JP6271443B2 - 制御放出組成物およびその使用方法 - Google Patents
制御放出組成物およびその使用方法 Download PDFInfo
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- JP6271443B2 JP6271443B2 JP2014558711A JP2014558711A JP6271443B2 JP 6271443 B2 JP6271443 B2 JP 6271443B2 JP 2014558711 A JP2014558711 A JP 2014558711A JP 2014558711 A JP2014558711 A JP 2014558711A JP 6271443 B2 JP6271443 B2 JP 6271443B2
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
- A61K31/542—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with heterocyclic ring systems
- A61K31/545—Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins, cefaclor, or cephalexine
- A61K31/546—Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins, cefaclor, or cephalexine containing further heterocyclic rings, e.g. cephalothin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
- A61J3/00—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms
-
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Description
−活性薬剤の制御可能な放出プロファイル
−例えば、動物の授乳期中の乳房炎などの状態の治療における短い出荷制限期間(WHP);
−貯蔵後または投与前の良好な再分散性
−注入または他の投与方法の容易さ
−治療領域への組成物の良好な分布
−任意の疾患または状態の治療または予防用の異なる活性薬剤と一緒の使用に適合させることができ、さらに、その活性薬剤の制御および/または持続放出に適合可能な組成物基剤
−異なる治療計画(すなわち、異なる制御放出プロファイル)に対応できるように適合可能な組成物基剤、および/または
−製造の容易さ、および薬学的に許容可能な賦形剤が使用可能であること、
が挙げられ得る。
所定量のコロイド状シリカ
少なくとも1種の油および
少なくとも1種の界面活性剤、
を含有する基剤と、を含有し、
組成物の粘度は、100 1/sの剪断速度と20℃の温度において1000mPas未満である。
−例えば、治療期間中、活性薬剤濃度をMIC90超に維持するのに使用できる活性薬剤の制御可能な放出プロファイル
−注入、再分散および/または乳房中の良好な分布を容易にする低粘度、および/または
−他の現在入手可能な乳房炎組成物に比べてより短いWHP、
の提供に役立つためである。
活性薬剤
好ましくは、活性薬剤は、抗生物質、抗生物質の組み合わせ、または非抗生物質活性薬剤と組み合わせた抗生物質である。本発明者らは、乳房炎の治療で有効であるという理由により、好ましい抗生物質は、クロキサシリンであることを認めている。
本明細書の全体を通して、用語のコロイド状シリカは、約1nm〜1000nm(1μm)の最大直径の単一シリカ粒子を含む粒子状無定形ヒュームドシリカを意味するものと解釈されるべきである。
本明細書の全体を通し、用語の界面活性剤は、液体の表面張力を下げる任意の化合物、2種の液体間の界面張力を下げる任意の化合物、または液体と固体との間の界面張力を下げる任意の化合物を意味すると解釈されるべきである。また、界面活性剤は、乳化剤、洗浄剤、湿潤剤、などとしての役割もできる。
多くの組成物で、油はビークルとして必要である。例えば、クロキサシリンまたはセファピリンなどの活性薬剤を含有する抗生物質組成物は、通常、油状ビークルをベースにしている。例えば、これは、組成物が乳頭管を介した注入または注射として投与されるのを容易にし、および/またはその保存可能期間中に充分な化学安定性を得るのに役立つ。
明らかに、組成物の粘度は、必要とされる特定の要求に合わせることができる。1部の組成物に対し、比較的高粘度を使用してもよい。他のものでは、増粘剤または高粘度油などの賦形剤を加えないで低粘度を維持できる。必要があれば、このような粘度調節剤も活性薬剤の放出プロファイルに寄与できる。
好ましくは、本明細書記載の組成物を使用して、授乳期中に乳房内注入により乳房炎が治療される。
本発明のさらなる態様では、大略上述された組成物を製造する方法が提供され、この方法は、
a)容器中で油と界面活性剤を混合し、均一油混合物を形成するステップと、
b)活性薬剤を油混合物中に分散させるステップと、
c)続けて、油混合物にコロイド状シリカを添加するステップと、
を含む。
コロイド状二酸化ケイ素などのヒュームドコロイド状シリカは、通常、粘度調節剤として、また特に、液体製剤の増粘剤として使用される。どのようにコロイド状シリカが使用されてきたかの一部の例を以下に示す。当技術分野で通常理解されている内容に沿って、コロイド状シリカは、組成物からの活性薬剤の放出を変えるのに役立つことが明らかにされたが、増粘剤として作用するという意味においてのみ役立つ。前に考察したように、通常、組成物が粘稠になるほど、活性薬剤の放出プロファイルが遅くなり、逆もまた同じである。これは、本発明の概念とは全く異なる。
