.
Claims (2)
1. the preparation method of a long-circulating nanoparticles, it is characterized in that, preparation process of the present invention is: get 5-Fu, PEG-PHDCA and phospholipid are dissolved in it in mixed organic solvents of oxolane and ethanol, consist of organic facies, under magnetic agitation, this organic facies slowly is added drop-wise to the aqueous phase of surfactant, after dropwising, continue to stir 1h, organic facies is fully spread, then reduction vaporization is removed organic solvent, obtain the nanoparticle colloidal state suspension of blueing color opalescence, this nanoparticle through the ultracentrifugation precipitation separation, is washed; With 4% mannitol solution ultra-sonic dispersion, lyophilization.
2. the preparation method of a kind of long-circulating nanoparticles according to claim 1 is characterized in that, preparation process of the present invention is: mixing speed 200rmin
-1, 25 ℃ of preparation temperatures, V
Water: V
OrganicBe 1.5: 1, the phospholipid consumption is 80mg.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201110284572 CN103006563A (en) | 2011-09-23 | 2011-09-23 | Preparation method of long-circulating nanoparticles |
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| CN 201110284572 CN103006563A (en) | 2011-09-23 | 2011-09-23 | Preparation method of long-circulating nanoparticles |
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| CN103006563A true CN103006563A (en) | 2013-04-03 |
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| CN 201110284572 Pending CN103006563A (en) | 2011-09-23 | 2011-09-23 | Preparation method of long-circulating nanoparticles |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2015092110A1 (en) * | 2013-12-19 | 2015-06-25 | Universidad De Granada | Polymer nanoparticles comprising poly(butyl cyanoacrylate) or poly(ε-caprolactone) for the use thereof in therapy |
| CN107412191A (en) * | 2016-02-16 | 2017-12-01 | 烟台大学 | A kind of long circulating lipid-polymer hybrid nanoparticle and preparation method thereof |
-
2011
- 2011-09-23 CN CN 201110284572 patent/CN103006563A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2015092110A1 (en) * | 2013-12-19 | 2015-06-25 | Universidad De Granada | Polymer nanoparticles comprising poly(butyl cyanoacrylate) or poly(ε-caprolactone) for the use thereof in therapy |
| CN107412191A (en) * | 2016-02-16 | 2017-12-01 | 烟台大学 | A kind of long circulating lipid-polymer hybrid nanoparticle and preparation method thereof |
| CN107412191B (en) * | 2016-02-16 | 2020-01-14 | 烟台大学 | Long-circulating lipid-polymer hybrid nanoparticles and preparation method thereof |
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Application publication date: 20130403 |