JP7447315B2 - 注射可能な医薬組成物及びその使用 - Google Patents
注射可能な医薬組成物及びその使用 Download PDFInfo
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- JP7447315B2 JP7447315B2 JP2022570365A JP2022570365A JP7447315B2 JP 7447315 B2 JP7447315 B2 JP 7447315B2 JP 2022570365 A JP2022570365 A JP 2022570365A JP 2022570365 A JP2022570365 A JP 2022570365A JP 7447315 B2 JP7447315 B2 JP 7447315B2
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- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 1
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- 150000002334 glycols Chemical class 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- FBPFZTCFMRRESA-UHFFFAOYSA-N hexane-1,2,3,4,5,6-hexol Chemical compound OCC(O)C(O)C(O)C(O)CO FBPFZTCFMRRESA-UHFFFAOYSA-N 0.000 description 1
- 238000000265 homogenisation Methods 0.000 description 1
- 238000003898 horticulture Methods 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- 238000010191 image analysis Methods 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 206010022000 influenza Diseases 0.000 description 1
- 229960003971 influenza vaccine Drugs 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 229940102213 injectable suspension Drugs 0.000 description 1
- 230000000749 insecticidal effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
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- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 229960003511 macrogol Drugs 0.000 description 1
- 229940049920 malate Drugs 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229960003439 mebendazole Drugs 0.000 description 1
- OPXLLQIJSORQAM-UHFFFAOYSA-N mebendazole Chemical compound C=1C=C2NC(NC(=O)OC)=NC2=CC=1C(=O)C1=CC=CC=C1 OPXLLQIJSORQAM-UHFFFAOYSA-N 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 229940057917 medium chain triglycerides Drugs 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
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- BWCRYQGQPDBOAU-WZBVPYLGSA-N milbemycin D Chemical compound C1C[C@H](C)[C@@H](C(C)C)O[C@@]21O[C@H](C\C=C(C)\C[C@@H](C)\C=C\C=C/1[C@]3([C@H](C(=O)O4)C=C(C)[C@@H](O)[C@H]3OC\1)O)C[C@H]4C2 BWCRYQGQPDBOAU-WZBVPYLGSA-N 0.000 description 1
- WTERNLDOAPYGJD-SFHVURJKSA-N monepantel Chemical compound C([C@@](C)(NC(=O)C=1C=CC(SC(F)(F)F)=CC=1)C#N)OC1=CC(C#N)=CC=C1C(F)(F)F WTERNLDOAPYGJD-SFHVURJKSA-N 0.000 description 1
- 229950003439 monepantel Drugs 0.000 description 1
