WO2000053252A1 - Device and method for delivering a material into the paranasal sinus cavities - Google Patents

Abstract

A device, and method for delivering materials such as medications or other therapeutic or diagnostic materials useful for treating sinus disease, to the middle meatus, and para-nasal sinuses, is provided (see Figure). The device has an elongated body portion with a distal end (15), a proximal end (13), and a passage therethrough extending from the proximal end to the distal end of the body portion (12).

Description

DEVICE AND METHOD FOR DELIVERING A MATERIAL INTO THE PARANASAL SINUS CAVITIES

1

CROSS-REFERENCE TO RELATED PROVISIONAL APPLICATIONS

The present application claims the benefit of the earlier filing date of U.S.

Provisional Patent Applications Serial Nos. 60/123,238, filed March 8, 1999, and 60/125,685, filed March 23, 1999, which are incorporated by reference herein in their entireties. FIELD OF THE INVENTION

The present invention relates to a device and method for treating sinus disease. More particularly, the present invention relates to a device and method for delivering a material into the middle meatus and paranasal sinus cavities. BACKGROUND OF THE INVENTION

Sinus disease is a common human affliction associated with substantial economic costs. In the United States alone, approximately 1 million cases of viral sinusitis, 20 million cases of bacterial sinusitis, and 200,000 cases of chronic sinusitis are reported each year. In the course of evaluating and treating these types of sinus disease, as well as cases of

allergic sinusitis, the common cold, and other sinus diseases, it is often desirable to deliver pharmaceutical agents, as well as other therapeutic and diagnostic materials, into the middle

meatus or, better still, the paranasal sinus cavities. The effective treatment of any sinus disease ultimately depends upon

delivering adequate quantities of therapeutic material into the paranasal sinus cavities. Unfortunately, conventional techniques for treating sinus disease have been unable to reliably

effect delivery of sufficient materials into the paranasal sinus cavities. Indeed, conventional techniques have been largely incapable of delivering effective quantities of therapeutic materials even as far as the middle meatus. The only techniques which have been able to reliably deliver sufficient quantities of materials into the paranasal sinus cavities are invasive, ^ involving punctures or the opening of passages through flesh and bone, and therefore viewed as alternatives of last resort.

Materials delivered into the nasal passages using conventional devices such as those involving nose drops, nasal sprays, or aerosols are substantially blocked from reaching

the middle meatus, and therefore the paranasal sinuses, by natural obstructions present in the nasal passages. Human nasal passages are variegated and sinuous due to the presence of three turbinates and other structures projecting from the lateral wall. The paranasal sinuses are air-filled cavities that drain in the nasal passages by narrow portals or ostea. As the

sinuses are surrounded by bone, the geometry of the nasal passages makes it difficult to directly access the sinus openings to deliver pharmaceuticals or other materials into the paranasal sinuses. A significant failing of such conventional devices is that they deliver

materials under the inferior turbinate, thereby rendering such materials incapable of

navigating the complex geometry of the nasal airways to reach the middle meatus or the

paranasal sinus cavities. Accordingly, conventional devices are largely incapable of delivering materials into the paranasal sinus cavities. Accordingly, it is desirable to identify a

device and method capable of safely, non-invasively, effectively and reliably depositing material, including medication, into the middle meatus and paranasal sinus cavities. SUMMARY OF THE INVENTION

The device and method of the present invention addresses the several

shortcomings and disadvantages of conventional techniques for treating sinus disease. The

device of the present invention generally includes an elongated body portion having a distal end and a proximal end, and a passage therethrough extending from the proximal end to the

distal end of the body portion. The distal end of the body portion may have a separate or

integral tip portion. The tip portion may have a spray orifice, and is anatomically curved for inserting the tip portion through the nasal passages and positioning it in the middle meatus (ostiomeatal complex). The curved portion of the tip portion includes a first curve or bend, and may include a second curve or bend that is disposed orthogonally to the first curve. The first and second curves preferably are selected to ensure that the tip portion of the device will

be positioned in line-of-sight to the top of the inferior turbinate bone in the subject or

patient's nasal cavity upon insertion of the device. Such positioning will permit a material to be deposited on top of the turbinate bone in the middle meatus of the subject's nasal cavity,

greatly increasing the ability of the material to reach the paranasal sinus cavities. Preferably,

the distal end of the device is coated with a low-friction, biocompatible lubricant or other material, such as Teflon® or K-Y Jelly®, to aid the comfortable insertion of the device.

