U.S. patent application number 10/232261 was filed with the patent office on 2003-02-13 for osmotic pump drug delivery systems and methods.
This patent application is currently assigned to MicroSolutions, Inc.. Invention is credited to Harper, Derek J., Milo, Charles F..
Application Number | 20030032947 10/232261 |
Document ID | / |
Family ID | 24003652 |
Filed Date | 2003-02-13 |
United States Patent
Application |
20030032947 |
Kind Code |
A1 |
Harper, Derek J. ; et
al. |
February 13, 2003 |
Osmotic pump drug delivery systems and methods
Abstract
Implantable osmotic pump devices and systems include multiple
osmotic pumps and/or semipermeable membranes to extend the useful
life cycle and functionality of the drug delivery system. Use of an
implantable system including multiple implantable osmotic pumps
allows different drugs to be administered from the same implanted
system. One or more of the semipermeable membranes of the system
may be initially sealed by an overlying impermeable membrane upon
implantation of the system into the patient. When the patient
develops a tolerance to a first drug or to a first dose of the
first drug, the impermeable membrane may be breached, to expose the
underlying semipermeable membrane to the osmotic pressure of the
patient at the implant site. This causes the infusion rate to
increase, thereby providing the patient with the needed relief
and/or other desired therapeutic effect. In the case of a multiple
pump system, breaching an impermeable membrane may cause the
infusion of a second drug. The second drug may potentiate a
therapeutic effect (such as an analgesic effect) of the first drug,
as is the case with Sufentanil and Clonidine.
Inventors: |
Harper, Derek J.; (Sana
Barbara, CA) ; Milo, Charles F.; (Atherton,
CA) |
Correspondence
Address: |
YOUNG LAW FIRM
A PROFESSIONAL CORPORATION
4370 ALPINE ROAD SUITE 106
PORTOLA VALLEY
CA
94028
|
Assignee: |
MicroSolutions, Inc.
|
Family ID: |
24003652 |
Appl. No.: |
10/232261 |
Filed: |
August 29, 2002 |
Related U.S. Patent Documents
|
|
|
|
|
|
Application
Number |
Filing Date |
Patent Number |
|
|
10232261 |
Aug 29, 2002 |
|
|
|
09503821 |
Feb 15, 2000 |
|
|
|
6471688 |
|
|
|
|
Current U.S.
Class: |
604/892.1 |
Current CPC
Class: |
A61M 2005/14513
20130101; A61M 2205/16 20130101; A61M 5/16827 20130101; A61M 5/145
20130101; A61M 5/14276 20130101 |
Class at
Publication: |
604/892.1 |
International
Class: |
A61K 009/22 |
Claims
What is claimed is:
1. An implantable osmotic pump system, comprising: a first osmotic
pump including a first semipermeable membrane; a second osmotic
pump including a second semipermeable membrane, and a single
catheter attached to both the first and the second osmotic
pumps.
2. The pump system of claim 1, wherein the catheter includes a
first lumen and a second lumen, the first lumen being connected to
the first osmotic pump and the second lumen being connected to the
second pump.
3. The pump system of claim 1, wherein the catheter includes a
single lumen with two side arms, one of the two side arms being
attached to the first pump and the other of the two side arms being
attached to the second pump, each of two side arms including an
internal lumen that feeds into the single lumen.
4. The pump system of claim 1, wherein the second semipermeable
membrane is sealed by an impermeable membrane.
5. The pump system of claim 4, wherein the impermeable membrane is
disposed over and away from said one of the first and second
semipermeable membranes so as to define a fluid tight compartment
therewith, the fluid tight compartment being filled with a
saturated saline solution.
6. The pump system of claim 4, wherein the impermeable membrane is
adapted to be punctured with a lancet when the pump system is
implanted in a patient.
7. The pump system of claim 4, wherein the impermeable membrane
comprises at least one of titanium, stainless steel, platinum,
platinum-iridium, polyethylene, PET and PETG.
8. The pump system of claim 1, wherein the first and second pumps
are preloaded with at least one pharmaceutical agent.
9. The pump system of claim 1, wherein the first pump is preloaded
with a first pharmaceutical agent at a first therapeutically
effective concentration and wherein the second pump is preloaded
with a second pharmaceutical agent at a second therapeutically
effective concentration.
10. The pump system of claim 9, wherein the first pharmaceutical
agent is a same pharmaceutical agent as the second pharmaceutical
agent.
11. The pump system of claim 10, wherein the first concentration is
a same concentration as the second concentration.
12. The pump system of claim 9, wherein the first pharmaceutical
agent is a different pharmaceutical agent than the second
pharmaceutical agent.
13. The pump system of claim 9, wherein the first pharmaceutical
agent potentiates a therapeutic property of the second
pharmaceutical agent.
14. The pump system of claim 9, wherein the first pharmaceutical
agent is an opioid and wherein the second pharmaceutical agent
includes a drug that potentiates an analgesic property of the first
pharmaceutical agent.
15. The pump system of claim 14, wherein the first pharmaceutical
agent includes Sufentanil and wherein the drug includes an alpha
2-adrenoreceptor agonist.
16. The pump system of claim 15, wherein the alpha 2-adrenoreceptor
agonist includes at least one of Clonidine and derivatives of
Clonidine
17. The pump system of claim 4, wherein the first and second pumps
are preloaded with at least one pharmaceutical agent.
18. The pump system of claim 4, wherein the first pump is preloaded
with a first pharmaceutical agent at a first therapeutically
effective concentration and wherein the second pump is preloaded
with a second pharmaceutical agent at a second therapeutically
effective concentration.
19. The pump system of claim 18, wherein the first pharmaceutical
agent is a same pharmaceutical agent as the second pharmaceutical
agent.
20. The pump system of claim 19, wherein the first concentration is
a same concentration as the second concentration.
21. The pump system of claim 18, wherein the first pharmaceutical
agent is a different pharmaceutical agent than the second
pharmaceutical agent.
22. The pump system of claim 18, wherein the first pharmaceutical
agent potentiates a therapeutic property of the second
pharmaceutical agent.
23. The pump system of claim 18, wherein the first pharmaceutical
agent is an opioid and wherein the second pharmaceutical agent
includes a drug that potentiates an analgesic property of the first
pharmaceutical agent.
24. The pump system of claim 23, wherein the first pharmaceutical
agent includes Sufentanil and wherein the drug includes an alpha
2-adrenoreceptor agonist.
25. The pump system of claim 24, wherein the alpha 2-adrenoreceptor
agonist includes Clonidine.
26. The pump system of claim 4, wherein the first pump is preloaded
with a first opioid and wherein the first pump is adapted to infuse
the first opioid at a first therapeutically effective range of
concentration and wherein the second pump is preloaded with a
second opioid and wherein the second pump is adapted to infuse the
second opioid at a second therapeutically effective range of
concentration after the semipermeable membrane is breached.
27. The pump system of claim 26, wherein the first opioid includes
one of Fentanyl and Sufentanil and wherein the second opioid
includes one of Fentanyl and Sufentanil.
28. The pump of claim 26, wherein the first opioid is a same opioid
as the second opioid and wherein the second pump is adapted to
infuse the second opioid at the first therapeutically effective
range when the first pump is out of the first opioid, upon
breaching the impermeable membrane.
29. A kit, comprising: a first osmotic pump including a first
semipermeable membrane; a second osmotic pump including a second
semipermeable membrane, and a single catheter adapted to attach to
both the first and the second osmotic pumps.
30. The kit of claim 29, wherein the catheter includes a first
lumen and a second lumen, the first lumen being adapted to connect
to the first osmotic pump and the second lumen being adapted to
connect to the second pump.
31. The kit of claim 29, wherein the catheter includes a single
lumen with two side arms, one of the two side arms being adapted to
attach to the first pump and the other of the two side arms being
adapted to attach to the second pump, each of two side arms
including an internal lumen that feeds into the single lumen.
32. The kit of claim 29, wherein the second semipermeable membrane
is sealed by an impermeable membrane.
33. The kit of claim 32, wherein the impermeable membrane is
disposed over and away from the said one of the first and second
semipermeable membrane so as to define a fluid tight compartment
therewith, the fluid tight compartment being filled with a
saturated saline solution.
34. The kit of claim 32, further including a lancet configured to
breach the impermeable membrane.
35. The kit of claim 29, wherein the first osmotic pumps is
preloaded with a first pharmaceutical agent and wherein the second
pump is preloaded with a second pharmaceutical agent.
36. The kit of claim 35, wherein the first pharmaceutical agent is
a same pharmaceutical agent as the second pharmaceutical agent.
37. The kit of claim 35, wherein the first pharmaceutical agent is
a different pharmaceutical agent as the second pharmaceutical
agent.
38. A drug delivery method, comprising the steps of: infusing a
first drug at a first therapeutically effective range of
concentration from a first implanted osmotic pump; infusing a
second drug at a second therapeutically effective range of
concentration from a second implanted osmotic pump; preventing the
first and second drugs from mixing until both the first and second
drugs reach an intended delivery site.
