CN101785867B - Preparation method of corn protein nano-particles - Google Patents
Preparation method of corn protein nano-particles Download PDFInfo
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- CN101785867B CN101785867B CN200910311905XA CN200910311905A CN101785867B CN 101785867 B CN101785867 B CN 101785867B CN 200910311905X A CN200910311905X A CN 200910311905XA CN 200910311905 A CN200910311905 A CN 200910311905A CN 101785867 B CN101785867 B CN 101785867B
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Abstract
The invention discloses a preparation method of corn protein nano-particles in the technical field of medicine preparation, comprising: adding zein to mixed solvent to prepare corn protein solution; pumping CO2 into a high-pressure reactor, and pumping the corn protein solution into the high-pressure reactor after the reactor gets the reaction pressure and the reaction temperature; adding CO2 to the high-pressure reactor further until the end of the drying of the residual solvent, then obtaining the corn protein nano-particles. For the corn protein nano-particles prepared in the invention, the particle has round and normal shape, uniform size, and 100-400 nm of diameter.
Description
Technical field
What the present invention relates to is the preparation method of a kind of medicine and food technology field, specifically is a kind of preparation method of corn protein nano-particles.
Background technology
The research that microsphere is used for pharmaceutical carrier starts from 20th century the mid-1970s, because it to the targeting of certain organs and tissue and the slow-releasing of drug release, has become the focus of controlled release agent type research.Microsphere can use for injection (quiet notes, intramuscular injection), oral, collunarium, subdermal implantation or articular cavity administration.Natural polymer medicament slow release system had both had the characteristics of general medicament slow release, as: the rate of release of regulating and control medicine is realized long-acting purpose; Reduce administration number of times and medicine irritation, reduce toxic and side effects, improve curative effect; Increase medicine stability; Cover the poor taste of medicine; Prevent that medicine is at inactivation of gastric etc.Again because the degradability of natural material self makes material degradation speed become the principal element of control drug release speed; In addition, the slower characteristics of drug release that are positioned at the system center have been offset in the degraded of material, and it is constant that drug release rate can be kept, and reaches zero level release dynamics pattern.(Wang Huajie, Liu Xinming, Wang Jinye. the progress of natural polymer medicine microsphere carrier material. the macromolecule circular, 2006,8:1-9)
Zein (zein) is main corn storage protein, accounts for the 40-50% of corn gluten protein.Because it can be dissolved in ethanol and was familiar with by people first in 1897.Zein is as the early existing report of the carrier material of slow releasing pharmaceutical, and wherein the zein microsphere is comparatively common, adopts phase separation method, spray drying method etc. usually.
Find through retrieval prior art, american documentation literature USP5271961 (preparation method of protein microsphere) and USP document number 5679377 (protein microsphere and using method thereof), Chinese patent literature CN1476825A (cereals alcohol soluble protein microsphere and preparation method) and CN1562373A (preparation method of Phytogenous alcohol-soluble protein microsphere solid dosage form) are the zein granules that utilizes phase separation method to prepare the different-grain diameter size and distribute, the slow release that is used for bioactivator in the body, can be used for oral, subcutaneous injection, intramuscular injection etc.
And spray drying method is only seen bibliographical information Zhao spray drying method for preparation nanoscale zein capsule and different formulations lysozyme release in vitro effect of kinetics (the Qixin Zhong to embedding, Minfeng Jin.J.Agric.Food Chem., 2009,57:3886-3894).The zein microcapsule of method for preparing all has the good slow release performance and shows the characteristic that anti-certain antipepsin decomposes, and is a kind of good enteric coatings material.And as natural biomacromolecule, zein has good biocompatibility and biodegradable characteristic.And food proteins is considered to safe nutritional thing (GRAS) usually, itself also nutritious value, this be biodegradable polymer such as polylactic acid can not compare.But said method all has certain limitation.Phase separation method is difficult to thoroughly remove solvent from the wall material, to obtain the microcapsule product of bone dry; The spray drying method serviceability temperature is higher, and the thermal sensitivity medicine is had destructiveness.
At the problems referred to above, supercritical fluid technology is suggested and is used to prepare corn protein nano-particles.Since its mild condition, the active component of survivable medicine.The material that is used as supercritical fluid is a lot, wherein critical temperature (the T of carbon dioxide
C=31.3 ℃) near room temperature, critical pressure (P
C=7.37MPa) not high, and nontoxic, tasteless, nonflammable yet, chemical inertness, low price is easily made high-pure gas, so use at most in practice.Supercritical carbon dioxide anti-solvent method (Supercritical Fluid Anti-solvent, SAS) as one of supercritical fluid technology, because characteristics such as liquid flux are easy to select, operation energy consumption is low and can operate, cause that pharmaceutical field more and more pays close attention under relatively low high pressure conditions.Diameter of particle with SAS method preparation is little, narrowly distributing, solvent residual amount are low, therefore has more superiority aspect the preparation of corn protein nano-particles.
