Formulation for preventing or reducing bleeding at a surgical site

Abstract

An implantable drug depot useful for preventing, reducing or treating bleeding at a surgical site beneath the skin in a patient is provided. The implantable drug depot comprises a therapeutically effective amount of clonidine or a pharmaceutically acceptable salt thereof, and at least one biodegradable polymer. The drug depot is capable of releasing clonidine or a pharmaceutically acceptable salt thereof over a period of at least three days.

1 . An implantable drug depot useful for preventing, reducing or treating bleeding at a surgical site beneath the skin in a patient, the implantable drug depot comprising: (1) a therapeutically effective amount of clonidine or a pharmaceutically acceptable salt thereof, and (2) at least one biodegradable polymer; wherein the drug depot is implantable locally at the surgical site to reduce, prevent or treat bleeding, the drug depot is capable of releasing the clonidine or pharmaceutically acceptable salt thereof over a period of at least three days and the polymer comprises one or more of poly(lactide-co-glycolide) (PLGA), polylactide (PLA), polyglycolide (PGA), D-lactide, D,L-lactide, L-lactide, D,L-lactide-co-ε-caprolactone, D,L-lactide-co-glycolide-co-ε-caprolactone or a combination thereof. 
     
     
         2 . An implantable drug depot according to  claim 1 , wherein the drug depot is disposed on or within a medical device and the drug depot releases the clonidine or pharmaceutically acceptable salt thereof over a period of 3 to 7 days. 
     
     
         3 . An implantable drug depot according to  claim 1 , wherein the polymer comprises about 60% to 99% of the total weight % of the drug depot. 
     
     
         4 . An implantable drug depot according to  claim 1 , wherein the drug depot releases (i) a bolus dose of the clonidine or pharmaceutically acceptable salt thereof at the surgical site over a first period of up to 48 hours and (ii) an effective amount of the clonidine or pharmaceutically acceptable salt thereof over a subsequent period of at least 3 days. 
     
     
         5 . An implantable drug depot according to  claim 1 , wherein the drug depot releases about 20% to about 99% of the clonidine relative to a total amount of the clonidine loaded in the drug depot over a period of 3 to 7 days after the drug depot is administered to the surgical site. 
     
     
         6 . An implantable drug depot according to  claim 1 , wherein the polymer is capable of degrading in 30 days or less after the drug depot is implanted at the surgical site. 
     
     
         7 . An implantable drug depot according to  claim 1 , wherein the clonidine is released in an amount between 0.05 ug and 3 mg per day for a period of 3 to 10 days to prevent, reduce or treat bleeding at the surgical site. 
     
     
         8 . An implantable drug depot according to  claim 1 , wherein the clonidine is present in an amount of about 0.1 to about 10 wt. % of the implantable drug depot and the polymer is present in an amount of about 75 to about 94 wt. % of the implantable drug depot, and the drug depot further comprises from about 5 to about 15 wt. % of an excipient. 
     
     
         9 . An implantable drug depot according to  claim 1 , wherein the clonidine is present in an amount of about 0.1 to about 10 wt. % of the implantable drug depot and the polymer comprises PLGA in an amount of about 75 to about 94 wt. % of the depot, and the depot further comprises from about 5 to about 15 wt. % mPEG. 
     
     
         10 . An implantable drug depot according to  claim 1 , wherein the drug depot can prevent, reduce or treat bleeding at the surgical site within 1 hour after implantation. 
     
     
         11 . An implantable drug depot useful for reducing, preventing or treating bleeding at a surgical site beneath the skin in a patient, the implantable drug depot comprising a therapeutically effective amount of clonidine or pharmaceutically acceptable salt thereof and a polymer; wherein the drug depot is implantable locally at the surgical site to reduce, prevent or treat bleeding, and the depot is capable of releasing (i) about 5% to about 45% of the clonidine relative to a total amount of the clonidine loaded in the drug depot over a first period of up to 48 hours and (ii) about 55% to about 99% of the clonidine relative to a total amount of the clonidine loaded in the drug depot over a subsequent period of at least 3 days. 
     
     
         12 . An implantable drug depot according to  claim 11 , wherein the polymer comprises one or more of poly(lactide-co-glycolide), polylactide, polyglycolide, polyorthoester, D-lactide, D,L-lactide, poly(D,L-lactide), L-lactide, poly(D,L-lactide-co-caprolactone), poly(D,L-lactide-co-glycolide-co-caprolactone), polycaprolactone or a combination thereof. 
     
     
         13 . An implantable drug depot according to  claim 11 , wherein the polymer comprises about 60% to about 90% of the total wt. % of the drug depot. 
     
     
         14 . An implantable drug depot according to  claim 11 , wherein the polymer is capable of degrading in 30 days or less after the drug depot is implanted at the surgical site. 
     
     
         15 . An implantable drug depot according to  claim 11 , wherein the clonidine is released in an amount between 0.05 ug and 3 mg per day during the subsequent period for at least 3 to 10 days to prevent, reduce or treat bleeding at the surgical site. 
     
     
         16 . An implantable drug depot according to  claim 11 , wherein the drug depot can prevent, reduce or treat bleeding at the surgical site within 1 hour after implantation. 
     
     
         17 . A method of preventing or treating bleeding at a surgical site in a patient, the method comprising administering one or more biodegradable drug depots comprising a therapeutically effective amount of a clonidine or pharmaceutically acceptable salt thereof locally to the surgical site to prevent or treat bleeding at the surgical site, wherein the drug depot releases an effective amount of the clonidine over a period of at least 3 days. 
     
     
         18 . A method according to  claim 17 , wherein the drug depot releases 0.1 ug to 100 ug of the clonidine over 24 to 48 hours for a period of at least 3 days to prevent or treat the bleeding at the surgical site. 
     
     
         19 . A method according to  claim 17 , wherein the drug depot comprises a polymer and the polymer comprises about 70% to about 90% of the total weight % of the drug depot. 
     
     
         20 . A method according to  claim 17 , wherein the drug depot releases (i) a bolus dose of the clonidine at the surgical site over a period up to 48 hours and (ii) an effective amount of the clonidine over a subsequent period of at least 3 days.