# US 11,028,222 B2 · Advanced processing of absorbable poly(p-dioxanone) containing high level of p-dioxanone monomer

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- Number: US 11,028,222 B2
- Document ID: US11028222B2
- Status: Granted
- Kind: B2
- Application number: 16/202,454
- Filed: 2018-11-28
- Published: 2020-05-28
- Granted: 2021-06-08
- Earliest claimed: 2018-11-28
- Assignees: Ethicon, Inc.
- Applicants: Ethicon, Inc.
- Inventors: Sasa Andjelic; Brian M. Kelly; Marc Wisnudel
- Web page: https://patentgrep.com/patent/US11028222B2

## CPC

- C08G 63/66: Polyesters containing oxygen in the form of ether groups (C08G63/42, C08G63/58 take precedence)
- C08G 63/785: {characterised by the apparatus used}
- C08G 63/85: Germanium, tin, lead, arsenic, antimony, bismuth, titanium, zirconium, hafnium, vanadium, niobium, tantalum, or compounds thereof {(C08G63/823 takes precedence)}
- C08J 3/12: Powdering or granulating
- C08K 5/18: with aromatically bound amino groups
- C08G 63/08: Lactones or lactides
- C08G 63/664: derived from hydroxy carboxylic acids
- C08G 63/89: Recovery of the polymer
- C08G 63/90: Purification; Drying
- C08L 67/04: Polyesters derived from hydroxycarboxylic acids, e.g. lactones (C08L67/06 takes precedence)
- C08G: MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08J: WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H (working, e.g. shaping, of plastics B29)
- C08K: Use of inorganic or non-macromolecular organic substances as compounding ingredients (paints, inks, varnishes, dyes, polishes, adhesives C09)
- C08L: COMPOSITIONS OF MACROMOLECULAR COMPOUNDS (compositions based on polymerisable monomers C08F, C08G; artificial filaments or fibres D01F; textile treating compositions D06)

## Abstract

The present invention is directed methods of making absorbable poly(p-dioxanone) pellets by melt polymerization of p-dioxanone conducted in a single reactor with a temperature regulator by charging a melt reactor with a mixture of p-dioxanone (PDO) monomer, initiator, catalyst, and optionally a dye; melt polymerizing the mixture in the melt reactor with sufficient agitation of the mixture to allow complete mixing of the monomer and for sufficient time to form a PDO polymer product having an unreacted PDO monomer content of at least 65 mole percent; placing the PDO polymer product under a vacuum to remove at least portion of unreacted PDO; discharging the PDO polymer product from the melt reactor directly into an in-line, underwater pelletizer to produce undried PDO pellets, collecting the undried PDO pellets, and storing the collected PDO pellets in the freezer or a vacuum chamber prior to drying.

## Claims

### Claim 1

A method of making absorbable poly(p-dioxanone) pellets by melt polymerization of p-dioxanone conducted in a single reactor with a temperature regulator, and comprising the steps of:
i. charging a melt reactor with a mixture of p-dioxanone (PDO) monomer, initiator, catalyst, and optionally a dye;
ii. melt polymerizing the mixture at a reaction temperature of between 95° C. and 145° C. in the melt reactor with sufficient agitation of the mixture to allow complete mixing of the monomer and for sufficient time to form a PDO polymer product having an unreacted PDO monomer content;
iii. placing the PDO polymer product under a vacuum for about 60 to 180 minutes to remove at least portion of unreacted PDO, as measured by monomer content, wherein the unreacted PDO monomer content after step (iii) is between about 15 mole percent to about 35 mole percent;
iv. discharging the PDO polymer product from the melt reactor directly into an in-line, underwater pelletizer to produce undried PDO pellets,
v. collecting the undried PDO pellets, and
vi. storing the collected PDO pellets in the freezer or a vacuum chamber.

### Claim 2 (depends on 1)

A method of claim 1, wherein the melt polymerization of PDO monomer is conducted in a single reactor in the presence of a monofunctional initiator at an initiator concentration of between 500:1 to 2,000:1 (mole of monomer:mole of initiator), and in the presence of a catalyst in the total amount of 30,000:1 to 300,000:1 (moles of monomer:moles of catalyst), for total reaction time of between 4 hours and 16 hours.

### Claim 3 (depends on 2)

A method of claim 2, wherein the monofunctional initiator is dodecanol.

### Claim 4 (depends on 2)

A method of claim 2, wherein the catalyst is stannous octoate.

### Claim 5 (depends on 2)

A method of claim 2, wherein the dye is D&C Violet Number 2 in a dye concentration of between 0.01 and 0.2 weight percentage.

### Claim 6 (depends on 1)

A method of claim 1, wherein pelletization is conducted by the underwater pelletizer having a pump and a cutter under following conditions:
a. Setting the melt reactor to an operating temperature of from 95° C. to 130° C.;
b. Initially setting the melt rector agitator at a rotational speed of between 2 RPM to 6 RPM or from about 20-40% of the rotational speed for step (ii);
c. Initially setting the pump speed in the pelletizer at about 5 RPM to about 7 RPM, and gradually increasing the pump speed to the range between 10 RPM and 15 RPM;
d. Setting the pelletizer to a die temperature of about 100° C. to 140° C.;
e. Setting the cutter to a rotational speed of between about 2,000 and 3,600 RPM.

### Claim 7 (depends on 1)

A method of claim 1 further comprising the step of drying the poly(p-dioxanone) pellets.

### Claim 8 (depends on 7)

A method of claim 7 wherein the poly(p-dioxanone) pellets are dried using a fluidized bed drying apparatus.

### Claim 9 (depends on 7)

A method of claim 7, wherein the drying is conducted using tumble dryers, equipped with vacuum and/or heating capabilities, including the steps of:
a. Transferring undried poly(p-dioxanone) pellets having an unreacted p-dioxanone monomer content of between about 15 mole percent to about 35 mole percent into a tumble drier,
b. applying a vacuum in the tumble drier at room temperature and reducing the moisture level in poly(p-dioxanone) pellets to less than 100 parts per million, as measured by a moisture analyzer;
c. setting the drier temperature to a starting drying temperature of about 55° C. and maintaining the heat and vacuum for about two to six hours;
d. setting the drier temperature to an intermediate drying temperature of about 75° C. and maintaining the heat and vacuum for about two to six hours;
e. setting the drier temperature to a final drying temperature from about 85° C. to 95° C. and maintaining the heat and vacuum for about 16 to 32 hours; and
f. collecting the dried poly(p-dioxanone) pellets.

### Claim 10 (depends on 9)

The method of claim 9, wherein the dried poly(p-dioxanone) pellets contain less than 4 mole % of unreacted PDO monomer at the end of drying process.

### Claim 11 (depends on 9)

The method of claim 9, wherein the dried poly(p-dioxanone) pellets have an inherent viscosity (IV) as measured in hexafluoroisopropanol at 25° C. and at a concentration of 0.10 g/dL of greater than 1.2 dl/g.

### Claim 12 (depends on 9)

The method of claim 9, wherein the dried poly(p-dioxanone) pellets have a weight average molecular weight (Mw) greater than 50,000 Daltons, as measured by gel permeation chromatography.

### Claim 13 (depends on 9)

The method of claim 9, wherein the dried poly(p-dioxanone) pellets have a crystallinity level greater than 45% as measured by Wide Angle X-ray Diffraction (WAXD) after being subjected to a heat treatment between about 60° C. and 90° C. for at least six hours.