JP6173547B2 - ボツリヌム毒素の凍結乾燥製剤 - Google Patents
ボツリヌム毒素の凍結乾燥製剤 Download PDFInfo
- Publication number
- JP6173547B2 JP6173547B2 JP2016173874A JP2016173874A JP6173547B2 JP 6173547 B2 JP6173547 B2 JP 6173547B2 JP 2016173874 A JP2016173874 A JP 2016173874A JP 2016173874 A JP2016173874 A JP 2016173874A JP 6173547 B2 JP6173547 B2 JP 6173547B2
- Authority
- JP
- Japan
- Prior art keywords
- botulinum toxin
- lyophilized formulation
- polysorbate
- pharmaceutical lyophilized
- methionine
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/66—Microorganisms or materials therefrom
- A61K35/74—Bacteria
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
- A61K38/4886—Metalloendopeptidases (3.4.24), e.g. collagenase
- A61K38/4893—Botulinum neurotoxin (3.4.24.69)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/02—Inorganic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/20—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/06—Anti-spasmodics, e.g. drugs for colics, esophagic dyskinesia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/10—Drugs for disorders of the urinary system of the bladder
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/06—Antimigraine agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y304/00—Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
- C12Y304/24—Metalloendopeptidases (3.4.24)
- C12Y304/24069—Bontoxilysin (3.4.24.69), i.e. botulinum neurotoxin
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Biochemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Immunology (AREA)
- Molecular Biology (AREA)
- Zoology (AREA)
- Inorganic Chemistry (AREA)
- Wood Science & Technology (AREA)
- Toxicology (AREA)
- General Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Urology & Nephrology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Dermatology (AREA)
- Ophthalmology & Optometry (AREA)
- Physical Education & Sports Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Biomedical Technology (AREA)
- Pain & Pain Management (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Medicinal Preparation (AREA)
Description
したがって、動物から由来せず、ボツリヌム毒素の活性を損失させない安定化剤が要求される。
これより、本発明者らは、ボツリヌム毒素が冷凍、冷蔵、常温及び高温を含む広い温度範囲でも活性を長期間維持し、貯蔵安定性に優れたボツリヌム毒素の凍結乾燥製剤を開発した。
本発明のボツリヌム毒素凍結乾燥製剤は、ボツリヌム毒素、メチオニン及びポリソルベートと、糖または糖アルコール及び/またはイオン化合物を含む滅菌された調剤液を凍結乾燥して準備した。
ボツリヌム毒素の安定性は、一定保管期間後に活性の持続として判断し、ボツリヌム毒素の活性の持続は、マウスLD50またはマウス致死率で測定した。上記凍結乾燥製剤の剤形を40℃、相対湿度70%で30日間保管し、これを生理食塩水で溶解後、2.5 LD50 IUに該当するボツリヌム毒素をマウス3匹の腹腔に注射し、2匹以上が致死に至る場合、これを安定性が持続するものと判断し、これを下記の表では、死亡率で表現した。マウスの死亡率が50%以上なら、ボツリヌム毒素の活性が維持されるものと評価されることができる。
力価測定法は、次のように実施する。検体2バイアルに生理食塩水2.8mLをそれぞれ加えて溶かした。ここで、4.4mLを取って生理食塩水1.45mLに入れた液を検液1とした。検液1の4.4mLを生理食塩水1.45mLに入れた液を検液2とした。同一の方法で8回さらに希釈し、それぞれを検液とした。検液3から検液6までの検液を重さが17〜22gのマウス(CD1、雌)に検液ごとに10匹の腹腔に匹当たり0.1mLずつ注射した後、3日後に致死率を測定し、Probit法で統計処理し、マウスLD50を求め、力価を求めた。
