Method of treatment for pruritus

A method of treating a pruritic skin area in a mammal by application to the affected area of a gel composition containing from about 60 to about 90% ethyl alcohol, from about 0.5 to about 30% water, at least one gelling agent and a pharmaceutically effective amount of a topically active, antipruritic, antihistaminic agent. The gel may be applied to the affected area from one to five times daily.

BACKGROUND OF THE INVENTION 
1. Field of the Invention 
The present invention relates to methods of treating pruritus. 
2. Description of the Prior Art 
Many pharmaceutical agents are available for the topical treatment of 
pruritus in humans and animals. Low to medium potency corticosteroids are 
often used to treat the inflammatory and pruritic manifestations of acute 
dermatitides. Topical antipruritics such as menthol, phenol and camphor 
and topical anesthetics (most commonly, benzocaine) are also frequently 
applied to relieve pruritus of the skin. 
In the case of mast cell-mediated (particularly histamine-mediated) 
pruritic manifestations, topical antihistamines, e.g., diphenhydramine, 
are sometimes effective in relieving itch and erythema. These topical 
preparations conventionally take the form of creams and lotions, which 
provide relatively short-duration antipruritic activity and must be 
applied frequently to continue relief from itching. 
SUMMARY OF THE INVENTION 
It is an object of the present invention to provide a method of effectively 
relieving pruritus in mammals, for extended periods of time without 
requiring frequent applications of topical medication. 
Another object of the present invention is to provide a method as aforesaid 
utilizing topical compositions which are safe and easy to apply and store. 
Still a further object of the present invention is to provide methods as 
aforesaid utilizing gel formulations of topically active antihistamines. 
In keeping with these objects and others that will become apparent 
hereinafter, the present invention resides, briefly stated, in a method of 
treating pruritus comprising the topical application of a gel containing 
from about 60 to about 90% by weight ethyl alcohol, from about 0.5 to 
about 30% by weight water, and from about 0.5 to about 5% of at least one 
gelling agent capable of gelling the alcohol-water system, together with a 
pharmaceutically effective amount of a topically active, antipruritic, 
antihistaminic agent. Preferred antihistamines include diphenhydramine and 
diphenhydramine hydrochloride. 
The gel compositions used in the novel methods may optionally include 
gelling enhancers, gel neutralizing agents, ultraviolet absorbing agents, 
emollients, humectants, clarifiers and coloring and fragrance additives. 
The compositions used in the present invention can be packaged in any 
standard containers known in the pharmaceutical and cosmetic arts to be 
suitable for storage and dispensing of gels for topical use, including any 
of a variety of tubes, bottles, pouches, and the like. The compositions 
are useful for the treatment of any topical pruritic condition known to be 
responsive to antihistamine therapy, including, by way of example, contact 
dermatitis, allergic dermatitis, urticaria, insect bites, mast cell 
disease and reactions to intradermal allergy testing. 
DETAILED DESCRIPTION OF THE INVENTION 
The aqueous topical gel compositions used in the methods of the present 
invention comprise from about 60% to about 90% by weight ethyl alcohol; 
from about 0.5% to about 30% by weight water, preferably purified or 
distilled; from about 0.5% to about 5% by weight of at least one gelling 
agent; and a pharmaceutically effective amount of a topically active, 
antipruritic, antihistaminic agent. 
As used herein, a "pharmaceutically effective amount" of a topically active 
antihistaminic agent means a percentage concentration of that agent known 
in the medical and pharmaceutical arts to be safe and effective in 
treating dermatological conditions--e.g., from about 0.5 to about 3.5% 
diphenhydramine or diphenhydramine HC1, and preferably from about 1 to 
about 2.5%. Various concentrations of the same active ingredient may be 
used to provide for variations in the age of the patient to be treated, 
the severity of the condition and the duration of the treatment. 
