IP Library › Granted Patent US 12,472,201
Granted Patent B2
US 12,472,201 · App. 17/981,348 · Granted Nov 18, 2025

Complexing agent salt formulations of pharmaceutical compounds

Inventors: Jeffrey Becker (Santa Barbara, CA); Gregg Peterson (Santa Barbara, CA); Jason Wallach (Philadelphia, PA)
Assignee: Bexson Biomedical, Inc.
A61K31/724A61K45/06
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Quick Facts
Patent No.
US 12,472,201
App. No.
17/981,348
Granted
Nov 18, 2025
Kind
B2
Abstract

Provided herein are pharmaceutical formulations and pharmaceutical compound salts which utilize complexing agents as counterions. Such formulations and salts are useful for treating a variety of disease and disorders.

Claims (38)

1 . A pharmaceutical composition, comprising:

(i) a cationic pharmaceutical compound, or an enantiomer, a mixture of enantiomers, or an isotopic variant thereof, comprising a protonated nitrogen atom,

wherein the cationic pharmaceutical compound is not ketamine; and

(ii) a substituted cyclodextrin comprising a plurality of anionic functional groups, wherein substantially all of the plurality of anionic functional groups of the substituted cyclodextrin are deprotonated, and at least one of the plurality of anionic functional groups acts as a counterion for the protonated nitrogen atom of the cationic pharmaceutical compound,

wherein a molar ratio of the cationic pharmaceutical compound to the substituted cyclodextrin is greater than 1:1, and

wherein the pharmaceutical composition comprising effective amounts of the cationic pharmaceutical compound and the substituted cyclodextrin has an osmolality, when in solution, that is at least about 10% less than a corresponding pharmaceutical composition prepared from a salt of the cationic pharmaceutical compound and a sodium salt of the substituted cyclodextrin.

2 . The pharmaceutical composition of claim 1 , wherein the substituted cyclodextrin is substituted with 3 to 8 anionic functional groups.

3 . The pharmaceutical composition of claim 2 , wherein the substituted cyclodextrin is sulfobutylether-β-cyclodextrin.

4 . The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition has a molar ratio of the substituted cyclodextrin to the cationic pharmaceutical compound from about 1:2 to about 1:10.

5 . The pharmaceutical composition of claim 4 , wherein the substituted cyclodextrin acts as the counterion to between 5 to 10 molecules of the cationic pharmaceutical compound.

6 . A method of therapy comprising:

administering a pharmaceutical composition to a human subject in need thereof, wherein the pharmaceutical composition comprises:

(i) a cationic pharmaceutical compound, or an enantiomer, a mixture of enantiomers, or an isotopic variant thereof, comprising a protonated nitrogen atom, wherein the cationic pharmaceutical compound is not ketamine; and

(ii) a substituted cyclodextrin comprising a plurality of anionic functional groups, wherein substantially all of the plurality of anionic functional groups of the substituted cyclodextrin are deprotonated, and at least one of the plurality of anionic functional groups acts as a counterion for the protonated nitrogen atom of the cationic pharmaceutical compound,

wherein a molar ratio of the cationic pharmaceutical compound to the substituted cyclodextrin is greater than 1:1, and

wherein the pharmaceutical composition comprising effective amounts of the cationic pharmaceutical compound and the substituted cyclodextrin has an osmolality, when in solution, that is at least about 10% less than a corresponding pharmaceutical composition prepared from a salt of the cationic pharmaceutical compound and a sodium salt of the substituted cyclodextrin.

7 . The method of claim 6 , wherein the substituted cyclodextrin is substituted with 3 to 8 anionic functional groups.

8 . The method of claim 7 , wherein the substituted cyclodextrin is sulfobutylether-β-cyclodextrin.

9 . The method of claim 6 , wherein the pharmaceutical composition has a molar ratio of the substituted cyclodextrin to the cationic pharmaceutical compound from about 1:2 to 1:10.

10 . The method of claim 9 , wherein the substituted cyclodextrin acts as the counterion to between 5 to 10 molecules of the cationic pharmaceutical compound.

