# US 11,304,913 B2 · Analgesic compositions

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- Number: US 11,304,913 B2
- Document ID: US11304913B2
- Status: Granted
- Kind: B2
- Application number: 16/869,797
- Filed: 2020-05-08
- Published: 2021-03-18
- Granted: 2022-04-19
- Earliest claimed: 2013-03-15
- Assignees: Vapogenix, Inc.
- Applicants: Vapogenix, Inc.
- Inventors: Danguole Spakevicius; Heather Giles; Terry Farmer
- Web page: https://patentgrep.com/patent/US11304913B2

## CPC

- A61K 31/08: acyclic, e.g. paraformaldehyde
- 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)}
- A61K 9/06: Ointments; Bases therefor; {Other semi-solid forms, e.g. creams, sticks, gels (composition of ointments, creams or gels A61K47/00)}
- A61K 9/08: Solutions {(composition of solutions A61K47/00)}
- A61K 9/70: Web, sheet or filament bases {; Films; Fibres of the matrix type containing drug (hollow drug-filled fibres A61K9/0092)}
- 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 31/02: Halogenated hydrocarbons
- 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 47/20: 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 47/32: Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers {, poly(meth)acrylates, or polyvinyl pyrrolidone}
- 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 47/38: Cellulose; Derivatives thereof
- A61P 17/02: for treating wounds, ulcers, burns, scars, keloids, or the like
- A61P 23/02: Local anaesthetics
- A61P 25/04: Centrally acting analgesics, e.g. opioids
- A61P 29/02: without antiinflammatory effect
- 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

The present invention provides compositions useful in reducing or preventing pain in a subject in need thereof. In one embodiment, the compositions comprise a halogenated volatile compound. The present invention further includes a method of reducing or preventing pain in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a composition of the invention. Dosing regimens contemplated within the invention include one-time administration, continuous administration or periodic administration.

## Claims

### Claim 1

A method of reducing or ameliorating pain in a subject,
the method comprising administering to the subject a therapeutically effective amount of a uniform composition comprising a halogenated volatile compound and hydroxypropyl cellulose (HPC);
wherein the halogenated volatile compound is selected from the group consisting of isoflurane, halothane, enflurane, sevoflurane, desflurane, methoxyflurane, and any mixtures thereof.

### Claim 2 (depends on 1)

The method of claim 1, wherein the composition comprises about 5% to about 95% w/w halogenated volatile compound.

### Claim 3 (depends on 1)

The method of claim 1, wherein the composition comprises about 50% to about 90% w/w halogenated volatile compound.

### Claim 4 (depends on 1)

The method of claim 1,
wherein the composition further comprises at least one selected from the group consisting of an alcohol; a polyol; an organic solvent; an organic carbonate; a fatty acid or a salt thereof; a polyethylene glycol (PEG); a polypropylene glycol (PPG); a copolymer of 2-(2-hydroxypropoxy)propan-1-ol (PPG-12) and 1-methylene bis-4-isocyanatocyclohexane (SMDI); a poloxamer; saccharine; 2-(2-ethoxyethoxy)-ethanol; a monoester of a (methyl vinyl ether-maleic acid) co-polymer; and any combinations thereof;
wherein the polyol is selected from the group consisting of ethylene glycol, propylene glycol, glycerol, and any mixtures thereof,
wherein the organic solvent is selected from the group consisting of dimethylsulfoxide (DMSO), dimethylisosorbide, and any mixtures thereof, and
wherein the organic carbonate is selected from the group consisting of propylene carbonate, ethylene carbonate and any mixtures thereof.

### Claim 5 (depends on 4)

The method of claim 4, wherein at least one applies:
the alcohol is selected from the group consisting of methanol, ethanol, n-propanol, isopropanol, n-butanol, sec-butanol, isobutanol, t-butanol, and any mixtures thereof;
the fatty acid or salt thereof is selected from the group consisting of myristoleic acid, palmitoleic acid, sapienic acid, oleic acid, elaidic acid, vaccenic acid, linoleic acid, linoelaidic acid, α-linolenic acid, arachidonic acid, eicosapentaenoic acid, erucic acid, docosahexaenoic acid, caprylic acid, capric acid, lauric acid, myristic acid, palmitic acid, stearic acid, arachidic acid, behenic acid, lignoceric acid, cerotic acid, and any combinations thereof;
the PEG is selected from the group consisting of PEG-200, PEG-300, PEG-400, PEG-600, PEG-[950-1,050], PEG-1,000, PEG-[1,300-1,600], PEG-[1,305-1,595], PEG-1,450, PEG-1,500, PEG-2,000, PEG-2,050, PEG-3,000, PEG-[3,000-3,700], PEG-3,350, PEG-4,000, PEG-4,600, PEG-6,000, PEG-8,000, PEG-10,000, PEG-12,000, PEG-20,000, PEG-35,000, and any mixtures thereof;
the monoester of the (methyl vinyl ether-maleic acid) co-polymer is n-butyl, isopropyl, ethyl, or any mixtures thereof;
the poloxamer comprises at least one of poloxamer 188, poloxamer 407, and any mixtures thereof.

