# US 11,026,919 B2 · Formulation for soft anticholinergic analogs

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- Number: US 11,026,919 B2
- Document ID: US11026919B2
- Status: Granted
- Kind: B2
- Application number: 17/107,942
- Filed: 2020-11-30
- Published: 2021-03-18
- Granted: 2021-06-08
- Earliest claimed: 2015-07-21
- Assignees: Bodor Laboratories, Inc.
- Applicants: Bodor Laboratories, Inc.
- Inventors: Nicholas S. Bodor; John J. Koleng; David Angulo
- Web page: https://patentgrep.com/patent/US11026919B2

## CPC

- A61K 31/40: having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K 8/34: Alcohols
- A61K 8/345: {containing more than one hydroxy group}
- A61K 8/37: Esters of carboxylic acids
- A61K 8/4913: {having five membered rings, e.g. pyrrolidone carboxylic acid}
- A61K 8/4926: {having six membered rings}
- A61K 8/585: {Organosilicon compounds}
- A61K 8/731: {Cellulose; Quaternized cellulose derivatives}
- A61K 8/891: saturated, e.g. dimethicone, phenyl trimethicone, C24-C28 methicone or stearyl dimethicone
- 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 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- 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 47/24: containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
- 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 17/00: Drugs for dermatological disorders
- A61P 25/02: for peripheral neuropathies
- A61Q 15/00: Anti-perspirants or body deodorants (deodorisation of air A61L9/00)
- C07D 207/12: Oxygen or sulfur atoms
- 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
- A61Q: SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

Topical formulations comprising soft glycopyrrolates are useful for treating excessive sweating conditions in subjects, such as humans suffering from hyperhidrosis. Preferably, at least one soft anticholinergic agent is provided in an effective amount or concentration in an anhydrous formulation that can inhibit excessive perspiration resulting from a condition such as hyperhidrosis.

## Claims

### Claim 1

An anhydrous topical gel composition comprising:
(a) a compound having the formula:
said compound having the R stereoisomeric configuration at the 2 position and the R, S or RS stereoisomeric configuration at the 1′ and 3′ positions, or being a mixture thereof;
(b) anhydrous ethanol;
(c) at least one gelling or viscosity-controlling ingredient comprising hydroxypropyl cellulose;
(d) citric acid;
(e) hexylene glycol;
(f) isopropyl myristate; and
(g) optionally, at least one additional carrier or excipient;
provided that said anhydrous topical gel composition comprises from about 1% to about 25% w/v or w/w of the compound of formula (2), said composition having greater storage stability compared to a composition comprising an aqueous solvent or aqueous buffer.

### Claim 2 (depends on 1)

The anhydrous topical gel composition of claim 1, wherein said anhydrous topical gel composition comprises at least one additional carrier or excipient.

### Claim 3 (depends on 1)

The anhydrous topical gel composition of claim 1, wherein the compound of formula (2) is selected from the group consisting of:
(i) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-(ethoxycarbonylmethyl)-1-methylpyrrolidinium bromide;
(ii) (2R) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-(ethoxycarbonylmethyl)-1-methylpyrrolidinium bromide;
(iii) (2R,3′R) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-(ethoxycarbonylmethyl)-1-methylpyrrolidinium bromide;
(iv) (2R,3′S) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-(ethoxycarbonylmethyl)-1-methylpyrrolidinium bromide;
(v) (2R,1′R,3′S) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-(ethoxycarbonylmethyl)-1-methylpyrrolidinium bromide;
(vi) (2R,1′S,3′S) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-(ethoxycarbonylmethyl)-1-methylpyrrolidinium bromide;
(vii) (2R,1′R,3′R) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-(ethoxycarbonylmethyl)-1-methylpyrrolidinium bromide; and
(viii) (2R,1′S,3′R) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-(ethoxycarbonylmethyl)-1-methylpyrrolidinium bromide.

### Claim 4 (depends on 1)

The anhydrous topical gel composition of claim 1, wherein said anhydrous topical gel composition comprises the compound of formula (2) at a concentration of from about 1% to about 20% w/v or w/w.

### Claim 5 (depends on 1)

The anhydrous topical gel composition of claim 1, wherein said anhydrous topical gel composition comprises the compound of formula (2) at a concentration of from about 2% to about 10% w/v or w/w.

### Claim 6 (depends on 1)

The anhydrous topical gel composition of claim 1, wherein said anhydrous topical gel composition is packaged in a multiple dose container that meters a dose of from about 0.5 ml to about 1.0 ml of the composition for each application.