39. The method of claim 38, wherein the preventing step is carried
out by attaching a catheter having a first and a second lumen to
the first and second osmotic pumps, the first lumen being in fluid
communication with the first osmotic pump and the second lumen
being in fluid communication with the second osmotic pump, a free
end of the catheter being disposed at the intended delivery
site.
40. The method of claim 38, wherein the first and second drugs are
therapeutically effective for at least one therapy selected from
pain therapy, hormone therapy, gene therapy, angiogenic therapy,
anti-tumor therapy, chemotherapy and/or other pharmaceutical
therapies.
41. An implantable osmotic pump system, comprising: a first osmotic
pump, including a first semipermeable membrane; a first impermeable
membrane initially sealing the first semipermeable membrane; a
second semipermeable membrane and a second impermeable membrane
initially sealing the second semipermeable membrane, and a second
osmotic pump, including a third semipermeable membrane; a third
impermeable membrane initially sealing the third semipermeable
membrane; a fourth semipermeable membrane and a fourth impermeable
membrane initially sealing the fourth semipermeable membrane.
42. The pump system of claim 41, wherein each of the first and
second pumps includes a proximal end, a distal end and a side wall
and wherein at least one of the first and second initially sealed
semipermeable membranes is fitted to a side wall of the first pump
and wherein at least one of the third and fourth initially sealed
semipermeable membranes is fitted to a side wall of the second
pump.
43. The pump system of claim 41, wherein each of the first and
second pumps includes a proximal and a distal end, and wherein a
catheter is attached to the distal end of the first pump is and to
the distal end of the second pump.
44. The pump system of claim 43, wherein the catheter includes a
first lumen and a second lumen, the first lumen being in fluid
communication with a pharmaceutical agent compartment of the first
pump and the second lumen being in fluid communication with a
pharmaceutical agent compartment of the second pump.
45. The pump system of claim 43, wherein the catheter includes a
single lumen with two side arms, one of the two side arms being
attached to the first pump and the other of the two side arms being
attached to the second pump, each of two side arms including an
internal lumen that feeds into the single lumen.
46. The pump system of claim 41, wherein each of the first to
fourth impermeable membranes is disposed over and away from the
first to fourth semipermeable membranes, respectively, so as to
define a first to fourth fluid tight compartment therewith,
respectively, each of the first to fourth fluid tight compartments
being filled with a saturated saline solution.
47. The pump system of claim 46, wherein each of the first to
fourth impermeable membranes is adapted to be punctured with a
lancet when the pump system is implanted in a patient.
48. The pump system of claim 41, wherein each of the first to
fourth impermeable membranes comprises at least one of titanium,
stainless steel platinum-iridium, polyethylene, PET and PETG.
49. The pump system of claim 41, wherein the first and second pumps
are preloaded with at least one pharmaceutical agent.
50. The pump system of claim 41, wherein the first pump is
preloaded with a first pharmaceutical agent at a first
therapeutically effective concentration and wherein the second pump
is preloaded with a second pharmaceutical agent at a second
therapeutically effective concentration.
51. The pump system of claim 50, wherein the first pharmaceutical
agent is a same pharmaceutical agent as the second pharmaceutical
agent.
52. The pump system of claim 51, wherein the first concentration is
a same concentration as the second concentration.
53. The pump system of claim 50, wherein the first pharmaceutical
agent is a different pharmaceutical agent than the second
pharmaceutical agent.
54. The pump system of claim 50, wherein the first pharmaceutical
agent potentiates a therapeutic property of the second
pharmaceutical agent.
55. The pump system of claim 50, wherein the first pharmaceutical
agent is an opioid and wherein the second pharmaceutical agent
includes a drug that potentiates an analgesic property of the first
pharmaceutical agent.
56. The pump system of claim 55, wherein the first pharmaceutical
agent includes Sufentanil and wherein the drug includes an alpha
2-adrenoreceptor agonist.
57. The pump system of claim 56, wherein the alpha 2-adrenoreceptor
agonist includes Clonidine.
58. The pump system of claim 50, wherein the first pharmaceutical
agent includes a first opioid and wherein the second pharmaceutical
agent includes a second opioid.
59. The pump system of claim 58, wherein the first opioid includes
one of Fentanyl and Sufentanil and wherein the second opioid
includes one of Fentanyl and Sufentanil.
60. The pump system of 41, wherein the first pump is adapted to
deliver a dose of Fentanyl of about 10 to about 300 milligrams per
day and wherein the second pump is adapted to deliver a dose of
Sufentanil of about 1 to about 25 micrograms per day.
61. The pump system of claim 59, wherein the second opioid includes
a combination of Sufentanil and Fentanyl.
62. The pump system of claim 56, wherein the drug includes a
combination of Sufentanil and the alpha 2-adrenoreceptor
agonist.
63. The pump system of claim 62, wherein the alpha 2-adrenoreceptor
agonist includes Clonidine.
64. The pump system of 41, wherein the first pump is adapted to
deliver a dose of Sufentanil of about 1 to about 25 micrograms per
day and wherein the second pump is adapted to deliver a dose of
Clonidine of about 25 to about 150 micrograms per day.
65. Method of using the pump system of claim 50, comprising the
steps of: breaching the first impermeable membrane; implanting the
pump system into a patient to start infusion of the first
pharmaceutical agent at a first therapeutically effective dose;
breaching the second impermeable membrane to start infusion of the
first pharmaceutical agent at a second therapeutically effective
dose when the patient develops a tolerance to the first dose;
breaching the third impermeable membrane to start infusion of the
second pharmaceutical agent at a third therapeutically effective
dose when the patient develops a tolerance to the first
pharmaceutical agent, and breaching the fourth impermeable membrane
to start infusion of the second pharmaceutical agent at a fourth
therapeutically effective dose when the patient develops a
tolerance to the third dose.
66. The method of claim 65, wherein the breaching steps are carried
out by puncturing the first to fourth impermeable membranes with a
lancet.
67. An implantable osmotic pump, comprising: a pump housing having
a proximal end, a distal end and a sidewall, the pump housing
defining a pharmaceutical agent compartment and an osmotic agent
compartment, the pharmaceutical agent compartment being separated
from the osmotic agent compartment by a movable piston; a first
semipermeable membrane fitted to the proximal end and a second
semipermeable membrane fitted to a portion of the sidewall defining
the osmotic engine compartment, both the first and second
semipermeable membranes being adapted to allow water to cross into
the osmotic engine compartment; an impermeable membrane sealing the
second semipermeable membrane, and an integrated lancet adapted to
breach the impermeable membrane.
68. The pump of claim 67, wherein the integrated lancet mechanism
is adapted to breach the impermeable membrane upon a manual
application of force on the mechanism.
69. The pump of claim 67, wherein the lancet mechanism includes a
spring biasing a lancet away from the impermeable membrane.
70. The pump of claim 67, wherein the integrated lancet mechanism
includes a plurality of through holes, the through holes allowing
water into the mechanism and in contact with the second
semipermeable membrane when the impermeable membrane is
breached.
71. The pump of claim 67, wherein the pharmaceutical agent
compartment is preloaded with a pharmaceutical agent and wherein
the pump is configured to infuse the pharmaceutical agent at a
first rate based upon a composition, thickness and surface area of
the first semipermeable membrane when the impermeable membrane is
intact and is configured to infuse the pharmaceutical agent at a
second infusion rate when the impermeable membrane has been
breached.
72. The pump of claim 71, wherein the second rate is based upon a
composition, thickness and surface area of the first and the second
semipermeable membranes.
73. The pump of claim 71, wherein the pharmaceutical agent includes
Fentanyl.
74. The pump of claim 73, wherein each of the first and second
rates is selected within the range of about 10 to about 300
milligrams per day.
75. The pump of claim 71, wherein the pharmaceutical agent includes
a combination of Fentanyl and Sufentanil.
76. The pump of claim 75, wherein each of the first and second
rates is selected within the range of about 1 to about 25
micrograms per day for Sufentanil and within the range of about 10
to about 30 milligrams per day of Fentanyl.
77. The pump of claim 71, wherein the pharmaceutical agent includes
a combination of Sufentanil and Clonidine.
78. The pump of claim 77, wherein each of the first and second
rates is selected within a range of about 1 to about 25 micrograms
per day for Sufentanil and within a range of about 25 to about 150
micrograms per day for Clonidine.
79. The pump of claim 67, wherein the pharmaceutical agent
compartment is preloaded with at least one pharmaceutical agent
that is therapeutically effective for at least one therapy selected
from a group including pain management, hormone therapy, gene
therapy, angiogenic therapy, anti-tumor therapy, chemotherapy
and/or other therapies.