(1)メチオニンとポリソルベート組合の選別
従来知られたボツリヌム毒素の安定化剤の構成成分であるヒト血清アルブミン、ポリソルベートの組合でヒト血清アルブミンを代替することができる安定化剤を選別した。
表2及び表3を通じて選別されたメチオニンとポリソルベート20を凍結乾燥製剤として使用する場合、メチオニン含量の範囲は、0.01〜10mg、ポリソルベート20の含量の範囲は、0.01〜1mgに計算された。しかし、この組合の安定化剤を凍結乾燥製剤として使用する場合、30日保管後に安定性が持続せず、したがって、安定性を維持することができる追加的な安定化剤を表4のように選別した。この際、ボツリヌム毒素100ユニット、メチオニン3mg、ポリソルベート202mgを使用した。
Claims (17)
- ボツリヌム毒素、ポリソルベート及びメチオニン;及び
糖、糖アルコール及びイオン化合物よりなる群から選択された1つ以上の成分を含み、
アルブミンを含まず、及び
ボツリヌム毒素の安定性が、40℃、相対湿度70%で少なくとも30日間保持される、
薬剤学的凍結乾燥製剤。 - ボツリヌム毒素の安定性が6ヶ月間保持される、請求項1に記載の薬剤学的凍結乾燥製剤。
- ボツリヌム毒素は、ボツリヌム血清型A、B、C、D、E、F及びGよりなる群から選択されたものである、請求項1に記載の薬剤学的凍結乾燥製剤。
- ボツリヌム毒素は、複合体化タンパク質を含有しない形態または 複合体化タンパク質を含有する複合体形態である、請求項1に記載の薬剤学的凍結乾燥製剤。
- ポリソルベートは、ポリソルベート20、40、60、80または100のうちいずれか1つである、請求項1に記載の薬剤学的凍結乾燥製剤。
- ポリソルベートは、ボツリヌム毒素100ユニット当たり0.01〜2mgで含まれる、請求項1に記載の薬剤学的凍結乾燥製剤。
- メチオニンは、ボツリヌム毒素100ユニット当たり0.01〜10mgで含まれる、請求項1に記載の薬剤学的凍結乾燥製剤。
- 糖は、トレハロース、スクロース、マルトース、フルクトース、ラフィノース、ラクトース及びグルコースよりなる群から選択された1つ以上である、請求項1に記載の薬剤学的凍結乾燥製剤。
- 糖は、ボツリヌム毒素100ユニット当たり0.1〜50mgで含まれる、請求項1に記載の薬剤学的凍結乾燥製剤。
- 糖アルコールは、シクロデキストリン、マンニトール、ソルビトール、グリセロール、キシリトール及びイノシトールよりなる群から選択された1つ以上である、請求項1に記載の薬剤学的凍結乾燥製剤。
- 糖アルコールは、ボツリヌム毒素100ユニット当たり0.1〜50mgで含まれる、請求項1に記載の薬剤学的凍結乾燥製剤。
- イオン化合物は、塩化ナトリウム、リン酸ナトリウム、リン酸アンモニウム、硫酸マグネシウム、酢酸ナトリウム、乳酸ナトリウム、コハク酸ナトリウム、プロピオン酸ナトリウム及びリン酸カリウムよりなる群から選択された1つ以上である、請求項1に記載の薬剤学的凍結乾燥製剤。
- イオン化合物は、ボツリヌム毒素100ユニット当たり0.1〜10mgで含まれる、請求項1に記載の薬剤学的凍結乾燥製剤。
- ボツリヌム毒素、ポリソルベート、メチオニン、糖及びイオン化合物を含み、アルブミンを含まず、及びボツリヌム毒素の安定性が、40℃、相対湿度70%で少なくとも30日間保持される、薬剤学的凍結乾燥製剤。
- ボツリヌム毒素の安定性が6ヶ月間保持される、請求項14に記載の薬剤学的凍結乾燥製剤。
- ボツリヌム毒素、ポリソルベート20、メチオニン、スクロース及び塩化ナトリウムを含み、アルブミンを含まず、及びボツリヌム毒素の安定性が、40℃、相対湿度70%で少なくとも30日間保持される、薬剤学的凍結乾燥製剤。
- ボツリヌム毒素の安定性が6ヶ月間保持される、請求項16に記載の薬剤学的凍結乾燥製剤。
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR20110029577 | 2011-03-31 | ||
KR10-2011-0029577 | 2011-03-31 | ||
KR1020120033374A KR101395064B1 (ko) | 2011-03-31 | 2012-03-30 | 보톨리눔 독소의 동결건조제제 |
KR10-2012-0033374 | 2012-03-30 |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2015202730A Division JP6005239B2 (ja) | 2011-03-31 | 2015-10-14 | ボツリヌム毒素の凍結乾燥製剤 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2016199599A JP2016199599A (ja) | 2016-12-01 |
JP6173547B2 true JP6173547B2 (ja) | 2017-08-02 |
Family
ID=47282510
Family Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2014502485A Active JP5826914B2 (ja) | 2011-03-31 | 2012-03-30 | ボツリヌム毒素の凍結乾燥製剤 |
JP2015202730A Active JP6005239B2 (ja) | 2011-03-31 | 2015-10-14 | ボツリヌム毒素の凍結乾燥製剤 |
JP2016173874A Active JP6173547B2 (ja) | 2011-03-31 | 2016-09-06 | ボツリヌム毒素の凍結乾燥製剤 |
Family Applications Before (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2014502485A Active JP5826914B2 (ja) | 2011-03-31 | 2012-03-30 | ボツリヌム毒素の凍結乾燥製剤 |
JP2015202730A Active JP6005239B2 (ja) | 2011-03-31 | 2015-10-14 | ボツリヌム毒素の凍結乾燥製剤 |
Country Status (22)
