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Claims  |
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I claim:
1. A method for diagnosing erectile dysfunction in a male individual,
comprising: (a) transurethrally administering to the individual a
vasodilating agent in an amount sufficient to induce erection of the
penis; (b) after erection has been induced, conducting penile hemodynamic
measurements, wherein the hemodynamic measurements include evaluation of
cavernosal artery peak systolic velocity, evaluation of cavernosal artery
end diastolic velocity, or both; and (c) determining from the results in
step (b) whether penile vascular insufficiency exists, such that it may be
concluded that the erectile dysfunction is or is not a result of
vasculogenic factors.
2. The method of claim 1, wherein the erectile dysfunction is impotence.
3. The method of claim 1, wherein the vasculogenic erectile dysfunction is
Peyronie's syndrome.
4. The method of claim 1, wherein step (a) is carried out by placing the
vasodilating agent in contact with the male urethra at a location between
the proximal portion of the fossa navicularis and the distal portion of
the pendulous urethra, such that the agent enters the individual's blood
stream through the urethral wall.
5. The method of claim 4, wherein the agent is administered in a dispersant
which releases the agent in the urethra at said depth at a weight ratio of
dispersant to agent of about 1:1 to 10:1, wherein the dose of agent is
selected so as not to exceed the dose retaining capacity of the urethra.
6. The method of claim 5, wherein approximately 50 mg of agent and
dispersant are administered transurethrally.
7. The method of claim 1, wherein a transurethral permeation enhancer is
administered with the vasodilating agent.
8. The method of claim 7, wherein the transurethral permeation enhancer and
vasodilating agent are administered simultaneously.
9. The method of claim 8, wherein the transurethral permeation enhancer and
vasodilating agent are administered in a single pharmaceutical
composition.
10. The method of claim 7, wherein the transurethral permeation enhancer
and vasodilating agent are administered sequentially.
11. The method of claim 1, wherein the vasodilating agent is selected from
the group consisting of nitrates, long- and short-acting .alpha.-blockers,
calcium blockers, ergot alkaloids, chlorpromazine, haloperidol, yohimbine,
natural and synthetic vasoactive prostaglandins and their analogs,
vasoactive intestinal peptides, dopamine agonists, opioid antagonists, and
mixtures thereof.
12. The method of claim 1, wherein step (b) is conducted using
ultrasonography.
13. The method of claim 12, wherein the ultrasonography is duplex
ultrasonography.
14. The method of claim 13, wherein step (b) is conducted by transmitting
ultrasound to each cavernosal artery, detecting ultrasound reflected
therefrom, detecting the frequency difference between the transmitted and
reflected ultrasound, and calculating the velocity of blood from the
frequency difference.
15. The method of claim 1, wherein step (b) is conducted using angiography.
16. The method of claim 1, wherein step (b) is conducted using a corpus
cavernosagram.
17. The method of claim 1, wherein the hemodynamic measurements include
evaluation of maximum arterial dilation.
18. A method for treating erectile dysfunction in a male individual,
comprising:
(a) determining whether or not the erectile dysfunction is due to
vasculogenic causes, comprising (i) transurethrally administering to the
individual a vasodilating agent in an amount sufficient to induce erection
of the penis, (ii) after erection has been induced, conducting penile
hemodynamic measurements, wherein the hemodynamic measurements include
evaluation of cavernosal artery peak systolic velocity, evaluation of
cavernosal artery end diastolic velocity, or both, (iii) determining from
the results in step (ii) whether penile vascular insufficiency exists,
thereby making a diagnosis as to whether the erectile dysfunction is
vasculogenic;
(b) if the diagnosis in step (a) is that the erectile dysfunction is
vasculogenic, transurethrally administering a vasodilating agent to the
patient within the context of a treatment regimen which is effective to
remedy the erectile dysfunction.
19. The method of claim 18, wherein step (b) is carried out by placing the
vasodilating agent in contact with the male urethra at a location between
the proximal portion of the fossa navicularis and the distal portion of
the pendulous urethra, such that the agent enters the individual's blood
stream through the urethral wall.
20. The method of claim 19, wherein the agent is administered in a
dispersant which releases the agent in the urethra at said depth at a
weight ratio of dispersant to agent of about 1:1 to 10:1, wherein the dose
of agent is selected so as not to exceed the dose retaining capacity of
the urethra.
21. The method of claim 18, wherein step (a)(ii) is conducted using
ultrasonography.
