# US 6,297,350 B1 · Process for the preparation of copolyesters

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- Number: US 6,297,350 B1
- Document ID: US6297350B1
- Status: Granted
- Kind: B1
- Application number: 09/424,935
- Filed: 2000-02-15
- Granted: 2001-10-02
- Earliest claimed: 1997-06-06
- Assignees: Ferring B.V.
- Inventors: Hans R. Kricheldorf; Ingrid Kreiser-Saunders; Dirk-Olaf Damrau
- Web page: https://patentgrep.com/patent/US6297350B1

## CPC

- C08G 64/30: using carbonates
- A61K 9/1647: {Polyesters, e.g. poly(lactide-co-glycolide)}
- A61K 9/204: {Polyesters, e.g. poly(lactide-co-glycolide)}
- B01J 31/04: containing carboxylic acids or their salts {(B01J31/0277 - B01J31/0298 take precedence; multi-metal carboxylate complexes like Pd (II) acetate, i.e. Pd3 (OAc) 6 or Cr(II)acetate, i.e. Cr2(OAc)4 B01J31/2226)}
- C07C 51/412: {by conversion of the acids, their salts, esters or anhydrides with the same carboxylic acid part}
- C08G 63/823: {for the preparation of polylactones or polylactides}
- A61K 47/34: Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers (A61K47/10 takes precedence)
- B01J 2231/14: Other (co) polymerisation, e.g. of lactides or epoxides
- C08G: MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- B01J: CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS

## Abstract

Copolyesters are prepared using cyclic esters or carbonates as monomers and a metallic salt of the formula Me2+X2 as catalyst. Me2+ represents Ca, Fe(II), Mg, Mn(II) or Zn, and X is an anion of an aminocarboxylic acid, hydroxycarboxylic acid or a halide. Monomer and catalyst are used in a monomer/catalyst ratio of greater than 100.

## Claims

### Claim 1

A process for the preparation of copolyesters using cyclic esters or cyclocarbonates or a mixture of at least one cyclic ester and at least one cyclocarbonate as monomers and a metallic salt of the formula Me2+X2 as catalyst, wherein Me2+ represents Ca, Fe(II), Mg, Mn(II) or Zn, and X is an anion of an aminocarboxylic acid, hydroxycarboxylic acid, bromide or iodide, that monomer and catalyst are used in a monomer/catalyst molar ratio of greater than 100, and the monomers are structurally different.

### Claim 2 (depends on 1)

A process according to claim 1, wherein Me2+ represents Fe(II), Mn(II) or Zn.

### Claim 3 (depends on 1)

A process according to claim 1, wherein said aminocarboxylic acid is 4-amino- or 4-(acetylamino)benzoic acid, a saturated or unsaturated C1-C18 acylaminobenzoic acid, an α- and ω-amino-C2-C6-alkanoic acid, or a N-acyl, N-alkoxycarbonyl or oligopeptide derivative thereof.

### Claim 4 (depends on 1)

A process according to claim 1, wherein X is mandelate, glycolate, iodide, bromide or lactate.

### Claim 5 (depends on 1)

A process according to claim 1, wherein iron lactate, manganese lactate or zinc lactate is used as catalyst.

### Claim 6 (depends on 1)

A process according to claim 1, wherein at least two different cyclic esters or cyclocarbonates or a mixture of at least one cyclic ester and at least one cyclocarbonate is used as monomers.

### Claim 7 (depends on 6)

A process according to claim 6, wherein a glycolide, a lactide, a lactone of the formula
a dioxanone of the formula
and/or an ester of the formula
is used as cyclic ester, in which n=1-12 and R represents H, CH3 and C2H5.

### Claim 8 (depends on 6)

A process according to claim 6, wherein a cyclocarbonate of the formula
is used as monomer, in which p=1-8, and R1 and R2 independently of one another represent H or straight-chain C1-C16 alkyl or, together with the carbon atom to which they are bound, form a 5- or 6-membered spiro ring.

### Claim 9 (depends on 6)

A process according to claim 6, wherein β-butyrolactone, ε-caprolactone, p-dioxanone and/or (L- or D, L)-δ-valerolactone is/are used as lactone.

### Claim 10 (depends on 1)

A process according to claim 1, wherein the polymerization is carried out in the melt in the absence of solvents.

### Claim 11 (depends on 1)

A process according to claim 1, wherein the polymerization is carried out at a temperature of 40 to 250° C.

### Claim 12 (depends on 1)

A process according to claim 1, wherein monomer and catalyst are used in a monomer/catalyst molar ratio of 150 to 15,000.

### Claim 13 (depends on 1)

A process according to claim 1, wherein, in addition, an alcohol is used as coinitiator.

### Claim 14 (depends on 13)

A process according to claim 13, wherein a vitamin, hormone and/or a pharmaceutical active ingredient is/are used as coinitiator.

### Claim 15 (depends on 1)

A process for the preparation of a medicament with controlled release of an active ingredient, comprising loading the polymer prepared according to claim 1 with a pharmaceutical active ingredient.

### Claim 16 (depends on 15)

A process according to claim 15, wherein said active ingredient is dissolved or suspended in a polymer solution and then coprecipitated jointly with the polymer.

### Claim 17 (depends on 1)

A copolyester produced by the process of claim 1.

### Claim 18 (depends on 1)

A medicament providing controlled release of an active ingredient, the medicament comprising an active ingredient incorporated in the copolymer produced by the process of claim 1.

### Claim 19 (depends on 1)

A process according to claim 1, wherein said hydroxycarboxylic acid is glycolic acid, β-hydroxybutyric acid, β-hydroxyvaleric acid, lactic acid, mandelic acid, 4-hydroxybenzoic acid, salicylic acid, or N-acetylsalicylic acid.

### Claim 20 (depends on 1)

A process according to claim 1, wherein X is bromide or iodide.

### Claim 21 (depends on 15)

A process according to claim 15, wherein said active ingredient and said polymer are dissolved in a solvent followed by freeze drying of this solution.

### Claim 22 (depends on 15)

A process according to claim 15 wherein said active ingredient is kneaded into said polymer.