Irritation relief using nonsteroidal anti-inflammatory compounds

A method of relieving irritation to a patient's mucous membrane is provided and comprises contacting the mucous membrane with a non-steroidal anti-inflammatory agent, such as diclofenac sodium, that may be instilled as a spray of drop-wise into the nasopharynx mucosa. The same methodology can also be employed to relieve irritation of a patient's nasopharynx mucosa resulting from anesthesia by endotracheal intubation. A method of administering anesthesia in order to reduce irritation of the tracheal mucosa is also provided and comprises the steps of instilling a quantity of diclofenac sodium solution into the patient's tracheal mucosa, allowing the diclofenac sodium to operate for a selected interval of time, intubating the patient with an anesthesia delivery tube after this interval of time, and delivering a selected anesthesia to the patient.

FIELD OF THE INVENTION 
The present invention broadly concerns methods of relieving irritation of a 
patient's mucous membrane. More particularly, however, the present 
invention concerns relief of irritation to the mucous membranes located in 
nasopharyngeal passageway. Specifically of concern is the relief of 
irritation which results from the endotracheal intubation of the patient, 
especially during anesthesia. 
BACKGROUND OF THE INVENTION 
Irritation of various mucous membranes can result from a variety of 
factors. On one hand, irritation may result from infections of the mucous 
membrane by a disease entity, such as occurs with strep throat. On the 
other hand, irritation of the mucous membranes can be caused directly by 
physical trauma to the mucous membrane, for example, by surgery or by 
abrasion from the insertion of a medical instrument. For example, the 
mucous membranes associated with the nasopharyngeal passage may be 
traumatized by insertion of a medical instrument such as a nasogastric 
tube, an anesthesia tube and the like. Types of surgery which can 
traumatize the nasopharyngeal passageway include tonsillectomies, 
tracheostomies, vocal cord surgery, etc. Here, irritation may occur to the 
buccal membrane, the oropharynx, the uvula, the trachea and/or the larynx. 
Of particular concern to the present invention, however, is the trauma 
caused to the various tracheal mucosa resulting from endotracheal 
intubation which accompanies general anesthesia. Here, an endotracheal 
tube is inserted into the throat of a patient undergoing general 
anesthesia, and a cuff is inflated to block the air passageway. The 
anesthesia is administered through the endotracheal tube. This anesthesia 
technique can traumatize the tracheal mucosa in several ways. First, the 
physical rubbing of the endotracheal tube against the tracheal mucosa 
tends to irritate this mucous membrane. The irritation can be exacerbated 
by the inflation of the cuff provided on the device. Second, the tracheal 
mucosa may be damaged by the anesthesia itself or by desiccation from the 
anesthetic agent. As a result, the patient typically experiences extreme 
discomfort following anesthesia in the form of a painful sore throat, 
which condition may persist for several days. 
Where a painful irritation of a mucous membrane results from a disease 
entity, it is not uncommon for a physician to prescribe a steroidal 
compound to alleviate the symptoms. One such example is the use of 
cortisone in cases where patient experiences extreme discomfort. The use 
of steroidal agents, however, are not generally prescribed for other 
trauma to a mucous membrane. Steroid compounds, of course, work by 
reducing swelling and have limited topical effect. They have the 
disadvantages of being slow acting or non-acting where the pain mechanism 
does not have associated swelling. Also, steroid compounds have the 
disadvantages of increasing the patient's susceptibility to secondary 
infections and having limited topical effect so that they are slow-acting. 
Topical anesthetics are sometimes are sometimes prescribed, such as 
xylocaine (viscous 4%), benzocaine and the like. Topical .anesthetics can 
work quickly, but are typically give relief for only a short duration. 
Further, while various nonsteroidal anti-inflammatory agents are known, 
they are not prescribed for conditions of irritation to the mucous 
membranes, in general, or to the irritation of the tracheal mucosa 
resulting from intubation, in particular. Non-steroidal anti-inflammatory 
agents have long been prescribed for systemic use, but, except for a 
limited use in the eye, have not been used topically. One non-steroidal 
anti-inflammatory drug, diclofenac sodium, has been topically used as an 
ophthalmic for dilation of the eye but is known to desensitize the 
epithelial layer of the eye from pain caused by abrasion or other 
irritations, especially as may accompany surgery of the eye. Thus, 
diclofenac sodium is sometimes used topically in the eye for such 
purposes. Of course, the epithelial layer, however, is not a mucous 
membrane, such that the use of diclofenac sodium on a mucous membrane is 
not suggested by this known regimen. Indeed, the cellular structure 
differences between a mucous membrane and the corneal epithelium are 
substantial. The corneal epithelium is a stratified squamous epithelium 
having no secretory cells. A mucous membrane, however, contains a high 
percentage of secretory cells and is histologically distinct. 
