1,4-dioxane-2,5-dione

Conditions: temp:180.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: ε-Caprolactone (170 g, 1.49 mole), glycolide (30 g, 0.26 mole), lauryl alcohol (1.37 g, 7.3×10-3 mole) and stannous octoate (0.052 g, 1.2×10-4 mole) were combined in a stirred reactor under nitrogen at 180° C. The mixture was stirred at 180° C. for 4.5 hours. The resulting polymer had an inherent viscosity of 0.68 dl/g (0.5 g/dl in CHCl3). The composition was determined by 1H NMR to be 85 wt. % ε-caprilactone and 15 wt. % glycolide.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Poly(DL-lactide-co-glycolide) with a molar ratio of lactide to glycolide of 75/25 (Birmingham Polymer, Inc.) was dissolved in NMP to give a solution with 45% by weight polymer. This solution was filled into 3.0 cc polyproylene syringes with a male luer lock fitting and terminally sterilized by exposure to gamma irradiation at 23.2-24.6 kilograys. The polymer molecular weight after irradiation was 15,094 daltons. Leuprolide acetate was dissolved in water, sterile filtered through 0.2 mm filter and filled into a polypropylene syringe with a male luer lock fitting. The aqueous solution was frozen and the water removed by vacuum to yield a lyophilized cake of leuprolide. The two syringes were connected together with a coupler immediately prior to use and the contents of the two syringes mixed by moving the material back and forth between the two syringes for 40 cycles to provide a formulation with 6% by weight of leuprolide acetate. The product was then pulled into the syringe with the male luer lock fitting one a one-half inch 20 gauge needle attached. to give a solution with 45% by weight polymer terminally sterilized by exposure to gamma irradiation at 23.2-24.6 kilograys The polymer molecular weight after irradiation sterile filtered through 0.2 mm filter filled into a polypropylene syringe with a male luer lock The aqueous solution was frozen the water removed by vacuum

Conditions: temp:170.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Glycolide (0.13 moles) was mixed with ε-caprolactone (1.18) and a catalytic amount of stannous octoate (0.262 mole) and 1-decanol (3.275 mole). The system was heated to 170° C. and was stirred at this temperature for 30 minutes. The reaction was then cooled to 120° C. Glycolide (0.65 moles) and dl-lactide (0.52 moles) were added to the prepolymer. After melting the second charge, the system was heated to 170° C. and was stirred at this temperature for 6.5 hours. At the conclusion of the reaction, the unreacted monomer was removed by heating at 130° C. under reduced pressure for 1.5 hours. The resulting polymer was characterized by DSC (for Tm), solution viscosity (for molecular dimensions), IR and NMR (for chemical composition). The reaction was then cooled to 120° C the system was heated to 170° C. was stirred at this temperature for 6.5 hours At the conclusion of the reaction the unreacted monomer was removed by heating at 130° C. under reduced pressure for 1.5 hours

Conditions: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Glycolide (0.21 moles) was mixed with ε-caprolactone (4.0 moles) and a catalytic amount of stannous octoate (0.8 mole) and glycolic acid (0.40 moles). The system was heated to 150° C. and was stirred at this temperature for 14 hours. At the conclusion of the reaction, the unreacted monomer was removed by heating at 120° C. under reduced pressure for 1 hour. The resulting polymer had a peak melting temperature of 54.3° C. as measured by DSC. At the conclusion of the reaction the unreacted monomer was removed by heating at 120° C. under reduced pressure for 1 hour

Conditions: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Glycolide (0.08865 moles) was mixed with ε-caprolactone (1.455 moles) and a catalytic amount of stannous octoate (0.3 moles) and tartaric acid (0.075 moles). The system was heated at 150° C. and was stirred at this temperature for 6 hours. At the conclusion of the reaction, the unreacted monomer was removed by heating at 120° C. under reduced pressure for 30 minutes. The resulting polymer had a peak melting temperature of 49.1° C. as measured by DSC and an Mw of 151,948 as measured by GPC. At the conclusion of the reaction the unreacted monomer was removed by heating at 120° C. under reduced pressure for 30 minutes

Conditions: temp:220.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1161 g (10 mols) of glycolide and 1441 g (10 mols) of L-lactide were placed in a glass reactor, and 10 ml of a toluene solution containing 0.26 g of stannous octoate and 9.0 g of lauryl alcohol were added to the reactor. Afterward, deaeration was carried out for 2 hours under reduced pressure, and the atmosphere in the reactor was then replaced with a nitrogen gas. This mixture was heated at 220° C. for 2 hours with stirring under the nitrogen atmosphere. While the temperature was maintained as it was, the deaeration was slowly performed by means of a vacuum pump through an exhaust pipe to reduce the pressure in the reactor to 3 mm Hg. One hour after the start of the deaeration, the monomers and low-molecular substances were not extracted any more, and the interior of the reactor was replaced with nitrogen and a resultant glycolic acid-lactic acid copolymer (hereinafter referred to as "PLGA") was then taken out. were added to the reactor While the temperature was maintained as it One hour after the start of the deaeration, the monomers and low-molecular substances were not extracted any more, and the interior of the reactor

