KR100924236B1 - 균일한 입도분포를 가지는 초미세입자의 신규한 제조방법 및 장치 - Google Patents
균일한 입도분포를 가지는 초미세입자의 신규한 제조방법 및 장치 Download PDFInfo
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- KR100924236B1 KR100924236B1 KR1020090055743A KR20090055743A KR100924236B1 KR 100924236 B1 KR100924236 B1 KR 100924236B1 KR 1020090055743 A KR1020090055743 A KR 1020090055743A KR 20090055743 A KR20090055743 A KR 20090055743A KR 100924236 B1 KR100924236 B1 KR 100924236B1
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Abstract
Description
실시 예 | 압축된유체 주입속도 | 약물용액 주입속도 | 가열압축기체 압력 및 온도 | 평균입도 (동적광산란법) | 레이져회절입도분석법 (부피기준) | |||
D10% | D50% | D90% | SPAN | |||||
1 | CO2-40 g/min | 18 g/min | 100 KPa,40℃ | 550.2 ㎚ | 0.51㎛ | 0.88㎛ | 2.11㎛ | 1.8 |
2 | CO2-40 g/min | 18 g/min | 100 KPa,80℃ | 535.4 ㎚ | 0.41㎛ | 0.76㎛ | 1.91㎛ | 2.0 |
3 | CO2-40 g/min | 18 g/min | 200 KPa,40℃ | 510.2 ㎚ | 0.39㎛ | 0.77㎛ | 1.71㎛ | 1.7 |
4 | CO2-40 g/min | 18 g/min | 200 kPa,80℃ | 490.5 ㎚ | 0.32㎛ | 0.73㎛ | 1.75㎛ | 2.0 |
5 | CO2-40 g/min | 12 g/min | 100 KPa,40℃ | 399.2 ㎚ | 0.35㎛ | 0.66㎛ | 1.46㎛ | 1.7 |
6 | CO2-40 g/min | 15 g/min | 200 KPa,40℃ | 470.2 ㎚ | 0.31㎛ | 0.71㎛ | 1.55㎛ | 1.7 |
7 | CO2-35 g/min R-22-5 g/min | 18 g/min | 300 KPa,120℃ | 486.7 ㎚ | 0.33㎛ | 0.71㎛ | 1.64㎛ | 1.8 |
8 | CO2-30 g/min Dimethylether - 10 g/min | 18 g/min | 500 KPa,120℃ | 453.8 ㎚ | 0.37㎛ | 0.75㎛ | 1.69㎛ | 1.8 |
9 | CO2-40 g/min | 18 g/min | 없음 | 958.6 ㎚ | 0.65㎛ | 1.12㎛ | 3.83㎛ | 2.8 |
실시 예 | 압축된유체 주입속도 | 약물용액 주입속도 | 가열압축기체 압력및온도 | 평균입도 (동적광산란법) | 레이져회절입도분석법(부피기준) | |||
D10% | D50% | D90% | SPAN | |||||
10 | CO2-40 g/min | 15 g/min | 100 KPa,40℃ | 515.6 ㎚ | 0.50㎛ | 0.89㎛ | 2.02㎛ | 1.7 |
11 | CO2-40 g/min | 15 g/min | 100 KPa,80℃ | 505.2 ㎚ | 0.49㎛ | 0.81㎛ | 1.95㎛ | 1.8 |
12 | CO2-40 g/min | 15 g/min | 200 KPa,80℃ | 450.5 ㎚ | 0.42㎛ | 0.79㎛ | 2.05㎛ | 2.1 |
13 | CO2-35 g/min R-22 - 5 g/min | 15 g/min | 400 KPa,120℃ | 432.8 ㎚ | 0.39㎛ | 0.74㎛ | 1.87㎛ | 2.0 |