図1は、現状市販されている参照製品に比べて、比較的低粘度の本発明の好ましい組成物を示す。本発明者らは、溶解溶媒中の回収率(図2〜6に示す)は、インビボでの放出速度を示すと考えている。
a)ミグリオール812、メチルパラベン、プロピルパラベンおよびスパン80をよく混合し、均質の油混合物を形成する。
b)混合物を140℃で3時間滅菌し、その後、室温に冷却する。
c)別の容器中に必要量のAerosilR972Pharmaを装填する。
d)140℃で3時間滅菌し、その後、室温に冷却する。
e)クロキサシリンナトリウムを滅菌油混合物中に分散し、均質化する。
f)滅菌AerosilR972Pharmaを滅菌油懸濁液中に分散させる。
g)混合物を均質化する。
2011年11月に開始した試験の一部として、詳細を下記に示す実施例18配合物のウシ乳房炎の治療での有効性を検討した。
実施例18の組成物の3つのバッチに関し安定性試験を行った。これらのバッチを、5mLのポリエチレンシリンジに充填し、25℃/60%RH、30℃/65%RHおよび40℃/75%RHの指定貯蔵温度と湿度条件で貯蔵した。ACVMにより推奨される規則的間隔でバッチの物理的および化学的特性を記録した。安定性データに基づくと、25℃の貯蔵温度で、少なくとも18ヶ月間の保存可能期間が期待される。
Claims (22)
- クロキサシリンおよびセファピリンから選択される、治療有効量の少なくとも1種の抗生物質であって、少なくとも1種の抗生物質の濃度が2%w/wから9.18%w/wである、抗生物質と、
前記少なくとも1種の抗生物質の制御放出を提供するために構成された基剤であって、
所定量の疎水性コロイド状シリカ、
少なくとも1種の油および
ソルビタンモノオレアートおよびPEG12−オレアートから選択される、少なくとも1種の界面活性剤
を含有する基剤と
を含有し、
100 1/sの剪断速度および20℃の温度において、粘度が1000mPas未満である、乳房内注入に適する組成物。 - 少なくとも1種の追加の活性薬剤を含有する、請求項1に記載の組成物。
- 前記追加の活性薬剤が非ステロイド性抗炎症剤である、請求項2に記載の組成物。
- 前記抗生物質が微粉化される、請求項1〜3のいずれか1項に記載の組成物。
- 前記疎水性コロイド状シリカが、ヒュームド疎水性コロイド状二酸化ケイ素である、請求項1〜4のいずれか1項に記載の組成物。
- 前記疎水性コロイド状シリカの濃度が、0.1〜5%w/wである、請求項1〜5のいずれか1項に記載の組成物。
- 前記疎水性コロイド状シリカの濃度が、1〜3%w/wである、請求項1〜6のいずれか1項に記載の組成物。
- 前記界面活性剤の濃度が、0.01〜10%w/wである、請求項1〜7のいずれか1項に記載の組成物。
- 前記基剤中の前記コロイド状シリカ/界面活性剤の比率が、1:100〜500:1である、請求項1〜8のいずれか1項に記載の組成物。
- 前記基剤中の前記疎水性コロイド状シリカ/界面活性剤の比率が、1:5〜6:1である、請求項1〜9のいずれか1項に記載の組成物。
- 前記基剤が、2種以上の界面活性剤を含有する、請求項1〜10のいずれか1項に記載の組成物。
- 前記油の粘度が、20℃において1〜100mPasである、請求項1〜11のいずれか1項に記載の組成物。
- 前記油の粘度が、20℃において40mPas未満である、請求項1〜12のいずれか1項に記載の組成物。
- 前記油が、中鎖トリグリセリド、軽質流動パラフィン、エチルオレアートおよびゴマ油からなる群より選択される、請求項1〜13のいずれか1項に記載の組成物。
- 前記油の密度が、0.80〜0.99g/cm3である、請求項1〜14のいずれか1項に記載の組成物。
- 前記組成物の粘度が、100 1/sの剪断速度および20℃の温度において300mPas未満である、請求項1〜15のいずれか1項に記載の組成物。
- 前記組成物の粘度が、100 1/sの剪断速度および20℃の温度において150mPas未満である、請求項1〜16のいずれか1項に記載の組成物。
- 請求項1〜17のいずれか1項に記載の組成物を製造する方法であって、
a)容器中で前記油と界面活性剤を混合し、均質な油混合物を形成するステップと、
b)前記抗生物質を前記油混合物中に分散させるステップと、
c)その後、前記疎水性コロイド状シリカを前記油混合物に添加するステップと
を含む方法。 - 治療を必要としている非ヒト動物を請求項1〜17のいずれか1項に記載の組成物で治療する方法であって、前記組成物を乳房内注入により前記動物に投与するステップを含む方法。
- 5g製剤組成物の1〜6用量を0〜120時間にわたり3回×24時間または6回×24時間投与する投与計画を含む、請求項19に記載の方法。
- 非ヒト動物の授乳期中の乳房炎の治療または予防のための、請求項19または20のいずれかに記載の方法。
- 治療または予防を必要としている動物の前臨床もしくは臨床型乳房炎の治療または予防のための、請求項1〜17のいずれか1項に記載の組成物。
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KR (1) | KR102100271B1 (ja) |
CN (2) | CN104244983A (ja) |
AU (1) | AU2013201147A1 (ja) |
BR (1) | BR112014021218A2 (ja) |
