KR101663150B1 - Porous polymer sphere, method for preparing thereof, and biodegradable materials for tissue engineering using the same - Google Patents

Abstract

In the present invention, the particle surface has a dense structure having nano-sized pores having an average pore size of 1 to 100 nm, and the inside of the particle has a pillar (column) having an average pore size larger than the average pore size of the particle surface. The present invention relates to a porous polymer particle having an asymmetric structure and a particle surface, which is a porous structure of a porous structure, and a biodegradable material for tissue engineering using the porous polymer particle.
The porous polymer particles of the present invention can be manufactured by a very simple method without using a toxic organic solvent, so that the process is simple and the manufacturing cost can be reduced. In addition, according to the method of the present invention, it is possible to manufacture porous fine particles without using any additive for forming pores and to easily control the particle size and to produce particles having various particle size distributions. Accordingly, the porous polymer particles according to the present invention can be applied to various biodegradable materials for tissue engineering depending on the particle size.

Description

TECHNICAL FIELD The present invention relates to a porous polymer particle, a method for producing the same, and a biodegradable material for tissue engineering using the porous polymer particle,

The present invention relates to a porous polymer particle, a method for producing the same, and a biodegradable material for tissue engineering using the same.

Tissue engineering, as enacted at the first tissue engineering symposium held in California in 1988, combines the basic concepts and techniques of life sciences and engineering to understand the relationship between structure and function of living tissue, It is an applied discipline that aims to maintain, improve or restore the function of our body by creating and transplanting substitute tissue.

The basic tissue engineering techniques are summarized as follows. First, a part of the tissue required from the patient's body is taken, and the cells are separated from the tissue. Then, the separated cells are expanded by the necessary amount through the culture and injected into the porous biodegradable polymer scaffold the cells are seeded, cultured for a certain period of time, and then the hybrid type cell / polymer structure is transplanted into the human body.

After transplantation, the cells are supplied with oxygen and nutrients by the diffusion of body fluids until the new blood vessels are formed. When blood vessels are grown in the body, blood cells are proliferated and differentiated to form new tissues and organs, and the polymer scaffold is decomposed It is to apply the technique which is lost.

Important factors in tissue engineering are the selection of appropriate cells to cultivate the necessary tissues, biodegradable materials that provide a framework for tissue formation, and in-vivo environments in which artificial organs manufactured by tissue engineering techniques are implanted.

The main requirement of biodegradable materials used in such tissue engineering is that the cells must adhere to the surface of the material to form a three-dimensional structure, The biodegradable material should be able to maintain its shape even after the biodegradable material has disintegrated after a certain period of time.

Around 1960, it was difficult to process biodegradable polymers such as poly (lactic acid), PLA, polyglycolic acid, and PGA, and it was difficult to process them and biodegraded during processing or during use. However, recently, it has been actively studied since biodegradability of materials can play an important role in tissue engineering. In particular, these biodegradable polymers have been approved by the US Food and Drug Administration (FDA) for use as non-toxic polymers in the human body.

However, biodegradable polymers generally used in porous supports and approved by the FDA for human use are hydrophobic, so that it is difficult to penetrate the aqueous solution containing oxygen / nutrients into the porous support. In addition, Surgery is an essential disk form. Therefore, when the cells are cultured on the polymer having the above-mentioned structure, the culture medium is not smoothly supplied to the inside of the polymer scaffold and necrosis of the cells is observed (the cells in the supporter are a culture medium containing oxygen / It is possible to survive in contact with the patient), and the complicated and troublesome surgical operation is also required for the actual patient.

In order to solve this problem, attention has been focused on porous particles having a micro-unit size enough to remove the conventional disc-shaped support and to inject injections or at least to minimize scratches in human application. Therefore, research on the production of porous particles using the freeze drying method, modified emulsion solvent evaporation method, incorporating gas pocket method, spinning disk atomization method and the like, and various tissue engineering fields such as artificial skin, artificial cartilage, bone filling material, Is being actively studied.

However, in spite of these intensive studies and necessity, it has been inevitable to use toxic organic solvents such as chloroform, methylene chloride, tetrahydrofuran, and hexafluoro-2-propanol in the process of preparing porous particles, As a result, there is a limit to use as a biomaterial, and there is also an environmental disadvantage.

