# US 11,298,569 B2 · Methods and compositions for modulating opioid withdrawal symptoms

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- Number: US 11,298,569 B2
- Document ID: US11298569B2
- Status: Granted
- Kind: B2
- Application number: 16/308,955
- Filed: 2017-06-13
- Published: 2019-11-21
- Granted: 2022-04-12
- Earliest claimed: 2016-06-13
- Assignees: UTI Limited Partnership
- Applicants: UTI Limited Partnership
- Inventors: Tuan Trang; Nicole Burma
- Web page: https://patentgrep.com/patent/US11298569B2

## CPC

- A61K 9/0014: {Skin, i.e. galenical aspects of topical compositions (non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00)}
- A01K 67/0275: Genetically modified vertebrates, e.g. transgenic
- A01K 67/0276: Knock-out vertebrates
- A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)}
- A61K 9/0053: {Mouth and digestive tract, i.e. intraoral and peroral administration}
- A61K 9/06: Ointments; Bases therefor; {Other semi-solid forms, e.g. creams, sticks, gels (composition of ointments, creams or gels A61K47/00)}
- A61K 9/7023: {Transdermal patches and similar drug-containing composite devices, e.g. cataplasms (galenical aspects of iontophoretic devices A61K9/0009; microneedle arrays A61K9/0021; buccal patches A61K9/006)}
- A61K 31/195: having an amino group
- A61K 31/4709: Non-condensed quinolines and containing further heterocyclic rings
- A61K 31/473: ortho- or peri-condensed with carbocyclic ring systems, e.g. acridines, phenanthridines
- A61K 38/08: Peptides having 5 to 11 amino acids {(A61K38/043 - A61K38/046 take precedence)}
- A61K 49/0008: {Screening agents using (non-human) animal models or transgenic animal models or chimeric hosts, e.g. Alzheimer disease animal model, transgenic model for heart failure}
- A61P 25/36: Opioid-abuse
- G01N 33/5058: {Neurological cells}
- A01K 2217/052: inducing gain of function
- A01K 2217/075: inducing loss of function, i.e. knock out
- A01K 2217/15: Animals comprising multiple alterations of the genome, by transgenesis or homologous recombination, e.g. obtained by cross-breeding
- A01K 2217/206: Animal model comprising tissue-specific expression system, e.g. tissue specific expression of transgene, of Cre recombinase
- A01K 2227/105: Murine
- 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)
- A01K: ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

A method of screening a compound or a composition for use in modulating opioid withdrawal symptoms in a mammal. The method comprises the steps of: selecting a group of test animals; separating the group into two subgroups; inducing Panx1 activation or expression in both subgroups; dosing a first subgroup with a candidate compound; dosing a second subgroup with a placebo; measuring ATP released in spinal microglia of test animals in the first subgroup and in the spinal microglia of test animals in the second subgroup; quantifying the difference in ATP released in spinal microglia of test animals in the first subgroup and in the spinal microglia of test animals in the second subgroup; if the difference in the ATP released in the first subgroup and the APT released in the second subgroup is greater than 25%, then formulating the candidate compound into a pharmaceutical composition.

## Claims

### Claim 1

A method of treating or ameliorating a plurality of symptoms of opioid withdrawal syndrome in a subject, comprising administering to the subject an effective amount of probenecid.

### Claim 2 (depends on 1)

The method according to claim 1, wherein the administration is topical administration.

### Claim 3 (depends on 1)

The method according to claim 1, wherein the administration is with a transdermal patch.

### Claim 4 (depends on 1)

The method according to claim 1, wherein the administration is by an oral dosage.

### Claim 5 (depends on 1)

The method according to claim 1, wherein the administration is by an injection.

### Claim 6 (depends on 5)

The method according to claim 5, wherein the administration is by a subcutaneous injection.

### Claim 7 (depends on 1)

The method according to claim 1, wherein the composition is a topical composition.

### Claim 8 (depends on 7)

The method according to claim 7, wherein the composition is in the form of a lotion, a cream, a gel, or a viscous liquid.

### Claim 9 (depends on 8)

The method according to claim 8, wherein the composition further comprises one or more of a skin penetration enhancer, an emollient, an emulsifying agent, a water miscible solvent, an alcohol, and mixtures thereof.

### Claim 10 (depends on 9)

The method according to claim 9, wherein the skin penetration enhancer is a non-cationic skin penetration enhancer.

### Claim 11 (depends on 1)

The method according to claim 1, wherein the subject is human.
