MINIATURE IMPLANTED DRUG DELIVERY DEVICES AND INSERTER SYSTEMS FOR INTRODUCING SUCH DEVICES
A system (10, 200) and corresponding method for introducing a drug delivery device (18, 218) through at least part of a biological barrier starts with the drug delivery device (18, 218) deployed within a channel of a hollow needle (12, 212), The hollow needle is inserted into the biological barrier and the drug delivery device is pushed forward by a suitable plunger. The drug delivery device is preferably anchored to the biological barrier through a radially expanding retention arrangement (36, 36′, 36a), and is preferably filled with a liquid drug after deployment via a filling needle (24, 222) extending within the channel of the hollow needle (12, 212).
The present invention relates to miniature drug delivery devices and, in particular, it concerns drug delivery devices with particularly low flow rates, and inserter systems for introducing such devices into the body.
It is known to provide an implantable device which delivers a drug slowly over a period of time. This approach avoids problems of patient compliance, and provides particular advantages where delivery of a drug to a specific target location allows use of much lower overall dosage than would be required for systemic delivery, possibly avoiding undesirable side effects.
In some cases, slow drug delivery is achieved by providing a drug is dispersed in a matrix of resorbable material and is gradually released as the matrix breaks down in the body. Examples of this approach may he found in U.S. Pat. Nos. 4,351,337 and 4,450,150 to Sidman. This approach typically does not achieve highly uniform drug release rates, and is not suitable for drugs which must be delivered in a liquid form or which have high diffusion rates through the matrix materials.
Examples of implantable devices for delivery of liquid drugs include, but are not limited to, U.S. Pat. Nos. 5,163,920, 4,428,397, 4,820,273, 5,061,242, 5,993,414, 6,183,461 and 5,836,935.
Certain potential applications of such devices impose particularly demanding conditions. For example, ocular applications pose a challenge as to how to anchor an implanted device so that it does not drift within the internal cavity of the eye. Furthermore, the procedure for introducing and anchoring a highly miniature drug delivery device is difficult to perform reliably and safely.
There is therefore a need for inserter systems for introducing and anchoring miniature drug delivery devices into a body structure such as the eye.
SUMMARY OF THE INVENTIONThe present invention is a system and method for introducing miniature drug delivery devices. The invention also provides various structures for such miniature drug delivery devices.
According to the teachings of an embodiment of the present invention there is provided, a method for introducing a drug delivery device, the method comprising the steps of: (a) inserting the drug delivery device via a channel of a hollow needle through at least part of at least one layer of a biological barrier; and (b) subsequent to the inserting, filling the drug delivery device with a quantity of liquid drug via a filling needle extending within the channel of the hollow needle.
According to a further feature of an embodiment of the present invention, the drug delivery device comprises a reservoir and a proximal filling port deployed to allow introduction of a volume of a liquid drug into the reservoir to be released over a period of time, and wherein the inserting and filling are performed using a system comprising: (a) a hollow needle having a central channel and a tip, the drug delivery device being deployed within the central channel of the hollow needle; (b) a plunger displaceable so as to push the drug delivery device along the central channel and beyond the tip of the hollow needle; and (c) a liquid injection device including a filling needle extending within the central channel of the hollow needle for engaging the filling port so as to allow filling of the reservoir after at least part of the reservoir has been advanced beyond the hollow needle.
According to a further feature of an embodiment of the present invention, the reservoir is an inflatable reservoir sized for deployment within the central channel when substantially empty and inflatable by filling with a liquid drug to assume a deployed size greater than dimensions of the central channel.
According to a further feature of an embodiment of the present invention, the filling needle extends through at least part of the plunger such that the filling needle engages the filling port prior to the inserting of the drug delivery device.
According to a further feature Of an embodiment of the present invention, the drug delivery device deployed within the hollow needle, the plunger, the filling needle and the liquid injection device pre-filled with a quantity of a liquid drug, are preassembled into a single integrated delivery system for implanting and filling the drug delivery device within the body.
According to a further feature of an embodiment of the present invention, the tip of the hollow needle is a beveled tip terminating at a point for introducing the drug delivery device into the biological barrier without formation of a prior incision.
According to a further feature of an embodiment of the present invention, there is also provided an abutment surface surrounding at least part of the hollow needle so as to define a depth of penetration, and wherein the plunger has a. predefined fully-advanced position, such that, after penetration of the tip into or through the biological barrier and advancing of the plunger, the drug delivery device extends to a predefined depth into the body.
According to a further feature of an embodiment of the present invention, the drug delivery device includes a radially expandable retention configuration configured to anchor the drug delivery device relative to a layer or layers of the biological barrier.
According to a further feature of an embodiment of the present invention, the drug delivery device includes a resiliently compressible retention configuration configured to anchor the drug delivery device relative to a layer or layers of the biological harrier.
According to a further feature of an embodiment of the present invention, the biological barrier includes the ocular sclera.
There is also provided according to the teachings of an embodiment of the present invention, a system for filling an implanted drug delivery device with a liquid, the system comprising: (a) a syringe comprising a syringe body for receiving a quantity of the liquid, a filling needle and a plunger; (b) a pressure measurement arrangement associated with the syringe for measuring a pressure of the liquid within the syringe; and (c) a processing system comprising a processor, the processing system being associated with the pressure measurement arrangement so as to receive fluid pressure measurements, wherein the processing system is configured to process the fluid pressure measurements to monitor for at least one alarm criteria.
According to a further feature of an embodiment of the present invention, the at least one alarm criteria includes the measured pressure dropping below a threshold minimum value.
According to a further feature of an embodiment of the present invention, the at least one alarm criteria includes the measured pressure exceeding a threshold maximum allowed value.
