KR101222408B1 - Preparation of uniform microparticles with inner pore structures and dimple structures on the surface by using a microfluidic device - Google Patents
Preparation of uniform microparticles with inner pore structures and dimple structures on the surface by using a microfluidic device Download PDFInfo
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Abstract
본 발명은 의료용도로 적용되는 생분해성 고분자를 기반으로 마이크로플루딕 디바이스를 이용하여 내부 및 외부에 구조적 복잡성을 보유하고 균일한 크기를 갖는 미립자 및 그 제조방법에 관한 것이다. 보다 상세하게는 연속상, 비 연속상 마이크로플루딕 디바이스를 튜브로 연결하는 단계와, 상기 튜브 내로 연속상을 위한 물 흐름을 도입하여 균일한 크기의 미립자를 형성하는 단계, 상기 미립자를 고형화시키는 단계를 포함하는 미립자의 제조방법이다. The present invention relates to a microparticle having a uniform size and having a structural complexity inside and outside using a microfluidic device based on a biodegradable polymer that is applied for medical use, and a method of manufacturing the same. More specifically, connecting a continuous, non-continuous microfluidic device into a tube, introducing a flow of water for the continuous phase into the tube to form particles of uniform size, and solidifying the particles. It is a method for producing the fine particles comprising a.
Description
본 발명은 의료용도로 적용되는 생분해성 고분자를 기반으로 하여 마이크로플루딕 디바이스를 이용하여 내부 및 외부에 구조적 복잡성을 보유하고 균일한 크기를 갖는 미립자 및 그 제조방법에 관한 것이다. 보다 상세하게는 연속상, 비 연속상 마이크로플루딕 디바이스를 튜브로 연결하는 단계와, 상기 튜브 내로 연속상을 위한 물 흐름을 도입하여 균일한 크기의 미립자를 형성하는 단계, 상기 미립자를 고형화시키는 단계를 포함하는 미립자의 제조방법이다.
The present invention relates to a microparticle having a uniform size and having a structural complexity inside and outside using a microfluidic device based on a biodegradable polymer that is applied for medical use, and a method of manufacturing the same. More specifically, connecting a continuous, non-continuous microfluidic device into a tube, introducing a flow of water for the continuous phase into the tube to form particles of uniform size, and solidifying the particles. It is a method for producing the fine particles comprising a.
이 발명을 지원한 국가연구개발사업National R & D project supporting this invention
과제고유번호 2010-0022097Project unique number 2010-0022097
부처명 한국연구재단Department Name Korea Research Foundation
연구사업명 기초연구사업-일반연구자지원사업-기본연구Research Project Basic Research Project-General Researcher Support Project-Basic Research
연구과제명 휘발성 phase change material을 이용한 내.외부 구조복잡성을 지닌 Project name: Internal and external structural complexity using volatile phase change material
새로운 초정밀 미립자 개발New ultra-fine particle development
주관기관 공주대학교 산학협력단Organized by Gongju University
연구기간 2010년 09월 01일 ~ 2011년 08월 31일
Period of Research September 01, 2010 ~ August 31, 2011
본 발명은 마이크로플루딕 디바이스를 이용하여 단순한 Oil-in-water(O/W) 에멀젼 방법으로 내부의 다공성 구조와 표면에 딤플 구조를 동시에 갖고(Chemical Communications, 2010, 46, 7433-7435) 균일한 크기의 미립구 및 그 제조방법에 관한 것이다. 균일한 크기의 미립자는 약물방출체계, 조직공학(Advanced Materials, 2009, 21, 2997-3001), 기능성 화장품 등의 다양한 용도로 적용되고 있다. PDMS를 기반으로 한 마이크로플루딕 디바이스는 채널이 새거나 고분자 파편으로 막히는 결함 등이 생겨 마이크로 캐필러리 튜브나 PVC 튜브를 이용한 마이크로플루딕 디바이스를 사용하고 있다(Small, 2009, 5, 454-459). 미립자 표면에 딤플을 갖게 되면 추가적인 약물 담지 site로 제공될 것으로 예상되며 표면적이 넓어 약물방출에 유용하다. 미립자 표면에 딤플을 만들기 위해 사용되는 기존 방법은 Pickering emulsion 방법으로 광경화물에 나노실리카 입자를 분산시켜(Journal of American Chemical Society, 2005, 127, 6271; Chemical Communications, 2005, 4205; Chemistry of Materials, 2007, 19, 4751) 제조될 수 있었다. 이와 같은 방법을 사용하였을 때 차후에 불산과 같은 용매를 통해 표면에 분산된 실리카 입자를 제거하는 추가공정이 요구되며 이 또한 합성 생분해성 고분자를 적용하기에 어려움이 있다.
