Claims for Patent: 11,844,837

Summary for Patent: 11,844,837

Title:	Compositions of a polyorthoester and an organic acid excipient
Abstract:	Delivery systems and compositions comprised of a biodegradable polyorthoester polymer, an organic acid excipient, and a basic drug are described, along with related methods.
Inventor(s):	Thomas B. Ottoboni, Lee Ann Lynn Girotti
Assignee:	Heron Therapeutics LLC
Application Number:	US17/209,078
Patent Claims:	1. A method for pain management, comprising: administering to a subject in need a composition comprising a polyorthoester, maleic acid, an aprotic solvent selected from N-methyl-2-pyrrolidone (NMP) and dimethyl sulfoxide (DMSO), and a therapeutically active agent dispersed or solubilized in the composition, wherein the therapeutically active agent is selected from the group consisting of bupivacaine, levobupivacaine, dibucaine, mepivacaine, procaine, lidocaine, tetracaine, and ropivacaine, and wherein the maleic acid is present in less than an equimolar amount when compared to the therapeutically active agent, such that the therapeutically active agent is present as a mixed salt-base and the composition is substantially free of crystals of the therapeutically active agent. 2. The method of claim 1, wherein the therapeutically active agent is solubilized in the composition. 3. The method of claim 1, wherein the polyorthoester is selected from polyorthoesters represented by Formulas I, II, III or IV: where: R is a bond, —(CH2)a—, or —(CH2)b−)—O—(CH2)c—; where a is an integer of 1 to 12, and b and c are independently integers from 1 to 5; R* is a C1-4 alkyl; Ro, R′ and R′″ are each independently H or C1-4 alkyl; n is an integer of at least 5; and A is R1, R2, R3, or R4, where R1 is an α-hydroxy acid containing subunit or where: p and q are integers that vary from between 1 and 20, where the average number of p or the average sum of p and q is between 1 and 7; R5 is hydrogen or C1-4 alkyl; and R6 is selected from the group consisting of where: s is an integer of 0 to 30; t is an integer of 2 to 200; and R7 is hydrogen or C1-4 alkyl; R2 is: R3 is: where: x is an integer ranging from 0 to 200; y is an integer ranging from 2 to 200; R8 is hydrogen or C1-4 alkyl; R9 and R10 are independently C1-12 alkylene; R11 is hydrogen or C1-6 alkyl and R12 is C1-6 alkyl; or R11 and R12 together are C3-10 alkylene; and R4 is the residue of a diol containing at least one functional group independently selected from amide, imide, urea, and urethane groups. 4. The method of claim 1, wherein the polyorthoester is represented by Formula III: wherein: R* is a C1-4 alkyl, n is an integer ranging from 5 to 400, and A in each subunit is R1 or R3, wherein: R1 is where p and q are each independently integers that range from between about 1 to 20, each R5 is independently hydrogen or C1-4 alkyl; and R6 is: where s is an integer from 0 to 10; t is an integer from 2 to 30; and R7 is hydrogen or C1-4 alkyl, R3 is: and x is an integer ranging from 1 to 100; y is an integer in a range from 2 to 30; and R8 is hydrogen or C1-4 alkyl. 5. The method of claim 1, wherein said administering comprises instilling the composition to a surgical site. 6. A method of prophylactic treatment of pain to a patient in need thereof, comprising: locally administering to the patient in need a composition comprising a polyorthoester, maleic acid, an aprotic solvent selected from N-methyl-2-pyrrolidone (NMP) and dimethyl sulfoxide (DMSO), and an amino-amide anesthetic a therapeutically active agent dispersed or solubilized in the composition, wherein the therapeutically active agent is selected from the group consisting of bupivacaine, levobupivacaine, dibucaine, mepivacaine, procaine, lidocaine, tetracaine, and ropivacaine, and wherein the maleic acid is present in less than an equimolar amount when compared to the therapeutically active agent amino-amide anesthetic, such that the therapeutically active agent is present as a mixed salt-base and the composition is substantially free of crystals of the therapeutically active agent. 7. The method of claim 6, wherein said locally administering is dispensing from a needle. 8. A method for managing or treating post-operative pain, comprising: administering to a subject in need a composition comprising a polyorthoester, maleic acid, an aprotic solvent selected from N-methyl-2-pyrrolidone (NMP) and dimethyl sulfoxide (DMSO), and an amino-amide anesthetic a therapeutically active agent dispersed or solubilized in the composition, wherein the therapeutically active agent is selected from the group consisting of bupivacaine, levobupivacaine, dibucaine, mepivacaine, procaine, lidocaine, tetracaine, and ropivacaine, and wherein the maleic acid is present in less than an equimolar amount when compared to the therapeutically active agent amino-amide anesthetic, such that the therapeutically active agent is present as a mixed salt-base and the composition is substantially free of crystals of the therapeutically active agent. 9. A method for reducing or preventing post-operative pain, comprising: administering to a subject in need a composition comprising a polyorthoester, maleic acid, an aprotic solvent selected from N-methyl-2-pyrrolidone (NMP) and dimethyl sulfoxide (DMSO), and a therapeutically active agent dispersed or solubilized in the composition, wherein the therapeutically active agent is selected from the group consisting of bupivacaine, levobupivacaine, dibucaine, mepivacaine, procaine, lidocaine, tetracaine, and ropivacaine, and wherein the maleic acid is present in less than an equimolar amount when compared to the therapeutically active agent, such that the therapeutically active agent is present as a mixed salt-base and the composition is substantially free of crystals of the therapeutically active agent.