WO2001008725A1

WO2001008725A1 - An apparatus for pharmaceutical delivery and the use thereof

Info

Publication number: WO2001008725A1
Application number: PCT/US2000/020240
Authority: WO
Inventors: David S. Silva
Original assignee: Silva David S
Priority date: 1999-07-30
Filing date: 2000-07-26
Publication date: 2001-02-08
Also published as: AU6374300A

Abstract

A pharmaceutical delivery device is described wherein a pharmaceutical agent can be continuously delivered to a target site within the body without the cost and complexity associated with other types of delivery devices. The pharmaceutical delivery device herein utilizes an endogenous pressure of the body to move the therapeutic composition from a reservoir to the target site. Thus, the device can be used anywhere a pressure gradient can be found in the body (i.e. cerebral spinal fluid, blood flow, digestive device, etc.). Further, the pharmaceutical delivery device as described herein may also encompass a pressure modulating component (300) and may be synthesized of biodegradable materials.

Description

AN APPARATUS FOR PHARMACEUTICAL DELIVERY AND THE USE THEREOF

BACKGROUND OF THE INVENTION FIELD OF THE INVENTION

The present invention relates in general to pharmaceutical delivery devices and in particular to an apparatus for pharmaceutical deliver and the use thereof.

DESCRIPTION OF THE RELATED ART Effective drug therapy encompasses much more than selecting a proper medicament to ameliorate symptoms. Physicians and pharmacists must also consider how medicament reaches its target site before being inactivated or eliminated. Thus, it is preferable to deliver the medicament locally at the target site if possible. For example, the ability to treat a disease affecting the brain requires either a pharmaceutical capable of penetrating the blood-brain barrier or the implanting of a device able to deliver the pharmaceutical directly to the brain.

The invention described herein involves a pharmaceutical delivery device capable of delivering a pharmaceutical locally to a target. Several types of pharmaceutical delivery devices have been previously described. Examples of such pharmaceutical delivery devices include: Howard (U.S. Patent No. 5,676,655), Laske (U.S. Patent No. 5,720,720), the Elsberry patents (U.S. Patent Nos. 5,735,814, 5,814,014, and 5,846,220), Rise (U.S. Patent No. 5,782,798), and Dreessen (U.S. 5,843,150).

Howard (5,676,655) discloses a method for implanting a neuroprosthetic pharmaceutical delivery apparatus into a target zone of a patient's brain for the purpose of reducing or eliminating defects from tinnitus. The apparatus includes a catheter inserted into either the patient's auditory cortex or thalamus. The catheter, through the assistance of an injectable pharmaceutical reservoir pump (e.g., Medtronics pump or an Alzet pump), microinfuses pharmaceuticals that suppress or eliminate abnormal neuroactivity in geographically separate locations of the patient's brain, eliminating the symptoms of tinnitus.

Laske (5,720,720) introduces a method for high-flow microinfusion that provides convection-enhanced delivery of agents into the brain and other solid tissue structures. The method requires the positioning of the tip of a diffusion catheter within the target tissue area and supplying a pharmaceutical agent through the catheter, while maintaining a pressure gradient from the tip of the catheter. The infusion catheter includes a plurality of elongated slits adjacent to a tapered portion of the catheter. The slits are parallel to the axis of the catheter and spaced symmetrically about the circumference. After the infusion catheter is positioned at its target site, it is connected to a pump (e.g. syringe pump, Model 22 Harvard), which delivers a desired agent and maintains a desired pressure gradient throughout delivery of the agent.

The Elsberry Patents 5,735.814 and 5,814.014 (a divisional of the 5,735,814 Patent) introduce a technique for infusing pharmaceuticals into the brain to treat neurodegenerative disorders. The technique employs the use of an implantable pump and catheter. The implantable pump is a mechanical pump comprising a motor and is further described in U.S. Patent No. 4,692,147.

The Elsberry Patent (5,846,220) describes a specific method for treating Alzheimer's disease. The method comprises delivering the pharmaceutical agents indomethacin or nonsteroidal anti-inflammatory agents having a cyclooxygenase inhibitor action directly to the hippocampus or the lateral ventricle of the brain. The apparatus for delivering the pharmaceutical agents consists of a catheter having a flexible distal end that is implanted directly into the hippocampus or lateral ventricle. The apparatus also includes a pump coupled to the catheter for delivering the pharmaceutical agents to the hippocampus or lateral ventricle. Rise (5,783,798) introduces a technique for using one or more pharmaceuticals for treating an eating disorder by means of using an implantable pump and catheter. The catheter is surgically implanted in the brain so that the distal end resides at the target site for pharmaceutical infusion. The proximal end of the catheter attaches to a mechanical infusion pump like the one described in U.S. Patent No. 4,692,147.

Lastly, Dreessen (5,843,150) describes a device and method for providing electrical and/or fluid treatment to a patient's brain. With respect to providing fluid, the device comprises a lead (e.g. catheter) and a pump, similar to the Medtronic Synciro Med pump.