The present invention is a simple oil-in-water (O / W) emulsion method using a microfluidic device to simultaneously have an internal porous structure and a dimple structure on the surface (Chemical Communications, 2010, 46 , 7433-7435). It relates to a microsphere of size and a manufacturing method thereof. Uniform particle size has been applied to various applications such as drug release system, tissue engineering (Advanced Materials, 2009, 21 , 2997-3001), functional cosmetics. Microfluidic devices based on PDMS use microfluidic devices using microcapillary tubes or PVC tubes due to leaking channels or defects blocked by polymer fragments (Small, 2009, 5 , 454-459). . Having dimples on the surface of the microparticles is expected to serve as an additional drug loading site and is useful for drug release due to its large surface area. Conventional methods used to make dimples on the surface of particulates are the Pickering emulsion method, which disperses nanosilica particles in photocuring (Journal of American Chemical Society, 2005, 127 , 6271; Chemical Communications, 2005, 4205; Chemistry of Materials, 2007 , 19 , 4751). When such a method is used, an additional step of removing silica particles dispersed on the surface through a solvent such as hydrofluoric acid is required later, which also makes it difficult to apply a synthetic biodegradable polymer.
본 발명은 연속상, 비 연속상 마이크로플루딕 디바이스를 튜브로 연결하는 단계와, 상기 튜브 내로 연속상을 위한 물 흐름을 도입하여 균일한 크기의 미립자를 형성하는 단계, 상기 미립자를 고형화시키는 단계를 포함하는 미립자의 제조방법 및 마이크로플루딕 디바이스 유량을 조절하여 미립구의 크기를 제어할 수 있고 동시에 내부의 다공성 구조와 표면에 딤플 구조를 갖는 미립자를 제조하는데 있다.
The present invention provides a method of connecting a continuous, non-continuous microfluidic device into a tube, introducing a water flow for the continuous phase into the tube to form particles of uniform size, and solidifying the particles. It is possible to control the size of the microspheres by adjusting the manufacturing method and the microfluidic device flow rate of the microparticles included, and at the same time to produce the microparticles having a dimple structure on the inside and the porous structure.
휘발성 탄화수소계 상변화 물질을 도입하여 내부 다공성 구조와 표면 딤플 구조를 갖고 연속상 튜브에 비 연속상 튜브를 연결한 마이크로플루딕 디바이스를 이용하여 균일한 크기의 미립자를 제조하였다.
A volatile hydrocarbon-based phase change material was introduced to prepare fine particles of uniform size using a microfluidic device having an internal porous structure and a surface dimple structure and connecting a non-continuous tube to a continuous tube.
본 발명의 마이크로플루딕 디바이스를 사용하여 에멀젼 (O/W emulsion)방법으로 내부 및 외부 모두에 구조적 복잡성을 보유하는 미립구를 제조할 수 있다. 뿐만 아니라 유량 조절로 미립구의 크기 조절이 용이하며 균일한 크기의 미립구를 얻을 수 있다.
