# US 10,478,408 B2 · Combination treatments for opioid crisis

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- Number: US 10,478,408 B2
- Document ID: US10478408B2
- Status: Granted
- Kind: B2
- Application number: 15/881,475
- Filed: 2018-01-26
- Published: 2019-08-01
- Granted: 2019-11-19
- Earliest claimed: 2018-01-26
- Applicants: Michael Presti
- Inventors: Michael Presti
- Web page: https://patentgrep.com/patent/US10478408B2

## CPC

- A61K 31/145: having sulfur, e.g. thiurams (>N—C(S)—S—C(S)—N< and >N—C(S)—S—S—C(S)—N<), Sulfinylamines (—N=SO), Sulfonylamines (—N=SO2) (isothiourea A61K31/155)
- A61K 31/137: Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine {or methadone}
- A61K 31/4468: having a nitrogen directly attached in position 4, e.g. clebopride, fentanyl
- A61K 31/485: Morphinan derivatives, e.g. morphine, codeine
- A61P 25/04: Centrally acting analgesics, e.g. opioids
- A61P 25/36: Opioid-abuse
- 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

A method of reducing the risk of medication-related overdose, death, or other injury associated with inappropriate consumption of alcohol in conjunction with prescription opioid analgesics, comprising: administering a combination medication having an effective amount of one or more opioid medications, and an effective amount of one or more aldehyde dehydrogenase inhibitors, in order to provide the powerful analgesic effects of the opioid in conjunction with a substance that prevents concomitant alcohol consumption, thereby reducing the risk of alcohol mediated opioid overdose or death. A combination medication, including an effective amount of one or more opioid medications, and an effective amount of one or more aldehyde dehydrogenase inhibitors and a pharmaceutically acceptable carrier.

## Claims

### Claim 1

A method of reducing the chances of alcohol mediated opioid overdose or death during maintenance therapy for management of pain, comprising:
selecting a subject for maintenance therapy for management of pain;
administering a single composition to the subject, comprising:
an effective amount of one or more opioid medications for the management of pain; and
an effective amount of one or more aldehyde dehydrogenase inhibitors sufficient to prevent alcohol consumption, the one or more aldehyde dehydrogenase inhibitors selected from disulfiram, calcium carbimide, coprine, cyanamide, 1-aminocyclopropanol, daidzin, cephalosporins, antidiabetic sulfonyl ureas, metronidazole, ampal, benomyl, citral and active isomers thereof, chloral hydrate, chlorpropamide analogs, (benzoyloxy)[4-chlorophenyl)sulfonyl]carbamic acid 1,1-dimethylethyl ester (NPI-1), 4-chloro-N-ethyl-N-[(propylamino)carbonyl]benzenesulfonamid (API-1), 3-(((3-(4-(methylsulfonamido)phenyl)-4-oxo-4H-chromen-7-yl)oxy)methyl)benzoic acid (CVT-10216), N,N-diethylaminobenzaldehyde (DEAB), gossypol, molinate, nitroglycerin, pargyline, or pharmaceutically acceptable salts thereof, enabling provision of the powerful analgesic effects of the opioid in a manner which prevents concomitant alcohol consumption, thereby reducing the risk of alcohol mediated opioid overdose or death during maintenance therapy for management of pain.

### Claim 2 (depends on 1)

The method of claim 1, wherein the aldehyde dehydrogenase inhibitor is disulfiram, or an pharmaceutically acceptable salts thereof.

### Claim 3 (depends on 1)

The method of claim 1, wherein the aldehyde dehydrogenase inhibitor is disulfiram, or pharmaceutically acceptable salts thereof.

### Claim 4 (depends on 1)

The method of claim 1, wherein the one or more opioid medications is one or more prescription opioid analgesics.

### Claim 5 (depends on 1)

The method of claim 1, wherein the one or more opioid medications comprises one or more of alfentanil, allylprodine, alphaprodine, anileridine, benzylmorphine, bezitramide, butorphanol, clonitazene, codeine, desomorphine, dextromoramide, dezocine, diampromide, diamorphone, dihydrocodeine, dihydromorphine, dimenoxadol, dimepheptanol, dimethylthiambutene, dioxaphetyl butyrate, dipipanone, eptazocine, ethoheptazine, ethylmethylthiambutene, ethylmorphine, etonitazene, fentanyl, heroin, hydrocodone, hydromorphone, hydroxypethidine, ketobemidone, levorphanol, levophenacylmorphan, lofentanil, meperidine, meptazinol, metazocine, metopon, morphine, myrophine, narceine, nicomorphine, norlevorphanol, nalorphine, nalbuphene, normorphine, norpipanone, opium, oxycodone, oxymorphone, papaveretum, pentazocine, phenadoxone, phenomorphan, phenazocine, phenoperidine, piminodine, piritramide, propheptazine, promedol, properidine, sufentanil, tilidine, and tramadol.