A common feature in all of the above described pharmaceutical delivery devices is the use of a pump. One common type of pump is the mechanical pump. In a mechanical pump, a motive force is applied to a liquid, which expels the liquid from the body of the pump. Battery-operated motors, inflated balloons, and the vapor pressure of volatile liquids are typically used to provide the motor force to drive such pumps. However, mechanical pumps suffer from particular disadvantages: complexity, expense, and fallibility.

A second type of pump is an osmotic pump. A common type of osmotic pump includes a chamber containing water, a chamber containing salt, and a chamber containing a pharmaceutical agent. The water chamber is separated from the salt chamber by a rigid membrane that is permeable to water but not to salt. The salt chamber is separated from the chamber containing the pharmaceutical agent by an impermeable partition, typically an impermeable resilient membrane. In operation, water flows through the rigid membrane to the salt chamber increasing the volume of the salt chamber and exerting pressure on the resilient membrane between the salt chamber and the chamber containing the pharmaceutical agent. The volume of the chamber containing the pharmaceutical agent is thereby reduced and expelled from the pump. A primary example of an osmotic pump is the Alzet Osmotic Pump (see http://www.alzet.com.). However, like mechanical pumps, the major disadvantages of osmotic pumps are their complexity and cost. The invention described herein, however, introduces a pharmaceutical delivery device that requires no pump. Rather, the delivery device utilizes an endogenous pressure of the body to create a flow of the pharmaceutical to the target site. For example, one embodiment of the delivery device comprises a first conduit having a distal end and a proximal end wherein the distal end is positioned within an area of the brain accessible to cerebral spinal fluid (CSF). The proximal end of the distal conduit is secured to a structure capable of serving as a pharmaceutical reservoir. A second conduit, having a distal end and a proximal end, is attached to the pharmaceutical reservoir at its proximal end. The distal end of the second conduit is positioned at a target site in the brain where a pharmaceutical agent is to be delivered. A shunt can also be positioned at the target site to maintain a positive flow into the target site and preclude the likelihood of edema in the brain.

A variety of types of pharmaceutical agents can be administered through the novel pharmaceutical device described herein. Examples include but are not limited to: commonly manufactured pharmaceuticals, emulsified pharmaceuticals, living cells that produce a therapeutic product, gene products, DNA, plasmids designed to alter genetic signals, dyes or markers used for diagnostics, endogenous or exogenous proteins intended to alter or affect the target tissue, growth factors, hormones, second messengers, or mRNA, etc. Other novel characteristics of the invention, which include not only the physical structure of the device but its method of operation, together with further objects and advantages of the invention, will be better understood from the following descriptions and figures. Each figure of a preferred embodiment, however, is merely intended to illustrate the invention by way of example. Thus, it is to be expressly understood that the drawings are for illustration and enabling purposes only, and therefore not intended in any fashion to be a definition of the limits of the invention.

SUMMARY OF THE INVENTION According to the principles of the present invention, a pharmaceutical delivery device is described wherein a pharmaceutical agent can be continuously delivered to a target site within the body without the cost and complexity associated with other types of delivery devices. The pharmaceutical delivery device herein utilizes an endogenous pressure of the body to move the therapeutic composition from a reservoir to the target site. Thus, the device can be used anywhere a pressure gradient can be found in the body (i.e. cerebral spinal fluid, blood flow, digestive device, etc.).

Further, the principles of the present invention disclose that the pharmaceutical delivery device as described herein may also encompass a pressure modulating component and may be synthesized of biodegradable materials.

BRIEF DESCRIPTION OF THE DRAWINGS

For a more complete understanding of the present invention, and the advantages thereof, reference is now made to the following descriptions taken in conjunction with the accompanying drawings, in which: FIGURES 1A and IB are a top- and side-view of a pharmaceutical delivery device without any modifications;

FIGURE 2 is a partially sectional view of a valve assembly; FIGURE 3 is another partially sectional view of a valve assembly; FIGURE 4 is a partially sectional view of conduits having a micro dialysis tip; FIGURE 5 is a partially sectional view of conduits having a loop dialysis tip; FIGURE 6 is another partially sectional view of conduits having another type of loop dialysis tip;

FIGURE 7 is a partially sectional view of a conduit aligned in a linear-flow dialysis;

FIGURE 8 is sagittal view of a human brain, which illustrates the use of the pharmaceutical delivery device;

FIGURE 9 is a view of the device and its modifications for use in delivering pharmaceuticals to the coronary region;

FIGURE 10 is an enlarged view of the pharmaceutical delivery device as it can be used in the cardio-vascular system; FIGURE 11 illustrates the use of the device with its modifications in connection with the digestive system;

FIGURE 12 is a partially sectional view of the target infuser;

FIGURE 13 is a side-view of an attachment to the device wherein the attachment provides for a dynamic endogenous pressure and means for maintaining a consistent flow rate from the lateral ventricle to a target site in the brain; and

FIGURE 14 is an enlarged view of the means of isolating flow between the target site and shunt flow within the target infuser.

