# US 12,109,303 B2 · Orally dissolving antimicrobial film compositions and methods of their use

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 12,109,303 B2
- Document ID: US12109303B2
- Status: Granted
- Kind: B2
- Application number: 18/302,720
- Filed: 2023-04-18
- Published: 2023-10-19
- Granted: 2024-10-08
- Earliest claimed: 2022-04-18
- Assignees: Isha Therapeutics LLC
- Applicants: ISHA Therapeutics LLC
- Inventors: Manoj P. Jadhav; Mangal Shailesh Nagarsenkar; Supriya Shrihari Shidhaye; Shivali Hargovind Tank
- Web page: https://patentgrep.com/patent/US12109303B2

## CPC

- A61K 9/006: {Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays}
- A61K 9/7007: {Drug-containing films, membranes or sheets (A61K9/0041, A61K9/0043, A61K9/006, A61K9/0063 take precedence)}
- A61K 31/7048: having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin {, digitoxin or digoxin}
- A61K 47/10: Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
- A61K 47/18: Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
- A61K 47/186: {Quaternary ammonium compounds, e.g. benzalkonium chloride or cetrimide}
- A61K 47/22: Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
- A61K 47/28: Steroids, e.g. cholesterol, bile acids or glycyrrhetinic acid
- A61K 47/32: Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers {, poly(meth)acrylates, or polyvinyl pyrrolidone}
- A61K 47/541: {Organic ions forming an ion pair complex with the pharmacologically or therapeutically active agent}
- A61P 31/10: Antimycotics
- C07H 17/08: Hetero rings containing eight or more ring members, e.g. erythromycins
- 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
- C07H: SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS (derivatives of aldonic or saccharic acids C07C, C07D; aldonic acids, saccharic acids C07C59/105, C07C59/285; cyanohydrins C07C255/16; glycals C07D; compounds of unknown constitution C07G; polysaccharides, derivatives thereof C08B; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification C12N15/00; sugar industry C13)

## Abstract

Disclosed herein are ionic liquid composition(s) of amphotericin B comprising amphotericin B; a complexing agent component; a solvent component comprising acidified solvent(s); and a solubilizing component. Disclosed composition(s) comprise at least two complexing agents and two or more constituents of the composition provide two or more functional activities. Ionic liquid composition(s) disclosed are in aspects provided as oral dissolve film(s) useful in the treatment of oral microbial infection(s), e.g., oral candidiasis. Disclosed ionic liquid composition(s) of amphotericin B and ODF(s) thereof have a solubility of amphotericin B in water of at least 3 mg/mL. ODF film(s) provided deliver a localized concentration of amphotericin B to the oral cavity of a recipient wherein the concentration of amphotericin B available for treating a source of a local infection is detectably or significantly greater than that provided by an orally delivered, intravenously delivered, or either orally or intravenously delivered treatment comprising amphotericin B.

## Claims

### Claim 1

An antifungal ionic liquid composition of amphotericin B comprising (1) amphotericin B; (2) a complexing agent component comprising a first complexing agent and a second complexing agent, wherein the first complexing agent and the second complexing agent form a single ionic complex with the amphotericin B; (3) a solvent component comprising an amount of at least one solvent compound and at least one solvent acidifying agent that when combined with the solvent compound forms an acidified solvent, wherein the at least one solvent acidifying agent further (a) represents one of the first or the second complexing agents forming the ionic complex with the amphotericin B and (b) detectably modulates the pH of the composition; and (4) a solubilizing component comprising an amount of at least one solubilizing agent which detectably or significantly increases the solubilization of the amphotericin B, wherein each of the solvent acidifying agent and the solvent compound are present in the composition in an amount representing between about 0.5% w/v and about 5% w/v of the composition.

### Claim 2 (depends on 1)

The antifungal ionic liquid composition of claim 1, wherein the amphotericin B is present in the composition in an amount representing between about 0.5% w/v and about 10% w/v of the composition.

### Claim 3 (depends on 1)

The antifungal ionic liquid composition of claim 1, wherein at least one of the first or second complexing agents is choline chloride.