80. A method of delivering a pharmaceutical agent, comprising the
steps of: implanting an osmotic pump including a first and a second
semipermeable membrane, the second impermeable membrane being
initially sealed by an impermeable membrane, the pump including an
integrated lancet mechanism adapted to breach the impermeable
membrane; infusing the pharmaceutical agent at a first infusion
rate based upon a composition, thickness and surface area of the
first semipermeable membrane; applying force to the lancet
mechanism to cause the mechanism to breach the impermeable membrane
and expose the initially sealed second semipermeable membrane, and
infusing the pharmaceutical agent at a second infusion rate that is
higher than the first infusion rate, the second infusion rate being
based upon a composition, thickness and surface area of the first
and the second semipermeable membranes.
81. The method of claim 80, wherein the force applying step is
carried out while the pump is implanted.
82. The method of claim 80, further including a step of palpating
or imaging the implanted pump to locate the integrated lancet
mechanism thereof prior to the force-applying step.
83. An implantable osmotic pump system, comprising: a pump housing
having a proximal end, a distal end and a sidewall, the pump
housing defining a pharmaceutical agent compartment and an osmotic
agent compartment, the pharmaceutical agent compartment being
separated from the osmotic agent compartment by a movable piston; a
first semipermeable membrane fitted to a portion of the sidewall
defining the osmotic engine compartment, the first semipermeable
membrane being adapted to allow water to cross into the osmotic
engine compartment; a first sealing member covering and sealing the
first semipermeable membrane.
84. The system of claim 83, further comprising a catheter attached
to the distal end of the pump housing, the catheter being in fluid
communication with the pharmaceutical agent compartment.
85. The system of claim 83, wherein the proximal end of the pump
housing is impermeable to water.
86. The system of claim 83, wherein the first sealing member
includes a spacer fitted to the sidewall, the spacer including an
impermeable membrane that is adapted to be breached by a
lancet.
87. The system of claim 86, wherein the pump housing and the spacer
are configured to allow the spacer to be screwed on the
sidewall.
88. The system of claim 86, wherein the spacer is fitted to the
pump housing by an ultrasonic weld.
89. The system of claim 86, wherein the impermeable membrane
includes at least one of titanium and stainless steel,
platinum-iridium, polyethylene, PET and PETG.
90. The system of claim 83, further comprising: at least one second
semipermeable membrane fitted to the portion of the sidewall
defining the osmotic engine compartment, the at least one second
semipermeable membrane being adapted to allow water to cross into
the osmotic engine compartment; at least one second sealing member
covering and sealing a respective one of the at least one second
semipermeable membrane.
91. The system of claim 90, wherein the first and the at least one
second sealing members each include a spacer fitted to the
sidewall, the spacer including an impermeable membrane that is
adapted to be breached by a lancet.
92. The system of claim 91, wherein the impermeable membrane is
visible under fluoroscopy.
93. The system of claim 83, wherein at least the portion of the
sidewall defining the osmotic engine compartment is substantially
flat.
94. The system of claim 83, wherein the pump housing has a
generally rectangular shape with rounded atraumatic edges.
95. The system of claim 83, wherein the first sealing member
includes a first integrated lancet mechanism attached thereto, the
integrated lancet mechanism being adapted to breach the first
sealing member to expose the first semipermeable membrane.
96. The system of claim 83, wherein the pharmaceutical agent
compartment is preloaded with a pharmaceutical agent and wherein
the pharmaceutical agent includes Fentanyl.
97. The system of claim 96, wherein the pump system is configured
to infuse Fentanyl within a range of about 10 to about 300
milligrams per day.
98. The system of claim 96, wherein the pump system is configured
to infuse Sufentanil within a range of about 1 to about 25
micrograms per day.
99. The system of claim 83, wherein the pharmaceutical agent
compartment is preloaded with a pharmaceutical agent and wherein
the pharmaceutical agent includes a combination of Fentanyl and
Sufentanil.
100. The system of claim 99, wherein the pump system is configured
to infuse the combination of Fentanyl within a range of about 10 to
about 300 micrograms per day and Sufentanil within a range of about
1 to about 25 micrograms per day.
101. The system of claim 83, wherein the pharmaceutical agent
compartment is preloaded with a pharmaceutical agent and wherein
the pharmaceutical agent includes a combination of Sufentanil and
Clonidine, the Sufentanil being infused at within a range of about
1 to about 25 micrograms per day and the Clonidine being infused
within a range of about 25 to about 150 micrograms per day.
102. The system of claim 83, wherein the pharmaceutical agent
compartment is preloaded with at least one pharmaceutical agent
that is therapeutically effective for at least one therapy selected
from a group including pain management, hormone therapy, gene
therapy, angiogenic therapy, anti-tumor therapy, chemotherapy
and/or other therapies.
103. The kit of claim 37, wherein the first pharmaceutical agent
includes Fentanyl and the second pharmaceutical agent includes
Sufentanil.
104. The kit of claim 37, wherein the first pharmaceutical agent
includes Sufentanil and the second pharmaceutical agent includes
Clonidine.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is related in subject matter to commonly
assigned co-pending patent application Ser. No. 09/442,128 filed on
Nov. 16, 1999 entitled "Methods And Implantable Devices And Systems
For Long Term Delivery Of A Pharmaceutical Agent" (attorney docket
MICR5591), the disclosure of which is hereby incorporated herein in
its entirety.
[0002] This application is also related in subject matter to
commonly assigned co-pending patent application Ser. No. ______
filed on ______ and entitled "Osmotic Pump Delivery System With
Pre-Hydrated Membranes(s) And/Or Primable Catheter" (attorney
docket MICR5646), the disclosure of which is also hereby
incorporated herein in its entirety.
[0003] This application is also related in subject matter to
commonly assigned co-pending patent application Ser. No. ______
filed on ______ and entitled "Osmotic Pump Delivery System With
Flexible Drug Compartment" (attorney docket MICR5647), the
disclosure of which is also hereby incorporated herein in its
entirety.
BACKGROUND OF THE INVENTION
[0004] 1. Field of the Invention
[0005] The present invention relates generally to the field of drug
delivery systems. In particular, the present invention relates to
osmotic pump systems, devices, kits and associated methods for
shortening the time interval between implantation of the osmotic
pump system and delivery of a pharmaceutical agent to the patient.
The present invention also relates to osmotic implantable systems
and methods for delivering multiple drugs simultaneously (and/or
sequentially), implantable osmotic systems having redundant pumps,
as well as systems, methods and kits for delivering mixtures of
drugs and/or potentiating drugs.
[0006] 2. Description of the Related Art
[0007] Since the beginning of modern medicine, drugs have been
administered orally. Patients have taken pills as recommended by
their physician. The pills must pass through the digestive system
and then the liver before they reach their intended delivery site
(e.g., the vascular system). The actions of the digestive tract and
the liver often reduce the efficacy of medication; furthermore,
medications delivered systemically sometimes cause undesirable side
effects. Over the course of the past few decades, drug delivery
technology and administration has evolved from oral delivery to
site-specific delivery. In addition to the oral route of
administration, drugs are also routinely administered via the
vascular system (intravenous or IV). Intravenous drug delivery has
the advantage of bypassing the acidic and enzymatic action of the
digestive system. Unfortunately, IV administration requires the use
of a percutaneous catheter or needle to deliver the drug to the
vein. The percutaneous site requires extra cleanliness and
maintenance to minimize the risk of infection. Infection is such a
significant risk that IV administration is often limited to a
number of weeks, at most. In addition, the patient must wear an
external pump connected to the percutaneous catheter.
[0008] The next step in the evolution of drug delivery was the
implanted pump. The implanted pump is a device that is completely
implanted under the skin of a patient, thereby negating the need
for a percutaneous catheter. These implanted pumps provide the
patient with a drug at a constant or a programmed delivery rate.
Constant rate or programmable rate pumps are based on either
phase-change or peristaltic technology. When a constant, unchanging
delivery rate is required, a constant-rate pump is well suited for
long-term implanted drug delivery. If changes to the infusion rate
are expected, a programmable pump may be used in place of the
constant rate pump. Fully implanted constant rate and programmable
rate infusion pumps have been sold in the United States for human
use since the late 1970s and early 1980s, respectively. Two
problems associated with such 1970s and 1980s vintage constant rate
and programmable rate infusion pumps relate to their size and their
cost. Current implantable constant rate and programmable pumps are
about the size and shape of hockey pucks, and they typically are
sold to the hospital for $5,000-$9,000. The current implantable
pumps must be implanted in the Operating Room under general
anesthesia, which further increases costs, as well as the risk, and
discomfort to the patient. The size and cost of such pumps has
proven to be a substantial barrier to their use, and they are
rarely used to deliver medication. An added drawback of
phase-change and peristaltic pumps is that they must be refilled
with drug every 3-8 weeks. Refills constitute an added burden to
the caregiver, and add further costs to an already overburdened
healthcare system. The burden associated with such refills,
therefore, further limits the use of phase-change and peristaltic
pumps.
[0009] In the 1970s, a new approach toward implanted pump design
was commercialized for animal use only. The driving force of the
pumps based upon this new approach utilized the principle of
osmosis. Osmotic pumps may be much smaller than other constant rate
or programmable pumps, because their infusion rate can be very low.
