Bio-degradable/ absorbable polymer having reduced metal catalyst content, and process for production thereof

Abstract

The present invention provides a safe biodegradable and bioabsorbable polymer having an extremely low metal catalyst content, while retaining the properties desired for a medical implant or the like; and a process for producing the same. The present invention further provides a method for reducing the content of a metal catalyst in a biodegradable and absorbable polymer that can be applied on an industrial scale. A method for producing a biodegradable and bioabsorbable polymer having a metal catalyst content of less than 1 ppm in terms of a metal comprising the steps of (1) copolymerizing lactide and ε-caprolactone at a molar ratio ranging from 40 / 60 to 60 / 40 in the presence of the metal catalyst to produce a copolymer; and (2) washing the copolymer with a mixed solvent comprising acetic acid and isopropanol at a volume ratio ranging from 25 / 75 to 45 / 55 at less than 40° C., and drying the copolymer. 13. A method for producing a biodegradable and bioabsorbable polymer having a metal catalyst content of less than 1 ppm in terms of a metal comprising the steps of (1) copolymerizing lactide and ε-caprolactone at a molar ratio ranging from 65 / 35 to 85 / 15 in the presence of the metal catalyst to produce a copolymer; and (2) washing the copolymer with a mixed solvent comprising acetic acid and isopropanol at a volume ratio ranging from 45 / 55 to 55 / 45 at less than 40° C., and drying the copolymer.

Description

TECHNICAL FIELD[0001]The present invention relates to a biodegradable and bioabsorbable polymer having a low metal catalyst content (residual content), and a process for producing the same. Specifically, the invention relates to a technique for reducing the content of the metal catalyst in the biodegradable and bioabsorbable polymer obtained after synthesis using the metal catalyst.BACKGROUND ART[0002]Known examples of biodegradable and bioabsorbable polymers include polylactic acid, polyglycolic acid, polycaprolactone, trimethylene carbonate, polydioxane, copolymers thereof, and the like. They are degradable and absorbable in vivo, and are thus used in medical implant applications such as sutures, bone-joining materials, etc.[0003]Since a heavy metal-based catalyst such as tin octylate is widely used for the synthesis of such a polymer compound, the metal catalyst remains in the synthesized polymer compound. When the polymer compound is used as a material for a medical implant appl...

AI Technical Summary

Benefits of technology

[0012]Specifically, the present inventors found that the metal catalyst can be effectively removed, without causing a drastic drop in molecular weight, by copolymerizing lactide (lactic acid cyclic dimer) and ε-caprolactone at a molar ratio ranging from 40 / 60 to 60 / 40 using a metal catalyst to produce a copolymer, and washing the copolymer with a mixed solvent comprising acetic acid and isopropanol at a volume ratio ranging from 25 / 75 to 45 / 55, and drying the copolymer. Hereinafter, this invention is sometimes referred to as “First Embodiment”.

[0064]The biodegradable and bioabsorbable polymer of the present invention has an extremely low metal catalyst content of less than 1 ppm (in terms of a metal), and is safe when embedded in the body. Another feature of the invention is its easy general fabrication. Therefore, it is suitably used as a material for a medical device (a medical implant, etc.). Examples of medical implants include sutures, bone-joining materials, fracture fixation materials, tissue supplementation materials, tissue reinforcing materials, tissue covering materials, tissue regenerating base materials, tissue prosthetic materials, anti-adhesive materials, artificial blood vessels, artificial valves, stents, clips, fiber cloths, hemostatic materials, adhesives, coating agents, etc., which can be made by known production methods.EFFECTS OF THE INVENTION

Problems solved by technology

The metal catalyst, which varies according to species, may have harmful effects on the human body such as immunotoxicity, genetic toxicity, neurotoxicity, etc. when present at a certain concentration or more.

However, removal of the metal catalyst is not easy, and is often accompanied by industrial difficulties.

This method, however, requires a large amount of solvent, and causes a drastic drop in molecular weight due to the polymer dissolution.

Therefore, this is not appropriate for producing materials (e.g., medical devices) that require strength of a certain level or more.

Furthermore, since the polymer tends to contain many air bubbles when reprecipitated, the molded product of the polymer is also likely to contain bubbles.

Thus, it is not suitable for industrial manufacture.

Patent Document 2 discloses a method for producing copolymers of lactide and ε-caprolactone; however, it does not disclose the final metal catalyst content.

Furthermore, since the metal catalyst content used is too small, a long polymerization period is required.

Images