JP2022532854A - 点眼薬からの防腐剤の除去 - Google Patents
点眼薬からの防腐剤の除去 Download PDFInfo
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- JP2022532854A JP2022532854A JP2021564194A JP2021564194A JP2022532854A JP 2022532854 A JP2022532854 A JP 2022532854A JP 2021564194 A JP2021564194 A JP 2021564194A JP 2021564194 A JP2021564194 A JP 2021564194A JP 2022532854 A JP2022532854 A JP 2022532854A
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- 229960002494 tetracaine hydrochloride Drugs 0.000 description 1
- BJORNXNYWNIWEY-UHFFFAOYSA-N tetrahydrozoline hydrochloride Chemical compound Cl.N1CCN=C1C1C2=CC=CC=C2CCC1 BJORNXNYWNIWEY-UHFFFAOYSA-N 0.000 description 1
- 238000005979 thermal decomposition reaction Methods 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 229940033663 thimerosal Drugs 0.000 description 1
- 229960002663 thioctic acid Drugs 0.000 description 1
- 229940034744 timoptic Drugs 0.000 description 1
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- 239000010936 titanium Substances 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 210000001585 trabecular meshwork Anatomy 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- 229960002368 travoprost Drugs 0.000 description 1
- HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 description 1
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Abstract
Description
本出願は、2019年5月2日に出願された米国仮特許出願第62/842,071号の利益を主張するものであり、この出願は、参照により本出願の開示に組み込まれる。
本明細書で言及されるすべての刊行物、特許および特許出願は、各個々の刊行物、特許または特許出願が参照により組み込まれることが具体的かつ個別に示されるのと同じ程度に参照により本明細書に組み込まれる。参照により組み込まれる刊行物および特許または特許出願が本明細書に含まれる開示と矛盾する範囲に限り、本明細書は、そのような矛盾するいかなる資料に取って代わり、および/またはそれに優先されることを意図している。
いくつかの実施形態では、本開示は、防腐剤および治療剤を含む医薬製剤を提供する。製剤は、治療剤および防腐剤の溶液、乳濁液または懸濁液を含んでもよい。いくつかの実施形態では(例えば、防腐剤除去剤が、治療剤および防腐剤を含む溶液、乳濁液または懸濁液の一部を含んでもよい実施形態では)、製剤は、防腐剤除去剤を含んでもよい。他の実施形態では(例えば、防腐剤除去剤が、ボトルの首部内に位置してもよい実施形態では)、防腐剤除去剤は、治療剤および防腐剤を含む溶液、乳濁液または懸濁液とは別であってもよい。随意に、任意の実施形態では、溶液、乳濁液または懸濁液は加えて、1つ以上の薬学的に許容可能な賦形剤を含んでもよい。
本開示の実施形態は、眼に送達するための少なくとも1つの治療剤を提供する。治療剤は、流体に一体化され、流体は、容器から、酸化ポリオレフィン(OxPO)微粒子を含む多孔質ポリマーマトリクスを含むノズルを通って眼に流れる。いくつかの実施形態では、流体は、少なくとも1つの治療剤を含む溶液、乳濁液または懸濁液を含んでもよい。溶液、乳濁液または懸濁液は、2つ以上の治療剤を含んでもよい。
本開示は、本開示の治療剤の溶液、乳濁液または懸濁液用の1つ以上の防腐剤を提供する。防腐剤は、治療剤の溶液、乳濁液または懸濁液用の防腐剤として使用するための化合物および塩を含んでもよい。1つ以上の防腐剤は、例えば、微生物および/または真菌の増殖を防止することができる。1つ以上の防腐剤は、例えば、治療剤の物理的または化学的な劣化を防止することができる。
