Controlled release of biologically active compounds

• US 8,552,139 B2
• Filed: 05/31/2012
• Issued: 10/08/2013
• Est. Priority Date: 08/30/2007
• Status: Active Grant

• Current Assignee: Bezwada Biomedical, LLC
• Original Assignee: Bezwada Biomedical, LLC
• Inventors: Bezwada, Rao S
• Primary Examiner(s): Choi, Ling
• Assistant Examiner(s): WANG, CHUN CHENG
• Application Number:
  US13/484,391
• Publication Number:
  US 20130142752A1
• Time in Patent Office: 495 Days
• Field of Search: 528/74.5, 528/272, 424/426, 514/772.3, 523/105, 523/113
• US Class Current: 528/74.5
• CPC Class Codes: A61K 2800/10 General cosmetic use
• CPC Class Codes: A61K 31/785 Polymers containing nitrogen
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/32 Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers , poly(meth)acrylates, or polyvinyl pyrrolidone
• CPC Class Codes: 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
• CPC Class Codes: A61K 8/85 Polyesters
• CPC Class Codes: A61K 8/88 Polyamides
• CPC Class Codes: A61L 17/105 Polyesters not covered by A61L17/12
• CPC Class Codes: A61L 17/12 Homopolymers or copolymers of glycolic acid or lactic acid
• CPC Class Codes: A61L 17/145 Coating
• CPC Class Codes: A61L 27/18 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/34 Macromolecular materials
• CPC Class Codes: A61L 27/58 Materials at least partially resorbable by the body
• CPC Class Codes: A61L 31/06 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds A61L31/041 takes precedence
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: A61Q 19/00 Preparations for care of the skin
• CPC Class Codes: C07C 59/70 Ethers of hydroxy-acetic acid , e.g. substitutes on the ring
• CPC Class Codes: C07C 69/63 of saturated acids
• CPC Class Codes: C07C 69/736 the hydroxy group of the ester being etherified with a hydroxy compound having the hydroxy group bound to a carbon atom of a six-membered aromatic ring
• CPC Class Codes: C07D 311/36 : not hydrogenated in the hetero ring, e.g. isoflavones
• CPC Class Codes: C08G 63/16 : Dicarboxylic acids and dihydroxy compounds
• CPC Class Codes: C08G 63/672 : Dicarboxylic acids and dihydroxy compounds
• CPC Class Codes: C08G 69/40 : Polyamides containing oxygen in the form of ether groups C08G69/12, C08G69/32 take precedence
• CPC Class Codes: C08G 69/44 : Polyester-amides
• CPC Class Codes: C08L 67/04 : Polyesters derived from hydroxycarboxylic acids, e.g. lactones C08L67/06 takes precedence
• CPC Class Codes: C08L 77/12 : Polyester-amides

Abstract

The present invention relates to biodegradable polymers (e.g., polyesters and polyester amides) derived from functionalized biologically active compounds that can provide site specific delivery of bioactive compounds upon biodegradation in a controlled manner.

Claims

1. A composition comprising at least two different polymers, wherein each polymer is independently selected from:

a biodegradable polyester of formula III, VI, or XI, or a pharmaceutically acceptable salt thereof;

(A)

—

[(X)_a—

O—

R₁—

O—

(Y)_b—

(Y¹)_c—

R₂—

(X¹)_d]_m—

 

 

III

wherein the polyester of formula III is formed by condensation polymerization of monomers of formula I and II;

H—

(X)_a—

O—

R₁—

O—

(Y)_b—

H 

 

I

R₃—

(Y¹)_c—

R₂—

(X¹)_d—

R₄ 

 

II

B

—

[(Y²)_a—

R₅—

(X²)_b—

(X¹)_c—

O(O═

)C—

R₈—

C(═

O)O—

(Y¹)_d]_n—

 

 

VI

wherein the polyester of formula IV is formed by condensation polymerization of monomers of formula IV and V;

R₆—

(Y²)_a—

R₅—

(X²)_b—

R₇ 

 

