JP2008120836A - 増大したバイオアベイラビリティーを有する抗真菌組成物 - Google Patents
増大したバイオアベイラビリティーを有する抗真菌組成物 Download PDFInfo
- Publication number
- JP2008120836A JP2008120836A JP2008036719A JP2008036719A JP2008120836A JP 2008120836 A JP2008120836 A JP 2008120836A JP 2008036719 A JP2008036719 A JP 2008036719A JP 2008036719 A JP2008036719 A JP 2008036719A JP 2008120836 A JP2008120836 A JP 2008120836A
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- Japan
- Prior art keywords
- suspension
- liquid
- liquid suspension
- posaconazole
- effective amount
- 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.)
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Classifications
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- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/64—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with three nitrogen atoms as the only ring hetero atoms
- A01N43/647—Triazoles; Hydrogenated triazoles
- A01N43/653—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
-
- 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
- A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
- A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
-
- 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
- A61K9/10—Dispersions; Emulsions
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/10—Antimycotics
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
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Abstract
【解決手段】化学構造式(I)によって示される、抗真菌的に有効量の微粉化化合物、少なくとも1種の濃厚剤、非イオン性界面活性剤、および薬学的に受容可能な液体キャリアを含む液体懸濁物が開示される。この液体懸濁物の形態は、経口投与に適切な薬学的組成物を見出し、この薬学的組成物は、従来技術を越える重要な利点を提供する。本発明の液体懸濁物の利点としては、懸濁物の改善された均質性および懸濁物の分散の容易さが挙げられる。本発明の液体懸濁物中で安定である固形物は、再分散するのが困難な固体ケーキを形成しない。
【選択図】なし
Description
本発明は、以下の化学構造式I:
本発明者らは、ポサコナゾール(posaconazole)の微粉化粒子、以下の化学構造式I:
したがって、本発明は、以下を提供する。
(1) 液体懸濁物であって、該液体懸濁物は、以下の化学構造式I:
(2) 前記少なくとも1種の非イオン性界面活性剤が、エチレンオキシドおよびプロピレンオキシドのブロックコポリマー、飽和または不飽和のC8〜C20酸のグリコールエステルまたはグリセリルエステル、飽和または不飽和のC8〜C20酸のポリオキシエチレンエステル、飽和または不飽和のC8〜C20酸のポリオキシエチレンエーテル、飽和または不飽和のC10〜C20酸のポリビニルアルコールまたはソルビタンエステルである、項目1に記載の液体懸濁物。
(3) 前記少なくとも1種の非イオン性界面活性剤が、飽和または不飽和のC10〜C20酸のソルビタンエステルのポリオキシエチレン誘導体である、項目1に記載の液体懸濁物。
(4) 前記少なくとも1種の濃厚剤が、キサンタンガム、液糖、澱粉、セルロースおよびそれらの混合物から選択される、項目1に記載の液体懸濁物。
(5) キサンタンガムおよび液糖の組み合わせが、前記少なくとも1種の濃厚剤として使用される、項目1に記載の液体懸濁物。
(6) 前記式Iの微粉化化合物が、約1200nm〜約1600nmの平均粒径を有する、項目1に記載の液体懸濁物。
(7) 液体懸濁物であって、該液体懸濁物が、以下:
(a)以下の化学構造式I:
(b)少なくとも1種の有効量の濃厚剤;
(c)約4.0〜約6.0の範囲内に緩衝系pHを維持するために有効な量の緩衝系;
(d)少なくとも1種の有効量の非イオン性界面活性剤;および
(e)薬学的に受容可能な液体キャリア
を含む、液体懸濁物。
(8) 前記少なくとも1種の非イオン性界面活性剤が、飽和または非飽和のC10〜C20酸のソルビタンエステルのポリオキシエチレン誘導体である、項目7に記載の液体懸濁物。
(9) 前記ソルビタンエステルが、ソルビタンモノラウレート、ソルビタンモノオレアート、ソルビタンセスキオレアート、ソルビタントリオレアート、ソルビタンモノパルミテート、ソルビタンモノステアラートおよびソルビタントリステアラート、またはそれらの混合物から選択される、ソルビタンの脂肪酸エステルである、項目7に記載の液体懸濁物。
(10) 前記少なくとも1種の濃厚剤が、ガム、液糖、澱粉、セルロースおよびそれらの混合物から選択される、項目7に記載の液体懸濁物。
(11) キサンタンガムおよび液糖の組み合わせが、前記少なくとも1種の濃厚剤として使用される、項目7に記載の液体懸濁物。