In addition, it is necessary to use additives such as salt particles (paraffin particles) and excessive amount of hydrophilic or amphiphilic polymer aqueous solution for the formation of the pores on the surface of the biodegradable polymer, thereby complicating the process and increasing the cost, There is a problem that a separate process is required to be performed.

In addition, up to now, there is a problem that it is not possible to control the particle size which is necessary for expanding the use range of the particles.

Therefore, a biodegradable material that can be provided to the framework of tissue formation using environmentally friendly, porous structure and easy to control the particle size has not been developed yet.

 Novel fabrication of injectable PCL porous beads for use as an injectable cell carrier system (Journal of Biomedical Materials Research, 90B (2009) 521-530)

Accordingly, it is an object of the present invention to provide porous polymer particles which can form pores without the use of toxic organic solvents and additives for forming pores, and can easily control the size of fine particles.

It is another object of the present invention to provide a method for producing the above porous polymer particles.

In addition, the present invention also provides a biodegradable material for tissue engineering using the porous polymer particles.

The porous polymer particle according to an embodiment of the present invention has a dense structure in which nano-sized pores having an average pore size of 1 to 100 nm are formed, and the inside of the particle has an average pore size And has an asymmetric structure inside and a particle surface, which is a porous structure in the form of a column having a large average pore size.

The polymer may be selected from the group consisting of poly (lactic acid), poly (glycolic acid), poly-ε-caprolactone, polydioxanone, polylactic acid- Poly (lactic acid-co-glycolic acid), polydioxanone-co-ε-caprolactone copolymer), poly (lactic acid-co-glycolide polyhydroxybutyric acid-co-hydroxyvaleric acid, poly (phosphoester), polyethylene oxide-polylactic acid copolymer, polyethylene oxide- A biodegradable biodegradable polymer which is a mixture of at least one selected from the group consisting of a polylactic acid copolymer, a polylactic glycolic acid copolymer and a polyethylene oxide-polycaprolactone copolymer is preferable.

The average particle diameter of the particles is preferably 10 to 1,000 mu m.

According to another aspect of the present invention, there is provided a method for preparing a porous polymer particle, comprising: precipitating a polymer by injecting a polymer solution and a compressed gas into a non-porous medium; washing and drying the polymer precipitated in the non- And generating particles.

It is preferable that the polymer solution is injected into the non-solvent in the form of a droplet.

The non-solvent may be at least one selected from the group consisting of water, ethanol, methanol, isopropanol, hexane and ether.

Preferably, the polymer solution and the compressed gas are injected simultaneously using a dual injection nozzle device.

It is preferable that the double jet nozzle device is located at a distance of 1 to 50 cm from the non-solvent.

The compressed gas may be injected at a rate of 0.1 to 50 L / min.

The polymer solution may have a concentration of 1 to 50% by weight.

The solvent used for the preparation of the polymer solution is tetraglycol, 1-methyl-2-pyrrolidinone (NMP), triacetin and benzyl alcohol. ≪ / RTI >

The polymer may be selected from the group consisting of poly (lactic acid), poly (glycolic acid), poly-ε-caprolactone, polydioxanone, polylactic acid- Poly (lactic acid-co-glycolic acid), polydioxanone-co-ε-caprolactone copolymer), poly (lactic acid-co-glycolide polyhydroxybutyric acid-co-hydroxyvaleric acid, poly (phosphoester), polyethylene oxide-polylactic acid copolymer, polyethylene oxide- A biodegradable biodegradable polymer which is a mixture of at least one selected from the group consisting of a polyacrylic acid copolymer, a polylactic glycolic acid copolymer and a polyethylene oxide-polycaprolactone copolymer.

In addition, the present invention can provide a biodegradable material for tissue engineering using the porous polymer particles.

The biodegradable material for tissue engineering may be at least one selected from molded implants, bone fillers, and tissue engineering supports.

The porous polymer particles may have an average particle diameter of 10 to 1,000 mu m.