It is known that diclofenac sodium, that has a chemical formula of 
2-[(2,6-dichlorophenyl) amino]benzeneacetic acid, monosodium salt; 
C.sub.14 H.sub.10 Cl.sub.2 NO.sub.2 Na, will penetrate various membranes, 
as described in "Human Transbuccal Absorption of Diclofenac Sodium From a 
Proto-type Hydrogel Delivery Device", Pharmaceutical Research, Vol. 10, 
No. 1 (1993). In this article, hydrogel disks were loaded with diclofenac 
sodium in methanol-water. The hydrogel disk was placed on a non-permeable 
patch and then affixed by dental adhesive to the center of the patient's 
cheek with a non-permeable patch so that the hydrogel contacted the buccal 
mucosa for a period of four hours. The purpose of the study was to 
determine if the diclofenac sodium would penetrate the membrane and enter 
the blood stream. Accordingly, blood was withdrawn from the volunteer at 
varying intervals and assayed. In each case, the volunteer for the study 
was healthy so that the buccal membrane was not previously traumatized, 
and the study was not directed to examine the effect of the diclofenac 
sodium on the buccal membrane or to evaluate any relief of irritation 
arising from the diclofenac sodium. 
Accordingly, despite the various drugs available for the relief of 
irritation to mucous membranes, a need remains for agents which can 
adequately relieve pain and irritations to the mucous membranes without 
the disadvantages which accompany steroidal agents and existing topical 
anesthetics. Moreover, a long felt need has existed for a simple and 
effective technique of relieving irritation which results from the 
intubation of patients during anesthesia by relatively benign compounds. 
SUMMARY OF THE INVENTION 
It is an object of the present invention to provide a new and useful method 
of treating irritation to a mucous membrane. 
Another object of the present invention is to provide a method of relieving 
irritation to the mucous membrane without the use of steroidal agents. 
Still a further object of the present invention is to provide a method of 
treating irritation to mucous membranes using a non-steroidal 
anti-inflammatory agent such as diclofenac sodium. 
Yet another object of the present invention is to provide a method of 
relieving tracheal irritation of the tracheal mucosa resulting from 
anesthesia by tracheal intubation. 
Still a further object of the present invention is to provide a method for 
treating tracheal irritation which can be easily self-administered by the 
patient in a safe and effective manner. 
A further object of the present invention is to provide a method of 
administering anesthesia in a manner to reduce post-anesthesia pain to the 
patient. 
According to the present invention, then, a method of relieving irritation 
to a mucous membrane of a patient broadly comprises the step of contacting 
the mucous membrane with a non-steroidal anti-inflammatory agent. 
Preferably, this non-steroidal anti-inflammatory agent is diclofenac 
sodium. 
In particular, however, the method of the present invention is directed to 
relieving tracheal irritation of the tracheal mucosa of a patient which 
results from anesthesia by endotracheal intubation. Here, the method 
broadly includes the step of contacting the tracheal mucosa of the patient 
with an effective amount of a non-steroidal anti-inflammatory agent, such 
as diclofenac sodium. More specifically, however, the method according to 
the present invention instills the diclofenac sodium as a spray or 
drop-wise onto the tracheal mucosa. 
The method of the present invention may further be directed to a method of 
administering anesthesia to a patient in a manner to reduce the irritation 
of the nasopharynx mucosa comprising the steps of instilling a quantity of 
diclofenac sodium solution onto the nasopharynx mucosa prior to intubation 
of the patient. Next, a selected interval of time is allowed to lapse to 
allow the diclofenac sodium to penetrate the nasopharynx mucosa. Next, the 
patient is intubated with an anesthesia delivery tube, and the selected 
anesthesia is delivered to the patient.

These and other objects of the present invention will become more readily 
appreciated and understood from a consideration of the following detailed 
description of the exemplary embodiment. 
DETAILED DESCRIPTION OF THE EXEMPLARY EMBODIMENTS 
The present invention is directed generally to the topical use of 
non-steroidal anti-inflammatory agents in the treatment of irritation to 
mucous membranes. Specifically, however, the present invention is directed 
to a method of treating irritation to the nasopharynx mucosa which has 
resulted from the administration of a general anesthesia to a patient, 
such as occurs during tracheal intubation with an anesthesia delivery 
device. Thus, the present invention also concerns methods of administering 
general anesthesia to a patient. Specifically, this methodology 
incorporates the installation of diclofenac sodium onto the tracheal 
mucosa. 
STUDY A 
An initial indication that diclofenac sodium had the capability of reducing 
and even eliminating irritation to the tracheal membrane was conducted on 
a single patient, K.P., who had undergone general anesthesia by 
endotracheal intubation for nasal surgery. Unfortunately, during the use 
of the endotracheal tube, the uvula of the patient was crushed to a degree 
that the mucous membrane covering the uvula necrosed. Severe inflammation 
and pain resulted. The patient was treated by her plastic surgeon with 
analgesics for this pain, but she experienced little or no relief. As a 
test, it was suggested that diclofenac sodium could be applied topically 
to the uvula in a drop-wise manner which might relieve pain. A composition 
containing 0.1% (1 mg/mL) diclofenac sodium as an active ingredient and 
sold under the trademark Voltaren.RTM. (available from CIBAVision 
Ophthalmics of Atlanta, Ga.) was employed for this initial test. The 
inactive ingredients in this compound include boric acid, edetate disodium 
(1 mg/mL), polyoxyl 35 castor oil, purified water, sorbic acid (2 mg/mL) 
and tromethamine. Two to three drops of this compound was topically 
applied so that it contacted the uvula. This individual reported almost 
instantly (within three (3) minutes), dramatic relief from pain, and this 
relief lasted about four (4) hours. Accordingly, the individual instilled 
this solution, drop-wise, onto the uvula with the administration of 
approximately two to three drops every four (4) hours, and this regimen 
proved successful. 