22. The method of claim 21, wherein the ultrasonography is duplex
ultrasonography.
23. The method of claim 22, wherein step (a)(ii) is conducted by
transmitting ultrasound to each cavernosal artery, detecting ultrasound
reflected therefrom, detecting the frequency difference between the
transmitted and reflected ultrasound, and calculating the velocity of
blood from the frequency difference.
24. The method of claim 18, wherein step (a)(ii) is conducted using
angiography.
25. The method of claim 18, wherein the hemodynamic measurements include
evaluation of maximum arterial dilation.
26. The method of claim 18, wherein the erectile dysfunction is impotence.
27. The method of claim 18, wherein the vasculogenic erectile dysfunction
is Peyronie's syndrome.
28. The method of claim 18, wherein approximately 50 mg of agent and
dispersant are administered transurethrally.
29. The method of claim 18, wherein a transurethral permeation enhancer is
administered with the vasodilating agent.
30. The method of claim 29, wherein the transurethral permeation enhancer
and vasodilating agent are administered simultaneously.
31. The method of claim 30, wherein the transurethral permeation enhancer
and vasodilating agent are administered in a single pharmaceutical
composition.
32. The method of claim 29, wherein the transurethral permeation enhancer
and vasodilating agent are administered sequentially.
33. The method of claim 18, wherein the vasodilating agent is selected from
the group consisting of nitrates, long- and short-acting .alpha.-blockers,
calcium blockers, ergot alkaloids, chlorpromazine, haloperidol, yohimbine,
natural and synthetic vasoactive prostaglandins and their analogs,
vasoactive intestinal peptides, dopamine agonists, opioid antagonists, and
mixtures thereof.
34. A method for diagnosing erectile dysfunction in a male individual,
comprising: (a) transurethrally administering to the individual a
vasodilating agent in an amount sufficient to induce erection of the
penis; (b) after erection has been induced, conducting penile hemodynamic
measurements using NMR spectroscopy; and (c) determining from the results
in step (b) whether penile vascular insufficiency exists, such that it may
be concluded that the erectile dysfunction is or is not a result of
vasculogenic factors.
35. The method of claim 34, wherein the erectile dysfunction is impotence.
36. The method of claim 34, wherein the vasculogenic erectile dysfunction
is Peyronie's syndrome.
37. The method of claim 34, wherein step (a) is carried out by placing the
vasodilating agent in contact with the male urethra at a location between
the proximal portion of the fossa navicularis and the distal portion of
the pendulous urethra, such that the agent enters the individual's blood
stream through the urethral wall.
38. The method of claim 37, wherein the agent is administered in a
dispersant which releases the agent in the urethra at said depth at a
weight ratio of dispersant to agent of about 1:1 to 10:1, wherein the dose
of agent is selected so as not to exceed the dose retaining capacity of
the urethra.
39. The method of claim 38, wherein approximately 50 mg of agent and
dispersant are administered transurethrally.
40. The method of claim 34, wherein a transurethral permeation enhancer is
administered with the vasodilating agent.
41. The method of claim 40, wherein the transurethral permeation enhancer
and vasodilating agent are administered simultaneously.
42. The method of claim 41, wherein the transurethral permeation enhancer
and vasodilating agent are administered in a single pharmaceutical
composition.
43. The method of claim 40, wherein the transurethral permeation enhancer
and vasodilating agent are administered sequentially.
44. The method of claim 40, wherein the vasodilating agent is selected from
the group consisting of nitrates, long- and short-acting .alpha.-blockers,
calcium blockers, ergot alkaloids, chlorpromazine, haloperidol, yohimbine,
natural and synthetic vasoactive prostaglandins and their analogs,
vasoactive intestinal peptides, dopamine agonists, opioid antagonists, and
mixtures thereof.
45. The method of claim 34, wherein the vasodilating agent is selected from
the group consisting of nitrates, long- and short-acting .alpha.-blockers,
calcium blockers, ergot alkaloids, chlorpromazine, haloperidol, yohimbine,
natural and synthetic vasoactive prostaglandins and their analogs,
vasoactive intestinal peptides, dopamine agonists, opioid antagonists, and
mixtures thereof.
