JP7374081B2 - 改善された再吸収性ポリマーの精製方法 - Google Patents
改善された再吸収性ポリマーの精製方法 Download PDFInfo
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G63/00—Macromolecular compounds obtained by reactions forming a carboxylic ester link in the main chain of the macromolecule
- C08G63/88—Post-polymerisation treatment
- C08G63/90—Purification; Drying
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G63/00—Macromolecular compounds obtained by reactions forming a carboxylic ester link in the main chain of the macromolecule
- C08G63/02—Polyesters derived from hydroxycarboxylic acids or from polycarboxylic acids and polyhydroxy compounds
- C08G63/06—Polyesters derived from hydroxycarboxylic acids or from polycarboxylic acids and polyhydroxy compounds derived from hydroxycarboxylic acids
- C08G63/08—Lactones or lactides
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G63/00—Macromolecular compounds obtained by reactions forming a carboxylic ester link in the main chain of the macromolecule
- C08G63/78—Preparation processes
- C08G63/82—Preparation processes characterised by the catalyst used
- C08G63/823—Preparation processes characterised by the catalyst used for the preparation of polylactones or polylactides
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G63/00—Macromolecular compounds obtained by reactions forming a carboxylic ester link in the main chain of the macromolecule
- C08G63/78—Preparation processes
- C08G63/82—Preparation processes characterised by the catalyst used
- C08G63/85—Germanium, tin, lead, arsenic, antimony, bismuth, titanium, zirconium, hafnium, vanadium, niobium, tantalum, or compounds thereof
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08K—Use of inorganic or non-macromolecular organic substances as compounding ingredients
- C08K3/00—Use of inorganic substances as compounding ingredients
- C08K3/02—Elements
- C08K3/04—Carbon
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08K—Use of inorganic or non-macromolecular organic substances as compounding ingredients
- C08K5/00—Use of organic ingredients
- C08K5/04—Oxygen-containing compounds
- C08K5/09—Carboxylic acids; Metal salts thereof; Anhydrides thereof
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- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Polymers & Plastics (AREA)
- Organic Chemistry (AREA)
- Polyesters Or Polycarbonates (AREA)
- Other Resins Obtained By Reactions Not Involving Carbon-To-Carbon Unsaturated Bonds (AREA)
- Biological Depolymerization Polymers (AREA)