- 229960005121 morantel Drugs 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- YNFMRVVYUVPIAN-AQUURSMBSA-N nemadectin Chemical compound C1[C@H](O)[C@H](C)[C@@H](C(/C)=C/C(C)C)O[C@]11O[C@H](C\C=C(C)\C[C@@H](C)\C=C\C=C/2[C@]3([C@H](C(=O)O4)C=C(C)[C@@H](O)[C@H]3OC\2)O)C[C@H]4C1 YNFMRVVYUVPIAN-AQUURSMBSA-N 0.000 description 1
- 229950009729 nemadectin Drugs 0.000 description 1
- YNFMRVVYUVPIAN-UHFFFAOYSA-N nemadectin alpha Natural products C1C(O)C(C)C(C(C)=CC(C)C)OC11OC(CC=C(C)CC(C)C=CC=C2C3(C(C(=O)O4)C=C(C)C(O)C3OC2)O)CC4C1 YNFMRVVYUVPIAN-UHFFFAOYSA-N 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229960001920 niclosamide Drugs 0.000 description 1
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- SVMGVZLUIWGYPH-UHFFFAOYSA-N nitroscanate Chemical compound C1=CC([N+](=O)[O-])=CC=C1OC1=CC=C(N=C=S)C=C1 SVMGVZLUIWGYPH-UHFFFAOYSA-N 0.000 description 1
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- SGKGVABHDAQAJO-UHFFFAOYSA-N nitroxynil Chemical compound OC1=C(I)C=C(C#N)C=C1[N+]([O-])=O SGKGVABHDAQAJO-UHFFFAOYSA-N 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
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- 239000003921 oil Substances 0.000 description 1
- 229960005030 other vaccine in atc Drugs 0.000 description 1
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- BEZZFPOZAYTVHN-UHFFFAOYSA-N oxfendazole Chemical compound C=1C=C2NC(NC(=O)OC)=NC2=CC=1S(=O)C1=CC=CC=C1 BEZZFPOZAYTVHN-UHFFFAOYSA-N 0.000 description 1
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- JYWIYHUXVMAGLG-UHFFFAOYSA-N oxyclozanide Chemical compound OC1=C(Cl)C=C(Cl)C=C1NC(=O)C1=C(O)C(Cl)=CC(Cl)=C1Cl JYWIYHUXVMAGLG-UHFFFAOYSA-N 0.000 description 1
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- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
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- 229920001606 poly(lactic acid-co-glycolic acid) Polymers 0.000 description 1
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- QZWHWHNCPFEXLL-UHFFFAOYSA-N propan-2-yl n-[2-(1,3-thiazol-4-yl)-3h-benzimidazol-5-yl]carbamate Chemical compound N1C2=CC(NC(=O)OC(C)C)=CC=C2N=C1C1=CSC=N1 QZWHWHNCPFEXLL-UHFFFAOYSA-N 0.000 description 1
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- CCSONKKTCMHYFI-UHFFFAOYSA-N pyrido[3,4-f]quinoxaline Chemical class C1=NC=C2C3=NC=CN=C3C=CC2=C1 CCSONKKTCMHYFI-UHFFFAOYSA-N 0.000 description 1
