Skin permeation enhancer compositions

Claim 3

The method of claim 1, wherein the permeation enhancer composition contains approximately 35 wt. % to 90 wt. % lower aliphatic ester and 10 wt. % to 65 wt. % lower alkanol.

Claim 4

The method of claim 1, wherein the lower aliphatic ester is selected from the group consisting of methyl butrate, methyl propionate, methyl acetate, ethyl butrate, ethyl propionate, ethyl acetate, propyl butrate, propyl propionate and propyl acetate, and the lower alkanol is selected from the group consisting of methanol, ethanol, 1-propanol, 2-propanol, n-butanol, i-butanol, t-butanol, propylene glycol, ethylene glycol, and glycerin.

Claim 5

The method of claim 3, wherein the lower aliphatic ester is ethyl acetate and the lower alkanol is propylene glycol.

Claim 6

The method of claim 1, wherein the pharmacologically active agent is selected from the group consisting of timolol, captopril, nalbuphine, buprenorphine, and salts thereof.

Claim 7

The method of claim 1, wherein the pharmacologically active agent and the permeation enhancer composition are present in a single pharmaceutical composition, and wherein the composition further includes a pharmaceutically acceptable inert vehicle.

Claim 8

The method of claim 1, wherein the permeation enhancer composition further includes at least one additional permeation enhancing component.

Claim 9

The method of claim 7, wherein the at least one additional permeation enhancing component is selected from the group consisting of squalene, decylmethylsulfoxide and isopropyl myristate.

Claim 10

The method of claim 7, wherein the at least one additional permeation enhancing component is a surfactant.

Claim 15

The method of claim 11, wherein the permeation enhancer composition contains isopropyl myristate in an amount up to about 10 wt. %.

Claim 16

A composition of matter for the transdermal administration of a pharmacologically active agent, comprising: (a) a therapeutically effective amount of a pharmacologically active agent selected from the group consisting of timolol, captopril, nalbuphine, buprenorphine, and salts thereof; and (b) a permeation engancer composition comprising (i) approximately 35 wt. % to 90 wt. % of a lower aliphatic ester of a lower aliphatic carboxylic acid, containing a total of from three to six carbon atoms; and (ii) approximately 10 wt. % to 65 wt. % of a lower alkanol; and (iii) 0 wt. % to approximately 15 wt. % of an additional permeation enhancing component selected from the group consisting of squalene, decylmethyl sulfoxide, isopropyl myristate, and surfactant.

Claim 17

A composition of matter for the transdermal administration of a pharmacologically active agent, comprising: (a) a therapeutically effective amount of a pharmacologically active agent selected from the group consisting of timolol, captopril, nalbuphine, buprenorphine, and salts thereof; and (b) a permeation engancer composition comprising (i) approximately 35 wt. % to 90 wt. % of a lower aliphatic ester of a lower aliphatic carboxylic acid, containing a total of from three to six carbon atoms; and (ii) approximately 10 wt. % to 65 wt. % of a lower alkanol; and (iii) 0 wt. % to approximately 15 wt. % of an additional permeation enhancing component selected from the group consisting of squalene, decylmethyl sulfoxide, isopropyl myristate, and surfactant.

Claim 18

The composition of claim 13, comprising approximately 35 wt. % to 90 wt. % lower aliphatic ester and 10 wt. % to 65 wt. % lower alkanol.

Claim 19

The composition of claim 13, wherein the lower aliphatic ester is selected from the group consisting of methyl butrate, methyl propionate, methyl acetate, ethyl butrate, ethyl propionate, ethyl acetate, propyl butrate, propyl propionate and propyl acetate, and the lower alkanol is selected from the group consisting of methanol, ethanol, 1-propanol, 2-propanol, n-butanol, i-butanol, t-butanol, propylene glycol, ethylene glycol, and glycerin.

Claim 20

The composition of claim 15, wherein the lower aliphatic ester is ethyl acetate and the lower alkanol is propylene glycol.

Claim 21

The composition of claim 13, wherein the pharmacologically active agent is selected from the group consisting of timolol, captopril, nalbuphine, buprenorphine, and salts thereof.

Claim 22

The composition of claim 13, further including a pharmaceutically acceptable inert vehicle.

Claim 23

The composition of claim 13, wherein the permeation enhancer composition further includes at least one additional permeation enhancing component.

Claim 24

The composition of claim 19, wherein the at least one additional permeation enhancing component is selected from the group consisting of squalene, decylmethylsulfoxide and isopropyl myristate.

Claim 25

The composition of claim 19, wherein the at least one additional permeation enhancing component is a surfactant.

Claim 26

A composition for administering timolol maleate transdermally, comprising: (a) a therapeutically effective amount of timolol maleate; and (b) a permeation enhancer composition comprising approximately 70 wt. % to 90 wt. % ethyl acetate and 10 wt. % to 30 wt. % propylene glycol.