Microfluidic devices of the present invention can be used to produce microspheres that retain structural complexity both inside and outside by an emulsion (O / W emulsion) method. In addition, it is easy to control the size of the microspheres by adjusting the flow rate, it is possible to obtain a uniform size of the microspheres.
도 1은 실시예 1에 따라 제조된 마이크로플루딕 디바이스를 이용한 고분자 미립구의 제조방법을 나타내는 개략도이다.
도 2a, 도 2b, 도 2c은 실시예 1-1에 따라 제조된 고분자 미립구의 표면, 단면에 대한 주사전자 현미경 사진이다.
도 2d는 실시예 1-2 에 따라 제조된 고분자 미립구의 표면에 대한 주사전자 현미경 사진이다.
도 2e는 실시예 1-3 에 따라 제조된 고분자 미립구의 표면에 대한 주사전자 현미경 사진이다.
도 2f는 실시예 1-4에 따라 제조된 고분자 미립구의 표면에 대한 주사전자 현미경 사진이다.
도 2g는 실시예 1-5에 따라 제조된 고분자 미립구의 표면에 대한 주사전자 현미경 사진이다.
도 2h는 실시예 1-6에 따라 제조된 고분자 미립구의 표면에 대한 주사전자 현미경 사진이다.
도 2i, 도 2j는 비교예 1에 따라 제조된 고분자 미립구의 표면, 단면에 대한 주사전자 현미경 사진이다.1 is a schematic view showing a method for preparing polymer microspheres using a microfluidic device prepared according to Example 1. FIG.
2A, 2B and 2C are scanning electron micrographs of the surface and cross section of the polymer microspheres prepared according to Example 1-1.
2D is a scanning electron micrograph of the surface of the polymeric microspheres prepared according to Examples 1-2.
2E is a scanning electron micrograph of the surface of the polymer microspheres prepared according to Examples 1-3.
2F is a scanning electron micrograph of the surface of the polymeric microspheres prepared according to Examples 1-4.
2G is a scanning electron micrograph of the surface of the polymeric microspheres prepared according to Examples 1-5.
2H is a scanning electron micrograph of the surface of the polymer microspheres prepared according to Examples 1-6.
Figure 2i, Figure 2j is a scanning electron micrograph of the surface, cross-section of the polymer microspheres prepared according to Comparative Example 1.
본 발명은 고분자 미립자의 제조방법을 나타낸다. 본 발명은 (a) 비 연속상이 되는 생분해성 고분자 및 상변화 물질(phase change material(PCM))을 포함하는 고분자 용액을 제조하는 단계; (b) 친수성 계면활성제를 증류수에 용해시켜 연속상(continuous phase)을 제조하는 단계; (c) 연속상, 비 연속상 마이크로플루딕 디바이스를 튜브로 연결하는 단계; 및 (d) 상기 비 연속상과 연속상으로 마이크로플루딕 디바이스를 사용하여 O/W 에멀젼(oil-in-water)방식으로 고분자 미립구를 고형화시키는 단계를 포함하는 고분자 미립구의 제조방법을 나타낸다.
This invention shows the manufacturing method of a polymer microparticle. The present invention comprises the steps of (a) preparing a polymer solution comprising a biodegradable polymer and a phase change material (PCM) to be a non-continuous phase; (b) dissolving the hydrophilic surfactant in distilled water to produce a continuous phase; (c) connecting the continuous, non-continuous microfluidic device into a tube; And (d) solidifying the polymer microspheres in an O / W emulsion (oil-in-water) method using a microfluidic device in the non-continuous and continuous phases.
