CN1283350C - Method for preparing microcapsule by high-voltage electric field encystation and low-temperature extraction and solidification - Google Patents
Method for preparing microcapsule by high-voltage electric field encystation and low-temperature extraction and solidification Download PDFInfo
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- CN1283350C CN1283350C CN 200410084392 CN200410084392A CN1283350C CN 1283350 C CN1283350 C CN 1283350C CN 200410084392 CN200410084392 CN 200410084392 CN 200410084392 A CN200410084392 A CN 200410084392A CN 1283350 C CN1283350 C CN 1283350C
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Abstract
The present invention discloses a method for preparing a microcapsule by high-voltage electric field encystation and low-temperature extraction and solidification, which is characterized in that the method comprises the procedures: the mixed propanone liquid of core material and wall material passes through a microcapsule forming device of a high-voltage electric field; under the functions of electric field force added by the device, and a thruster, liquid balls with different particle diameters are made by adjusting electric field voltage and a liquid surface; the liquid balls are dropped in a liquid nitrogen container for freezing and solidifying the liquid balls to form a ball; the container is arranged in a low temperature environment at-60 DEG C to-90 DEG C, and the solid ball is slowly dissolved; then, propanone is carried away by an extractant so as to cause a polymer to generate deposition and cause a microcapsule to be solidified; ionized water is used for cleaning and centrifugation, and then freeze drying and storage are carried out to the microcapsule. The method has the actual effect that the method can prepare a microcapsule with regular shape, better dispersancy and higher encapsulation rate and medicine carrying capacity, and moreover, the method overcomes the defects of the low encapsulation rate, the poor dispersancy and easy agglomeration of the traditional preparing method of a microcapsule with biodegradability.
Description
Technical field
The present invention relates to a kind of new technology for preparing the biodegradable slow-release microcapsule, particularly a kind of method for preparing microcapsule by high-voltage electric field encystation and low-temperature extraction and solidification.
Background technology
Microencapsulation technology develops into now existing decades.It is found that make microballoon by microencapsulation technology with wall material packaging medicine after, have the medicine stability of raising, reach slowly-releasing or controlled release drug and improve advantage such as biocompatibility.Yet most of natural polymer wall materials of people's early detection can not be degraded in vivo, cause cylinder accumulation easily, are not suitable for intravenous injection, subdermal implantation, make the application of microcapsule product in human body be subjected to limitation.And in recent years, people have developed the degradable macromolecule wall of artificial synthesising biological material, as copolymer (PLGA) of PLA (PLA), polylactic acid-polyglycol copolymer (PLA-PEG) and polylactic acid poly glycolic acid etc.They have the chemical stability height, can degradation in vivo, can be used for advantages such as intravenous injection.Wherein PLA and PLGA are drug release carrier by the approval of U.S. FDA Food and Drug Admistraton.
Biodegradable polymer material is owing to its chemical stability height, poorly water-soluble are difficult for being prepared into microcapsules.Present most of PLA (PLA), polylactic-co-glycolic acid copolymer (PLGA) biodegradable microcapsules all adopt emulsification dispersion method and phase separation method preparation etc.Solvent evaporated method is preparation method commonly used in the emulsification dispersion method, mainly comprises single emulsion method (O/W, O/O) and two emulsion method (W/O/W), and the shortcoming of single emulsion method is the envelop rate of water soluble drug low, is generally about 20%.And answer (two) newborn method (W/O/W) also is PLGA microcapsule preparation method commonly used in recent years.It can hinder the medicine distribution effectively and enter continuous phase, thereby envelop rate is improved, and it is reported that envelop rate can reach 40%~70% with the microcapsules of multi-emulsion method preparation.Multi-emulsion method more goes a step further on the basis of single emulsion method, however the weak point of there is also: and 1. microcapsules are prominent releases seriously; 2. the microcapsules out-of-shape is assembled easily, disperses bad; 3. add emulsifying agent and surfactant, the easy sex change of protein medicaments; Problems such as 4. medicine still exists in the loss of aqueous phase, and envelop rate is general.Except the emulsification dispersion method, main technology of preparing also comprises be separated (cohesion) method and spray drying process etc.The microcapsule granule of (cohesion) method that is separated preparation is easy to reunite, and is difficult to production application; Though and the employing spray drying process can successfully be prepared PLA, PLGA microcapsules, because in the preparation process, microcapsules can attach to the inwall of spraying-drier, this makes that product loses in a large number in spraying-dry run, and product is reunited.
Summary of the invention
The objective of the invention is provides a kind of method for preparing microcapsule by high-voltage electric field encystation and low-temperature extraction and solidification to prepare the slow-release microcapsule of Biodegradable material in order to overcome problems of the prior art.High-voltage field is combined with the low-temperature extraction method, make up a kind of new technology for preparing the biodegradable microcapsules.
Technical scheme of the present invention is, a kind of method for preparing microcapsule by high-voltage electric field encystation and low-temperature extraction and solidification, and its method step is:
1, core is suspended in the acetone soln of wall material that concentration is 1%~6% (W/V);
2, above-mentioned suspension is passed through the described high voltage electric field microcapsules of ZL00218100.2 shaped device, under device applied field power and propeller effect, by adjusting voltage of electric field, adjusting distance and syringe fltting speed between syringe lower end and the liquid nitrogen liquid level, make the liquid ball of different-grain diameter;
3, the liquid globule is gone in the container of the pure kind of extractants of being equipped with of device and-196 ℃ of liquid nitrogen the liquid ball is freezed solid formation ball;
4, container is placed-60 ℃~-90 ℃ low temperature environments, utilize the freezing point difference between pure kind of extractants and the acetone, make the extractant can be molten earlier, and acetone mixes the ball that freezes of liquid and slowly dissolves;
5, with pure kind of extractants acetone is taken away then, made polymer produce deposition, microcapsules are solidified;
6, with washed with de-ionized water, centrifugal, freeze-drying was preserved to be measured after curing was finished.
