JPWO2019175096A5

JPWO2019175096A5 -

Info

Publication number: JPWO2019175096A5
Application number: JP2020548695A
Authority: JP
Publication date: 2022-03-16

Claims

A transdermal therapeutic system for transdermal administration of buprenorphine, comprising a buprenorphine-containing layer structure.
The buprenorphine-containing layer structure is
A) The lining layer and
B) A buprenorphine-containing layer,
The buprenorphine-containing layer is
a) A therapeutically effective amount of buprenorphine and
b) Carboxylic acid and
With the buprenorphine-containing layer,
Including
The transdermal treatment system comprises the silicone acrylic hybrid polymer.

The transdermal treatment system according to claim 1, wherein the buprenorphine-containing layer is a buprenorphine-containing matrix layer, preferably a buprenorphine-containing pressure-sensitive adhesive layer.

The buprenorphine is contained in an amount of 2% by weight to 20% by weight, preferably 3% by weight to 15% by weight, more preferably 3% or more and less than 10% based on the buprenorphine-containing layer. Alternatively, the transdermal treatment system according to any one of 2.

The carboxylic acid is contained in an amount sufficient to solubilize the therapeutically effective amount of buprenorphine, preferably the carboxylic acid is 2% by weight to 20% by weight based on the buprenorphine-containing layer. The transdermal treatment system according to any one of claims 1 to 3, which is contained in an amount of 3% by weight to 15% by weight, more preferably 4% by weight to 12% by weight.

The carboxylic acid is selected from the group consisting of C ₃ to C ₂₄ carboxylic acids, preferably.
The carboxylic acid is selected from the group consisting of oleic acid, linoleic acid, linolenic acid, levulinic acid, and mixtures thereof.
In particular, the transdermal treatment system according to any one of claims 1 to 4, wherein the carboxylic acid is levulinic acid.

The carboxylic acid and the buprenorphine are contained in an amount ratio of 0.3: 1 to 5: 1.
Preferably, the carboxylic acid is levulinic acid, and the levulinic acid and the buprenorphine are contained in an amount ratio of 0.3: 1 to 5: 1, according to any one of claims 1 to 5. The described transdermal treatment system.

The process according to any one of claims 1 to 6, wherein the at least one silicone acrylic hybrid polymer is a silicone acrylic hybrid pressure-sensitive adhesive having a weight ratio of 5:95 to 95: 5 to an acrylate of silicone. Skin treatment system.

The at least one silicone acrylic hybrid polymer is a silicone acrylic hybrid pressure sensitive adhesive having a weight ratio of 40:60 to 60:40 of silicone to acrylate, preferably.
The transdermal treatment system according to any one of claims 1 to 7, wherein the ethylenically unsaturated monomer forming the acrylate contains 2-ethylhexyl acrylate and methyl acrylate in a ratio of 40:60 to 70:30.

The at least one silicone acrylic hybrid polymer has a solid content of 500 cP to 3,500 cP, preferably 1,000 cP to 3,000 cP, more preferably 1,200 cP to 1,800 cP at 25 ° C. and a solid content of 50% in ethyl acetate. A silicone acrylic hybrid pressure sensitive adhesive characterized by a solution viscosity of, and / or the at least one silicone acrylic hybrid pressure sensitive adhesive at 0.1 rad / s at 30 ° C., preferably less than 1.0e9 poise. The transdermal treatment system according to any one of claims 1 to 8, wherein is characterized by a complex viscosity of 1.0e5 poise to 9.0e8 poise, more preferably 9.0e5 poise to 7.0e6 poise.

The silicone acrylic hybrid polymer is
(A) A silicon-containing pressure-sensitive adhesive composition containing an acrylate or methacrylate functional group,
(B) Ethylene unsaturated monomer and
(C) Initiator and
Silicone acrylic hybrid pressure sensitive adhesive containing the reaction products of
Preferably, the silicon-containing pressure-sensitive adhesive composition containing the acrylate or methacrylate functional group is
(A1) Silicone resin and
(A2) Silicone polymer and
(A3) A silicon-containing encapsulant containing an acrylate or methacrylate functional group,
The transdermal treatment system according to any one of claims 1 to 9, which is a condensation reaction product of the above.