The tip portion may be configured to be detachable from the body portion of

the device. If the tip portion is detachable, it can also be disposable, reducing the cost of

using the device. Of course, the entire device may be configured so as to be disposable after

one or more uses. The proximal end of the body portion is configured to receive a material to be directed through the passage in the body portion and out the tip portion of the device. The

device also may include a reservoir attached to the proximal end of the body portion, which

may be used to hold a quantity of material for delivery. A pressure device also may be operatively attached to the device of the present invention, the pressure device being configured to apply pressure sufficient to deliver a material, such as a liquid medication, through the body portion and out the tip portion (distal portion) of the device and into a

subject's middle meatus. The pressure device may be further configured (or a separate pressure device may be employed) to apply pressure sufficient to increase the pressure in the subject's nasal passages and thereby assist the movement of the material into one or more of the subject's paranasal cavities from the middle meatus. The pressure device may be formed

as a component separate from the device of the present invention, and may be configured to also function as the reservoir. The reservoir and pressure device, whether alone or in

combination, may include, for example, a syringe, a flexible bulb, or a clinical pressure system of the type frequently found in physician's offices. Where a clinical pressure system is to be utilized, the device of the present invention may include an adaptor to attach to such a

system.

The device also may include a guide attached to the body portion of the device, the guide being designed to assist in properly inserting the distal end of the body

portion of the device into a subject's nasal cavity. The guide may include one or more of an

insertion limiting portion, an abutment portion, and a vestibule locating portion. Generally, the method of the present invention includes two steps. The first step of the method of the present invention includes delivering a material into the subject's - ^'. middle meatus. The second step of the method includes applying pressure in the subject's

nasal passages sufficient to deliver the material into one or more of the subject's paranasal

sinus cavities. The first step of the method of the present invention may further include providing a device, such as the device of the present invention, for delivering the material

into the middle meatus, and ultimately into one or more of the subject's paranasal sinus cavities. The second step of the method of the present invention may be performed, for

example, by having the subject perform a nose blow or Valsalva's maneuver, or by providing a pressure device capable of increasing the pressure in the subject's nasal passages, such that a pressure is applied which is sufficient to deliver the material into one or more of the

subject's paranasal sinus cavities.

The foregoing and other features, objects and advantages of the present

invention will be apparent from the following detailed description, taken in connection with the accompanying figures, the scope of the invention being set forth in the appended claims.

BRIEF DESCRIPTION OF THE DRAWINGS

The accompanying drawings, which are incorporated into and form a part of

the instant specification, illustrate several aspects and embodiments of the present invention and, together with the description herein, serve to explain the principles of the invention. The

drawings are provided only for the purpose of illustrating preferred embodiments of the

invention and are not to be construed as limiting the invention. In the drawings: FIG. 1 is an elevational side view of one embodiment of the device of the present invention.

FIG. 2A is a cross-sectional side view of one embodiment of a tip portion of the device of the present invention.

FIG. 2B is an elevational top view of the tip portion of the embodiment of the device of FIG. 2A.

FIG. 3 is a partial orthogonal representation of the human nasal passages, illustrating the preferred insertion of the embodiment of the device of FIG. 1.

FIG. 4 is a partial cross-sectional representation of the human nasal passages, illustrating the insertion of another embodiment of the device of the present invention.

FIG. 5 is a graph illustrating the intranasal pressure time history for a human

subject during a nose blow.

FIG. 6 is a graph illustrating the effect of the application of an external

pressure transient on aqueous fluid flow over time into a typical human maxillary sinus. FIG. 7 is a graph illustrating the effect of an external pressure transient on total

aqueous fluid flow in a typical human maxillary sinus.

DETAILED DESCRIPTION OF THE INVENTION

The present invention includes a method and device for delivering a material

into the middle meatus, and ultimately into the paranasal sinus cavities (maxillary, ethmoid,

sphenoid and frontal). The device and method of the present invention can be designed to

deliver a number of materials including liquids, gases, powders, and slurries for a number of

different purposes, such as diagnostic and therapeutic purposes, among others. One embodiment of the device of the present invention is illustrated in FIG. 1.

As shown in that figure, the device 10 generally includes an elongated body portion 12 having a proximal end 13 and a distal end 15. Body portion 12 defines a passage therein extending from proximal end 13 to distal end 15. Body portion 12 may be constructed in various lengths as appropriate to the needs and circumstances of use. For example, body portion 12 is

anatomically shaped and constructed of a length such that device 10 may be held at proximal

end 13 for insertion into a human nose, and extension into the middle meatus at distal end 15. Such a body portion 12 may be further refined to custom-fit a particular human subject. Body portion 12 may be constructed of any suitable material or combination of materials, including

one or more thermoplastics or other materials which are biocompatible, sufficiently soft to be comfortable to a human or other subject, and sufficiently rigid to retain their shape, yet not so rigid as to be uncomfortably unyielding when being positioned in a subject's nasal passages. It may have a cross-section that is cylindrical, or any other shape that is advantageous for

design or application purposes. The cross-section of device 10 preferably is as small as

possible.