상기에서 상기 (a) 단계의 생분해성 비정질 고분자로서 폴리에스테르계 고분자를 사용할 수 있으며, 바람직하게는 폴리락트산-폴리글리콜산의 공중합체(Poly(lactic acid-co-glycolic acid)(PLGA, 락틱산의 함량은 50 ~ 65%, 글리콜릭산은 35 ~ 50%) 또는 폴리(D,L-락트산)(Poly(D,L-lactic acid) (PDLA)) 또는 폴리D,L-락트산-폴리카프로락톤의 공중합체(Poly(D,L-lactide-co-caprolactone))가 적합하다. 비분해성 비정질 고분자로서 폴리술폰(Poly(sulfone)(PSf))도 사용이 가능하다. 결정성 고분자는 미립구 표면에 딤플이 생기지 않고 기공이 생긴다.
As the biodegradable amorphous polymer of step (a), a polyester-based polymer may be used, and a copolymer of polylactic acid-polyglycolic acid (Poly (lactic acid-co-glycolic acid) (PLGA, lactic acid) Content is 50-65%, glycolic acid is 35-50%) or poly (D, L-lactic acid) (PDLA)) or polyD, L-lactic acid-polycaprolactone Poly (D, L-lactide-co-caprolactone) is suitable. Poly (sulfone) (PSf) can also be used as non-degradable amorphous polymer. No dimples, no pores.
상기에서 상기 (a) 단계의 유기용매는 생분해성 고분자 및 소수성 계면활성제와의 혼화성이 요구되며, 물과는 상분리가 일어날 것이 요구된다. 유기용매는 상기의 요건을 만족하는 경우라면 특별히 제한되지는 않지만, 디클로로메탄을 사용하는 것이 바람직하다.
In the above (a) step, the organic solvent is required to be miscible with the biodegradable polymer and hydrophobic surfactant, it is required that the phase separation with water. The organic solvent is not particularly limited as long as it satisfies the above requirements, but dichloromethane is preferably used.
상기에서 상기 (a) 단계의 유기상을 위해 사용되는 용매로는 디클로로메탄이며 고분자와 상변화 물질은 전체 유기용매에 대해 5 ~ 10% 중량부로 용해한다.
The solvent used for the organic phase of step (a) is dichloromethane and the polymer and the phase change material are dissolved at 5 to 10% by weight based on the total organic solvent.
상기에서 상기 (a) 단계의 상변화 물질(phase change material(PCM))은 온도의 변화에 의해 상이 변화하는 것으로 휘발성 탄화수소 물질을 의미하며 상온에서 미립자를 제조시에 2-methylpentane을 사용하는 것이 바람직하다.
The phase change material (PCM) of the step (a) is a phase change by the change of temperature means a volatile hydrocarbon material, it is preferable to use 2-methylpentane when preparing the fine particles at room temperature Do.
상기에서 상기 (a) 단계의 고분자와 상변화 물질의 농도가 전체 고분자용액에 대한 농도가 5%(w/w)미만이 되도록 첨가되면 묽어서 입자 모양이 구형이 되지 못하고 10%(w/w)초과가 되도록 첨가될 시에는 진해서 올바른 입자 모양이 되지 못해 바람직하게는 5 내지 10%(w/w)가 되도록 첨가하는 것이 바람직하다.
When the concentration of the polymer and the phase change material in step (a) is added so that the concentration of the total polymer solution is less than 5% (w / w), the particles are diluted to form a spherical shape and 10% (w / w). When added to the excess, it is preferable to add so that it becomes thick and does not become a proper particle shape, preferably 5 to 10% (w / w).
삭제delete
상기에서 상기 (a) 단계의 생분해성 고분자와 상변화 물질의 비율은 8:2 에서 6:4 사이에 두어야 구형을 갖추면서 표면의 딤플을 갖는 구조의 미립자를 제조할 수 있다.
Wherein the ratio of the biodegradable polymer and the phase change material in the step (a) should be placed between 8: 2 to 6: 4 to have a spherical shape can be produced fine particles having a structure with a dimple on the surface.