- Processes Of Treating Macromolecular Substances (AREA)
Description
本発明は、工業生産に適した再吸収性ポリマーの改善された精製方法に関する。本発明による再吸収性ポリマー中の金属触媒濃度は、好ましくは1ppm未満である。この方法を使用して、実質的に金属を含まない高分子量ポリマーを得ることができる。
生分解性ポリマーは、環境に優しいポリマーとして追求されてきた。過去30年間にわたるこれらの材料の合成、製造、および処理の進歩により、パッケージングから、より洗練された生物医学デバイスへの実用化が促進されている。脂肪族ポリエステルは、特に魅力的なクラスの生分解性ポリマーであり、特に乳酸およびグリコール酸から誘導されたポリマーである。このような脂肪族ポリエステルは、生分解性であるだけでなく、生体吸収性でもある。生理学的システムでは、ポリマーの残留物は、最終的に自然の経路によって排除または代謝される(H.K. Makadiaら Polymers, 2011年, 3, 1377)。
一態様では、ポリマーを有機溶媒に溶解してポリマー溶液を生成すること;ポリマー溶液を活性炭および添加剤と組み合わせること;貧溶媒沈殿法により精製ポリマーを回収することによって、スズ含有再吸収性ポリマー中の残留スズ含有量を1ppm未満に低減する方法であって、前記方法は、精製ポリマーの形成をもたらす方法が開示されている。
本発明による再吸収性ポリマーおよびプロセスを開示かつ説明する前に、本明細書に記載された態様は、特定のプロセス、化合物、合成方法、物品、デバイスまたは使用に限定されず、当然のことながら変化し得ることを理解されたい。また、本明細書で使用される用語は、特定の態様のみを説明するためのものであり、本明細書で特に定義されていない限り、限定することを意図していないことも理解されたい。
本明細書で使用されるすべての技術用語および科学用語は、他に定義されていない限り、当業者によって一般に理解される意味と同じ意味を有する。矛盾がある場合には、定義を含めて、本明細書が統制することとする。好ましい方法および材料を以下に記載するが、本明細書に記載のものと類似の、または同等の方法および材料を本発明の実施または試験に使用することができる。本明細書で言及されるすべての出版物、特許出願、特許およびその他の参考文献は、それらを参照することによりその全体が本明細書中に組み込まれるものとする。本明細書で開示される材料、方法、および実施例は、単なる例示であり、限定することを意図するものではない。
(a)有機溶媒にポリマーを溶解してポリマー溶液を生成すること;
(b)ポリマー溶液を活性炭および添加剤と組み合わせること;ここで、前記方法によって精製ポリマーが形成される;および
(c)精製ポリマーを貧溶媒沈殿法によって回収すること
を含む、方法。
以下の実施例は、本発明の精製方法を例示するために提供される。それらは、本発明をそれらの内容に限定することなく、例として記載された可能な方法としてのみ意図されている。
D,L-ラクチドおよびグリコリドを、2-エチルヘキサン酸スズにより触媒され、かつアルコールにより開始されるバルク重合に供した。エステル末端基を有する、得られたポリ(D,L-ラクチド-コ-グリコリド)を特性決定すると、121kDaの平均分子量(Mw)、GPCによる1.6のMw/Mn、および残留スズ含有量90ppmを有していた。
D,L-ラクチドを、2-エチルヘキサン酸スズにより触媒され、グリコール酸により開始されるバルク重合に供した。酸末端基を有する、得られたポリ(D,L-ラクチド)を特性決定すると、186kDaの平均分子量(Mw)、GPCによる1.7のMw/Mn、および残留スズ含有量89ppmを有していた。
ポリマーの熱安定性は、乾燥配合処理、例えばホットメルト押出中の重要なパラメータである。水分、加水分解されたモノマーおよびオリゴマー、ならびに残留金属が、ポリ(D,L-ラクチド)の熱安定性に影響を及ぼす重要な要因であることが報告された(D. Camら Polymer 38, 1997年, 1879~1884)。1.2dL/gのIVを有するポリ(D,L-ラクチド)を4つの異なる方法により処理して、様々な量の残留スズおよび残留モノマー含有量を有する4つの生成物が得られた。これらの処理されたポリ(D,L-ラクチド)の分析結果を第3表に列記する。これらのポリマーを窒素保護下に230℃で2時間にわたり保持することによって、その熱安定性を調査した。図1に示すように、アリコートを様々な時点で採取し、それらの質量平均分子量をGPCで特性決定した。
Claims (2)
- スズ含有再吸収性ポリマー中の残留スズ含有量を1ppm未満に低減する方法であって、
(a)有機溶媒にポリマーを溶解してポリマー溶液を生成すること;
(b)前記ポリマー溶液を活性炭および添加剤と組み合わせること;ここで、前記方法によって精製ポリマーが形成される;および
(c)前記精製ポリマーを貧溶媒沈殿法によって回収すること
を含み、
その際、
前記再吸収性ポリマーが、直鎖状または分枝鎖状ポリマーであって、ポリ(L-ラクチド)、ポリ(D-ラクチド)、ポリ(DL-ラクチド)、ポリ(L-ラクチド-コ-グリコリド)、ポリ(D-ラクチド-コ-グリコリド)、およびポリ(DL-ラクチド-コ-グリコリド)から選択され、かつ
前記添加剤が、乳酸であって、前記溶媒の20質量%までであり、かつ前記活性炭が、前記直鎖状ポリマーの9質量%までであるか、または、前記添加剤が、乳酸であって、前記溶媒の20質量%までであり、かつ前記活性炭が、前記分枝鎖状ポリマーの50~100質量%である、
方法。 - 前記添加剤および前記活性炭を、ポリマー溶液に2~4時間さらす、請求項1記載の方法。
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