# US 9,750,785 B2 · Vasopressin formulations for use in treatment of hypotension

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- Number: US 9,750,785 B2
- Document ID: US9750785B2
- Status: Granted
- Kind: B2
- Application number: 15/426,703
- Filed: 2017-02-07
- Published: 2017-06-08
- Granted: 2017-09-05
- Earliest claimed: 2015-01-30
- Assignees: Par Pharmaceutical, Inc.
- Applicants: Par Pharmaceutical, Inc.
- Inventors: Matthew Kenney; Vinayagam Kannan; Sunil Vandse; Suketu Sanghvi
- Web page: https://patentgrep.com/patent/US9750785B2

## CPC

- A61K 38/095: Oxytocins; Vasopressins; Related peptides
- 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 31/19: Carboxylic acids, e.g. valproic acid (salicylic acid A61K31/60)
- A61K 47/02: Inorganic compounds
- 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
- G01N 30/74: Optical detectors {(measurement of intensity, velocity, spectral content, polarisation, or phase of infrared, visible or ultraviolet light G01J)}
- G01N 30/88: Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86
- G01N 2030/027: {Liquid chromatography}
- G01N 2030/8831: {involving peptides or proteins}
- 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)
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

Provided herein are peptide formulations comprising polymers as stabilizing agents. The peptide formulations can be more stable for prolonged periods of time at temperatures higher than room temperature when formulated with the polymers. The polymers used in the present invention can decrease the degradation of the constituent peptides of the peptide formulations.

## Claims

### Claim 1

A pharmaceutical composition comprising, in a unit dosage form, from about 0.01 mg/mL to about 0.07 mg/mL of vasopressin or a pharmaceutically-acceptable salt thereof, wherein the unit dosage form further comprises impurities that are present in an amount of 0.9% to 1.7%, wherein the impurities have from about 85% to about 100% sequence homology to SEQ ID NO.: 1, and wherein the unit dosage form has a pH of 3.7-3.9.

### Claim 2 (depends on 1)

The pharmaceutical composition of claim 1, wherein the impurities comprise a plurality of peptides, wherein the impurities are determined based on:
(a) injecting the unit dosage form into a high pressure liquid chromatography apparatus, wherein the apparatus comprises:
(i) a chromatography column containing adsorbent particles as a stationary phase;
(ii) a first mobile phase passing through the chromatography column, wherein the first mobile phase is phosphate buffer at pH 3; and
(iii) a second mobile phase passing through the chromatography column, wherein the second mobile phase is a 50:50 acetonitrile:water solution;
(b) running the unit dosage form through the chromatography column for 55 minutes;
(c) eluting the vasopressin and the plurality of peptides from the chromatography column using a gradient of the first mobile phase, and a gradient of the second mobile phase, wherein each of the first and second mobile phase are run at a flow rate of 1 mL/min through the chromatography column;
(d) passing the eluted vasopressin and the plurality of peptides through a UV detector to generate a UV spectrum of the eluted vasopressin and the plurality of peptides;
(e) identifying a peptide of the plurality of peptides based on a retention time of the peptide of the plurality of peptides relative to a standard; and
(f) calculating an amount of the peptide of the plurality of peptides based on an integration of a peak obtained for the peptide of plurality of peptides from the UV spectrum.

### Claim 3 (depends on 1)

The pharmaceutical composition of claim 1, wherein the impurities comprise SEQ ID NO.: 2, and SEQ ID NO.: 2 is present in the unit dosage form in an amount of 0.1 to 0.3%.

### Claim 4 (depends on 1)

The pharmaceutical composition of claim 1, wherein the impurities comprise SEQ ID NO.: 3, and SEQ ID NO.: 3 is present in the unit dosage form in an amount of 0.1%.

### Claim 5 (depends on 1)

The pharmaceutical composition of claim 1, wherein the impurities comprise SEQ ID NO.: 4, and SEQ ID NO.: 4 is present in the unit dosage form in an amount of 0.2% to 0.4%.

### Claim 6 (depends on 1)

The pharmaceutical composition of claim 1, wherein the impurities comprise SEQ ID NO.: 7, and SEQ ID NO.: 7 is present in the unit dosage form in an amount of 0.3% to 0.6%.

### Claim 7 (depends on 1)

The pharmaceutical composition of claim 1, wherein the impurities comprise SEQ ID NO.: 10, and SEQ ID NO.: 10 is present in the unit dosage form in an amount of 0.1%.

### Claim 8 (depends on 1)

The pharmaceutical composition of claim 1, wherein the impurities comprise SEQ ID NO.: 2 and SEQ ID NO.: 4, and SEQ ID NO.: 2 is present in the unit dosage form in an amount of 0.1% to 0.3% and SEQ ID NO.: 4 is present in the unit dosage form in an amount of 0.2% to 0.4%.

### Claim 9 (depends on 8)

The pharmaceutical composition of claim 8, wherein the impurities further comprise SEQ ID NO.: 3, SEQ ID NO.: 7, and SEQ ID NO.: 10, and SEQ ID NO.: 3 is present in the unit dosage form in an amount of 0.1%, SEQ ID NO.: 7 is present in the unit dosage form in an amount of 0.3% to 0.6%, and SEQ ID NO.: 10 is present in the unit dosage form in an amount of 0.1%.

### Claim 10 (depends on 1)

The pharmaceutical composition of claim 1, further comprising sodium acetate.

### Claim 11 (depends on 1)

The pharmaceutical composition of claim 1, the unit dosage form further comprising a pH adjusting agent.