상기에서 상기 (b) 단계의 연속상은 폴리비닐알코올(polyvinyl alcohol, PVA) 수용액을 사용하고, 폴리비닐알코올은 물에 대한 농도가 바람직하게는 1 내지 3%(w/w)가 되도록 첨가될 수 있다. 이때 폴리비닐알코올의 분자량은 13,000 내지 23,000이며, 가수분해도는 87 내지 89%가 바람직하다. 상기 친수성 계면활성제는 포화농도 이상의 약물 입자를 균일하게 분산시키기 위하여 사용된다. 상기 친수성 계면활성제로는 폴리옥시에틸렌-폴리옥시프로필렌 블록 공중합체(polyoxyethylene-polyoxypropyene block copolymer) 및 폴리옥시에틸렌 소르비탄 지방산 에스테르계 (polyoxyethylene sorbitan fatty ester, Tween 계열)로 이루어진 군 중에서 선택된 하나 이상의 성분을 사용할 수 있으며, 바람직하게는 폴리옥시에틸렌 소르비탄 지방산 에스테르 계열의 계면활성제를 사용하며, 그 중에도 폴리옥시에틸렌 소르비탄 모노라우레이트(polyoxyethylene sorbitan monolaurate, 상품명: Tween 20)을 사용할 수 있다. 상기 친수성 계면활성제는 물에 대한 농도가 바람직하게는 0.02wt%가 되도록 첨가되며 미생물 번식을 방지하기 위해 Sodium azide는 0.01wt%가 첨가될 수 있다.
In the continuous phase of the step (b) using a polyvinyl alcohol (polyvinyl alcohol, PVA) aqueous solution, polyvinyl alcohol may be added so that the concentration to water is preferably 1 to 3% (w / w). have. The molecular weight of the polyvinyl alcohol is 13,000 to 23,000, the hydrolysis degree is preferably 87 to 89%. The hydrophilic surfactant is used to uniformly disperse drug particles above a saturated concentration. The hydrophilic surfactant may include at least one component selected from the group consisting of a polyoxyethylene-polyoxypropyene block copolymer and a polyoxyethylene sorbitan fatty acid ester (Tween series). Preferably, a polyoxyethylene sorbitan fatty acid ester-based surfactant may be used, and among these, polyoxyethylene sorbitan monolaurate (trade name: Tween 20) may be used. The hydrophilic surfactant is preferably added in a concentration of 0.02 wt% to water, and 0.01 wt% of sodium azide may be added to prevent microbial propagation.
상기에서 상기 (c) 단계의 튜브는 내경이 800마이크로미터이고 비 연속상 주사기 바늘의 크기는 30G를 사용하였다.
The tube of step (c) has an internal diameter of 800 micrometers and the size of the non-continuous syringe needle was used 30G.
상기에서 상기 (d) 단계의 이러한 과정 중에서 상변화 물질(PCM)이 상기 미세입자 내로 봉입되고 상변화 물질의 거동으로 내부 및 외부에 동시에 구조적 복잡성을 갖는 미세입자가 생성된다.
In this process of the step (d), the phase change material (PCM) is encapsulated into the microparticles and the microparticles having structural complexity at the same time inside and outside are generated by the behavior of the phase change material.
상기에서 상기 (d) 단계에서 고형화된 미립구 세척과정이 추가된다.
In the above (d) step, the solidified microspheres washing process is added.
본 발명을 통해 제조된 고분자 미립구는 상기에서 상기 (d) 단계의 연속상, 비 연속상 흐름의 유량을 조절함으로써 고분자 미립구 크기를 제어할 수 있고 생분해성 고분자인 폴리락트산-폴리글리콜산의 공중합체(PLGA), 폴리락트산(PDLA)는 우수한 생체적합성 특성과 생분해성 특성으로 약물, 예방 및 진단용 화학물, 치료용 백신 담지체, 조직공학용 지지체 등 다양한 의료용도에 적용되고 있다.