IV

H—

(X¹)_c—

O(O═

)C—

R₈—

C(═

O)O—

(Y¹)_d—

H 

 

V

(E)

—

[(Y)_e—

R₁₃—

C(═

O)O—

(Y)_f]_g—

 

 

XI

wherein the polyester of formula XI is formed by self condensation polymerization of a monomer of formula X;

R₁₄—

(Y)_e—

R₁₃—

C(═

O)O—

(Y)_f—

H 

 

X

wherein;

m, n, and q are each independently an integer from about 5 to about 1000;

R₁, R₅, and R₁₃ are each independently the remaining portion of a biologically active compound;

R₂ and R₈ are each independently the remaining portion of a biologically active compound or non-biologically active compound;

R₃, R₄, R₆, R₇, and R₁₄ are each independently selected from Cl, F, Br, and I;

X, X¹, and X² are independently at each occurrence —

OC(═

O)CH₂—

(inverse glycolic acid moiety), —

OC(═

O)CH(CH₃)—

(inverse lactic acid moiety), —

OC(═

O)CH₂OCH₂CH₂—

(inverse dioxanone acid moiety), —

OC(═

O)CH₂CH₂CH₂CH₂CH₂—

(inverse caprolactone acid moiety), —

OC(═

O)(CH₂ )_y—

, or —

OC(═

O)(OCH₂CH₂)_z—

;

Y, Y¹, and Y² are independently at each occurrence —

CH₂C(═

O)O—

(glycolic acid moiety), —

CH(CH₃)C(═

O)O—

(lactic acid moiety), —

CH₂CH₂OCH₂C(═

O)O—

(dioxanone moiety), —

CH₂CH₂CH₂CH₂CH₂C(═

O)O—

(caprolactone moiety), —

(CH₂ )_yC(═

O)O—

, or —

(CH₂CH₂O)_zCH₂C(═

O)O—

;

each y and z is independently an integer from about 2 to about 24;

each a, b, c, and d is independently an integer from about 1 to about 6;

each e is independently an integer from about 1 to about 6; and

each f is independently an integer from about 0 to about 6.

17. A drug delivery system comprising at least one polymer according to claim 1 physically admixed with a biologically or pharmacologically active agent, wherein the polymer is selected from:

a biodegradable polyester of formula III, VI, or XI, or a pharmaceutically acceptable salt thereof;

(A)

—

[(X)_a—

O—

R₁—

O—

(Y)_b—

(Y¹)_c—

R₂—

(X¹)_d]_m—

 

 

III

wherein the polyester of formula III is formed by condensation polymerization of monomers of formula I and II;

H—

(X)_a—

O—

R₁—

O—

(Y)_b—

H 

 

I

R₃—

(Y¹)_c—

R₂—

(X¹)_d—

R₄ 

 

II

(B)

—

[(Y²)_a—

R₅—

(X²)_b—

(X¹)_c—

O(O═

)C—

R₈13 C(═

O)O—

(Y¹)_d]_n—

 

 

VI

wherein the polyester of formula IV is formed by condensation polymerization of monomers of formula IV and V;

R₆—

(Y²)_a—

R₅—

(X²)_b—

R₇ 

 

IV

H—

(X¹)_c—

O(O═

)C—

R₈—

C(═

O)O—

(Y¹)_d—

H 

 

V

(E)

—

[(Y)_e—

R₁₃ —

C(═

O)O—

(Y)_f]_g—

 

 

XI

wherein the polyester of formula XI is formed by self condensation polymerization of a monomer of formula X;

R₁₄—

(Y)_e—

R₁₃—

C(═

O)O—

(Y)_f—

H 

 

X

wherein;

m, n, and q are each independently an integer from about 5 to about 1000;

R₁, R₅, and R₁₃ are each independent the remaining portion of a biologically active compound;

R₂ and R₈ are each independently the remaining portion of a biologically active compound or non-biologically active compound;

R₃,R₄, R₆, R₇, and R₁₄ are each independent selected from Cl, F, Br, and I;

