CN103127005A - Preparation method of novel dopamine brain-targeting nano-particles - Google Patents
Preparation method of novel dopamine brain-targeting nano-particles Download PDFInfo
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- CN103127005A CN103127005A CN2013100601386A CN201310060138A CN103127005A CN 103127005 A CN103127005 A CN 103127005A CN 2013100601386 A CN2013100601386 A CN 2013100601386A CN 201310060138 A CN201310060138 A CN 201310060138A CN 103127005 A CN103127005 A CN 103127005A
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Abstract
The invention discloses a preparation method of novel dopamine brain-targeting nano-particles. According to the method, a certain concentration of a polyvinyl alcohol water solution is prepared, and is subjected to standing overnight; the solution is cooled, and Tween-60 is added; a polyer/dichloromethane solution is prepared; the solution is completely dissolved, and polyvinyl pyrrolidone and Span-60 are dissolved into the dichloromethane solution; the mixture is stirred until sufficiently dissolved, such that an oil phase is obtained; dopa with different ratios are dissolved, such that an internal water phase is obtained; under magnetic stirring, the internal water phase is slowly added into the oil phase by using a barrel syringe; stirring and emulsification are continued under the speed; the oil phase is transferred into an outer water phase by using a pipette gun; the temperature is increased, such that dichloromethane is evaporated; the product is washed multiple times by using double-distilled water, and is filtered and lyophilized until constant weight is achieved, such that DA-packaging polymer microspheres are obtained. The novel degradable biological nano-grade material provided by the invention has relatively high bioavailability. The preparation method has the advantages of simple method, low cost, and high stability.
Description
Technical field
The invention belongs to macromolecular material and medical domain, relate in particular to a kind of preparation method of novel dopamine brain targeted nano granule.
Background technology
At present, along with being on the increase of aging crowd, the cerebral retrogressive disease more and more is subject to people's attention, and wherein, parkinson disease are had a strong impact on people's quality of life by the disease of extensive concern.Parkinsonian pathogenesis understood, due to the degeneration of substantia nigra dopaminergic neuron.At present both at home and abroad consistent treatment measure is oral levodopa, because this medicine can pass through blood brain barrier, through the effect of decarboxylase, changes dopamine into and plays a role in brain.
Present existing problems: medication dose increases gradually, and side effect is more and more serious, until dead, has a strong impact on patient's life-span and quality of life, and cost is high, has brought serious financial burden for family and society.
Summary of the invention
The purpose of the embodiment of the present invention is to provide a kind of preparation method of novel dopamine brain targeted nano granule, be intended to solve present medication dose and increase gradually, side effect is more and more serious, until dead, have a strong impact on patient's life-span and quality of life, the problem that cost is high.
The embodiment of the present invention is achieved in that a kind of preparation method of novel dopamine brain targeted nano granule, and this preparation method adopts emulsion-solvent evaporation method to prepare the PLA-PEG polymer microballoon, comprises the following steps:
1. outer aqueous phase system: configure certain density polyvinyl alcohol water solution, high pressure dissolving after hold over night, cooling after, the Tween-60 that adds;
2. oil-based system: prepared polymer/dichloromethane solution, fully after dissolving, polyvinylpyrrolidone, Span-60 are dissolved in dichloromethane solution, stir it is fully dissolved as oil phase;
3. interior water: after the DOPA dissolving of different proportion, as interior water;
4. under magnetic agitation,, slowly join in oil phase interior water with Syringe injector, continue stirring and emulsifying under this speed;
5. with liquid-transfering gun, oil phase is moved into outer water, mixing speed is heightened continued to stir, temperature is raise, make the dichloromethane volatilization, with distilled water to product repeatedly wash, filtration, lyophilization be to constant weight, can obtain wrapping the polymer microballoon of year DA.
Further, configure certain density polyvinyl alcohol water solution, concentration is 0.5-1.5%, high pressure dissolving after hold over night, cooling after, add the Tween-60 of 0.2wt.%.
Further, oil-based system: prepared polymer/dichloromethane solution 15mL, concentration is 2-10%, fully after dissolving, 1.0g polyvinylpyrrolidone, Span-60 are dissolved in dichloromethane solution, stir it is fully dissolved as oil phase; Span and Tween-60 ratio adopted three groups of data 3: 1; 2: 1; 1: 1.
Further, interior water: after the DOPA dissolving of different proportion, concentration is 10-30%, as interior water, is 4-5 with the salt acid for adjusting pH.
Further, carry out magnetic agitation under rotating speed 1000-2000rpm,, slowly join in oil phase interior water with Syringe injector, continue stirring and emulsifying 2h under this speed.
Further, with liquid-transfering gun, oil phase is moved into outer water, after mixing speed is heightened 2000-3000rpm continuation stirring 12h, temperature is elevated to 35 ℃, make dichloromethane volatilization, with distilled water to product repeatedly wash, filtration, lyophilization be to constant weight, can obtain wrapping the polymer microballoon that carries DA.
Further, change technological parameter, make microsphere diameter less than 100nm.
The novel degradable Bio-Nano-Materials of the present invention's preparation, higher bioavailability; Preparation method is simple, and cost is low, and stability is high.
Description of drawings
Fig. 1 is the flow chart of the preparation method of the novel dopamine brain targeted nano granule that provides of the embodiment of the present invention.
The specific embodiment
In order to make purpose of the present invention, technical scheme and advantage clearer, below in conjunction with embodiment, the present invention is further elaborated.Should be appreciated that specific embodiment described herein only in order to explain the present invention, is not intended to limit the present invention.