### Claim 6 (depends on 4)

The method of claim 4, wherein the composition comprises at least one of the following:
about 2% to about 20% w/w alcohol;
about 5% to about 20.25% w/w polyol;
about 5% to about 50% w/w organic solvent;
about 2.5% w/w organic carbonate;
about 1% to about 5% w/w fatty acid or a salt thereof;
about 6% to about 78% w/w PEG;
about 15% to about 20% w/w monoester of a (methyl vinyl ether-maleic acid) co-polymer;
about 5% to about 15% w/w copolymer of PPG-12 and SMDI;
about 2% w/w saccharine;
about 15% to about 20% w/w PPG;
about 1% to about 5% w/w poloxamer.

### Claim 7 (depends on 4)

The method of claim 4, wherein the alcohol is ethanol, and wherein the composition comprises a % w/w ethanol concentration selected from the group consisting of: about 8.25%, about 10%, about 10.5%, about 12.5%, about 14.25%, about 15%, and about 20% w/w.

### Claim 8 (depends on 4)

The method of claim 4, wherein the composition comprises a % w/w 2-(2-ethoxyethoxy)-ethanol concentration selected from the group consisting of about 5% and about 10% w/w.

### Claim 9 (depends on 4)

The method of claim 4, wherein the composition comprises a w/w polyol concentration selected from the group consisting of: about 5%, about 8%, about 14.75%, about 15%, about 15.25% and about 20.25% w/w.

### Claim 10 (depends on 4)

The method of claim 4, wherein the composition comprises from about 10% to about 50% w/w organic solvent.

### Claim 11 (depends on 1)

The method of claim 1, wherein the composition comprises about 1% to about 5% w/w HPC.

### Claim 12 (depends on 1)

The method of claim 1, wherein the composition comprises a w/w HPC concentration selected from the group consisting of: about 1.75%, about 2%, about 2.25%, about 2.5%, and about 5% w/w.

### Claim 13 (depends on 4)

The method of claim 4, wherein the composition comprises about 3% w/w fatty acid or a salt thereof.

### Claim 14 (depends on 4)

The method of claim 4, wherein the composition comprises a % w/w PEG concentration selected from the group consisting of: about 6%, about 9%, about 10%, about 15%, about 18.25%, about 20%, about 20.5% and about 78%.

### Claim 15 (depends on 4)

The method of claim 4, wherein the composition comprises about 20% w/w monoester of a (methyl vinyl ether-maleic acid) co-polymer.

### Claim 16 (depends on 4)

The method of claim 4, wherein the composition comprises about 10% w/w copolymer of PPG-12 and SMDI.

