US5160741A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Reduction or prevention of skin irritation by drugs
Assignee: Alza Corp
•
Filing: 1991-11-13
•
Granted: 1992-11-03
•
Expires: 2011-11-13
Abstract
Abstract The present invention provides a method of reducing or preventing skin irritation of a weak base drug by inhibiting the accumulation of the drug in the lysosomes. The drug is irritating to humans, i.e., the drug is susceptible to inducing skin or mucosa irritation in a human when the drug is transdermally administered to the human at a therapeutically effective rate. Irritation reduction or prevention is induced by coadministering to the skin or mucosa of the human: (a) a therapeutically effective amount of a weak base drug which is irritating to humans, at a therapeutically effective rate over a predetermined period of time; and (b) an effective amount of an agent capable of inhibiting the lysosomal uptake of the drug to reduce or prevent irritation to the skin or mucosa.
Inventors
- 👤 Michel J. N. Cormier
- 👤 Philip W. Ledger
- 👤 Alfred Amkraut
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-26 00:29
CPC Classifications
A; A61; A61K; A61K31/00; A61K31/70; A61K47/00; A61K47/02; A61K47/06; A61K47/16; A61K47/18; A61K9/00; A61K9/0012; A61K9/0014
Claims Analysis
Total Claims: 27
Claim 1
Independent Claim
131 words
A method of reducing or preventing human skin irritation during transdermal administration to a human of a weak base drug, which drug is capable of accumulating in the lysosomes and is susceptible to inducing skin irritation in the human when the drug is transdermally administered, the method comprising coadministering to a selected site on the skin or mucosa of the human: (a) a therapeutically effective amount of the weak base drug, at a therapeutically effective rate over a predetermined period of time; and (b) an effective amount of a lysosomal uptake-inhibiting agent capable of inhibiting the lysosomal uptake of the drug to reduce or prevent irritation to the skin or mucosa, the amount of the lysosomal uptake-inhibiting agent being from 0.01 wt % to 20 wt % of the drug/agent composition.
Claim 2
Independent Claim
131 words
A method of reducing or preventing human skin irritation during transdermal administration to a human of a weak base drug, which drug is capable of accumulating in the lysosomes and is susceptible to inducing skin irritation in the human when the drug is transdermally administered, the method comprising coadministering to a selected site on the skin or mucosa of the human: (a) a therapeutically effective amount of the weak base drug, at a therapeutically effective rate over a predetermined period of time; and (b) an effective amount of a lysosomal uptake-inhibiting agent capable of inhibiting the lysosomal uptake of the drug to reduce or prevent irritation to the skin or mucosa, the amount of the lysosomal uptake-inhibiting agent being from 0.01 wt % to 20 wt % of the drug/agent composition.
Claim 3
Dependent Claim
30 words
A method according to claim 1 wherein the drug and the agent are coadministered transdermally from a matrix placed in drug and agent transmitting relation with the skin or mucosa.
Claim 4
Dependent Claim
12 words
A method according to claim 1 wherein the agent is an ionophore.
Claim 5
Dependent Claim
12 words
A method according to claim 3 wherein the agent is an monensin.
Claim 6
Dependent Claim
24 words
A method according to claim 3 wherein the ionophore is present in an amount of from 0.01 wt % to about 5 wt %.
Claim 7
Dependent Claim
15 words
A method according to claim 1 wherein the agent is a weak base competitor compound.
Claim 8
Dependent Claim
13 words
A method according to claim 6 wherein the agent is an amphiphilic amine.
Claim 9
Dependent Claim
25 words
A method according to claim 7 wherein the agent is chosen from ammonia and its salts, small molecular weight amines and their salts and aminoalcohols.
Claim 10
Dependent Claim
12 words
A method according to claim 8 wherein the agent is ammonium chloride.
Claim 11
Dependent Claim
27 words
A method according to claim 6 wherein the weak base competitor compound is present in an amount of from 0.2 wt % to about 20 wt %.
Claim 12
Dependent Claim
19 words
A method according to claim 1 wherein the drug is propranolol and the agent is monensin or ammonium chloride.
Claim 13
Dependent Claim
35 words
A method according to claim 1 wherein the drug is chloroquine and the agent is monensin, (R)(+)-1,1'-bi-2-naphthol, nigericin, valinomycin, gramicidin D, nonactin, A23187, carbonyl cyanide m-chlorophenylhydrazone, ammonium chloride, diethylamine, isopropylamine, ethanolamine, diethanolamine, triethanolamine or tromethamine.
Claim 14
Dependent Claim
22 words
A method according to claim 1 wherein the drug is selected from clemastine, imipramine, chlorpromazine and quinacrine, and the agent is monensin.