14 | CO2-40 g/min | 15 g/min | 없음 | 962.5 ㎚ | 0.66㎛ | 1.21㎛ | 3.94㎛ | 2.7 |
15 | CO2-40 g/min | 18 g/min | 200 KPa,40℃ | 435.6 ㎚ | 0.39㎛ | 0.85㎛ | 1.92㎛ | 1.8 |
16 | CO2-35 g/min R-22 - 5 g/min | 18 g/min | 500 KPa,80℃ | 423.1 ㎚ | 0.40㎛ | 0.81㎛ | 1.79㎛ | 1.7 |
17 | CO2-40 g/min | 18 g/min | 없음 | 812.2 ㎚ | 0.61㎛ | 1.25㎛ | 3.75㎛ | 2.5 |
실시 예 | 압축된유체 주입속도 | 약물용액 주입속도 | 가열압축기체 압력및온도 | 평균입도 (동적광산란법) | 레이져회절입도분석법(부피기준) | |||
D10% | D50% | D90% | SPAN | |||||
18 | CO2-40 g/min | 12 g/min | 200 KPa,40℃ | 402.2 ㎚ | 0.35㎛ | 0.61㎛ | 1.23㎛ | 1.4 |
19 | CO2-40 g/min | 15 g/min | 200 KPa,40℃ | 465.5 ㎚ | 0.39㎛ | 0.69㎛ | 1.42㎛ | 1.5 |
20 | CO2-40 g/min | 18 g/min | 200 KPa,40℃ | 550.2 ㎚ | 0.45㎛ | 0.79㎛ | 1.91㎛ | 1.8 |
21 | CO2-35 g/min Dimethylether - 5 g/min | 18 g/min | 350 KPa,80℃ | 541.3 ㎚ | 0.47㎛ | 0.77㎛ | 1.83㎛ | 1.8 |
22 | CO2-30 g/min Dimethylether - 10 g/min | 18 g/min | 500 KPa,120℃ | 524.3 ㎚ | 0.41㎛ | 0.73㎛ | 1.77㎛ | 1.9 |
실시 예 | 압축된유체 주입속도 | 약물용액 주입속도 | 용액 농도 | 가열압축기체 압력및온도 | 평균입도 (동적광산란법) | 레이져회절입도분석법(부피기준) | |||
D10% | D50% | D90% | SPAN | ||||||
23 | CO2-40g/min | 15g/min | 5㎎/㎖ | 200 KPa,40℃ | 395.5 ㎚ | 0.33㎛ | 0.62㎛ | 1.18㎛ | 1.4 |
24 | CO2-40g/min | 15g/min | 10㎎/㎖ | 200 KPa,40℃ | 462.4 ㎚ | 0.43㎛ | 0.69㎛ | 1.46㎛ | 1.5 |
25 | CO2-40g/min | 15g/min | 20㎎/㎖ | 200 KPa,40℃ | 593.2 ㎚ | 0.56㎛ | 0.81㎛ | 2.01㎛ | 1.8 |
실시 예 | 압축된유체 주입속도 | 약물용액 주입속도 | 용액 농도 | 가열압축기체 압력및온도 | 평균입도 (동적광산란법) | 레이져회절입도분석법(부피기준) | |||
D10% | D50% | D90% | SPAN | ||||||
26 | CO2-40g/min | 15g/min | 5㎎/㎖ | 200KPa,40℃ | 672.4㎚ | 0.45㎛ | 0.89㎛ | 1.65㎛ | 1.3 |
27 | CO2-40g/min | 15g/min | 10㎎/㎖ | 200KPa,40℃ | 713.5㎚ | 0.49㎛ | 0.94㎛ | 1.89㎛ | 1.5 |
28 | CO2-40g/min | 15g/min | 20㎎/㎖ | 200KPa,40℃ | 767.7㎚ | 0.52㎛ | 0.99㎛ | 2.12㎛ | 1.6 |
실시 예 | 압축된유체 주입속도 | 약물용액 주입속도 | 가열압축 기체 압력및온도 | 조성 | 평균입도 (동적 광산란법) | 레이져회절입도분석법 (부피기준) | |||
D10% | D50% | D90% | SPAN | ||||||
29 | CO2-40g /min | 15g/min | 200KPa,80℃ | 약물:PVP 30=1:19 | 560.7㎚ | 0.45㎛ | 0.82㎛ | 2.13㎛ | 2.0 |