DESCRIPTION OF THE PREFERRED EMBODIMENTS The principles of the present invention and their advantages are best understood by referring to the illustrated embodiment depicted in FIGURES 1-14 of the drawings, in which like numbers designate like parts.

A pharmaceutical delivery device, which permits for the delivery of pharmaceuticals to the brain and other regions of the body, is described wherein the device can continuously deliver a fluid-like therapeutic composition (which can comprise a pharmaceutical agent) to a target site within the body without the cost and complexity associated with other types of delivery devices.

The pharmaceutical delivery device herein utilizes an endogenous pressure of the body to move the therapeutic composition from a reservoir to the target site. Thus, the device can be used anywhere a pressure gradient can be found in the body (i.e. cerebral spinal fluid, blood flow, digestive device, etc.). An embodiment of the pharmaceutical delivery device described herein can be of numerous components and arrangements thereof. Although various embodiments exist for the pharmaceutical delivery device, preferred embodiments and the use thereof are depicted in FIGURES 1-14.

FIGURES 1A and IB depict a top- and side-view of the configuration of a pharmaceutical delivery device 10. It should be noted that actual physical embodiments of the apparatus disclosed in the present figures may be scaled differently depending on the application; the scaling of the present figures is therefore for illustrative purposes only. Additionally, edges shown in the figures may be rounded or smoothed and tubular structures may have elliptical or polygonal cross-sections, as well as circular cross-sections. In general, the device 10 comprises a central assembly 20. a valve assembly 30, a first conduit 80, target dialysis membrane 100, a second conduit 110, a target infuser 135, a third conduit 150, a fourth conduit 175, and a shunt 200. All parts of the device operate together to deliver a fluid-like therapeutic composition 27 to a target site 500 while precluding any edema-like effects in the tissue of the target site 500. The conduits 80, 1 10. 150 and 175 can be treated as one continuous conduit. These conduits, either independently or collectively, can be a cannula, catheter or a form of tubing.

The conduits 80, 110, 150, 175, shunt 200, target infuser 135, central assembly 20, and valve assembly 30 are preferably made from biodegradable materials known to those skilled in the art. Preferred biodegradable materials can be generally classified into eight groups, which include:[l] biodegradable linear aliphatic polyesters and their copolymers (i.e., polyglycolide, polylactide, polycaprolactone, polyhydroxybutyrate), [2] copolymers of these and other monomers including poly(glycolide-trimethylene-carbonate), poly(L-lactic acid-L-lysine) and others; [3] polyanhidrides, [4] poly(orthoesters), [5] poly(ester-ethers) like poly(p-dioxanone); [6] biodegradable polysaccarides like hyaluronic acid, chitin and chitosan; [7] poly-amino acids like poly-L-glutamic acid and poly-L-lysine; and [8] inorganic biodegradables such as phosphazine and poly[bis(carboxy-latophenoxy) phosphazine]. Polyethylene glycol (PEG,)poly-L-lactic acid (PLLA), poly-&-caprolactone (PCL), and poly(p-dioxanone)(PDO) is also a preferred biodegradable material.

Materials can be selected by their crystallinity as single polymers or copolymer, polymer mixtures, or situations where different parts of the device are manufactured of different polymers to achieve the desired biodegradation of the device for the duration of a treatment period. Materials can be selected based on their method of degradation, which includes but is not limited to hydrolysis, enzyme degradation, or photodegradation depending on the photosource. This list of acceptable biodegradable polymers should not be construed as exhaustive. Additionally, the length of the expected course of treatment (e.g., weeks, months or years) is a factor in selecting the biodegradable material.

Manufacture of the components of the pharmaceutical drug delivery device 10 incorporate common practices regarding the use of biodegradable polymers. For example, the forming of the pharmaceutical drug delivery device 10 from the biodegradable materials typically involves heating the material to their melting point. The material can then be cased. shaped, molded, extruded or machined, or similarly manipulated using a solvent system.

Continuing with FIGURE 1, central assembly 20 comprises a pharmaceutical depot 25. which is capable of supporting a pre-dissolution solid or fluid-like therapeutic composition 27. This composition can be combined with numerous medicaments needed to treat the tissue at target site 500. The pharmaceutical depot 25 is fiowingly engaged at its distal end 28 to conduit 110. At the proximal end 29 of pharmaceutical depot 25, the pharmaceutical depot 25 is fiowingly engaged to valve assembly 30.

In one preferred embodiment, valve assembly 30 is fiowingly engaged to proximal end 85 of conduit 80 by attachment member 50. In this embodiment, it is preferable to have a filter 51 , constructed for example of Teflon or PTFE, positioned downstream from pharmaceutical depot 25 for filtering out particulates. In yet another preferred embodiment, valve assembly 30 can be fiowingly engaged to distal end 28 of conduit 110 by attachment member 50. In either of the embodiments, attachment member 50 is an elbow joint made from the biodegradable materials previously discussed. The distal end 90 of conduit 80 resides in an area of the body where an endogenous pressure resides, thus connecting central assembly 20 to a portion of the body that produces an endogenous pressure (FIGURES 8, 9, 10, and 11 provide different examples of endogenous pressures located in the body). Preferably, the inner surfaces of depot 25 and conduits 80, 110, 150 and 175 are lined or coated with a material which inhibits the adhesion of living cells, platelets and other organic and inorganic particulates thereto.

