JP2021528436A - 顎関節変性疾患の治療用の持続放出性組成物およびその方法 - Google Patents
顎関節変性疾患の治療用の持続放出性組成物およびその方法 Download PDFInfo
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Abstract
Description
本発明は、国立歯科および頭蓋顔面研究所によって授与されたR41 DE028215の下、米国合衆国政府の支援を受けてなされた。したがって、米国合衆国政府は、本明細書および特許請求の範囲に開示される本発明において、一定の権利を有する。
[優先権の主張]
本出願は、2018年6月22日に出願された米国特許仮出願第62/688,545号の優先権を主張するものであり、その全内容は参照により本明細書に組み込まれている。
種々の投薬形態のための薬理学的に受容可能なキャリアは当技術分野において既知である。例えば、既知の固体調製物のための賦形剤、潤滑剤、バインダ、および崩壊剤;既知の液体調製物のための溶媒、可溶化剤、懸濁化剤、等張化剤、緩衝剤、および鎮静剤。いくつかの実施形態では、医薬組成物が一つ以上の防腐剤、酸化防止剤、安定化剤などの一つ以上の追加成分を含む。レミントン(Remington)の「薬学の科学及び実践第21版(The Science and Practice of Pharmacy、21st ed)」、リピンコット(2006)(Lippincott(2006))を参照されたく、その内容は参照のため、全体的に本明細書に組み込まれている。
1)高分子量ヒアルロン酸−スクレロスチンハイドロゲルの合成
以下の材料を合成に使用した:高分子量ヒアルロン酸ナトリウム(HA)(平均分子量2000kDa)(ライフバイオメディカ(Life Biomedical)社製、カタログ番号:HA2M)、3%BSA PBS、スクレロスチン(SOST)(R&Dシステム(R&D system)社製、カタログ番号:1406−ST−025/CF)、1mlのシリンジ(BDツベルクリンシリンジ(BD Tuberculin Syringes)社製、14−826−87)、5mlのファルコン丸底プロピレンチューブ(サーモフィッシャーサイエンティフィック(Fisher scientific)社製、カタログ番号:14−959−11A)、インスタント密封滅菌パウチ(フィッシャー ブランド(FisherBrand)、#01−812−54)。
媒介物:0.1mlの3%BSA PBS
SOST:0.1mlの1.5ug/mlSOST.22.5ul×(200ug/ml再構成したSOST)/3ml3%BSA PBS
HMW HA:0.1mlの2%HA(3mlの3%BSA PBS中に0.06gのHMW HAを含む)
HMW HA−SOST:HMW HA中に0.1mlの2ug/mlのSOST(3mlの2ug/mlのSOST中に0.06gのHMW HAを含む)を含む。
スクレロスチン−ヒアルロン酸ヒドロゲルおよびスクレロスチンの放出曲線。前述手順に従って、スクレロスチン(1μg、R&D 1406−ST/CF)を、2%高分子量ヒアルロン酸(HMW HA、2000kDa、ライフバイオメディカ社製)または2%および3%低分子量(LMW HA、500 KDa、ライフバイオメディカ社製)中に混合した。ヒドロゲルを0.4μm孔径のポリエステル膜の挿入物を有する12mmトランズウェル(Transwell(R)、サーモフィッシャーサイエンティフィック社製、07−200−161)上に入れ、37oCで12ウェルプレート中のPBSに培養した。累積放出曲線をプロットするため、製造業者の指示に従って、定量的サンドイッチ酵素結合免疫吸着技術を使用して、示された各時点でスクレロスチンの濃度を測定した。簡単に言うと、標準またはサンプル(100μL)を各ウェルに添加し、37℃で2時間培養し、続いてビオチン化抗ヒトスクレロスチン抗体のいずれかを用いて37℃で1時間一次抗体処理をした。抗体検出のために、100μLのHRP−アビジンを37℃で1時間置いた。洗浄後、TMB基質を各ウェルに添加し、37℃で15−30分間置き、続いて50μLの停止液を添加した。450nmでマイクロプレートリーダーを用いて各ウェルの光学濃度(OD)を測定した。スクレロスチン濃度は、各サンプルのODを標準曲線と比較することによって計算した。
本発明は、米国国立衛生研究所によって授与されたDE022060およびDE028215の下、米国合衆国政府の支援を受けてなされた。したがって、米国合衆国政府は、本発明において、一定の権利を有する。
[優先権の主張]
本出願は、2018年6月22日に出願された米国特許仮出願第62/688,545号の優先権を主張するものであり、その全内容は参照により本明細書に組み込まれている。
Claims (36)
- 顎関節変性疾患を治療するための組成物であって、スクレロスチンおよび高分子量ヒアルロン酸のヒドロゲルを含む、組成物。
- 請求項1に記載の組成物において、
前記スクレロスチンの濃度が組成物の約5ng/100μl〜1mg/100μlであり、高分子量ヒアルロン酸の濃度が約0.1wt%〜10wt%である、組成物。 - 請求項1に記載の組成物において、
前記スクレロスチンの濃度が組成物の約50ng/100μl〜5μg/100μlであり、高分子量ヒアルロン酸の濃度が約0.5wt%〜5wt%である、組成物。 - 請求項1に記載の組成物において、