30 | CO2-40g /min | 15g/min | 400KPa,80℃ | 약물:PVP K30:소디움라우릴설페이트=1:15:4 | 505.3㎚ | 0.42㎛ | 0.88㎛ | 1.92㎛ | 1.7 |
31 | CO2-40g /min | 15g/min | 400KPa,40℃ | 약물:PVP K30:비타민 E 티피지에스=1:15:4 | 850.7㎚ | 0.51㎛ | 1.43㎛ | 2.61㎛ | 1.5 |
32 | CO2-40g /min | 15g/min | 200KPa,40℃ | 약물:PVP K30:수크로스에스터15=1:15:4 | 601.5㎚ | 0.49㎛ | 1.02㎛ | 2.15㎛ | 1.6 |
실시 예 | 압축된 유체 주입속도 | 약물용액 주입속도 | 가열압축 기체 압력및온도 | 조성 | 평균입도 (동적 광산란법) | 레이져회절입도분석법 (부피기준) | |||
D10% | D50% | D90% | SPAN | ||||||
33 | CO2-40g /min | 15g/min | 300 KPa, 40℃ | 약물:PVP VA64=1:5 | 603.5㎚ | 0.56㎛ | 0.89㎛ | 1.82㎛ | 1.4 |
34 | CO2-40g /min | 15g/min | 100 KPa, 40℃ | 약물: PVP VA64:겔루시르 44/14=1:4:1 | 806.2㎚ | 0.53㎛ | 1.33㎛ | 2.21㎛ | 1.3 |
35 | CO2-40g /min | 15g/min | 50 KPa, 40℃ | 약물: PVP VA64:비타민 E 티피지에스=1:4:1 | 875.2㎚ | 0.51㎛ | 1.52㎛ | 2.89㎛ | 1.6 |
실시 예 | 압축된 유체 주입속도 | 약물용액 주입속도 | 가열압축 기체 압력및온도 | 조성 | 평균입도 (동적 광산란법) | 레이져회절입도분석법 (부피기준) | |||
D10% | D50% | D90% | SPAN | ||||||
36 | CO2-40 g/min | 15g /min | 300KPa, 40℃ | 약물:HPMC =1:5 | 672.5㎚ | 0.51㎛ | 0.91㎛ | 1.96㎛ | 1.6 |
37 | CO2-40 g/min | 15g /min | 100KPa, 40℃ | 약물:HPMC:폴록사머 =1:4:1 | 820.7㎚ | 0.59㎛ | 1.46㎛ | 2.85㎛ | 1.5 |
38 | CO2-40 g/min | 15g /min | 50KPa, 40℃ | 약물:HPMC :Myrj 52=1:4:1 | 1015.2㎚ | 0.68㎛ | 1.55㎛ | 4.1㎛ | 2.2 |
39 | CO2-35 g/min R-22-5 g/min | 15g /min | 300KPa, 80℃ | 약물:HPMC =1:5 | 667.4㎚ | 0.49㎛ | 0.90㎛ | 1.93㎛ | 1.7 |
40 | CO2-30 g/min R-22-10 g/min | 15g /min | 300KPa, 120℃ | 약물:HPMC =1:5 | 659.5㎚ | 0.48㎛ | 0.87㎛ | 1.91㎛ | 1.6 |
Claims (15)
- 평균입자크기 0.02~3 미크론의 균일 입도분포를 가진 초미세입자 제조방법에 있어서,용질을 액상용제에 용해시켜 얻어진 액상용액 혹은 분산액과 30~90 ℃의 온도와 60~300 bar로 압축된 유체를 연속적으로 접촉시키고 혼합유닛에 주입하여 균질하게 혼합시킴으로써 단일상 또는 콜로이드상으로 이루어지는 형태의 혼합물을 제조하는 단계;상기 혼합물을 노즐을 통해 가열된 압축 기체와 함께 건조 기체가 흐르고 있는 상압상태의 증발관(evaporation chamber)에 분무건조하여 초미세입자를 형성시키는 단계;상기 형성된 초미세입자를 회수하는 단계;를 포함하는 것을 특징으로 하는 제조된 분체의 10 부피% 이하가 0.02 micron 이하의 크기를 가지며 동시에 90 부피% 이상이 3 micron 이하의 크기를 가지는 균일한 입도분포를 가진 평균입자크기 0.02~3 micron의 초미세입자 제조방법.
