P-dioxanone monomer

Polydioxanone (PDS) is obtained by a ring-opening polymerization of the p-dioxanone monomer. It is characterized by a glass transition temperature in the range of -10°C to 0°C and a degree of crystallinity of about 55%. Materials prepared with PDS show enhanced flexibility due to the... 

One synthetic route to p-dioxanone monomer (Doddi et al., 1977) is by first reacting the monosodium salt of ethylene glycol with chloroacetic acid. Sodium metal is dissolved in a large excess of ethylene glycol under a stream of nitrogen to form the monosodium salt of ethylene glycol. 

The partially purified crystalline p-dioxanone monomer (100 grams) is then filtered using a Buchner funnel and then added to a Erlenmeyer flask along with 75 grams of ethyl acetate. The mixture is stirred until the monomer dissolves. Stirring is then stopped the solution is cooled to O C and 1 gram of pure p-dioxanone seed cry stals are added. The mixture is then allowed to stand at-30°C for 12 hours, then filtered and dried. Sixty grams of pure p-dioxanone are obtained (30% yield). 

The polymerization of p-dioxanone has been described in several references (Doddi et al, 1977 Shalaby and Koelmel, 1984 Jamiolkowski et al, 1989). As described above, highly purified p-dioxanone monomer is polymerized in the presence of an organometallic catalyst such as diethyl zinc or zirconium acetylacetone to obtain high molecular weight, fiber forming polymer (Figure 5). 

The proportion of glycolide that is added to the mixture of p-dioxanone homopolymer and monomer can be varied, and in the examples that follow, it is from 3 to 25 weight percent, based on total weight of the reaction mixture (i.e., total weight of glycolide, p-dioxanone homopolymer, and p-dioxanone monomer). 

For the preparation of block copolymers, c-caprolactone is polymerized into a prepolymer and then reacted tvith p-dioxanone monomer. This results in a copol)Tner with a center block of c-caprolactone and one or two end blocks of p-dioxanone. This forms block copol) mers with a diblock (AB) or triblock (ABA) architecture (Fagpre 9). Diblock copolymers can be prepared by first prepolymerizing f-caprolactone with a monofunctional initiator such as 1-dodecanol, followed by polymerization with p-dioxanone monomer. 

Step 2 Copolymerization of lactide, and poly(p-dioxanone) homopolymer and p-dioxanone monomer to form segmented copolymer... 

It is obtained by ROP of the monomer p-dioxanone. The process requires heat and an organometallic catalyst like zirconium acetylacetonate or zinc L-lactate. The reaction is shown in Figure 1.11. 

The copolymers have two glass transition temperatures one for the p-dioxanone block (-13°C) and the other ranging from -32°C to 52°C based on the feed ratio of the three co-monomers. The melting temperature ranged from 99°C to 107°C. The heat of fusion was the highest for the pure poly-p-dioxanone (45 J/g) and decreased with an increase in the other two co-monomers. The level of crystallinity ranged from 32% for the pure poly-p-dioxanone to 9% with 25/25/50 feed ratio of trimethylene carbonate/ -caprolactone/p-dioxanone. 

The following describes the syTnthesis, physical characteristics and in vitro/in vivo properties of poly(p-dioxanone) and its copolymers with other lactone derived absorbable polyesters and related structures, as well as the synthesis of the monomer, p-dioxanone. 

Furthermore, since impurities in the monomer feed can limit molecular weight, monomers must be highly pure and great care must be taken to use dry glassware and glove box procedures when setting up a polymerization run. Additionally, the formed crude polymer, especially poly(p-dioxanone) and its copolymers, will contain unreacted monomer in amounts typically greater than 1 %. Vacuum or other extraction techniques must be utilized to remove residual monomer and catalyst in order to obtain polymers with optimized properties. 

Like poly(p-dioxanone) homopolymer, copolymers of PDO and lactide can be prepared by several conventional polymerization means. The most commercially viable method relies upon melt polymerization. Since a thermodynamic equilibrium between the monomer (p-dioxanone) and the polymer [poly (p-dioxanone) ], results during polymerization (Bezwada et al, 1987, 1990) in conversions ranging from... 

Segmented copolymers of p-dioxanone/glycolide (Bezwada, Shalaby and Newman, 1987) can be prepared by a similar method as segmented copohnners of p-dioxanone/L(-)lactide. Firstly, p-dioxanone (PDO) monomer is melt pohnner-ized to produce a mixture of poly(p-dioxanone) homopolymer and pedioxanone monomer. 

Thus, p-dioxanone homopol Tner is prepared, as described previously, by charging pure p-dioxanone, dodecanol, and a catalytic amoimt of stannous octoate in toluene solution (0.0025 mole percent based on monomer) to an appropriate reactor, and heating under an inert dry nitrogen atmosphere at 90°C for one hour. 

Then, to a flame dried, 250 ml round bottom three-neck flask, equipped with a overhead stirrer, nitrogen inlet and stopper, 25.0 g of the poly(p-dioxanone) homopolymer was added. The flask was equipped with a vacuum adapter. Vacuum was applied and the flask was lowered into a silicone oil bath heated at 80°C. Heating at 80°C under high vacuum was maintained for 16 hours to remove any residual water and to remove as much residual monomer as possible (i.e., 2 wt%). 

Synthesis involves the formation of apoly(alkylene carbonate) prepolymer formed from intermediates of organic carbonate moieties by reaction of a diol and organic carbonate monomer at elevated temperatures in the presence of a catalyst such as stannous octoate. Diols include 1,6-hexanediol, 1,4-butanediol and 1,8-octanediol, wi hile carbonates include diphenyl carbonate and dibutyl carbonate. p-Dioxanone is then added to form the poly(p-dioxanone-co-alkylene carbonate) copolymer. 

The resulting poly(p-dioxanone-co-hexamethylene carbonate) copolymer was cooled to room temperature, isolated, ground, and dried at 80°C under high vacuum to remove any unreacted monomer. The copolymer had an I.V. of 0.38 dL/g. 

Molecular weights and viscosities can be controlled by the type of initiator and by the ratio of initiator to monomer. Handling properties of the coating copolymers can be controlled by changing the mole ratios of p-dioxanone, lactide and glycolide. 

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