11 . The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition is formulated as an inhalable powder.

12 . The pharmaceutical composition of claim 1 , wherein the cationic pharmaceutical compound and the substituted cyclodextrin has an osmolality, when in solution, that is at least about 20% less than a corresponding pharmaceutical composition prepared from a salt of the cationic pharmaceutical compound and a sodium salt of the substituted cyclodextrin.

13 . The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition is formulated as a solid.

14 . The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition is formulated as a liquid.

15 . The pharmaceutical composition of claim 14 , wherein the pharmaceutical composition has a pH that is within about 0.2 pH units to about 2 pH units of the pKa of the cationic pharmaceutical compound.

16 . The pharmaceutical composition of claim 14 , wherein the pharmaceutical composition has a pH of about 4 to about 7.

17 . The pharmaceutical composition of claim 1 , wherein the cationic pharmaceutical compound comprises a basic nitrogen atom having a pKa of about 4 to about 12.

18 . The pharmaceutical composition of claim 1 , wherein the osmolality of the solution is determined on an osmometer.

19 . The pharmaceutical composition of claim 18 , wherein the osmolality is determined using saline solutions freshly prepared with sodium chloride and run as positive controls.

20 . The pharmaceutical composition of claim 18 , wherein the osmolality is determined by calculating the mean from back-to-back triplicate measurements.

21 . The pharmaceutical composition of claim 6 , wherein the osmolality of the solution is determined on an osmometer.

22 . The pharmaceutical composition of claim 6 , wherein the cationic pharmaceutical compound and the substituted cyclodextrin has an osmolality, when in solution, that is at least about 20% less than a corresponding pharmaceutical composition prepared from a salt of the cationic pharmaceutical compound and a sodium salt of the substituted cyclodextrin.

23 . A pharmaceutical composition, comprising:

(i) a cationic pharmaceutical compound, or an enantiomer, a mixture of enantiomers, or an isotopic variant thereof, comprising a protonated nitrogen atom,

wherein the cationic pharmaceutical compound is not ketamine; and

(ii) a substituted cyclodextrin comprising a plurality of anionic functional groups, wherein substantially all of the plurality of anionic functional groups of the substituted cyclodextrin are deprotonated, and at least one of the plurality of anionic functional groups acts as a counterion for the protonated nitrogen atom of the cationic pharmaceutical compound,

wherein a molar ratio of the cationic pharmaceutical compound to the substituted cyclodextrin is greater than 1:1, and

wherein the pharmaceutical composition comprising effective amounts of the cationic pharmaceutical compound and the substituted cyclodextrin, when in solution, has an osmolality that is at least about 50 mOsm/kg less than a corresponding pharmaceutical composition prepared from a salt of the cationic pharmaceutical compound and a sodium salt of the substituted cyclodextrin.

Assignments (4)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 27, 2026
From: BEXSON BIOMEDICAL, INC.
To: PKX BIO, INC.
Reel/Frame 075811/0381 →
RELEASE OF SECURITY INTEREST Recorded Apr 21, 2026
From: STEVANATO GROUP, S.P.A.
To: BEXSON BIOMEDICAL, INC.
Reel/Frame 074432/0480 →
SECURITY INTEREST Recorded Jul 27, 2023
From: BEXSON BIOMEDICAL, INC.
To: STEVANATO GROUP, S.P.A.
Reel/Frame 064406/0164 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 11, 2022
From: BECKER, JEFFREY; PETERSON, GREGG; WALLACH, JASON
To: BEXSON BIOMEDICAL, INC.
Reel/Frame 061741/0075 →
Continuity (7)
Continuation 17546880 · Dec 9, 2021
Continuation PCTUS2021059760 · Nov 17, 2021
Provisional Application 63115445 · Nov 18, 2020
Provisional Application 63115458 · Nov 18, 2020
Provisional Application 63115451 · Nov 18, 2020
Provisional Application 63115453 · Nov 18, 2020
Related Publication 20230124101A1 · Apr 20, 2023
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