The gelling agents utilized in the subject compositions can be any agents 
which create a stable gel matrix in the presence of substantial quantities 
of alcohol and water. Preferred gelling agents for use in the present 
invention include the water-soluble, carboxyvinyl polymers known as 
carbomers or, by their commercial name, "CARBOPOLS" (B.F. Goodrich 
Chemical Co., Cleveland, Ohio). Carbomers are also alcohol-soluble but 
require neutralization for use in non-polar systems. A variety of 
effective neutralizing agents are known, including sodium hydroxide, 
potassium hydroxide and sodium bicarbonate, but preferred for the purposes 
of the present invention are polar organic amines such as triethanolamine 
and tetrahydroxypropyl ethylenediamine. Generally from about 0.2% to about 
5% by weight of such neutralizing agents are sufficient to render the 
carbomer-created gels non-polar. 
Optional ingredients in the gel compositions used in the novel methods 
include gelling enhancers, ultraviolet absorbers (to prevent degradation 
and discoloration of the gels), emollients and humectants. Suitable 
gelling enhancers include, by way of example, from about 0.1% to about 3% 
hydroxymethyl- and hydroxyethylcellulose. 
Any of a variety of ultraviolet absorbers, emollients and humectants may be 
incorporated into the gels of the present invention to improve their 
stability, feel, and anti-drying properties when applied to the skin. 
Benzophenones are known ultraviolet absorbers which are effective in 
preventing gel degradation, particularly when a transparent or 
semi-transparent container is used. Effective emollients and humectants 
include, for example, lactate esters of fatty alcohols and glycerin. 
In order to create a transparent gel, which may be preferable for esthetic 
reasons and for consumer acceptance, a gel clarifying agent may be added 
to the subject composition. An example of such agents which is highly 
effective in creating a transparent gel is "COSMEDIA" (Henkel, Ambler, 
Pa.), which is a polyacrylamidomethylpropane sulfonic acid. 
It has been found that the preferred range of alcohol concentration for use 
in the gel compositions is from about 60 to about 80%, because 
formulations containing in excess of 80% alcohol, while suitable for the 
purposes of the invention, form less stable gels. Similarly, the preferred 
range of water concentrations is from about 8 to about 30% of the total 
composition. 
Due to their high alcohol concentrations, the subject gels do not require 
any added preservatives. 
The gels used in the present invention may be prepared by any conventional 
process known in the pharmaceutical and cosmetic arts. By one preferred 
procedure, the water (preferably in distilled or purified form) and all 
but 5-10% of the alcohol are combined with the primary gelling agent and 
agitated. Any gelling enhancers utilized are added to this phase. 
A second phase is prepared by mixing the pharmaceutically effective amount 
of the active ingredient, generally from about 0.5% to about 5% of the 
total composition by weight, with the remaining alcohol. If necessary, the 
mixture may be carefully heated to 60.degree. C. to assist in solubilizing 
the active ingredient. A small amount (0.05-1% by weight) of an 
ultraviolet absorber may optionally be added to this phase. The first and 
second phases are then rapidly mixed together until a homogeneous gel is 
obtained. 
Humectants and emollients, comprising in total from about 1% to about 10% 
of the total weight of the composition, and a gelling agent neutralizer, 
comprising from about 1% to about 5% of the weight of the composition may 
also be mixed together to form another optional phase, which is preferably 
mixed into the first phase before addition of the phase containing the 
active ingredient. Coloring or fragrance additives may be mixed into the 
final gel product until suitable appearance and odor is obtained. 
The gels used in the novel method, due to their high alcohol concentration 
and the presence of water, also act as good penetration enhancers for the 
incorporated antihistaminic ingredients by altering the stratum corneum 
and enhancing its permeability. This effect increases the potency of the 
topical agents which must penetrate below the outer skin surface in order 
to achieve good antipruritic activity. 
The subject compositions are easy to package in conventional containers, 
tubes and pouches and have good stability upon long term storage at 
ambient temperatures. In such tubes, containers and pouches, the gels may 
be easily transported in an individual's pocket, purse or carrying bag and 
small quantities may be effectively dispensed for use with little waste 
and discomfort due to spillage. The compositions are also of pleasant 
appearance, odor and consistency, and are water washable and 
non-irritating, all of which promotes and enhances the patient's desire to 
use the compositions as needed and/or as prescribed by a physician. 
The novel method of the present invention comprises the application of 
antihistamine-containing gels as described above to an affected skin area 
of a mammal to relieve pruritus. The gels are applied from 1 to about 5 
times daily in sufficient quantities to cover the affected area, and 
provide a high degree of antipruritic activity for an extended period of 
time, up to six hours or more. By contrast, prior art antihistaminic 
creams and lotions provide relief of short duration and must be applied 
frequently.

