JP2010512859A - ポリマーの使用 - Google Patents
ポリマーの使用 Download PDFInfo
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- JP2010512859A JP2010512859A JP2009541680A JP2009541680A JP2010512859A JP 2010512859 A JP2010512859 A JP 2010512859A JP 2009541680 A JP2009541680 A JP 2009541680A JP 2009541680 A JP2009541680 A JP 2009541680A JP 2010512859 A JP2010512859 A JP 2010512859A
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Abstract
Description
本発明のチオール基含有ポリマーのヒドロキシル基掃去能を、デオキシリボース試験(Halliwellら、Food Chem. Toxicol. 33 (1995):601-617)を用いて評価した。この試験系では、ヒドロキシル基は、デオキシリボースを攻撃する鉄イオンによって生成される。得られた分解生成物はチオバルビツール酸と反応して、ピンク色の剤になり、この剤の吸収を測定する。この方法を用いることにより、本発明のチオール基含有ポリマーのヒドロキシル基掃去能と錯化能の両方を試験する。
インビトロ試験を用いて、皮膚の脂質の酸化を抑制するチオール基含有ポリマーの能力を評価した。例えば紫外線に起因する細胞内脂質過酸化は、ヒトの皮膚/真皮の損傷を招く。
皮内投与するために以下の調製物を調製した。2gのチオール基含有ヒアルロン酸を、無菌の等張リン酸緩衝剤に溶解し、撹拌して、部分的に架橋したポリマーを生成し、それを注射器に満たして殺菌した。0.1mlのこの調製物を、ウサギの背部に皮内注射した。この投与は、翌日には消失する最小の局所刺激をもたらした。チオール基含有ヒアルロン酸によって形成されたデポーは、2週間の試験期間全体にわたり触覚によって認めることができた。
皮下投与用調製物および皮内投与用調製物を以下のように調製した。無菌のチオール基含有ヒアルロン酸1gを、pH7.4である無菌リン酸緩衝剤100mlに、無菌状態で酸素の不存在下溶解した。この調製物のオスモル濃度をNaClの添加によって調節し、200〜400mOsm/kgの溶液オスモル濃度を得た。溶液をフラスコに満たし、気体を通さないように塞いだ。
調製物を以下のように調製した。無菌のチオール基含有ヒアルロン酸3gを、pH7.4である無菌リン酸緩衝剤100mlに、無菌状態で溶解し、部分的に架橋させた。その後、NaClの推奨添加によってオスモル濃度を調節し、200〜400mOsm/kgの溶液オスモル濃度を得た。溶液をフラスコに満たし、気体を通さないように塞いだ。
肛門管で自然に発生する緩衝作用を補うことによって肛門失禁を防ぐため、内肛門括約筋の増大にチオール基含有ポリマーが使用されてきた。尿道括約筋を増大するためにも、同じ調製物が使用された(US 5,785,642参照)。失禁は、特に妊娠後に骨盤底が著しく弱くなった女性にとって、しばしば起こる問題である。常套法によって骨盤底筋を強化できないならば、尿道増大のための物質の注入が良好な代替法である。
チオール基含有ポリマー、特にチオール基含有ヒアルロン酸の別の利点を、この実施例で示す。チオール基含有ヒアルロン酸および架橋ヒアルロン酸粒子含有市販調製物は、ヒアルロニダーゼによって分解される。いずれの場合も、ヒアルロン酸は分解された。その分解は、チオール基含有ヒアルロン酸の場合、未変性ヒアルロン酸と同程度であり、生成断片は、架橋ヒアルロン酸含有粒子よりはるかに大きい分子量を示す。このことは、ジスルフィド架橋が酵素によって分解されず、架橋度が、架橋ヒアルロン酸粒子よりはるかに高いという事実に由来する。従って、本発明の架橋チオール基含有ヒアルロン酸は、架橋ヒアルロン酸粒子より投与部位により長く留まる。
Claims (13)
- ベースポリマーが多糖類である、組織増大用インプラントを製造するためのチオール基含有ポリマーの使用。
- チオール基含有ポリマーが、少なくとも10,000g/mol、好ましくは少なくとも25,000g/mol、特に少なくとも50,000g/molの分子量を有することを特徴とする、請求項1に記載の使用。
- ポリマー内でチオール基が分子間および/または分子内ジスルフィド結合を形成することを特徴とする、請求項1または2に記載の使用。
- ポリマーのチオール基部分が、ポリマー1gあたり20μmol超、好ましくはポリマー1gあたり50μmol超、特にポリマー1gあたり100μmol超であることを特徴とする、請求項1〜3のいずれかに記載の使用。
- チオール基含有ポリマーが、チオール基含有ヒアルロン酸、チオール基含有キトサン、およびこれらポリマーの組み合わせからなる群から選択されることを特徴とする、請求項1〜4のいずれかに記載の使用。
- 本発明のポリマーのチオール基が好ましくはシステイン、システアミンまたはN−アセチル−システインから誘導されることを特徴とする、請求項1〜5のいずれかに記載の使用。
- インプラントが、ゲルまたは水溶液として、好ましくは単相調製物として供給されることを特徴とする、請求項1〜6のいずれかに記載の使用。
- インプラントが付加的にキトサンおよび/またはヒアルロン酸を含んでなることを特徴とする、請求項1〜7のいずれかに記載の使用。
