Self-regenerating drug administration device

An implantable dispenser for infusing a desired drug into the blood stream. The dispenser is adapted to be spliced into a blood vessel so that blood flows freely through it. Within the dispenser is a replaceable biomass cartridge containing a colony of microorganisms which produce the drug.

BACKGROUND OF THE INVENTION 
1. Field of the Invention 
This invention pertains to the field of implantable medical devices, and in 
particular to implantable drug dispensers. 
2. State of the Prior Art 
Various types of drug delivery systems are well known in the prior art. The 
simplest and most common of these systems employs an elevated container 
attached to a tube which is coupled to a needle inserted into the 
patient's body. In such a system the rate of flow is controlled by a valve 
which sets the drip rate of the drug from the container into the tube. 
This primary disadvantage of this system is the mobility limitation 
imposed on patients. 
Recently, much progress has been made toward the production of completely 
implantable infusion systems. Most such systems employ a reservoir for 
containing the drug, a tube leading from the reservoir to a delivery site, 
and a valve controlling the rate of flow of the drug into the body. Some 
systems rely on simple diffusion of the drug, however, most systems employ 
a pumping mechanism to force the drug into the delivery site. Miniaturized 
roller pumps and pressurized reservoirs are two common approaches to 
providing such a pumping force. 
Common to all of the implantable systems is the need to refill the 
reservoir at regular intervals. Typically this is accomplished by 
providing the reservoir with a puncturable septum and mounting the 
reservoir immediately under the skin so that it may be filled by 
hypodermic syringe. The necessity to regularly refill the reservoir has an 
inherent disadvantage in that each time the hypodermic needle pierces the 
skin and enters the reservoir, it carries with it minute amounts of tissue 
and debris which contaminate the drug supply and tend to clog the fluid 
passageways within the dispenser. 
In order to contain a sufficient quantity of the drug to provide for 
release over an extended period of time, the prior art devices are 
generally filled with a drug in concentrated form. The concentrated form 
of the drug in some cases leads to crystallization of the drug and 
blockage of the fluid passageways within the dispenser. 
Recently, research has been undertaken which is directed toward the use of 
body cells cultured outside the body to produce drugs such as insulin. 
Such research is described in the article "A Hybrid Artificial Pancreas" 
by Chick, et al., vol. XXI Trans. Amer. Soc. Artif. Int. Organs, 1975. 
This article discloses that beta cells may be cultured on semipermeable 
membranes of a type used for artificial kidneys. The particular membrane 
utilized is fabricated of XM-50 acrylic copolymer with a maximum molecular 
weight of 50,000 and is manufactured by Amicon Corp. of Lexington, MA. 
These membranes are permeable to glucose and insulin, as well as to 
oxygen, carbon-dioxide and water. 
SUMMARY OF THE INVENTION 
The present invention provides a drug dispenser which is believed to avoid 
the cited disadvantages of the prior art structures. The present invention 
describes an implantable drug dispenser which does not require regular 
refilling because the drug is manufactured within the dispenser. Further, 
the dispenser is adapted to be spliced in line with a blood vessel, so 
that blood flows freely through the dispenser at all times, providing for 
instant dilution of the drug, eliminating clogging problems due to drug 
crystallization. 
The dispenser is designed around a replaceable biomass cartridge. This 
cartridge contains a colony of microorganisms which produce the desired 
drug. These microorganisms may be isolated colonies of body cells which 
produce the desired drug. Alternatively, a colony of a genetically 
modified bacteria may serve as the source of the desired drug. Recently, 
the technology of gene splicing has become well known and early successes 
have been recorded, using modified E. Coli bacteria. For purposes of the 
present invention, the bacterial colony should be growth-limited to avoid 
overpopulation of the biomass cartridge. 
The desired organisms are contained within a semipermeable membrane 
capsule. In order to maximize the surface area for delivery of the drug 
maximizing the diffusion rate of the product into the blood stream it may 
be desirable to encapsulate colonies of the microorganisms within smaller 
membrane units within the membrane capsule. These smaller membrane units 
may take the form of microspheres. The semipermeable membrane capsule 
surrounds the microspheres and allows for passage of glucose and oxygen 
carried by the blood stream into the capsule and the passage of bacterial 
carbon dioxide, water and the drug out of the capsule and into the blood 
stream. The capsule is mounted within a replaceable biomass cartridge and 
floats freely therein. The biomass cartridge is, in turn, mounted within a 
dispenser body adapted for splicing into a blood vessel. 
As assembled, the dispenser presents a smooth bore through which blood may 
flow, bathing the membrane capsule. Dissolved oxygen and glucose flow 
through the membrane capsule while blood cells and large protein 
structures such as antibodies flow past the capsule. The central bore of 
the dispenser is flared at each end to provide a smooth transition from 
the blood vessel to the dispenser, minimizing clotting and damage to blood 
cells. 
The microorganisms, sustained by glucose and oxygen within the blood, do 
not require replacement on a regular basis. If replacement of the capsule 
should become necessary, the dispenser body is constructed so that it may 
be disassembled and the cartridge containing the membrane capsule removed 
and replaced with another capsule. A change in the type of drug or in the 
dosage of the drug may be effected by replacing the cartridge with a 
second cartridge having organisms adapted to produce a different drug or 
to produce greater amount of the drug. 
