Botulinum toxin prefilled plastic syringe

Patent metadata

Field	Value
Publication number	US-11219717-B2
Application number	US-201916459382-A
Country	US
Kind code	B2
Filing date	Jul 1, 2019
Priority date	Feb 3, 2015
Publication date	Jan 11, 2022
Grant date	Jan 11, 2022

Abstract

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

First claim

The invention claimed is:

1. A prefilled plastic syringe comprising an aqueous botulinum toxin formulation, the plastic syringe comprising
(a) a plastic syringe barrel 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 contacting the aqueous botulinum toxin formulation during storage and/or injection,
wherein the toxin activity is not reduced by more than 25%, relative to the initial toxin activity, upon storage of the prefilled plastic syringe for 12 months at 5° C. or 3 months at 25° C., and
wherein the aqueous botulinum toxin formulation comprises sodium chloride and a stabilizing protein selected from albumin or gelatin, and the pH of the aqueous botulinum toxin formulation during storage is maintained in a range of 6.1 to 7.3.

2. The prefilled plastic syringe of claim 1 , wherein the number of sub-visible particles of equal to or greater than 10 μm is below 1000/ml during storage for 6 to 24 months at 2° C. to 25° C.

3. The prefilled plastic syringe of claim 1 , wherein the pH value is not increased or decreased by more than 10%, relative to the initial pH value, during storage of the prefilled syringe for 6 to 24 months at 2° C. to 25° C.

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

5. A prefilled plastic container comprising an aqueous botulinum toxin formulation, wherein the toxin activity is not reduced by more than 25%, relative to the initial toxin activity, upon storage of the prefilled container for 12 months at 5° C. or 3 months at 25° C.,
wherein the aqueous botulinum toxin formulation comprises sodium chloride and a stabilizing protein selected from albumin or gelatin, and
wherein the aqueous botulinum toxin formulation in the prefilled container does not contain a buffer.

6. The prefilled plastic syringe of claim 1 , wherein the barrier layer of the syringe barrel is a silicone-free layer or a silicone layer.

7. The prefilled plastic syringe of claim 1 , wherein the elastomeric material of the outlet engaging portion and/or the plunger stopper is selected from isoprene rubber (IS), butadiene rubber (BR), butyl rubber, halogenated butyl rubber, and styrene-butadiene rubber, and mixtures thereof, or wherein the optional coating on the outlet engaging portion and/or the plunger stopper is a crosslinked silicone coating or a fluoropolymer coating, or wherein the elastomeric material of the outlet engaging portion and/or the plunger stopper is selected from isoprene rubber (IS), butadiene rubber (BR), butyl rubber, halogenated butyl rubber, and styrene-butadiene rubber, and mixtures thereof, and the optional coating on the outlet engaging portion and/or the plunger stopper is a crosslinked silicone coating or a fluoropolymer coating.

8. A kit comprising a prefilled plastic syringe according to claim 1 and, optionally, instructions for use of said prefilled plastic syringe.

9. A method for the treatment of a disease or condition caused by or associated with hyperactive cholinergic innervation of muscles or exocrine glands in a patient, the method comprising locally administering an effective amount of botulinum toxin to a muscle or exocrine gland of the patient by injection using the prefilled plastic syringe according to claim 1 .

10. A method for the cosmetic treatment of the skin, the method comprising locally administering an effective amount of botulinum toxin to a patient by intradermal, subdermal or subcutaneous injection using the prefilled plastic syringe according to claim 1 .

11. The method for the cosmetic treatment of the skin according to claim 10 , wherein the method treats wrinkles of the skin and facial asymmetries.

12. The pre-filled plastic syringe of claim 1 , wherein the cylindrical wall has an interior surface coated with a barrier layer.

13. The prefilled plastic syringe of claim 1 , wherein the optional coating on the outlet engaging portion is present and is a crosslinked silicone coating or a fluoropolymer coating.

14. The pre-filled plastic syringe of claim 1 , wherein the optional coating on the plunger stopper is present and is a crosslinked silicone coating or a fluoropolymer coating.

15. The pre-filled plastic syringe of claim 1 , wherein the stabilizing protein in the aqueous botulinum toxin formulation comprises albumin.

16. The pre-filled plastic syringe of claim 1 , wherein the stabilizing protein in the aqueous botulinum toxin formulation comprises gelatin.

17. The kit of claim 8 , wherein the instructions for use of said prefilled plastic syringe is present.

18. The method for the treatment of a disease or condition caused by or associated with hyperactive cholinergic innervation of muscles or exocrine glands in a patient according to claim 9 , wherein the disease or condition is selected from the group consisting of dystonia, spasticity, paratonia, diskinesia, focal spasm, strabismus, pain, wound healing, tremor, tics, migraine, sialorrhea and hyperhidrosis.

Assignees

• Merz Pharma Gmbh & Co Kgaa

Inventors

• Vogt Markus

Classifications

• A61J1/06 Primary

  Ampoules or carpules (syringe ampoules or carpules A61M5/28) · CPC title

• A61M2205/0222

  Materials for reducing friction · CPC title

• A61M5/31513 Primary

  Piston constructions to improve sealing or sliding · CPC title

• A61M5/31505

  Integral with the syringe barrel, i.e. connected to the barrel so as to make up a single complete piece or unit · CPC title

• A61K9/0019 Primary

  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) · CPC title