In the porous polymer particle according to the present invention, pores having an average pore size of nanosize are formed on the surface of the particles, and a porous structure having many columns is formed inside the particles.

Also, the porous polymer particles of the present invention can be manufactured by a very simple method without using a toxic organic solvent, so that the process is simple and the manufacturing cost can be reduced.

In addition, according to the method of the present invention, it is possible to manufacture porous fine particles without using any additive for forming pores and to easily control the particle size and to produce particles having various particle size distributions.

Accordingly, the porous polymer particles according to the present invention can be applied to various biodegradable materials for tissue engineering depending on the particle size.

1 is a schematic view showing a process for producing porous polymer particles according to the present invention,
2 is a SEM photograph of the surface and cross-section of the porous polymer particle according to Example 1,
3 is an SEM photograph of porous polymer particles having various particle sizes according to Example 1,
4 is a size distribution diagram of the porous polymer particles according to the N ₂ gas flow rate in Example 1. FIG.

Hereinafter, the present invention will be described in more detail.

The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. As used herein, the singular forms "a,""an," and "the" include singular forms unless the context clearly dictates otherwise. Also, " comprise "and / or" comprising "when used herein should be interpreted as specifying the presence of stated shapes, numbers, steps, operations, elements, elements, and / And does not preclude the presence or addition of one or more other features, integers, operations, elements, elements, and / or groups.

TECHNICAL FIELD The present invention relates to a porous polymer particle, a method for producing the porous polymer particle and a biodegradable material for tissue engineering using the porous polymer particle.

Porosity in the 'porous polymer particles' used in the specification of the present invention means that the polymer particles according to the present invention have a structure in which a large number of pores are formed on the surface and inside (cross-section) of the polymer particles.

In addition, as shown in FIG. 2, the 'porous structure in the form of a column' of the present invention is a structure in which the pores (pores) formed in the polymer particle of the present invention do not have the same diameter, Is not constant), meaning that each porous structure has a columnar or columnar shape.

The porous polymer particle according to the present invention has a dense structure in which nano-sized pores having an average pore size of 1 to 100 nm are formed, and the inside of the particle has an average pore size smaller than the average pore size of the particle surface And has an asymmetric structure inside and a particle surface which is a porous structure in the form of a large column (column).

That is, the porous polymer particles according to the present invention are used for human transplantation in which cultured and proliferated cells are seeded, cultured for a certain period of time, and then transplanted into the human body. After the transplantation, the cells are required to be supplied with oxygen and nutrients by diffusion of the body fluid until the new blood vessel is formed. Therefore, it is desirable that the space between the particles and the particles provides a space suitable for diffusion of body fluids and growth of new blood vessels.

For this, the porous polymer particle according to the present invention has a relatively dense structure due to its relatively small average pore size, and the inner layer of the particle has a relatively large pore size ) Type asymmetric porous structure, thereby facilitating the introduction of various physiologically active substances (adsorption / specific binding on a wide porous surface) and rapid release (a porous form of a physiologically active substance desorbed on a porous surface) Is emitted in the absence of an interference element.

The pores formed on the surface are preferably nano-sized with an average diameter of 1 to 100 nm in terms of the adhesion of the particle surface of the cells and the permeation of the physiologically active substance. In addition, the column-like pores formed in the inner layer of the particles should have a larger average pore size than the pore size of the surface.

The polymer that can be used in the preparation of the porous polymer particles according to the present invention is selected from the group consisting of poly (lactic acid), poly (glycolic acid), poly-ε-caprolactone, poly For example, polydioxanone, poly (lactic acid-co-glycolic acid), polydioxanone-co-ε-caprolactone), polylactic acid- Caprolactone), polyhydroxybutyric acid-co-hydroxyvaleric acid, poly (phosphoester), polyhydroxybutyric acid-co-hydroxyvaleric acid, , A biodegradable biodegradable polymer which is a mixture of at least one selected from the group consisting of polyethylene oxide-polylactic acid copolymer, polyethylene oxide-polylactic glycolic acid copolymer and polyethylene oxide-polycaprolactone copolymer.