Claim 27

A composition for administering timolol maleate transdermally, comprising: (a) a therapeutically effective amount of timolol maleate; and (b) a permeation enhancer composition comprising approximately 70 wt. % to 90 wt. % ethyl acetate and 10 wt. % to 30 wt. % propylene glycol.

Claim 28

A composition for administering captopril transdermally, comprising: (a) a therapeutically effective amount of captopril; and (b) a permeation enhancer composition comprising 50 wt. % to 70 wt. % ethyl acetate, 25 wt. % to 45 wt. % propylene glycol, and up to about 15 wt. % isopropyl myristate.

Claim 29

A composition for administering captopril transdermally, comprising: (a) a therapeutically effective amount of captopril; and (b) a permeation enhancer composition comprising 50 wt. % to 70 wt. % ethyl acetate, 25 wt. % to 45 wt. % propylene glycol, and up to about 15 wt. % isopropyl myristate.

Claim 30

The composition of claim 23, wherein the permeation enhancer composition contains up to about 10 wt. % isopropyl myristate.

Claim 31

A laminated composite for administering a pharmacologically active agent through a selected area of skin over a sustained time period, comprising: (a) a backing layer that is substantially impermeable to the pharmacologically active agent; (b) a reservoir layer comprising an adhesive polymer and defining the basal surface of the device for adhering to the skin; (c) a therapeutically effective amount of pharmacologically active agent selected from the group consisting of timolol, captopril, nalbuphine, buprenorphine, and salts thereof; and (d) a permeation enhancer composition comprising (i) approximately 35 wt. % to 90 wt. % of a lower aliphatic ester of a lower aliphatic carboxylic acid, containing a total of from three to six carbon atoms; and (ii) approximately 10 wt. % to 65 wt. % of a lower alkanol; and (iii) 0 wt. % to approximately 15 wt. % of an additional permeation enhancing component selected from the group consisting of squalene, decylmethyl sulfoxide, isopropyl myristate, and surfactant.

Claim 32

A laminated composite for administering a pharmacologically active agent through a selected area of skin over a sustained time period, comprising: (a) a backing layer that is substantially impermeable to the pharmacologically active agent; (b) a reservoir layer comprising an adhesive polymer and defining the basal surface of the device for adhering to the skin; (c) a therapeutically effective amount of pharmacologically active agent selected from the group consisting of timolol, captopril, nalbuphine, buprenorphine, and salts thereof; and (d) a permeation enhancer composition comprising (i) approximately 35 wt. % to 90 wt. % of a lower aliphatic ester of a lower aliphatic carboxylic acid, containing a total of from three to six carbon atoms; and (ii) approximately 10 wt. % to 65 wt. % of a lower alkanol; and (iii) 0 wt. % to approximately 15 wt. % of an additional permeation enhancing component selected from the group consisting of squalene, decylmethyl sulfoxide, isopropyl myristate, and surfactant.

Claim 33

The method of claim 25, wherein the lower aliphatic ester is selected from the group consisting of methyl butrate, methyl propionate, methyl acetate, ethyl butrate, ethyl propionate, ethyl acetate, propyl butrate, propyl propionate and propyl acetate, and the lower alkanol is selected from the group consisting of methanol, ethanol, 1-propanol, 2-propanol, n-butanol, i-butanol, t-butanol, propylene glycol, ethylene glycol, and glycerin.

Claim 34

The method of claim 26, wherein the lower aliphatic ester is ethyl acetate and the lower alkanol is propylene glycol.

Claim 35

The laminated composite of claim 25 wherein the adhesive polymer is selected from the group consisting of polysiloxanes, polyacrylates, polyurethanes and tacky rubbers.

Claim 36

The laminated composite of claim 25, further comprising a release rate controlling means in the flow path of the pharmacologically active from the reservoir layer to the skin.

Claim 37

The laminated composite of claim 29, wherein the release rate controlling means is an ethylene-vinyl acetate, ethylene vinyl acetate organic acid terpolymer, polyamide, polyester; or acrylic resin membranes.

Claim 38

The method of claim 25, wherein the pharmacologically active agent is selected from the group consisting of timolol, captopril, nalbuphine, buprenorphine, and salts thereof.

Claim 39

A permeation enhancer composition comprising (i) approximately 25 wt. % to 55 wt. % of a lower aliphatic ester of a lower aliphatic carboxylic acid; and (ii) approximately 40 wt. % to 74 wt. % of a lower alkanol; and (iii) up to approximately 1 wt. % to 5 wt. % isopropyl myristate.

Claim 40

A permeation enhancer composition comprising (i) approximately 25 wt. % to 55 wt. % of a lower aliphatic ester of a lower aliphatic carboxylic acid; and (ii) approximately 40 wt. % to 74 wt. % of a lower alkanol; and (iii) up to approximately 1 wt. % to 5 wt. % isopropyl myristate.