The ethylenically unsaturated monomer is selected from the group consisting of aliphatic acrylates, aliphatic methacrylates, alicyclic acrylates, alicyclic methacrylates, and combinations thereof.
Each of the compounds has a maximum of 20 carbon atoms in the alkyl group, preferably the ethylenically unsaturated monomer has a ratio of 40:60 to 70:30, preferably 65:35 to 55 :. The transdermal treatment system according to claim 10, wherein the combination of 2-ethylhexyl acrylate and methyl acrylate in a ratio of 45 or 55:45 to 45:50.

The silicone acrylic hybrid polymer comprises a silicone polymer, a silicone resin and a reaction product of the silicone polymer.
The transdermal treatment system according to any one of claims 1 to 11, wherein the acrylic polymer is covalently crosslinked and / or covalently bonded to the silicone polymer and / or the silicone resin.

The transdermal treatment system preferably further comprises at least one non-hybrid polymer, which is a non-hybrid pressure sensitive adhesive based on polysiloxane, polyisobutylene, styrene-isoprene-styrene block copolymers, acrylates, or mixtures thereof. The transdermal treatment system according to any one of claims 1 to 12, wherein the at least one non-hybrid polymer is a polysiloxane or acrylate-based non-hybrid pressure-sensitive adhesive.

The transdermal treatment system further comprises at least one non-hybrid polymer.
The non-hybrid polymer (s) and the silicone acrylic hybrid polymer (s) are in an amount ratio of 0.1: 1 to 5: 1, preferably 0.5: 1 to 2: 1. The transdermal treatment system according to any one of claims 1 to 13, which is contained in.

The at least one silicone acrylic hybrid polymer has the buprenorphine-containing layer
a) A therapeutically effective amount of buprenorphine and
b) Carboxylic acid and
c) With at least one silicone acrylic hybrid polymer,
The transdermal treatment system according to any one of claims 1 to 14, which is contained in the buprenorphine-containing layer so as to include.

The buprenorphine-containing layer is a buprenorphine-containing biphasic matrix layer having a therapeutically effective amount of buprenorphine and an internal phase containing the carboxylic acid and an external phase containing the at least one silicone acrylic hybrid polymer.
The internal phase forms dispersed deposits in the external phase.
Preferably, the transdermal treatment system according to claim 1 or 15, wherein the dispersed deposit has a maximum sphere size of 5 μm to 65 μm.

The buprenorphine-containing layer further comprises at least one non-hybrid polymer.
Preferably, the at least one silicone acrylic hybrid polymer and the at least one non-hybrid polymer have the buprenorphine-containing layer.
a) A therapeutically effective amount of buprenorphine and
b) Carboxylic acid and
c) With at least one silicone acrylic hybrid polymer,
d) With at least one non-hybrid polymer
The transdermal treatment system according to any one of claims 1 to 16, which is contained in the buprenorphine-containing layer so as to include.

The transdermal treatment system according to any one of claims 1 to 17, wherein the buprenorphine-containing layer is a buprenorphine-containing pressure-sensitive adhesive layer and represents a skin contact layer.

The buprenorphine-containing layer is the silicone acrylic hybrid polymer in an amount of 20% by weight to 90% by weight, preferably 30% by weight to 85% by weight, and more preferably 35% by weight to 85% by weight based on the buprenorphine-containing layer. 1-18.
The transdermal treatment system according to any one of the above.

The buprenorphine-containing layer structure further comprises a C) skin contact layer on the buprenorphine-containing layer.
The transdermal therapeutic system according to any one of claims 1 to 16, wherein the at least one silicone acrylic hybrid polymer is contained in the skin contact layer, and the buprenorphine-containing layer contains a non-hybrid polymer.

The buprenorphine-containing layer structure further comprises a C) skin contact layer on the buprenorphine-containing layer.
The transdermal treatment system according to any one of claims 1 to 17, wherein the at least one silicone acrylic hybrid polymer is contained in both the buprenorphine-containing layer and the skin contact layer.

The buprenorphine-containing layer structure is 0.3 mg / cm ² to 3.0 mg / cm ² , preferably 0.5 mg / cm ² or more and 1.2 mg / c based on the buprenorphine-containing layer.
Less than m ² or 0.5 mg / cm ² or more and less than 0.8 mg / cm ² or 0.6 mg /
The transdermal therapeutic system according to any one of claims 1 to 21, which contains buprenorphine in an amount of more than cm ² and not more than 1.6 mg / cm ² .