46. A method for treating erectile dysfunction in a male individual,
comprising:
(a) determining whether or not the erectile dysfunction is due to
vasculogenic causes, comprising (i) transurethrally administering to the
individual a vasodilating agent in an amount sufficient to induce erection
of the penis, (ii) after erection has been induced, conducting penile
hemodynamic measurements using NMR spectroscopy, (iii) determining from
the results in step (ii) whether penile vascular insufficiency exists,
thereby making a diagnosis of the erectile dysfunction is vasculogenic;
(b) if the diagnosis in step (a) is that the erectile dysfunction is
vasculogenic, transurethrally administering a vasodilating agent to the
patient within the context of a treatment regimen which is effective to
remedy the erectile dysfunction.
47. The method of claim 46, wherein the erectile dysfunction is impotence.
48. The method of claim 46, wherein the vasculogenic erectile dysfunction
is Peyronie's syndrome.
49. The method of claim 46, wherein step (a) is carried out by placing the
vasodilating agent in contact with the male urethra at a location between
the proximal portion of the fossa navicularis and the distal portion of
the pendulous urethra, such that the agent enters the individual's blood
stream through the urethral wall.
50. The method of claim 49, wherein the agent is administered in a
dispersant which releases the agent in the urethra at said depth at a
weight ratio of dispersant to agent of about 1:1 to 10:1, the amount of
said dose not exceeding the dose retaining capacity of the urethra.
51. The method of claim 50, wherein the amount of agent and dispersant that
is administered transurethrally is approximately 50 mg. |
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Description |
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TECHNICAL FIELD
This invention relates generally to the diagnosis of erectile dysfunction.
More particularly, the invention relates to a novel noninvasive procedure
for diagnosing erectile dysfunction, particularly vasculogenic erectile
dysfunction, by measuring various penile hemodynamic parameters subsequent
to transurethral administration of a selected vasoactive agent. The
invention additionally relates to kits for carrying out the diagnostic
method, and to methods of treatment deriving from the diagnosis.
BACKGROUND
Impotence is the consistent inability to achieve or sustain an erection of
sufficient rigidity for sexual intercourse. It has recently been estimated
that approximately 10 million American men are impotent (R. Shabsigh et
al., "Evaluation of Erectile Impotence," Urology 32:83-90 (1988); W. L.
Furlow, "Prevalence of Impotence in the United States," Med. Aspects Hum.
Sex. 19:13-6 (1985)). Impotence is recognized to be an age-dependent
disorder, with an incidence of 1.9 percent at 40 years of age and 25
percent at 65 years of age (A. C. Kinsey et al., "Age and Sexual Outlet,"
in Sexual Behavior in the Human Male, A. C. Kinsey et al., eds.,
Philadelphia, Pa,: W. B. Saunders, 218-262 (1948)). In 1985 in the United
States, impotence accounted for more than several hundred thousand
outpatient visits to physicians (National Center for Health Statistics,
National Hospital Discharge Survey, 1985, Bethesda, Md., Department of
Health and Human Services, 1989 DHHS publication no. 87-1751). Depending
on the nature and cause of the problem, treatments include psychosexual
therapy, hormonal therapy, administration of vasodilators such as
nitroglycerin and .alpha.-adrenergic blocking agents (".alpha.-blockers"),
oral administration of other pharmaceutical agents, vascular surgery,
implanted penile prostheses, vacuum constriction devices and external aids
such as penile splints to support the penis or penile constricting rings
to alter the flow of blood through the penis.
A number of causes of impotence have been identified, including
vasculogenic, neurogenic, endocrinologic and psychogenic. Impotence can
also be a side effect of various classes of therapeutic drugs, or can be
associated with various diseases, including diabetes, multiple sclerosis
and sickle cell anemia. Impotence resulting from any one of these causes
can be exacerbated by additional factors such as cigarette smoking, a poor
diet, or the like.
Vasculogenic impotence occurs either as a result of arterial occlusion--the
obstruction of adequate blood flow to the penile arteries necessary for
erection--or as a result of cavernovenous leakage, i.e., excess venal
outflow. As explained by Krane et al., "Medical Progress: Impotence," The
New England Journal of Medicine 321(24):1628-1639 (1989), alteration in
the flow of blood to and from the penis is believed to be the most
frequent organic cause of impotence.
Current methods of diagnosing vasculogenic impotence or other vasculogenic
erectile disorders involve measurement of penile hemodynamics after
inducing an erection by direct injection of a vasoactive agent into the
corporal cavernosum. For example, T. I-Sheng Hwang et al., "Impotence
Evaluated by the Use of Prostaglandin E1," The Journal of Urology
141:1357-1359 (1989), describes a method for diagnosing impotence using
intracavernous injection of prostaglandin E1, followed by subcutaneous
injection of .sup.133 xenon to enable hemodynamic evaluation of penile
vascularity. Reference may also be had to R. Virag et al., "Intracavernous
Injection of Papaverine as a Diagnostic and Therapeutic Method in Erectile
Failure," Angiology--Journal of Vascular Diseases, February 1984, pp.