Valve assembly 30, as depicted in FIGURES 1. 2 and 3, comprises an inner cylindrical component 31, an outer cylindrical component 32, adjustable valve 35, a plurality of openings 36, 37, 38, means 40 for adjusting valve 35, and gasket 45. A preferred means for adjusting valve 35 is the use of an adjuster knob 40 as illustrated in FIGURE 1. Other preferred means for adjusting valve 35 is a control device 250 electrically wired to the valve 35 or a wireless remote control having a receiver device on the valve 35. Gasket 45 prevents the leakage of fluid from valve 35 at adjuster knob 40. Inner cylindrical component 31 is rotationally engaged in the outer cylindrical component

32. The inner cylindrical component 31 can rotate within the outer cylindrical component 32, which remains static with respect to central assembly 20. The outer cylindrical component 32 acts as a gasket sealing the entire surface area of inner cylindrical component 31. One end of the cylindrical component 32 is closed (end 41) as the other remains open (end 42) to receive the endogenous fluid creating the pressure that drives the pharmaceutical delivery device 10. Turning now to FIGURE 3, the outer cylindrical component 32 is depicted more definitively. The outer cylindrical component 32 comprises at least one opening 33, which is fiowingly engaged to the pharmaceutical depot 25. Open end 42 receives the endogenous fluid flowing from conduit 80 through attachment member 50, and into inner cylindrical component 31.

Turning back to FIGURE 2, the plurality of openings 36, 37, and 38 of inner cylindrical component 31 are of various sizes. The various sizes of the openings assist in controlling the amount of endogenous fluid entering into the pharmaceutical depot 25. Opening 36 has an area which is greater than opening 37, which is greater than the area of opening 38. When the pharmaceutical delivery device 10 is in operation, the operator can select either openings 36, 37 or 38 to control the amount of endogenous fluid (pressure) entering the pharmaceutical depot 25. Additionally, the operator can elect to use only a portion of the openings 36, 37, and 38 to more finely control the endogenous fluid flow (pressure) into the pharmaceutical depot 25. In another embodiment the type of valve, number or size of openings merely illustrate a possible means to control flow. This object 32 is merely illustrative of a valve component capable of controlling the flow of fluid into 25.

Returning to FIGURE 1, the distal end 28 of the central assembly 20 attaches to a proximal end 115 of conduit 110. When valve 35 is open (i.e. one of openings 36, 37, or 38) and aligned with the opening 33 at outer cylindrical component 32 and the opening at the proximal end 29 of pharmaceutical depot 25, the fluid-like therapeutic composition 27 flows from pharmaceutical depot 25 into conduit 110. The conduit 110 has a distal end 120 that is fiowingly engaged to a target infuser 135. The target infuser 135 is preferably made from the biodegradable materials as previously discussed.

Target infuser 135 is further depicted in FIGURE 12. Considering FIGURES 1. 12 and 14 collectively, target infuser 135 specifically attaches to conduit 1 10 via attachment member 400. Preferably, a gasket 405 is adhered to the attachment member 400, which further connects the attachment member 400 to the bypass tubing 410. Bypass tubing 410 includes a space 420 wherein the fluid-like therapeutic composition 27 flows through and into conduit 150. The distal end 425 of bypass tubing 410 completely encompasses conduit 150 and is closed. Bypass tubing 410 contains two (2) openings 480 and 490, which are specifically illustrated in FIGURE 14. Opening 480 is of a diameter such that conduit 175 can be securely attached within opening 480 during operation of device 10. Opening 490 is of a diameter such that conduit 150 can be securely attached within opening 480 during operation of device 10. Bypass tubing 410 is of a size such that the shown space tubing receives bypass tubing 410, in a manner such that 410 is equidistant from the luminal, paillar surface of 430. The flow of fluid-like therapeutic composition 27 travels through bypass tubing 410, via conduit 110 and into the conduit 150 where it enters target site 500 through dialysis membrane 100 (See FIGURES 4-7 hereinafter for a more specific discussion). Excess fluid at target site 500 can travel through dialysis membrane 100 and into conduit 175. From conduit 175, the excess fluid enters shunt space tubing 430 at cavity 440 and flows into shunt 200, which extends to an area of lower pressure within the body or to the exterior surface of the body. An outer covering 450 encases the bypass tubing 410 and shunt space tubing 430. The shunt 200 is fixably attached to the outer covering 450.