Country | Link |
---|---|
US (3) | US8920795B2 (ja) |
EP (3) | EP3241547B1 (ja) |
JP (3) | JP5826914B2 (ja) |
KR (1) | KR101395064B1 (ja) |
CN (2) | CN103596580A (ja) |
AU (2) | AU2012233845B2 (ja) |
BR (1) | BR112013025256B1 (ja) |
CA (1) | CA2831908C (ja) |
CO (1) | CO6821888A2 (ja) |
DK (2) | DK2692350T4 (ja) |
ES (2) | ES2810098T3 (ja) |
HK (1) | HK1246174A1 (ja) |
HU (1) | HUE050037T2 (ja) |
IL (1) | IL228607B (ja) |
MX (2) | MX355771B (ja) |
PL (2) | PL3241547T3 (ja) |
PT (1) | PT3241547T (ja) |
RU (2) | RU2574011C2 (ja) |
SG (3) | SG194039A1 (ja) |
SI (1) | SI3241547T1 (ja) |
WO (1) | WO2012134240A2 (ja) |
ZA (1) | ZA201308115B (ja) |
Families Citing this family (27)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2578250C (en) * | 2004-07-26 | 2013-03-05 | Merz Pharma Gmbh & Co. Kgaa | Therapeutic composition with a botulinum neurotoxin |
US8323666B2 (en) * | 2005-08-01 | 2012-12-04 | Allergan, Inc. | Botulinum toxin compositions |
KR101087017B1 (ko) * | 2007-07-10 | 2011-12-09 | (주)메디톡스 | 보툴리눔 독소의 안정성이 개선된 약제학적 액상 조성물 |
KR102005930B1 (ko) | 2008-12-31 | 2019-07-31 | 레반스 테라퓨틱스, 아이엔씨. | 주사용 보툴리눔 독소 제제 |
BRPI1015938A2 (pt) | 2009-06-25 | 2016-09-27 | Revance Therapeutics Inc | formulações da toxina botulínica livre de albumina |
RU2574011C2 (ru) * | 2011-03-31 | 2016-01-27 | Меди-Токс Инк. | Лиофилизированный препарат ботулотоксина |
US9480731B2 (en) * | 2013-12-12 | 2016-11-01 | Medy-Tox, Inc. | Long lasting effect of new botulinum toxin formulations |
KR20170093780A (ko) | 2014-09-02 | 2017-08-16 | 아메리칸 실버, 엘엘씨 | 보툴리눔 톡신 및 콜로이드 은 입자 |
JP6781508B2 (ja) * | 2014-11-18 | 2020-11-04 | 塩野義製薬株式会社 | 安定化されたペプチド組成物 |
KR101737387B1 (ko) | 2015-06-01 | 2017-05-18 | 유용우 | 2차 발효 홍삼을 이용한 건강기능식품의 제조방법 |
MX2018008855A (es) * | 2016-03-02 | 2018-11-29 | Merz Pharma Gmbh & Co Kgaa | Composicion que comprende toxina botulinica. |
CN109803672A (zh) | 2016-09-13 | 2019-05-24 | 阿勒根公司 | 稳定的非蛋白质梭菌毒素组合物 |
KR101744900B1 (ko) | 2017-01-20 | 2017-06-08 | 주식회사 대웅 | 보툴리눔 독소를 포함하는 안정한 액상 조성물 |
CN107540732B (zh) * | 2017-08-31 | 2020-07-14 | 青海省畜牧兽医科学院 | 一种d型肉毒毒素的仿生矿化加工方法及应用 |
KR101968873B1 (ko) * | 2018-09-21 | 2019-04-29 | 아이큐어 주식회사 | 세포 침투 효과가 우수한 보툴리늄 유래 펩타이드를 포함하는 화장료 조성물 |
WO2020111852A1 (ko) * | 2018-11-30 | 2020-06-04 | 주식회사 휴온스글로벌 | 보툴리눔 독소의 안정화 액상 조성물 |
KR102259423B1 (ko) * | 2018-11-30 | 2021-06-02 | 주식회사 휴온스바이오파마 | 보툴리눔 독소의 안정화 액상 조성물 |
CN113573727A (zh) | 2019-02-21 | 2021-10-29 | 梅尔兹制药公司 | 肉毒神经毒素用于治疗震颤的新用途 |
CN110637814B (zh) * | 2019-10-22 | 2021-11-19 | 青海省畜牧兽医科学院 | 一种d型肉毒毒素的微囊化制备方法 |
WO2021086123A1 (ko) * | 2019-10-31 | 2021-05-06 | 휴젤㈜ | 보툴리눔 독소에 대한 마이크로 구조체 제형화 기술 |
EP4186520A4 (en) | 2020-07-23 | 2024-05-01 | Medytox Inc. | THERAPEUTIC AGENT AGAINST CANCER |
KR102414997B1 (ko) * | 2020-09-29 | 2022-06-29 | 주식회사 엘지생활건강 | 안정성이 개선된 재조합 보툴리눔 독소 경쇄 단백질 조성물 |