79-87, who describe a method for diagnosing erectile failure involving
intracavernous injection of papaverine and measurement of subsequent
arterial changes using Doppler ultrasound.
Such diagnostic techniques, involving injection of vasoactive agents using
a hypodermic needle, are painful and frequently unacceptable to patients.
In addition, intracorporeal injections have been associated with priapism,
development of fibrosis at the injection site and hematomas.
There is accordingly a need in the art for a noninvasive method of
diagnosing erectile dysfunction, particularly vasculogenic erectile
dysfunction. As used herein, the term "vasculogenic erectile dysfunction"
is used to refer not only to vasculogenic impotence, but also to
Peyronie's syndrome, a condition characterized by fibrosis of the
cavernous tissue and associated painful and distorted penile erection. The
term is also used to refer to erectile dysfunction resulting from local
vascularized injury or vasculogenic changes.
Accordingly, the method of the invention is useful to diagnose vasculogenic
erectile dysfunction, i.e., to determine whether or not a patient's
impotence is due to vasculogenic causes. Unlike the diagnostic methods of
the prior art, the present technique is noninvasive, fast, cost-effective,
and easy to perform.
SUMMARY OF THE INVENTION
Accordingly, it is a primary object of the present invention to address the
aforementioned need in the art, by providing a novel technique for
diagnosing erectile dysfunction, i.e., for determining whether or not a
patient's erectile dysfunction is due to vasculogenic causes.
It is another object of the invention to provide a method for diagnosing
vasculogenic erectile dysfunction which involves transurethral
administration of a vasodilating agent followed by measurement of penile
hemodynamics.
It is still another object of the invention to provide such a method
wherein the measurement of penile hemodynamics is conducted using
ultrasound or nuclear magnetic resonance ("NMR") spectroscopy.
It is yet another object of the invention to provide such a method wherein
the vasculogenic erectile dysfunction is impotence or Peyronie's syndrome.
It is a further object of the invention to provide such a method wherein
the hemodynamic parameters which are measured include cavernosal artery
peak systolic velocity, cavernosal artery end diastolic velocity, maximum
arterial dilation, and pressure.
It is still a further object of the invention to provide such a method
wherein the vasodilating agent is a nitrate (e.g., nitroglycerin,
isosorbide dinitrate, or nitric oxide compounds), a short-acting
.alpha.-blocker, an ergot alkaloid, or a prostaglandin.
Additional objects, advantages and novel features of the invention will be
set forth in part in the description which follows, and in part will
become apparent to those skilled in the art upon examination of the
following, or may be learned by practice of the invention.
In one aspect of the invention, a vasodilating agent is administered
transurethrally to the patient undergoing evaluation, in an amount
sufficient to induce erection of the penis and to maintain the erection
for a time period sufficient to allow measurement of the hemodynamic
parameters of interest. After erection has been induced, hemodynamic
parameters such as cavernosal artery peak systolic velocity (PSV)
cavernosal artery end diastolic velocity (EDV), and maximum arterial
dilation are evaluated, preferably using duplex ultrasonography, although
other techniques may be used as well. Pressure may also be measured, using
a simple cuffing technique or a corpus cavernosagram. Based on the results
of the hemodynamic evaluation, a determination is made as to whether there
is penile vascular insufficiency; this will generally be the case when the
measured PSV, EDV, maximum arterial dilation and/or pressure are below
certain predetermined values.
In another aspect of the invention, a method is provided for treating
erectile dysfunction. The method involves conducting the aforementioned
diagnostic procedure, determining whether the patient's erectile
dysfunction is due to vasculogenic causes, and treating the patient in a
manner that comports with the diagnosis.
In a further aspect of the invention, a kit is provided for conducting the
diagnostic method. Generally, the kit will include at minimum the drug to
be administered, a device for administering the drug transurethrally, a
sealed container housing the drug and device prior to use, and written
instructions for carrying out the diagnostic method. The kit may include a
means for administering the drug at different doses, or it may include
different drugs. Measurement instruments may be included in the kit as
well.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a cross-sectional view of one embodiment of a device which may be
used in conjunction with the present invention, to administer a drug
transurethrally.