Turning back to the FIGURES 4-7 provide partially sectional views of distal ends 160 and 177 of respective conduits 150 and 175 as they interact at the target site 500 in the body. FIGURE 4 depicts a microdialysis tip comprising a dialysis membrane 100 at the distal ends 160 and 177 of respective conduits 150 and 175. (It should be noted that the bifurcation of conduits 150 and 175 can also take place outside the tissue, with their subsequent convergence near the target area). The fluid-like therapeutic composition 27 flows from the pharmaceutical depot 25 into the conduit 150 and through the dialysis membrane 100 to the target site 500. To prevent the effects of edema and/or other types of swelling within the target site 500, and to maintain the pressure gradient, fluid at the target site can travel away from the target site 500 through dialysis membrane 100 into inner conduit 175. The conduit 175 has a smaller circumference than conduit 150 and can therefore more readily receive excess flow. Conduit 175 extends from the target site 500 to a shunt 200 where the excess fluid is extracted to a region of the body having lower pressure or from the body entirely. The length of inner conduit 175 can be of variable lengths depending on the pressure and tissue density located at the target site 500. The inventor refers the reader to Laske (U.S. Patent 5,720,720) for an understanding of diffusion rates into various tissue type, in particular brain tissue.

FIGURE 5 depicts a loop dialysis tip at the distal end 160 and 177 of respective conduits 150 and 175. A fitting 180 separates conduits 150 and 175 at their respective distal ends. The fitting 180 is preferably made of a biodegradable material as previously discussed. Additionally, support 190, which is also preferably derived of a similar biodegradable material as previously discussed extends along the outer surface of conduits 150 and 175. The fluid-like composition 27 flows through conduit 150 through dialysis membrane 100 into the target site 500. The internal pressure at the target site 500 can be relieved by allowing excess fluid at target site 500 to flow back through dialysis membrane 100, through conduit 175 and into shunt 200 where the excess fluid is extracted to a region of the body having lower pressure or from the body entirely.

The dialysis tip depicted in FIGURE 6 is similar to the dialysis tip described in FIGURE

5 except for a few modifications. The conduit 175 of FIGURE 6 has a smaller circumference than the conduit 175 of FIGURE 5. This is to assist in removing excess fluid more readily from target site 500. Additionally, the smaller conduit 175 of FIGURE 6 resides within a separate conduit 190 which extends approximately to the target infuser 135. The purpose of positioning conduit 175 into conduit 190 is to alter the flow of fluid from the target site 500 and provide another means that can assist in adjusting the pressure at the target site 500.

FIGURE 7 depicts yet another type of flow dialysis. In FIGURE 7, conduit 150 attaches to dialysis membrane 100 at its distal end 160 preferably by a sealant 105. A preferred sealant can be methylacrylate vet-bond or SuperGlue®, although any sealant that is inert to the body and maintains a strong bond would suffice. Dialysis membrane 100 extends linearly from conduit 150 to shunt 200. Shunt 200 extends to the outer surface of the body and is fixably attached to structural support 198 by a sealant similar to sealant 105. Dialysis membrane 100 extends beyond the proximal end 201 of the shunt 200 and attaches to structural supports 198 by sealant 105. In this embodiment of the invention, shunt 200 does not reside at target infuser 135, but proceeds immediately to a low pressure location. The linear flow dialysis, as illustrated in FIGURE 7, allows for the flow of fluid-like therapeutic composition 27 to diffuse through dialysis membrane 100 to target site 500. The pressure at the target site 500 is maintained at a relatively constant level as a result of the excess fluid being taken up by dialysis membrane 100 and vacated into shunt 200, where the excess fluid is extracted to a region of the body having lower pressure or from the body entirely.

Turning to FIGURE 13, pharmaceutical delivery device 10 can further comprise a pressure modulating component (PMC) 300. The PMC 300 provides for a dynamic endogenous pressure that may be present within the cerebral spinal device under extraordinary movement or acceleration of forces. PMC 300 as depicted in FIGURE 13, is fiowingly engaged to pharmaceutical delivery device 10. The preferred embodiment of the PMC 300 as depicted in FIGURE 13 comprises an electronic control device 305, a balloon carrier cannula 310. a first conduit 340, pressure sensor 375 and a balloon-like apparatus 390.

For example, as cerebral spinal fluid (CSF) travels from the conduit 80 through valve assembly 30 and into pharmaceutical depot 25, where the CSF contacts a pressure sensor 375. Preferably the pressure sensor 375 is securely attached within the pharmaceutical depot 25. Moreover, fluid flow should be laminar rather than turbulent to prevent clotting (if blood pressure is the drawing force), bubbles or other impediments. The CSF drives the fluid-like therapeutic composition 27 within pharmaceutical depot 25 past barrier 800.through the conduit 110 and into target infuser 135. From the target infuser 135, the therapeutic composition 27 flows into conduit 150, through dialysis membrane 100 and into the target site 500. The pressure sensor 375 records the pressure within pharmaceutical depot 25 and transmits this recording to the control device 305, which has a preset pressure level in which the pressure sensor recordings are compared. Should a pressure change occur within the pharmaceutical depot 25, as a result of either pressure increase or decrease, a balloon-like structure 390 can be discharged into the ventricular system and inflated or deflated to maintain the desired preset pressure level previously input in control device 305. To maintain the integrity of the ventricular system, the balloon-like apparatus 390 can inflate and deflate either as needed by the patient or during times of immobility (i.e. sleep). The balloon-like apparatus 390 can be inflated through application of a syringe device injecting a bio-inert fluid into the balloon-like apparatus. An example of a bio-inert fluid can be phosphate buffer solution, phosphate buffered saline or hepes.