The buprenorphine-containing layer further contains a viscosity-increasing substance, preferably in an amount of 0.1% by weight to 8% by weight, or 1% by weight to 6% by weight, based on the buprenorphine-containing layer. The transdermal treatment system according to any one of 22.

The viscosity-increasing substances include cellulose derivatives such as methyl cellulose, ethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, carboxymethyl cellulose, sodium carboxymethyl cellulose, microcrystalline cellulose, high molecular weight polyacrylic acid and / or salts thereof and /. Or selected from the group consisting of derivatives thereof, such as esters, polyvinylpyrrolidone, colloidal silicone dioxide, sodium alginate, tragacant, xanthan gum, bentonite, carrageenan and guar gum, and mixtures thereof.
23. The transdermal therapeutic system according to claim 23, wherein the viscosity increasing substance is polyvinylpyrrolidone.

Any of claims 1 to 24, wherein the buprenorphine-containing layer structure provides a tack of 0.6N to 8.0N, preferably more than 0.8N and 8.0N or less, more preferably 1.2N to 6.0N. The transdermal treatment system according to item 1.

It provides the skin permeation rate of buprenorphine as measured in a comparative study using a commercially available buprenorphine reference transdermal treatment system at 36 hour time intervals from 48th to 84th hour, which is therapeutically effective. And / or the skin permeation rate of buprenorphine as measured in a comparative test using a commercially available buprenorphine reference transdermal treatment system at a time interval of 72 hours from the 96th hour to the 168th hour, which is therapeutically effective. Buprenorphine skin as measured in a comparative study using a commercially available buprenorphine reference transdermal treatment system at 96 hour time intervals from 72 hours to 168 hours that are provided and / or therapeutically effective. When measured in a comparative test using a commercially available buprenorphine reference transdermal therapy system at 120 hour time intervals from 48 hours to 168 hours, which provide permeation rates and / or are therapeutically effective. The transdermal therapeutic system according to any one of claims 1 to 25, which provides a skin permeation rate of buprenorphine.

Preferably, the transdermal treatment system is applied to the patient's skin for more than 3 days, 3.5 days, 4 days, or 7 days for treatment, preferably for the treatment of pain. The transdermal treatment system according to any one of 26.

The method for manufacturing a transdermal treatment system according to any one of claims 1 to 27.
1) A buprenorphine-containing coating composition.
a) Buprenorphine and
b) Carboxylic acid and
c) Solvent and
The step of providing the buprenorphine-containing coating composition comprising
2) A step of coating the release liner with an amount of the buprenorphine-containing coating composition to provide a desired region weight.
3) A step of drying the buprenorphine-containing coating composition to provide the buprenorphine-containing layer, and a step of providing the buprenorphine-containing layer.
4) A step of laminating the buprenorphine-containing layer on the lining layer to provide a buprenorphine-containing layer structure, and
5) Optionally, the activator-free coating composition is coated and dried according to steps 2 and 3, the release liner of the buprenorphine-containing layer is removed, and an additional skin contact layer is laminated on the buprenorphine-containing layer. To provide a buprenorphine-containing layer structure having a desired release region by providing the additional skin contact layer by
6) The process of punching out individual systems from the buprenorphine-containing layer structure,
7) Optionally, an active substance-free self-adhesive layer structure comprising a lining layer and an activator-free pressure-sensitive adhesive layer as well, and having a larger active substance-free self-adhesive layer structure than the individual systems of the buprenorfin-containing self-adhesive layer structure. And the process of adhering to the system
Including
At least one silicone acrylic hybrid polymer composition is added to the buprenorfin-containing coating composition in step 1, or if an additional skin contact layer is provided, the activator-free coating in step 5. It is added to the composition or to both the buprenorfin-containing coating composition in step 1 and the activator-free coating composition in step 5.
Preferably, the above-mentioned production method, wherein the at least one silicone acrylic hybrid polymer composition is a silicone acrylic hybrid pressure-sensitive adhesive in ethyl acetate or n-heptane.