CA (1) | CA2865555C (ja) |
CL (1) | CL2014002227A1 (ja) |
CO (1) | CO7061074A2 (ja) |
CR (1) | CR20140396A (ja) |
DK (1) | DK2819699T3 (ja) |
DO (1) | DOP2014000195A (ja) |
ES (1) | ES2740958T3 (ja) |
HR (1) | HRP20191412T1 (ja) |
HU (1) | HUE045495T2 (ja) |
MX (1) | MX366726B (ja) |
NI (1) | NI201400096A (ja) |
PH (1) | PH12014501919A1 (ja) |
PL (1) | PL2819699T3 (ja) |
PT (1) | PT2819699T (ja) |
RU (1) | RU2627429C2 (ja) |
SI (1) | SI2819699T1 (ja) |
SV (1) | SV2014004796A (ja) |
WO (1) | WO2013129944A1 (ja) |
ZA (1) | ZA201406267B (ja) |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
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MX358248B (es) * | 2012-07-17 | 2018-08-10 | Bayer New Zealand Ltd | Formulaciones antibioticas inyectables que contienen penetamato y triacetina. |
RU2019123307A (ru) * | 2017-01-20 | 2021-02-20 | М Эт П Фарма Аг | Фармацевтические композиции для назального введения для снижения рисков воздействия загрязнителей воздуха |
CN114847280A (zh) * | 2022-07-07 | 2022-08-05 | 山东实力农业股份有限公司 | 一种包含脂肽的生物刺激剂组合物的制备方法 |
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IL58462A0 (en) | 1978-10-27 | 1980-01-31 | Beecham Group Ltd | Intramammary compositions comprising a penicillin |
IL58461A0 (en) | 1978-10-27 | 1980-01-31 | Beecham Group Ltd | Intramammary compositions comprising a clavulanic acid salt |
EP0058015A3 (en) | 1981-02-05 | 1982-08-25 | Beecham Group Plc | Treatment of infections |
JPS60169431A (ja) * | 1984-02-14 | 1985-09-02 | Nippon Zenyaku Kogyo Kk | β−ラクタム環を有する化合物を含有する安定な抗菌剤及びその製造法 |
EP0212875A3 (en) | 1985-08-12 | 1988-06-15 | William Gough Tucker | Medicinal composition and method of making same |
JPS6289617A (ja) * | 1985-08-12 | 1987-04-24 | ウイリアム ガウフ タツカ− | 薬剤組成物およびその調製方法 |
GB8531609D0 (en) | 1985-12-23 | 1986-02-05 | Beecham Group Plc | Compounds |
US4980175A (en) | 1989-01-03 | 1990-12-25 | Leonard Chavkin | Liquid orally administrable compositions based on edible oils |
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US5122377A (en) | 1990-11-19 | 1992-06-16 | A.H. Robins, Company, Incorporated | Oral delivery system for veterinary drugs |
GB2338896B (en) | 1998-07-02 | 2003-05-21 | Reckitt & Colmann Prod Ltd | Chewable Capsules |
US20020009478A1 (en) | 1998-08-24 | 2002-01-24 | Douglas Joseph Dobrozsi | Oral liquid mucoadhesive compositions |
US6787342B2 (en) * | 2000-02-16 | 2004-09-07 | Merial Limited | Paste formulations |