EXAMPLE 1 The pharmaceutical delivery device 10 is conducive for delivering fluid-like therapeutic composition 27 to a particular region of the brain. FIGURE 8 illustrates such an application. The distal end 90 of the conduit 80 is first positioned within a lateral ventricle of the brain. The central assembly 20 is preferably fixated to a region of the brain directly superior to the position of conduit 80 as it resides in a ventricle of the brain. Preferably, central assembly 20 is implanted within the skull so that the superior surface of the central assembly 20 is flush with the superior surface of the skull. Conduits 150 and 175 are then implanted into the region of the brain comprising the target site 500.

After the pharmaceutical delivery device 10 has been properly implanted into the brain, the openings in valve assembly 30 are arranged so that cerebral spinal fluid can travel into conduit 80 through valve assembly 30 and into the pharmaceutical reservoir 25. The pressure created within pharmaceutical depot 25 by the cerebral spinal fluid causes the fluid-like therapeutic composition 27 to travel into conduit 110 and into target infuser 135. From target infuser 135, which is preferably fixated in the Dura mater or skull at a location superior to target site 500, the fluid-like therapeutic composition flows into conduit 150. The fluid-like therapeutic composition 27 then flows through dialysis membrane 100 and contacts the damaged or diseased tissue at target site 500. As a result, the damaged and/or diseased tissue receives the necessary medication.

The flow of the fluid-like therapeutic composition 27 enters the target site 500, causing the pressure within target site 500 to increase because the area is limited by the surrounding tissues. Thus, to prevent the occurrence of edema in the brain or damage to surrounding tissue, fluid residing within the target site 500 can flow back through the dialysis membrane 100 and enter conduit 175, which extends beyond conduit 150 at the target site 500. The fluid traveling in conduit 175 can then enter shunt 200 and be vacated to a region of the body having lower pressure on the exterior surface of the body. EXAMPLE 2

Whereas the pharmaceutical delivery device 10 used in the brain relies on the pressure generated by the cerebral spinal fluid, the coronary bypass modification of the pharmaceutical delivery device 10 relies on swift cardiac blood flow. Device 10 can be used in conjunction with the circulatory system to treat tumors, bone marrow cancer, and other conditions in which the ability to bypass damaged tissue and specifically target pharmaceuticals is advantageous. FIGURE 9 illustrates device 10 on the aortic arch. However, the preferred location for grafting is any large artery involving high-pressure blood flow.

The blood flow within the large, high-pressured artery or aortic arch travels into the pharmaceutical depot 25 of the central assembly 20, through the conduit 80, which is surgically attached to the aortic arch such that distal end 90 of the conduit 80 proceeds into the inner lining of the aortic arch tissue. The blood flow travels through conduit 80 and into pharmaceutical depot 25 where it drives fluid-like therapeutic composition 27 into conduit 1 10, which connects to the target site 500. FIGURE 10 provides a more detailed illustration of device 10 in conjunction with the circulatory device. Conduit 1 10 is made of an inert substance having a resilient strength similar to that of a healthy artery. A preferred substance would be a biodegradable material as previously discussed, modified to be nonthrombogenic.

Because the pharmaceutical delivery device 10 resides internally, a control device 250 is required to regulate the flow of the fluid-like therapeutic composition 27 to the target site 500. Control device 250 is securely attached to valve assembly 30 of device 10 by control wire 265. Control device 250 can thus adjust the opening of valve assembly 30 and control the flow of blood through device 10. A preferred control device would be an electronic device as known by those skilled in the art of electronics. Other possible devices for controlling the opening of valve assembly 30 would be through use of a wireless remote control device. The control device 250 can be located in any body cavity preferred by the surgeon.

EXAMPLE 3

FIGURE 11 depicts device 10 operating in conjunction with the intestinal device. Central assembly 20 can be grafted onto the common bile duct to utilize the emulsion salts ejected by the gall bladder. However, unlike cerebral spinal fluid or blood, bile salts do not continuously flow from the gall bladder. Bile salts, rather, are ejected through contraction of the gall bladder when the volume of bile salts reaches approximately 40.0 to 70.0 mL. Once the bile salts are released into the common bile duct, the emulsification salts can flow through conduit 80 (not depicted in FIGURE 11), which is surgically fixated within the interlining of the common bile duct. From the conduit 80, the bile salts flow through open valve assembly 30 (also not depicted in FIGURE 1 1) and into pharmaceutical depot 25. The emulsification salt can then react with the pharmaceutical agent of the fluid-like composition 27, which requires emulsification before becoming active. Alternatively, the emulsification salts can degrade encapsulation-media material, such as in the case of lipid or polymer based microspheres used to convey the pharmaceutical agent. The pharmaceutical agent then passes from the pharmaceutical reservoir 25 and into conduit 1 10, which is surgically inserted into a region of the duodenum preferred by the surgeon. The pharmaceutical agent is then absorbed into the intestine and delivered to the target site through the circulatory system.