An example of such a pump is described listed in U.S. Pat. No.
5,728,396, the disclosure of which is hereby incorporated herein in
its entirety. This patent discloses an implantable osmotic pump
that achieves a sustained delivery of leuprolide. The pump includes
an impermeable reservoir that is divided into a water-swellable
agent chamber and a drug chamber. Fluid from the body is imbibed
through a semi permeable plug into the water-swellable agent
chamber and the drug is released through a diffusion outlet at a
substantially constant rate.
[0010] However, osmotic pumps of this type are configured to
deliver a single drug (or a single combination of drugs) at a time
and at a single delivery rate. Should the patient develop a
tolerance to the drug and require an increased dose to alleviate
pain, for example, such a single drug/single dose pump is unable to
provide the needed relief. In such a case, the physician may need
to supplement the drug delivered by the implanted pump with another
drug or more of the same drug, delivered via an intravenous route,
for example. This, however, defeats the purpose of the implanted
pump, namely to provide a self-contained drug delivery system that
operates with little or no discomfort to the patient. What are
needed, therefore, are novel implantable pumps and pump systems
able to deliver a drug at more than a single rate.
[0011] There may be instances, moreover, when a simple increased
dose of the same drug is ineffective to achieve the desired
therapeutic result. In such cases, the administration of another
drug may be indicated, whether in place of or in addition to the
originally delivered drug. Conventional osmotic pumps, however, are
single drug or single drug combination devices: they can only
infuse a single drug or a single combination of drugs at a time. To
administer another drug, several alternatives are available, all of
which involve significant discomfort to the patient. One such
alternative is to administer the other drug intravenously while the
osmotic pump remains is implanted. Another alternative is to
surgically remove the originally implanted drug and to implant
another osmotic pump configured to deliver the other drug. These
alternatives are also the only ones available when the implanted
osmotic pump fails to function or runs out of drug, whether at the
end of its useful life or whether the pump fails unexpectedly. What
are also needed, therefore, are implantable osmotic pump systems
configured for the selective delivery of more than one drug or more
than one drug combination, at individually selectable rates. Also
needed are implantable osmotic pump systems that include a built-in
backup drug delivery system, the backup system being effective to
continue the delivery of the drug when the primary delivery system
reaches the end of its useful life or fails unexpectedly.
SUMMARY OF THE INVENTION
[0012] It is an object of the present invention, therefore, to
provide novel implantable pumps and pump systems adapted to deliver
a drug at more than a single rate. It is another object of the
present invention to provide implantable osmotic pump systems
configured for the selective delivery of more than one drug or more
than one drug combination, at individually selectable rates. A
still further object of the present invention is to provide osmotic
pump systems that include a built-in backup drug delivery system,
the backup system being effective to continue the delivery of the
drug when the primary delivery system reaches the end of its useful
life or fails unexpectedly.
[0013] In accordance with the above-described objects and those
that will be mentioned and will become apparent below, an
implantable osmotic pump system, according to an embodiment of the
present invention includes a first osmotic pump including a first
semipermeable membrane; a second osmotic pump including a second
semipermeable membrane, and a single catheter attached to both the
first and the second osmotic pumps.
[0014] The catheter may include a first lumen and a second lumen,
the first lumen being connected to the first osmotic pump and the
second lumen being connected to the second pump. Alternatively, the
catheter may include a single lumen with two side arms, one of the
two side arms being attached to the first pump and the other of the
two side arms being attached to the second pump, each of two side
arms including an internal lumen that feeds into the single lumen.
The second semipermeable membrane may be sealed by an impermeable
membrane. The impermeable membrane may be disposed over and away
from semipermeable membrane so as to define a fluid tight
compartment therewith. The impermeable membrane may be adapted to
be punctured with a lancet when the pump system is implanted in a
patient and may include, for example, titanium, stainless steel, a
polymer such as polyethylene, polyethylene terephthalate (PET) or
PETG and/or any biologically inert material adapted to be breached
by a lancet or like device.
[0015] The first and second pumps may be preloaded with one or more
pharmaceutical agents. The first pump may be preloaded with a first
pharmaceutical agent at a first therapeutically effective
concentration and the second pump may be preloaded with a second
pharmaceutical agent at a second therapeutically effective
concentration. The first pharmaceutical agent may be the same
pharmaceutical agent as the second pharmaceutical agent or a
different agent. Likewise, the first concentration may be at the
same or different as the second concentration. The first
pharmaceutical agent may potentiate a therapeutic property of the
second pharmaceutical agent. For example, the first pharmaceutical
agent may be an opioid and the second pharmaceutical agent may
include a drug that potentiates an analgesic property of the first
pharmaceutical agent, such as the alpha 2-adrenoreceptor agonist
Clonidine.
[0016] The first pump may be preloaded with a first opioid and the
first pump may be adapted to infuse the first opioid at a first
therapeutically effective range of concentration. Likewise, the
second pump may be preloaded with a second opioid and the second
pump may be adapted to infuse the second opioid at a second
therapeutically effective range of concentration after the
semipermeable membrane is breached. The first opioid may include
Fentanyl and/or Sufentanil and the second opioid may include
Fentanyl and/or Sufentanil. The first opioid may be the same opioid
as the second opioid and the second pump may be adapted to infuse
the second opioid at the first therapeutically effective range when
the first pump is out of the first opioid, upon breaching the
impermeable membrane.
[0017] The present invention may also be viewed as a kit,
comprising a first osmotic pump including a first semipermeable
membrane; a second osmotic pump including a second semipermeable
membrane, and a single catheter adapted to attach to both the first
and the second osmotic pumps.
[0018] The second semipermeable membrane may be sealed by an
impermeable membrane. The impermeable membrane may be disposed over
and away from the one of the first and second semipermeable
membrane so as to define a fluid tight compartment therewith. A
lancet configured to breach the impermeable membrane may also be
included in the kit. The first and second osmotic pumps may be
preloaded with first and second pharmaceutical agent(s),
respectively. For example, the first pharmaceutical agent may
include Fentanyl and the second pharmaceutical agent includes
Sufentanil. Alternatively, the first pharmaceutical agent may
include Sufentanil and the second pharmaceutical agent may include
Clonidine.
[0019] The present invention is also a drug delivery method,
comprising the steps of infusing a first drug at a first
therapeutically effective range of concentration from a first
implanted osmotic pump; infusing a second drug at a second
therapeutically effective range of concentration from a second
implanted osmotic pump; preventing the first and second drugs from
mixing until both the first and second drugs reach an intended
delivery site.
[0020] The preventing step may be carried out by attaching a
catheter having a first and a second lumen to the first and second
osmotic pumps, the first lumen being in fluid communication with
the first osmotic pump and the second lumen being in fluid
communication with the second osmotic pump, a free end of the
catheter being disposed at the intended delivery site. The first
and second drugs may be therapeutically effective for pain therapy,
hormone therapy, gene therapy, angiogenic therapy, anti-tumor
therapy, chemotherapy and/or other pharmaceutical therapies.
[0021] According to another aspect thereof, the present invention
is an implantable osmotic pump system, comprising: a first osmotic
pump, including a first semipermeable membrane; a first impermeable
membrane initially sealing the first semipermeable membrane; a
second semipermeable membrane and a second impermeable membrane
initially sealing the second semipermeable membrane, and a second
osmotic pump, including a third semipermeable membrane; a third
impermeable membrane initially sealing the third semipermeable
membrane; a fourth semipermeable membrane and a fourth impermeable
membrane initially sealing the fourth semipermeable membrane.
[0022] Each of the first and second pumps may include a proximal
end, a distal end and a sidewall. One or both of the first and
second initially sealed semipermeable membranes may be fitted to a
side wall of the first pump and one or both of the third and fourth
initially sealed semipermeable membranes may be fitted to a side
wall of the second pump. Each of the first and second pumps may
include a proximal and a distal end, and a catheter may be attached
to the distal end of the first pump and to the distal end of the
second pump. Each of the first to fourth impermeable membranes may
be disposed over and away from the first to fourth semipermeable
membranes, respectively, so as to define a first to fourth fluid
tight compartment therewith, respectively. Each of the first to
fourth impermeable membranes may be adapted to be punctured with a
lancet when the pump system is implanted in a patient. The
impermeable membranes may include titanium, stainless steel,
platinum-iridium, polyethylene, PET and PETG and/or any
biologically inert material that is impermeable to water. The first
and second pumps may be preloaded with pharmaceutical agent(s). For
example, the first pump may be adapted to deliver a dose of
Fentanyl of about 10 to about 300 milligrams per day and the second
pump may be adapted to deliver a dose of Sufentanil of about 1 to
about 25 micrograms per day. Alternately, the first pump may be
adapted to deliver a dose of Sufentanil of about 1 to about 25
micrograms per day and the second pump may be adapted to deliver a
dose of Clonidine of about 25 to about 150 micrograms per day.