### Claim 17 (depends on 4)

The method of claim 4, wherein the composition is selected from the group consisting of:
(a) about 28% w/w DMSO, about 10% w/w copolymer of PPG-12 and SMDI, about 2% w/w HPC, and about 60% w/w isoflurane;
(b) about 25% w/w DMSO, about 5% w/w HPC, and about 70% w/w isoflurane;
(c) about 3% w/w oleic acid, about 14.75% w/w propylene glycol, about 1.75% w/w HPC, about 20.5% w/w PEG-400, and about 60% w/w isoflurane;
(d) about 23% w/w DMSO, about 15% w/w PPG-400, about 2% w/w HPC, and about 60% w/w isoflurane;
(e) about 8% w/w propylene glycol, about 2% w/w HPC, about 20% w/w isopropyl alcohol, and about 70% w/w isoflurane;
(f) about 38.25% w/w DMSO, about 1.75 w/w HPC, and about 60% w/w isoflurane;
(g) about 3% w/w oleic acid, about 15% w/w propylene glycol, about 14.25% w/w ethanol, about 1.75% w/w HPC, about 1% w/w poloxamer 407, about 5% w/w poloxamer 188, and about 60% w/w isoflurane;
(h) about 10.5% w/w ethanol, about 20% w/w monoester of a (methyl vinyl ether-maleic acid) co-polymer, about 2.5% w/w propylene carbonate, about 5% w/w 2-(2-ethoxyethoxy)ethanol, about 2% w/w HPC, and about 60% w/w isoflurane;
(i) about 35% w/w DMSO, about 5% w/w HPC, and about 60% w/w isoflurane;
(j) about 3% w/w oleic acid, about 15.25% w/w propylene glycol, about 10% w/w ethanol, about 1.75% w/w HPC, about 10% w/w PEG-400, and about 60% w/w isoflurane;
(k) about 10% w/w copolymer of PPG-12 and SMDI, about 8.25% w/w ethanol, about 20% w/w monoester of a (methyl vinyl ether-maleic acid) co-polymer, about 1.75% w/w HPC, and about 60% w/w isoflurane;
(l) about 10% w/w DMSO, about 5% w/w HPC, and about 85% w/w isoflurane;
(m) about 20% w/w DMSO, about 5% w/w HPC, and about 75% w/w isoflurane;
(n) about 3% w/w oleic acid, about 14.75% w/w propylene glycol, about 2.25% w/w HPC, about 20% w/w PEG-400, and about 60% w/w isoflurane;
(o) about 3% w/w oleic acid, about 15% w/w propylene glycol, about 2% w/w HPC, about 20% w/w PEG-400, and about 60% w/w isoflurane;
(p) about 20% w/w monoester of a (methyl vinyl ether-maleic acid) co-polymer, about 1.75% w/w HPC, about 18.25% w/w PEG-400, and about 60% w/w isoflurane;
(q) about 18% w/w DMSO, about 20% w/w monoester of a (methyl vinyl ether-maleic acid) co-polymer, about 2% w/w HPC, and about 60% w/w isoflurane;
(r) about 5% w/w DMSO, about 5% w/w HPC, and about 90% w/w isoflurane;
(s) about 3% w/w oleic acid, about 10% w/w copolymer of PPG-12 and SMDI, about 15.25% w/w propylene glycol, about 10% w/w ethanol, about 1.75% w/w HPC, and about 60% w/w isoflurane;
(t) about 37.5% w/w DMSO, about 2.5% w/w HPC, and about 60% w/w isoflurane; and
(u) about 3% w/w oleic acid, about 20.25% w/w propylene glycol, about 15% w/w ethanol, about 1.75% w/w HPC, and about 60% w/w isoflurane.

### Claim 18 (depends on 1)

The method of claim 1, wherein the composition is incorporated in a medical patch.

### Claim 19

A method of reducing or ameliorating pain in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a uniform composition comprising a halogenated volatile compound and a monoester of a (methyl vinyl ether-maleic acid) co-polymer;
wherein the halogenated volatile compound is selected from the group consisting of isoflurane, halothane, enflurane, sevoflurane, desflurane, methoxyflurane, and any mixtures thereof.

### Claim 20 (depends on 19)

The method of claim 19, wherein the composition comprises about 5% to about 95% w/w halogenated volatile compound.

### Claim 21 (depends on 19)

The method of claim 19, wherein the composition comprises about 50% to about 90% w/w halogenated volatile compound.

### Claim 22 (depends on 19)

The method of claim 19,
wherein the composition further comprises at least one selected from the group consisting of an alcohol; a polyol; an organic solvent; an organic carbonate; a fatty acid or a salt thereof; a polyethylene glycol (PEG); a polypropylene glycol (PPG); a copolymer of 2-(2-hydroxypropoxy)propan-1-ol (PPG-12) and 1-methylene bis-4-isocyanatocyclohexane (SMDI); a poloxamer; saccharine; 2-(2-ethoxyethoxy)-ethanol; hydroxypropyl cellulose (HPC); and any combinations thereof;
wherein the polyol is selected from the group consisting of ethylene glycol, propylene glycol, glycerol, and any mixtures thereof,
wherein the organic solvent is selected from the group consisting of dimethylsulfoxide (DMSO), dimethylisosorbide, and any mixtures thereof, and
wherein the organic carbonate is selected from the group consisting of propylene carbonate, ethylene carbonate and any mixtures thereof.

### Claim 23 (depends on 22)

The method of claim 22, wherein at least one applies:
the alcohol is selected from the group consisting of methanol, ethanol, n-propanol, isopropanol, n-butanol, sec-butanol, isobutanol, t-butanol, and any mixtures thereof;
the fatty acid or salt thereof is selected from the group consisting of myristoleic acid, palmitoleic acid, sapienic acid, oleic acid, elaidic acid, vaccenic acid, linoleic acid, linoelaidic acid, α-linolenic acid, arachidonic acid, eicosapentaenoic acid, erucic acid, docosahexaenoic acid, caprylic acid, capric acid, lauric acid, myristic acid, palmitic acid, stearic acid, arachidic acid, behenic acid, lignoceric acid, cerotic acid, and any combinations thereof;
the PEG is selected from the group consisting of PEG-200, PEG-300, PEG-400, PEG-600, PEG-[950-1,050], PEG-1,000, PEG-[1,300-1,600], PEG-[1,305-1,595], PEG-1,450, PEG-1,500, PEG-2,000, PEG-2,050, PEG-3,000, PEG-[3,000-3,700], PEG-3,350, PEG-4,000, PEG-4,600, PEG-6,000, PEG-8,000, PEG-10,000, PEG-12,000, PEG-20,000, PEG-35,000, and any mixtures thereof;
the poloxamer comprises at least one of poloxamer 188, poloxamer 407, and any mixtures thereof.