Although the invention has been described with reference to a specific embodiments, these descriptions are not meant to be construed in a limiting sense. Various modifications of the disclosed embodiments, as well as alternative embodiments of the invention will become apparent to persons skilled in the art upon reference to the description of the invention. It should be appreciated by those skilled in the art that the conception and the specific embodiment disclosed may be readily utilized as a basis for modifying or designing other structures for carrying out the same purposes of the present invention. It should also be realized by those skilled in the art that such equivalent constructions do not depart from the spirit and scope of the invention as set forth in the appended claims.

It is therefore, contemplated that the claims will cover any such modifications or embodiments that fall within the true scope of the invention.

Claims

WHAT IS CLAIMED:

1. A pharmaceutical delivery device for providing localized treatment against diseases or ailments comprising: a conduit having a first opened end and a second opened end wherein said conduit receives an endogenous fluid; and a reservoir capable of supporting a fluid, said conduit extends through said reservoir in a manner to allow said medicament to flow from said reservoir into said conduit and towards said second end of said conduit, which is positioned in a target area.

2. A pharmaceutical delivery device as provided in Claim 1 wherein said device is implanted into the skull.

3. A pharmaceutical delivery device as provided in Claim 1 wherein said device is implanted into an artery or appropriate vessel of the cardiovascular system.

4. A pharmaceutical delivery device as provided in Claim 1 wherein said device is implanted in the common bile duct.

5. A pharmaceutical delivery device as provided in Claim 1 wherein said device is made from biodegradable materials from the group consisting of biodegradable linear aliphatic polyesters and their copolymers, copolymers of biodegradable linear aliphatic polyesters and other monomers including poly(glycolide-trimethylene-carbonate), poly(L-lactic acid-L-lysine) and others, polyanhydrides, poly(orthoesters), poly(ester-ethers), biodegradable polysaccarides, poly-amino acids, inorganic biodegradables, and polyethylene glycol.

6. A pharmaceutical delivery device as provided in claim 1 wherein said reservoir is part of a central assembly that is fiowingly engaged to said conduit at a valve assembly of said central assembly, said valve assembly is fiowingly engaged to said reservoir, said reservoir is capable of maintaining a fluid to be delivered to a target area.

7. A pharmaceutical delivery devices as provided in claim 1 further comprising a pressure modulating component that is fiowingly engaged to said pharmaceutical delivering device.

8. A pharmaceutical delivery device as provided in Claim 1 further comprising a pressure modulating component.

9. A method according to Claim 2 wherein said fluid includes a medicament to treat said target area.

10. A method for administering a fluid to a target area using an endogenous pressure in conjunction with a device comprising a conduit capable of transporting a fluid to a target area and a reservoir capable of supporting a fluid, said reservoir is fixedly attached to said conduit in a manner to allow said pharmaceutical mixture to flow from said reservoir into said conduit to said target area.

11. A pharmaceutical delivery device, which employs the use of an endogenous body pressure to drive a fluid to a target area comprising: a first conduit having a distal and a proximal end, said distal end is at a region of the body having an endogenous pressure; a central assembly fiowingly engaged to said proximal end of said first conduit at a valve assembly of said central assembly, said valve assembly being fiowingly engaged to a proximal end of a pharmaceutical depot of said central assembly, said pharmaceutical depot being capable of maintaining a pharmaceutical agent to be delivered to a target site; and a second conduit having a proximal end and a distal end, wherein said proximal end is fiowingly engaged to a pharmaceutical depot of said central assembly and said distal end is inserted at the target region for the pharmaceutical composition.

12. A method for treating diseases or ailments using a pharmaceutical delivery device, which employs the use of an endogenous body pressure to drive a pharmaceutical to a target area comprising: a first conduit having a distal end and a proximal end, said distal end is at a region of the body having an endogenous pressure; a central assembly fiowingly engaged to said proximal end of said first conduit at a valve assembly of said central assembly, said valve assembly being fiowingly engaged to a proximal end of a pharmaceutical depot of said central assembly, said pharmaceutical depot being capable of maintaining a pharmaceutical agent to be delivered to a target site; and a second conduit having a proximal end and a distal end, wherein said proximal end is fiowingly engaged to said pharmaceutical depot of said central assembly and said distal end is positioned in said target area.

13. A pharmaceutical delivery device, which employs the use of an endogenous body pressure to drive a pharmaceutical to a target area comprising: a first conduit having a distal end and a proximal end, said distal end is at a region of the body having an endogenous pressure; a central assembly fiowingly engaged to said proximal end of said first conduit at a valve assembly of said central assembly, said valve assembly being fiowingly engaged to a proximal end of a pharmaceutical depot of said central assembly, said pharmaceutical depot being capable of maintaining a pharmaceutical agent to be delivered to a target site; a second conduit having a proximal end and a distal end, wherein said proximal end is fiowingly engaged to a pharmaceutical depot of said central assembly and said distal end is inserted at the target region for the pharmaceutical composition; and a pressure modulating component that is fiowingly engaged to the pharmaceutical delivering device to regulate extreme pressures in said pharmaceutical delivering device.

