# US 11,433,046 B2 · Compositions and methods for treating epilepsy, seizures and other conditions

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- Number: US 11,433,046 B2
- Document ID: US11433046B2
- Status: Granted
- Kind: B2
- Application number: 17/308,910
- Filed: 2021-05-05
- Published: 2021-08-19
- Granted: 2022-09-06
- Earliest claimed: 2019-12-10
- Assignees: Tulex Pharmaceuticals Inc.
- Applicants: Tulex Pharmaceuticals Inc.
- Inventors: Yu-Hsing Tu; Ashok Perumal; Kalyan Kathala; Romona Bhattacharya
- Web page: https://patentgrep.com/patent/US11433046B2

## CPC

- A61K 31/357: having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel
- A61J 1/06: Ampoules or carpules (syringe ampoules or carpules A61M5/28)
- A61J 7/0023: {Spoons}
- A61J 7/0046: {Cups, bottles or bags}
- A61J 7/0053: {Syringes, pipettes or oral dispensers}
- A61K 9/0053: {Mouth and digestive tract, i.e. intraoral and peroral administration}
- A61K 9/0095: {Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches (A61K9/0007 takes precedence; eatable gels or foams A61K9/0056; oral mucosa adhesive forms A61K9/006)}
- A61K 9/08: Solutions {(composition of solutions A61K47/00)}
- A61K 9/10: Dispersions; Emulsions
- A61K 9/14: Particulate form, e.g. powders, {Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles (microspheres A61K9/16; microcapsules A61K9/50; nanocapsules, nanoparticles of the matrix type A61K9/51)}
- A61K 9/48: Preparations in capsules, e.g. of gelatin, of chocolate {(A61K9/0004 takes precedence; bite capsules A61K9/0056)}
- A61K 31/047: having two or more hydroxy groups, e.g. sorbitol
- A61K 31/235: having an aromatic ring attached to a carboxyl group
- A61K 31/25: with polyoxyalkylated alcohols, e.g. esters of polyethylene glycol
- A61K 31/7008: Compounds having an amino group directly attached to a carbon atom of the saccharide radical, e.g. D-galactosamine, ranimustine
- A61K 38/005: {Enzyme inhibitors (protease inhibitors A61K38/55)}
- A61K 47/10: Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
- A61K 47/12: Carboxylic acids; Salts or anhydrides thereof
- A61K 47/14: Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
- A61K 47/183: {Amino acids, e.g. glycine, EDTA or aspartame}
- A61K 47/20: containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
- A61K 47/22: Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
- A61K 47/26: Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
- A61K 47/34: Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers (A61K47/10 takes precedence)
- A61K 47/36: Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K 47/42: Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein (oligopeptides having up to five amino acids {A61K47/183}; polyamino acids A61K47/34)
- A61K 47/6939: {the polymer being a polysaccharide, e.g. starch, chitosan, chitin, cellulose or pectin}
- A61P 25/00: Drugs for disorders of the nervous system
- 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)
- A61J: CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Compositions are provided for the liquid oral administration of topiramate and its salts. The invention further provides methods for treating diseases and disorders using the compositions.

## Claims

### Claim 1

A method for treating a disease or disorder, or a symptom thereof, consisting of orally administering to a patient in need thereof a pharmaceutical composition,
wherein the pharmaceutical composition is an oral liquid pharmaceutical composition, wherein the liquid pharmaceutical composition is formulated as a solution and wherein the pharmaceutical composition consists of:
(1) topiramate, or a pharmaceutically acceptable addition salt thereof, in an amount of about 25 mg/ml in the liquid pharmaceutical composition;
(ii) a solvent component comprising one or more organic solvents in an amount of from about 80% to about 120% w/v in the liquid pharmaceutical composition, wherein the solvent component consists of glycerin in an amount of 60% to 65% w/v and polyethylene glycol of molecular weight about 400 in an amount of 45% to 55% w/v;
(iii) one or more preservatives selected from parabens, benzyl alcohol, benzoic acid, sorbic acid, sodium benzoate, and ascorbic acid;
(iv) one or more sweeteners; and
(v) a flavor component;
wherein the liquid pharmaceutical composition is administered to the patient at 25 mg/ml of topiramate, or a pharmaceutically acceptable addition salt thereof,
wherein the pharmaceutical composition is substantially anhydrous, wherein the disease or disorder, or symptom thereof, is selected from: epilepsy, onset seizures, primary generalized tonic-clonic seizures, seizures associated with Lennox-Gastaut syndrome, and migraine.

### Claim 2 (depends on 1)

The method of claim 1 wherein the composition is administered to the patient from a direct dosing device.

### Claim 3 (depends on 2)

The method of claim 2, wherein the direct dosing device is a measuring device with graduations.

### Claim 4 (depends on 2)

The method of claim 2, wherein the direct dosing device is an oral syringe.

### Claim 5 (depends on 1)

The method of claim 1, wherein the patient is not a pediatric patient.

### Claim 6 (depends on 1)

The method of claim 1, wherein the patient is from 2-16 years old.

### Claim 7 (depends on 1)

The method of claim 1, wherein the patient is an adult.

### Claim 8 (depends on 2)

The method of claim 2, further comprising the step of filling the direct dosing device with the composition by withdrawing said composition from a dosage dispensing unit.

### Claim 9 (depends on 8)

The method of claim 8, wherein the amount of the liquid pharmaceutical composition transferred to the direct dosing device is sufficient to provide from 12 mg to 1000 mg of topiramate or a pharmaceutically acceptable addition salt thereof.

### Claim 10 (depends on 1)

The method of claim 1, wherein the liquid pharmaceutical composition consists of the following components:
(i) polyethylene glycol 400 in an amount of about 50% w/v;
(ii) one or more parabens in an amount of about 2.4% w/v;
(iii) glycerin in an amount of 60% w/v to 65% w/v;
(iv) topiramate, or a pharmaceutically acceptable addition salt thereof, in an amount of about 25 mg/ml;
(v) one or more sweeteners in an amount of about 1% w/v; and
(vi) a flavor component comprising one or more flavor compounds, the flavor component being in an amount of about 0.2% w/v.

### Claim 11 (depends on 1)

The method of claim 1, wherein the liquid pharmaceutical composition has one or more of the following features:
(a) a refractive index of from about 1.3 to about 1.38;
(b) a viscosity of 300-600 cps; or
(c) a density of 1.1-1.3.

### Claim 12 (depends on 1)

The method of claim 1, wherein the topiramate is in the form of a free acid.

### Claim 13 (depends on 1)

The method of claim 1, wherein the solvent component consists of:
polyethylene glycol 400 in an amount of about 50% w/v; and
glycerin in an amount of about 63% w/v.

### Claim 14 (depends on 1)

The method of claim 1, wherein the disease or disorder, or symptom thereof, is partial-onset seizures.

### Claim 15 (depends on 1)

The method of claim 1, wherein the disease or disorder, or symptom thereof, is a primary generalized tonic-clonic seizure.

### Claim 16 (depends on 1)

The method of claim 1, wherein the disease or disorder, or symptom thereof, is a seizure associated with Lennox-Gastaut syndrome.

### Claim 17 (depends on 1)

The method of claim 1, wherein the disease or disorder, or symptom thereof, is migraine.