Formulation of calcium channel blockers for treatment of sars-cov-2 induced covid-19 and other respiratory viruses through pulmonary delivery

Abstract

The invention relates to a formulation of Calcium Channel Blocker (CCB) through pulmonary delivery using an inhaler, nebulizer or a similar delivery system against a novel coronavirus Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) induced COVID-19 and other respiratory viruses such as influenza, SARS, MERS etc. The formulation comprises verapamil hydrochloride at a concentration between 15 mg/mL and 25 mg/mL, sodium chloride at a concentration of 6.25 mg/mL and distilled water at a volume between q.s. to 1 mL. The formulation is administered as pulmonary delivery through nasal spray. The calcium signaling plays an important role in entry and replication of virus in the host cell and hence targeting the calcium channels or pumps that mediate the mobility of the intracellular calcium is an effective target for SARS-CoV-2 infection.

1 . A formulation for treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) induced Coronavirus Disease 2019 (COVID-19), the formulation comprises:
 a. verapamil hydrochloride at a concentration in the range between 15 mg/mL and 25 mg/mL;   b. sodium chloride at a concentration of 625 mg/mL, and   c. distilled water at a volume between q.s. to 1 mL   
     
     
         2 . The formulation as claimed in  claim 1 , wherein the formulation with a concentration of verapamil hydrochloride at 20.0 mg/mL at pH 4.09 and 60° C. is stable for 33 days. 
     
     
         3 . The formulation as claimed in  claim 1 , wherein the formulation inhibited Ribonucleic acid (RNA) replication of SARS-COV-2 in human liver cell line. 
     
     
         4 . The formulation as claimed in  claim 1 , wherein the formulation inhibited calcium channel by disrupting the movement of calcium thus halting the calcium signaling. 
     
     
         5 . The formulation as claimed in  claim 1 , wherein verapamil hydrochloride at a concentration of 10 mg/kg inhibited the levels of interleukin-1b (IL-)b), Tumor Necrosis Factor (TNF-a) and Monocyte Chemoattractant Protein-1 (MCP-1) in serum and activities of Myeloperoxidase (MPO), Lactate Dehydrogenase (LDH) and Superoxide Dismutase (SOD), Malondialdehyde (MDA) content and lung wet/dry ratio in lipopolysaccharide-induced pathological damage in mouse. 
     
     
         6 . The formulation as claimed in  claim 1 , wherein verapamil hydrochloride exhibited antiviral activity in Chronic obstructive pulmonary disease (COPD). 
     
     
         7 . The formulation as claimed in  claim 1 , wherein the formulation is administered as pulmonary delivery in the form of a nasal spray. 
     
     
         8 . The formulation as claimed in  claim 1 , wherein the formulation is administered as pulmonary delivery through inhalation or nebulization. 
     
     
         9 . The formulation as claimed in  claim 1 , wherein the formulation is administered through a spray device. 
     
     
         10 . The formulation as claimed in  claim 1 , wherein the spray device has the ability to deliver less concentration of verapamil hydrochloride i.e. 2.5 mg/actuation or spray.