X, X¹, and X² are independent at each occurrence —

OC(═

O)CH₂—

(inverse glycolic acid moiety), —

OC(═

O)CH(CH₃)—

(inverse lactic acid moiety), —

OC(═

O)CH₂OCH₂CH₂—

(inverse dioxanone acid moiety), —

OC(═

O)CH₂CH₂CH₂CH₂CH₂—

(inverse caprolactone acid moiety), —

OC(═

O)(CH₂)_y—

, or —

OC(═

O)CH₂(OCH₂CH₂ )_z—

;

Y, Y¹, and Y² are independently at each occurrence —

CH₂C(═

O)O—

(glycolic acid moiety), —

CH(CH₃)C(═

O)O—

(inverse lactic acid moiety), —

CH₂CH₂OCH₂C(═

O)O—

(dioxanone moiety), —

CH₂CH₂CH₂CH₂CH₂C(═

O)O—

(caprolactone moiety), —

(CH₂)_yC(═

O)O—

, or —

(CH₂CH₂O)_zCH₂C(═

O)O—

;

each y and z is independently an integer from about 2 to about 24;

each a, b, c, and d is independently an integer from about 1 to about 6;

each e is independently an integer from about 1 to about 6; and

each f is independently an integer from about 0 to about 6.

18. A drug delivery system of claim 17, wherein the biologically or pharmacologically active agent is physically embedded or dispersed into the polymer and the polymer is in the form of a polymeric matrix.

2. A cosmetic composition comprising a cosmetic ingredient and at least one polymer selected from:

a biodegradable polyester of formula III, VI, or XI, or a pharmaceutically acceptable salt thereof;

(A)

—

[(X)_a—

O—

R₁—

O—

(Y)_b—

(Y¹)_c—

R₂—

(X¹)_d]_m—

 

 

III

wherein the polyester of formula III is formed by condensation polymerization of monomers of formula I and II;

H—

(X)_a—

O—

R₁—

O—

(Y)_b—

H 

 

I

R₃—

(Y¹)_c—

R₂—

(X¹)_d—

R₄ 

 

II

(B)

—

[(Y²)_a—

R₅—

(X²)_b—

(X¹)_c—

O(O═

)C—

R₈—

C(═

O)O—

(Y¹)_d]_n—

 

 

VI

wherein the polyester of formula IV is formed by condensation polymerization of monomers of formula IV and V;

R₆—

(Y²)_a—

R<sub>5—

(X</sub>²)_b—

R₇ 

 

IV

H—

(X¹)_c—

O(O═

)C—

R₈—

C(═

O)O—

(Y¹)_d—

H 

 

V

(E)

—

[(Y)_e—

R₁₃—

C(═

O)O—

(Y)_f]_g—

 

 

XI

wherein the polyester of formula XI is formed by self condensation polymerization of a monomer of formula X;

R₁₄—

(Y)_e—

R₁₃—

C(═

O)O—

(Y)_f—

H 

 

X

wherein;

m, n, and q are each independently an integer from about 5 to about 1000;

R₁, R₅, and R₁₃ are each independent the remaining portion of a biologically active compound;

R₂ and R₈ are each independently the remaining portion of a biologically active compound or non-biologically active compound;

R₃, R₄, R₆, R₇, and R₁₄ are each independent selected from Cl, F, Br, and I;

X, X¹, and X² are independent at each occurrence —

OC(═

O)CH₂—

(inverse glycolic acid moiety), —

OC(═

O)CH(CH₃)—

(inverse lactic acid moiety), —

OC(═

O)CH₂OCH₂CH₂—

(inverse dioxanone acid moiety), —

OC(═

O)CH₂CH₂CH₂CH₂CH₂—

(inverse caprolactone acid moiety), —

OC(═

O)(CH₂)_y—

, or —

OC(═

O)CH₂—

(OCH₂CH₂)_z—

;

Y, Y¹, and Y² are independently at each occurrence —

CH₂C(═

O)O—

(glycolic acid moiety), —

CH(CH₃)C(═

O)O—

(lactic acid moiety), —

CH₂CH₂OCH₂C(═

O)O—

(dioxanone moiety), —

CH₂CH₂CH₂CH₂CH₂C(═

O)O—

(caprolactone moiety), —

(CH₂)_yC(═

O)O—

, or —

(CH₂CH₂O)_zCH₂C(═

O)O—

;

each y and z is independently an integer from about 2 to about 24;

each a, b, c, and d is independently an integer from about 1 to about 6;

each e is independently an integer from about 1 to about 6; and

each f is independently an integer from about 0 to about 6.