Proximal end 13 is configured to receive a material to be directed into the passage in body portion 12. For example, proximal end 13 may include a reservoir 14, as in

FIG. 1 , or otherwise be connected to a reservoir 14, containing a material to be delivered to

the middle meatus of a subject's nasal passages. Reservoir 14 may be any type of device

capable of holding a material for introduction into the passage through body portion 12. For example, reservoir 14 may be constructed as a flexible bulb such as that used in connection

with conventional blood pressure measurement devices, as illustrated in FIG. 1, or may comprise a conventional syringe or any other device capable of containing the material to be

delivered. The volume of reservoir 14 must be large enough to contain a volume of a chosen

material sufficient for that material to effect the desired purpose once it reaches the subject's paranasal sinuses. For example, where it is desired to therapeutically treat a subject's sinus disease, the reservoir should be capable of holding a volume of the chosen material which is

sufficient for the material to be therapeutically effective.

As shown generally in FIGS. 1 and 2 A, distal end 15 of body portion 12 incorporates a first curve 17 which, for use in connection with human subjects, is in the range

of approximately 20 to 45 degrees. The range of the curve may be different for animal subjects than for humans, and may be custom fit for optimal effect for a given subject. First

curve 17 is designed to facilitate the insertion of device 10 through a subject's nasal vestibule

and into the anterior portion of the middle meatus. Once device 10 is inserted, as illustrated in FIG. 3, distal end 15 of device 10 will be positioned in line-of sight of the space between the inferior turbinate and the middle turbinate bone, and therefore in line of sight with the

sinus ostia, allowing delivery of the material from the middle meatus and into one or more of

the paranasal sinus cavities. Due to first curve 17, distal end 15 of device 10 is able, when so positioned, to maintain a spray direction ensuring an optimum spray pattern for the delivery of material into the anterior portion of the middle meatus. The incorporation of first curve 17

also serves to reduce or eliminate the drowning sensation that may otherwise be experienced

by a subject.

As shown in FIGS. 1-4, distal end 15 of body portion 12 may have an integral

or detachable tip portion 16. Preferably, tip portion 16 contains first curve 17, provides the desirably elliptical shape for distal end 15 of body portion 12 (as is discussed in greater detail

below), and where a powder or liquid spray is desired, is equipped with a spray orifice similar to those used in conventional spray devices in order to provide a fine or coarse powder or

liquid spray. Tip portion 16 may be constructed from any suitable material, such as one or more thermoplastics. In the embodiment of FIGS. 2 A and 2B, for example, tip portion 16 is a heat-shrunk thermoplastic sheath 19 over a looped stainless steel spring wire 20. Of course,

tip portion 16 may be fabricated without wire 20 to define its shape, for example, by blow

molding, extrusion or injection molding. As another alternative, for example, tip portion 16

may be formed by embedding a small diameter tube (e.g., Teflon® spaghetti tube) in an elastomeric material, the latter of which may be cast or cured to form the desired shape. Tip portion 16, or distal end 15 itself if a tip portion is not employed, preferably is coated with a

biocompatible material or lubricant, such as Teflon® or K-Y Jelly®, to aid the insertion of device 10 through the subject's nasal vestibule and into the anterior portion of the subject's

middle meatus. Tip portion 16 preferably has an elliptical shape. In the embodiment of

FIGS. 2A and 2B, this shape is formed by the looped stainless steel wire previously

discussed, and tip portion 16 has a cross-section measuring approximately 2 millimeters by 4

millimeters. In this embodiment, first curve 17 lies in the plane of the 2 millimeter

dimension. The overall length of device 10 in the embodiment of FIG. 1 is between 8 and 12 centimeters and the length from the distal end 18 of tip portion 16 to the start of first curve 17

is 5 centimeters.

Distal end 15 of body portion 12 preferably includes a second curve 19 in an

orthogonal relationship to first curve 17. Where a tip portion 16 is employed, as illustrated in FIG. 2B, second curve 19 is imparted to tip portion 16 over the same length of body portion 12 where first curve 17 occurs. Second curve 19 is generally less than or equal to approximately 30 degrees, and preferably is approximately 20 degrees. The magnitude of

second curve 19 may be optimized, like first curve 17, in accordance with the anatomy of a particular subject. Although not essential to the efficacy of device 10, second curve 19 may operate in conjunction with orthogonal curve 17 to further facilitate the insertion of device 10 through the nasal vestibule and into the anterior portion of the middle meatus.