The 'biocompatible biodegradable polymer' is not only biocompatible to the extent that the porous polymer particles of the present invention used in the human body have no specific side effects in vivo, but also used for human transplantation, And that it has biodegradability so that it can be degraded after organ formation.

The average particle diameter of the porous polymer particles according to the present invention is preferably 10 to 1,000 占 퐉 in terms of surface adhesion of cells, diffusion of body fluid, induction of growth of new blood vessels, and ease of injection.

According to another aspect of the present invention, there is provided a method for preparing a porous polymer particle, comprising: precipitating a polymer by injecting a polymer solution and a compressed gas into a non-porous medium; washing and drying the polymer precipitated in the non- And a step of generating particles, and the detailed procedure thereof is as shown in FIG. 1, below.

In the preparation of the biocompatible polymer solution according to the present invention, tetraglycol, 1-methyl-2-pyrrolidinone (NMP), triacetin and benzyl And at least one solvent selected from the group consisting of benzyl alcohol. The biocompatible polymer solution may be prepared by appropriately changing the solution at room temperature (RT) to a temperature not higher than the boiling point of the solvent according to the polymer used.

The present invention has an effect that can be produced even when a toxic organic solvent is not used and a harmless solvent is used as in the prior art.

When dissolved in the solvent, the concentration of the biocompatible polymer solution is preferably 1 to 50% by weight, more preferably 10 to 30% by weight, in the preparation of the porous polymer particles, and when the polymer solution is less than 1% by weight There is a problem that the precipitation of the polymer is not formed or the physical properties are weak. When it exceeds 50% by weight, the viscosity of the solution is high and it is difficult to dissolve or to handle.

It goes without saying that the present invention may additionally include other polymers having hydrophilicity and biocompatibility within the scope of the present invention, in addition to the biocompatible polymers as described above.

Specific examples of the hydrophilic polymer include polymers containing a large amount of ethylene oxide (-CH ₂ CH ₂ O) or hydroxy (-OH) functional groups, such as polyethylene oxide-polypropylene oxide polyethylene oxide-polylactic acid copolymer (PEO-PPO copolymer, Pluronic series), polyethylene oxide-copolylacetic acid (PEO-PLA), polyethylene oxide- (PEO-PLGA)), polyethylene oxide-polycaprolactone (PEO-PCL), polyethylene oxide (PEO), polyvinyl alcohol (PVA), polyoxyethylene alkyl ether Polyoxyethylene alkyl ethers (Brij Series), polyoxyethylene castor oil derivatives (Cremophores), polyoxyethylene sorbitan phytate But are not limited to, polyoxyethylene sorbitan fatty acid esters (Tween Series) and polyoxyethylene stearates.

The hydrophilic polymer is preferably contained in an amount of 0.1 to 20% by weight of the entire biocompatible polymer. If the hydrophilic polymer is used in an amount of less than 0.1% by weight, there is a problem that the produced porous polymer particles do not exhibit hydrophilicity. When the hydrophilic polymer is used in an amount exceeding 20% by weight, precipitation is not formed or physical properties are weakened.

After preparing the biocompatible polymer solution as described above, the solution is injected through a double injection nozzle together with a compressed gas and immersed in a non-solvent to prepare porous polymer particles.

The non-solvent used for the precipitation of the polymer solution may be at least one selected from the group consisting of ethanol, methanol, isopropanol, hexane and ether, but is not limited thereto.

The precipitation time can be performed for 1 minute to 12 hours, and can be appropriately adjusted according to the desired porous polymer particle size.

As shown in FIG. 1, when the polymer solution injected as described above is immersed in the non-solvent, a polymer precipitate starts to form on the surface where the polymer solution of the particle type meets the non-solvent, (10 to 1000 탆) are formed in the porous membrane, and the concentration of the polymer solution is decreased as the distance from the non-porous membrane is decreased. As a result, the pore size becomes larger than the average pore size of the surface. Layer is formed. That is, a membrane having a porous layer having a different pore size is formed while the non-solvent is exchanged with the solvent used in the biocompatible polymer solution.

Accordingly, the surface layer of the porous polymer particle according to the present invention has a relatively dense structure due to a relatively small average pore size as shown in FIG. 2, and the inner layer of the particle has a relatively large average pore size ) Type of pores.