3. An implantable medical device or coating, comprising at least one polymer selected from:

a biodegradable polyester of formula III, VI, or XI, or a pharmaceutically acceptable salt thereof;

(A)

—

[(X)_a—

O—

R₁—

O—

(Y)_b—

(Y¹)_c—

R₂—

(X¹)_d]_m—

 

 

III

wherein the polyester of formula III is formed by condensation polymerization of monomers of formula I and II;

H—

(X)_a—

O—

R₁—

O—

(Y)_b—

H 

 

I

R₃—

(Y¹)_c—

R₂—

(X¹_d—

R₄ 

 

II

(B)

—

[(Y²)_a—

R₅—

(X²)_b—

(X¹)_c—

O(O═

)C—

R₈—

C(═

O)O—

(Y¹)_d]n—

 

 

VI

wherein the polyester of formula IV is formed by condensation polymerization of monomers of formula IV and V;

R₆—

(Y²)_a—

R₅—

(X²)_b—

R₇ 

 

IV

H—

(X¹)_c—

O(O═

)C—

R₈—

C(═

O)O—

(Y¹)_d—

H 

 

V

(E)

—

[(Y)_e—

R₁₃—

C(═

O)O—

(Y)_f]_g—

 

 

XI

wherein the polyester of formula XI is formed by self condensation polymerization of a monomer of formula X;

R₁₄—

(Y)_e—

R₁₃—

C(═

O)O—

(Y)_f—

H 

 

X

wherein;

m, n, and q are each independently an integer from about 5 to about 1000;

R₁, R₅, and R₁₃ are each independent the remaining portion of a biologically active compound;

R₂ and R₈ are each independently the portion of a biologically active compound or non-biologically active compound;

R₃, R₄, R₆, R₇, and R₁₄ are each independent selected from Cl, F, Br, and I;

X, X¹, and X² are independent at each occurrence —

OC(═

O)CH₂—

(inverse glycolic acid moiety), —

OC(═

O)CH(CH₃)—

(inverse lactic acid moiety), —

OC(═

O)CH₂OCH₂CH₂—

(inverse dioxanone acid moiety), —

OC(═

O)CH₂CH ₂CH ₂CH₂CH₂—

(inverse caprolactone acid moiety), —

OC(═

O)(CH₂)_y—

, or —

OC(═

O)CH₂(OCH₂CH₂)_z—

;

Y, Y¹, and Y² are independently at each occurrence —

CH₂C(═

O)O—

(glycolic acid moiety), —

CH(CH₃)C(═

O)O—

(lactic acid moiety), —

CH₂CH₂OCH₂C(═

O)O—

(dioxanone moiety), —

CH₂CH₂CH₂CH₂CH₂C(═

O)O—

(caprolactone moiety), —

(CH₂)_yC(═

O)O—

, or —

(CH₂CH₂O)_zCH₂C(═

O)O—

;

each y and z is independently an integer from about 2 to about 24;

each a, b, c, and d is independently an integer from about 1 to about 6;

each e is independently an integer from about 1 to about 6; and

each f is independently an integer from about 0 to about 6.

4. An implantable medical device or coating of claim 3, wherein the polymer has been further polymerized with a lactone monomer selected from glycolide, lactide, ε

-caprolactone, trimethylene carbonate, ether lactones, morpholinediones, and p-dioxanone.

5. An implantable medical device or coating of claim 3, wherein the device is a stent.

6. An implantable medical device or coating of claim 5, wherein the polymer has been further polymerized with a lactone monomer selected from glycolide, lactide, ε

-caprolactone, trimethylene carbonate, ether lactones, morpholinediones, and p-dioxanone.

