Synthetic resins or natural rubbers -- part of the class 520 ser – Synthetic resins – From carboxylic acid or derivative thereof
Reexamination Certificate
2001-05-03
2002-09-10
Truong, Duc (Department: 1711)
Synthetic resins or natural rubbers -- part of the class 520 ser
Synthetic resins
From carboxylic acid or derivative thereof
C528S50200C, C528S486000, C528S501000, C528S503000, C428S364000
Reexamination Certificate
active
06448367
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to a method of producing poly(p-dioxanone), poly(p-dioxanone) monofilaments and a method of producing the same. More particularly, this invention relates to poly(p-dioxanone) monofilaments which can retain high mechanical properties for a long time and are suitable for use as surgical sutures, a method of producing the same, and a method of producing poly(p-dioxanone) which is suitable for use as a raw material for such monofilaments.
2. Background Art
The poly(p-dioxanone) monofilaments commercially available as PDSII (tradename) from Ethicon, Inc. of U.S.A. are known as having a very high resistance to hydrolysis. Monocryl (tradename of Ethicon), Maxon (tradename of ACC), Biosyn (tradename of U.S. Surgical). etc. are known as other synthetic monofilament sutures. The latter monofilaments are hydrolyzable more quickly than PDSII, and are not effective for applications calling for a longer period of resistance to hydrolysis, but are used only for short-term applications. It has been necessary to use polycaprolactone monofilaments, etc. for applications calling for a longer period of hydrolysis resistance. As a matter of fact, however, they have hardly been used, since they are insufficient in heat resistance and are too slow in hydrolysis.
The recent progress in medical treatment has brought about a growing population of elderly people. They, however, require a long time for healing because of their advanced age, and sutures which require extraction are used for those people, since ordinary decomposable monofilament sutures become lower in strength before the healing of a wound or incision. There has been a demand for monofilament sutures which are more resistant to hydrolysis and higher in safety.
Doddi et al. produce absorbable monofilaments of poly(p-dioxanone). See e.g. Japanese Patent Publication No. 36785/1985 and U.S. Pat. No. 4,052,988. Japanese Patent Application Laid-Open No. 316745/1998 discloses a method of producing poly(p-dioxanone) having a high molecular weight and a narrow molecular weight distribution (Mw/Mn). The former monofilaments are described as having a molecular weight controlled by the amount of an organic metal catalyst and the monomer purity and providing sutures having a viscosity of at least 0.5 dl/g in a tetrachloroethane solution. An increase in molecular weight, however, results in a higher catalyst content and cannot be said to be a good method from a safety standpoint, even if the catalyst may be removed later. The latter polymer also has its molecular weight controlled by the amount of stannous 2-ethylhexanoate and has a catalyst content far from what is intended by the inventor of this invention. It cannot be said to be a good method from a safety standpoint even if the catalyst may be removed.
Japanese Patent Application Laid-Open No. 52205/1996 discloses a method of producing poly(p-dioxanone) having a high solution viscosity and surgical monofilaments having a viscosity of 2.3 to 8.0 dl/g in a solution containing hexafluoroisopropanol as a solvent. It also states that poly(p-dioxanone) can be produced by a one-step process of polymerization in which a reactor suited for a polymer of high viscosity is employed, or by a two-step process in which a prepolymer having a low molecular weight is subjected to two steps of polymerization in a solid state. It further states that the contents of the reactor are discharged onto a curing tray when there has been obtained a polymer having a viscosity of 100 to 500 cp. The resulting polymer certainly has a high molecular weight (an intrinsic viscosity of 2.64 dl/g), and an increase in molecular weight is intended for obtaining a somewhat improved resistance to hydrolysis. There is, however, no specific statement showing the resistance of filaments to hydrolysis, but there is only a statement of the results obtained from an injection molded product having a high molecular weight. Moreover, there is no statement at all about e.g. the deterioration of the polymer resulting by shearing from stirring, but the combination of polymerization in a liquid phase under stirring and polymerization in a solid phase is rather considered as being employed for an efficient transfer.
Known methods of producing monofilaments are disclosed in Japanese Patent Application Laid-Open No. 206143/1991, U.S. Pat. Nos. 5,294,395and 5,451,461, etc. More specifically, there is disclosed a method in which the monofilament to be drawn after spinning has its skin layer exposed to heat at a temperature above its melting point to produce a monofilament-having a two-layer crystal structure differing between its skin and core. This method is commonly known as a zone drawing method, and is characterized by melting the skin to some extent and imparting softness to it, while maintaining a high crystallinity in the core, and thereby keeping the filament hydrolyzable. The method, however, requires the use of poly(p-dioxanone) having a high molecular weight as a raw material for the filament, since it is partly caused to undergo thermal decomposition. It cannot be considered as a good method from an economical standpoint, either, since it involves a complicated process and requires special equipment. Moreover, it is considered as sacrificing the hydrolysis resistance of the polymer. Thus, it is understood that it is necessary to produce a polymer having a high molecular weight suitable for zone drawing.
Under these circumstances, it is an object of this invention to provide monofilaments of poly(p-dioxanone) which are superior in hydrolysis resistance and safety to the known products such as PDSII, a method of producing the same and a method of producing poly(p-dioxanone) which is useful as a raw material therefor.
DISCLOSURE OF THE INVENTION
As a result of our careful study, we, the inventors of this invention, have unexpectedly found as a basis for our invention that stannous 2-ethylhexanoate which has hitherto been believed as a liquid forms a solid at a low temperature upon purification by distillation, etc., and that if the ring opening polymerization of p-dioxanone is started in a liquid phase by using stannous 2-ethylhexanoate of high purity as a catalyst, and is switched over to polymerization in a solid phase at a lower temperature by stopping stirring when the viscosity of the product of polymerization reaction (or its stirring load) has increased above a specific level, there is obtained poly(p-dioxanone) giving a spun filament which is superior in hydrolysis resistance to any polymer obtained by using an unpurified catalyst, though both of the polymers have an equal molecular weight. Thus, the invention has been achieved.
According to a first aspect of this invention, there is provided a method of producing poly(p-dioxanone) by the ring opening polymerization of p-dioxanone in the presence of a catalyst and an initiator, which comprises starting the ring opening polymerization of p-dioxanone in a liquid phase under stirring at a temperature of 85 to 105° C. after adding 0.002 to 0.005 mol percent of stannous 2-ethylhexanoate forming a white crystal at a temperature of 0° C. as the catalyst and 0.01 to 0.1 mol percent of initiator thereto, and stopping stirring when a stirring load has increased by 10 to 100 percent over an initial load, while lowering the temperature to a range of 65 to 85° C., to continue the polymerization in a solid phase.
After the polymerization in a solid phase, an inert gas is preferably supplied at a temperature of 60 to 80° C. and a pressure not exceeding 10 mm Hg to remove unreacted p-dioxanone so that there may be obtained a polymer having an unreacted p-dioxanone content not exceeding 0.5 percent by weight, and the polymerization is preferably continued until a conversion of at least 95 percent by weight to poly(p-dioxanone) is attained. In either event, it is preferable to use p-dioxanone having a water content not exceeding 150 ppm. It is preferable to use stannous 2-ethylhexanoate having a melting point of −3° C. or h
Akieda Hideyuki
Kajita Minoru
Ozu Kazuhiro
Shioya Yoshikatsu
Burns Doane Swecker & Mathis L.L.P.
Mitsui Chemicals Inc.
Truong Duc
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