The following examples provide detailed illustrations of formulations for 
the gel compositions used in the present invention as well as methods of 
treatment employing the same. These examples are not intended, however, to 
limit or restrict the scope of the invention in any way, and should not be 
construed as providing methods, conditions, ingredients or starting 
materials which must be utilized exclusively to practice the present 
invention. 
EXAMPLE 1 
Antihistaminic Gel 
Five kilograms of an antihistaminic gel were prepared utilizing the 
following ingredients: 
______________________________________ 
Percentage of 
Ingredient Quantity Total (w/w) 
______________________________________ 
Phase A 
CARBOPOL 940 (carboxyvinyl 
50.0 g 1.0% 
polymer, B. F. Goodrich Chemical 
Co., Cleveland, Ohio) 
NATROSAL 250 HHF 10.0 g 0.2% 
(hydroxyethyl cellulose, 
Hercules, Inc., Wilmington, 
Delaware) 
Alcohol USP 2.75 kg 55.0% 
Purified Water 1.32 kg 26.3% 
Phase B 
CERAPHYL (C.sub.12-15 alcohols 
125.0 g 2.5% 
lactate, Van Dyk & Co., 
Belleville, New Jersey) 
Glycerin 125.0 g 2.5% 
QUADROL POLYOL 135.0 g 2.7% 
(tetrahydroxy- 
propyl ethylenediamine, 
BASF Wyandotte Corp.) 
Phase C 
Menthol 15.0 g 2.7% 
UVINUL MS-40 (benzophenone, 
5.0 g 0.1% 
BASF Wyandotte Corp., Parsippany, 
New Jersey) 
Diphenhydramine HCl 100.0 g 2.0% 
Alcohol USP 250.0 g 5.0% 
Phase D 
FDC Blue #1 0.0125 g .00025% 
______________________________________ 
The alcohol an purified water of Phase A were mixed in a steam-jacketed 
stainless steel kettle. The Carbopol 940 gelling agent and Natrosal 250 
gelling enhancer were sprinkled into the alcohol/water mixture with rapid 
mixing. 
The ingredients of Phase B were accurately weighed and then charged into a 
separate steam-jacketed stainless steel kettle where they were thoroughly 
mixed. Phase B was then added to Phase A with continued mixing to form a 
gel. 
The ingredients of Phase C were subsequently mixed and added to the gel 
with continued agitation until homogeneous. Phase D was then added to the 
gel and mixing continued until uniform color and consistency were 
obtained. 
EXAMPLES 2-3 
Antihistaminic Gels 
The procedure of Example 1 was repeated with the relative proportions of 
the ingredients changed as follows: 
______________________________________ 
Weight Percentages 
Ingredients Ex. 2 Ex. 3 
______________________________________ 
CARBOPOL 940 1.25% 1.5% 
NATROSAL 250 HHF 0.25% 0.3% 
Alcohol USP (Phase A) 
70.0% 85.0% 
Purified Water 12.1% 0.55% 
CERAPHYL 2.5% .5% 
Glycerin 2.5% 0.5% 
QUARDOL POLYOL 3.8% 4.05% 
Menthol 0.5% 0.5% 
UVINUL MS-40 0.1% 0.1% 
Diphenhydramine HCl 
2.0% 2.0% 
Alcohol USP (Phase C) 
5.0% 5.0% 
______________________________________ 
EXAMPLE 4 
Method of Treatment for Pruritus 
A human patient suffering from a histamine-mediated, pruritic skin eruption 
is treated by applying a sufficient amount of a gel according to Example 1 
to cover the affected area with a thin film. The gel is applied from one 
to five times daily, as needed. 
It will thus be shown that there are provided compositions and methods 
which achieve the various objects of the invention, and which are well 
adapted to meet the conditions of practical use. 
As various possible embodiments might be made of the above invention, and 
as various changes might be made in the embodiments set forth above, it is 
to be understood that all matters herein described are to be interpreted 
as illustrative and not in a limiting sense. 
What is claimed as new and desired to be protected by Letters Patent is set 
forth in the appended claims.