7. An implantable medical device or coating of claim 3, wherein the device is a scaffold for tissue engineer comprising a porous structure for the attachment and proliferation of cells.

8. An implantable medical device or coating of claim 7, wherein the polymer has been further polymerized with a lactone monomer selected from glycolide, lactide, ε

-caprolactone, trimethylene carbonate, ether lactones, morpholinediones, and p-dioxanone.

9. An implantable medical device or coating of claim 3, wherein the device is a coating for a stent.

10. An implantable medical device or coating of claim 9, wherein the polymer has been further polymerized with a lactone monomer selected from glycolide, lactide, ε

-caprolactone, trimethylene carbonate, ether lactones, morpholinediones, and p-dioxanone.

11. An implantable medical device or coating of claim 3, wherein the coating is a suture coating.

12. An implantable medical device or coating of claim 3, wherein the device is a suture.

13. An implantable medical device or coating of claim 3, wherein the polymer is a biodegradable polyester having formula III or a pharmaceutically acceptable salt thereof:

—

[(X)_a—

O—

R₁—

O—

(Y)^b—

(Y¹)_c—

R₂—

(X¹)_d]_m—

 

 

III.

14. An implantable medical device or coating of claim 3, wherein the polymer is a biodegradable polyester having formula VI or a pharmaceutically acceptable salt thereof:

—

[(Y²)_a—

R₅—

(X²)_b—

(X¹)_c—

O(O═

)C—

R₈—

C(═

O)O—

(Y¹)_d]_n—

 

 

VI.

15. An implantable medical device or coating of claim 3, wherein the polymer is a biodegradable polyester having formula XI or a pharmaceutically acceptable salt thereof:

—

[(Y)_e—

R₁₃—

C(═

O)O—

(Y)_f]_g—

 

 

XI.

16. An implantable medical device or coating of claim 3, wherein the polymer is a biodegradable polyester of claim 14, wherein the non-biologically active compound is a dicarboxylic compound selected from:

19. An antimicrobial agent comprising at least one polymer selected from:

a biodegradable polyester of formula III, VI, or XI, or a pharmaceutically acceptable salt thereof;

(A)

—

[(X)_a—

O—

R₁—

O—

(Y)^b—

(Y¹)_c—

R₂—

(X¹)_d]_m—

 

 

III

wherein the polyester of formula III is formed by condensation polymerization of monomers of formula I and II;

H—

(X)_a—

O—

R₁—

O—

(Y)_b—

H 

 

I

R₃—

(Y¹)_c—

R₂—

(X¹)_d—

R₄ 

 

II

(B)

—

[(Y²)_a—

R₅—

(X²)_b—

(X¹)_c—

O(O═

)C—

R₈—

C(═

O)O—

(Y¹)_d]_n—

 

 

VI

wherein the polyester of formula IV is formed by condensation polymerization of monomers of formula IV and V;

R₆—

(Y²)_a—

R₅—

(X²)_b—

R₇ 

 

IV

H—

(X¹)_c—

O(O═

)C—

R₈—

C(═

O)O—

(Y¹)_d—

H 

 

V

(E)

—

[(Y)_e—

R₁₃—

C(═

O)O—

(Y)_f]_g—

 

 

XI

wherein the polyester of formula XI is formed by self condensation polymerization of a monomer of formula X;

R₁₄—

(Y)_e—

R₁₃—

C(═

O)O—

(Y)_f—

H 

 

X

wherein;

m, n, and q are each independently an integer from about 5 to about 1000;

R₁, R₅, and R₁₃ are each independent the remaining portion of a biologically active compound;

R₂ and R₈ are each independently the remaining portion of a biologically active compound or non-biologically active compound;

R₃, R₄, R₆, R₇, and R₁₄ are each independent selected from Cl, F, Br, and I;

X, X¹, and X² are independent at each occurrence —

OC(═

O)CH₂—

(inverse glycolic acid moiety), —

CH(CH₃)C(═

O)O—

(inverse lactic acid moiety), —

OC(═

O)CH₂OCH₂CH₂—

(inverse dioxanone acid moiety), —

OC(═

O)CH₂CH₂CH₂CH₂CH₂—

(inverse caprolactone acid moiety), —

OC(═

O)(CH₂)_y—

, or —

OC(═

O)CH₂(OCH₂CH₂)_z—

;