[0023] This pump system may be used by carrying out steps of
breaching the first impermeable membrane; implanting the pump
system into a patient to start infusion of the first pharmaceutical
agent at a first therapeutically effective dose; breaching the
second impermeable membrane to start infusion of the first
pharmaceutical agent at a second therapeutically effective dose
when the patient develops a tolerance to the first dose; breaching
the third impermeable membrane to start infusion of the second
pharmaceutical agent at a third therapeutically effective dose when
the patient develops a tolerance to the first pharmaceutical agent,
and breaching the fourth impermeable membrane to start infusion of
the second pharmaceutical agent at a fourth therapeutically
effective dose when the patient develops a tolerance to the third
dose. The breaching steps may be carried out by puncturing the
first to fourth impermeable membranes with a lancet.
[0024] According to still another embodiment, an implantable
osmotic pump, comprises a pump housing having a proximal end, a
distal end and a sidewall, the pump housing defining a
pharmaceutical agent compartment and an osmotic agent compartment,
the pharmaceutical agent compartment being separated from the
osmotic agent compartment by a movable piston; a first
semipermeable membrane fitted to the proximal end and a second
semipermeable membrane fitted to a portion of the sidewall defining
the osmotic engine compartment, both the first and second
semipermeable membranes being adapted to allow water to cross into
the osmotic engine compartment; an impermeable membrane sealing the
second semipermeable membrane, and an integrated lancet adapted to
breach the impermeable membrane.
[0025] The integrated lancet mechanism may be adapted to breach the
impermeable membrane upon a manual application of force on the
mechanism. A spring may bias a lancet away from the impermeable
membrane. The integrated lancet mechanism may include a plurality
of through holes, the through holes allowing water into the
mechanism and in contact with the second semipermeable membrane
when the impermeable membrane is breached. The pharmaceutical agent
compartment may be preloaded with a pharmaceutical agent and the
pump may be configured to infuse the pharmaceutical agent at a
first rate based upon a composition, thickness and surface area of
the first semipermeable membrane when the impermeable membrane is
intact and may be configured to infuse the pharmaceutical agent at
a second infusion rate when the impermeable membrane has been
breached. The second rate may be based upon the composition,
thickness and surface area of the first and the second
semipermeable membranes. The pharmaceutical agent may include
Fentanyl, infused within the range of about 10 to about 300
milligrams per day. The pharmaceutical agent may include a
combination of Fentanyl and Sufentanil, infused within the range of
about 1 to about 25 micrograms per day for Sufentanil and within
the range of about 10 to about 30 milligrams per day of Fentanyl.
Alternately still, the pharmaceutical agent may include a
combination of Sufentanil and Clonidine, infused within a range of
about 1 to about 25 micrograms per day for Sufentanil and within a
range of about 25 to about 150 micrograms per day for
Clonidine.
[0026] A method of delivering a pharmaceutical agent, according to
a still further embodiment, comprises the steps of implanting an
osmotic pump including a first and a second semipermeable membrane,
the second impermeable membrane being initially sealed by an
impermeable membrane, the pump including an integrated lancet
mechanism adapted to breach the impermeable membrane; infusing the
pharmaceutical agent at a first infusion rate based upon a
composition, thickness and surface area of the first semipermeable
membrane; applying force to the lancet mechanism to cause the
mechanism to breach the impermeable membrane and expose the
initially sealed second semipermeable membrane, and infusing the
pharmaceutical agent at a second infusion rate that is higher than
the first infusion rate, the second infusion rate being based upon
a composition, thickness and surface area of the first and the
second semipermeable membranes. The force-applying step may be
carried out while the pump is implanted. A further step of
palpating the implanted pump to locate the integrated lancet
mechanism thereof prior to the force-applying step may also be
carried out.
[0027] An implantable osmotic pump system, according to another
embodiment of the present invention, comprises a pump housing
having a proximal end, a distal end and a sidewall, the pump
housing defining a pharmaceutical agent compartment and an osmotic
agent compartment, the pharmaceutical agent compartment being
separated from the osmotic agent compartment by a movable piston; a
first semipermeable membrane fitted to a portion of the sidewall
defining the osmotic engine compartment, the first semipermeable
membrane being adapted to allow water to cross into the osmotic
engine compartment and a first sealing member covering and sealing
the first semipermeable membrane.
[0028] The proximal end of the pump housing may be impermeable to
water. The first sealing member may include a spacer fitted to the
sidewall, the spacer including an impermeable membrane that is
adapted to be breached by a lancet. The pump housing and the spacer
may be configured to allow the spacer to be screwed on the
sidewall. The spacer may be fitted to the pump housing by an
ultrasonic weld.
[0029] The system may further include at least one second
semipermeable membrane fitted to the portion of the sidewall
defining the osmotic engine compartment, the second semipermeable
membrane(s) being adapted to allow water to cross into the osmotic
engine compartment; at least one second sealing member covering and
sealing a respective one of the at least one second semipermeable
membrane. The first and the at least one second sealing members may
each include a spacer fitted to the sidewall, the spacer including
an impermeable membrane that is adapted to be breached by a lancet.
The impermeable membrane may be visible under fluoroscopy. At least
the portion of the sidewall defining the osmotic engine compartment
may be substantially flat and the pump housing may have a generally
rectangular shape with rounded atraumatic edges.
BRIEF DESCRIPTION OF THE DRAWINGS
[0030] For a further understanding of the objects and advantages of
the present invention, reference should be made to the following
detailed description, taken in conjunction with the accompanying
figures, in which:
[0031] FIG. 1a illustrates an implantable osmotic pump system
including a first and second implantable pump connected to a dual
lumen catheter, the pump system being in a state wherein the second
pump is not enabled.
[0032] FIG. 1b illustrates the implantable pump system of FIG. 1a,
in a state wherein the second pump is being enabled.
[0033] FIG. 1c illustrates an implantable osmotic pump system
according to a further embodiment of the present invention, wherein
the pump system is in a state wherein the second pump is fully
enabled and wherein the pump system is connected to a single lumen
catheter.
[0034] FIG. 2a illustrates an implantable osmotic pump system
according to another embodiment of the present invention, wherein
the pump system is connected to a dual lumen catheter.
[0035] FIG. 2b illustrates an implantable osmotic pump system
according to a still further embodiment of the present invention,
wherein the pump system is connected to a single lumen
catheter.
[0036] FIG. 3a illustrates an osmotic pump system and
pharmaceutical agent delivery method, according to an embodiment of
the present invention.
[0037] FIG. 3b illustrates the pump system of FIG. 3a, in a state
wherein an impermeable membrane is being breached to expose a
second semipermeable membrane to the patient environment.
[0038] FIG. 3c illustrates the pump system of FIG. 3b, after the
second semipermeable membrane has been exposed to the patient
environment.
[0039] FIG. 4a shows a top view of an implantable osmotic pump
system, according to a still further embodiment of the present
invention.
[0040] FIG. 4b shows a side view of the implantable osmotic pump
system of FIG. 4a.
[0041] FIG. 5 shows a top view of an intact impermeable membrane
suitable for use with the pump systems of FIGS. 1a through 4b, as
seen through fluoroscopy.
[0042] FIG. 6 shows a top view of the impermeable membrane of FIG.
5, after having been breached by a lancet, as seen through
fluoroscopy.
DESCRIPTION OF THE INVENTION
[0043] FIG. 11a illustrates an implantable osmotic delivery system,
kit and method according to an embodiment of the present invention.
As shown therein, the osmotic pump system 100 according to the
present invention includes a first pump 101 and a second pump 102.
The first and pump 101 includes an osmotic engine compartment 107
and a pharmaceutical agent compartment 108 that are separated from
one another by a movable piston 111 (shown in dashed lines).
Similarly, the second implantable osmotic pump 102 includes an
osmotic engine compartment 109 and a pharmaceutical agent
compartment 110 that are separated from one another by a movable
piston 112 (also shown in dashed lines). Each of the osmotic pumps
101 and 102 has a proximal and a distal end. A catheter 113 is
attached to the distal end of each of the first and second pumps
101, 102. The catheter 113 may be a dual lumen catheter as shown in
FIGS. 1a and 1b and include a first lumen and a second lumen, the
first lumen being connected to the first osmotic pump 101 and the
second lumen being connected to the second pump 102. One advantage
of a dual lumen catheter, such as shown at reference numeral 113 in
FIGS. 1a and 1b is that pharmaceutical agents (infused from the
first and second pumps 101, 102) that interact can be infused and
intentionally not mixed together until they reach the intended
delivery site. This may be useful for such drug delivery
applications such as hormone therapy or chemotherapy.
[0044] Alternatively, the catheter 113 may be a single lumen
catheter as shown in FIG. 1c. Such a catheter 113 may include a
single lumen with two side arms, one of the two side arms being
attached to the first pump 101 and the other of the two side arms
being attached to the second pump 102, each of two side arms
including an internal lumen that feeds into the single lumen. In
whichever configuration, an internal lumen of the catheter is in
fluid communication with each of the pharmaceutical agent
compartments 108, 110 of the first and second pumps 101, 102,
respectively.