治療剤および防腐剤の溶液、乳濁液または懸濁液が本明細書で提供される。いくつかの実施形態では、治療上有効な量の、本開示の防腐剤および/または治療剤のいずれか1つの任意の化合物または塩を含む組成物が本明細書に提供される。いくつかの実施形態では、治療溶液、乳濁液または懸濁液は、本明細書に記載の方法のいずれかで使用されてもよい。溶液、乳濁液または懸濁液は、1つ以上の薬学的に許容可能な賦形剤をさらに含んでもよい。
親水性薬剤
粒子マトリクス中のAPIおよびBAKの分布係数の計算
OxPO粒子中の親水性薬剤およびBAKの分布係数は、薬物取り込み研究によって得る。OxPOマトリクスに分布した薬剤またはBAKの質量は、濃縮水性薬剤/PBSまたはBAK/PBS添加溶液中に失われる薬剤またはBAKの量を観測することによって求める。逆相UPLC分析を使用して経時変化測定によって、水相濃縮物から薬剤の損失量を定量化した。
ホットプレート付きスターラー上で、0.1N酢酸水溶液1Lを含有した2Lビーカーに、OxHDPE(Honeywell、A-C 395A、篩下画分63~125um)約70gを添加した。この混合物を、65℃~70℃で1時間撹拌しながら加熱した。生成物は、63μmの篩上で濾取し、DI水約3Lで十分に洗浄した。洗浄したOxHDPEを真空オーブン内で周囲温度で乾燥させ、白色の粉末約65gを得た。この粉末のBAKの分布係数を求めたところ、360であった。同様に、他のOxPOを洗浄した。洗浄溶液は、0.1N酢酸水溶液か、0.1N水酸化アンモニウム水溶液のいずれかの中性水とした。
UPLCシステムは、バイナリポンプ、オンラインデガッサ、カラムヒータ、オートサンプラー、およびUV/Vis検出器を備えたWaters Aquity UPLC(Waters、アメリカ合衆国マサチューセッツ州ミルフォード)から構成される。データ収集およびデータ分析は、Empower 3 FR 4(Waters)を使用して行った。分離は、Waters HSS(C18 1.8um、VanGuardプレカラム)で保護したWaters ULC(HSSC18、1.8μm、3.0mm×100mmカラム)を使用して達成した。
20mlシンチレーションバイアルに、試験するOxPO0.2gおよび通常のPBS中の1000ppmのBAK溶液5.0mlを加えた。バイアルに蓋をし、ロータリーシェーカー上で2日間旋回させた。上澄み溶液を、0.45ミクロンフィルタを通して濾過し、あらゆる固体を除去した。濾過された液体の一部をアセトニトリルで1:1に希釈し、上記のようにUPLC分析を行った。
20mlシンチレーションバイアルに、試験するOxPO0.1gおよびAPI製剤5.0mlを加えた。バイアルに蓋をし、ロータリーシェーカー上で2日間旋回させた。上澄み溶液を、0.45ミクロンフィルタを通して濾過し、あらゆる固体を除去した。濾過された液体の一部を50%アセトニトリル水溶液で100:1に希釈し、上記のようにUPLC分析を行った。元のAPI溶液の一部を濾過し、希釈し、そして、比較基準としてUPLC分析を行った。
20mlシンチレーションバイアルに、試験するOxPO0.2gおよび通常のPBS中の1000ppmのBAK溶液5.0mlを加えた。バイアルに蓋をし、ロータリーシェーカー上で48時間旋回させた。上澄み溶液を、0.45μmフィルタを通して濾過し、あらゆる固体を除去した。濾過された液体の一部をアセトニトリルで1:1に希釈し、上記のようにUPLC分析を行った。OxPOに吸着したBAKと、溶液中に残存したBAKの比を計算するために、以下の式を用いた(PC=分布係数):
PC=[(BAK初期濃度-BAK最終濃度)×溶液重量]/OxPO重量×BAK最終濃度
例えば、BAK初期濃度が1000ppmであった場合は、溶液5.0gおよびOxPO粉末0.20gを使用すると、BAK最終濃度は14ppmであり、PC=1761であった。この試験では、望ましくはPC値>50であり、好ましくはPC値>100であり、PC値>1000では、BAKがほぼ完全に吸着されることを示した。
様々な粒子径に分類し、中性溶液、酸性溶液または塩基性溶液で洗浄し、乾燥させたOxPOの値を求めるために、上記の分布係数試験を使用した。
超純水60.0gに、ヒドロキシエチルセルロース(Natrosol 250H)0.090gを添加し、溶液を一晩攪拌して溶解した。その後、クエン酸ナトリウム二水和物0.176gおよびマンニトール0.960gを加え、混合物を完全に溶解するまで撹拌した。ドルゾラミド塩酸塩1.37g、チモロールマレイン酸塩0.420g、および10%BAK水溶液0.045gを添加して組み込んだ。0.01N NaOH溶液でpHを調整して、5.65にした。以下に、最終設定濃度を報告する。
先端部の出口に、25μmフィルタが設けられた空の点眼容器の先端に、OxPO約0.40~0.45mgを充填し、OxPOの充填物を定位置に保持するために、裏打ち材のフィルタを貼り付けた。OxPOの充填物の重量を記録した。次いで、API/BAK検液5mlを含有した8ml容量の点眼容器ボトルの首部に、充填した先端部を挿入した。
上記のように、OxHDPE(A-C 395、125~250μm、酸洗浄)を充填した6つの点眼容器ボトルに、チモロール5.0mg/ml、ドルゾラミド20.0mg/mlおよびBAK75μg/mlを名目上含有した上記の製剤5mlを加えた。1日2回(8時間間隔をあけて、午前・午後に)各ボトルから滴液を得て、APIおよびBAKに対して、HPLC分析を行った。その結果を以下の表にまとめる。この実験では、OxPOが、30日間の試験期間にわたって、>95%のBAKを除去し、かつ、>95%のAPIを保持する能力を有することが示された。