Y, Y¹, and Y² are independently at each occurrence —

CH₂C(═

O)O—

(glycolic acid moiety),—

CH(CH₃)C(═

O)O—

(lactic acid moiety), —

CH₂CH₂OCH₂C(═

O)O—

(dioxanone moiety), —

CH₂CH₂CH₂CH₂CH₂C(═

O)O—

(caprolactone moiety), —

(CH₂)_yC(═

O)O—

, or —

(CH₂CH₂O)_zCH₂C(═

O)O—

;

each y and z is independently an integer from about 2 to about 24;

each a, b, c, and d is independently an integer from about 1 to about 6;

each e is independently an integer from about 1 to about 6; and

each f is independently an integer from about 0 to about 6.

20. A method for treating a disease in a patient, comprising administering to an animal in need of such therapy, an effective amount of at least one polymer selected from:

a biodegradable polyester of formula III, VI, or XI, or a pharmaceutically acceptable salt thereof;

(A)

—

[(X)_a—

O—

R₁—

O—

(Y)_b—

(Y¹)_c—

R₂—

(X¹)_d]_m—

 

 

III

wherein the polyester of formula III is formed by condensation polymerization of monomers of formula I and II;

H—

(X)_a—

O—

R₁—

O—

(Y)_b—

H 

 

I

R₃—

(Y¹)_c—

R₂—

(X¹)_d—

R₄ 

 

II

(B)

—

[(Y²)_a—

R₅—

(X²)_b—

(X¹)_c—

O(O═

)O—

(Y¹)_d]_n—

 

 

VI

wherein the polyester of formula IV is formed by condensation polymerization of monomers of formula IV and V;

R₆—

(Y²)_a—

R₅—

(X²)_b—

R₇ 

 

IV

H—

(X¹)_c—

O(O═

)C—

R₈—

C(═

O)O—

(Y¹)_d—

H 

 

V

(E)

—

[(Y)_e—

R₁₃—

C(═

O)O—

(Y)_f]_g—

 

 

XI

wherein the polyester of formula XI is formed by self condensation polymerization of a monomer of formula X;

R₁₄—

(Y)_e—

R₁₃—

C(═

O)O—

(Y)_f—

H 

 

X

wherein;

m, n, and q are each independently an integer from about 5 to about 1000;

R₁, R₅, and R₁₃ are each independent the remaining portion of a biologically active compound;

R₂ and R₈ are each independently the remaining portion of a biologically active compound or non-biologically active compound;

R₃, R₄, R₆, R₇, and R₁₄ are each independently selected from Cl, F, Br, and I;

X, X¹, and X² are independent at each occurrence —

OC(═

O)CH₂—

(inverse glycolic acid moiety), —

OC(═

O)CH(CH₃)—

(inverse lactic acid moiety), —

OC(═

O)CH₂OCH₂CH₂—

(inverse dioxanone acid moiety), —

OC(═

O)CH₂CH₂CH₂CH₂CH₂—

(inverse caprolactone acid moiety), —

OC(═

O)(CH₂)_y—

, or —

OC(═

O)CH₂(OCH₂CH₂)_z—

;

Y, Y¹, and Y² are independently at each occurrence —

CH₂C(═

O)O—

(glycolic acid moiety), —

CH(CH₃)C(═

O)O—

(lactic acid moiety), —

CH₂CH₂OCH₂C(═

O)O—

(dioxanone moiety), —

CH₂CH₂CH₂CH₂CH₂C(═

O)O—

(caprolactone moiety), —

(CH₂)_yC(═

O)O—

, or —

(CH₂CH₂O)_zCH₂C(═

O)O—

;

each y and z is independently an integer from about 2 to about 24;

each a, b, c, and d is independently an integer from about 1 to about 6;

each e is independently an integer from about 1 to about 6; and

each f is independently an integer from about 0 to about 6.