- 제 1 항에 있어서,액상용제는 정제수, 메탄올, 에탄올, 프로판올, 이소프로판올, 부탄올, 옥탄올, 아세톤, 메틸에틸케톤, 메틸이소부틸케톤, N-헥산, 에틸아세테이트, 디클로로메탄, 클로로포름, 아세트산, N-메틸피롤리돈, 디메틸설폭사이드, 디메틸아마이드 또는 디메틸포름아마이드로 이루어진 군으로부터 선택되는 적어도 1종 이상인 것을 특징으로 하는 초미세입자 제조방법.
- 제 1 항에 있어서,압축된 유체는 30~90 ℃ 및 60~300 bar의 온도 및 압력범위를 가지는 클로로플루오로카본류, 하이드로클로로플루오로카본류, 하이드로플루오로카본류, 플루오로카본류, 디메틸에테르, 디에틸에테르, 디이소프로필에테르, 디-tert-부틸에테르, 이산화탄소 또는 암모니아로 이루어진 군으로부터 선택되는 적어도 1종 이상인 것을 특징으로 하는 초미세입자 제조방법.
- 제 1 항에 있어서,혼합유닛은 액상용제와 압축된 유체가 극대화된 접촉면적을 통해 효율적으로 혼합되기 위해 금속, 세라믹, 강화유리, 동으로 제조된 충진제로 채워진 압력 용기 혹은 교반장치가 달려있는 압력 용기인 것을 특징으로 하는 초미세입자 제조방법.
- 제 1 항에 있어서,단일상 또는 콜로이드상 형태의 혼합물은 60-300 bar, 20-100 ℃의 압력 및 온도 조건을 가지는 것을 특징으로 하는 초미세입자 제조방법.
- 제 1 항에 있어서,노즐은 분사유출부에서 압축된 유체와 액상용액으로 이루어진 단일상 혹은 콜로이드상 형태의 혼합물과 가열된 압축기체를 접촉시켜 분사를 가능하게 하는 형태의 장치로 다중유체 동축노즐을 포함한 2유체 이상의 다중 유체 노즐인 것을 특징으로 하는 초미세입자 제조방법.
- 제 1 항에 있어서,가열된 압축 기체는 공기, 질소, 아르곤 중 선택되는 적어도 1종 이상인 기체로 60-1000 kPa의 압력과 30~120 ℃의 온도를 가지는 것을 특징으로 하는 초미세입자 제조방법.
- 제 1 항에 있어서,건조기체는 공기, 질소, 아르곤 중 선택되는 1종 이상인 기체로 20-300 ℃의 온도를 가지고 0.1~10.0 m3/min의 유량으로 연속적으로 흐르는 것을 특징으로 하는 방법.
- 제 1 항에 있어서,초미세입자의 회수는 금속 혹은 고분자 재질의 필터 및 망 등이나 기류의 흐름을 이용해 집진하는 사이클론을 사용하는 것을 특징으로 하는 초미세입자 제조방법.
- 제 1 항에 있어서,용질은 생리활성 물질로는 단백질, 펩타이드, 뉴클레오타이드, 기능성식품, 약학적 물질 또는 약학적 제제로부터 선택되는 적어도 1종 이상인 것을 특징으로 하는 초미세입자 제조방법.
- 제 10 항에 있어서,생리활성 물질은 사이클로스포린, 실로스타졸, 메게스테롤 아세테이트, 라이소자임, 두타스체라이트, 이트라코나졸 또는 펠로디핀 중에서 선택되는 1종 이상인 것을 특징으로 하는 초미세입자 제조방법.
- 제 11 항의 제조방법으로 제조된 분체의 10 부피% 이하가 0.02 micron 이하의 크기를 가지며 동시에 90 부피% 이상이 3 micron 이하의 크기를 가지는 균일한 입도분포를 가진 평균입자크기 0.02~3 micron의 초미세입자의 생리활성 물질.
- 제 10 항에 있어서,용질로 사용되는 생리활성 물질은 약학적 허용가능한 첨가제를 함유하고 있는 것을 특징으로 하는 초미세입자 제조방법.
