High molecular weight polyesterpolycarbonates and the use thereo

Details High molecular weight polyesterpolycarbonates and the use thereo High molecular weight polyesterpolycarbonates and the use thereo

1996-06-24

1997-12-16

Mosley, Terressa

Synthetic resins or natural rubbers -- part of the class 520 ser

Synthetic resins

From carboxylic acid or derivative thereof

427 2, 523105, 523113, 524381, 528176, 528196, 528361, C08G 6308

Patent

active

056986610

DESCRIPTION:

BRIEF SUMMARY
The present invention relates to polyesterpolycarbonates of general formula (I) ##STR4## wherein a is an integer from 2 to 300; R.sub.1 and R.sub.2, which can be the same or different, are each a polyester residue of formula (II) ##STR5## wherein x and y are integers from 0 to 100, the ratio (x/x+y)*100, being comprised between 0 and 100, with the proviso that x and y are not 0 at the same time; R.sub.3 and R.sub.4, which can be the same or different, are each a straight or branched chain aliphatic hydrocarbon residue having from 1 to 4 carbon atoms; R.sub.5 is a straight or branched chain aliphatic hydrocarbon residue having from 2 to 18 carbon atoms or a cycloaliphatic hydrocarbon residue having from 3 to 8 carbon atoms, optionally bearing one or more straight or branched alkyl substituents; or it is a polyoxyalkylene residue of formula (III): ##STR6## wherein: R.sub.6 is hydrogen or methyl, n is an integer from 1 to 3 and m is an integer from 1 to 200; the two --R.sub.3 --COO and --R.sub.4 --COO groups being randomly distributed in the polyester residue, with the proviso that the polyesterpolycarbonates of formula (I) have intrinsic viscosity not lower than 0.45 dl/g.
Generally, the polymers used as carriers for controlled release drugs must be biocompatible, non toxic, free from impurities. Particularly, biodegradable polymers must give non-toxic, non-cancerogenic, non-teratogenic degradation products and must be easily eliminated.
The factors which affect biodegradability are chemical structure, morphology and particle size. Among these factors, crystallinity plays an important role, in view both of biodegradability and technology of polymer processing.
The common microencapsulation techniques comprise coacervation, evaporation of the emulsified solvent, coextrusion. The latter is the preferred technique since it avoids the use of solvents and accordingly implies no toxicologic problems due to solvent residues.
Extrudible polymers must be stable at the coextrusion temperature, have a softening point nor too high, to avoid drug decomposition, nor too low, to avoid storage problems.
Examples of pharmaceutical formulations, in which the drug (active ingredient) is incorporated in a biodegradable matrix, are well known in the art. Reference may be made to "Biodegradable Polymers as Drug Delivery Systems", ed. by M. Chasin and R. Langer, Marcel Drekker Inc., Orlando, Fla., 1985; "Formes Pharmaceutiques Nouvelles", P. Buri, F. Puisieux, E. Dalker, J. P. Benoit, Technique and documentation (Lavoisier), Paris, 1985; "Biodegradable Polymers for controlled Release of Peptides and Proteins", F. G. Hutchison and B. J. A. Furr, in Drug Carrier Systems, F. H. D. Roerdink and A. M. Kroom eds., John Wiley and Sons, Chichester, 1989; "Controlled Release of Biologically Active Agents" Richard Baker, John Wiley and Sons, New York, 1987.
Different kinds of polymers have been used for the above purposes and among these polycarbonates showed appropriate biocompatibility characteristics. Kawaguchi et al. (Chem. Pharm. Bull. vol. 31, n. 4, 1400-1403, 1983) disclose the biodegradability of polyethylene carbonate and polypropylene carbonate tablets and the possibility to obtain biocompatible materials having programmed degradation by suitably admixing the two polycarbonates.
Polycarbonates have been well known for a long time. Aliphatic polycarbonates are well known for example from DE 2546534, published on Apr. 28, 1977, JP 6224190, published on Oct. 22, 1987, JP 1009225, published on Jan. 12, 1989, which provide them as plastifying agents and intermediates for the preparation of polyurethanes (see also U.S. Pat. No. 4,105,641, issued Aug. 8, 1978).
Also polycarbonates having homo- and copolymeric nature have been proposed.
In U.S. Pat. No. 4,716,203 (American Cyanamid), issued on Dec. 29, 1987, diblock and triblock copolymers are disclosed, having a first block of glycolic acid ester linked with trimethylene carbonate; triblock copolymers have an intermediate block obtained from ethylene oxide homopolymer or ethylene oxide-c

REFERENCES:
patent: 4705820 (1987-11-01), Wang et al.
1297a Macromolecular Rapid Communications 15 (1994) Sep., No. 9, Zug, CH, "New High-molecular-weight poly9ester-carbonates) by chain extension of . . . " by M. Penco et al.

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