### Claim 4 (depends on 3)

The antifungal ionic liquid composition of claim 3, wherein the choline chloride is present in the composition as the second complexing agent, and the ratio of the first complexing agent to the choline chloride in the composition is between about 5:1 and about 1:1 based on the percent weight/volume of each constituent in the composition.

### Claim 5 (depends on 4)

The antifungal ionic liquid composition of claim 4, wherein the ratio of the first complexing agent to the choline chloride is about 4:1 based on the percent weight/volume of each constituent in the composition.

### Claim 6 (depends on 1)

The antifungal ionic liquid composition of claim 1, wherein the at least one solubilizing agent is present in the composition in an amount of between about 2.5% w/v and about 10% w/v of the composition.

### Claim 7 (depends on 1)

The antifungal ionic liquid composition of claim 1, wherein the solubility in water of the amphotericin B provided by the composition is at least about 3 mg/mL.

### Claim 8 (depends on 1)

The antifungal ionic liquid composition of claim 1, wherein (1) the at least one solvent compound is dimethyl acetamide; (2) the at least one acidifying agent is ascorbic acid; (3) the at least one solubilizing agent is D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS); or (4) the composition exhibits any combination of (1)-(3).

### Claim 9 (depends on 1)

A pharmaceutically acceptable composition in the form of an oral dissolve film comprising the antifungal ionic liquid composition of claim 1.

### Claim 10 (depends on 8)

A pharmaceutically acceptable composition in the form of an oral dissolve film comprising the antifungal ionic liquid composition of claim 8.

### Claim 11

An antifungal ionic liquid composition of amphotericin B comprising (1) amphotericin B; (2) a complexing agent component comprising a first complexing agent and a second complexing agent, wherein the first complexing agent and the second complexing agent form a single ionic complex with the amphotericin B; (3) a solvent component comprising an amount of at least one solvent compound and at least one solvent acidifying agent that when combined with the solvent compound forms an acidified solvent, wherein the at least one solvent acidifying agent further (a) represents one of the first or the second complexing agents forming the ionic complex with the amphotericin B and (b) detectably modulates the pH of the composition; and (4) a solubilizing component comprising an amount of at least one solubilizing agent which detectably or significantly increases the solubilization of the amphotericin B, wherein (a) at least one of the first complexing agent and the second complexing agent, (b) the one or more solvent compounds, and (c) the at least one solubilizing agent, are present in the composition in an about 1:1:1 ratio with one another based on the percent weight/volume of each in the composition.

### Claim 12 (depends on 11)

The antifungal ionic liquid composition of claim 11, wherein the amphotericin B is present in the composition in an amount representing between about 0.5% w/v and about 10% w/v of the composition.

### Claim 13 (depends on 11)

The antifungal ionic liquid composition of claim 11, wherein at least one of the first or second complexing agents is choline chloride.

### Claim 14 (depends on 13)

The antifungal ionic liquid composition of claim 13, wherein the ratio of the first complexing agent to the choline chloride is between about 5:1 and about 1:1 based on the percent weight/volume of each constituent in the composition.

### Claim 15 (depends on 11)

The antifungal ionic liquid composition of claim 11, wherein the at least one solubilizing agent is present in the composition in an amount of between about 2.5% w/v and about 10% w/v of the composition.

### Claim 16 (depends on 11)

The antifungal ionic liquid composition of claim 11, wherein the solubility in water of amphotericin B provided by the composition is at least about 3 mg/mL.

### Claim 17 (depends on 11)

The antifungal ionic liquid composition of claim 11, wherein (1) the at least one solvent compound is dimethyl acetamide; (2) the at least one acidifying agent is ascorbic acid; (3) the at least one solubilizing agent is D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS); or (4) the composition exhibits any combination of (1)-(3).

### Claim 18 (depends on 11)

A pharmaceutically acceptable composition in the form of an oral dissolve film comprising the antifungal ionic liquid composition of claim 11.

### Claim 19 (depends on 14)

A pharmaceutically acceptable composition in the form of an oral dissolve film comprising the antifungal ionic liquid composition of claim 14.

### Claim 20 (depends on 17)

A pharmaceutically acceptable composition in the form of an oral dissolve film comprising the antifungal ionic liquid composition of claim 17.