Device 10 may include, or be adapted for use with, a pressure device

operatively attached to device 10 to apply pressure sufficient to deliver a material from proximal end 13, through the passage in body portion 12, out tip portion 16 and into a subject's middle meatus. The same pressure device, or an additional pressure or flow device,

may be designed to selectively increase the pressure or flow in a subject's nasal passages

sufficiently to facilitate the delivery of material to the middle meatus, or sufficiently to

facilitate the delivery of such material to one or more of the paranasal sinus cavities. Examples of such a device include a common syringe or flexible bulb, both of which may

serve a dual purpose as the pressure device and reservoir 14. For example, the flexible bulb serving as reservoir 14 in FIG. 1 could be manually compressed to create a pressure, forcing a

sufficient volume of liquid medicine or other material in reservoir 14 through the passage in

body portion 12 and into a subject's middle meatus or paranasal sinuses. However, the pressure device and reservoir 14 need not be so combined, as the pressure device may

comprise, for example, a separate hand-held pressure applicator, a positive pressure pump or

a clinical pressure system of the type commonly found in physician's offices. The pressure device must be capable of delivering a level of pressure which is effective to drive a sufficient volume of medicines or other selected materials into the middle meatus, or better still, the paranasal sinuses. As is discussed in greater detail below, a pressure of approximately 66 mm-Hg has been found to be sufficient to drive material from

the middle meatus into the paranasal sinuses, but lower pressures (perhaps as low as 60 mm-

Hg or lower) are also expected to be sufficient. A pressure regulator preferably is used in

combination with or as part of the pressure device to ensure that the pressure applied to a subject's nasal passages will not reach a level at which tissue damage or the introduction of

air to the bloodstream may result. It is believed that pressures up to approximately 80 mm-

Hg are generally safe for use in human nasal passages, although pressures as high as 176 mm-

Hg have been safely demonstrated during sneezing with nostrils occluded.

Referring now to FIG. 4, device 10 may include a guide 22 configured to assist a user in comfortably and effectively positioning distal end 15 of body portion 12 into a

subject's nasal passages. In the embodiment of FIG. 4, for example, guide 22 is designed to include an insertion limiting portion 24 that, by having a cross section larger than the vestibule of a subject's nose, prevents device 10 from extending into a subject's nasal

passages more than a preselected distance. Guide 22 also may be constructed to include a

vestibule locating portion 28 which may serve the same function as an insertion limiting

portion, or may alternatively or additionally serve to seat device 10 in the vestibule of a subject's nose. Another potential feature of guide 22 is an abutment portion 26 configured to

assist the proper and consistent application of device 10 by ensuring a proper angle and

orientation relative to a subject's body. For example, the abutment portion 26 of guide 22 shown in FIG. 4 is configured to comfortably abut a human subject's upper lip. As an

alternative embodiment, guide 22 may be separate from device 10 and placed in the vestibule of a subj ect' s nose prior to use of the device.

Guide 22 may be attached to, or integrally formed with, device 10. Alternatively, guide 22 may be configured so that, once guide 22 is in place in the vestibule

of a subject's nose, body portion 12 of device 10 may be inserted through a passage in guide

22 and into the subject's nasal passages. In such an embodiment, guide 22 preferably includes a manually operable cam (not shown) or other device for selectively fixing guide 22

to body portion 12, so that the position of guide 22 relative to distal end 15 of body portion 12 may be adjusted as needed.

The present invention also includes a non-invasive method for delivering a material into one or more of a subject's paranasal sinus cavities. In generally, the method of the present invention involves two principle steps. The first step is to deliver a quantity of

material into the subject's middle meatus. The second step is to apply a pressure to the

subject's nasal passages sufficient to deliver the material into one or more of the subject's

paranasal sinus cavities.

The first step of the method of the present invention may be carried out with the subject's head positioned parallel to the floor or in another inclined or reclined position,

or with the subject in the supine position, to increase the residence time of the material

delivered in the middle meatus. The second step also may be performed while the subject's head is in same position, or in another position provided that the second step of the method is

performed before the material has drained from the middle meatus. The material preferably is delivered to the middle meatus in the first step using a device, such as those illustrated in the

embodiments of FIGS. 1-4, configured to consistently deposit a selected amount of material in the middle meatus with maximum efficacy and comfort.