### Claim 24 (depends on 22)

The method of claim 22, wherein the composition comprises at least one of the following:
about 2% to about 20% w/w alcohol;
about 5% to about 20.25% w/w polyol;
about 5% to about 50% w/w organic solvent;
about 2.5% w/w organic carbonate;
about 1% to about 5% w/w fatty acid or a salt thereof;
about 6% to about 78% w/w PEG;
about 5% to about 15% w/w copolymer of PPG-12 and SMDI;
about 2% w/w saccharine;
about 15% to about 20% w/w PPG;
about 1% to about 5% w/w poloxamer;
about 1% to about 5% w/w HPC.

### Claim 25 (depends on 22)

The method of claim 22, wherein the alcohol is ethanol, and wherein the composition comprises a % w/w ethanol concentration selected from the group consisting of: about 8.25%, about 10%, about 10.5%, about 12.5%, about 14.25%, about 15%, and about 20% w/w.

### Claim 26 (depends on 22)

The method of claim 22, wherein the composition comprises a w/w 2-(2-ethoxyethoxy)-ethanol concentration selected from the group consisting of about 5% and about 10% w/w.

### Claim 27 (depends on 22)

The method of claim 22, wherein the composition comprises a % w/w polyol concentration selected from the group consisting of: about 5%, about 8%, about 14.75%, about 15%, about 15.25% and about 20.25% w/w.

### Claim 28 (depends on 22)

The method of claim 22, wherein the composition comprises from about 10% to about 50% w/w organic solvent.

### Claim 29 (depends on 22)

The method of claim 22, wherein the composition comprises a w/w HPC concentration selected from the group consisting of: about 1.75%, about 2%, about 2.25%, about 2.5%, and about 5% w/w.

### Claim 30 (depends on 22)

The method of claim 22, wherein the composition comprises about 3% w/w fatty acid or a salt thereof.

### Claim 31 (depends on 22)

The method of claim 22, wherein the composition comprises a w/w PEG concentration selected from the group consisting of: about 6%, about 9%, about 10%, about 15%, about 18.25%, about 20%, about 20.5% and about 78%.

### Claim 32 (depends on 19)

The method of claim 19, wherein the monoester of the (methyl vinyl ether-maleic acid) co-polymer is n-butyl, isopropyl, ethyl, or any mixtures thereof.

### Claim 33 (depends on 19)

The method of claim 19, wherein the composition comprises about 15% to about 20% w/w monoester of (methyl vinyl ether-maleic acid) co-polymer.

### Claim 34 (depends on 19)

The method of claim 19, wherein the composition comprises about 20% w/w monoester of (methyl vinyl ether-maleic acid) co-polymer.

### Claim 35 (depends on 22)

The method of claim 22, wherein the composition comprises about 10% w/w copolymer of PPG-12 and SMDI.

### Claim 36 (depends on 22)

The method of claim 22, wherein the composition is selected from the group consisting of:
(a) about 12.5% w/w ethanol, about 20% w/w monoester of a (methyl vinyl ether-maleic acid) co-polymer, about 2.5% w/w propylene carbonate, about 5% w/w 2-(2-ethoxyethoxy)ethanol, and about 60% w/w isoflurane;
(b) about 10.5% w/w ethanol, about 20% w/w monoester of a (methyl vinyl ether-maleic acid) co-polymer, about 2.5% w/w propylene carbonate, about 5% w/w 2-(2-ethoxyethoxy)ethanol, about 2% w/w HPC, and about 60% w/w isoflurane;
(c) about 10% w/w copolymer of PPG-12 and SMDI, about 8.25% w/w ethanol, about 20% w/w monoester of a (methyl vinyl ether-maleic acid) co-polymer, about 1.75% w/w HPC, and about 60% w/w isoflurane;
(d) about 20% w/w monoester of a (methyl vinyl ether-maleic acid) co-polymer, about 1.75% w/w HPC, about 18.25% w/w PEG-400, and about 60% w/w isoflurane;
(e) about 18% w/w DMSO, about 20% w/w monoester of a (methyl vinyl ether-maleic acid) co-polymer, about 2% w/w HPC, and about 60% w/w isoflurane.

### Claim 37 (depends on 19)

The method of claim 19, wherein the composition is incorporated in a medical patch.