Claims (77)
- 薬剤を含む溶液、懸濁液または乳濁液から防腐剤を除去するための粒子のプラグであって、当該粒子のプラグは、酸化ポリオレフィン(OxPO)を含むポリマー微粒子を含み、
ここで、前記微粒子は、異形の剛性を有する凝集体であり、透水性が0.01Da超の粒子のプラグを形成し、前記溶液、乳濁液または懸濁液用容器の吐出口に適合し、OxPOの前記微粒子は、溶液中に、除去される防腐剤の吸着される部分、および/または、送達される薬剤をさらに含み、粒子のプラグは、前記溶液、乳濁液または懸濁液から前記防腐剤を迅速かつ選択的に除去する、粒子のプラグ。 - 前記酸化ポリオレフィン(OxPO)は、エチレン、プロピレン、1-ブテン、4-メチル-1-ペンテン、3-メチル-1-ブテン、4,4-ジメチル-1-ペンテン、3-メチル-1-ペンテン、4-メチル-1-ヘキセン、5-エチル-1-ヘキセン、6-メチル-1-ヘプテン、1-ヘキセン、1-ヘプテン、1-オクテン、1-ノネン、または1-デセンのホモポリマーまたはコポリマーから選択される、請求項1に記載の粒子のプラグ。
- 前記酸化ポリオレフィン(OxPO)は、エチレンのホモポリマーまたはコポリマーから選択される、請求項1に記載の粒子のプラグ。
- 前記酸化ポリオレフィン(OxPO)は、酸化高密度ポリエチレン(OxHDPE)である、請求項3に記載の粒子のプラグ。
- 前記酸化ポリオレフィン(OxPO)は、フィッシャー・トロプシュ法によって形成されるポリマーから選択される、請求項1に記載の粒子のプラグ。
- 前記薬剤は、チモロールマレイン酸塩、レボフロキサシン、ドルゾラミド、ブリモニジン酒石酸塩、またはそれらの組み合わせから選択される、請求項1に記載の粒子のプラグ。
- 前記防腐剤は、塩化ベンザルコニウム(BAK)を含む、請求項1に記載の粒子のプラグ。
- 薬剤溶液、懸濁液または乳濁液から防腐剤を除去する方法であって、該方法は、
容器を提供する工程であって、前記容器は、延在する吐出口と、少なくとも1つの薬剤および防腐剤を含む前記薬剤溶液、懸濁液または乳濁液を保持するためのチャンバとを有し、前記延在する吐出口内に請求項1に記載の粒子のプラグを含む、工程と、
前記粒子のプラグを通して前記薬剤溶液、懸濁液または乳濁液を押し出す工程と、を含む、方法。 - 前記粒子のプラグに前記薬剤および/または前記防腐剤を予め添加する工程をさらに含む、請求項8に記載の方法。
- 前記薬剤は、チモロールマレイン酸塩、レボフロキサシン、ドルゾラミド、ブリモニジン酒石酸塩、またはそれらの組み合わせを含む、請求項8に記載の方法。
- 前記防腐剤は、塩化ベンザルコニウム(BAK)である、請求項8に記載の方法。
- 医薬製剤を送達するための器具であって、該器具は、
請求項1の粒子のプラグと、
1つ以上の有効治療成分および防腐剤を含む医薬製剤と、を含み、
ここで、前記医薬製剤が前記粒子のプラグを通して押し出されると、前記防腐剤の少なくとも90%が選択的に除去され、一方で送達される前記医薬製剤中に前記1つ以上の有効治療成分の少なくとも90%が保持される、器具。 - 前記器具は、前記医薬製剤の液滴を吐出するための点眼ボトルであり、ここで、前記粒子のプラグを通して押し出される前記医薬製剤の液滴毎に、吐出される液滴中の前記1つ以上の有効治療成分の濃度は、前記点眼ボトルの中の前記医薬製剤の濃度の少なくとも90%である、請求項12に記載の器具。
- 前記粒子のプラグは、粒子の充填層を含む、請求項12に記載の器具。
- 前記器具は、前記粒子のプラグを通じて前記医薬製剤を押し出しながら、前記粒子のプラグを保持するためのホルダアセンブリを有する、請求項12に記載の器具。
- 前記粒子のプラグは、製剤入口面および製剤出口面を含み、前記ホルダアセンブリは、前記粒子のプラグの溶液の入口面および溶液の出口面にフィルタを含む、請求項15に記載の器具。
- 前記ホルダアセンブリは、前記粒子のプラグの周りに溶液透過性の袋を含む、請求項15に記載の器具。
- 前記粒子のプラグは焼結されて、多孔質モノリスとして前記粒子のプラグは融着される、請求項12に記載の器具。
- 前記粒子のプラグは、少なくとも100である前記防腐剤の分布係数と、1未満である各有効成分の分布係数とを有する、請求項12に記載の器具。
- 前記粒子のプラグは、前記薬剤で予め平衡化される、請求項12に記載の器具。
- 前記器具は、製造から、使用されるために患者によって受け取られるまで、前記粒子のプラグを通して前記医薬製剤を押し出す位置に前記器具を保持する包装をさらに含む、請求項12に記載の器具。
- 防腐剤除去具であって、該防腐剤除去具は、
酸化高密度ポリエチレン(OxHDPE)微粒子を含み、
ここで、前記微粒子は、異形の剛性を有する凝集体であり、
前記微粒子は、透水性が0.01Da超の粒子のプラグを形成し、
前記粒子のプラグは、溶液、乳濁液または懸濁液用容器の吐出口に適合し、
前記OxHDPE微粒子は、除去される防腐剤の吸着される部分、および、送達される治療剤をさらに含み、前記粒子のプラグは、前記溶液、乳濁液または懸濁液から前記防腐剤を迅速かつ選択的に除去する、防腐剤除去具。 - 防腐剤除去具であって、該防腐剤除去具は、
酸化ポリオレフィン(OxPO)微粒子を含み、
ここで、前記微粒子は、異形の剛性を有する凝集体であり、
