Transdermal therapeutic system containing nicotine and silicone acrylic hybrid polymer

Patent metadata

Field	Value
Publication number	US-2021052569-A1
Application number	US-201916979577-A
Country	US
Kind code	A1
Filing date	Mar 11, 2019
Priority date	Mar 13, 2018
Publication date	Feb 25, 2021
Grant date	—

Abstract

The present invention relates to transdermal therapeutic systems (TTS) for the transdermal administration of nicotine comprising a nicotine-containing layer structure, said nicotine-containing layer structure comprising A) a backing layer and B) a nicotine-containing layer, wherein the transdermal therapeutic system comprises a silicone acrylic hybrid polymer.

First claim

1 . Transdermal therapeutic system for the transdermal administration of nicotine comprising a nicotine-containing layer structure, said nicotine-containing layer structure comprising:
A) a backing layer; and B) a nicotine-containing layer;
wherein the transdermal therapeutic system comprises a silicone acrylic hybrid polymer, and
wherein the nicotine-containing layer comprises at least 0.8 mg/cm 2 nicotine.

2 . Transdermal therapeutic system according to claim 1 ,
wherein the silicone acrylic hybrid polymer is a silicone acrylic hybrid pressure-sensitive adhesive.

3 . Transdermal therapeutic system according to claim 1 or 2 ,
wherein the nicotine-containing layer is a matrix layer, and preferably is a nicotine-containing pressure-sensitive adhesive layer.

4 . Transdermal therapeutic system according to any one of claims 1 to 3 ,
wherein the nicotine-containing layer comprises:
1. nicotine; and
2. the silicone acrylic hybrid polymer.

5 . Transdermal therapeutic system according to any one of claims 1 to 4 ,
wherein the nicotine-containing layer comprises at least 0.90 mg/cm 2 , preferably at least 0.95 mg/cm 2 , more preferably at least 1.15 mg/cm 2 nicotine, and/or
wherein the nicotine-containing layer comprises less than 5.0 mg/cm 2 , less than 4.0 mg/cm 2 , less than 3.0 mg/cm 2 , less than 2.0 mg/cm 2 or less than 1.7 mg/cm 2 nicotine.

6 . Transdermal therapeutic system according to any one of claims 1 to 5 ,
wherein the area weight of the nicotine-containing layer is at least 80 g/m 2 or is at least 90 g/m 2 or ranges from 80 to 300 g/m 2 , preferably from 90 to 270 g/m 2 , and more preferably from 100 to 230 g/m 2 .

7 . Transdermal therapeutic system according to any one of claims 1 to 6 ,
wherein the amount of nicotine in the nicotine-containing layer ranges from 2 to 15%, preferably from 3 to 12% and more preferably from 4 to 10% of the nicotine-containing layer, and/or
wherein the amount of nicotine contained in the transdermal therapeutic system ranges from 5 to 90 mg, preferably from 8 to 75 mg, and most preferably from 10 to 60 mg.

8 . Transdermal therapeutic system according to any one of claims 1 to 7 ,
wherein the nicotine-containing layer structure does not comprise an additional skin contact layer, or
wherein the nicotine-containing layer structure comprises an additional skin contact layer, and
wherein the additional skin contact layer comprises or does not comprise nicotine, and preferably does not comprise nicotine, and
wherein the additional skin contact layer is a pressure-sensitive adhesive layer comprising a silicone acrylic hybrid polymer, a non-hybrid polymer and preferably a non-hybrid pressure-sensitive adhesive, or any mixture thereof.

9 . Transdermal therapeutic system according to any one of claims 1 to 8 ,
wherein the silicone acrylic hybrid polymer is a silicone acrylic hybrid pressure-sensitive adhesive obtainable from
(a) a silicon-containing pressure-sensitive adhesive composition comprising acrylate or methacrylate functionality.

10 . Transdermal therapeutic system according to any one of claims 1 to 9 ,
wherein the silicone acrylic hybrid polymer is a silicone acrylic hybrid pressure-sensitive adhesive comprising the reaction product of
(a) a silicon-containing pressure-sensitive adhesive composition comprising acrylate or methacrylate functionality;
(b) an ethylenically unsaturated monomer; and
(c) an initiator,

wherein preferably the silicon-containing pressure-sensitive adhesive composition comprising acrylate or methacrylate functionality comprises the condensation reaction product of
(a1) a silicon resin,
(a2) a silicone polymer, and
(a3) a silicon-containing capping agent comprising acrylate or methacrylate functionality.