The polymer microspheres prepared according to the present invention can control the size of the polymer microspheres by controlling the flow rate of the continuous and non-continuous phase flows of the step (d), and the copolymer of polylactic acid-polyglycolic acid as a biodegradable polymer. (PLGA) and polylactic acid (PDLA) have been applied to various medical applications such as drugs, prophylactic and diagnostic chemicals, therapeutic vaccine carriers, and tissue engineering supports due to their excellent biocompatibility and biodegradability.
실시예Example
1 One
오일상인 고분자용액은 디클로로메탄 대 폴리락트산-폴리글리콜산의 공중합체(락트산:글리콜산의 몰비 = 65:35, 분자량 40,000 ~75,000)와 상변화 물질인 2-메틸펜탄의 합을 9 대 1의 중량부로 용해시켰고, 2-메틸펜탄은 1 중량부에 대해 0.3 중량부를 용해시켰다. 외부 연속상은 1wt% 폴리비닐알코올 수용액을 사용하였다.
The polymer solution, which is an oil phase, is a 9 to 1 sum of a copolymer of dichloromethane to polylactic acid-polyglycolic acid (molar ratio of lactic acid to glycolic acid = 65:35, molecular weight 40,000 to 75,000) and 2-methylpentane, a phase change material. It dissolved in parts by weight, and 2-methylpentane dissolved 0.3 parts by weight relative to 1 part by weight. The outer continuous phase used an aqueous 1 wt% polyvinyl alcohol solution.
비 연속상인 고분자용액과 외부 연속상을 마이크로플루딕 디바이스로 도입하였다. 내경이 800마이크로미터인 튜브를 사용하고 비 연속상 주사기 바늘 크기는 30G를 사용하였다. 고분자 미립구의 크기는 연속상의 유량을 조절함으로써 조절 가능하였다. 비 연속상 흐름은 0.1ml/hr로 하였고 외부 연속상 흐름에 대해서 100ml/hr, 200ml/hr 등으로 조절함으로써 고분자 미립구 크기를 230±10마이크로미터, 200±10마이크로미터로 조절할 수 있었다. 고형화된 미립구 세척 후에 상온 건조한 뒤 진공 오븐에 넣어 24시간 동안 건조시켰다.
A non-continuous phase polymer solution and an external continuous phase were introduced into the microfluidic device. A tube with an internal diameter of 800 micrometers was used and a non-continuous syringe needle size of 30 G was used. The size of the polymer microspheres was adjustable by adjusting the flow rate of the continuous phase. Non-continuous phase flow was 0.1ml / hr, and the microparticle size could be adjusted to 230 ± 10 micrometers and 200 ± 10 micrometers by adjusting the external continuous phase flow to 100ml / hr, 200ml / hr, and so on. After washing the solidified microspheres, the mixture was dried at room temperature and placed in a vacuum oven for 24 hours.
실시예Example
1-1 1-1
유상인 고분자용액 중의 폴리락트산-폴리글리콜산의 공중합체(Poly(lactic acid-co-glycolic acid)(PLGA))와 상변화 물질을 7 대 3의 비율로 섞은 것을 제외하고는 실시예 1과 동일한 방법으로 미립구를 제조하였다. 도 2a, 도 2b, 도 2c 에는 형성된 균일한 미세입자들의 표면과 단면의 주사전자 현미경 사진을 나타내었다.
Same as Example 1, except that a polylactic acid-polyglycolic acid copolymer (Poly (lactic acid-co-glycolic acid) (PLGA)) and a phase change material were mixed in a ratio of 7 to 3 in an oily polymer solution. Microspheres were prepared by the method. 2A, 2B and 2C show scanning electron micrographs of the surface and cross section of uniform microparticles formed.
실시예Example
1-2 1-2
유상인 고분자용액 중의 폴리(D,L-락트산)(Poly(D,L-lactic acid)(PDLA))과 상변화 물질을 7 대 3의 비율로 섞은 것을 제외하고는 실시예 1과 동일한 방법으로 미립구를 제조하였다. 도 2d에는 형성된 미세입자의 표면의 주사전자 현미경 사진을 나타내었다.