前記微粒子は、透水性が0.01Da超の粒子のプラグを形成し、
前記粒子のプラグは、溶液、乳濁液または懸濁液用容器の吐出口に適合し、
前記OxPO微粒子は随意に、除去される防腐剤の吸着される部分、および、送達される治療剤を含み、前記粒子のプラグは、前記溶液、乳濁液または懸濁液から前記防腐剤を迅速かつ選択的に除去する、防腐剤除去具。 - 前記酸化ポリオレフィン(OxPO)は、エチレン、プロピレン、1-ブテン、4-メチル-1-ペンテン、3-メチル-1-ブテン、4,4-ジメチル-1-ペンテン、3-メチル-1-ペンテン、4-メチル-1-ヘキセン、5-エチル-1-ヘキセン、6-メチル-1-ヘプテン、1-ヘキセン、1-ヘプテン、1-オクテン、1-ノネン、または1-デセンのホモポリマーまたはコポリマーから選択される、請求項23に記載の粒子のプラグ。
- 前記酸化ポリオレフィン(OxPO)は、エチレンのホモポリマーまたはコポリマーから選択される、請求項23に記載の粒子のプラグ。
- 前記酸化ポリオレフィン(OxPO)は、酸化高密度ポリエチレン(OxHDPE)である、請求項25に記載の粒子のプラグ。
- 前記酸化ポリオレフィン(OxPO)は、フィッシャー・トロプシュ法によって形成されるポリマーから選択される、請求項23に記載の粒子のプラグ。
- 前記異形の剛性を有する凝集体は、角が粗い粒子であり、前記角が粗い粒子は、250ミクロン未満の径を含む、請求項22に記載の防腐剤除去具。
- 前記角が粗い粒子は、150ミクロン未満の径を含む、請求項28に記載の防腐剤除去具。
- 前記防腐剤は、塩化ベンザルコニウムを含む、請求項22~29のいずれか1項に記載の防腐剤除去具。
- 前記防腐剤は、SofZiaまたはPuriteである、請求項22~30のいずれか1項に記載の防腐剤除去具。
- 前記治療剤は、チモロールマレイン酸塩、レボフロキサシン、ドルゾラミド、ブリモニジン酒石酸塩、ビマトプロスト、テトラヒドロゾリン、またはオロパタジンの少なくとも1つを含む、請求項22~31のいずれか1項に記載の防腐剤除去具。
- 前記治療剤は、チモロールマレイン酸塩およびブリモニジン酒石酸塩を含む、請求項31に記載の防腐剤除去具。
- 前記治療剤は、チモロールマレイン酸塩を含む、請求項31に記載の防腐剤除去具。
- 請求項22~34のいずれか1項に記載の防腐剤除去具を使用して、薬剤溶液、懸濁液または乳濁液から防腐剤を除去する方法であって、該方法は、
容器を提供する工程であって、前記容器は、延在する吐出口と、少なくとも1つの薬剤および防腐剤を含む前記薬剤溶液、懸濁液または乳濁液を保持するためのチャンバとを有し、前記薬剤溶液、懸濁液または乳濁液から防腐剤を除去するための粒子のプラグを含み、前記粒子のプラグは、前記延在する吐出口内にある、工程と、
前記粒子のプラグを通して前記薬剤溶液、懸濁液または乳濁液を押し出す工程と、を含む、方法。 - 前記粒子のプラグに前記薬剤または前記防腐剤を予め添加する工程をさらに含む、請求項35に記載の方法。
- 医薬製剤を送達するための器具であって、該器具は、請求項22~36のいずれか1項の粒子のプラグと、1つ以上の有効成分および防腐剤を含む医薬製剤と、を含み、ここで、前記医薬製剤が前記粒子のプラグを通して押し出されると、前記防腐剤の少なくとも90%が選択的に除去され、一方で送達される前記医薬製剤中にすべての有効成分の少なくとも90%が保持される、器具。
- 前記器具は、前記医薬製剤の液滴を吐出するための点眼ボトルであり、ここで、前記粒子のプラグを通して押し出される前記薬剤溶液の液滴毎に、吐出される液滴中の前記有効成分の濃度は、前記点眼ボトルの中の前記医薬製剤の濃度の少なくとも90%である、請求項37に記載の器具。
- 前記器具は、前記粒子のプラグを通して前記薬剤溶液を押し出しながら、前記粒子のプラグを保持するためのホルダアセンブリを有する、請求項37または38に記載の器具。
- 前記粒子のプラグは、製剤入口面および製剤出口面を含み、前記ホルダアセンブリは、前記粒子のプラグの前記製剤入口面および製剤出口面にフィルタを含む、請求項37~39のいずれか1項に記載の器具。
- 前記器具は、製造から、使用されるために患者によって受け取られるまで、前記粒子のプラグを通して前記薬剤溶液、懸濁液または乳濁液を押し出す位置に前記器具を保持する包装をさらに含む、請求項37~40のいずれか1項に記載の器具。
- 眼科用製剤から防腐剤を除去するための器具であって、該器具は、
中に配置される溶液、乳濁液または懸濁液を含むリザーバの吐出口内に配置されるポリマーマトリクスを含み、
ここで、前記溶液、乳濁液または懸濁液は、除去される防腐剤、および、眼科用剤を含み、
前記ポリマーマトリクスは、前記溶液、乳濁液または懸濁液に対して透過性であるワックスを含み、前記ポリマーマトリクスは、酸化高密度ポリエチレン(OxHDPE)微粒子を含み、前記ポリマーマトリクスは、前記眼科用剤の分布係数よりも大きい前記防腐剤の分布係数を有し、前記防腐剤の除去のための時間尺度は、前記溶液、乳濁液または懸濁液が前記ポリマーマトリクスを通じて前記リザーバの外部に流れる時間尺度より短い、器具。 - 前記OxHDPEは、DIN EN ISO2114によって測定された場合に約30mgKOH/gの酸価を含む、請求項42に記載の器具。
- 前記OxHDPEは、DGF M-III 3によって測定された場合に125℃と135℃の間の滴点を含む、請求項42に記載の器具。
