WO2011152618A4 - 국소 근마비 효과를 갖는 비확산형 보툴리눔 독소와 그의 정제방법 - Google Patents
국소 근마비 효과를 갖는 비확산형 보툴리눔 독소와 그의 정제방법 Download PDFInfo
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- A61K38/4886—Metalloendopeptidases (3.4.24), e.g. collagenase
- A61K38/4893—Botulinum neurotoxin (3.4.24.69)
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- C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
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- C12Y304/24—Metalloendopeptidases (3.4.24)
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Abstract
Description
A260/A280 | ||||
pH 4.5 | pH 5.0 | pH 5.5 | pH 6.0 | |
pI | 0.76± 0.15 | 0.69± 0.09 | 0.67± 0.05 | 0.63± 0.08 |
pII | 0.50± 0.05 | 0.55± 0.04 | 0.55± 0.03 | 0.81± 0.19 |
pIII | 0.76± 0.10 | 0.82± 0.13 | 0.84± 0.12 | 0.79± 0.09 |
Total LD50(Unit) | ||||
pH 4.5 | pH 5.0 | pH 5.5 | pH 6.0 | |
기존 산침전법 정제물(전시료) | 5± 0.8 | 5± 1 | 5± 0.8 | 5± 1.2 |
pI | 1.5± 0.4 | 3± 0.5 | 2± 0.4 | 2± 0.8 |
pII | 0.2± 0.2 | 1± 0.2 | 3± 0.4 | 0.4± 0.2 |
pIII | - | 0.2± 0.1 | 0.2± 0.1 | 2± 1 |
(단위: 105 U) |
A260/A280 | ||||
0.25 ml | 0.5ml | 1ml | 2ml | |
pI | 0.67± 0.08 | 0.64± 0.07 | 0.68± 0.09 | 0.67± 0.13 |
pII | 0.55± 0.02 | 0.56± 0.01 | 0.55± 0.04 | 0.55± 0.03 |
pIII | 0.85± 0.14 | 0.84± 0.09 | 0.82± 0.18 | 0.84± 0.24 |
Total LD50(Unit) | ||||
0.25 ml | 0.5 ml | 1 ml | 2 ml | |
기존 산침전법 정제물(전시료) | 2.5± 0.5 | 5± 1 | 10± 4 | 20± 5 |
pI | 0.8± 0.2 | 1.6± 0.4 | 5± 2 | 15± 4.8 |
pII | 1.6± 0.2 | 4± 0.6 | 4± 0.9 | 4± 1.5 |
pIII | 0.2± 0.1 | 0.4± 0.1 | 0.8± 0.2 | 0.6± 0.3 |
(단위: 105 U) |
Score | 측정 기준 |
0 | 정상 쥐의 발 모양새와 걸음걸이 |
1 | 발가락은 모아지지 않았으나 걸을 때 다리를 끈다. |
2 | 1의 기준과 함께 발가락이 모아져 있다. |
3 | 2의 기준과 함께 발마디가 안쪽으로 굽어있다. |
4 | 3의 기준과 함께 발이 다리근육쪽으로 완전히 붙어있으며 다리를 못 쓴다. |
분획 | 마우스 우하지주사시 마비부위 |
체내 확산형 활성 분획 | 우하지, 횡경막, 좌하지 등 체내 여러 부위 |
체내 비확산형 활성 분획 | 우하지 |
체내 확산형 비활성 분획 | - |
Mg | Fe | Zn | |
pII | 183.0 ± 19.3* | 105.4 ± 22.1** | 332.6 ± 140.8*** |
시판제품 | 78.1 ± 7.4* | 39.6 ± 3.3 | 65.6 ± 25.9 |
* p<0.0015, ** p<0.011, ***p<0.045 |
Claims (3)
- 정제된 보툴리눔 독소 A 형 제제를 pH는 4.5 내지 6.5 범위, 염화나트륨(NaCl)의 농도를 0.02 내지 0.2M로 조절하여 첨가한 음이온 이온교환수지 크로마토그래피를 수행하여 아분획을 분리하는 단계; 및상기 아분획 중 A260/A280의 값이 0.4 내지 0.6 수준을 유지하는 비확산성 보툴리눔 독소 분획을 수득하는 단계를 포함하여 이루어지는 것을 특징으로 하는 비확산형 보툴리눔 독소의 정제방법.
- 청구항 1에 의하여 분리 정제된 것으로,독소 100U/ml당 Zn 이온이 적어도 150ppb, Fe 이온이 적어도 80ppb, Mg 이온이 적어도 140ppb로 포함되는 것을 특징으로 하는 비확산형 보툴리눔 독소.
- 청구항 2의 비확산형 보툴리눔 독소를 그의 반수치사량의 1.5 내지 3배의 양으로 마우스 우하지에 주사하고, 우하지 근육과 호흡근의 마비 여부와 치사여부를 판단하는 것을 특징으로 하는 비확산형 보툴리눔 독소를 판별하는 방법.
