# US 11,077,071 B2 · Phytonadione compositions and related methods

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- Number: US 11,077,071 B2
- Document ID: US11077071B2
- Status: Granted
- Kind: B2
- Application number: 16/043,582
- Filed: 2018-07-24
- Published: 2018-11-15
- Granted: 2021-08-03
- Earliest claimed: 2015-02-27
- Assignees: Exela Holdings, Inc.
- Applicants: Exela Holdings, Inc
- Inventors: Phanesh Koneru; Sreerarama Murthy Mallipeddi; Jonathan E. Sterling
- Web page: https://patentgrep.com/patent/US11077071B2

## CPC

- A61K 31/122: having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
- A61J 1/05: for collecting, storing or administering blood, plasma or medical fluids {(multiple bags systems for separating or storing blood components A61M1/0209); Infusion or perfusion containers}
- 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 47/26: Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
- A61K 47/44: Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin (synthetic glycerides, e.g. medium-chain triglycerides, A61K47/14)
- 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)
- A61J: CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE

## Abstract

Stable Phytonadione compositions for parenteral administration are provided which comprise (E) isomer of phytonadione at or greater than 97% w/w as the active ingredient, and is substantially free of (Z) isomer. Said compositions are stable, sterile, and particulate-free. Further, said compositions reduce or avoid allergic reactions to benzyl alcohol and polysorbate. In some aspects, the compositions are free or substantially free of benzyl alcohol and/or reduced amounts of polysorbate. Methods of manufacture and methods of administration also provided.

## Claims

### Claim 1

A stable, injectable, sterile, particulate-matter-free, aqueous phytonadione composition comprising Phytonadione in its (E) isomer form that has less than or equal to 3% w/w of its (Z) isomer, at a concentration of from about 100 ug/ml to about 20 mg/ml;
and is free of benzyl alcohol.

### Claim 2 (depends on 1)

The composition of claim 1, wherein said (Z) isomer is present from 0.5% to less than or equal to 3% w/w of the (E) isomer.

### Claim 3 (depends on 1)

The composition of claim 1, wherein said composition is free of cremophor.

### Claim 4 (depends on 1)

The composition of claim 1, wherein said composition is free of propylene glycol.

### Claim 5 (depends on 1)

The composition of claim 1, wherein the composition comprises less than 1:10 ratio of (E)-isomer of phytonadione:
polysorbate.

### Claim 6 (depends on 1)

The composition of claim 1, wherein said composition is provided in a non-reacting glass or non-reacting polymeric container selected from a vial container or a pre-filled syringe container.

### Claim 7 (depends on 6)

The composition of claim 6, wherein the non-reacting polymeric container is made of polyethylene or polypropylene or a combination thereof.

### Claim 8 (depends on 1)

The composition of claim 1, wherein an epoxide derivative of the (E) isomer of phytonadione is present at less than 4% w/w of the (E) isomer.

### Claim 9 (depends on 1)

A method comprising: administering the composition of claim 1 to a mammal.

### Claim 10 (depends on 9)

The method of claim 9, wherein the mammal is a human.

### Claim 11

A method of reducing an anaphylactic reaction associated with phytonadione administration comprising:
administering a composition comprising Phytonadione in its (E) isomer form that is substantially free of its (Z) isomer, at a concentration of from about 0.1 mg/ml to about 20 mg/ml; and optionally a pH adjuster, wherein the composition has a pH of from about 3.5 to about 8.0, wherein said (Z) isomer is present at about 3% w/w or less of the (E) isomer; and wherein said composition is free of benzyl alcohol and cremophor, and comprises a polysorbate at a concentration of less than about 1:10 ratio of (E) isomer of phytonadione: polysorbate.

### Claim 12 (depends on 11)

The method of claim 11, wherein the composition is administered from a vial or a pre-filled syringe wherein the vial or pre-filled syringe is selected from a non-reacting glass or polymeric material.