前記スクレロスチンの濃度が組成物の約1μg/100μlであり、高分子量ヒアルロン酸の濃度が約2wt%である、組成物。 - 請求項1に記載の組成物において、
スクレロスチンおよび高分子量ヒアルロン酸を主成分して構成される、組成物。 - 請求項2に記載の組成物において、
スクレロスチンおよび高分子量ヒアルロン酸を主成分して構成される、組成物。 - 請求項3に記載の組成物において、
スクレロスチンおよび高分子量ヒアルロン酸を主成分して構成される、組成物。 - 請求項4に記載の組成物において、
スクレロスチンおよび高分子量ヒアルロン酸を主成分して構成される、組成物。 - 請求項1に記載の組成物において、
前記ヒアルロン酸の平均分子量が約800kDa〜8000kDaである、組成物。 - 請求項1に記載の組成物において、
前記ヒアルロン酸の平均分子量が約1000kDa〜6000kDaである、組成物。 - 請求項1に記載の組成物において、
前記ヒアルロン酸の平均分子量が約2000kDaである、組成物。 - 顎関節変性疾患を治療するための組成物であって、PLGA微小球にカプセル化スクレロスチンを含む、組成物。
- 請求項12に記載の組成物において、
前記スクレロスチンの濃度が組成物の約5ng/100μl〜1mg/100μlであり、PLGAの濃度が約0.1wt%〜10wt%である、組成物。 - 請求項12に記載の組成物において、
前記スクレロスチンの濃度が組成物の約50ng/100μl〜5μg/100μlであり、PLGAの濃度が約0.5wt%〜5wt%である、組成物。 - 請求項12に記載の組成物において、
前記スクレロスチンの濃度が組成物の約1μg/100μlであり、PLGAの濃度が約0.2wt%である、組成物。 - 請求項12に記載の組成物において、
スクレロスチンおよびPLGAを主成分して構成される、組成物。 - 請求項13に記載の組成物において、
スクレロスチンおよびPLGAを主成分して構成される、組成物。 - 請求項14に記載の組成物において、
スクレロスチンおよびPLGAを主成分して構成される、組成物。 - 請求項15に記載の組成物において、
スクレロスチンおよびPLGAを主成分して構成される、組成物。 - 請求項12に記載の組成物において、
前記PLGAが50:50のグリコール酸および乳酸モノマーとなる共重合体である、組成物。 - 請求項20に記載の組成物において、
前記PLGAの平均分子量が30,000Da〜60,000Daである、組成物。 - 顎関節変性疾患を治療するための組成物であって、スクレロスチンに共役結合したスクレロスチンを含む、組成物。
- 請求項22に記載の組成物において、
前記スクレロスチンの濃度が組成物の約5ng/100μl〜1mg/100μlであり、高分子量ヒアルロン酸の濃度が約0.1wt%〜10wt%である、組成物。 - 請求項22に記載の組成物において、
前記スクレロスチンの濃度が組成物の約50ng/100μl〜5μg/100μlであり、高分子量ヒアルロン酸の濃度が約0.5wt%〜5wt%である、組成物。 - 請求項22に記載の組成物において、
前記スクレロスチンの濃度が組成物の約1μg/100μlであり、高分子量ヒアルロン酸の濃度が約0.2wt%である、組成物。 - 請求項22に記載の組成物において、
スクレロスチンおよび高分子量ヒアルロン酸を主成分して構成される、組成物。 - 請求項23に記載の組成物において、
スクレロスチンおよび高分子量ヒアルロン酸を主成分して構成される、組成物。 - 請求項24に記載の組成物において、
スクレロスチンおよび高分子量ヒアルロン酸を主成分して構成される、組成物。 - 請求項25に記載の組成物において、
スクレロスチンおよび高分子量ヒアルロン酸を主成分して構成される、組成物。 - 請求項22に記載の組成物において、
前記ヒアルロン酸の平均分子量が約800kDa〜8000kDaである、組成物。 - 請求項22に記載の組成物において、
前記ヒアルロン酸の平均分子量が約1000kDa〜6000kDaである、組成物。 - 請求項22に記載の組成物において、
前記ヒアルロン酸の平均分子量が約2000kDaである、組成物。 - 顎関節変性疾患の治療を必要とする患者の前記顎関節変性疾患を治療する方法であって、請求項1の組成物、請求項23の組成物、および請求項22の組成物から選択される治療有効量の組成物を前記患者に投与することを含む、方法。
- 請求項33に記載の方法において、前記組成物が請求項5の組成物、請求項6の組成物、請求項7の組成物、および請求項8の組成物から選択される、方法。
- 請求項33に記載の方法において、前記組成物が請求項16の組成物、請求項17の組成物、請求項18の組成物、および請求項19の組成物から選択される、方法。
- 請求項33に記載の方法において、前記組成物が請求項27の組成物、請求項28の組成物、請求項29の組成物、および請求項30の組成物から選択される、方法。
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JOURNAL OF TISSUE ENGINEERING, vol. 9, JPN6023004695, 13 May 2018 (2018-05-13), pages 1 - 12, ISSN: 0004983444 * |
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