Method for preparing polymer microparticles by spray process

Abstract

The present invention relates to a method for preparing polymer microparticles by a spray process, wherein a polymer solution obtained by dissolving a polyester-based polymer in ethylene carbonate (hereinafter, referred to as “EC”), which is a solvent, is sprayed at a low temperature hydrocarbon or alcohol solution, thereby preparing frozen EC/polymer microparticles, the frozen EC/polymer microparticles are dissolved in a salt aqueous solution, thereby dissolving and removing EC, and the residual EC in water is removed by washing.

Claims

1. A method for preparing biodegradable polymer microparticles, comprising: dissolving a biodegradable polyester polymer in ethylene carbonate (EC) to obtain a polymer/EC solution; spraying the polymer/EC solution onto an alcohol selected from the group consisting of methanol or ethanol or an aqueous solution thereof where the alcohol has a temperature between −20° C. and 0° C., thus obtaining frozen polymer/EC microparticles; dissolving and removing EC from the polymer/EC microparticles by adding the polymer/EC microparticles into a salt aqueous solution; and filtering and washing the microparticles with water so as to eliminate the remaining EC, thus obtaining biodegradable polymer microparticles.

2. The method of claim 1, wherein the biodegradable polyester polymer is a polymer selected among Polylactic acid (PLA), Polyglycolic acid (PGA), Poly(D,L-lactic-co-glycolic acid) (PLGA), Polycaprolactone (PCL), poly(valerolactone), poly(hydroxybutyrate) and poly(hydroxy valerate) and has a weight average molecular weight of 10,000 to 250,000.

3. The method of claim 1, wherein the concentration of biodegradable polyester polymer dissolved in the ethylene carbonate (EC) is 1 to 25% (w/v).

4. The method of claim 1, wherein the concentration of salt in the salt aqueous solution is 5 to 30% (w/v) and wherein the salt is NaCl or CaCl.sub.2.

Description

BRIEF DESCRIPTION OF DRAWINGS

(1) FIG. 1 is a photo of microparticles taken by an electron microscope and prepared by a method of the present invention (X 700; polymer solution concentration: 5%; spraying amount: 1 ml/min; air spraying speed: 5 L/min; freezing solvent: n-Hexane; freezing tank temperature: −10° C.).

(2) FIG. 2 is a photo of microparticles taken by an electron microscope and prepared by a method of the present invention (X 1,000; polymer solution concentration: 5%; spraying amount: 1 ml/min; air spraying speed: 5 L/min; freezing solvent: n-Hexane; freezing tank temperature: 0° C.)

(3) FIG. 3 is a photo of microparticles taken by an electron microscope and prepared by a method of the present invention (X 1,500; polymer solution concentration: 5%; spraying amount: 1 ml/min; air spraying speed: 5 L/min; freezing solvent: EtOH; freezing tank temperature: −10° C.).

(4) FIG. 4 is a photo of microparticles taken by an electron microscope and prepared by a method of the present invention (X 500; polymer solution concentration: 5%; spraying amount: 1 ml/min; air spraying speed: 5 L/min; freezing solvent: EtOH; freezing tank temperature: −5° C.).

(5) FIG. 5 is a photo of microparticles taken by an electron microscope and prepared by a method of the present invention (X 700; polymer solution concentration: 5%; spraying amount: 1 ml/min; air spraying speed: 5 L/min; freezing solvent: 75% EtOH aqueous solution; freezing tank temperature: −5° C.).

(6) FIG. 6 is a photo of microparticles taken by an electron microscope and prepared by a method of the present invention (X 800; polymer solution concentration: 5%; spraying amount: 1 ml/min; air spraying speed: 5 L/min; freezing solvent: 75% EtOH aqueous solution; freezing tank temperature: 5° C.).

BEST MODES FOR CARRYING OUT THE INVENTION

(7) The exemplary embodiment 1 among the exemplary embodiments below is the best mode for the present invention.

MODES FOR CARRYING OUT THE INVENTION

(8) The exemplary embodiments of the present invention will be described below.

(9) It should be understood that the embodiments below are provided for only illustrative purposes, and the contents of the present invention are not limited to the exemplary embodiments below.