FIG. 2 is a cross-sectional view of a second embodiment of such a device.
FIG. 3 is an exploded view of a penile insert which may be used in
conjunction with the present invention.
FIG. 4 is a side view, partly in section, of an inserter/container assembly
for introducing a drug into the urethra.
FIG. 5 is a top view of the inserter/container of FIG. 4.
FIG. 6 is a side view of another inserter construction for introducing a
drug into the urethra.
FIG. 7 is a cross-section through the inserter of FIG. 6 in the filling
position.
FIG. 8 is a cross-section through the inserter of FIG. 6 in the loaded
position.
FIG. 9 is an exploded view of a further embodiment of a device which may be
used in conjunction with the present method.
FIGS. 10 through 13 are graphs illustrating a comparison of a diagnostic
method using transurethral administration of a vasodilating agent with the
diagnostic method of the prior art, wherein the vasodilating agent is
administered by intracorporeal injection.
DETAILED DESCRIPTION OF THE INVENTION
Before describing the present invention in detail, it is to be understood
that this invention is not limited to particular drugs, transurethral
delivery systems or equipment for conducting penile hemodynamic
measurements, as such may, of course, vary. It is also to be understood
that the terminology used herein is for the purpose of describing
particular embodiments only, and is not intended to be limiting.
It must be noted that, as used in this specification and the appended
claims, the singular forms "a", "an" and "the" include plural referents
unless the context clearly dictates otherwise. Thus, for example,
reference to "a vasodilating agent" or "vasodilator" includes a mixture of
two or more such agents, reference to "a transurethral permeation
enhancer" includes mixtures of two or more enhancers, and the like.
In describing and claiming the present invention, the following terminology
will be used in accordance with the definitions set out below.
The terms "transurethral" or "intraurethral" as used to specify the mode of
administration of vasodilator are used interchangeably to refer to
delivery of the drug into the urethra such that drug contacts and passes
through the wall of the urethra and enters into the bloodstream.
"Penetration enhancement" or "permeation enhancement" as used herein
relates to an increase in the permeability of the skin or mucosal tissue
to a selected pharmacologically active agent, i.e., so as to increase the
rate at which the drug permeates through the skin and enters the
bloodstream. "Transurethral permeation enhancers" increase the
permeability of the urethral wall to drugs administered as described
herein.
"Carriers" or "vehicles" as used herein refer to carrier materials suitable
for transurethral drug administration, and include any such materials
known in the art, e.g., any liquid, gel, solvent, liquid diluent,
solubilizer, or the like, which is nontoxic and which does not interact
with other components of the composition in a deleterious manner.
In order to carry out the method of the invention, a selected vasodilating
agent is initially administered transurethrally to induce an erection.
Suitable vasodilators include, but are not limited to: nitrates such as
nitroglycerin and isosorbide dinitrate; long and short acting
.alpha.-blockers such as phenoxybenzamine, dibenamine, doxazosin,
terazosin, phentolamine, tolazoline, prazosin and trimazosin; ergot
alkaloids such as ergotamine and ergotamine analogs, e.g., acetergamine,
brazergoline, bromerguride, cianergoline, delorgotrile, disulergine,
ergonovine maleate, ergotamine tartrate, etisulergine, lergotrile,
lysergide, mesulergine, metergoline, metergotamine, nicergoline,
pergolide, propisergide, proterguride and terguride; antihypertensive
agents such as diazoxide, hydralazine and minoxidil; chlorpromazine;
haloperidol; yohimbine; naturally occurring prostaglandins such as
PGE.sub.1, PGA.sub.1, PGB.sub.1, PGF.sub.1.alpha., 19-hydroxy-PGA.sub.1,
19-hydroxy-PGB.sub.1, PGE.sub.2, PGA.sub.2, PGB.sub.2,
19-hydroxy-PGA.sub.2, 19-hydroxy-PGB.sub.2, PGE.sub.3, and
PGF.sub.3.alpha. ; semisynthetic or synthetic derivatives of natural
prostaglandins, including carboprost tromethamine, dinoprost tromethamine,
dinoprostone, gemeprost, metenoprost, sulprostone and tiaprost; vasoactive
intestinal peptides; and any other agent which is capable of producing an
erection when administered transurethrally. For example, dopamine agonists
such as apomorphine and bromocriptine, and opioid antagonists such as
naltrexone have been reported to induce erection and they may also be
useful in conjunction with this invention. See S. Lal et al.,
"Apomorphine: Clinical Studies on Erectile Impotence and Yawning," Prog.
