# US 2021/0330631 A1 · Formulation of calcium channel blockers for treatment of sars-cov-2 induced covid-19 and other respiratory viruses through pulmonary delivery

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- Number: US 2021/0330631 A1
- Document ID: US20210330631A1
- Status: Published application
- Kind: A1
- Application number: 17/234,112
- Filed: 2021-04-19
- Published: 2021-10-28
- Earliest claimed: 2020-04-28
- Assignees: Manoj Purushottam Jadhav
- Inventors: Manoj Purushottam Jadhav; Ramakrishna Devarakonda
- Web page: https://patentgrep.com/patent/US20210330631A1

## CPC

- A61K 31/277: having a ring, e.g. verapamil
- A61K 9/0078: {for inhalation via a nebulizer such as a jet nebulizer, ultrasonic nebulizer, e.g. in the form of aqueous drug solutions or dispersions}
- A61K 47/02: Inorganic compounds
- A61P 31/14: for RNA viruses
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## 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.

## Claims

### Claim 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

### Claim 2 (depends on 1)

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.

### Claim 3 (depends on 1)

The formulation as claimed in claim 1, wherein the formulation inhibited Ribonucleic acid (RNA) replication of SARS-COV-2 in human liver cell line.

### Claim 4 (depends on 1)

The formulation as claimed in claim 1, wherein the formulation inhibited calcium channel by disrupting the movement of calcium thus halting the calcium signaling.

### Claim 5 (depends on 1)

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.

### Claim 6 (depends on 1)

The formulation as claimed in claim 1, wherein verapamil hydrochloride exhibited antiviral activity in Chronic obstructive pulmonary disease (COPD).

### Claim 7 (depends on 1)

The formulation as claimed in claim 1, wherein the formulation is administered as pulmonary delivery in the form of a nasal spray.

### Claim 8 (depends on 1)

The formulation as claimed in claim 1, wherein the formulation is administered as pulmonary delivery through inhalation or nebulization.

### Claim 9 (depends on 1)

The formulation as claimed in claim 1, wherein the formulation is administered through a spray device.

### Claim 10 (depends on 1)

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.