- 前記OxHDPEは、DIN 51579によって測定された場合に約0.98グラム/立方センチメートルの密度を含む、請求項42に記載の器具。
- 前記OxHDPEは、DIN EN ISO3104によって測定された場合に190℃で4.00mPasの粘度を含む、請求項42に記載の器具。
- 前記OxHDPEは、125ミクロンサイズと250ミクロンサイズの間の粒子を含む、請求項42に記載の器具。
- 前記ポリマーマトリクスは、OxHDPEのホモポリマーである、請求項42に記載の器具。
- 前記防腐剤は、塩化ベンザルコニウムを含む、請求項42に記載の器具。
- 前記防腐剤は、SofZiaまたはPuriteである、請求項42に記載の器具。
- 前記治療剤は、チモロールマレイン酸塩、レボフロキサシン、ドルゾラミド、ブリモニジン酒石酸塩、ビマトプロスト、テトラヒドロゾリン、またはオロパタジンの少なくとも1つを含む、請求項42に記載の器具。
- 前記治療剤は、チモロールマレイン酸塩およびブリモニジン酒石酸塩を含む、請求項42に記載の器具。
- 前記治療剤は、チモロールマレイン酸塩を含む、請求項42に記載の器具。
- 眼科用製剤から防腐剤を除去するための器具であって、該器具は、
中に配置される溶液、乳濁液または懸濁液を含むリザーバであって、前記溶液、乳濁液または懸濁液は、除去される防腐剤、および、眼科用剤を含む、リザーバと、
リザーバの吐出口内に配置されるポリマーマトリクスと、を含み、
前記ポリマーマトリクスは、前記溶液、乳濁液または懸濁液に対して透過性であるワックスを含み、前記ポリマーマトリクスは、酸化ポリオレフィン(OxPO)微粒子を含み、前記ポリマーマトリクスは、前記ポリマーマトリクスを通過する200マイクロリットル体積の前記溶液、乳濁液または懸濁液に対して50%超の前記防腐剤を吸着する、器具。 - 前記酸化ポリオレフィン(OxPO)は、エチレン、プロピレン、1-ブテン、4-メチル-1-ペンテン、3-メチル-1-ブテン、4,4-ジメチル-1-ペンテン、3-メチル-1-ペンテン、4-メチル-1-ヘキセン、5-エチル-1-ヘキセン、6-メチル-1-ヘプテン、1-ヘキセン、1-ヘプテン、1-オクテン、1-ノネン、または1-デセンのホモポリマーまたはコポリマーから選択される、請求項54に記載の粒子のプラグ。
- 前記酸化ポリオレフィン(OxPO)は、エチレンのホモポリマーまたはコポリマーから選択される、請求項54に記載の粒子のプラグ。
- 前記酸化ポリオレフィン(OxPO)は、酸化高密度ポリエチレン(OxHDPE)である、請求項56に記載の粒子のプラグ。
- 前記酸化ポリオレフィン(OxPO)は、フィッシャー・トロプシュ法によって形成されるポリマーから選択される、請求項23に記載の粒子のプラグ。
- 前記リザーバは、前記眼科用製剤を送達するためのノズルに連結される、請求項54に記載の器具。
- 前記リザーバは圧縮性があり、前記リザーバの圧縮により、前記ノズルの吐出口に液滴を形成する、請求項59に記載の器具。
- 前記液滴は、約200マイクロリットル体積を含み、前記液滴は、約2秒以内に形成される、請求項60に記載の器具。
- 前記OxPOは、DIN EN ISO2114によって測定された場合に約30mgKOH/gの酸価を含む、請求項54に記載の器具。
- 前記OxPOは、DGF M-III 3によって測定された場合に125℃と135℃の間の滴点を含む、請求項54に記載の器具。
- 前記OxPOは、DIN 51579によって測定された場合に約0.98グラム/立方センチメートルの密度を含む、請求項54に記載の器具。
- 前記OxPOは、DIN EN ISO3104によって測定された場合に190℃で4.00mPasの粘度を含む、請求項54に記載の器具。
- 前記OxPOは、125ミクロンサイズと250ミクロンサイズの間の粒子を含む、請求項54に記載の器具。
- 前記ポリマーマトリクスは、OxHDPEのホモポリマーである、請求項54に記載の器具。
- 前記防腐剤は、塩化ベンザルコニウムを含む、請求項54に記載の器具。
- 前記防腐剤は、SofZiaまたはPuriteである、請求項54に記載の器具。
- 前記治療剤は、チモロールマレイン酸塩、レボフロキサシン、ドルゾラミド、ブリモニジン酒石酸塩、ビマトプロスト、テトラヒドロゾリン、またはオロパタジンの少なくとも1つを含む、請求項54に記載の器具。
- 前記治療剤は、チモロールマレイン酸塩およびブリモニジン酒石酸塩を含む、請求項54に記載の器具。
- 前記治療剤は、チモロールマレイン酸塩を含む、請求項54に記載の器具。
- 前記OxHDPEは、DIN EN ISO2114によって測定された場合に約30mgKOH/gの酸価を含む、請求項57に記載の器具。
- 前記OxHDPEは、DGF M-III 3によって測定された場合に125℃と135℃の間の滴点を含む、請求項57に記載の器具。
- 前記OxHDPEは、DIN51579によって測定された場合に約0.98グラム/立方センチメートルの密度を含む、請求項57に記載の器具。
- 前記OxHDPEは、DIN EN ISO3104によって測定された場合に190℃で4.00mPasの粘度を含む、請求項57に記載の器具。
- 前記OxHDPEは、125ミクロンサイズと250ミクロンサイズの間の粒子を含む、請求項57に記載の器具。