Once the material has been delivered to the subject's middle meatus, the second step of the present invention may be performed by applying a pressure in the subject's

nasal cavity sufficient to drive a sufficient volume of the material from the middle meatus

into one or more of the paranasal sinus cavities. This application of pressure may be accomplished in any suitable manner. For example, the subject may be asked to blow the

subject's nose, or to perform Valsalva's maneuver (i.e., with nose and mouth closed). Although such methods of applying pressure have the potential disadvantage that the magnitude of the pressure actually applied is unknown, the inventors hereof have found that such methods typically provide pressures sufficient to drive substantial volumes of the material delivered to the middle meatus into one or more of the paranasal sinuses. Another

way to apply the requisite pressure is by external means, such as using a pump or other device

as described previously in connection with device 10 of the embodiments of FIGS. 1-4. This

second step of the method of the present invention uses the air that is naturally present in the subject's sinus cavities as a "surge tank" that contracts under the application of fluid pressure

in the subject's nasal passages. This contraction allows the flow of material into the subject's

paranasal sinus cavities through natural passages present in the subject's nasal passageway.

It will now be appreciated that the present invention solves many disadvantages of conventional techniques for treating sinus disease, including but not limited

to acute viral sinusitis (as with the common cold), acute bacterial sinusitis, chronic sinusitis which has not been subject to surgery, and allergic sinusitis. For example, the device and method of the present invention represent a non-invasive technique by which to ensure that

material, such as a topical medication, will reach the middle meatus. In addition, the present

invention greatly increases the user's ability to ensure that an effective dosage of medication or other material will be deposited in the middle meatus, and not merely be deposited on one or more of the various nasal surfaces leading to the middle meatus and thereby wasted. The

device of the present invention also ensures that the selected material will be able to be

deposited, with a maximum of comfort and safety, in the anterior portion of the middle meatus so that it may more easily be directed into one or more of the paranasal sinuses, and provides for the application of a pressure sufficient to ensure that the material reaches one or

more of the paranasal sinuses. In addition, the device of the present invention may be made

to be adjustable and capable of being optimized to the anatomy of a particular subject.

Example 1 Materials and Methods Healthy adult volunteers with no history of nasal symptoms for one month

prior to the time of the volunteers' selection were recruited. Intranasal pressures were measured during nose blowing, sneezing, and coughing with a Millar SP-524 catheter pressure transducer (catheter diameter 2.5 French, transducer diameter 3.0 French) positioned above the inferior turbinate and a DSP Traq-Q data acquisition system. Data was sampled at

200 Hz and anti-aliasing filtering was performed at 66 Hz. The effective bandwidth of sensor

signals was approximately 0.02-66 Hz.

Nose blowing (both nostrils open or one occluded) and coughing were initiated voluntarily by the subjects. Sneezing (both nostrils and mouth open or both nostrils

and mouth occluded) was induced by touching the inferior turbinate with a cotton swab t saturated with histamine (concentration 25 mg/mL).

Limited coronal CT scans of the paranasal sinuses were obtained with subjects

in the supine position, using a standard clinical imager. Non-ionic iodinated contrast media

(Iohexol 350, Nycomed, Princeton, NJ) was instilled prior to nose blowing, coughing, or sneezing. In 3 volunteers, 3 mL of contrast were instilled into the nasopharynx followed by

nose blowing while the volunteer remained supine. This procedure was repeated 3 times, and then a limited, direct coronal CT image was obtained with the subject in the prone position. In the fourth volunteer, who was unable to cooperate with the application of contrast into the nasopharynx because of his gag reflex, 5 mL of contrast were instilled onto the floor of each

nasal cavity with the subject supine. The volunteer then blew his nose, and a CT scan was

obtained. In one volunteer, 3 mL of contrast were placed in the nasopharynx by way of mouth followed by repeated forceful voluntary coughing. This procedure was repeated with 4

mL of contrast, and a CT was obtained with the subject prone. In a second volunteer, 4 mL of contrast was put into the nasopharynx once. The volunteer coughed forcefully and repeatedly

twice. A second application of contrast was not made because of a large amount of residual contrast in the nasopharynx after the first coughing episode. In a third volunteer who had excessive gagging with stimulation of the nasopharynx, 6 mL of contrast were applied onto

the floor of the nose on each side followed by 4 episodes of voluntary coughing with the

volunteer supine. The general procedure for instilling contrast into the nasopharynx for

sneezing was the same as above, except that contrast was only instilled once because repeated episodes of sneezing could not be elicited. One subject who received 2 mL of contrast while

supine sneezed 2 times following histamine challenge. A second volunteer who received 4 mL of contrast sneezed once, and a third who received 6 mL of contrast sneezed 4 times. Simulated sneezes were studied in the remaining 2 volunteers.

