# US 10,765,649 B2 · Stable aqueous capsaicin injectable formulations and medical uses thereof

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- Number: US 10,765,649 B2
- Document ID: US10765649B2
- Status: Granted
- Kind: B2
- Application number: 16/695,831
- Filed: 2019-11-26
- Published: 2020-03-26
- Granted: 2020-09-08
- Earliest claimed: 2016-11-02
- Assignees: Centrexion Therapeutics Corporation
- Applicants: Centrexion Therapeutics Corporation
- Inventors: Drazen Ostovic; Gary Fred Musso
- Web page: https://patentgrep.com/patent/US10765649B2

## CPC

- A61K 31/165: having aromatic rings, e.g. colchicine, atenolol, progabide
- 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 31/05: Phenols {(cannabinoids A61K31/658)}
- A61K 31/167: having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61K 47/14: Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
- 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 47/547: {Chelates, e.g. Gd-DOTA or Zinc-amino acid chelates; Chelate-forming compounds, e.g. DOTA or ethylenediamine being covalently linked or complexed to the pharmacologically- or therapeutically-active agent}
- A61K 47/55: the modifying agent being also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug
- A61P 25/00: Drugs for disorders of the nervous system
- 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 invention provides stable, aqueous capsaicin injectable formulations, a unit dose containing such injectable formulations, medical kits, and methods for using such injectable formulations and unit doses to treat patients suffering from pain, such as osteoarthritic knee pain. The stable, aqueous capsaicin injectable formulations may contain, for example, capsaicin, a solubilizing agent (e.g., a polyethylene glycol ester of a (C15-C25) hydroxyalkanoic acid), an antioxidant, and water.

## Claims

### Claim 1

An aqueous, capsaicin injectable formulation, comprising
a. about 0.04% (w/w) to about 0.06% (w/w) of capsaicin;
b. about 0.5% (w/w) to about 1.5% (w/w) of a solubilizing agent, wherein the solubilizing agent comprises
and polyethylene glycol;
c. about 0.005% (w/w) to about 0.015% (w/w) of an antioxidant;
d. about 0.2% (w/w) to about 1% (w/w) of an alkali metal acetate;
e. about 0.01% (w/w) to about 0.05% (w/w) of a chelating agent;
f. about 0.3% (w/w) to about 0.9% (w/w) of a tonicity modifier;
g. at least 96% (w/w) water; and
having a pH in the range of about 5 to about 6; wherein the formulation contains less than 1% (w/w) of capsaicin-dimer having the following structure:

### Claim 2 (depends on 1)

The formulation of claim 1, wherein the solubilizing agent comprises (a) from 68% (w/w) to 72% (w/w) of a mixture of
and (b) from 28% (w/w) to 32% (w/w) polyethylene glycol.

### Claim 3 (depends on 1)

The formulation of claim 1, wherein any polyethylene glycol or polyethylene glycolyl each independently have a weight-average molecular weight in the range of about 600 g/mol to about 750 g/mol.

### Claim 4 (depends on 1)

The formulation of claim 1, wherein any polyethylene glycol or polyethylene glycolyl each independently have a weight-average molecular weight of about 660 g/mol.

### Claim 5 (depends on 2)

The formulation of claim 2, wherein any polyethylene glycol or polyethylene glycolyl each independently have a weight-average molecular weight in the range of about 600 g/mol to about 750 g/mol.

### Claim 6 (depends on 2)

The formulation of claim 2, wherein any polyethylene glycol or polyethylene glycolyl each independently have a weight-average molecular weight of about 660 g/mol.

### Claim 7 (depends on 1)

The formulation of claim 1, wherein upon storage at 25° C. for 24 weeks, the formulation contains less than 0.6% (w/w) of the capsaicin-dimer.

### Claim 8 (depends on 2)

The formulation of claim 2, wherein upon storage at 25° C. for 24 weeks, the formulation contains less than 0.6% (w/w) of the capsaicin-dimer.

### Claim 9 (depends on 5)

The formulation of claim 5, wherein upon storage at 25° C. for 24 weeks, the formulation contains less than 0.6% (w/w) of the capsaicin-dimer.

### Claim 10 (depends on 6)

The formulation of claim 6, wherein upon storage at 25° C. for 24 weeks, the formulation contains less than 0.6% (w/w) of the capsaicin-dimer.

### Claim 11 (depends on 1)

The formulation of claim 1, wherein the formulation contains less than 0.1% (w/w) of 5-oxo-capsaicin.