KR20220114183A (ko) * | 2021-02-08 | 2022-08-17 | 주식회사 대웅 | 장기 저장이 가능한 보툴리눔 독소 동결건조 제형 조성물 |
KR20230001254A (ko) | 2021-06-28 | 2023-01-04 | (주)메디톡스 | 재조합 보툴리눔 독소 타입 a 경쇄, 재조합 보툴리눔 독소 및 이의 조성물, 용도 및 방법 |
KR20230001260A (ko) | 2021-06-28 | 2023-01-04 | (주)메디톡스 | 재조합 보툴리눔 독소 타입 a 경쇄, 재조합 보툴리눔 독소 및 이의 조성물, 용도 및 방법 |
KR102427362B1 (ko) | 2021-11-11 | 2022-08-01 | (주)이니바이오 | 보툴리눔 독소 제제의 건조 공정 |
WO2023085849A1 (ko) * | 2021-11-15 | 2023-05-19 | (주)메디톡스 | 보툴리눔 독소 조성물 |
Family Cites Families (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5756468A (en) * | 1994-10-13 | 1998-05-26 | Wisconsin Alumni Research Foundation | Pharmaceutical compositions of botulinum toxin or botulinum neurotoxin and methods of preparation |
CN1258379C (zh) | 2000-02-08 | 2006-06-07 | 阿勒根公司 | 肉毒杆菌毒素药物组合物 |
US20030118598A1 (en) | 2000-02-08 | 2003-06-26 | Allergan, Inc. | Clostridial toxin pharmaceutical compositions |
DE10333317A1 (de) | 2003-07-22 | 2005-02-17 | Biotecon Therapeutics Gmbh | Formulierung für Proteinarzneimittel ohne Zusatz von humanem Serumalbumin (HSA) |
GB2416122A (en) * | 2004-07-12 | 2006-01-18 | Ipsen Ltd | Botulinum neurotoxin composition |
US8323666B2 (en) * | 2005-08-01 | 2012-12-04 | Allergan, Inc. | Botulinum toxin compositions |
US8137677B2 (en) * | 2005-10-06 | 2012-03-20 | Allergan, Inc. | Non-protein stabilized clostridial toxin pharmaceutical compositions |
CN101175478A (zh) * | 2005-10-06 | 2008-05-07 | 阿勒根公司 | 非蛋白稳定的梭菌毒素药物组合物 |
MX2009012990A (es) * | 2007-06-01 | 2010-04-01 | Merz Pharma Gmbh & Co Kgaa | Proceso para proporcionar un relajante muscular estable a la temperatura sobre la base del componente neurotoxico de toxina botulinica. |
KR101087017B1 (ko) * | 2007-07-10 | 2011-12-09 | (주)메디톡스 | 보툴리눔 독소의 안정성이 개선된 약제학적 액상 조성물 |
CN105833254A (zh) * | 2008-12-10 | 2016-08-10 | 阿勒根公司 | 梭菌毒素药物组合物 |
KR101135449B1 (ko) * | 2009-03-10 | 2012-04-13 | 한국과학기술연구원 | 헤파라나제 활성 측정용 이온 복합체 나노 입자 및 그 제조방법 |
EP2248518B1 (en) * | 2009-04-17 | 2013-01-16 | Merz Pharma GmbH & Co. KGaA | Formulation for stabilizing proteins, peptides or mixtures thereof. |
RU2574011C2 (ru) * | 2011-03-31 | 2016-01-27 | Меди-Токс Инк. | Лиофилизированный препарат ботулотоксина |
US8617569B2 (en) * | 2012-03-12 | 2013-12-31 | William J. Binder | Treatment of migraine headache with diffusion of toxin in non-muscle related foraminal sites |
-
2012
- 2012-03-30 RU RU2013148119/15A patent/RU2574011C2/ru active
- 2012-03-30 MX MX2016004606A patent/MX355771B/es unknown
- 2012-03-30 US US14/008,326 patent/US8920795B2/en active Active
- 2012-03-30 ES ES17168989T patent/ES2810098T3/es active Active
- 2012-03-30 EP EP17168989.6A patent/EP3241547B1/en active Active
- 2012-03-30 SG SG2013073622A patent/SG194039A1/en unknown
- 2012-03-30 KR KR1020120033374A patent/KR101395064B1/ko active IP Right Grant