Results

A summary of the results of the foregoing testing is provided in the following table.

Table 1

As shown in Table 1 , the mean (± SD) maximum transient intranasal pressure measured in the 4 subjects during multiple nose blows was 66 (± 14) mm-Hg. Pressure transients from nose blowing with both nostrils open (N = 21) did not differ from those with

one nostril occluded (N = 14). Therefore, all nose blowing measurements were combined on

the analysis (N = 35). A graph of the increase in intranasal pressure measured with a transducer in the nasal passages of one of the human volunteers performing a voluntary nose blow is shown in FIG 5. The graph of FIG. 5 illustrates an increase in intranasal pressure of

over 60 mm-Hg for one of the volunteers during a nose blow. The mean (± SD) peak

intranasal pressure from 18 voluntary coughing bouts was 6.6 (± 2.6) mm-Hg, and that from 1 minute of tidal breathing by each of 4 subjects was 0.9 (± 0.4) mm-Hg. The mean pressure

associated with nose blowing was significantly different (p < 0.01, Student's t-test). When a i subject's mouth and nose were closed during a histamine-induced sneeze, large increases in transient intranasal pressure occurred. Two subjects did this by trapping a sneeze with a

tissue, resulting in peak pressures of 176 and 128 mm-Hg for one subject and 88 mm-Hg for the other.

As can be seen in Table 1, the mean (± SD) durations of the intranasal pressure transients were 1.9 (± 0.6), 2.2 (± 0.6), and 0.4 (± 0.2) seconds with nose blows, coughing

bouts, and sneezes, respectively. Even when sneezing occurred with the subject's mouth

closed and nose occluded, the mean duration of the pressure transient was only 0.56 seconds,

which was considerably shorter than that observed with a typical nose blow. With tidal breathing, intranasal pressure transients were characterized by sinusoidal waves of long duration and very small amplitude.

Modeling of Nasal Fluid Flow in the Maxillary Sinus A simple fluid model was used to demonstrate nasal fluid flow. This model incorporated a middle meatus and an infundibulum filled with viscous fluid and a spherical

maxillary sinus cavity partially filled with air at a standard atmospheric pressure of 760 mm-

Hg. The maxillary sinus cavity had a volume of 14.25 mL and the cylindrical infundibulum

had a diameter of 3 mm and a length of 7 mm. These parameters are within normal ranges

for the maxillary sinus (Goldman, Principles and Practice of Rhinology (1987)). A

logarithmic model of visco-elastic fluid was used in the simple model based on previous

measurements of nasal mucus showing a viscosity of over 500 Pa-s at shear rates of 0.01 1/s and of less than 0.02 Pa-s at shear rates of 100 1/s. A half sine pressure transient with an

amplitude equal to the average maximum pressure measured in the experiments was used in i the model for both the nose blowing and sneezing. The sine half period used for each activity was equal to the average duration of each event as found experimentally.

The graph of FIG. 6 was developed by modeling the measured parameters as

set forth in Table 1. As illustrated in FIG. 6, the model indicates that 1.0 mL of viscous nasal

fluid may be pushed into the maxillary sinus from the mean pressure transient associated with

a nose blow (66.2 mm-Hg). This is a substantial volume, and 20 times the volume of fluid contained in the lumen of the infundibulum (0.05 mL). On the other hand, a typical sneeze

(with both nostrils open) generated an intranasal pressure (4.6 mm-Hg) that could only move an amount of viscous fluid into the maxillary sinus which is less than the volume contained in the infundibulum. The difference in maximum pressure transients and durations between nose blows and sneezes accounts for a large part, but not all, of the amount of the fluid flow

into the sinus. Another significant contribution to fluid movement is the effect of shear rate

on nasal fluid viscosity. In the model, nose blowing was associated with a maximum shear

rate in the infundibulum of over 1500 1/s. This shear rate would result in a low fluid viscosity in the range of 0.001 Pa-s. In contrast, with sneezing the maximum shear rate only

approximated 180 1/s, resulted in a viscosity of over 0.01 Pa-s. In addition, the low

maximum shear rate with sneezing occurs over a much shorter time period than does the

much higher shear rate associated with nose blowing. During a normal sneeze, the nasal fluid

remains considerably more viscous and resistant to flow into the sinus than it does with the

large shear rate that accompanies a nose blow. CT Examinations with Intranasal Contrast Medium

Following nose blowing, contrast was seen in the ostiomeatal complex and in

the ethmoid and sphenoid sinuses of all four volunteers, and contrast was present in the infundibulum and maxillary and frontal sinuses of 2 of 4 subjects. In addition, contrast

outlined occasional bubbles in the maxillary and sphenoid sinuses of one of the subjects after nose blowing. Following histamine induced sneezes, contrast did not appear in the

infundibulum or sinus cavities of any of the volunteers. Similarly, contrast was not detected

in these areas following simulated sneezing in 2 volunteers. Following coughing, the CT

scan of one of 3 subjects showed a small amount of contrast in the infundibulum bilaterally. Otherwise, cough was not associated with contrast being in the paranasal sinuses.