The actual effect of this method is: this method is owing to just be separated into core wall material mixture grain micron ball uniformly before solidifying, and then solidify slowly, therefore, on the one hand can not break up the micro-capsule shell or produce that big hole causes microballoon prominently to release serious, envelop rate, the medicine carrying amount is low owing to the big pressure that liquid-liquid extraction produces; Before solidifying, just microcapsules are disperseed on the other hand, make not produce gathering by good dispersion when microcapsules solidify.No matter polymer begins deposition from what direction, can prepare regular shape on the principle, disperse microcapsules preferably.These characteristics are compared as the coacervation that is separated, multi-emulsion method etc. with respect to other method has certain advantage, have relatively high expectations for the control of polymer sedimentation in the solidification process and viscosity condition and should not control because of these methods, control bad easily cause microcapsules prominent release serious, produce gathering, envelop rate and the decline of medicine carrying amount.And this method has overcome the defective of these methods.In addition, the preparation process of this method is carried out under anhydrous condition, and for the embedding of hydrophilic protein class material, its envelop rate can have than higher level.This method is operation in low temperature environment, and does not add emulsifying agent and surfactant, has superiority for thermal sensitivity medicines such as polypeptide protein classes.
Description of drawings
Fig. 1 is a microcapsules shaped device schematic diagram,
Fig. 2 is the method for preparing microcapsule by high-voltage electric field encystation and low-temperature extraction and solidification flow chart.
In Fig. 1,1. high-pressure electrostatic field generator, 2. high pressure generator positive pole, 3. high pressure generator negative pole, 4. syringe, 5. propeller, 6. support, 7. liquid nitrogen, the microballoon that 8. freezes, the ethanol that 9. freezes
The specific embodiment
In conjunction with the accompanying drawings, be that 1: 9 insulin, the embodiment of poly (lactic acid-glycolic acid) copolymer are further described the present invention with mass ratio:
1, according to insulin: the polylactic-co-glycolic acid copolymer 1: 9 ratio is dissolved in insulin in the polylactic-co-glycolic acid copolymer acetone soln of 3.5% (W/V);
2, get the plastic measuring glass of 200mL, pour into absolute ethyl alcohol 20ml in the bottom, liquid nitrogen with-196 ℃ freezes it, adds liquid nitrogen to required liquid level, the insulin for preparing, PLGA suspension is passed through the microcapsules shaped device of high voltage electric field, as shown in Figure 1, under electric field force and propeller effect, (as 3.3~3.6kV), liquid level is apart from (25~35mm) by adjusting certain voltage, reach fltting speed, prepare the liquid ball of different-grain diameter.
3, to go into that being equipped with in-196 ℃ of liquid nitrogen plastic measuring glass of device freeze the liquid ball be solid shape ball to the liquid globule.
4, plastic measuring glass is placed-88 ℃ low temperature environment, (freezing point of ethanol is-117.3 ℃ to utilize freezing point difference between ethanol and the acetone, acetone is-94.6 ℃), the ethanol extraction agent is earlier molten, and the acetone that freezes mixes liquid liquid ball because the slowly dissolving near freezing point.
5, with the ethanol extraction agent acetone is taken away then, made polymer produce deposition, microcapsules are solidified, and the time of curing is 2 days.
6, with washed with de-ionized water, centrifugal, freeze-drying was preserved to be measured after curing was finished.
Know that from experiment working as voltage of electric field is 3.4kV, the liquid level distance is 35mm, fltting speed is 20mm/min, the insulin capsule particle diameter that makes is less than 200 μ m, envelop rate is 83.2%, and the medicine carrying amount is 8.82%, and slowly-releasing is 7 days, substantially can satisfy the needs of sustained release preparation, solve the burden that the diabetic is brought because of frequent injection every day.
Claims (1)
1, a kind of method for preparing microcapsule by high-voltage electric field encystation and low-temperature extraction and solidification is characterized in, its method step is:
(1) core is suspended in the acetone soln of wall material that concentration is 1%~6% (W/V);
(2) above-mentioned suspension is passed through the described high voltage electric field microcapsules of ZL00218100.2 shaped device, under device applied field power and propeller effect, by adjusting voltage of electric field, adjusting distance and syringe fltting speed between syringe lower end and the liquid nitrogen liquid level, make the liquid ball of different-grain diameter;
(3) the liquid globule is gone in the container of the pure kind of extractants of being equipped with of device and-196 ℃ of liquid nitrogen the liquid ball is freezed solid formation ball;
(4) container is placed-60 ℃~-90 ℃ low temperature environments, utilize the freezing point difference between pure kind of extractants and the acetone, make the extractant can be molten earlier, and acetone mixes the ball that freezes of liquid and slowly dissolves;
(5) with pure kind of extractants acetone is taken away then, made polymer produce deposition, microcapsules are solidified;
(6) with washed with de-ionized water, centrifugal, freeze-drying was preserved to be measured after curing was finished.
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CN1283350C true CN1283350C (en) | 2006-11-08 |
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CN106914196A (en) * | 2017-04-11 | 2017-07-04 | 江南大学 | It is a kind of that the method for carrying water microcapsules is prepared based on liquid hoodle |
CN108272119A (en) * | 2018-02-07 | 2018-07-13 | 南昌大学 | A kind of device preparing microcapsules by temperature control solidification |
CN110693003A (en) * | 2019-10-23 | 2020-01-17 | 华南理工大学 | Emulsion gel embedded with fat-soluble vitamins and production method thereof based on pulsed electric field |
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