Claim 15
Dependent Claim
164 words
A transdermal drug delivery device for transdermally administrating a weak base drug to a human, which drug is capable of accumulating in the lysosomes and is susceptible to inducing skin or mucosal irritation in the human when the drug is transdermally administered, the device comprising: (a) a matrix adapted to be placed in drug and lysosomal uptake-inhibiting agent transmitting relation with a selected site on the skin or mucosa of the human, the matrix containing sufficient amounts of drug and lysosomal uptake-inhibiting agent to continuously and co-extensively administer to the skin or mucosal site: (1) a therapeutically effective amount of the weak base drug, at a therapeutically effective rate over a predetermined period of time; and (2) an effective amount of a lysosomal uptake-inhibiting agent capable of inhibiting the lysosomal uptake of the drug to reduce or prevent irritation to the skin or mucosa, the amount of the lysosomal uptake-inhibiting agent being from 0.01 wt % to 20 wt % of the drug/agent composition.
Claim 16
Dependent Claim
164 words
A transdermal drug delivery device for transdermally administrating a weak base drug to a human, which drug is capable of accumulating in the lysosomes and is susceptible to inducing skin or mucosal irritation in the human when the drug is transdermally administered, the device comprising: (a) a matrix adapted to be placed in drug and lysosomal uptake-inhibiting agent transmitting relation with a selected site on the skin or mucosa of the human, the matrix containing sufficient amounts of drug and lysosomal uptake-inhibiting agent to continuously and co-extensively administer to the skin or mucosal site: (1) a therapeutically effective amount of the weak base drug, at a therapeutically effective rate over a predetermined period of time; and (2) an effective amount of a lysosomal uptake-inhibiting agent capable of inhibiting the lysosomal uptake of the drug to reduce or prevent irritation to the skin or mucosa, the amount of the lysosomal uptake-inhibiting agent being from 0.01 wt % to 20 wt % of the drug/agent composition.
Claim 17
Dependent Claim
12 words
A method according to claim 14 wherein the agent is an ionophore.
Claim 18
Dependent Claim
12 words
A method according to claim 15 wherein the agent is an monensin.
Claim 19
Dependent Claim
24 words
A method according to claim 15 wherein the ionophore is present in an amount of from 0.01 wt % to about 5 wt %.
Claim 20
Dependent Claim
15 words
A method according to claim 14 wherein the agent is a weak base competitor compound.
Claim 21
Dependent Claim
13 words
A method according to claim 18 wherein the agent is an amphiphilic amine.
Claim 22
Dependent Claim
25 words
A method according to claim 19 wherein the agent is chosen from ammonia and its salts, small molecular weight amines and their salts and aminoalcohols.
Claim 23
Dependent Claim
12 words
A method according to claim 20 wherein the agent is ammonium chloride.
Claim 24
Dependent Claim
27 words
A method according to claim 18 wherein the weak base competitor compound is present in an amount of from 0.2 wt % to about 20 wt %.
Claim 25
Dependent Claim
19 words
A method according to claim 14 wherein the drug is propranolol and the agent is monensin or ammonium chloride.
Claim 26
Dependent Claim
35 words
A method according to claim 14 wherein the drug is chloroquine and the agent is monensin, (R)(+)-1,1'-bi-2-naphthol, nigericin, valinomycin, gramicidin D, nonactin, A23187, carbonyl cyanide m-chlorophenylhydrazone, ammonium chloride, diethylamine, isopropylamine, ethanolamine, diethanolamine, triethanolamine or tromethamine.
Claim 27
Dependent Claim
22 words
A method according to claim 14 wherein the drug is selected from clemastine, imipramine, chlorpromazine and quinacrine, and the agent is monensin.
References Cited (Backward Citations)
US3598122A
Cited
US3598123A
Cited
US3598122B1
Cited
US3991755A
Cited
US4274420A
Cited
US4141359A
Cited
US4325367A
Cited
US4250878A
Cited
US4391278A
Cited
US4398545A
Cited
US4286592A
Cited
US4314557A
Cited
US4379454A
Cited
US4474570A
Cited
US4419092A
Cited
GB2124485A
Cited
US4559222A
Cited
US4640689A
Cited
US4557723A
Cited
US4708716A
Cited
US4573995A
Cited
US4702732A
Cited
EP0267051A2
Cited
US4983395A
Cited
US4885154A
Cited
US4855294A
Cited
US4908213A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1995-11-03 | 1996-05-04 | 1996-11-03 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1999-11-03 | 2000-05-04 | 2000-11-03 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2003-11-03 | 2004-05-04 | 2004-11-03 | $7700.00 | Window Closed / Lapsed |