The fluid model confirms that pressure transients of magnitudes seen

physiologically in nose blows and Valsalva's maneuver are sufficient to drive a substantial flow of material into one or more of the sinus cavities from the nasal passages, and that coughing and sneezing (nostrils/mouth open) do not generate pressures sufficient to cause such flows. As can be seen in FIG. 7, the model predicts that varying the peak amplitude of

the pressure transient changes the amount of material that flows from the nasal passages into

the sinus.

It is believed that the many advantages of the present invention will now be

apparent to those skilled in the art. It will also be apparent that a number of variations and

modifications may be made thereto without departing from the spirit and scope of the

foregoing written description. Accordingly, the foregoing description is to be construed as illustrative only, rather than limiting. The present invention is limited only by the scope of the following claims.

Claims

We claim:

1. A device for delivering materials into a subject's middle meatus, said device comprising:

an elongated body portion having a proximal end and a distal end, said body

portion having a passage therethrough from said proximal end to said distal end of said body portion;

said distal end of said body portion being anatomically curved for insertion of

said distal end into the middle meatus of a subject's nasal passages; and

said proximal end of said body portion being configured to receive a selected quantity of material to be directed through said passage through said body portion and out said distal end of said body portion of said device, wherein a selected quantity of a material may be deposited in said passage through said body portion and delivered directly to the

middle meatus of a subj ect.

2. The device of claim 1 , wherein said distal end has a tip portion and a first curve, said

first curve being located on said tip portion of said distal end.

3. The device of claim 2, wherein said first curve is configured for positioning said tip portion in line-of-sight of the top of the inferior turbinate bone in a subject's nasal cavity,

wherein a material may be deposited on top of the turbinate bone in the middle meatus of a

subject's nasal cavity.

4. The device of claim 2, wherein said distal end further comprises a second curve, said

first curve and said second curve being configured orthogonally with respect to each other, and both said first and said second curves said first curve and said second curve being configured for positioning said tip portion in line-of-sight of the top of the inferior turbinate

bone in a subject's nasal cavity, wherein a material may be deposited on top of the inferior

turbinate bone in the middle meatus of a subject's nasal cavity.

5. The device of claim 4, wherein said first curve is between 20 and 45 degrees and said

second curve is less than or equal to 30 degrees.

6. The device of claim 5, wherein said second curve is 20 degrees.

7. The device of claim 4, wherein said tip portion is 8 to 12 cm in length, and said first and second orthogonal curves are located within the five centimeters adjacent to said distal

end of said tip portion.

8. The device of claim 3, wherein said tip portion comprises a spray orifice.

9. The device of claim 1 , further comprising a reservoir attached to said proximal end of

said body portion of said device.

10. The device of claim 9, wherein said reservoir comprises a flexible bulb.

11. The device of claim 9, wherein said reservoir comprises a syringe.

12. The device of claim 9, wherein said reservoir comprises a pressure application device.

13. The device of claim 1 , further comprising a pressure application device.

14. The device of claim 13, wherein said pressure application device is capable of increasing the pressure in the subject's nasal passages to at least 60 mm-Hg.

15. The device of claim 14, wherein said pressure application device is capable of increasing the pressure in the subject's nasal passages to 80 mm-Hg.

16. The device of claim 15, wherein said pressure application device comprises a pressure

regulator to limit the pressure applied to the subject's nasal passages.

17. The device of claim 13, wherein said device for increasing nasal passage pressure

comprises a flexible bulb.

18. The device of claim 13, wherein said device for increasing nasal passage pressure

comprises a syringe.

19. The device of claim 13, wherein said device for increasing nasal passage pressure comprises a clinical pressure system. ι

20. The device of claim 1 , wherein said proximal end of said body portion is adapted to connect to a clinical pressure system for increasing nasal passage pressure.

21. The device of claim 1 , wherein said body portion has a cylindrical cross-section.

22. The device of claim 21 , wherein said passage through said body portion has a cylindrical cross-section.

23. The device of claim 1, wherein said body portion comprises a flexible plastic.

24. The device of claim 23, wherein said distal end comprises a tip portion having a

shape, and said body portion comprises a wire looped at said distal end of said body portion

to form said shape of said tip portion.