- インプラントが更に付加的に、好ましくは、消炎剤、抗リウマチ剤、鎮痛剤、抗感染薬、抗ウィルス剤、抗生剤、抗真菌剤、殺菌剤、化学療法薬、鎮痙薬、ビタミン、細胞増殖抑制剤、局所麻酔薬、抗アレルギー薬、抗ヒスタミン薬、抗炎症薬、抗静脈瘤薬、痔疾治療薬、皮膚治療薬、婦人科用剤、眼科用剤、泌尿器科用剤、鼻科用剤および耳科用剤からなる群からの少なくとも1種の有効成分、および/または好ましくは、緩衝塩、防腐剤、所望のオスモル濃度に調節するための賦形剤、所望の粘度に調節するための賦形剤、安定剤、軟化剤、被覆剤、フロー剤、バインダー、滑剤、充填剤、乾燥剤、崩壊剤、溶剤、可溶化剤、および調製物の相溶性を高めるための賦形剤からなる群からの少なくとも1種の医薬品賦形剤を含んでなることを特徴とする、請求項1〜8のいずれかに記載の使用。
- インプラントが、0.001〜100重量%、好ましくは0.01〜90重量%、より好ましくは0.05〜80重量%の濃度でチオール基含有ポリマーを含んでなることを特徴とする、請求項1〜9のいずれかに記載の使用。
- 増大される組織が、皮膚組織、筋組織および結合組織からなる群から選択されることを特徴とする、請求項1〜10のいずれかに記載の使用。
- 請求項1〜6および9のいずれかに記載されているような少なくとも1種のチオール基含有ポリマーを含んでなるインプラント。
- 請求項1〜6および9のいずれかに記載されているようなチオール基含有ポリマーを皮下および/または皮内に投与することを特徴とする、皮膚の美容整形術のための方法並びに皮膚の老化を遅らせるおよび/または予防するための方法。
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US6308372B1 (en) | 1998-07-23 | 2001-10-30 | Mitsuba Corporation | Mounting structure of wiper apparatus |
JP2013537050A (ja) * | 2010-09-09 | 2013-09-30 | バイオレゲン バイオメディカル (チャンヂョウ) カンパニー リミテッド | メルカプト修飾度の低いメルカプト修飾生体適合性高分子誘導体とその架橋材料、およびこれらの使用法 |
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JP2017514916A (ja) * | 2014-05-07 | 2017-06-08 | クロマ−ファーマ ゲゼルシャフト エム.ベー.ハー. | 水性点眼液およびドライアイ症候群の治療方法 |
JP2020500953A (ja) * | 2016-11-07 | 2020-01-16 | クロマ−ファーマ ゲゼルシャフト エム.ベー.ハー. | 硫化水素放出ポリマー化合物 |
JP2021526934A (ja) * | 2018-06-15 | 2021-10-11 | クロマ−ファーマ ゲゼルシャフト エム.ベー.ハー. | 安定化されたヒアルロン酸 |
JP2021526933A (ja) * | 2018-06-15 | 2021-10-11 | クロマ−ファーマ ゲゼルシャフト エム.ベー.ハー. | 架橋ポリマーを含むヒドロゲル組成物 |
JP2021528138A (ja) * | 2018-06-15 | 2021-10-21 | クロマ−ファーマ ゲゼルシャフト エム.ベー.ハー. | 架橋ポリマーを含むヒドロゲル組成物 |
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EP2107913A2 (en) | 2009-10-14 |
DK2107913T3 (da) | 2012-05-21 |
PT2107913E (pt) | 2012-05-10 |
CA2673323C (en) | 2013-07-16 |
BRPI0722061A2 (pt) | 2014-04-01 |
ES2391862T3 (es) | 2012-11-30 |
US9597277B2 (en) | 2017-03-21 |
US20100028399A1 (en) | 2010-02-04 |
EP2107913B1 (en) | 2012-02-15 |
WO2008077172A2 (en) | 2008-07-03 |
CN101622017A (zh) | 2010-01-06 |
AU2007336692B2 (en) | 2013-12-12 |
JP5513893B2 (ja) | 2014-06-04 |
CY1112623T1 (el) | 2016-02-10 |
CN101622017B (zh) | 2018-09-11 |
ATE545436T1 (de) | 2012-03-15 |
SI2107913T1 (sl) | 2012-05-31 |
PL2107913T3 (pl) | 2012-07-31 |
RU2009128235A (ru) | 2011-01-27 |
AU2007336692A1 (en) | 2008-07-03 |
BRPI0722061B1 (pt) | 2018-05-15 |
BRPI0722061B8 (pt) | 2021-06-22 |
CA2673323A1 (en) | 2008-07-03 |
RU2432181C2 (ru) | 2011-10-27 |
WO2008077172A3 (en) | 2009-05-14 |
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