Accordingly, more expanded studies was designed for a larger population of 
patients who were receiving general anesthesia by tracheal intubation for 
various cosmetic surgery. Two such studies were performed. The results are 
as follows: 
STUDY B 
In this test, approximately two to three drops of the diclofenac sodium 
solution (Voltaren.RTM.) was mixed with approximately 2 cc of a water 
soluble lubricating ointment, and this mixture was applied to a distal 
portion of the endotracheal tube which contacts the tracheal mucosa during 
general anesthesia. The patient was then intubated with endotracheal tube 
so that the ointment containing the diclofenac sodium was placed in 
contact with the trachea. This technique was used with a total of seven 
patients, and the patients were then queried following general anesthesia 
to determine whether any discomfort resulted from the intubation. The 
results are reported in the following Table I: 
TABLE I 
______________________________________ 
Post-Intubation 
Patient Surgery Type Discomfort 
______________________________________ 
C. C. Liposuction Yes 
N. R. Cepsulection Yes 
R. B. Blepharoplasty Some 
K. J. Septo Rhino No 
A. A. Face Lift Yes 
J. S. Stomach Tuck Some 
M. R. Body Lift Some 
______________________________________ 
Accordingly, it was learned from this initial study of the seven patients 
that substantial discomfort still resulted in three of the patients 
although four patients received some relief from discomfort. One patient, 
K. J., reported no discomfort. Accordingly, it appeared that some relief 
to tracheal irritation occurred by the incorporation of the diclofenac 
sodium in to the lubricating ointment, it was thought that the ointment 
sufficiently diluted the amount of diclofenac sodium which reached the 
mucous membrane. Thus, it is proposed that a larger quantity of diclofenac 
sodium be used if placed in the lubricating ointment. 
STUDY C 
Accordingly, a second test was devised wherein the tracheal mucosa was 
contacted directly with the Voltaren.RTM. solution without incorporating 
the solution into the lubricating ointment. Here, approximately 0.25 cc of 
Voltaren was instilled directly as a spray onto the vocal cords and the 
trachea of the patient prior to intubation for general anesthesia. A 
blunted and curved 22 gauge needle and syringe was used as the delivery 
vehicle and contact of the mucous membrane by the spray was visually 
confirmed. After spraying the tracheal mucosa with the diclofenac 
solution, an interval of approximately one to five minutes was allowed to 
lapse before the patient was intubated. A group of fifteen patients were 
studied utilizing this technique, and the results were dramatic. These 
results are reported in the following Table II: 
TABLE II 
______________________________________ 
Post-Intubation 
Patient Surgery Type Discomfort 
______________________________________ 
K. O. Breast Augmentation 
No 
and Rhinoplasty 
M. R. Excision Multiple Cysts 
No 
R. W. Reduction Fracture 
No 
(Nose) 
K. T. Face Lift No 
P. W. Liposuction No 
K. R. Septo Rhinoplasty No 
S. L. Face Lift No 
K. K. Excision Mass Chest 
No 
P. P. Mastopexy No 
C. P. Capsulectomy No 
E. E. Mammoplasty No 
M. L. Face Lift No 
C. H. Stomach Tuck No 
H. T. Rhinoplasty Minimal 
C. P. Blepharoplasty No 
______________________________________ 
As can be seen in Table II, all fifteen patients reported relief from 
irritation resulting from the intubation for the general anesthetic. Only 
one patient out of the fifteen reported any discomfort, and this 
discomfort was rated by the patient as minimal. 
Diclofenac sodium, as noted above, falls in the general class of 
non-steroidal anti-inflammatory compounds. It's method of pain suppression 
appears to be the on-site blockage of nerve pulses. The relief that 
occurred to the patients was rapid enough to rule out an anti-inflammatory 
relief mechanism as providing the pain suppression, and the pain blockage 
would not be a central nervous system blockage due to the topical 
application. 
From the results of these studies, it would appear that other 
non-steroidal, anti-inflammatory compounds such as flurbiprofen, ketorolac 
and suprofen, among others, might hold promise in suppressing pain arising 
from irritation to the various mucous membranes. Indeed, there is the 
potential to use such mild non-steroidal anti-inflammatories to give 
relief in many existing situations from oral surgery to urogenital 
surgery, as well as from pain of diseases that result in inflammation or 
irritation of a mucous membrane. 
Accordingly, the present invention has been described with some degree of 
particularity directed to the exemplary embodiment of the present 
invention. It should be appreciated, though, that the present invention is 
defined by the following claims construed in light of the prior art so 
that modifications or changes may be made to the exemplary embodiment of 
the present invention without departing from the inventive concepts 
contained herein.