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Application Number | Priority Date | Filing Date | Title |
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US201962842071P | 2019-05-02 | 2019-05-02 | |
US62/842,071 | 2019-05-02 | ||
PCT/US2020/030801 WO2020223527A2 (en) | 2019-05-02 | 2020-04-30 | Preservative removal from eye drops |
Publications (2)
Publication Number | Publication Date |
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JP2022532854A true JP2022532854A (ja) | 2022-07-20 |
JPWO2020223527A5 JPWO2020223527A5 (ja) | 2023-05-15 |
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JP2021564194A Pending JP2022532854A (ja) | 2019-05-02 | 2020-04-30 | 点眼薬からの防腐剤の除去 |
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US (3) | US11723838B2 (ja) |
EP (1) | EP3962621A4 (ja) |
JP (1) | JP2022532854A (ja) |
KR (1) | KR20220005070A (ja) |
CN (1) | CN114096339B (ja) |
AR (1) | AR118828A1 (ja) |
AU (1) | AU2020266590A1 (ja) |
CA (1) | CA3138304A1 (ja) |
IL (1) | IL287662A (ja) |
MA (1) | MA55095A (ja) |
MX (1) | MX2021013381A (ja) |
SG (1) | SG11202112122YA (ja) |
WO (1) | WO2020223527A2 (ja) |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
MA55095A (fr) | 2019-05-02 | 2022-03-09 | Tearclear Corp | Élimination de conservateur de gouttes oculaires |
WO2021127564A1 (en) * | 2019-12-19 | 2021-06-24 | TearClear Corp. | Preservative removal from eye drops |
JP2023536900A (ja) * | 2020-08-05 | 2023-08-30 | ティアークリアー コープ. | 眼科用製剤からの防腐剤除去のためのシステムおよび方法 |
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US3293112A (en) | 1963-05-06 | 1966-12-20 | Grace W R & Co | Amino-cross linked oxidized alpha-olefin polymer |
US3322711A (en) | 1963-10-17 | 1967-05-30 | Allied Chem | Polymer oxidation process and emulsion therefrom |
DE1570652A1 (de) | 1964-03-09 | 1970-03-26 | Allied Chem | Verfahren zur Herstellung von oxydiertem Polyaethylen |
DE3112163A1 (de) | 1981-03-27 | 1982-10-14 | Basf Ag, 6700 Ludwigshafen | Verfahren zur herstellung von emulgierbarem polyethylen durch oxidation von polyethylen im wirbelbettreaktor |
DE3720953A1 (de) | 1987-06-25 | 1989-01-05 | Basf Ag | Verfahren zur oxidation von polyethylen |
US5013459A (en) * | 1989-11-09 | 1991-05-07 | Dow Corning Corporation | Opthalmic fluid dispensing method |
US5080800A (en) | 1990-01-08 | 1992-01-14 | Ciba-Geigy Corporation | Process for removing components from solutions |