21. A method of claim 20, wherein the disease is cancer.

22. A method of claim 20, wherein the disease is selected from psoriasis, inflammatory bowel disease, skin cancer, and a brain tumor.

23. A method for producing an effect in a patient comprising administering to an animal in need of such therapy, an effective amount of at least one polymer selected from:

a biodegradable polyester of formula III, VI, or XI, or a pharmaceutically acceptable salt thereof and the effect being selected from an analgesic effect, anti-inflammatory effect, anti-bacterial effect, an anti-fungal effect, an immunosuppressive effect, an anti-thrombotic effect, and an anti-infective effect, wherein;

(A)

—

[(X)_a—

O—

R₁—

O—

(Y)^b—

(Y¹)_c—

R₂—

(X¹)_d]_m—

 

 

III

wherein the polyester of formula III is formed by condensation polymerization of monomers of formula I and II;

H—

(X)_a—

O—

R₁—

O—

(Y)_b—

H 

 

I

R₃—

(Y¹)_c—

R₂—

(X¹)_d—

R₄ 

 

II

(B)

—

[(Y²)_a—

R₅—

(X²)_b—

(X¹)_c—

O(O═

)C—

R₈—

C(═

O)O—

(Y¹)_d]_n—

 

 

VI

wherein the polyester of formula IV is formed by condensation polymerization of monomers of formula IV and V;

R₆—

(Y²)_a—

R₅—

(X²)_b—

R₇ 

 

IV

H—

(X¹)_c—

O(O═

)C—

R₈—

C(═

O)O—

(Y¹)_d—

H 

 

V

(E)

—

[(Y)_e—

R₁₃—

C(═

O)O—

(Y)_f]_g—

 

 

XI

wherein the polyester of formula XI is formed by self condensation polymerization of a monomer of formula X;

R₁₄—

(Y)_e—

R₁₃—

C(═

O)O—

(Y)_f—

H 

 

X

wherein;

m, n, and q are each independently an integer from about 5 to about 1000;

R₁, R₅, and R₁₃ are each independent the remaining portion of a biologically active compound;

R₂ and R₈ are each independently the remaining portion of a biologically active compound or non-biologically active compound;

R₃, R₄, R₆, R₇, and R₁₄ are each independent selected from Cl, F, Br, and I;

X, X¹, and X² are independently at each occurrence —

OC(═

O)CH₂—

(inverse glycolic acid moiety), —

OC(═

O)CH(CH₃)—

(inverse lactic acid moiety), —

OC(═

O)CH₂OCH₂CH₂—

(inverse dioxanone acid moiety), —

OC(═

O)CH₂CH₂CH₂CH₂CH₂—

(inverse caprolactone acid moiety), —

OC(═

O)(CH₂)_y—

, or —

OC(═

O)CH₂(OCH₂CH₂ )_z—

;

Y, Y¹, and Y² are independently at each occurrence —

CH₂C(═

O)O—

(glycolic acid moiety), —

CH(CH₃)C(═

O)O—

(lactic acid moiety), —

CH₂CH₂OCH₂C(═

O)O—

(dioxanone moiety), —

CH₂CH₂CH₂CH₂CH₂C(═

O)O—

(caprolactone moiety), —

(CH₂)_yC(═

O)O—

, or —

(CH₂CH₂O)_zCH₂C(═

O)O—

;

each y and z is independently an integer from about 2 to about 24;

each a, b, c, and d is independently an integer from about 1 to about 6;

each e is independently an integer from about 1 to about 6; and

each f is independently an integer from about 0 to about 6.

24. A method of claim 23, wherein the effect is an anti-inflammatory effect.

25. A method of claim 23, wherein the effect is an anti-bacterial effect.

26. A method of claim 23, wherein the effect is an anti-fungal effect.

27. A method of claim 23, wherein the effect is an immunosuppressive effect.

28. A method of claim 23, wherein the effect is an anti-thrombotic effect.

29. A method of claim 23, wherein the effect is an anti-infective effect.

30. A method of claim 23, wherein the effect is an analgesic effect.