### Claim 12 (depends on 2)

The formulation of claim 2, wherein the formulation contains less than 0.1% (w/w) of 5-oxo-capsaicin.

### Claim 13 (depends on 6)

The formulation of claim 6, wherein the formulation contains less than 0.1% (w/w) of 5-oxo-capsaicin.

### Claim 14 (depends on 1)

The formulation of claim 1, wherein upon storage at 25° C. for 24 weeks, the formulation contains less than 0.1% (w/w) of 5-oxo-capsaicin.

### Claim 15 (depends on 2)

The formulation of claim 2, wherein upon storage at 25° C. for 24 weeks, the formulation contains less than 0.1% (w/w) of 5-oxo-capsaicin.

### Claim 16 (depends on 4)

The formulation of claim 4, wherein upon storage at 25° C. for 24 weeks, the formulation contains less than 0.1% (w/w) of 5-oxo-capsaicin.

### Claim 17 (depends on 6)

The formulation of claim 6, wherein upon storage at 25° C. for 24 weeks, the formulation contains less than 0.1% (w/w) of 5-oxo-capsaicin.

### Claim 18 (depends on 8)

The formulation of claim 8, wherein upon storage at 25° C. for 24 weeks, the formulation contains less than 0.1% (w/w) of 5-oxo-capsaicin.

### Claim 19 (depends on 10)

The formulation of claim 10, wherein upon storage at 25° C. for 24 weeks, the formulation contains less than 0.1% (w/w) of 5-oxo-capsaicin.

### Claim 20

An aqueous, capsaicin injectable formulation, comprising
a. about 0.04% (w/w) to about 0.06% (w/w) of capsaicin;
b. about 0.8% (w/w) to about 1.2% (w/w) of a solubilizing agent, wherein the solubilizing agent comprises (a) about 70% (w/w) of a mixture of
and (b) about 30% (w/w) polyethylene glycol;
c. about 0.005% (w/w) to about 0.015% (w/w) of dibutylhydroxytoluene;
d. about 0.2% (w/w) to about 1% (w/w) of sodium acetate;
e. about 0.01% (w/w) to about 0.05% (w/w) of ethylenediaminetetraacetic acid or a salt thereof;
f. about 0.3% (w/w) to about 0.9% (w/w) of sodium chloride;
g. at least 96% (w/w) water; and
having a pH in the range of about 5 to about 6; wherein the formulation contains less than 1% (w/w) of capsaicin-dimer having the following structure:

### Claim 21 (depends on 20)

The formulation of claim 20, wherein any polyethylene glycol or polyethylene glycolyl each independently have a weight-average molecular weight in the range of about 600 g/mol to about 750 g/mol.

### Claim 22 (depends on 20)

The formulation of claim 20, wherein any polyethylene glycol or polyethylene glycolyl each independently have a weight-average molecular weight of about 660 g/mol.

### Claim 23 (depends on 20)

The formulation of claim 20, wherein upon storage at 25° C. for 24 weeks, the formulation contains less than 0.6% (w/w) of the capsaicin-dimer.

### Claim 24 (depends on 21)

The formulation of claim 21, wherein upon storage at 25° C. for 24 weeks, the formulation contains less than 0.6% (w/w) of the capsaicin-dimer.

### Claim 25 (depends on 22)

The formulation of claim 22, wherein upon storage at 25° C. for 24 weeks, the formulation contains less than 0.6% (w/w) of the capsaicin-dimer.

### Claim 26 (depends on 20)

The formulation of claim 20, wherein the formulation contains less than 0.1% (w/w) of 5-oxo-capsaicin.

### Claim 27 (depends on 22)

The formulation of claim 22, wherein the formulation contains less than 0.1% (w/w) of 5-oxo-capsaicin.

### Claim 28 (depends on 20)

The formulation of claim 20, wherein upon storage at 25° C. for 24 weeks, the formulation contains less than 0.1% (w/w) of 5-oxo-capsaicin.

### Claim 29 (depends on 22)

The formulation of claim 22, wherein upon storage at 25° C. for 24 weeks, the formulation contains less than 0.1% (w/w) of 5-oxo-capsaicin.

### Claim 30 (depends on 25)

The formulation of claim 25, wherein upon storage at 25° C. for 24 weeks, the formulation contains less than 0.1% (w/w) of 5-oxo-capsaicin.