Exemplary Embodiments 1-6

Exemplary Embodiment 1

(10) 5% (W/V) polymer solution was prepared by melting 2.5 g of polylactic acid (PLA) the average molecular weight of which is 110,000 in 50 ml of EC (Ethylene carbonate). The polymer solution was sprayed onto n-hexane cooled to −10° C. with a spraying amount of 1 ml/min and 5 L/min of the amount of spraying air. At this time, the sprayed polymer solution was frozen into spherical shapes on the low temperature n-hexane.

(11) The frozen microparticles were collected and were placed for 48 hours in 100 ml of 25% (w/v) NaCl aqueous solution which was cooled to −10° C., and the EC component was dissolved and was filtered, thus obtaining polymer microparticles from which the EC had been filtered and eliminated. The obtained mixture was washed with 500 ml of distilled water, and the remaining EC was eliminated, and the mixture was frozen and dried, thus finishing the preparation of biodegradable polymer microparticles according to the present invention.

Exemplary Embodiment 2

(12) The method of the exemplary embodiment 1 was performed except that the polymer solution which had been dissolved in the EC was dropped onto the n-hexane at −5° C., thus preparing biodegradable polymer microparticles.

Exemplary Embodiment 3

(13) 5% (W/V) polymer solution was prepared by melting 2.5 g of polylactic acid (PLA) the average molecular weight of which is 110,000 in 50 ml of EC (Ethylene carbonate). The polymer solution was sprayed onto ethanol cooled to −10° C. with a spraying amount of 1 ml/min and 5 L/min of the amount of spraying air. At this time, the sprayed polymer solution was frozen into circular shapes on the low temperature ethanol.

(14) The frozen microparticles were collected and washed with 500 ml of distilled water, and the remaining EC was eliminated and frozen and dried, thus finishing the preparation of biodegradable polymer microparticles of the present invention.

Exemplary Embodiment 4

(15) The method of the exemplary embodiment 3 was performed except that the polymer solution which had been dissolved in the EC was dropped onto the ethanol at −5° C., thus preparing biodegradable polymer microparticles.

Exemplary Embodiment 5

(16) In addition, the method of the exemplary embodiment 3 was performed except that the polymer solution which had been dissolved in the EC was dropped onto 75% ethanol aqueous solution at −10° C., thus preparing biodegradable polymer microparticles.

(17) Exemplary embodiment 6. In addition, the method of the exemplary embodiment 3 was performed except that the polymer solution which had been dissolved in the EC was dropped onto 75% ethanol aqueous solution at 5° C., thus preparing biodegradable polymer microparticles.

Experimental Examples

(18) In order to confirm the characteristics of each biodegradable polymer micro particle prepared by the exemplary embodiments 1 to 6 of the present invention, the types and manufacturing yields of the microparticles were measured with respect to the thusly prepared biodegradable polymer microparticles. At this time, the types of the microparticles were measures using the photos thereof taken by the electron microscope. The manufacturing yields were calculated by measuring the amount of microparticles which were finally collected, as compared to the amount of the inputted polymers.

(19) As a result, as seen in FIGS. 1 to 6 and the table 1 below, the frozen solvent of the EC polymer solution was produced into spherical microparticles in the n-hexane, and the frozen solvent was produced into circular shapes in the aqueous solution thereof. As for the types of the microparticles prepared by the preparing method of the present invention, the microparticles are sized to be well administrated into a human body. In case of the microparticles prepared in the ethanol and aqueous solution thereof, the microparticles were formed in circular shapes to which the cell can well adhere, so the microparticles of the present invention can be usefully used as cell carriers.

(20) TABLE-US-00001 TABLE 1 Preparation condition; 5% PLA/EC solution, spraying speed; 1 ml/min, air spraying amount; 5 L/min Freezing Freezing temperature Types of Size of micro Yields solvent ° C. microparticles particle μm % n-Hexane −10 Porous 100~300 μm 81 0 80 EtOH −10 Circular 83 −5  shape 82 75% EtOH −5 82 5 81

INDUSTRIAL APPLICABILITY

(21) The present invention is a useful invention which can provide a method for preparing polymer microparticles which allows to inject using a syringe a spherical shaped or circular shaped biodegradable polymer micro particle carrier. In particular, the circular shaped microparticles may enhance an adhering force of cell, so it can be used as a cell carrier, which may allow to develop a biological industry.