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- RNVYQYLELCKWAN-UHFFFAOYSA-N solketal Chemical compound CC1(C)OCC(CO)O1 RNVYQYLELCKWAN-UHFFFAOYSA-N 0.000 description 1
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- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
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- 229940095064 tartrate Drugs 0.000 description 1
- UWHCKJMYHZGTIT-UHFFFAOYSA-N tetraethylene glycol Chemical compound OCCOCCOCCOCCO UWHCKJMYHZGTIT-UHFFFAOYSA-N 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 150000005326 tetrahydropyrimidines Chemical class 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 239000004308 thiabendazole Substances 0.000 description 1
- 229960004546 thiabendazole Drugs 0.000 description 1
- WJCNZQLZVWNLKY-UHFFFAOYSA-N thiabendazole Chemical compound S1C=NC(C=2NC3=CC=CC=C3N=2)=C1 WJCNZQLZVWNLKY-UHFFFAOYSA-N 0.000 description 1
- 235000010296 thiabendazole Nutrition 0.000 description 1
- YFNCATAIYKQPOO-UHFFFAOYSA-N thiophanate Chemical compound CCOC(=O)NC(=S)NC1=CC=CC=C1NC(=S)NC(=O)OCC YFNCATAIYKQPOO-UHFFFAOYSA-N 0.000 description 1
- 229950007146 tigolaner Drugs 0.000 description 1
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- 238000012546 transfer Methods 0.000 description 1
- 229920000428 triblock copolymer Polymers 0.000 description 1
- 229960000323 triclabendazole Drugs 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 238000002255 vaccination Methods 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Images
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- Medicinal Preparation (AREA)
Description
(a)ミクロスフェアであって、
(a1)前記ミクロスフェアの重量に基づく約1%~約40%w/wの1以上の生理活性大環状ラクトン、及び
(a2)前記ミクロスフェアの重量に基づく約60%~約99%w/wのポリカプロラクトン(polycaprolactone:PCL)
を含む、ミクロスフェア、
(b)式(I)のイソオキサゾリン化合物の粒子であって、
R1=ハロゲン、CF3、OCF3、CN、
n=0~3、好ましくは1、2又は3の整数、
R2=C1~C3-ハロアルキル、好ましくはCF3又はCF2Cl、
T=1以上の基Yで置換されていてもよい5~12員の単環式環系又は二環式環系、
Y=メチル、ハロメチル、ハロゲン、CN、NO2、NH2-C=S、又は2つの隣接する基Yが一緒になって、鎖、とりわけ3員鎖又は4員鎖を形成し;
Q=X-NR3R4、又は、1以上の基で置換されていてもよい5員N-ヘテロアリール環;
X=CH2、CH(CH3)、CH(CN)、CO、CS、
R3=水素、メチル、ハロエチル、ハロプロピル、ハロブチル、メトキシメチル、メトキシエチル、ハロメトキシメチル、エトキシメチル、ハロエトキシメチル、プロポキシメチル、エチルアミノカルボニルメチル、エチルアミノカルボニルエチル、ジメトキシエチル、プロピニルアミノカルボニルメチル、N-フェニル-N-メチル-アミノ、ハロエチルアミノカルボニルメチル、ハロエチルアミノカルボニルエチル、テトラヒドロフリル、メチルアミノカルボニルメチル、(N,N-ジ-メチルアミノ)-カルボニルメチル、プロピルアミノカルボニルメチル、シクロプロピルアミノカルボニルメチル、プロペニルアミノカルボニルメチル、ハロエチルアミノカルボニルシクロプロピル、