Neuropsychopharmacology 13:329-339 (1989) and A. Fabbri et al.,
"Endorphins in Male Impotence, Evidence for Naltrexone Stimulation of
Erectile Activity in Patient Therapy," Psychoneuroendocrinology
14(89):103-111.
Additionally, simultaneous administration of two or more vasodilating
agents may be desirable and may in some cases exhibit a synergistic
effect.
The vasodilator will typically be administered in a pharmaceutical
composition containing one or more selected carriers or excipients, as
noted above. Examples of suitable carriers for use herein include water,
silicone, waxes, petroleum jelly, polyethylene glycol, propylene glycol,
liposomes, sugars such as mannitol and lactose, and a variety of other
materials. The composition may also include transurethral permeation
enhancers, e.g., dimethylsulfoxide (DMSO), dimethyl formamide (DMF),
N,N-dimethylacetamide (DMA), decylmethylsulfoxide (C.sub.10 MSO),
polyethylene glycol monolaurate (PEGML), glycerol monolaurate, lecithin,
the 1-substituted azacycloheptan-2-ones, particularly
1-n-dodecylcyclazacycloheptan-2-one (available under the trademark
Azone.RTM. from Nelson Research & Development Co., Irvine, Calif.),
alcohols, or the like.
The amount of vasodilating agent administered is selected such that it is
sufficient to induce an erection. As explained in co-pending patent
application Ser. No. 07/514,397, entitled "Treatment of Erectile
Dysfunction" (published internationally as WO91/16021), the disclosure of
which is incorporated by reference herein, transurethral administration of
vasodilator can be carried out in a number of different ways. For example,
the drug can be introduced into the urethra from a flexible tube, squeeze
bottle, pump or aerosol spray. The agent may also be contained in
coatings, pellets or suppositories which are absorbed, melted or bioeroded
in the urethra. In certain embodiments which are illustrated in FIGS. 1
and 3, the agent is included in a coating on the exterior surface of a
penile insert.
Referring now to FIG. 1, a penile insert 1 comprises a shaft portion 2
which is sized to be easily and comfortably inserted into the male
urethra. It is preferable, however, that the end of shaft 2 is provided
with an enlarged terminal portion 3 configured to prevent complete
insertion into the urethra and to facilitate removal of the device after
the agent has been delivered. The internal end of shaft portion 2 is
preferably provided with a rounded, blunted end to prevent discomfort on
insertion and is typically from about 3 to 5 millimeters in diameter and
from about 2 to 12 centimeters in length.
The insert itself may be made from any pharmacologically acceptable
material and although it may be rigid, it is preferred that the device be
relatively soft and flexible for purposes of comfort, merely having
sufficient rigidity to facilitate insertion. For this purpose, various
pharmaceutically acceptable natural or synthetic rubber or polymeric
materials may be used, such as natural rubber, silicone rubber, ethylene
vinyl acetate (EVA) copolymers, polyethylene, polypropylene,
polycarbonate, polyester, polyurethane and polyisobutylene polymers.
Although the vasoactive agent and any carriers, enhancers, or the like may
be dispersed throughout the body of the insert 1, it is preferable that
the agent be concentrated on the urethra-contacting surfaces of the device
in order to permit rapid absorption of the agent and any carrier,
enhancer, or the like. As shown in FIG. 1, the shaft portion 2 of the
insert 1 is provided with an agent-containing coating 4 which comprises
the desired agent dose and, if used, a permeation enhancer, dispersed
throughout a rapidly releasing carrier. The coating 4 may be applied to
the insert by means of dip coating in an appropriate agent-containing
bath, spray coating, heat melt coating, evaporation of a fixed volume of a
solution or suspension of the agent in a volatile vehicle or by
co-extrusion of an agent-containing layer onto the surface of shaft 2, for
example.
To facilitate insertion, coating 4 preferably has lubricating properties
and may contain materials such as polyethylene glycol ("PEG"), propylene
glycol, or hydroxy alkyl celluloses, for example, which are or become
slippery upon insertion into the urethra. Materials such as glycerol
monolaurate, polyethylene glycol monolaurate, and glycerol monolaurate,
for example, may combine permeation enhancing properties with lubricating
properties.
To facilitate adherence of the drug coatings to the penile insert, the
surfaces to which the coatings are applied may be slightly roughened.
Also, to provide a visual indication of complete agent release, the
coating, instead of being clear and transparent, can be selected to
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