[0045] The proximal end of each of the first and second implantable
osmotic pumps 101, 102 is fitted with a semipermeable membrane 104,
105 through which water from the patient may cross to reach the
osmotic engine compartments 107, 109, respectively. Each of the
semipermeable membranes 104, 105 may include, for example, a
cellulose acetate composition. When the semipermeable membranes
104, 105 come into contact with water from the patient, the
differential osmotic pressure across the semipermeable membranes
104, 105 causes the material in the osmotic engine compartments
107, 109 (i.e., the osmotic engine) to enlarge in volume and push
on the movable piston 111, 112, respectively. This pushing of the
movable pistons 111, 112 in the distal direction causes a
corresponding decrease in the volume of the pharmaceutical agent
compartments 108, 110 and causes the pharmaceutical agent(s) 114
contained therein to infuse through the infusion lumen(s) of the
catheter 113 to the intended delivery site at the distal most end
of the catheter 113.
[0046] As shown in FIGS. 1a through 1c, the semipermeable membrane
105 of the second pump 102 may be initially sealed by an
impermeable membrane 103. Indeed, the impermeable membrane 103 may
be disposed over and away from the semipermeable membrane 105
fitted to the proximal end of the second osmotic pump 102 so as to
define a fluid tight compartment therewith. The impermeable
membrane 103 may be adapted, according to an embodiment of the
present invention, to be punctured with a lancet 115 when the pump
system 100 is implanted in a patient (not shown). The impermeable
membrane 103 may include titanium, stainless steel,
platinum-iridium, polyethylene, PET and PETG, for example.
Alternatively, the impermeable membrane 103 may be formed of any
material or combinations of biologically inert materials that are
impermeable to water and are adapted to be breached upon the
application of force thereon with a lancet or like device.
[0047] According to an embodiment of the present invention, each of
the first and second pumps 101, 102 may be preloaded with one or
more pharmaceutical agents. That is, the pharmaceutical agent
compartment 108 of the first pump 101 may be preloaded with one or
more pharmaceutical agents 114 and the pharmaceutical agent
compartment 110 of the second pump 102 may be preloaded with one or
more pharmaceutical agents 114. The first pump 101 may be preloaded
with a first pharmaceutical agent 114 at a first therapeutically
effective concentration and the second pump 102 may be preloaded
with a second pharmaceutical agent 114 at a second therapeutically
effective concentration. The first pump 101 may be preloaded with
the same or different than the pharmaceutical agent 114 preloaded
in the second pump 102. Similarly, the concentration of the
pharmaceutical agent 114 in the first pump 101 may be the same or
different than the concentration of the pharmaceutical agent 114 in
the second pump 102.
[0048] According to an advantageous embodiment of the present
invention, the pharmaceutical agent 114 preloaded in one of the
pumps 101, 102 potentiates the therapeutic property or properties
of the pharmaceutical agent 114 preloaded in the other of the pumps
101, 102. For example, one of the pumps 101,102 may be preloaded
with an opioid and the other of the pumps 101, 102 may be preloaded
with a pharmaceutical agent that potentiates the analgesic property
of the opioid. For example, the first pump 101 may be preloaded
with Sufentanil and the second pump 102 may be preloaded with a
drug or a combination of drugs that includes one or more alpha
2-adrenoreceptor agonists. An example of such an alpha
2-adrenoreceptor agonist is Clonidine, which is a drug that
potentiates the analgesic properties of Sufentanil.
[0049] As shown in FIGS. 1a through 1c, the first pump 101 infuses
the pharmaceutical agent 114 preloaded therein after the system 100
is implanted into the patient, as its semipermeable membrane 104 is
in contact with water from the patient's body. The second pump 102,
however, does not initially infuse any pharmaceutical agent 114
into the patient, as its semipermeable membrane 105 is initially
sealed (FIG. 1a) from the patient by the impermeable membrane 103.
A cylindrical spacer 106 may support the impermeable membrane 103
over the semipermeable membrane 105 so as to define a fluid tight
compartment therewith. The fluid tight compartment may be filled
with a saturated saline solution, to thereby maintain equal osmotic
pressure on either side of the semipermeable membrane 105.
[0050] When the patient develops a tolerance to the pharmaceutical
agent 114 infused by the first pump 101 or when the first pump 101
runs out of pharmaceutical agent 114 or otherwise unexpectedly
fails, the surgeon may locate (by palpation or by an imaging
technique such as fluoroscopy, for example) the impermeable
membrane 103 and puncture it through the patient's skin. This may
be done while the system 100 is fully implanted in the patient.
When the impermeable membrane 103 is breached by a lancet 115 or
the like, water (shown by the arrows leading toward the
semipermeable membrane 105) from the patient may now reach the
semipermeable membrane 105 and increase the osmotic differential
pressure across the semipermeable membrane 105 and cause the second
osmotic pump 102 to begin infusing the pharmaceutical agent(s)
preloaded therein. When the second pump 102 is used as a backup,
the second pump 102 significantly increases the useful life of the
system 101. When used with the first pump 101, the second pump 102
allows the pump system 100 to deliver an increased dose of
pharmaceutical agent 114 or a more therapeutically potent
combination of drugs than would be possible with only a single
pump.
[0051] FIG. 2a illustrates an implantable osmotic pump system 200
according to another embodiment of the present invention. The pump
system 200 of FIG. 2a is connected to a dual lumen catheter 213.
FIG. 2b illustrates an implantable osmotic pump system 200
according to a further embodiment of the present invention, wherein
the pump system 200 is connected to a single lumen catheter 213.
Considering now FIGS. 2a and 2b collectively, the osmotic pump
system 200 shown therein includes a first osmotic pump 201 and a
second osmotic pump 202. The first osmotic pump 201 includes a
first semipermeable membrane 205 and a first impermeable membrane
203 initially sealing the first semipermeable membrane 205. The
first osmotic pump 201 also includes a second semipermeable
membrane 217 and a second impermeable membrane 215 initially
sealing the second semipermeable membrane 217. The second osmotic
pump 202 includes a third semipermeable membrane 206 and a third
impermeable membrane 204 initially sealing the third semipermeable
membrane 206. The second pump 202 also includes a fourth
semipermeable membrane 218 and a fourth impermeable membrane 216
initially sealing the fourth semipermeable membrane 218. The first
implantable osmotic pump 201 and the second implantable osmotic
pump 202 are each connected to two single (FIG. 2b) or to one dual
(FIG. 2a) lumen catheter 213.
[0052] As shown in FIGS. 2a and 2b, at least one of the first and
second semipermeable membranes 205, 217 of the first osmotic pump
201 is fitted to a sidewall of the first pump 201. FIGS. 2a and 2b
show the first semipermeable membrane 205 fitted to the proximal
end of the pump 201. However, both the first and the second
semipermeable membranes 205, 217 may be fitted to the sidewall of
the first pump 201, which may facilitate access thereto, depending
on the orientation of the implanted pump system 200 within the
patient. Likewise, at least one of the third and fourth
semipermeable membranes 206, 218 of the second osmotic pump 202 is
fitted to a sidewall of the second pump 202. FIGS. 2a and 2b show
the third semipermeable membrane 206 fitted to the proximal end of
the pump 202. However, both the third and fourth semipermeable
membranes 206, 218 may be fitted to the sidewall of the second pump
202, as discussed above relative to the first pump 201.
Alternatively still, the pump system 200 may be configured so as to
fit any of the first to fourth semipermeable membranes 205, 217,
206, 218 to the respective proximal ends or sidewalls of the first
and second pumps 201, 202, each of the first to fourth
semipermeable membranes 205, 217, 206, 218 being initially sealed
by the first to fourth impermeable membranes 203, 215, 204, 216,
respectively. The impermeable membranes 203, 215, 204, 216 may, for
example, be formed of or include titanium, stainless steel,
platinum-iridium, polyethylene, PET and PETG or any other
biologically inert material that is impermeable to water. According
to an embodiment of the present invention, each of the first to
fourth impermeable membranes 203, 215, 204, 216 may be disposed
over and away from the first to fourth semipermeable membranes 205,
217, 206, 218, respectively, so as to define first to fourth fluid
tight compartments 221, 219, 222, 220 therewith, respectively. Each
of the first to fourth fluid tight compartments 221, 219, 222, 220
may include a volume of saturated saline solution therein, to
maintain equal osmolarity across the semipermeable membranes 205,
217, 206, 218 until the impermeable membranes 203, 215, 204, 216
are breached (punctured, for example) by a lancet (115 in FIGS.