R4=水素、エチル、メトキシメチル、ハロメトキシメチル、エトキシメチル、ハロエトキシメチル、プロポキシメチル、メチルカルボニル、エチルカルボニル、プロピルカルボニル、シクロプロピルカルボニル、メトキシカルボニル、メトキシメチルカルボニル、アミノカルボニル、エチルアミノカルボニルメチル、エチルアミノカルボニルエチル、ジメトキシエチル、プロピニルアミノカルボニルメチル、ハロエチルアミノカルボニルメチル、シアノメチルアミノカルボニルメチル又はハロエチルアミノカルボニルエチル;又は
R3及びR4が一緒になって、
式(I)のイソオキサゾリン化合物の粒子、および
c)水性担体
を含み、
ここで、前記ミクロスフェア(a)及び前記化合物(b)の粒子が、前記水性担体(c)に懸濁されている。
i)溶媒蒸発、回転ディスク微粒化又は噴霧乾燥、および、任意に、得られた生成物のふるい分けによって、大環状ラクトンのミクロスフェア(a)を調製する工程、
ii)式(I)のイソオキサゾリン化合物の粒子を調製する工程、
iii)1以上の懸濁剤及び/又は1以上の湿潤剤を水に溶解することによって水性担体を調製する工程、並びに
iv)工程i)から得られた粒子及び工程ii)から得られたミクロスフェアを水性担体と混合する工程
を含む。
(A)上記で定義したミクロスフェアと式(I)のイソオキサゾリン化合物の粒子との混合物を含む第1の容器、
(B)上記で定義した水性担体を有する第2の容器、並びに
(C)動物への注射の前に前記水性担体において前記ミクロスフェア及び前記粒子を再構成するための指示書
を含む。
R1=ハロゲン、CF3、OCF3、CN、
n=0~3、好ましくは1、2又は3の整数、
R2=C1~C3-ハロアルキル、好ましくはCF3又はCF2Cl、
T=1以上の基Yで置換されていてもよい5~12員の単環式環系又は二環式環系、
Y=メチル、ハロメチル、ハロゲン、CN、NO2、NH2-C=S、又は2つの隣接する基Yが一緒になって、鎖、とりわけ3員鎖又は4員鎖を形成し、
Q=X-NR3R4、又は、1以上の基で置換されていてもよい5員N-ヘテロアリール環、
X=CH2、CH(CH3)、CH(CN)、CO、CS、
R3=水素、メチル、ハロエチル、ハロプロピル、ハロブチル、メトキシメチル、メトキシエチル、ハロメトキシメチル、エトキシメチル、ハロエトキシメチル、プロポキシメチル、エチルアミノカルボニルメチル、エチルアミノカルボニルエチル、ジメトキシエチル、プロピニルアミノカルボニルメチル、N-フェニル-N-メチル-アミノ、ハロエチルアミノカルボニルメチル、ハロエチルアミノカルボニルエチル、テトラヒドロフリル、メチルアミノカルボニルメチル、(N,N-ジ-メチルアミノ)-カルボニルメチル、プロピルアミノカルボニルメチル、シクロプロピルアミノカルボニルメチル、プロペニルアミノカルボニルメチル、ハロエチルアミノカルボニルシクロプロピル、
R4=水素、エチル、メトキシメチル、ハロメトキシメチル、エトキシメチル、ハロエトキシメチル、プロポキシメチル、メチルカルボニル、エチルカルボニル、プロピルカルボニル、シクロプロピルカルボニル、メトキシカルボニル、メトキシメチルカルボニル、アミノカルボニル、エチルアミノカルボニルメチル、エチルアミノカルボニルエチル、ジメトキシエチル、プロピニルアミノカルボニルメチル、ハロエチルアミノカルボニルメチル、シアノメチルアミノカルボニルメチル又はハロエチルアミノカルボニルエチル;若しくは、
R3及びR4が一緒になって、
式(I)のイソオキサゾリン化合物の粒子、及び/又は
式(II)による化合物の粒子
ここで、T-1、T-3及びT-4において、基Yは、好ましくは、水素、ハロゲン、メチル、ハロメチル、エチル又はハロエチルである。
ここで、R3、R4、X及びZAは、上記で定義した通りであり、
ZBは、
ZDは、
R1a、R1b、R1cは、互いに独立して、水素、Cl又はCF3であり、より好ましくは、R1a及びR1cは、Cl又はCF3であり、そして、R1bは、水素であり、
Tは、
ここで、Yは、メチル、Cl、Br、F、CN又はC(S)NH2であり、
Qは、上記の通りである。
本発明の別の態様は、本発明による注射可能な動物用組成物を調製する方法であり、前記方法は、以下の工程を含む;
i)式(I)のイソオキサゾリン化合物及び/又は式(II)の化合物の粒子を調製し、
ii)溶媒蒸発、回転ディスク微粒化又は噴霧乾燥によってミクロスフェア(a)を調製し、得られた生成物をふるい分けし、
iii)1以上の懸濁剤及び/又は1以上の湿潤剤と水とを溶解することによって水性担体を調製し、
iv)工程i)から得られた粒子及び工程ii)から得られたミクロスフェアを水性担体に添加するか、又はその逆に添加する。
工程i)において、式(I)のイソオキサゾリン化合物及び/又は式(II)の化合物の粒子が調製される。当該粒子は、例えば、国際公開第2019/091940号に記載されている方法に従って調製され得る。
工程ii)において、ミクロスフェア(a)は、溶媒蒸発、回転ディスク微粒化又は噴霧乾燥によって、そして、任意に、得られた生成物をふるい分けすることによって、調製される。
工程iii)において、水性担体は、1以上の懸濁剤及び/又は1以上の湿潤剤と、任意の他の賦形剤とを水に溶解することによって調製される。1以上の懸濁剤及び/又は1以上の湿潤剤と、任意の生理学的に許容されるさらなる賦形剤(類)とが、水に、又は水及び水混和性液体に、好ましくは水に懸濁されることが好ましい。水混和性液体に関しては、上記と同じである。