14. A pharmaceutical delivery device as provided in Claim 13, wherein said pressure modulating component comprises an inflatable element.

15. A pharmaceutical delivery device as provided in Claim 13 wherein said device is implanted into the skull.

16. A pharmaceutical delivery device as provided in Claim 13 wherein said device is in an artery.

17. A pharmaceutical delivery device as provided in Claim 13 wherein said device is implanted in the common bile duct.

18. A method for treating humans using a pharmaceutical delivery device, which employs the use of an endogenous body pressure to drive a pharmaceutical to a target site in the body comprising: a first conduit having a distal and a proximal end, said distal end is at a region of the body having an endogenous pressure; a central assembly fiowingly engaged to said proximal end of said first conduit at a valve assembly of said central assembly, said valve assembly being fiowingly engaged to a proximal end of a pharmaceutical depot of said central assembly, said pharmaceutical depot being capable of maintaining a pharmaceutical agent to be delivered to a target site; a second conduit having a proximal end and a distal end, wherein said proximal end is fiowingly engaged to a pharmaceutical depot of said central assembly and said distal end is inserted at the target region for the pharmaceutical composition; and a pressure modulating component that is fiowingly engaged to the pharmaceutical delivering device to regulate extreme pressures in said pharmaceutical delivering device comprised of an electronic control device, a balloon-carrier cannula, a conduit, a pressure sensor, and a balloon-like apparatus.

19. A method for treating humans using an implantable pharmaceutical delivery device, which employs the use of an endogenous body pressure to drive a pharmaceutical to a target site in the body comprising: a first conduit having a distal and a proximal end. said distal end is at a region of the body having an endogenous pressure; a central assembly fiowingly engaged to said proximal end of said first conduit at a valve assembly of said central assembly, said valve assembly being fiowingly engaged to a proximal end of a pharmaceutical depot of said central assembly, said pharmaceutical depot being capable of maintaining a pharmaceutical agent to be delivered to a target site; a second conduit having a proximal end and a distal end. wherein said proximal end is fiowingly engaged to a pharmaceutical depot of said central assembly and said distal end is inserted at the target region for the pharmaceutical composition; and a pressure modulating component that is fiowingly engaged to the pharmaceutical delivering device to regulate extreme pressures in said pharmaceutical delivering device comprised of an electronic control device, a balloon-carrier cannula, a conduit, a pressure sensor, and a balloon-like apparatus.

20. A pharmaceutical delivery device for providing localized treatment for diseases and ailments, comprising: a first conduit having a proximal end and a distal end, said distal end of said first conduit can receive an endogenous fluid; a reservoir capable of supporting a medicament, said reservoir is attached to said proximal end of said first conduit; and a second conduit having a proximal end and a distal end, said proximal end of said second conduit is attached to said reservoir to allow said medicament to flow from said reservoir as a result of said endogenous fluid flowing into said first conduit thereby producing a pressure gradient to move said medicament from said reservoir through said second conduit and from said distal end of said second conduit into a target area requiring treatment from said medicament.

21. A pharmaceutical delivery device as provided in Claim 20 wherein said device is made from biodegradable materials from the group consisting of biodegradable linear aliphatic polyesters and their copolymers. copolymers of biodegradable linear aliphatic polyesters and other monomers including poly(glycolide-trimethylene-carbonate), poly(L-lactic acid-L-lysine) and others, polyanhydrides, poly(orthoesters), poly(ester-ethers). biodegradable polysaccarides, poly-amino acids, inorganic biodegradables, and polyethylene glycol.

22. A pharmaceutical delivery device as provided in Claim 20 wherein said pharmaceutical delivery device is used to deliver a medicament to a target area in the brain.

23. A pharmaceutical delivery device as provided in Claim 20 further comprising a pressure modulating component that is fiowingly engaged to said pharmaceutical delivering device, said pressure modulating component regulates pressure or extreme pressures in said pharmaceutical delivering device.

24. A pharmaceutical delivery device as provided in Claim 20 wherein said pharmaceutical device uses the cerebral spinal fluid to create a pressure gradient for delivering said medicament to said target area of the brain.

25. A pharmaceutical delivery system for providing localized treatment for diseases and ailments, comprising: a first conduit having a proximal end and a distal end, said distal end of said first conduit can receive an endogenous fluid; a reservoir capable of supporting a medicament, said reservoir is attached to said proximal end of said first conduit; a second conduit having a proximal end and a distal end, said proximal end of said second conduit is attached to said reservoir to allow said medicament to flow from said reservoir as a result of said endogenous fluid flowing into said first conduit thereby producing a pressure gradient throughout said pharmaceutical delivery system to move said medicament from said reservoir through said second conduit and from said distal end of said second conduit into a target area requiring treatment from said medicament.