Linezolid formulations

Abstract

The present invention relates to injectable, thermosensitive hydrogel compositions comprising linezolid for relieving and/or treating chronic low back pain (CLBP).

1 . An injectable pharmaceutical formulation comprising:
 (a) an effective amount of linezolid,   (b) a thermosensitive hydrogel comprising poloxamer and iohexol, and   (c) optionally, at least one pharmaceutically acceptable excipient,   
       wherein linezolid forms a suspension in the thermosensitive hydrogel. 
     
     
         2 - 18 . (canceled) 
     
     
         19 . A method of treating or preventing pain in a subject, the method comprising administering to the subject an injectable pharmaceutical composition, wherein the injectable pharmaceutical composition comprises:
 (a) an effective amount of linezolid;   (b) a thermosensitive hydrogel comprising a poloxamer and iohexol; and   (c) optionally, at least one pharmaceutically acceptable excipient;   
       wherein the linezolid forms a suspension in the thermosensitive hydrogel. 
     
     
         20 . The method of  claim 19 , wherein the pain is at least one of lower back pain, acute pain, sub-acute pain, chronic pain, local pain, radicular pain, referred pain, lumbar pain, or cervical pain. 
     
     
         21 . The method of  claim 20 , wherein the lumbar pain or cervical pain is associated with at least one of Modic changes or bone edema. 
     
     
         22 . The method of  claim 19 , wherein the subject is suspected of having, or has, a bacterial infection in the lower back. 
     
     
         23 . The method of  claim 19 , wherein the administration of the injectable pharmaceutical composition comprises injection into an intervertebral disc, intervertebral space, intra-articular space, ligament, tendon, tendon and bone junction, or site adjacent to bone edema in the subject. 
     
     
         24 . The method of  claim 19 , wherein the administration of the injectable pharmaceutical composition comprises injection adjacent to or into a site of Modic change or bone edema in the subject. 
     
     
         25 . A method of simultaneously (1) relieving or ameliorating pain in a subject and (2) eliminating a bacterial infection in a cervical, thoracic, lumbar or sacral vertebra of the subject, the method comprising administering to the subject an injectable pharmaceutical composition by injection to an area in, near or around the infected vertebrae of the subject, wherein the injectable pharmaceutical composition comprises:
 (a) an effective amount of linezolid;   (b) a thermosensitive hydrogel comprising a poloxamer and iohexol; and   (c) optionally, at least one pharmaceutically acceptable excipient;   
       wherein the linezolid forms a suspension in the thermosensitive hydrogel. 
     
     
         26 - 27 . (canceled) 
     
     
         28 . A thermosensitive hydrogel comprising:
 (a) poloxamer 407 present in the hydrogel at a concentration of from about 10% to about 17% by weight of the hydrogel; and   (b) Iohexol present in the hydrogel at a concentration of from about 14.5% to about 62.5% by weight of the hydrogel,   
       wherein the hydrogel forms a gel at a temperature between 26° C. and 36° C. 
     
     
         29 . The method of  claim 19 , wherein the linezolid is linezolid Form II. 
     
     
         30 . The method of  claim 19 , wherein the poloxamer is poloxamer 407 present in an amount of from about 9.5% to about 17% by weight of the injectable pharmaceutical composition. 
     
     
         31 . The method of  claim 30 , wherein the poloxamer 407 is present in an amount of from about 10.8% to about 12.8% by weight of the injectable pharmaceutical composition. 
     
     
         32 . The method of  claim 19 , wherein iohexol is present in an amount of from about 14% to about 59% by weight of the injectable pharmaceutical composition. 
     
     
         33 . The method of  claim 32 , wherein iohexol is present in an amount of from about 17% to about 30% by weight of the injectable pharmaceutical composition. 
     
     
         34 . The method of  claim 19 , wherein the suspension gels at a temperature from about 26° C. to about 38° C. 
     
     
         35 . The method of  claim 34 , wherein the suspension gels at a temperature from about 32° C. to about 36° C. 
     
     
         36 . The method of  claim 34 , wherein the suspension gels at a temperature from about 26° C. to about 32° C. 
     
     
         37 . The method of  claim 19 , wherein the concentration of linezolid is from about 1% to about 20% by weight of the injectable pharmaceutical composition. 
     
     
         38 . The method of  claim 19 , wherein:
 the linezolid is linezolid Form II present in an amount of from about 2.5% to about 20% by weight of the injectable pharmaceutical composition;   the iohexol is present in an amount of from about 17% to about 30% by weight of the injectable pharmaceutical composition; and   the poloxamer is present in an amount of from about 10.8% to about 12.8% by weight of the injectable pharmaceutical composition.   
     
     
         39 . The method of  claim 19 , wherein the injectable pharmaceutical composition is formulated for administration to at least one of an intervertebral disc, intervertebral space, intra-articular space, or site adjacent to bone edema of the subject, or is formulated for administration to or near at least one of a bone, joint, ligament, tendon, or tendon and bone junction of the subject. 
     
     
         40 . The method of  claim 39 , wherein the bone, joint, ligament or tendon is a bone, joint, ligament, or tendon associated with the spine of the subject. 
     
     
         41 . The method of  claim 40 , wherein the bone, joint, ligament, or tendon associated with the spine of the subject is further associated with a cervical, thoracic, lumbar or sacral vertebra of the subject. 
     
     
         42 . A method of manufacturing a kit for preparing an injectable pharmaceutical composition comprising linezolid and a thermosensitive hydrogel, the method comprising:
 (a) milling the linezolid to a defined powder to produce a linezolid defined powder;   (b) preparing a unit of the linezolid defined powder from step (a) and sterilizing the unit;   (c) preparing and sterilizing the thermosensitive hydrogel to produce a sterilized thermosensitive hydrogel;   (d) providing instructions for suspending the unit of the linezolid defined powder from step (b) in the sterilized thermosensitive hydrogel from step (c) to produce the injectable pharmaceutical composition; and   (e) assembling a kit comprising the unit of the linezolid defined powder from step (b), the sterilized thermosensitive hydrogel from step (c), and the instructions from step (d);   
       wherein:
 the linezolid is linezolid Form II; and 
 the thermosensitive hydrogel comprises poloxamer 407 and iohexol. 
 
     
     
         43 . A kit made by the method of  claim 42 . 
     
     
         44 . A method of preparing an injectable pharmaceutical composition comprising linezolid and a thermosensitive hydrogel, the method comprising:
 (a) milling the linezolid to a defined powder to produce a linezolid defined powder;   (b) preparing a unit of the linezolid defined powder from step (a) and sterilizing the unit;   (c) preparing and sterilizing the thermosensitive hydrogel to produce a sterilized thermosensitive hydrogel; and   (d) suspending the unit of the linezolid defined powder from step (b) in the sterilized thermosensitive hydrogel from step (c) to produce the injectable pharmaceutical composition;   
       wherein:
 the linezolid is linezolid Form II; and 
 the thermosensitive hydrogel comprises poloxamer 407 and iohexol. 
 
     
     
         45 . An injectable pharmaceutical composition made by the method of  claim 44 .