25. The device of claim 24, wherein said shape of said tip portion is elliptical, with major

and minor diameters of 4 mm and 2 mm, respectively.

26. The device of claim 24, wherein said wire is a stainless steel spring wire, and said tip

portion comprises a heat shrunk thermoplastic tube over said stainless steel spring wire.

27. The device of claim 23, wherein said tip portion is manufactured by blow molding.

28. The device of claim 23, wherein said tip portion is manufactured by embedding small-

diameter tube in an elastomeric material.

29. The device of claim 1 , wherein said distal end comprises a tip portion, said tip portion being configured to be detachable from said distal end of said body portion.

30. The device of claim 1, wherein said distal end comprises a tip portion, said tip portion

being said tip portion being coated with a low-friction material.

31. The device of claim 1 , further comprising a guide, said guide being configured to assist proper insertion of said distal end of said body portion into a subject's nasal passages.

32. The device of claim 31 , wherein said guide is adjustably attached to said body portion.

33. The device of claim 31, wherein said guide comprises an insertion limiting portion.

34. The device of claim 31 , wherein said guide comprises a vestibule locating portion.

35. The device of claim 31 , wherein said guide comprises an abutment portion.

36. A device for delivering materials into one or more of a subject's paranasal sinuses,

--NX -_* said device comprising:

an elongated body portion having a proximal end and a distal end, said body portion having a passage therethrough from said proximal end to said distal end of said body portion, and said distal end of said body portion having a tip portion and first and second

orthogonal curves, said first and second orthogonal curves being located on said tip portion of

said distal end; a guide operatively attached to said body portion to assist proper insertion of said distal end of said body portion into a subject's nasal passages; a flexible bulb operatively attached to said proximal end of said body portion,

said flexible bulb being configured to serve as a reservoir and as a device for increasing nasal

passage pressure, wherein a selected quantity of material disposed within said flexible bulb

may be directed into one or more of a subject's paranasal sinus cavities.

37. A method for delivering a material into one or more of a subject' s paranasal sinus

cavities, said method comprising: delivering a selected quantity of material into a subject's middle meatus; and applying pressure in the subject's nasal passages sufficient, and thereby

directing the material into one or more of the subject's paranasal sinus cavities.

38. The method of claim 37, wherein said step of applying pressure comprises increasing the pressure in the subject's nasal passages to at least 60 mm-Hg of pressure.

39. The method of 38, wherein said step of applying pressure further comprises increasing

the pressure in the subject's nasal passages to at least 80 mm-Hg of pressure.

40. The method of claim 37, further comprising, prior to said step of delivering a material into a subject's middle meatus, providing a device for delivering said material into the

subject's middle meatus.

41. The method of claim 38, wherein said step of providing a device for delivering

material into the subject's middle meatus includes providing a device comprising:

an elongated body portion having a proximal end and a distal end, said body portion having a passage therethrough from said proximal end to said distal end of said body

portion; said distal end of said body portion being anatomically curved for insertion of

said distal end into the middle meatus of a subject's nasal passages; and

said proximal end of said body portion being configured to receive a selected

quantity of material to be directed through said passage through said body portion and out

said distal end of said body portion of said device, wherein a selected quantity of a material

may be deposited in said passage through said body portion and delivered directly to the

middle meatus of a subject.

42. The method of claim 40, wherein said step of providing a device comprises optimizing said device for use in connection with a subject.

43. The method of claim 37, further comprising, prior to said step of delivering a selected

quantity of material into a subject's middle meatus, positioning the subject's head parallel to

the floor.

44. The method of claim 37, wherein said step of applying pressure comprises providing a

device for increasing nasal passage pressure.

45. The method of claim 44, wherein said step of providing a device for increasing nasal passage pressure comprises providing a flexible bulb.

46. The method of claim 44, wherein said step of providing a device for increasing nasal passage pressure comprises providing a syringe.

47. The method of claim 44, wherein said step of providing a device for increasing nasal

passage pressure comprises providing a clinical pressure system.

48. The method of claim 37, wherein said step of applying pressure comprises having the

subject perform Valsalva's maneuver.

49. The method of claim 37, wherein said step of applying pressure comprises having the subject perform a nose blow.

50. The method of claim 37, wherein said step of directing the material into one or more

of the subject's paranasal sinus cavities comprises delivering said therapeutic material.

51. The method of claim 37, wherein said step of directing the material into one or more of the subject's paranasal sinus cavities comprises delivering a diagnostic material into one or

more of the subject's paranasal sinus cavities.