1a-1c) or other suitable device. According to the present
invention, the second and fourth semipermeable membranes 217, 218
may be fitted to the sidewall of the first and second pumps 201,
202 in such a manner as to allow water to cross into the osmotic
engine compartments 207, 209 of the first and second pumps 201,
202, respectively. In other words, the second and fourth
semipermeable membrane 217, 218 are in fluid communication with the
osmotic engine compartments 207, 209, respectively. As water
crosses the first to fourth impermeable membranes 205, 217, 206,
218, the osmotic engine within each of the compartments 207, 209
expands and pushes upon respective movable pistons 211, 212 of the
first and second pumps 201, 202 in the distal direction. This
pushing correspondingly reduces the volumes of the therapeutic
agent compartments 208, 210 and infuses the pharmaceutical agent(s)
214 from the first and second pumps 201, 202 and into the (single
or dual lumen) catheter 213 to the delivery site within the
patient.
[0053] According to the present invention, the system 200 may be
implanted into the patient with at least one of the semipermeable
membranes 205, 217, 206, 218 exposed. To do so, the surgeon would
breach one of the first to fourth impermeable membranes 203, 215,
204, 216 immediately prior to implantation of the pump system 200
into the patient. The system 200 may also be implanted without any
of the impermeable membranes 203, 215, 204, 216 breached. In that
case, however, the pump system 200 will not begin infusing any
pharmaceutical agent 214 until at least one of the impermeable
membranes 203, 215, 204, 216 is breached to expose a corresponding
semipermeable membrane 205, 217, 206, 218 to water from the
patient.
[0054] Each of the first and second pumps 201, 202 may be preloaded
with one or more pharmaceutical agents 214. Indeed, the first pump
201 may be preloaded with a first pharmaceutical agent 214 at a
first therapeutically effective concentration. Likewise, the second
pump 202 may be preloaded with a second pharmaceutical agent 214 at
a second therapeutically effective concentration. The pumps 201,
202 may also infuse the pharmaceutical agent(s) 214 at a first and
second therapeutically effective rate, wherein the first rate may
be equal or different to the second rate. The first pump 201 may be
preloaded with a lesser or greater volume of the pharmaceutical
agent 214 as may be preloaded into the second pump 202. The pumps
201, 202 may be preloaded with the same or a different
pharmaceutical agent (opioids or non-opioids) 214 or combination(s)
of pharmaceutical agents 214. In like manner, the concentrations of
the pharmaceutical agent(s) 214 preloaded in the first and second
pumps 201, 202 may be identical or dissimilar, depending upon the
therapy prescribed by the patient's physician.
[0055] When the osmotic pump system 200 is used as a therapeutic
tool within the context of pain management, for example, the system
200 may be implanted into the patient and the first impermeable
membrane 203 may be breached by a lancet (as shown at 115 in FIGS.
1a, 1b and 1c) to start infusion of a first opioid (for example) at
a first therapeutically effective dose. As the patient develops a
tolerance to the first dose, or needs additional drug to relieve
their pain, the second impermeable membrane 215 may be breached to
start infusion of the first opioid at a second therapeutically
effective dose. As the patient develops a tolerance to the first
opioid, the third impermeable membrane 204 may be breached to start
infusion of a second drug (opioid or non-opioid) at a third
therapeutically effective dose. As the patient develops a tolerance
to the third dose of the second drug or needs additional drug to
relieve their pain, the fourth impermeable membrane 216 may be
breached to start infusion of the second drug at a fourth
therapeutically effective dose. It should be noted, however, that
the sequence with which the impermeable membranes are breached may
be modified at will. For example, the above-detailed sequence may
be modified by substituting the second impermeable membrane 215 for
the first impermeable membrane 203 and by substituting the fourth
impermeable membrane 216 for the third impermeable membrane 204.
Other sequences are possible. The first dose is dependent upon the
surface area, thickness and composition of the first semipermeable
membrane 205, as well as upon the degree of hydration of the
implantation site within the patient. The second dose (which is
infused when both the first and second semipermeable membranes 205,
217 are exposed to the patient) is dependent upon the first dose,
as well as upon the surface are, thickness and composition of the
second semipermeable membrane 217, as well as upon the degree of
hydration of the implantation site within the patient. Similarly,
the third dose is dependent upon the surface area, thickness and
composition of the third semipermeable membrane 206, as well as
upon the degree of hydration of the implantation site within the
patient. The fourth dose (which is infused when both the third and
fourth semipermeable membranes 206, 218 are exposed to the patient)
is dependent upon the third dose, as well as upon the surface are,
thickness and composition of the third semipermeable membrane 218,
as well as upon the degree of hydration of the implantation site
within the patient. These doses, therefore, may be selected by
appropriately varying the above parameters upon manufacture of the
pump system 200.
[0056] According to one advantageous embodiment, the first
pharmaceutical agent 214 preloaded in the first osmotic pump 201
may potentiate a therapeutic property or properties of the second
pharmaceutical agent 214 preloaded in the second osmotic pump 202,
or vice-versa. For example, staying within the context of pain
management, the first pharmaceutical agent 214 may be an opioid and
the second pharmaceutical agent 214 may include a drug that
potentiates an analgesic property or properties of the first
pharmaceutical agent 214. For example, the first pharmaceutical
agent may include Sufentanil and the second pharmaceutical agent
214 may include an alpha 2-adrenoreceptor agonist, such as
Clonidine.
[0057] According to another embodiment of the present invention,
the first and second osmotic pumps 201, 202 may be preloaded with
first and second opioids, respectively. The first opioid may
include Fentanyl and/or Sufentanil and the second opioid may also
include Fentanyl and/or Sufentanil. For example, the first pump 201
may be adapted to deliver a dose of Fentanyl of about 10 to about
300 milligrams per day and the second pump 202 may be adapted to
deliver a dose of Sufentanil of about 1 to about 25 micrograms per
day, depending upon the clinical presentation of the patient. In
the case wherein the first pump is preloaded with Sufentanil and
the second pump is preloaded with an alpha 2-adrenoreceptor agonist
such as Clonidine, the first pump 210 may be configured to deliver
a dose of Sufentanil of about 1 to about 25 micrograms per day and
the second pump 202 may be adapted to deliver a dose of Clonidine
of about 25 to about 150 micrograms per day, again depending upon
the clinical presentation of the patient.
[0058] FIGS. 3a through 3c illustrate an osmotic pump system 300
and a pharmaceutical agent delivery method, according to a further
embodiment of the present invention. As shown therein, the pump
system 300 includes an integrated lancet mechanism 301 that may be
actuated while the pump system 300 is implanted into the patient
without, however, breaching the skin 350 and subcutaneous tissue
351 of the patient. Indeed, the implantable osmotic pump system 300
includes a catheter 313 and a pump housing 305 having a proximal
end, a distal end and a sidewall, the pump housing 305 defining a
pharmaceutical agent compartment 340 and an osmotic agent
compartment 320. The pharmaceutical agent compartment 340 is
separated from the osmotic agent compartment 320 by a movable
piston 330 (shown in dashed lines in FIGS. 3a through 3c). A first
semipermeable membrane 310 may be fitted to the proximal end of the
pump system 300 and a second semipermeable membrane 304 may be
fitted to a portion of the sidewall defining the osmotic engine
compartment 320. Both the first and second semipermeable membranes
310, 304 allow water from the patient to cross into the osmotic
engine compartment 320. As shown, an impermeable membrane 303 may
seal the second semipermeable membrane 304. The integrated lancet
mechanism 301 may be fitted over the impermeable membrane 303 such
as to breach the underlying impermeable membrane 303 upon the
application of force thereon. To bias the lancet mechanism 301 away
from the impermeable membrane 303, the mechanism may include a
spring 380, in compression. The spring 380 biases the lancet 302 of
the mechanism 301 away from the impermeable membrane 303 for as
long as the physician does not apply sufficient force on the
mechanism to overcome the biasing force of the spring 380 and cause
the lancet 302 to move in a direction normal to the longitudinal
axis of the pump housing 305 to breach the impermeable membrane
304. This force on the mechanism 301 may be applied by means, for
example, of the physician's thumb, shown at reference numeral 360
in FIG. 3b. Once breached, the impermeable membrane 303 allows
water to reach the second semipermeable membrane 304 via the
through holes 370 in the integrated lancet mechanism 301, as shown
at FIG. 3c.
[0059] According to an embodiment of the present invention, the
pharmaceutical agent compartment 340 may be preloaded with a
pharmaceutical agent or agents 314 and the pump system 300 may be
configured to infuse the pharmaceutical agent(s) at a first rate
based upon the composition, thickness and surface area of the first
semipermeable membrane 310 when the impermeable membrane 303 is
intact. The pump system 300 may be configured to infuse the
pharmaceutical agent(s) at a second infusion rate when the
impermeable membrane 303 has been breached by the application of
force to the integrated lancet mechanism 301. The second infusion
rate, therefore, is based upon the composition, thickness and
surface area of the second semipermeable membrane 304, as well as
upon the first infusion rate. In other words, the second rate is
the sum of the respective infusion rates contributed by each of the
first and second semipermeable membranes 310, 304.