### Claim 7 (depends on 1)

The anhydrous topical gel composition of claim 1, wherein said anhydrous topical gel composition is packaged in a single or unit dose container that delivers a single or unit dose of about 0.5 ml to about 1.0 ml of the composition for each application.

### Claim 8 (depends on 1)

The anhydrous topical gel composition of claim 1, wherein the compound of formula (2) is (2R, 3′R) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-(ethoxycarbonylmethyl)-1-methylpyrrolidinium bromide.

### Claim 9 (depends on 1)

The anhydrous topical gel composition of claim 1, wherein said anhydrous topical gel composition further comprises DIMETHICONOL BLEND 20.

### Claim 10 (depends on 1)

The anhydrous topical gel composition of claim 1, wherein a dose of from about 0.5 ml to about 2.0 ml is applied.

### Claim 11

A method of treating hyperhidrosis in a subject, said method comprising topically administering an anhydrous topical gel composition to skin of an area of a subject suffering from hyperhidrosis, before bedtime, such that, compared to untreated, baseline conditions, sweat production is reduced by at least 25% for at least six (6) hours; and such that sweat production is reduced by an amount substantially equivalent to an amount that sweat production is reduced as compared to untreated, baseline conditions, following administration of a composition comprising the same concentration of glycopyrrolate, and with an improved safety profile compared to topical glycopyrrolate,
wherein said anhydrous topical gel composition comprises:
(a) a compound having the formula:
said compound having the R stereoisomeric configuration at the 2 position and the R, S or RS stereoisomeric configuration at the 1′ and 3′ positions, or being a mixture thereof;
(b) anhydrous ethanol;
(c) at least one gelling or viscosity-controlling ingredient comprising hydropropyl cellulose;
(d) citric acid;
(e) hexylene glycol;
(f) isopropyl myristate; and
(g) optionally, at least one additional carrier or excipient;
provided that said anhydrous topical gel composition comprises from about 1% to about 25% w/v or w/w of the compound of formula (2), said composition having greater storage stability compared to a composition comprising an aqueous solvent or aqueous buffer,
wherein the anhydrous topical gel composition is administered by application to an anatomic area selected from a hand palm area, a foot plantar area, a groin area, an axilla area, and a facial area of the subject.

### Claim 12 (depends on 11)

The method of claim 11, wherein said anhydrous topical gel composition comprises at least one additional carrier or excipient.

### Claim 13 (depends on 11)

The method of claim 11, wherein the compound of formula (2) is selected from the group consisting of:
(i) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-(ethoxycarbonylmethyl)-1-methylpyrrolidinium bromide;
(ii) (2R) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-(ethoxycarbonylmethyl)-1-methylpyrrolidinium bromide;
(iii) (2R,3′R) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-(ethoxycarbonylmethyl)-1-methylpyrrolidinium bromide;
(iv) (2R,3′S) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-(ethoxycarbonylmethyl)-1-methylpyrrolidinium bromide;
(v) (2R,1′R,3′S) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-(ethoxycarbonylmethyl)-1-methylpyrrolidinium bromide;
(vi) (2R,1′S,3′S) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-(ethoxycarbonylmethyl)-1-methylpyrrolidinium bromide;
(vii) (2R,1′R,3′R) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-(ethoxycarbonylmethyl)-1-methylpyrrolidinium bromide; and
(viii) (2R,1′S,3′R) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-(ethoxycarbonylmethyl)-1-methylpyrrolidinium bromide.

### Claim 14 (depends on 11)

The method of claim 11, wherein said anhydrous topical gel composition comprises the compound of formula (2) at a concentration of from about 1% to about 20% w/v or w/w.

### Claim 15 (depends on 11)

The method of claim 11, wherein said anhydrous topical gel composition comprises the compound of formula (2) at a concentration of from about 2% to about 10% w/v or w/w.

### Claim 16 (depends on 11)

The method of claim 11, wherein said anhydrous topical gel composition is packaged in a multiple dose container that meters a dose of from about 0.5 ml to about 1.0 ml of the composition for each application.

### Claim 17 (depends on 11)

The method of claim 11, wherein said anhydrous topical gel composition is packaged in a single or unit dose container that delivers a single or unit dose of about 0.5 ml to about 1.0 ml of the composition for each application.

### Claim 18 (depends on 11)

The method of claim 11, wherein the compound of formula (2) is (2R, 3′R) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-(ethoxycarbonylmethyl)-1-methylpyrrolidinium bromide.

### Claim 19 (depends on 11)

The method of claim 11, wherein said anhydrous topical gel composition further comprises DIMETHICONOL BLEND 20.

### Claim 20 (depends on 11)

The method of claim 11, wherein a dose of from about 0.5 ml to about 2.0 ml is applied.