Further, the porous structure can be manufactured by a very simple method without using any additive for forming the porous structure, so that the process is simple and the manufacturing cost can be reduced.

During the preparation of the porous polymer particles of the present invention, it is preferable to inject compressed gas together when the polymer solution is immersed in the non-solvent. This is because the polymer solution is immersed in the solvent in a droplet state by injecting a compressed gas, To prepare polymer particles. The 'compressed gas' means a gas compressed to such a degree as to apply a constant pressure when injecting the polymer solution, and may include, for example, nitrogen gas, an inert gas such as argon gas, or atmospheric air.

The compressed gas is preferably sprayed at a rate of 0.1 to 50 L / min to produce porous particles having an average particle size of about 10 to 1,000 μm and various particle sizes.

In addition, it is preferable that the compressed gas and the polymer solution are injected at the same time by using a double injection nozzle device. Here, as shown in FIG. 1, the 'dual injection nozzle device' means that a nozzle for injecting compressed gas is formed in an outer portion thereof, and a nozzle for injecting a polymer solution is formed in a central portion thereof.

The double jet nozzle apparatus is preferable because the polymer solution injected at a distance of 1 to 50 cm from the non-solvent can be injected into the non-solvent in a spherical (droplet state) state to be precipitated as polymer particles.

The size of the porous polymer particles according to the present invention can be controlled by adjusting the injection rate of the polymer solution and the injection speed of the compressed gas, and is preferably about 10 to 1,000 μm, but is not limited thereto.

The polymer particles precipitated as described above may be prepared by further conventional processes such as washing and drying, which are generally known methods and are not particularly limited.

The porous polymer particles according to the present invention manufactured through the above process have various distributions with an average particle size of 10 to 1000 μm. Therefore, it can be applied to a variety of human implantable uses such as molded implants, bone fillers, and tissue engineering supports depending on the particle size.

For example, among the above porous polymer particles, particles having an average particle size of 100 탆 or less can be applied as molded implants for molding purposes. Among the above porous polymer particles, particles having an average particle size of 100 to 300 탆 can be applied as a support for tissue engineering for the purpose of treating urinary incontinence / incontinence. Among the above porous polymer particles, particles having an average particle size of 300 탆 or more can be applied as a bone filler.

It is needless to say that, when used for each of the above-mentioned applications, the physical properties required for each application should be maintained.

Hereinafter, preferred embodiments of the present invention will be described in detail. The following examples are intended to illustrate the present invention, but the scope of the present invention should not be construed as being limited by these examples. In the following examples, specific compounds are exemplified. However, it is apparent to those skilled in the art that equivalents of these compounds can be used in similar amounts.

Example  1: Porosity PLGA  Manufacturing of particles

A biocompatible biodegradable polymer solution was prepared by dissolving polylactic acid-glycolic acid copolymer (PLGA; LA / GA = 85/15), which exhibits biocompatibility, in 10 weight% of tetraglycols harmless to human body.

The prepared polymer solution was transferred into a 10-mL syringe, the tip of the syringe was connected to a stainless steel needle, and then the needle was attached to the double injection nozzle apparatus. At this time, the distance between the end of the spray nozzle device and the non-solvent surface was fixed to 10 cm.

The polymer solution was injected into the center of the double injection nozzle at a rate of 12 mL / h using a syringe pump. N ₂ gas was injected at a constant flow rate (2, 2.5, 3, 4 L / min) The polymer solution and the N ₂ gas were injected into the non-solvent by injection into the outer part of the dual injection nozzle in four different ways.

As soon as the sprayed polymer solution comes into contact with the non-solvent (30% ethanol), the polymer precipitates on the surface of the polymer solution, and after the first 1 hour of precipitation, The remaining solvent was completely washed by exchanging with ultrapure water for 6 hours.

The washed particles were dried to prepare final porous polymer particles.

Experimental Example  1: Porosity PLGA  Check particle size and particle distribution

The porous polymer particles prepared in Example 1 were separated by size using a micro sieve to obtain porous PLGA particles having a uniform shape.