In the same manner as in Example 1, except that poly (D, L-lactic acid) (PDLA) and a phase change material were mixed in an oily polymer solution in a ratio of 7 to 3. Microspheres were prepared. 2D shows a scanning electron micrograph of the surface of the formed microparticles.
실시예Example
1-3 1-3
유상인 고분자용액 중의 폴리D,L-락트산-폴리카프로락톤의 공중합체(Poly(D,L-lactide-co-caprolactone))는 90 대 10의 중량비로 중합하여 상변화 물질과 7 대 3의 비율로 섞은 것을 제외하고는 실시예 1과 동일한 방법으로 미립구를 제조하였다. 도 2e에는 형성된 미세입자의 표면의 주사전자현미경 사진을 나타내었다.
Poly (D, L-lactide-co-caprolactone) copolymer in an oily polymer solution (Poly (D, L-lactide-co-caprolactone)) was polymerized in a weight ratio of 90 to 10 to a phase-change material and a ratio of 7 to 3. Microspheres were prepared in the same manner as in Example 1 except for mixing with. 2E shows a scanning electron micrograph of the surface of the formed microparticles.
실시예Example
1-4 1-4
유상인 고분자용액 중의 폴리D,L-락트산-폴리카프로락톤의 공중합체(Poly(D,L-lactide-co-caprolactone))는 80 대 20의 중량비로 중합하여 상변화 물질과 7 대 3의 비율로 섞은 것을 제외하고는 실시예 1과 동일한 방법으로 미립구를 제조하였다. 도 2f에는 형성된 미세입자의 표면의 주사전자현미경 사진을 나타내었다.
Poly (D, L-lactide-co-caprolactone) copolymer in an oily polymer solution (Poly (D, L-lactide-co-caprolactone)) was polymerized in a weight ratio of 80 to 20 to a phase-change material and a ratio of 7 to 3. Microspheres were prepared in the same manner as in Example 1 except for mixing with. 2F shows a scanning electron micrograph of the surface of the formed microparticles.
실시예Example
1-5 1-5
유상인 고분자용액 중의 폴리D,L-락트산-폴리카프로락톤의 공중합체(Poly(D,L-lactide-co-caprolactone))는 75 대 25의 중량비로 중합하여 상변화 물질과 7 대 3의 비율로 섞은 것을 제외하고는 실시예 1과 동일한 방법으로 미립구를 제조하였다. 도 2g에는 형성된 미세입자의 표면의 주사전자현미경 사진을 나타내었다.
Poly (D, L-lactide-co-caprolactone) copolymer in an oily polymer solution (Poly (D, L-lactide-co-caprolactone)) was polymerized in a weight ratio of 75 to 25 to a phase-change material and a ratio of 7 to 3. Microspheres were prepared in the same manner as in Example 1 except for mixing with. 2G shows a scanning electron micrograph of the surface of the formed microparticles.
실시예Example
1-6 1-6
유상인 고분자용액 중의 폴리술폰(Poly(sulfone)(PSf))과 상변화 물질을 7 대 3의 비율로 섞은 것을 제외하고는 실시예 1과 동일한 방법으로 미립구를 제조하였다. 도 2h에는 형성된 미세입자의 표면의 주사전자 현미경 사진을 나타내었다.
Microspheres were prepared in the same manner as in Example 1, except that polysulfone (PSf) and a phase change material in an oily polymer solution were mixed at a ratio of 7 to 3. 2h shows a scanning electron micrograph of the surface of the formed microparticles.
비교예Comparative example
1 One
유상인 고분자용액중의 폴리락트산-폴리글리콜산의 공중합체(Poly(lactic acid-co-glycolic acid)(PLGA))를 단독으로 사용한 것을 제외하고는 실시예 1과 동일한 방법으로 미립구를 제조하였다. 도 2i, 도 2j에는 형성된 미세입자의 표면과 단면의 주사전자 현미경 사진을 나타내었다.