11 . Transdermal therapeutic system according to any one of claims 1 to 8 ,
wherein the silicone acrylic hybrid polymer comprises a reaction product of a silicone polymer, a silicone resin and an acrylic polymer, wherein the acrylic polymer is covalently self-crosslinked and covalently bound to the silicone polymer and/or the silicone resin.

12 . Transdermal therapeutic system according to any one of claims 1 to 11 ,
wherein the silicone acrylic hybrid polymer contains a continuous, silicone external phase and a discontinuous, acrylic internal phase, or
wherein the silicone acrylic hybrid polymer contains a continuous, acrylic external phase and a discontinuous, silicone internal phase.

13 . Transdermal therapeutic system according to any one of claims 1 to 12 ,
wherein the nicotine-containing layer comprises or does not comprise a non-hybrid polymer,
wherein the non-hybrid polymer preferably is a non-hybrid pressure-sensitive adhesive,
wherein the non-hybrid polymer is preferably selected from polysiloxanes, polyisobutylenes, styrene-isoprene-styrene block copolymers and acrylic polymers, and/or
wherein the nicotine-containing layer does not comprise a permeation enhancer, and/or
wherein the nicotine-containing layer does not comprise any further excipient or additive.

14 . Transdermal therapeutic system according to any one of claims 1 to 13 ,
wherein the nicotine-containing layer comprises further excipients or additives selected from the group consisting of cross-linking agents, solubilizers, fillers, tackifiers, film forming agents, plasticizers, stabilizers, softeners, substances for skincare, permeation enhancers, pH regulators, and preservatives.

15 . Transdermal therapeutic system according to any one of claims 1 to 14 for use in a method of treatment, and
preferably for use in a method of treating nicotine addiction, in a method of smoking cessation treatment, in a method of treating Parkinson's disease or in a method of treating Alzheimer's disease.

16 . A method of treatment, and preferably a method of treating nicotine addiction and/or a method of smoking cessation treatment, a method of treating Parkinson's disease or a method of treating Alzheimer's disease,
including applying a transdermal therapeutic system according to any one of claims 1 to 14 to the skin of a patient.

17 . A process for manufacturing a nicotine-containing pressure-sensitive adhesive layer comprising the steps of:
1) combining at least the components nicotine and a silicone acrylic hybrid polymer in a solvent to obtain a coating composition; 2) coating the coating composition onto a backing layer or a release liner; and 3) drying the coated coating composition to form the nicotine-containing pressure-sensitive adhesive layer.

18 . The process according to claim 17 ,
further comprising the step of drying a silicone acrylic hybrid polymer solution in ethyl acetate and dissolving the obtained silicone acrylic hybrid polymer in hexane prior to step 1), wherein the solvent preferably is selected from alcoholic solvents, in particular methanol, ethanol, isopropanol and mixtures thereof, and from non-alcoholic solvents, in particular ethyl acetate, hexane, n-heptane, petroleum ether, toluene, and mixtures thereof, and more preferably is selected from hexane.

Assignees

• Lts Lohmann Therapie Systeme Ag

Inventors

• Linn Michael
• Schmitz Christoph
• Böhm Rolf
• Emgenbroich Marco

Classifications

• A61K9/7084

  Transdermal patches having a drug layer or reservoir, and one or more separate drug-free skin-adhesive layers, e.g. between drug reservoir and skin, or surrounding the drug reservoir; Liquid-filled reservoir patches · CPC title

• A61K9/7069 Primary

  obtained otherwise than by reactions only involving carbon to carbon unsaturated bonds, e.g. polysiloxane, polyesters, polyurethane, polyethylene oxide · CPC title

• A61P25/26

  Psychostimulants, e.g. nicotine, cocaine · CPC title

• A61P25/28

  for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia · CPC title

• A61K31/465 Primary

  Nicotine; Derivatives thereof · CPC title