Conditions: temp:180.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: ε-Caprolactone (57.1 g, 0.5 mole), glycolide (1.1 g, 9.5 mole), glycolic acid (7.6 g, 0.1 mole) and stannous octoate (0.5 ml of 0.1M solution in toluene, 20 mg, 5×10-5 mole) were added to a glass reactor. The reactor was purged with dry nitrogen gas. The reactor was heated in an oil bath at 180° C. under nitrogen for 12 hours, while the contents were magnetically stirred. The final composition was determined by 1H NMR is shown to be essentially the same as the theoretical. The Tm is -62° C., and the Tg is 37° C. The reactor was purged with dry nitrogen gas is -62° C.

Conditions: temp:180.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: ε-Caprolactone (57.1 g, 0.5 mole), glycolide (1.1 g, 9.5 mole), glycolic acid (7.6 g, 0.1 mole) and stannous octoate (0.5 ml of 0.1M solution in toluene, 20 mg, 5×10-5 mole) were added to a glass reactor. The reactor was purged with dry nitrogen gas. The reactor was heated in an oil bath at 180° C. under nitrogen for 12 hours, while the contents were magnetically stirred. The final composition was determined by 1H NMR is shown to be essentially the same as the theoretical. The Tm is -62° C., and the Tg is 37° C. The reactor was purged with dry nitrogen gas is -62° C.

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: ε-Caprolactone (456.6 g., 4 mole), glycolide (24.4 g, 0.21 mole), glycolic acid (30.4 g, 0.4 mole), and stannous octoate (4 ml. of 0.2 M solution in toluene, 0.8 mmole) were transferred to a predried, stirred reactor. The polymerization charge was treated as follows: (1) after purging with dry argon, the charge was heated to 50° C. under reduced pressure (about 0.1 mm Hg) for 30 min.; (b) the reaction pressure was returned to atmospheric and the polymerization charge was heated to 150° C. while stirring, and kept at this temperature for 14 hours; © the temperature of the polymer was lowered to 120° C. and vacuum was applied for about 35 min. before cooling to 80° C. and bringing the pressure to one atmosphere with argon; and (d) the polymer was transferred to a predried jar for storage at room temperature and reduced pressure. The final composition was determined by NMR and shown to be essentially the same as expected. The polymerization charge was treated (1) after purging with dry argon (b) the reaction pressure charge was heated to 150° C. while stirring was lowered to 120° C. vacuum was applied for about 35 min. before cooling to 80° C. was transferred to a predried jar for storage at room temperature

Conditions: temp:180.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: ε-Caprolactone (57.1 g, 0.5 mole), glycolide (1.1 g, 9.5 mmole), glycolic acid (7.6 g, 0.1 mole) and stannous octoate (0.5 ml of 0.1 M solution in toluene, 20 mg, 5×10−5 mole) were added to a glass reactor. The reactor was purged with dry nitrogen gas. The reactor was heated in an oil bath at 180° C. under nitrogen for 12 hours, while the contents were magnetically stirred. The final composition was determined by 1H NMR is shown to be essentially the same as the theoretical. The Tg is −62° C., and the Tm is 37° C. The reactor was purged with dry nitrogen gas is 37° C.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Polymerization and post-treatment were performed in the same manner as in Polymer Preparation Example 1 except that a mixture of 200 g of glycolide and 10 g of ethylene oxalate (1,4-dioxane-2,3-dione) was used in place of 210 g of glycolide, thereby obtaining a glycolic acid-ethylene oxalate copolymer [Polymer (P-2)]. The same process was conducted repeatedly to prepare a necessary amount of Polymer (P-2). Polymerization

Conditions: temp:180.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A flame dried, 250 ml, round bottom, single neck flask is charged with 90 g (0.789 mole) of ε-caprolactone, 10 g (0.0862 mole) of glycolide, 7.96 ml (40 millimole/mole of total monomer) of distilled 1-dodecanol, and 0.121 ml of stannous octoate (0.33 molar solution in toluene). The reaction flask is purged with nitrogen three times before venting with nitrogen. The reaction mixture is heated to 180° C. and maintained there for 4.5 hours. The copolymer is isolated, characterized, and tested for absorption. The results are reported in Table 1. A flame dried The reaction flask is purged with nitrogen three times maintained there for 4.5 hours The copolymer is isolated tested for absorption