(A)第1の容器であって、
請求項1から14のいずれか一項に記載のミクロスフェアと、請求項1から14のいずれか一項に記載の式(I)のイソオキサゾリン化合物及び/又は請求項1から14のいずれか一項に記載の式(II)の化合物の粒子との混合物を含む、第1の容器、
(B)1以上の湿潤剤及び/又は1以上の懸濁剤と水とを含む水性担体を有する第2の容器、および、
(C)請求項1から14のいずれか一項に記載のミクロスフェアと、請求項1から14のいずれか一項に記載の式(I)のイソオキサゾリン化合物又は請求項1から14のいずれか一項に記載の式(II)の化合物の粒子とを、注射前に前記水性担体を用いて再構成するための指示書
を含む。
本発明の別の態様は、動物での寄生生物の侵襲を処置及び/又は予防するのに使用するための、本発明の注射可能な動物用組成物である。本発明の組成物は、注射によって非経口投与される。
11.25gのポリビニルアルコールを1500mLの脱イオン水に溶解した。別途、4.5gのポリカプロラクトン及び0.5gのモキシデクチンを、50mLのジクロロメタンに溶解した。330rpm及び20℃で上記の水溶液をオーバーヘッド撹拌しながら、ジクロロメタンを含む溶液をこの水溶液に滴下した。得られたエマルジョンを4時間撹拌した。ミクロスフェアを75μmのふるいで単離し、脱イオン水ですすいだ後、室温で風乾した。
6.0gのモキシデクチン及び54.0gのポリカプロラクトンを、690mLのジクロロメタンに溶解し、そして、4℃に冷却した。この溶液を、150g/分で、30フィートの高さから2500rpmで回転する直径4インチのカスタムディスク上に供給した。微粒化空間を19℃に冷却した。得られた粒子を収集し、420μmのふるい、次いで250μmのふるいを通過させてミクロスフェアを得た。
2.5gのモキシデクチン及び22.5gのポリカプロラクトンを、475mLのアセトンに溶解し、そして、4℃に冷却した。カスタムステンレス鋼回転ディスク微粒化チャンバ(直径約4フィートの円錐体)を35℃に加熱した。その微粒化チャンバには、上部中央にディスクが収容され、回転しており、円錐体の底部にサイクロン収集器が接続されている。約5000rpmで回転する直径3インチのステンレス鋼ディスク上に、上記の溶液を50g/分でポンプ輸送した。得られた粒子を収集してミクロスフェアを得た。
37.0gのポリカプロラクトン及び4.2gのモキシデクチンを、800mLのアセトンに溶解した。その混合物を、600μm二流体ノズル(ノズル圧力3.2バール)を介して、入口温度25℃、チャンバ温度19℃及び出口温度19.54℃のPro-C-epT 4M8実験用噴霧乾燥機内に、6~7g/分で微粒化した。得られた粒子を収集してミクロスフェアを得た。
モキシデクチン及びポリカプロラクトン(PCL)を含むミクロスフェアの試料、並びにモキシデクチン薬物物質の試料を、それぞれ20mL血清バイアルに入れた。次いで、滅菌のために、モキシデクチン及びポリカプロラクトンを含むミクロスフェアに、ガンマ線及び電子ビームの両方によって15kGy、20kGy及び25kGyの照射を行った。5℃又は周囲温度(23℃)のいずれかで、窒素オーバーレイあり又はなしでミクロスフェアを滅菌した。試料をアッセイでの変化について評価した。%アッセイを非照射アッセイの%として報告した。結果を下の表1に示す。
フルララネルを、73~77℃でイソプロパノールに溶解した。溶液を濾過し、晶析装置反応器に移した。混合物を48~52℃に冷却し、シーディングした。30分間のシーディング後熟成の後、混合物を20℃に冷却した(シード床)。得られた懸濁液の一部を第二の反応器(溶解器)に移し、完全に溶解するまで、最高70℃まで加熱した。晶析装置に残ったスラリーを最高54℃まで加熱した。晶析装置の内容物を溶解器に移し、0.40BV/hの再循環定流量(バッチ体積=10V→4.0V/h)で2.5時間かけて晶析装置に戻した。溶解器から晶析装置への溶液の移動が完了したら、スラリーを54℃で5時間熟成させた。次いで、非常に遅い冷却勾配、すなわち、6時間かけて54℃から45℃まで(0.025℃/分)、15時間かけて45℃から0℃まで(3℃/時間)の冷却を開始した。スラリーを-10℃で1時間熟成させ、次いで、洗浄を施さずに濾過によって生成物を単離した。次いで、湿った生成物を乾燥させた。
16.0gのフルララネル及び16.0gのポリ(ラクチド-コ-グリコリド)50:50を、285.0gのジクロロメタンに溶解した。約3000rpmで回転している直径4インチのカスタムディスク上に、溶液を約100g/分で供給した。60°の角度が付けられた底部円錐体を有するカスタムポリエチレン正方形(4x4x4フィート)エンクロージャにディスクを取り付けた。微粒化の過程で、エンクロージャを乾燥空気で加温し、上部を54.2~54.7℃、底部を36.3~38.1℃とした。
実施例3からのモキシデクチンのミクロスフェア及び実施例7からのフルララネルの粒子を含むバイアルを、17mLの実施例6の水性担体で再構成した。再構成中、モキシデクチンのミクロスフェア及びフルララネルの粒子を含有するバイアルを、担体の添加の間、水平に保持しながら回転させた。
-サンプリング前に1分間、2分間又は3分間激しく手で振盪、