As shown in FIG. 3, it was confirmed that porous polymer particles having various average diameters can be prepared according to the injection rate of the inert gas (FIG. 3).

In addition, the distribution of N ₂ gas was controlled by the injection rate. It was confirmed that as the injection velocity increases, the distribution of small particles increases and the distribution of larger particles increases as the injection velocity decreases (see Table 1 and FIG. 4) .

N ₂ injection speed (L / min) Average particle diameter (占 퐉) and distribution 10 to 99 100-199 200 ~ 299 300 to 420 421-499 500 to 1000 2 5.701254 23.83124 26.7959 7.867731 0.684151 35.11973 2.5 9.265176 29.79233 14.77636 2.476038 41.61342 2.076677 3 10.84711 13.53306 12.60331 35.12397 27.06612 0.826446 4 13.79781 37.02186 13.25137 33.33333 1.36612 1.229508

Experimental Example  2: Porosity PLGA  Identification of particle structure

The surface and cross-sectional structure of the porous PLGA particles prepared according to Example 1 were observed through an electron-scanning electron microscope (SEM). The results are shown in FIG.

As shown in FIG. 2, the porous polymer particles prepared according to Example 1 of the present invention have nano-sized pores having an average pore size of 5 to 50 nm formed on a surface (surface layer) It has been confirmed that the asymmetric structure has a porous structure in the form of a plurality of columns.

Example  2: Porosity PCL  Manufacturing of particles

Polycaprolactone (PCL), which shows biocompatibility, was added to tetraglycol which is harmless to human body in an amount of 12% by weight and dissolved at 90 캜 to prepare a polymer solution.

The syringe, needle and double jet nozzle were wrapped with a hot wire and maintained at a temperature of 90 ° C. The syringe was connected to a stainless needle, gave. At this time, the distance between the end of the spray nozzle and the surface of the precipitating solution was fixed to 10 cm.

The polymer solution was injected into the central part of the dual injection nozzle at a rate of 10 mL / h using a syringe pump, and N ₂ gas was injected into the outer part of the dual injection nozzle at a constant flow rate (2 to 10 L / min) The polymer solution was injected into a precipitating solution at room temperature.

As soon as the injected polymer solution comes into contact with the non-solvent (50% methanol), the polymer precipitates on the surface of the polymer solution, and after the first 1 hour of precipitation, an excess amount of fresh The remaining solvent was completely washed by exchanging with ultrapure water for 6 hours. After washing, the micropores were dried and microporous PCL particles having uniform morphology separated by size were obtained.

It was observed that the surface / cross-sectional structure and the particle size distribution of the porous PCL particles prepared above were similar to those of Example 1.

Example  3: Porosity PDO  Manufacturing of particles

Polydioxanone (PDO), which shows biocompatibility, was added to tetraglycol which is harmless to human body in an amount of 10% by weight and dissolved at 150 캜 to prepare a polymer solution.

The syringe, the needle and the double injection nozzle were wrapped with a hot wire, and the temperature was maintained at 150 ° C. The syringe was connected to a stainless needle, gave. At this time, the distance between the end of the spray nozzle and the surface of the precipitating solution was fixed to 10 cm.

The polymer solution was injected into the central part of the dual injection nozzle at a rate of 8 mL / h using a syringe pump, and N ₂ gas was injected into the outer part of the dual injection nozzle at a constant flow rate (2 to 20 L / min) The polymer solution was injected into a precipitating solution at room temperature.

As soon as the injected polymer solution and the non-solvent (5% isopropanol) come into contact with each other, the polymer precipitates on the surface of the polymer solution, and after the first 1 hour of precipitation, The remaining solvent was completely washed by exchanging with fresh ultrapure water for 6 hours. After washing, the dried PDO particles were separated by size using a micro sieve.

It was observed that the surface / cross-sectional structure and the particle size distribution of the porous PDO particles prepared above were similar to those of Example 1.

Example  4: Porosity PLGA / Pluronic  Fabrication of F127 particles

(PLGA; LA / GA = 85/15) showing biocompatibility and Pluronic F127 having biocompatibility and hydrophilicity were mixed at a weight ratio of 95/5, and the mixture was added to tetraglycol, which is harmless to human body, to 10 weight % To prepare a biocompatible biodegradable polymer solution.