Further objects, features and advantages of the invention will become 
apparent upon a consideration of the following drawings and detailed 
description.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT 
FIG. 1 illustrates a side sectional view of the membrane capsule 13 used in 
the present invention. The membrane capsule consists of membrane 12, 
formed as an elongated capsule, encloses product producing bacteria or 
other microorganisms (not illustrated). Membrane 12 may be constructed of 
materials known to the art, such as the XM-SO acrylic copolymer discussed 
above. Membranous microspheres 10 float freely within membrane capsule 12, 
and may be made of the same material. Membrane 12 is of sufficient 
permeability to allow the passage of water, oxygen and nutrients into the 
membrane capsule and to allow passage of the product drug and waste 
products of the microorganisms out of the capsule. 
FIG. 2 illustrates the replaceable biomass cartridge of the present 
invention. The cartridge consists of a cylindrical cartridge body 14 
having a tubular bore 28 running through its length. O-rings 16 and 18 are 
molded on cartridge body 14 at its proximal end and O-rings 20 and 22 are 
similarly molded on cartridge body 14 at its distal end. Mounted within 
bore 28, at each end of cartridge body 14 are retaining screens 24 and 26. 
Membrane capsule 12 is mounted within cartridge body 14 and is retained 
therein by screens 24 and 26. Membrane capsule 12 is of smaller diameter 
than bore 28 so that blood cells and other large structures within the 
blood incapable of passing through the semipermeable membrane may pass 
freely through the cartridge body 14. The apertures in screens 24 and 26 
are also of sufficient size to permit such passage. In use, membrane 
capsule 13 floats freely within cartridge body 14. Because the membrane is 
flexible, but not elastic, membrane capsule 12 is of essentially fixed 
diameter, preventing blockage of bore 28 by membrane capsule 12. 
Cartridge body 14 is preferably a biocompatible, nonthrombogenic plastic 
such as polyurethane or Teflon.RTM.. Screens 24 and 26 are preferably of 
similar materials. 
The preferred embodiment shows the membrane floating freely within the bore 
of the cartridge, however, other embodiments wherein the membrane is 
attached to the cartridge body are believed to be within the scope of the 
invention. 
FIG. 3 illustrates a cut-away view of the present invention. The drawing 
illustrates the relationship between the cartridge and the dispenser body, 
and the method of attachment of the dispenser body segments. Cartridge 15 
is shown inserted in proximal dispenser body segment 30. Proximal 
dispenser body segment 30 is provided with a first bore 44 of equal 
diameter to bore 28 of cartridge body 14. Proximal dispenser body segment 
30 is also provided with a second bore 48 which is of equal diameter to 
O-rings 16 and 18 of cartridge body 14. When inserted, bore 44 aligns with 
bore 28. The proximal end 31 of proximal dispenser body segment is tapered 
to an outer diameter 33 of appropriate size for splicing to a blood 
vessel. By varying diameter 33, the dispenser may be adapted to use in 
blood vessels of differing sizes. Bore 44 is provided with a smooth flare 
46 as illustrated. O-rings 40 and 42 are molded on first dispenser body 
segment 30 and surround its proximal end 31. At its distal end, proximal 
dispenser body segment 30 is provided with a reduced diameter segment 32. 
Distal dispenser body segment 50 is provided with a third bore 56 of equal 
diameter to bore 28 of cartridge body 14, with a fourth bore 60 which is 
of equal diameter to O-rings 20 and 22, and with a fifth bore 62 which is 
of equal diameter to O-rings 34, 36 and 38 of proximal dispenser body 
segment 30. The distal end 51 of distal dispenser body segment 50 is 
tapered to an outer diameter 53 of appropriate size for splicing to a 
blood vessel. Third bore 56 is provided with a smooth flare 58, and distal 
dispenser body segment 50 is constructed so that the length of fifth bore 
62 is equal to the length of reduced diameter segment 32 of proximal 
dispenser body segment 30 and so that fourth bore 60 is of length equal to 
the protrusion of cartridge 14 from reduced diameter segment 32. The 
frictional fit of the O-rings and bores both seals the dispenser and holds 
it together. 
By so constructing the present invention, blood may flow smoothly from the 
proximal end of proximal dispenser body segment, through cartridge body 14 
at the distal end of distal dispenser body segment 50. By providing such a 
smooth flow path, clotting is minimized and damage to blood cells is 
reduced. Ramped sections 46 and 54 provide a smooth transition from the 
blood vessel to the dispenser body. Dispenser body segments 30 and 50 are 
preferable made of a biocompatible, nonthrombogenic plastic such as 
polyurethane or Tefon.RTM.. 
The preferred embodiment of the dispenser employs O-rings as means for 
sealing the points of attachment of the dispenser body segments and of the 
cartridge body and as means for attachment. However, other means of 
sealing and attachment such as screw threads, are believed to be within 
the scope of the invention. 
FIG. 4 illustrates a cross-sectional view of the present invention. First 
dispenser body segment 30, cartridge body 14 and membrane capsule 12 are 
shown in cross-section. O-ring 18, screen 24, and microsphere 10 are also 
visible. 
FIG. 5 shows the present invention as installed in a vein. Vein 64 is 
severed. One end of vein 64 is pushed over the proximal end 31 of proximal 
dispenser body segment 30 and the other end of vein 64 is pushed over the 
distal end 31 of distal dispenser body segment 50. O-rings 40, 42, 52 and 
54 provide a fluid seal. Suture 66 is tied around vein 64 between O-rings 
40 and 42, stabilizing vein 64 with respect to proximal dispenser body 
segment 30 and further enhancing the fluid seal. Suture 68 similarly 
anchors and seals vein 64 to the distal end 31 of distal dispenser body 
segment 50.