Summary of the invention
The present invention is directed to the prior art above shortcomings, a kind of preparation method of corn protein nano-particles is provided, provide new data for the supercritical carbon dioxide anti-solvent legal system is equipped with natural polymer medicine microsphere carrier technology.Make it can be used for the pharmaceutical carrier of humans and animals, with the problem that solves because of untoward reaction in the too high organism that causes of some drugs local concentration, by the carrier degradation in vivo, medicine spreads gradually and reaches slow release effect, thereby minimizing medicine frequency, reduce the blood concentration peak valley phenomenon, improve drug effect and safety.
The present invention is achieved by the following technical solutions:
The present invention includes following steps:
The first step, zein is added in the mixed solvent, be made into corn protein solution;
Described mixed solvent is meant: acetone-dimethyl sulfoxine system solvent, acetone-methanol system solvent or ethanol-dichloromethane system solvent.
The concentration of zein is 5～100mg/mL in the described corn protein solution.
Second the step, with CO
2Pump in the autoclave, after arriving reaction pressure and reaction temperature, in autoclave, pump into corn protein solution.
Described reaction pressure is 8～15MPa.
Described reaction temperature is 32～50 ℃.
The described corn protein solution that pumps in autoclave, its flow velocity is 0.5～1.25mL/min.
The 3rd goes on foot, further feeds CO in autoclave
2, finish until the residual solvent drying, promptly obtain corn protein nano-particles, this grain shape rounding, size is even, and particle diameter is between the 100-400nm.
The present invention is simple to operate, and the corn protein nano-particles particle diameter that makes is little, narrowly distributing, and solvent residual amount is low.Can be used in the pharmaceutical carrier of humans and animals, all dissolve in the medicine of above-mentioned dicyandiamide solution, particularly are insoluble in the medicine of water, can use this pharmaceutical carrier to prepare the medicament slow release capsule, improve the holdup time of medicine in blood, reduce drug side effect, improve bioavailability of medicament.
Description of drawings
Fig. 1 is the sample sem photograph of embodiment 1.
Fig. 2 is the sample nano particle size analysis result of embodiment 1.
The specific embodiment
Below embodiments of the invention are elaborated, present embodiment is being to implement under the prerequisite with the technical solution of the present invention, provided detailed embodiment and concrete operating process, but protection scope of the present invention is not limited to following embodiment.
Following examples all detect by scanning electron microscope analysis and nano particle size analysis, the scanning electron microscope analysis instrument is the Japanese JEOL JSM-7401F of a company type field emission scan formula ultramicroscope, and the nano particle size analytical tool is the Britain ZS90 of a MalvernInstruments company type nano particle size analyser.
Be illustrated in figure 1 as the corn protein nano-particles sem photograph;
Embodiment 1
With quality is the zein of 300mg, is dissolved in volume ratio and is in the 15ml mixed solvent of 7: 3 acetone and dimethyl sulfoxine, is mixed with the corn protein solution of 20mg/ml.Carbon dioxide is pumped in the autoclave, and the question response still pumps into corn protein solution with the flow velocity of 1.0ml/min after reaching the preset value of 40 ℃ of temperature, pressure 10MPa and stablizing 5min.After solution pump is intact, after continuing to feed carbon dioxide 30min, stop to feed carbon dioxide, the granule in the reactor is collected in pressure release, promptly obtains corn protein nano-particles.
Corn protein nano-particles use emission scan formula electron microscope observation granule-morphology with preparation.Pressed powder directly is bonded on the conducting resinl behind metal spraying under the vacuum state, observes.The result as shown in Figure 1.
The corn protein nano-particles of preparation is detected particle diameter and distribution with the nano particle size analyser, disperse testing sample with deionized water before detecting, and in Ultrasound Instrument, disperse 1min.The particle size distribution of gained corn protein nano-particles as shown in Figure 2, between 140nm-370nm.Wherein, ordinate is the quantity percentage ratio of corn protein nano-particles, and abscissa is the particle diameter (nm) of corn protein nano-particles.The mean diameter of gained corn protein nano-particles is 265nm.
Embodiment 2
With quality is the zein of 150mg, is dissolved in volume ratio and is in the 15ml mixed solvent of 7: 3 acetone and dimethyl sulfoxine, is mixed with the corn protein solution of 10mg/ml.Carbon dioxide is pumped in the autoclave, and the question response still pumps into corn protein solution with the flow velocity of 1.0ml/min after reaching the preset value of 40 ℃ of temperature, pressure 10MPa and stablizing 5min.After solution pump is intact, after continuing to feed carbon dioxide 30min, stop to feed carbon dioxide, the granule in the reactor is collected in pressure release, promptly obtains corn protein nano-particles.
The particle diameter of corn protein nano-particles and the detection that distributes are with embodiment 1, and particle size distribution is between 110nm-300nm, and mean diameter is 217nm.