As shown in Figure 1, the invention provides a kind of preparation method of novel dopamine brain targeted nano granule, concrete technical scheme is as follows:
Emulsion-solvent evaporation method prepares PLA-PEG polymer microballoon process:
1. outer aqueous phase system: configure (0.5-1.5%) aqueous solution of certain density PVA (polyvinyl alcohol), high pressure dissolving after hold over night, cooling after, add the Tween-60 of 0.2wt.%;
2. oil-based system: prepared polymer/dichloromethane solution 15mL (2-10%), fully after dissolving, 1.0gPVP (polyvinylpyrrolidone), Span-60 (three groups of data of Span and the employing of Tween-60 ratio 3: 1; 2: 1; 1: 1) be dissolved in dichloromethane solution, stirring is fully dissolved as oil phase it;
3. interior water: after the DOPA of different proportion (10-30%) dissolving (the salt acid for adjusting pH is 4-5), as interior water;
4. (1000-2000) rpm under magnetic agitation,, slowly join in oil phase interior water with Syringe injector, continues stirring and emulsifying 2h under this speed.
5. with liquid-transfering gun, oil phase is moved into outer water, after mixing speed is heightened 2000-3000rpm continuation stirring 12h, temperature is elevated to 35 ℃, makes the dichloromethane volatilization, with distilled water to product repeatedly wash, filtration, lyophilization be to constant weight, can obtain wrapping the polymer microballoon that carries DA.
6. change technological parameter, make microsphere diameter less than 100nm.
The above is only preferred embodiment of the present invention, not in order to limiting the present invention, all any modifications of doing within the spirit and principles in the present invention, is equal to and replaces and improvement etc., within all should being included in protection scope of the present invention.
Claims (7)
1. the preparation method of a novel dopamine brain targeted nano granule, is characterized in that, this preparation method adopts emulsion-solvent evaporation method to prepare the PLA-PEG polymer microballoon, comprises the following steps:
1. outer aqueous phase system: configure certain density polyvinyl alcohol water solution, high pressure dissolving after hold over night, cooling after, the Tween-60 that adds;
2. oil-based system: prepared polymer/dichloromethane solution, fully after dissolving, polyvinylpyrrolidone, Span-60 are dissolved in dichloromethane solution, stir it is fully dissolved as oil phase;
3. interior water: after the DOPA dissolving of different proportion, as interior water;
4. under magnetic agitation,, slowly join in oil phase interior water with Syringe injector, continue stirring and emulsifying under this speed;
5. with liquid-transfering gun, oil phase is moved into outer water, mixing speed is heightened continued to stir, temperature is raise, make the dichloromethane volatilization, with distilled water to product repeatedly wash, filtration, lyophilization be to constant weight, can obtain wrapping the polymer microballoon of year DA.
2. the preparation method of novel dopamine brain targeted nano granule as claimed in claim 1, is characterized in that, configures certain density polyvinyl alcohol water solution, and concentration is 0.5-1.5%, high pressure dissolving after hold over night, cooling after, add the Tween-60 of 0.2wt.%.
3. the preparation method of novel dopamine brain targeted nano granule as claimed in claim 1, it is characterized in that, oil-based system: prepared polymer/dichloromethane solution 15mL, concentration is 2-10%, fully after dissolving, 1.0g polyvinylpyrrolidone, Span-60 are dissolved in dichloromethane solution, stir it is fully dissolved as oil phase; Span and Tween-60 ratio adopted three groups of data 3: 1; 2: 1; 1: 1.
4. the preparation method of novel dopamine brain targeted nano granule as claimed in claim 1, is characterized in that, interior water: after the DOPA dissolving of different proportion, concentration is 10-30%, as interior water, is 4-5 with the salt acid for adjusting pH.
5. the preparation method of novel dopamine brain targeted nano granule as claimed in claim 1, it is characterized in that, carry out magnetic agitation under rotating speed 1000-2000rpm, with Syringe injector with interior water, slowly join in oil phase, continue stirring and emulsifying 2h under this speed.
6. the preparation method of novel dopamine brain targeted nano granule as claimed in claim 1, it is characterized in that, with liquid-transfering gun, oil phase is moved into outer water, after mixing speed is heightened 2000-3000rpm continuation stirring 12h, temperature is elevated to 35 ℃, make dichloromethane volatilization, with distilled water to product repeatedly wash, filtration, lyophilization be to constant weight, can obtain wrapping the polymer microballoon that carries DA.
7. the preparation method of novel dopamine brain targeted nano granule as claimed in claim 1, is characterized in that, changes technological parameter, makes microsphere diameter less than 100nm.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1682704A (en) * | 2004-04-14 | 2005-10-19 | 中南大学 | Levodopa nano preparation and its preparing method |
| CN101953782A (en) * | 2009-07-21 | 2011-01-26 | 上海禾丰制药有限公司 | Production method for dopamine hydrochloride injection |
| CN102755323A (en) * | 2012-07-03 | 2012-10-31 | 中国人民解放军第三军医大学第三附属医院 | Medicinal composition for treating periodontitis and method for preparing sustained-release microsphere by using same |
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- 2013-02-21 CN CN201310060138.6A patent/CN103127005B/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1682704A (en) * | 2004-04-14 | 2005-10-19 | 中南大学 | Levodopa nano preparation and its preparing method |
| CN101953782A (en) * | 2009-07-21 | 2011-01-26 | 上海禾丰制药有限公司 | Production method for dopamine hydrochloride injection |
| CN102755323A (en) * | 2012-07-03 | 2012-10-31 | 中国人民解放军第三军医大学第三附属医院 | Medicinal composition for treating periodontitis and method for preparing sustained-release microsphere by using same |
Non-Patent Citations (1)
| Title |
|---|
| 江丽欢: "多巴胺受体激动剂的药理研究进展", 《中国实用医药》 * |
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