# US 11,433,081 B2 · Compositions and methods for pain management

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- Number: US 11,433,081 B2
- Document ID: US11433081B2
- Status: Granted
- Kind: B2
- Application number: 16/960,286
- Filed: 2019-01-07
- Published: 2021-02-25
- Granted: 2022-09-06
- Earliest claimed: 2018-01-05
- Assignees: LoMed, Inc.
- Applicants: LoMed, Inc.
- Inventors: Dennis J. Bonner
- Web page: https://patentgrep.com/patent/US11433081B2

## CPC

- A61K 31/5513: 1,4-Benzodiazepines, e.g. diazepam {or clozapine}
- A61K 31/166: having the carbon of a carboxamide group directly attached to the aromatic ring, e.g. procainamide, procarbazine, metoclopramide, labetalol
- A61K 31/195: having an amino group
- A61K 31/225: Polycarboxylic acids
- A61K 31/365: Lactones
- A61K 31/4178: not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
- A61K 31/439: the ring forming part of a bridged ring system, e.g. quinuclidine (8-azabicyclo [3.2.1] octanes A61K31/46)
- A61K 31/4468: having a nitrogen directly attached in position 4, e.g. clebopride, fentanyl
- A61K 31/485: Morphinan derivatives, e.g. morphine, codeine
- A61K 31/495: having six-membered rings with two {or more} nitrogen atoms as the only ring heteroatoms, e.g. piperazine {or tetrazines}(A61K31/48 takes precedence {; with three nitrogen atoms A61K31/53})
- A61K 31/55: having seven-membered rings, e.g. azelastine, pentylenetetrazole
- A61K 47/38: Cellulose; Derivatives thereof
- A61P 23/00: Anaesthetics
- 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

Disclosed herein, in part, are pharmaceutical compositions comprising an opioid agonist such as codeine or a pharmaceutically acceptable salt thereof, hydroxyzine or a pharmaceutically acceptable salt thereof, a gabapentinoid, optionally a 5-HT3 antagonist and a pharmaceutically acceptable excipient. Methods of treating neuropathic and nociceptive pain comprising administering a disclosed pharmaceutical composition to a subject in need thereof is also provided herein

## Claims

### Claim 1

A pharmaceutical composition comprising:
codeine or a pharmaceutically acceptable salt thereof;
hydroxyzine or a pharmaceutically acceptable salt thereof;
a gabapentinoid;
optionally a 5-HT3 antagonist; and
a pharmaceutically acceptable excipient.

### Claim 2 (depends on 1)

The pharmaceutical composition of claim 1, wherein the 5-HT3 antagonist is present and is selected from the group consisting of ondansetron or a pharmaceutically acceptable salt thereof, tropisetron, granisetron, dolasetron, palonosetron, ramosetron, galanolactone, mirtazapine, olanzapine, cisapride, renzapride and metoclopramide.

### Claim 3 (depends on 2)

The pharmaceutical composition of claim 2, wherein the 5-HT3 antagonist is ondansetron or a pharmaceutically acceptable salt thereof.

### Claim 4 (depends on 1)

The pharmaceutical composition of claim 1, wherein the gabapentinoid is selected from the group consisting of gabapentin or a pharmaceutically acceptable salt thereof, gabapentin encarbil, and atagabalin.

### Claim 5 (depends on 1)

The pharmaceutical composition of claim 1, comprising gabapentin and ondansetron HCl.

### Claim 6 (depends on 1)

The pharmaceutical composition of claim 1, further comprising a stool softener and/or a constipation agent, wherein the stool softener or constipation agent is docusate or a pharmaceutically acceptable salt thereof, or naloxegol.

### Claim 7 (depends on 1)

The pharmaceutical composition of claim 1, wherein the pharmaceutically acceptable excipient is methyl cellulose.

### Claim 8 (depends on 1)

The pharmaceutical composition of claim 1, wherein the composition comprises about 20 mg to about 120 mg codeine or a pharmaceutically acceptable salt thereof.

### Claim 9 (depends on 1)

The pharmaceutical composition of claim 1, wherein the composition comprises about 60 mg or about 120 mg codeine phosphate.

### Claim 10 (depends on 8)

The pharmaceutical composition of claim 8, wherein the composition comprises about 50 mg or about 100 mg docusate sodium.

### Claim 11 (depends on 1)

The pharmaceutical composition of claim 1, wherein the composition comprises about 10 mg to about 110 mg hydroxyzine or a pharmaceutically acceptable salt thereof.

### Claim 12 (depends on 7)

The pharmaceutical composition of claim 7, wherein the composition comprises about 1 mg to about 4 mg ondansetron HCl.

### Claim 13 (depends on 7)

The pharmaceutical composition of claim 7, wherein the composition comprises about 100 mg to about 1200 mg gabapentin.

### Claim 14

A pharmaceutical composition for treating neuropathic and deep tissue pain, comprising:
(a) about 60 mg or about 120 mg codeine phosphate;
(b) about 50 mg or about 100 mg hydroxyzine HCl;
(c) about 4 mg ondansetron HCl;
(d) about 300 mg or about 1200 mg gabapentin;
(e) about 100 mg docusate sodium; and
(f) a pharmaceutically acceptable excipient for controlled release.

### Claim 15

A pharmaceutical composition comprising:
about 60 mg or 120 mg codeine phosphate;
about 20 mg to about 100 mg hydroxyzine HCl;
optionally about 150 mg to about 600 mg gabapentin; and
a pharmaceutically acceptable excipient.

### Claim 16 (depends on 15)

The pharmaceutical composition of claim 15, further comprising about 1 mg to about 4 mg ondansetron HCl.

### Claim 17

An unit pharmaceutical composition comprising:
about 30 mg or about 60 mg codeine phosphate;
about 25 mg or about 50 mg hydroxyzine HCl;
about 150 mg, about 300 mg, about 600 mg, or about 1200 mg gabapentin;
about 2 mg ondansetron HCl;
about 50 mg docusate Na; and
a pharmaceutically acceptable excipient.

### Claim 18 (depends on 1)

The pharmaceutical composition of claim 1, wherein when administered to a patient one, two or three times daily, provides a substantially lower pain score as compared to a patient's pain score when administered a fentanyl patch 50 μg or 70 μg; oxycodone 15 mg orally every 6 hours, 2 times daily or 4 times daily, oxycodone 30 mg twice daily, morphine 30 mg every 12 hours, or any combination thereof.

### Claim 19 (depends on 1)

The pharmaceutical composition of claim 1, wherein when administered to a patient one, two or three times daily, provides a substantially less dysphoria or withdrawal symptoms as compared to a patient's pain score when administered a fentanyl patch 50 μg or 70 μg; oxycodone 15 mg orally every 6 hours, 2 times daily or 4 times daily, oxycodone 30 mg twice daily, morphine 30 mg every 12 hours, or any combination thereof.

### Claim 20 (depends on 1)

The pharmaceutical composition of claim 1, wherein when administered to a patient one, two or three times daily, the patient has improved mental clarity as compared to a patient when administered a fentanyl patch 50 μg or 70 μg;
oxycodone 15 mg orally every 6 hours, 2 times daily or 4 times daily, oxycodone 30 mg twice daily, morphine 30 mg every 12 hours, or any combination thereof.

### Claim 21 (depends on 1)

The pharmaceutical composition of claim 1, wherein the composition provides about 20 MME or less of the codeine per dose, or less than 90 MME per day, when administered one, two or three times a day.

### Claim 22 (depends on 1)

A method of treating neuropathic and nociceptive pain in a patient in need thereof comprising administering to the patient a composition of claim 1.