(12) キサンタンガムおよび液体グルコースの組み合わせが、前記濃厚剤として使用される、項目7に記載の液体懸濁物。
(13) 前記緩衝系が、クエン酸ナトリウムおよびクエン酸を含む、項目7に記載の液体懸濁物。
(14) 前記薬学的に受容可能な液体キャリアが、精製水、グルコース、およびグリセリンの組み合わせである、項目7に記載の液体懸濁物。
(15) 前記式Iの微粉化化合物が、約1200nm〜約1600nmの平均粒径を有する、項目7に記載の液体懸濁物。
(16) 液体懸濁物であって、該液体懸濁物が、以下:
(a)以下の化学構造式I:
ここで該式Iの微粉化化合物が、約1200nm〜約1600nmの範囲内の平均粒径を有する、微粉化化合物、
(b)飽和または不飽和のC12〜C18酸のソルビタンエステルの、有効量のポリオキシエチレン誘導体;
(c)約4.0〜約6.0の範囲内にpHを維持するに十分な、有効量の緩衝系;
(d)2種の濃厚剤の、有効量の組み合わせであって、ここで一方が液糖である、組み合わせ;および
(e)薬学的に受容可能な液体キャリア
を含む、液体懸濁物。
(17)以下の化学構造式I:
(18) 懸濁物であって、該懸濁物が、薬学的に受容可能な液体キャリア中に、抗真菌的に有効量の、以下の化学構造式I:
(19) 組成物であって、該組成物が、以下の構造式I:
む物質の組成物。
(20)懸濁物中に、以下の化学構造式I:
本発明は、薬学的に受容可能な液体キャリア中にある抗真菌性化合物ポサコナゾール(posaconazole)の微粉化粒子の安定な懸濁液を提供する。本発明の懸濁液は、25℃で3日間よりも長い間静置して貯蔵した場合、沈澱することなく安定である。(以下の表1を参照のこと)。
オキシドのブロックコポリマー、飽和もしくは不飽和のC8〜C20酸のグリコールエステルまたはグリセリルエステル、飽和もしくは不飽和のC8〜C20酸のポリオキシエチレンエステル、飽和もしくは不飽和のC8〜C20酸のポリオキシエチレンエーテル、ならびに飽和もしくは不飽和のC10〜C20酸のポリビニルアルコールまたはソルビタンエステルが挙げられる。好ましくは、この非イオン性界面活性剤は、飽和または不飽和のC10〜C20酸のソルビタンエステルであり、そしてより好ましくは、このソルビタンエステルは、ソルビタンモノラウレート、ソルビタンモノオレアート、ソルビタンセスキオレアート、ソルビタントリオレアート、ソルビタンモノパルミテート、ソルビタンモノステアラートおよびソルビタントリステアラート、またはそれらの混合物から選択されるソルビタンの脂肪酸エステルである。
bは、約20〜約60、より好ましくは、約20〜約56;または約20〜27にわたる整数である。
の市販の薬剤が挙げられる。キサンタンガム、液糖(liquid sugar)、デンプン、セルロース、およびこれらの混合物は、好ましい増粘剤である。より好ましいのは、キサンタンガムおよび液糖の組み合わせであり、そして最も好ましくは、キサンタンガム、NFおよびグルコース、NFの組み合わせである。好ましくは、キサンタンガムが、約1mg/ml〜約5mg/mlの量で存在し、そしてより好ましくは、キサンタンガムが、約3mg/mlの量で存在する。好ましくは、グルコースNFは、約200〜約500mg/ml、そしてより好ましくは、約350mg/mlの量で存在する。本発明の増粘剤の有効量は、約1〜約500mg/ml、より好ましくは、約200〜約500mg/ml、最も好ましくは、約353mg/mlであり得る。本発明の増粘剤は、最小限の攪拌で構成した後、処方物の懸濁を容易にし、そして長時間にわたって懸濁液の迅速な沈澱およびケーキ形成を防止する。
実施例2は、実施例1の手順を用いて調製した本発明の範囲内での処方物の別の例であり、そしてpH4.5を有する。
能および均質性の両方の容易さを有する。
)として定義する。
ここでC(tf)は、時間(tf)で線形回帰から決定された推定の濃度である。
CL=用量/AUC(I)
分布の見掛けの容積(Vdarea/F)を、末期の速度定数(K)に対する全身クリアランスの速度から計算した。
Claims (1)
- 明細書に記載の発明。
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AR033096A1 (es) | 2003-12-03 |
CA2443089C (en) | 2011-11-01 |
PL363965A1 (en) | 2004-11-29 |
NZ528363A (en) | 2005-04-29 |
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NO20034419D0 (no) | 2003-10-02 |
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HUP0400856A2 (hu) | 2004-08-30 |
PL212985B1 (pl) | 2012-12-31 |
WO2002080678A1 (en) | 2002-10-17 |
US20030055067A1 (en) | 2003-03-20 |
CA2443089A1 (en) | 2002-10-17 |
PE20020994A1 (es) | 2002-11-01 |
JP4308902B2 (ja) | 2009-08-05 |
KR20030087052A (ko) | 2003-11-12 |
HUP0400856A3 (en) | 2012-09-28 |
CN1499930A (zh) | 2004-05-26 |
NO20034419L (no) | 2003-12-02 |
TWI311464B (en) | 2009-07-01 |
US8263600B2 (en) | 2012-09-11 |
EP2090165A2 (en) | 2009-08-19 |
EP2090165A3 (en) | 2012-03-28 |
JP2004527525A (ja) | 2004-09-09 |
KR100607742B1 (ko) | 2006-08-01 |
ZA200307684B (en) | 2005-03-30 |
BR0208626A (pt) | 2004-03-09 |
CN100415234C (zh) | 2008-09-03 |
AU2002257104B2 (en) | 2006-02-09 |
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