US20040033938A1 (en) * | 2000-09-12 | 2004-02-19 | Britten Nancy J. | Cyclooxygenase-2 inhibitor and antibacterial agent combination for intramammary treatment of mastitis |
WO2003063877A1 (en) * | 2002-02-01 | 2003-08-07 | Akzo Nobel N.V. | Cefquinome composition for intra-mammary administration in cattle |
GB2398005B (en) | 2002-02-20 | 2005-09-14 | Strides Arcolab Ltd | Orally administrable pharmaceutical formulation |
AU2003269311A1 (en) * | 2002-10-08 | 2004-05-04 | Ancare New Zealand Ltd. | Antibiotic formulation for intramammary administration in milking animals |
ATE390124T1 (de) | 2002-12-16 | 2008-04-15 | Intervet Int Bv | Behandlung von mastitis mit einer kombination aus prednisolon und cephalosporin |
US7842791B2 (en) * | 2002-12-19 | 2010-11-30 | Nancy Jean Britten | Dispersible pharmaceutical compositions |
US20080153894A1 (en) * | 2002-12-19 | 2008-06-26 | Pharmacia Corporation | Cyclooxygenase-2 inhibitor and antibacterial agent combination for intramammary treatment of mastitis |
MXPA05006858A (es) | 2002-12-26 | 2005-11-23 | Solution Biosciences Inc | Composiciones y metodos para el control de mastitis bovina. |
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KR100822519B1 (ko) | 2005-02-15 | 2008-04-16 | 주식회사종근당 | 위장 내에서 제어방출되는 단일 매트릭스 정제 |
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BRPI1002601E2 (pt) * | 2010-06-01 | 2020-06-30 | Embrapa Pesquisa Agropecuaria | composição nanoestruturada de uso veterinário para administração de fármacos |
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- 2013-02-27 JP JP2014558711A patent/JP6271443B2/ja active Active
- 2013-02-27 KR KR1020147023706A patent/KR102100271B1/ko active IP Right Grant
- 2013-02-27 CN CN201380011138.5A patent/CN104244983A/zh active Pending
- 2013-02-27 CA CA2865555A patent/CA2865555C/en active Active
- 2013-02-27 PL PL13755420T patent/PL2819699T3/pl unknown
- 2013-02-27 ES ES13755420T patent/ES2740958T3/es active Active
- 2013-02-27 US US14/380,902 patent/US10828311B2/en active Active
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- 2013-02-27 BR BR112014021218-0A patent/BR112014021218A2/pt not_active Application Discontinuation
- 2013-02-27 RU RU2014135524A patent/RU2627429C2/ru active
- 2013-02-27 CN CN201910863593.7A patent/CN110604819A/zh active Pending
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- 2014-08-26 PH PH12014501919A patent/PH12014501919A1/en unknown
- 2014-08-26 CO CO14187211A patent/CO7061074A2/es unknown
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