The prepared polymer solution was transferred into a 10-mL syringe, the tip of the syringe was connected to a stainless steel needle, and then the needle was attached to the double injection nozzle apparatus. At this time, the distance between the end of the spray nozzle device and the non-solvent surface was fixed to 10 cm.

The polymer solution was injected into the center of the double injection nozzle at a rate of 12 mL / h using a syringe pump. N ₂ gas was injected at a constant flow rate of 2, 2.5, 3, 4 L / min And the polymer solution was injected into the non-solvent by injection into the outer part of the dual injection nozzle differently.

As soon as the sprayed polymer solution comes into contact with the non-solvent (30% ethanol), the polymer precipitates on the surface of the polymer solution, and after the first 1 hour of precipitation, The remaining solvent was completely washed by exchanging with ultrapure water for 6 hours.

The washed particles were dried to prepare final porous polymer particles.

It was observed that the surface / cross-sectional structure and particle size distribution of the porous PLGA / Pluronic F127 particles prepared above were similar to those of Example 1.

Claims (15)

The particle surface has a dense structure with nano-sized pores having an average pore size of 1 to 100 nm,
The inside of the particle has an average pore size larger than the average pore size of the particle surface and the pores formed inside the polymer particle do not have the same diameter but have a porous structure having a length in one direction, Shaped porous structure,
The surface of the particle has a relatively small average pore size to form a dense structure and the inner layer of the particle has a columnar porous structure that is relatively larger than the average pore size of the surface, Has an asymmetric structure,
The polymer may be selected from the group consisting of poly (lactic acid), poly (glycolic acid), poly-ε-caprolactone, polydioxanone, polylactic acid- Poly (lactic acid-co-glycolic acid), polydioxanone-co-ε-caprolactone copolymer), poly (lactic acid-co-glycolide polyhydroxybutyric acid-co-hydroxyvaleric acid, poly (phosphoester), polyethylene oxide-polylactic acid copolymer, polyethylene oxide- Wherein the biodegradable polymer is a biocompatible biodegradable polymer comprising one or more selected from the group consisting of a polylactic acid copolymer, a polylactic glycolic acid copolymer, and a polyethylene oxide-polycaprolactone copolymer.
delete The method according to claim 1,
Wherein the average particle diameter of the porous polymer particles is 10 to 1,000 占 퐉.
At least one non-solvent selected from the group consisting of water, ethanol, methanol, isopropanol, hexane and ether
Poly (lactic acid), poly (glycolic acid), poly-ε-caprolactone, polydioxanone, polylactic acid-glycolic acid copolymer (poly (lactic acid-co-glycolic acid), polydioxanone-co-ε-caprolactone), and poly (lactic acid-co-ε-caprolactone )), Which is a mixture of two or more kinds of biocompatible biodegradable polymers,
At least one human selected from the group consisting of tetraglycol, 1-methyl-2-pyrrolidinone (NMP), triacetin and benzyl alcohol. Spraying a compressed gas and a polymer solution dissolved in a harmless solvent to precipitate the polymer,
And washing and drying the polymer precipitated in the non-solvent to produce porous polymer particles.
5. The method of claim 4,
Wherein the polymer solution is injected into the non-solvent in a droplet-like spherical shape.
delete 5. The method of claim 4,
Wherein the polymer solution and the compressed gas are simultaneously injected using a dual injection nozzle device.
8. The method of claim 7,
Wherein the double jet nozzle device is positioned at a distance of 1 to 50 cm from the non-solvent.
5. The method of claim 4,
Wherein the compressed gas is injected at a rate of 0.1 to 50 L / min.
5. The method of claim 4,
Wherein the polymer solution has a concentration of 1 to 50% by weight.
delete delete A biodegradable material for tissue engineering using the porous polymer particles according to claim 1.
14. The method of claim 13,
The biodegradable biodegradable material for tissue engineering is at least one selected from the group consisting of molded implants, bone fillers, and tissue engineering supports.
14. The method of claim 13,
Wherein the porous polymer particles have an average particle size of 10 to 1,000 占 퐉.

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