Priority Applications (8)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201180028634.2A CN102985102B (zh) | 2010-05-31 | 2011-05-13 | 引起局部肌麻痹的非扩散型肉毒杆菌毒素及其精制方法 |
AU2011262499A AU2011262499B2 (en) | 2010-05-31 | 2011-05-13 | Non-diffusive botulinum toxin causing local muscle paralysis, and purification method thereof |
EP11789976.5A EP2578228B1 (en) | 2010-05-31 | 2011-05-13 | Non-diffusive botulinum toxin causing local muscle paralysis, and purification method thereof |
JP2013513102A JP5919608B2 (ja) | 2010-05-31 | 2011-05-13 | 局所筋麻痺効果を有する非拡散型ボツリヌス毒素とその精製方法 |
ES11789976.5T ES2659820T3 (es) | 2010-05-31 | 2011-05-13 | Toxina botulínica no difusiva que provoca una parálisis muscular localizada y procedimiento de purificación de la misma |
US13/700,867 US9598683B2 (en) | 2010-05-31 | 2011-05-13 | Non-diffusive botulinum toxin causing local muscle paralysis, and purification method thereof |
US15/422,129 US10369235B2 (en) | 2010-05-31 | 2017-02-01 | Non-diffusive botulinum toxin causing local muscle paralysis, and purification method thereof |
US15/422,083 US20170145399A1 (en) | 2010-05-31 | 2017-02-01 | Non-diffusive botulinum toxin causing local muscle paralysis, and purification method thereof |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR1020100051076A KR101134146B1 (ko) | 2010-05-31 | 2010-05-31 | 국소 근마비 효과를 갖는 비확산형 보툴리눔 독소와 그의 정제방법 |
KR10-2010-0051076 | 2010-05-31 |
Related Child Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US13/700,867 A-371-Of-International US9598683B2 (en) | 2010-05-31 | 2011-05-13 | Non-diffusive botulinum toxin causing local muscle paralysis, and purification method thereof |
US15/422,083 Division US20170145399A1 (en) | 2010-05-31 | 2017-02-01 | Non-diffusive botulinum toxin causing local muscle paralysis, and purification method thereof |
US15/422,129 Division US10369235B2 (en) | 2010-05-31 | 2017-02-01 | Non-diffusive botulinum toxin causing local muscle paralysis, and purification method thereof |
Publications (4)
Publication Number | Publication Date |
---|---|
WO2011152618A2 WO2011152618A2 (ko) | 2011-12-08 |
WO2011152618A9 WO2011152618A9 (ko) | 2012-03-22 |
WO2011152618A3 WO2011152618A3 (ko) | 2012-05-24 |
WO2011152618A4 true WO2011152618A4 (ko) | 2012-07-12 |
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Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/KR2011/003547 WO2011152618A2 (ko) | 2010-05-31 | 2011-05-13 | 국소 근마비 효과를 갖는 비확산형 보툴리눔 독소와 그의 정제방법 |
Country Status (8)
Country | Link |
---|---|
US (3) | US9598683B2 (ko) |
EP (1) | EP2578228B1 (ko) |
JP (2) | JP5919608B2 (ko) |
KR (1) | KR101134146B1 (ko) |
CN (1) | CN102985102B (ko) |
AU (1) | AU2011262499B2 (ko) |
ES (1) | ES2659820T3 (ko) |
WO (1) | WO2011152618A2 (ko) |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
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KR101134146B1 (ko) | 2010-05-31 | 2012-04-19 | 메덱스젠 주식회사 | 국소 근마비 효과를 갖는 비확산형 보툴리눔 독소와 그의 정제방법 |
KR101775682B1 (ko) * | 2015-11-30 | 2017-09-06 | 주식회사 대웅 | 보툴리눔 독소의 제조방법 |
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- 2011-05-13 JP JP2013513102A patent/JP5919608B2/ja not_active Expired - Fee Related
- 2011-05-13 ES ES11789976.5T patent/ES2659820T3/es active Active
- 2011-05-13 CN CN201180028634.2A patent/CN102985102B/zh not_active Expired - Fee Related
- 2011-05-13 US US13/700,867 patent/US9598683B2/en not_active Expired - Fee Related
- 2011-05-13 EP EP11789976.5A patent/EP2578228B1/en not_active Revoked
- 2011-05-13 AU AU2011262499A patent/AU2011262499B2/en not_active Ceased
- 2011-05-13 WO PCT/KR2011/003547 patent/WO2011152618A2/ko active Application Filing
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2015
- 2015-05-07 JP JP2015094777A patent/JP5998419B2/ja not_active Expired - Fee Related
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2017
- 2017-02-01 US US15/422,083 patent/US20170145399A1/en not_active Abandoned
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Also Published As
Publication number | Publication date |
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WO2011152618A9 (ko) | 2012-03-22 |
US20130071331A1 (en) | 2013-03-21 |
ES2659820T3 (es) | 2018-03-19 |
JP2013533856A (ja) | 2013-08-29 |
KR20110131572A (ko) | 2011-12-07 |
US20170143849A1 (en) | 2017-05-25 |
CN102985102A (zh) | 2013-03-20 |
CN102985102B (zh) | 2016-06-08 |
US20170145399A1 (en) | 2017-05-25 |
AU2011262499A1 (en) | 2013-01-24 |
JP5998419B2 (ja) | 2016-09-28 |
EP2578228A4 (en) | 2013-10-02 |
JP5919608B2 (ja) | 2016-05-18 |
WO2011152618A3 (ko) | 2012-05-24 |
WO2011152618A2 (ko) | 2011-12-08 |
AU2011262499B2 (en) | 2015-01-22 |
US9598683B2 (en) | 2017-03-21 |
JP2015200659A (ja) | 2015-11-12 |
US10369235B2 (en) | 2019-08-06 |
KR101134146B1 (ko) | 2012-04-19 |
EP2578228A2 (en) | 2013-04-10 |
EP2578228B1 (en) | 2017-11-15 |
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