- 2012-03-30 MX MX2013011119A patent/MX338436B/es active IP Right Grant
- 2012-03-30 DK DK12765216.2T patent/DK2692350T4/da active
- 2012-03-30 ES ES12765216T patent/ES2636680T5/es active Active
- 2012-03-30 BR BR112013025256-1A patent/BR112013025256B1/pt active IP Right Grant
- 2012-03-30 HU HUE17168989A patent/HUE050037T2/hu unknown
- 2012-03-30 SG SG10202013124XA patent/SG10202013124XA/en unknown
- 2012-03-30 SI SI201231811T patent/SI3241547T1/sl unknown
- 2012-03-30 WO PCT/KR2012/002418 patent/WO2012134240A2/ko active Application Filing
- 2012-03-30 SG SG10201605324PA patent/SG10201605324PA/en unknown
- 2012-03-30 CN CN201280016784.6A patent/CN103596580A/zh active Pending
- 2012-03-30 PL PL17168989T patent/PL3241547T3/pl unknown
- 2012-03-30 EP EP20172705.4A patent/EP3756656B1/en active Active
- 2012-03-30 RU RU2015150422A patent/RU2640922C1/ru active
- 2012-03-30 JP JP2014502485A patent/JP5826914B2/ja active Active
- 2012-03-30 CN CN201910264812.XA patent/CN109925284A/zh active Pending
- 2012-03-30 AU AU2012233845A patent/AU2012233845B2/en active Active
- 2012-03-30 EP EP12765216.2A patent/EP2692350B2/en active Active
- 2012-03-30 DK DK17168989.6T patent/DK3241547T3/da active
- 2012-03-30 PT PT171689896T patent/PT3241547T/pt unknown
- 2012-03-30 CA CA2831908A patent/CA2831908C/en active Active
- 2012-03-30 PL PL12765216.2T patent/PL2692350T5/pl unknown
-
2013
- 2013-09-29 IL IL228607A patent/IL228607B/en active IP Right Grant
- 2013-10-29 CO CO13256647A patent/CO6821888A2/es not_active Application Discontinuation
- 2013-10-30 ZA ZA2013/08115A patent/ZA201308115B/en unknown
-
2014
- 2014-11-05 US US14/533,735 patent/US9198958B2/en active Active
-
2015
- 2015-10-14 JP JP2015202730A patent/JP6005239B2/ja active Active
- 2015-11-30 US US14/954,261 patent/US20160089442A1/en not_active Abandoned
-
2016
- 2016-02-19 AU AU2016201040A patent/AU2016201040B2/en active Active
- 2016-09-06 JP JP2016173874A patent/JP6173547B2/ja active Active
-
2018
- 2018-05-03 HK HK18105697.5A patent/HK1246174A1/zh unknown
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6173547B2 (ja) | ボツリヌム毒素の凍結乾燥製剤 | |
US10293034B2 (en) | Pharmaceutical liquid composition of botulinum toxin with improved stability and method of use | |
BRPI0613001B1 (pt) | Composições farmacêuticas de toxina clostrídica estabilizada por uma não-proteína | |
JPS63230085A (ja) | 安定なフラクト−スデヒドロゲナ−ゼ組成物 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20161006 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20161011 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20170605 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20170704 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6173547 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |