Formulations for the delivery of active ingredients

Abstract

This invention relates generally to in vivo delivery of active ingredient formulations. More particularly, this invention relates to formulations of active ingredients that further comprise an agent, methods of making such formulations, and methods of using the same.

What is claimed is: 
     
         1 . A pharmaceutical composition comprising an active ingredient and an in vivo stabilizing amount of an agent,
 wherein the agent is associated with an adverse effect in vivo caused by the administration of the active ingredient without the agent, and   wherein the in vivo stabilizing amount is the amount that substantially saturates the binding sites of the active ingredient to the agent.   
     
     
         2 . The pharmaceutical composition of  claim 1 , wherein the active ingredient is selected from the group consisting of a nucleic acid, a peptide, and a small organic molecule, or a combination thereof. 
     
     
         3 . The pharmaceutical composition of  claim 1 , wherein the active ingredient is an oligonucleotide decoy. 
     
     
         4 . The pharmaceutical composition of  claim 1 , wherein the active ingredient is a nucleic acid comprising one or more transcription factor binding sites. 
     
     
         5 . The pharmaceutical composition of  claim 1 , wherein the active ingredient is an oligonucleotide decoy useful for the treatment of pain or modulation of nociceptive signaling. 
     
     
         6 . The pharmaceutical composition of  claim 1 , wherein the active ingredient is a nucleic acid comprising SEQ ID NOs: 1-40, 42, 45, 47-52, or 53. 
     
     
         7 . The pharmaceutical composition of  claim 1 , wherein the agent is an ion, a protein, a carbohydrate, an alcohol, a lipid, or a vitamin. 
     
     
         8 . The pharmaceutical composition of  claim 1 , wherein the agent is associated with an adverse effect caused by the administration of the active ingredient to the nervous system. 
     
     
         9 . The pharmaceutical composition of  claim 8 , wherein the agent is associated with an adverse effect caused by the administration of the active ingredient without the agent in CSF, neuronal parenchyma, or conjunctive tissue. 
     
     
         10 . The pharmaceutical composition of  claim 8 , wherein administration is by injection. 
     
     
         11 . The pharmaceutical composition of  claim 9 , wherein the agent is a cation or a vitamin. 
     
     
         12 . The pharmaceutical composition of  claim 11 , wherein the cation is a calcium ion, a magnesium ion, or a potassium ion. 
     
     
         13 . The pharmaceutical composition of  claim 11 , wherein the cation is a metal ion. 
     
     
         14 . The pharmaceutical composition of  claim 1 , wherein the agent is associated with an adverse effect caused by the administration of the active ingredient without the agent in blood. 
     
     
         15 . The pharmaceutical composition of  claim 14 , wherein the agent is a cation or a vitamin. 
     
     
         16 . The pharmaceutical composition of  claim 15 , wherein the cation is a calcium ion, a magnesium ion, or a potassium ion. 
     
     
         17 . The pharmaceutical composition of  claim 15 , wherein the cation is a metal ion. 
     
     
         18 . The pharmaceutical composition of  claim 1 , wherein the resulting free agent amount within the pharmaceutical composition is at a level less than a predetermined level. 
     
     
         19 . The pharmaceutical composition of  claim 1 , wherein the resulting free agent amount within the pharmaceutical composition is at a level greater than a predetermined level. 
     
     
         20 . The pharmaceutical composition of  claim 18 , wherein the predetermined level is the endogenous level of the agent. 
     
     
         21 . The pharmaceutical composition of  claim 1 , wherein the active ingredient is a nucleic acid and the agent is calcium ion and wherein the pharmaceutical composition is formulated for intrathecal administration. 
     
     
         22 . The pharmaceutical composition of  claim 1 , wherein the active ingredient is an oligonucleotide decoy and the agent is calcium ion and wherein the pharmaceutical composition is formulated for intrathecal administration. 
     
     
         23 . The pharmaceutical composition of  claim 1 , wherein the molar ratio or the weight ratio of the active ingredient to the agent ranges from about 1:1000 to about 1000:1. 
     
     
         24 . The pharmaceutical composition of  claim 1 , wherein the active ingredient is a nucleic acid and the agent is calcium ion as comprised in calcium chloride, and wherein the weight ratio of the active ingredient to calcium chloride is from about 1:1, 2:1, 4:1, 5:1, 15:1, 30:1, 50:1, 100:1, 200:1, 250:1, 300:1, 400:1, or 500:1, or any range derivable therein. 
     
     
         25 . The pharmaceutical composition of  claim 1 , wherein the active ingredient is an oligonucleotide decoy and the agent is calcium ion as comprised in calcium chloride, and wherein the weight ratio of the active ingredient to calcium chloride is from about 1:1, 2:1, 4:1, 5:1, 15:1, 30:1, 50:1, 100:1, 200:1, 250:1, 300:1, 400:1, or 500:1, or any range derivable therein. 
     
     
         26 . The pharmaceutical composition of  claim 1 , wherein the active ingredient is an oligonucleotide decoy and the agent is a cation or a vitamin. 
     
     
         27 . The pharmaceutical composition of  claim 26 , wherein the cation is a calcium ion, a magnesium ion, or a potassium ion. 
     
     
         28 . The pharmaceutical composition of  claim 26 , wherein the cation is a metal ion. 
     
     
         29 . The pharmaceutical composition of  claim 1  further comprising a buffer. 
     
     
         30 . The pharmaceutical composition of  claim 1 , wherein the active ingredient is an oligonucleotide decoy, the agent is calcium ion and wherein the pharmaceutical composition further comprises a non-phosphate based buffer. 
     
     
         31 . A method of reducing an adverse effect of an active ingredient comprising administering the active ingredient with an in vivo stabilizing amount of an agent,
 wherein the agent is associated with the adverse effect of the active ingredient caused by the administration of the active ingredient without the agent, and   wherein the in vivo stabilizing amount is the amount that substantially saturates the binding sites of the active ingredient to the agent.   
     
     
         32 . A method for treating or managing pain in a subject comprising administering to the subject the pharmaceutical composition of  claim 1 , wherein the active ingredient is an oligonucleotide decoy comprising one or more binding sites for EGR1 and wherein the agent is a calcium ion.