- 제 13 항에서,약학적 허용가능한 첨가제는 하이드로프록시 메틸셀룰로스, 하이드록시프로필셀룰로스, 폴리바이닐피롤리돈, 폴리에틸렌글라이콜, 소듐 라우릴 설페이트, 다이옥틸설포숙시네이트, 젤라틴, 카세인, 레시틴(포스파타이드), 텍스트란, 검 아카시아, 콜레스테롤, 트라가칸트, 스테아르산, 벤즈알코늄 클로라이드, 칼슘 스테아레이트, 글리세롤 모노스테아레이트, 세토스테아릴 알콜, 세토마크로골 유화 왁스, 소르비탄 에스터, 폴리옥시에틸렌 알킬 에테르, 폴리옥시에틸렌 캐스터 오일 유도체, 폴리옥시에틸렌 소르비탄 지방산 에스터(Tweens), 폴리에틸렌 글리콜, 폴리옥시에틸렌스테아레이트, 콜로이드성 실리콘 다이옥사이드, 포스페이트, 카복시메틸셀룰로스, 칼슘, 카복시메틸셀룰로스 소듐, 메틸셀룰로스, 하이드록시에틸셀룰로스, 하이프로멜로스 프탈레이트, 비결정 셀룰로스, 마그네슘 알루미늄 실리케이트, 트라이에탄올아민, 폴리바이닐 알콜, 에틸렌 옥사이드 및 포름 알데히드를 갖는 4-(1,1,3,3-테트라메틸부틸)-페놀 중합체, 폴록사머, 에틸렌 옥사이드 및 프로필렌 옥사이드의 블록 공합체임), 폴록사민, 에틸렌다이아민에 프로필렌 옥사이드 에틸렌 옥사이드의 순차적인 첨가에 의해 유도된 4작용성 블록 공중합체, 테트로닉 1508, 알킬 아릴 폴리에테르 설포네이트인 트리톤 X-200, 수크로스 스테아레이트 및 수크로스 다이스테아레이트의 혼합물인 크로데타스(Crodestas) F-110, 올린(Olin)-IOG 또는 계면활성제 10-G, 크로데스타스 SL-40, 및 C18H37CH2(CON(CH3)-CH2(CHOH)4(CH2OH)2인 SA9OHCO, 데카노일-N-메틸글루카마이드, n-데실 β-D-글루코피라노사이드, n-데실 β-D-말토피라노사이드, n-도데실 β-D-글루코피라노사이드, n-도데실 β-D-말토사이드, 헵타노일-N-메틸글루카마이드, n-헵틸 β-D-글루코피라노사이드, n-헵틸β-D-티오글루코사이드, n-헥실 β-D-티오글루코사이드, 노나노일-N-메틸글루카마이드, n-노일 β-D-글루코피라노사이드, 옥타노일 N-메틸글루카마이드, n-옥틸 β-D-글루코피라노사이드, 옥틸 β-D-티오글로코피라노사이드, PEG-인지질, PEG-콜레스테롤, PEG-콜레스테롤 유도체, PEG-바이타민 A, PEG-바이타민 E, PEG 유도된 바이타민 E인 바이타민 E 티피쥐에스, 리소자임, 바이닐 피롤리돈 또는 바이닐 아세테이트의 공중합체로부터 선택되는 적어도 1종 이상인 것을 특징으로 하는 초미세입자 제조방법.
- 용질의 액상용액 또는 분산액 제조 및 이송장치;초임계 압축유체를 수용하는 압축유체 저장용기 및 이송장치;상기 용질의 액상용액 또는 분산액과 상기 초임계 압축유체가 연속적으로 접촉시키게 하여 단일상 또는 콜로이드상의 혼합물 유체가 이루어지는 혼합 반응용기;가열된 압축 건조공기를 수송하기 위한 압축 건조기체 공급장치;상기 혼합 반응용기의 단일상 또는 콜로이드상 혼합물 유체와 상기 가열된 압축 건조기체를 각각 동축노즐의 내측과 외측을 통해 상압상태의 증발관에 분무건조시켜 초미세입자를 제조하는 반응용기; 및상기 형성된 초미세입자를 회수하는 회수장치;를 포함하는 제 1 항 내지 제 14 항 중 어느 한 항에 따른 제조방법을 수행 하기 위한 장치.
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WO2010150964A1 (ko) | 2010-12-29 |
US20110200678A1 (en) | 2011-08-18 |
JP2011526836A (ja) | 2011-10-20 |
US8734830B2 (en) | 2014-05-27 |
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