-サンプリング前に3分間激しく手で振盪し、注射器を使用して5回混合、又は、
-サンプリング前に3分間激しく手で振盪し、注射器を使用して5回混合し、そして、20秒間ボルテックスする。
[実施例10.1]
実施例1のように製造されたモキシデクチン含有ミクロスフェア、及び実施例8に示すように製造されたPLGAミクロスフェア中のフルララネルの、すぐに使用できる注射可能な懸濁液を、10mg/kg体重(body weight:BW)のフルララネル及び0.17mg/kg BWのモキシデクチンで、3匹のビーグル犬に単回皮下投与した。試験品の局所耐性を、最長84日の間隔で評価した。
実施例2及び3のように製造されたモキシデクチン含有ミクロスフェア、並びに実施例7のように製造されたフルララネル粒子の、3つの注射可能な懸濁液を、17mLの実施例6の水性担体で再構成し、15mg/kg BWのフララネル及び0.17mg/kg BWのモキシデクチンで8匹のビーグル犬に単回皮下投与した。
グループ2及びグループ3-ミクロスフェアは実施例2に相当し、この場合、グループ2は15kGで照射し、グループ3は25kGで照射した。
Claims (10)
- 注射用の動物用医薬組成物であって、該組成物は、
(a)ミクロスフェアであって、
(a1)前記ミクロスフェアの重量に基づく1%~40%w/wのモキシデクチン、及び
(a2)前記ミクロスフェアの重量に基づく60%~99%w/wのポリカプロラクトン(polycaprolactone:PCL)
を含むミクロスフェア、
(b)フルララネルの粒子、および、
(c)水性担体
を含み、
ここで、
前記ミクロスフェア(a)の体積加重粒径分布のD50が、8μm~250μmであり、
そして、
前記ミクロスフェア(a)及びフルララネル(b)の粒子が、前記水性担体(c)に懸濁されている、動物用医薬組成物。 - 水性担体が懸濁液を含み、そして、懸濁剤が、カルボキシメチルセルロースナトリウム、ポリビニルピロリドン、メチルセルロース及びそれらの混合物から選択される、請求項1に記載の動物用医薬組成物。
- 水性担体が、湿潤剤を含み、そして、湿潤剤がポロキサマーである、請求項1または2に記載の動物用医薬組成物。
- 請求項1から3のいずれか一項に記載の注射用の動物用医薬組成物を調製する方法であって、該方法は、
i)溶媒蒸発、回転ディスク微粒化又は噴霧乾燥、および、任意に、得られた生成物をふるい分けする、ことによって、モキシデクチンのミクロスフェア(a)を調製する工程、
ii)フルララネルの粒子を調製する工程、
iii)1以上の懸濁剤及び/又は1以上の湿潤剤を水に溶解することによって水性担体を調製する工程、および
iv)工程i)から得られた前記粒子及び工程ii)から得られた前記ミクロスフェアを前記水性担体と混合する工程
を含む、方法。 - キットであって、該キットは、
(A)請求項1から3のいずれか一項に記載のミクロスフェアとフルララネルの粒子との混合物を含む第1の容器、
(B)請求項1から3のいずれか一項に記載の水性担体を含む第2の容器、および
(C)動物への注射の前に前記水性担体において前記ミクロスフェア及び前記粒子を再構成するための指示書
を含む、キット。 - 動物における寄生生物の侵襲を処置及び/又は予防するのに使用するための、請求項1から3のいずれか一項に記載の動物用医薬組成物。
- 皮下注射又は筋肉内注射によって前記動物に投与される、請求項6に記載の動物用医薬組成物。
- 前記動物用医薬組成物の投与レジメが、6ヶ月に1回又は12ヶ月に1回である、請求項6又は7に記載の動物用医薬組成物。
- 前記動物がペットである、請求項6から8のいずれか一項に記載の動物用医薬組成物。
- 前記動物がイヌである、請求項9に記載の動物用医薬組成物。
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FI4153133T3 (fi) | 2024-01-30 |
WO2021233967A1 (en) | 2021-11-25 |
IL298259A (en) | 2023-01-01 |
EP4153133A1 (en) | 2023-03-29 |
JP2023523476A (ja) | 2023-06-05 |
AU2021277491B2 (en) | 2024-05-16 |
JP2024010068A (ja) | 2024-01-23 |
CA3182659A1 (en) | 2021-11-25 |
ES2969653T3 (es) | 2024-05-21 |
CN115666514A (zh) | 2023-01-31 |
MX2022014493A (es) | 2022-12-13 |
US20230310386A1 (en) | 2023-10-05 |
AU2021277491A1 (en) | 2022-12-01 |
EP4153133B1 (en) | 2023-11-08 |
PT4153133T (pt) | 2024-01-12 |
CL2022003194A1 (es) | 2023-02-03 |
BR112022022923A2 (pt) | 2022-12-20 |
CO2022016630A2 (es) | 2022-11-29 |
DK4153133T3 (da) | 2024-02-05 |
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