Embodiment 3
With quality is the zein of 300mg, is dissolved in volume ratio and is in the 15ml mixed solvent of 7: 3 acetone and dimethyl sulfoxine, is mixed with the corn protein solution of 20mg/ml.Carbon dioxide is pumped in the autoclave, and the question response still pumps into corn protein solution with the flow velocity of 1.0ml/min after reaching the preset value of 32 ℃ of temperature, pressure 10MPa and stablizing 5min.After solution pump is intact, after continuing to feed carbon dioxide 30min, stop to feed carbon dioxide, the granule in the reactor is collected in pressure release, promptly obtains corn protein nano-particles.
The particle diameter of corn protein nano-particles and the detection that distributes are with embodiment 1, and particle size distribution is between 105nm-280nm, and mean diameter is 197nm.
Embodiment 4
With quality is the zein of 300mg, is dissolved in volume ratio and is in the 15ml mixed solvent of 7: 3 acetone and dimethyl sulfoxine, is mixed with the corn protein solution of 20mg/ml.Carbon dioxide is pumped in the autoclave, and the question response still pumps into corn protein solution with the flow velocity of 1.0ml/min after reaching the preset value of 40 ℃ of temperature, pressure 15MPa and stablizing 5min.After solution pump is intact, after continuing to feed carbon dioxide 30min, stop to feed carbon dioxide, the granule in the reactor is collected in pressure release, promptly obtains corn protein nano-particles.
The particle diameter of corn protein nano-particles and the detection that distributes are with embodiment 1, and particle size distribution is between 100nm-210nm, and mean diameter is 162nm.
Claims (5)
1. the preparation method of a corn protein nano-particles is characterized in that, may further comprise the steps:
The first step, zein is added in the mixed solvent, be made into corn protein solution;
Second the step, with CO
2Pump in the autoclave, after arriving reaction pressure and reaction temperature, in autoclave, pump into corn protein solution;
The 3rd goes on foot, further feeds CO in autoclave
2, finish until the residual solvent drying, promptly obtain corn protein nano-particles;
Described corn protein nano-particles, this grain shape rounding, size is even, and particle diameter is between the 100-400nm;
Described mixed solvent is meant: acetone-dimethyl sulfoxine system solvent, wherein: acetone-dimethyl sulfoxine system is meant that volume ratio is 7: 3 the acetone and the mixed liquor of dimethyl sulfoxine.
2. the preparation method of corn protein nano-particles according to claim 1 is characterized in that, the concentration of zein is 5～100mg/mL in the described corn protein solution.
3. the preparation method of corn protein nano-particles according to claim 1 is characterized in that, described reaction pressure is 8～15MPa.
4. the preparation method of corn protein nano-particles according to claim 1 is characterized in that, described reaction temperature is 32～50 ℃.
5. the preparation method of corn protein nano-particles according to claim 1 is characterized in that, the described corn protein solution that in autoclave, pumps into, and its flow velocity is 0.5～1.25mL/min.
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| CN101785867B true CN101785867B (en) | 2011-11-16 |
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| CN103445282B (en) * | 2013-07-19 | 2014-12-31 | 华南理工大学 | Preparation method of corn peptide glycosylation product nano particles embedding lipid-soluble vitamins |
| CN105054073B (en) * | 2015-08-10 | 2018-02-27 | 华南理工大学 | A kind of water miscible vitamine D3 nano particle and preparation method thereof |
| CN106420666A (en) * | 2016-11-25 | 2017-02-22 | 沈阳师范大学 | Preparation method and device of glycosylation zein nano-carrier |
| TWI834984B (en) * | 2021-07-30 | 2024-03-11 | 寶齡富錦生技股份有限公司 | Controlled-release oral formulation and preparation method thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1476825A (en) * | 2003-07-04 | 2004-02-25 | 中国科学院上海有机化学研究所 | Grain prolamin microsphere and preparation method |
| CN1562373A (en) * | 2004-03-25 | 2005-01-12 | 上海交通大学 | Method for preparing solid dosage forms type microsphere of alcohol soluble protein from source of plants |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1476825A (en) * | 2003-07-04 | 2004-02-25 | 中国科学院上海有机化学研究所 | Grain prolamin microsphere and preparation method |
| CN1562373A (en) * | 2004-03-25 | 2005-01-12 | 上海交通大学 | Method for preparing solid dosage forms type microsphere of alcohol soluble protein from source of plants |
Non-Patent Citations (3)
| Title |
|---|
| Qixin Zhong et al..Application of Supercritical Anti-Solvent Technologies for the Synthesis of Delivery Systems of Bioactive Food Components.《Food Biophysics》.2008,第3卷第186-190页. * |
| Qixin Zhong et al..Sustained release of lysozyme from zein microcapsules produced by a supercritical anti-solvent process.《Food Chemistry》.2008,第115卷(第2期),第697-700页. * |
| 林长春等.超临界抗溶剂技术在纳米营养物制备中的应用进展.《食品科学》.2009,第30卷(第07期),第246-250页. * |
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