Botulinum toxin prefilled container

Patent metadata

Field	Value
Publication number	US-12434002-B2
Application number	US-202117356300-A
Country	US
Kind code	B2
Filing date	Jun 23, 2021
Priority date	Dec 23, 2014
Publication date	Oct 7, 2025
Grant date	Oct 7, 2025

Abstract

The present invention relates to a prefilled glass container, such as a prefilled glass syringe, comprising an aqueous botulinum toxin formulation. The aqueous botulinum toxin formulation in the prefilled container is stable at low to ambient temperature for a prolonged time period. Furthermore, the present invention relates to a kit comprising the botulinum toxin prefilled container, and to the use of the botulinum toxin prefilled container in therapeutic and cosmetic applications.

First claim

The invention claimed is:

1. A method for the cosmetic treatment of the skin, the method comprising administering an effective amount of botulinum toxin to a patient using a prefilled glass syringe comprising an aqueous botulinum toxin formulation,
wherein the glass syringe comprises
(a) a syringe barrel made of glass including a proximal end and a distal end, and a cylindrical wall extending therebetween and defining a barrel lumen, the syringe barrel having a distally projecting tip with a fluid passage extending therethrough and communicating with the barrel lumen, wherein the cylindrical wall has an interior surface optionally coated with a barrier layer,
(b) a capping device having an outlet engaging portion sealingly engaging and closing the distal open outlet end of the syringe, wherein the outlet engaging portion is made of an elastomeric material that optionally has a coating on its surface, and
(c) a plunger rod assembly which extends into the proximal end of the syringe barrel and includes a plunger stopper in sliding fluid-tight engagement with the cylindrical wall of the barrel lumen, wherein the plunger stopper is made of an elastomeric material, which optionally has a coating on at least a portion of the plunger stopper that contacts the aqueous botulinum toxin formulation during storage and/or injection,
wherein the elastomeric material of the outlet engaging portion is selected from isoprene rubber (IS), butadiene rubber (BR), butyl rubber, halogenated butyl rubbers, styrene-butadiene rubber, and mixtures thereof, and the elastomeric material of the plunger stopper is selected from isoprene rubber (IS), butadiene rubber (BR), butyl rubber, halogenated butyl rubbers, styrene-butadiene rubber, and mixtures thereof, and
wherein the toxin activity is not reduced by more than 25%, relative to the initial toxin activity, upon storage of the prefilled glass syringe for 12 months at 5° C. or 12 months at 25° C.

2. The method of claim 1 , wherein the effective amount of botulinum toxin is locally administered to a patient.

3. The method of claim 1 , wherein the effective amount of botulinum toxin is administered to a patient by intramuscular, intradermal, subdermal or subcutaneous injection.

4. The method of claim 3 , wherein the effective amount of botulinum toxin is administered to a patient by intramuscular injection.

5. The method of claim 3 , wherein the effective amount of botulinum toxin is administered to a patient by intradermal, subdermal or subcutaneous injection.

6. The method of claim 1 , comprising treating wrinkles and lines of the skin and facial asymmetries.

7. The method of claim 6 , wherein the wrinkles and lines of the skin comprise upper facial rhytides, platysmal bands, glabellar frown lines, horizontal forehead lines, nasolabial folds, chin folds, mental ceases, marionette lines, buccal commissures, perioral wrinkles, crow's feet, and jawlines.

8. The method of claim 1 , wherein the botulinum toxin is administered in a total amount of 1 to 50 U.

9. The method of claim 1 , wherein the toxin activity is not reduced by more than 15%, relative to the initial toxin activity, upon storage of the prefilled glass syringe for 12 months at 5° C. or 12 months at 25° C.

10. The method of claim 1 , wherein the number of subvisible particles of equal to or greater than 10 μm is below 1000/ml during storage of the prefilled glass syringe for 6 to 24 months at 2° C. to 30° C.

11. The method of claim 1 , wherein the pH value of the aqueous botulinum toxin formulation is not increased or decreased by more than 10%, relative to the initial pH value, upon storage of the prefilled glass syringe for 6 to 12 months at 5° C. or 25° C., or wherein the pH of the aqueous botulinum toxin formulation during storage of the prefilled glass syringe is maintained in the range of 6.0 to 7.5, or both.

12. The method of claim 1 , wherein the botulinum toxin in the aqueous formulation in the prefilled glass syringe is present at a concentration of 10 U/ml to 1000 U/ml.

13. The method of claim 1 , wherein the aqueous botulinum toxin formulation in the prefilled glass syringe does not contain a buffer.

14. The method of claim 1 , wherein the optional coating on the outlet engaging portion is a crosslinked silicone coating or a fluoropolymer coating or wherein the optional coating on the plunger stopper is a crosslinked silicone coating or a fluoropolymer coating or wherein the optional coating on the outlet engaging portion and the optional coating on the plunger stopper are a crosslinked silicone coating or a fluoropolymer coating.

15. The method of claim 1 , wherein the barrier layer of the syringe barrel of the prefilled glass syringe is a silicone-free layer or a silicone layer.

Assignees

• Merz Pharma Gmbh & Co Kgaa

Inventors

• Vogt Markus

Classifications

• A61K2800/87

  Application Devices; Containers; Packaging · CPC title

• A61K2800/91

  Injection · CPC title

• A61K8/64

  Proteins; Peptides; Derivatives or degradation products thereof · CPC title

• A61K47/42

  Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein (oligopeptides having up to five amino acids {A61K47/183}; polyamino acids A61K47/34) · CPC title

• C12Y304/24069

  Bontoxilysin (3.4.24.69), i.e. botulinum neurotoxin · CPC title