Biodegradable polymers, compositions, articles and methods for making and using the same
AssigneeThe Johns Hopkins University School of Medicine
InventorsHai-Quan Mao, Kam W. Leong
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Abstract
Biodegradable polymer compositions that degrade in vivo into non-toxic residues are described. In part, the present invention is directed to such polymers containing phosphorus and desaminotyrosyl L-tyrosine linkages in the polymer backbone. Processes for preparing such polymers, compositions containing such polymers and biologically active substances, articles useful for implantation or injection into the body fabricated from the compositions, and methods for controllably releasing biologically active substances using the polymers, are also described.
Claims72
A biodegradable polymer comprising at least about five monomeric units shown in formula I:
- wherein independently for each monomeric unit of said biodegradable polymer:
- (a) Ar are independently aryl moieties;
- (b) X are independently selected for each occurrence in said monomeric unit from the group consisting of O and S;
- (c) Y is selected from the group consisting of phosphonamidite, phosphoramidite, phosphorodiamidate, phosphomonoester, phosphodiester, phosphotriester, phosphonate, phosphonate ester, phosphorothioate, thiophosphate ester, phosphinate, and phosphite;
- (d) R and R1 are independently aliphatic groups;
- (e) n and m are independently selected from the group consisting of 0, 1, 2 or 3;
- and
- (f) * are independently selected for each occurrence in said monomeric unit from the group consisting of another monomeric unit of said biodegradable polymer and a chain terminating group;
- wherein said biodegradable polymer is biocompatible before and upon biodegradation.
A process for preparing a biodegradable polymer comprising at least about five of the recurring monomeric units of formula I:
- wherein each of said monomeric unit of said biodegradable polymer:
- (a) Ar are independently aryl moieties;
- (b) X are independently selected for each occurrence in said monomeric unit from the group consisting of O and S;
- (c) Y is selected from the group consisting of phosphonamidite, phosphoramidite, phosphorodiamidate, phosphomonoester, phosphodiester, phosphotriester, phosphonate, phosphonate ester, phosphorothioate, thiophosphate ester, phosphinate, and phosphite;
- (d) R and R1 are independently aliphatic groups;
- (e) n and m are independently selected from the group consisting of 0, 1, 2 or 3;
- and
- (f) * are independently selected for each occurrence in said monomeric unit from the group consisting of another monomeric unit of said biodegradable polymer and a chain terminating group;
- said process comprising reacting an amino acid derivative with a phosphorous-based compound to form the biodegradable polymer of formula I, wherein said biodegradable polymer is biocompatible before and upon biodegradation.
A biodegradable polymer comprising at least about five monomeric units shown in formula II:
- wherein independently for each monomeric unit of said biocompatible polymer:
- (a) Ar are independently aryl moieties;
- (b) X are independently selected for each occurrence in said monomeric unit from the group consisting of O and S;
- (c) Q1 is selected from the group consisting of O and S,
- (d) Q2 is selected from the group consisting of O, S and NE;
- (e) R is selected from the group consisting of H, alkyl, alkenyl, alkynyl, aryl and heterocycle;
- (f) R′ is selected from the group consisting of hydrogen, alkyl, —O-alkyl, aryl, —O-aryl, heterocycle, —O-heterocycle, and —N(R9)R10, wherein R9 and R10 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, —(CH2)i-R80, and heterocycle comprising R9, R10, said N atom of said N(R9)R10, and 4 to 8 atoms in the ring structure, wherein R80 is selected from the group consisting of aryl, cycloalkyl, cycloalkenyl, heterocycle, and polycycle;
- (g) R1 is selected from the group consisting of H and a lower alkyl;
- (h) n and m are independently selected from the group consisting of 0, 1, 2 or 3;
- and
- (i) * are independently selected for each occurrence in said monomeric unit from the group consisting of another monomeric unit of said biodegradable polymer and a chain terminating group;
- wherein said biodegradable polymer is biocompatible before and upon biodegradation.
Dependencies are inferred from the claim text.