Microspheres were prepared in the same manner as in Example 1 except that a polylactic acid-polyglycolic acid copolymer (Poly (lactic acid-co-glycolic acid) (PLGA)) in an oily polymer solution was used alone. 2I and 2J show scanning electron micrographs of the surface and cross section of the formed fine particles.
Claims (10)
(b) 폴리비닐알코올을 물에 용해시켜 연속상을 제조하는 단계;
(c) (a) 단계에서 제조된 고분자 용액과 (b) 단계에서 제조된 연속상을 마이크로플루딕 디바이스에 튜브로 연결하여 도입하는 단계;
(d) 마이크로플루딕 디바이스를 사용하여 O/W 에멀젼(oil-in-water)방식으로 내부의 다공성 구조와 표면에 딤플 구조를 갖고 균일한 크기를 갖는 미립구를 제조하는 방법. (a) a polymer selected from the group consisting of copolymers of polylactic acid-polyglycolic acid, poly (D, L-lactic acid), copolymers of polyD, L-lactic acid-polycaprolactone and polysulfones; And preparing 2-methylpentane as a phase change material (PCM);
(b) dissolving polyvinyl alcohol in water to prepare a continuous phase;
(c) introducing the polymer solution prepared in step (a) and the continuous phase prepared in step (b) by connecting a tube to a microfluidic device;
(d) A method for producing microspheres having a uniform size and a porous structure therein and a dimple structure on the surface by an O / W oil-in-water method using a microfluidic device.
상기 튜브 내로 연속상을 위한 물 흐름을 도입하여 균일한 크기의 미립자를 형성하는 단계, 및
상기 미립자를 고형화시키는 단계를 포함하는, 내부의 다공성 구조와 표면에 딤플 구조를 갖고 균일한 크기를 갖는 미립구의 제조방법. External continuous phase solution comprising polyvinyl alcohol; And a polymer and a phase change material selected from the group consisting of a copolymer of polylactic acid-polyglycolic acid, a copolymer of poly (D, L-lactic acid), a polyD, L-lactic acid-polycaprolactone and polysulfone. Connecting a polymer solution containing methylpentane; to a microfluidic device via a tube;
Introducing a flow of water for the continuous phase into the tube to form particles of uniform size, and
And solidifying the fine particles, having a dimple structure on the surface and a porous structure therein and having a uniform size.
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| CN111261849B (en) * | 2018-12-03 | 2022-10-21 | 成都市银隆新能源有限公司 | Method for preparing solid spherical material for negative electrode of lithium ion battery by using microfluidic technology |
| KR102464808B1 (en) * | 2022-04-13 | 2022-11-09 | (주)인벤티지랩 | Method for producing micro-particles containing moxidectin and sustained-release injection composition comprising micro-particles prepared by the method |
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| KR20100117948A (en) * | 2009-04-27 | 2010-11-04 | 한양대학교 산학협력단 | Porous microsphere for pulmonary administration and manufacturing method thereof |
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| KR20080020954A (en) * | 2006-09-01 | 2008-03-06 | 도소 가부시키가이샤 | Microchannel structure and fine-particle production method using the same |
| KR20090128287A (en) * | 2008-06-10 | 2009-12-15 | 충남대학교산학협력단 | Production method of mono-dispersion alginate bead applying microfluidic chip using singular direction shearing force, and capsulation method of the cell |
| KR100963435B1 (en) | 2008-06-19 | 2010-06-17 | 한국과학기술연구원 | Method of preparing biodegradable covered porous polymer microspheres for sustained-release drug delivery and tissue regeneration |
| KR20100117948A (en) * | 2009-04-27 | 2010-11-04 | 한양대학교 산학협력단 | Porous microsphere for pulmonary administration and manufacturing method thereof |
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