### Claim 6 (depends on 5)

The method of claim 5, wherein the one or more opioid medications is morphine, methadone, hydrocodone, oxycodone, hydromorphone, fentanyl, or codeine.

### Claim 7 (depends on 6)

The method of claim 6, wherein the one or more opioid medications consists essentially of one or more of morphine, methadone, hydrocodone, hydromorphone, oxycodone, fentanyl, or codeine.

### Claim 8 (depends on 1)

The method of claim 1, wherein the subject is prescribed one or more opioid medications for the management of chronic pain.

### Claim 9 (depends on 1)

The method of claim 1, wherein the subject is prescribed one or more opioid medications for the management of acute pain.

### Claim 10

A method of reducing the chances of alcohol mediated opioid overdose or death during maintenance therapy for management of pain, comprising:
selecting a subject for maintenance therapy for management of pain;
administering in a single dose a single combination medication, comprising:
an effective amount of an opioid medication for the management of pain selected from alfentanil, allylprodine, alphaprodine, anileridine, benzylmorphine, bezitramide, butorphanol, clonitazene, codeine, desomorphine, dextromoramide, dezocine, diampromide, diamorphone, dihydrocodeine, dihydromorphine, dimenoxadol, dimepheptanol, dimethylthiambutene, dioxaphetyl butyrate, dipipanone, eptazocine, ethoheptazine, ethylmethylthiambutene, ethylmorphine, etonitazene, fentanyl, heroin, hydrocodone, hydromorphone, hydroxypethidine, ketobemidone, levorphanol, levophenacylmorphan, lofentanil, meperidine, meptazinol, metazocine, metopon, morphine, myrophine, narceine, nicomorphine, norlevorphanol, nalorphine, nalbuphene, normorphine, norpipanone, opium, oxycodone, oxymorphone, papaveretum, pentazocine, phenadoxone, phenomorphan, phenazocine, phenoperidine, piminodine, piritramide, propheptazine, promedol, properidine, sufentanil, tilidine, and tramadol; and
an effective amount of one or more aldehyde dehydrogenase inhibitors selected from disulfiram, calcium carbimide, coprine, cyanamide, 1-aminocyclopropanol, daidzin, cephalosporins, antidiabetic sulfonyl ureas, metronidazole, ampal, benomyl, citral and active isomers thereof, chloral hydrate, chlorpropamide analogs, (benzoyloxy)[4-chlorophenyl)sulfonyl]carbamic acid 1,1-dimethylethyl ester (NPI-1), 4-chloro-N-ethyl-N-[(propylamino)carbonyl]benzenesulfonamid (API-1), 3-(((3-(4-(methylsulfonamido)phenyl)-4-oxo-4H-chromen-7-yl)oxy)methyl)benzoic acid (CVT-10216), N,N-diethylaminobenzaldehyde (DEAB), gossypol, molinate, nitroglycerin, pargyline, or pharmaceutically acceptable salts thereof, enabling provision of the powerful analgesic effects of the opioid in a manner which prevents concomitant alcohol consumption, thereby reducing the risk of alcohol mediated opioid overdose or death during maintenance therapy for management of chronic pain.

### Claim 11 (depends on 10)

The method of claim 10, wherein the aldehyde dehydrogenase inhibitor is disulfiram, or a pharmaceutically acceptable salts thereof.

### Claim 12 (depends on 10)

The method of claim 10 wherein the aldehyde dehydrogenase inhibitor consists essentially of disulfiram, or pharmaceutically acceptable salts thereof.

### Claim 13 (depends on 10)

The method of claim 10, wherein the one or more opioid medications comprises morphine, hydrocodone, oxycodone, hydromorphone, fentanyl, or codeine.

### Claim 14 (depends on 13)

The method of claim 13, wherein the one or more opioid medications consists essentially of one or more of morphine, hydrocodone, hydromorphone, oxycodone, fentanyl, or codeine.

### Claim 15 (depends on 10)

The method of claim 10, wherein the subject is prescribed one or more opioid medications for the management of chronic pain.

### Claim 16 (depends on 10)

The method of claim 10, wherein the subject is prescribed one or more opioid medications for the management of acute pain.