US5056689A (en) | 1990-01-08 | 1991-10-15 | Ciba-Geigy Corporation | Apparatus for removing components from solutions |
EP0631770B1 (en) * | 1993-06-25 | 1998-07-22 | Alcon Cusi, S.A. | New use of polymeric membranes in the dispensing of pharmaceutical solutions that contain quaternary ammonium compounds as preservatives and corresponding dose dispensor |
US5401811A (en) | 1994-05-03 | 1995-03-28 | Eastman Chemical Company | Continuous process for the oxidation of polyethylene |
US5611464A (en) | 1995-05-30 | 1997-03-18 | Ciba Geigy Corporation | Container for preserving media in the tip of a solution dispenser |
US20050255152A1 (en) * | 2002-04-18 | 2005-11-17 | President And Fellows Of Harvard College | System for enhanced targeted delivery |
WO2005066219A1 (en) | 2003-04-01 | 2005-07-21 | Honeywell International Inc. | Process for oxidizing linear low molecular weight polyethylene |
CN102670568A (zh) * | 2003-05-28 | 2012-09-19 | 莫诺索尔克斯有限公司 | 基于聚氧乙烯的薄膜及由其制造的药物传递系统 |
GB0521536D0 (en) | 2005-10-22 | 2005-11-30 | Invibio Ltd | Fiducial marker |
US7622031B2 (en) | 2007-01-15 | 2009-11-24 | Honeywell International Inc | Method for preparing oxidized polyolefin waxes |
US20100285192A1 (en) * | 2008-01-29 | 2010-11-11 | Universite Catholique De Louvain | Method for filtering a liquid |
FR2934572A1 (fr) | 2008-07-31 | 2010-02-05 | Thea Lab | Embout pour flacon de conditionnement de liquide a distribuer goutte a goutte. |
EP2396070A4 (en) * | 2009-02-12 | 2012-09-19 | Incept Llc | ACTIVE COMPOSITION WITH HYDROGEL PLUGS |
WO2010138253A2 (en) | 2009-05-29 | 2010-12-02 | Exxonmobil Chemical Patents Inc. | Polyolefin adhesive compositions and method of making thereof |
FR2955842B1 (fr) | 2010-02-04 | 2012-03-16 | Thea Lab | Flacon de conditionnement d'un liquide a tete de distribution goutte a goutte |
JP5923942B2 (ja) | 2011-11-18 | 2016-05-25 | 日立化成株式会社 | 半導体封止用エポキシ樹脂組成物およびそれを用いた半導体装置 |
WO2016025560A1 (en) | 2014-08-13 | 2016-02-18 | University Of Florida Research Foundation, Inc. | Preservative removal from eye drops |
RU2697844C9 (ru) | 2014-11-25 | 2019-10-01 | Аллерган, Инк. | Стабилизированные композиции для офтальмологического применения, содержащие омега-3-кислоты |
EP3547986A4 (en) | 2016-12-02 | 2020-05-06 | University of Florida Research Foundation, Inc. | PRESERVATIVE REMOVAL FROM EYE DROPS |
