# US 10,765,683 B2 · Stable formulations for parenteral injection of small molecule drugs

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- Number: US 10,765,683 B2
- Document ID: US10765683B2
- Status: Granted
- Kind: B2
- Application number: 14/812,515
- Filed: 2015-07-29
- Published: 2016-06-02
- Granted: 2020-09-08
- Earliest claimed: 2012-06-27
- Assignees: Xeris Pharmaceuticals, Inc.
- Applicants: Xeris Pharmaceuticals, Inc.
- Inventors: Steven J. Prestrelski; Nancy Scott
- Web page: https://patentgrep.com/patent/US10765683B2

## CPC

- A61K 31/5513: 1,4-Benzodiazepines, e.g. diazepam {or clozapine}
- 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 9/08: Solutions {(composition of solutions A61K47/00)}
- A61K 31/137: Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine {or methadone}
- A61K 31/167: having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
- A61K 31/352: condensed with carbocyclic rings, e.g. methantheline {(cannabinoids A61K31/658)}
- A61K 31/4045: Indole-alkylamines; Amides thereof, e.g. serotonin, melatonin
- A61K 31/4196: 1,2,4-Triazoles
- A61K 31/496: Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
- A61K 31/55: having seven-membered rings, e.g. azelastine, pentylenetetrazole
- A61K 31/675: having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
- A61K 31/7036: having at least one amino group directly attached to the carbocyclic ring, e.g. streptomycin, gentamycin, amikacin, validamycin, fortimicins
- A61K 47/10: Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
- A61K 47/14: Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
- 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
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/06: Antimigraine agents
- A61P 25/08: Antiepileptics; Anticonvulsants
- A61P 25/22: Anxiolytics
- 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

Disclosed is a stable liquid formulation for parenteral injection comprising a biocompatible non-aqueous solvent and a small molecule drug, or a salt thereof, solubilized within the non-aqueous solvent, wherein the liquid formulation comprises less than 10% by weight residual water, and wherein the volume of the liquid formulation to be parenterally injected is from 0.1 μl to 3 ml.

## Claims

### Claim 1

A parenteral injection device comprising:
an injection device containing an injectable composition comprising:
(a) a dimethylsulfoxide (DMSO) solvent; and
(b) a benzodiazepine, or a salt thereof, solubilized within the solvent, wherein the benzodiazepine is present in the injectable composition in an amount up to its solubility limit, wherein the benzodiazepine consists of diazepam,
wherein the injectable composition comprises less than 5% by weight residual water, and the volume of the injectable composition to be parenterally injected is 3 ml or less.

### Claim 2 (depends on 1)

The injection device of claim 1, wherein the injection device is a syringe, a pen injection device, an auto-injector device, an external or implantable pump, or a perfusion bag.

### Claim 3 (depends on 1)

The injection device of claim 1, wherein the injectable composition comprises 50 mg/ml to 300 mg/ml of diazepam.

### Claim 4 (depends on 1)

The injection device of claim 1, wherein the volume of the injectable composition to be parenterally injected is from 0.1 μl to 1 μl.

### Claim 5 (depends on 1)

The injection device of claim 1, wherein the volume of the injectable composition to be parenterally injected is from 1 μl to 10 μl.

### Claim 6 (depends on 1)

The injection device of claim 1, wherein the volume of the injectable composition to be parenterally injected is from 10 μl to 1 ml.

### Claim 7 (depends on 1)

The injection device of claim 1, wherein the volume of the injectable composition to be parenterally injected is from 1 ml to 3 ml.

### Claim 8 (depends on 1)

A method of using the injection device of claim 1 to a subject, the method comprising parenterally injecting the injectable composition to the subject.

### Claim 9 (depends on 8)

The method of claim 8, wherein the injectable composition is parenterally injected with a syringe, a pen injection device, an auto-injector device, an external or implantable pump, or a perfusion bag.

### Claim 10 (depends on 8)

The method of claim 8, wherein the injectable composition is not diluted prior to administration.

### Claim 11 (depends on 1)

A method of treating anxiety, muscle spasms, or seizures, the method comprising parenterally injecting the injectable composition using the injection device of claim 1 to a subject in need thereof.

### Claim 12 (depends on 11)

The method of claim 11, wherein the injectable composition is parenterally injected with a syringe, a pen injection device, an auto-injector device, an external or implantable pump, or a perfusion bag.

### Claim 13 (depends on 11)

The method of claim 11, wherein the injectable composition is not diluted prior to administration.