[0060] When the pump system 300 is first implanted in the patient,
the first semipermeable membrane 310 is exposed to the osmotic
pressure of the patient's subcutaneous tissue 351, which causes the
osmotic engine within the osmotic engine compartment 320 to expand
at a first rate based upon the surface area, composition and
thickness of the first semipermeable membrane 310. In this state,
the osmotic engine pushes against the movable piston 330, causing
the pharmaceutical agent 314 to be infused at a first rate. When
the patient develops a tolerance to the first infusion rate, the
physician may locate the integrated lancet mechanism 301 (by feel
or through an imaging technique) and apply force thereon with his
or her finger 360, as shown in FIG. 3b. This causes the impermeable
membrane 303 to be breached and the underlying second semipermeable
membrane 304 to be exposed to the osmotic pressure of the patient's
subcutaneous tissue 351. The osmotic engine is now expanding at a
second rate that is related to the surface area, thickness and
composition of the second semipermeable membrane 304, as well as
that of the first semipermeable membrane 310. The osmotic engine
then pushes on the movable piston 330, thereby causing the
pharmaceutical agent to be infused at the second rate.
[0061] In one embodiment, a pharmaceutical agent 314 may be
preloaded within the pharmaceutical agent compartment 340. For
example, the compartment 340 may enclose Fentanyl, which may be
infused within the range of about 10 to about 300 milligrams per
day, dependent upon the clinical presentation of the patient and
the delivery site. Alternatively, the pharmaceutical agent 314 may
include a combination of Fentanyl and Sufentanil. Such a
combination (mixture) may be infused at a rate selected within the
range of about 1 to about 25 micrograms of Sufentanil per day,
again depending upon the clinical presentation of the patient and
the delivery site of the drug within the patient. Alternatively
still, the pharmaceutical agent 314 may be or include a combination
of Sufentanil and Clonidine, which combination may be infused
within a range of about 1 to about 25 micrograms per day for
Sufentanil and within a range of about 25 to about 150 micrograms
per day for Clonidine, both dependent upon the clinical
presentation of the patient and the delivery site.
[0062] Pain management medications are not the only medications for
which the devices, methods and systems disclosed herein find
advantageous application. Indeed, the pharmaceutical agent
compartment 340 may be preloaded with one or more pharmaceutical
agents that are therapeutically effective for hormone therapy, gene
therapy, angiogenic therapy, anti-tumor therapy, chemotherapy
and/or other therapies.
[0063] FIG. 4a shows a top view of an implantable osmotic pump
system 400, according to a still further embodiment of the present
invention, whereas FIG. 4b shows a side view thereof. Considered
collectively, FIGS. 4a and 4b show an implantable osmotic pump
system 400 comprising a pump housing 401 having a proximal end, a
distal end and a sidewall, the pump housing 401 defining a
pharmaceutical agent compartment 440 and an osmotic agent
compartment 420. The pharmaceutical agent compartment 440 is
separated from the osmotic agent compartment 420 by a movable
piston 412, shown in dashed lines. A first semipermeable membrane
404 is fitted to a portion of the sidewall defining the osmotic
engine compartment 420 and is adapted to allow water to cross into
the osmotic engine compartment 420 because of the osmotic pressure
at the implantation site. A first sealing member 406 covers and
seals the first semipermeable membrane 404. A catheter 413 may be
attached to the distal end of the pump housing 401, the catheter
413 being in fluid communication with the pharmaceutical agent
compartment 440. As shown in FIGS. 4a and 4b, the proximal end of
the pump housing 401 is impermeable to water, as it does not
include a semipermeable membrane fitted thereto, unlike the device
shown in FIGS. 1a through 3c.
[0064] The first sealing member 406 may include a (cylindrical, for
example) spacer 415 fitted to the sidewall, the spacer 415 being
covered by an impermeable membrane 407 that is adapted to be
breached by a lancet. The pump housing 401 and the spacer 415 may
each include mating threads to allow the spacer 415 to be screwed
on the sidewall. Alternatively, the spacer 415 may be fitted to the
pump housing 401 by an ultrasonic weld. The impermeable membrane
407 may include, for example, titanium, stainless steel,
platinum-iridium, polyethylene, PET and PETG or any biologically
inert material that is impermeable to water.
[0065] As shown most clearly in FIG. 4b, at least one second
semipermeable membrane 405 may be fitted to the portion of the
sidewall defining the osmotic engine compartment 420, the second
semipermeable membrane(s) 405 being adapted to allow water to cross
into the osmotic engine compartment 420 when subjected to osmotic
pressure from the patient. Each of the second semipermeable
membranes 405 may be covered and sealed by a respective second
sealing member 406. In turn, the second sealing member(s) 406
include a spacer 415 fitted to the sidewall, the spacer 415
including an impermeable membrane 407 (FIG. 4b) that is adapted to
be breached by a lancet, as shown at reference 115 in FIGS. 1a
through 1c. To facilitate localization of the impermeable
membrane(s) 407 after the system 400 is implanted into the patient,
the impermeable membrane(s) 407 may include a radiopaque
material--a material that is visible under fluoroscopy. For
example, the impermeable membrane(s) 407 may include titanium,
stainless steel, platinum, platinum-iridium, PET and/or PETG. To
render the membrane(s) 407 made of PET or PETG visible under
fluoroscopy, a radiopaque material such as gold or aluminum, for
example, may be sputtered thereon. FIG. 5 shows a top view of an
intact impermeable membrane 407, whereas FIG. 6 shows a top view of
the same impermeable membrane 407 after being breached by a
lancet.
[0066] As shown in FIG. 4a, the pump housing 401 may accommodate an
array of semipermeable membranes 404, 405, each initially covered
and sealed by a sealing member 406. Each semipermeable membrane
404, 405, in turn, may be exposed to the patient's osmotic pressure
by breaching an impermeable membrane 407 covering each sealing
member 406. To accommodate these semipermeable membranes 404, 405
and their corresponding sealing members 406, at least the portion
of the sidewall defining the osmotic engine compartment 420 may be
substantially flat, as most clearly shown in FIG. 4b. In turn, to
accommodate this substantially flat sidewall portion, the pump
housing 401 may have a generally rectangular shape with rounded,
atraumatic edges. Each sealing member 406, as detailed with respect
to FIGS. 3a through 3c, may be fitted with an integrated lancet
mechanism 301 (FIGS. 3a-3c) adapted to breach the impermeable
membrane 407 of the sealing member 406 to expose the underlying
semipermeable membrane 404 or 405. As with the embodiments of FIGS.
1a through 3c, each of the sealing members 406 may define a fluid
tight compartment with a respective underling semipermeable
membrane 404, 405. These fluid tight compartments may be filled
with a saturated saline solution to maintain equal osmolarity on
either side of the semipermeable membrane 404, 405 until the
semipermeable membrane 404, 405 is exposed to water from the
patient, as disclosed in co-pending and commonly assigned U.S.
patent application Ser. No. 09/442,128 filed on Nov. 6, 1999 and
entitled "Methods And Implantable Devices And Systems For Long Term
Delivery Of A Pharmaceutical Agent" and/or co-pending and commonly
assigned U.S. patent application entitled "Osmotic Pump Delivery
System With Pre-Hydrated Membrane And Primable Catheter", attorney
docket number MICR5646, the disclosures of both of which are hereby
incorporated herein in their entireties.
[0067] Upon implantation of the pump system 400, the first
semipermeable membrane 404 is exposed to the osmotic pressure of
the patient, which causes the osmotic engine within the osmotic
engine compartment 420 to expand at a first rate based upon the
surface area, composition and thickness of the first semipermeable
membrane 404. In this state, the osmotic engine pushes against the
movable piston 412, causing the pharmaceutical agent 414 to be
infused at a first rate. When the patient develops a tolerance to
the first infusion rate, the physician may locate one of the second
sealing members 406 by touch or by fluoroscopy, for example, and
breach the impermeable membrane 407 thereof (as shown by the dashed
lines of the breached impermeable membrane 407 in FIG. 4b). This
causes the corresponding underlying second semipermeable membrane
405 to be exposed to the osmotic pressure of the patient. The
osmotic engine now expands at a second rate that is related to the
surface area, thickness and composition of the second semipermeable
membrane 405, as well as that of the first semipermeable membrane
404. The osmotic engine then pushes on the movable piston 412,
thereby causing the pharmaceutical agent 414 to be infused at the
second rate. As the patient develops a tolerance to the second
rate, another sealing member 406 is located, the impermeable
membrane 407 thereof breached to thereby cause the pharmaceutical
agent 414 to be infused at a third rate. Additional impermeable
members 407 are breached as the patient develops a tolerance to the
previous infusion rate, until the desired therapeutic effect is
achieved.
[0068] The pump system 400 may be preloaded with the same variety
of drugs discussed above relative to FIGS. 3a through 3c and the
description thereof is incorporated herein in its entirety, as if
repeated here in full.
[0069] While the foregoing detailed description has described
preferred embodiments of the present invention, it is to be
understood that the above description is illustrative only and not
limiting of the disclosed invention. Those of skill in this art
will recognize other alternative embodiments and all such
embodiments are deemed to fall within the scope of the present
invention. Thus, the present invention should be limited only by
the claims as set forth below.
* * * * *