AU2018338345A1 (en) * | 2017-09-25 | 2020-04-02 | University Of Florida Research Foundation, Inc. | Preservative removal from eye drops containing hydrophilic drugs |
TW202005623A (zh) | 2018-04-06 | 2020-02-01 | 美商蒂克利爾公司 | 用於輸送治療劑之系統及方法 |
SG11202108457UA (en) | 2019-02-06 | 2021-09-29 | Tearclear Corp | Systems and methods for preservative removal from ophthalmic formulations comprising complexing agents |
MA55095A (fr) | 2019-05-02 | 2022-03-09 | Tearclear Corp | Élimination de conservateur de gouttes oculaires |
JP2023536900A (ja) | 2020-08-05 | 2023-08-30 | ティアークリアー コープ. | 眼科用製剤からの防腐剤除去のためのシステムおよび方法 |
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2020
- 2020-04-30 MA MA055095A patent/MA55095A/fr unknown
- 2020-04-30 US US16/862,918 patent/US11723838B2/en active Active
- 2020-04-30 CA CA3138304A patent/CA3138304A1/en active Pending
- 2020-04-30 EP EP20798350.3A patent/EP3962621A4/en active Pending
- 2020-04-30 KR KR1020217039479A patent/KR20220005070A/ko unknown
- 2020-04-30 AR ARP200101230A patent/AR118828A1/es unknown
- 2020-04-30 AU AU2020266590A patent/AU2020266590A1/en active Pending
- 2020-04-30 SG SG11202112122YA patent/SG11202112122YA/en unknown
- 2020-04-30 CN CN202080048648.XA patent/CN114096339B/zh active Active
- 2020-04-30 JP JP2021564194A patent/JP2022532854A/ja active Pending
- 2020-04-30 WO PCT/US2020/030801 patent/WO2020223527A2/en unknown
- 2020-04-30 MX MX2021013381A patent/MX2021013381A/es unknown
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- 2021-10-28 IL IL287662A patent/IL287662A/en unknown
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- 2023-06-28 US US18/215,733 patent/US20240173208A1/en active Pending
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IL287662A (en) | 2021-12-01 |
US20200345583A1 (en) | 2020-11-05 |
CN114096339B (zh) | 2024-04-12 |
AR118828A1 (es) | 2021-11-03 |
KR20220005070A (ko) | 2022-01-12 |
MX2021013381A (es) | 2021-11-25 |
US11723838B2 (en) | 2023-08-15 |
EP3962621A4 (en) | 2022-11-30 |
MA55095A (fr) | 2022-03-09 |
WO2020223527A2 (en) | 2020-11-05 |
US20240173208A1 (en) | 2024-05-30 |
WO2020223527A3 (en) | 2021-04-29 |
EP3962621A2 (en) | 2022-03-09 |
US20200346186A1 (en) | 2020-11-05 |
CA3138304A1 (en) | 2020-11-05 |
AU2020266590A1 (en) | 2021-12-16 |
SG11202112122YA (en) | 2021-11-29 |
US11096865B2 (en) | 2021-08-24 |
CN114096339A (zh) | 2022-02-25 |
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