According to a further feature of an embodiment of the present invention, the processing system is configured to generate a warning under conditions of the alarm criteria.
According to a further feature of an embodiment of the present invention, there is also provided a display associated with the processor, and wherein the processing system is configured to determine from the measured pressure a quantity of the liquid within the drug delivery device, and to display on the display an indication of the quantity of the liquid within the drug delivery device.
There is also provided according to the teachings of an embodiment of the present invention, a method for filling an implanted drug delivery device with a liquid, the method comprising: (a) providing the aforementioned filling system containing a quantity of the liquid; (b) inserting the filling needle into the drug delivery device and advancing the plunger of the syringe; and (c) monitoring an output of the processing system for an indication of the at least one alarm condition,
According to a further feature of an embodiment of the present invention, advancing of the plunger is interrupted, to allow measurement of the liquid pressure under zero-flow conditions.
The invention is herein described, by way of example only, with reference to the accompanying drawings, wherein:
The present invention is, according to a first aspect, a system and method for introducing a drug delivery device into a body. This first aspect of the invention may be implemented with a range of drug delivery devices, particularly those having a reservoir for storing a quantity of liquid drug for slow release. Other aspects of the present invention relate to devices and methods for refilling and retrieving the corresponding drug delivery devices.
The principles and operation of systems, methods and devices according to the present invention may be better understood with reference to the drawings and the accompanying description.
Referring now to the drawings,
In general terms, system 10 includes a hollow needle 12, having a central channel 14 and a tip 16, and a drug delivery device 18 comprising a reservoir for receiving a volume of a liquid drug to be released over a period of time. Drug delivery device 18 is small relative to the overall dimensions of system 10, and is best seen in
In certain particularly preferred embodiments, the reservoir of drug delivery device 18 is an inflatable reservoir sized for deployment within central channel 14 when substantially empty, and inflatable by filling with a liquid drug to assume a deployed size greater than dimensions of the central channel. Thus, when empty, drug delivery device 18 has lateral dimensions less than the inner diameter of channel 14, as shown in
The aforementioned approach of introducing the drug delivery device in a collapsed state and subsequently filling it facilitates introduction of the device via a much smaller needle canula than would otherwise be possible. Thus, certain preferred embodiments of the present invention employ a hollow needle 12 with internal diameter less than 2 millimeters. In certain particularly delicate applications such as ocular application, it may be preferred to employ internal diameters of less than 1 millimeter, and most preferably less than 0.5 millimeter. The deployed volume of the drug delivery device after filling is typically at least 10 times greater than the empty volume during deployment, thereby facilitating controlled delivery of relatively large quantities of drug.
According to certain particularly preferred embodiments of the present invention, introduction of the substantially empty drug delivery device and. filling of the device are performed sequentially using a single deployment system, as illustrated here. Thus, in the preferred example illustrated here, system 10 includes a liquid injection device, such as a filling syringe 22 (visible in
In the particularly preferred non-limiting example illustrated herein, filling needle 24 is integrated with plunger 20 so that the filling needle engages the filling port prior to advancing of the drug delivery device. In this case, according to certain preferred implementations, the engagement of filling needle 24 with filling port 26 is performed as a preparatory step prior to insertion of hollow needle 12 into the biological barrier. This is illustrated here with reference to the external views of
In a particularly preferred implementation, drug delivery device 18 is introduced and filled sequentially by a single integrated delivery system. Thus, the delivery system includes hollow needle 12, plunger 20, filling needle 24 and filling syringe 22, pre-filled with a quantity of a liquid drug, as illustrated in
Turning now to additional features of the preferred exemplary embodiment of
In the case of a pointed needle tip, a preferred sequence for insertion of needle tip 16 is illustrated schematically in
Referring to
According to another aspect of certain preferred embodiments of the present invention, drug delivery device 18 includes a radially expandable retention configuration 36 configured to anchor the drug delivery device within a layer, or between layers, of the biological barrier. According to a first implementation of this feature, as illustrated in
In the example of ocular deployment as exemplified in the drawings, the structure of the biological barrier of eye 100 is made up of a number of different layers, here designated schematically as layers 102, 104 and 106, corresponding to the conjunctiva, sclera and choroid, respectively. In this case, it is particularly preferred that the length of hollow needle 12 projecting from abutment surface 28a is chosen to correspond roughly to the depth of the boundary between two of the layers 104 and 106, so that expandable retention configuration 36 becomes lodged between layers 104 and 106 when deployed. Radially expandable retention configuration 36 then serves to anchor one end of drug delivery device 18 between the layers after removal of the delivery system, as shown
Referring parenthetically to
Although shown here in the context of a multi-layer biological barrier, it should be noted that similar structures may be used to anchor the device of the present invention relative to a single layer barrier, or relative to other body structures, all as will be clear to a person having ordinary skill in the art according to the particular intended application.
Regarding drug delivery device 18 itself, this aspect of the present invention may be implemented with a wide range of drug delivery devices that are based on an inflatable bladder-type reservoir for storing and slowly releasing a quantity of a liquid drug composition or the like. A number of non-limiting examples of suitable drug delivery devices may be found in co-pending international application publication no. WO 2011/101833 filed Feb. 22, 2011, and related U.S. patent application Ser. No. 13/430,730, filed 27 Mar. 2012, which do not constitute prior art. These examples regulate flow rates for release of the liquid drug by employing fine channels formed in facing surfaces between two parts of the drug delivery device, preferably also provide pressure-responsive regulation of the flow rate, or by use of a flow path passing through a porous block which may be biodegradable.
The operation of system 10 will now be clearly understood. In preparation for use, distal tip portion 28 is first retracted towards main block 30 to engage filling needle 24 with filling port 26, as illustrated in
Turning now to
Thus, in general terms, similar to system 10, system 200 includes a hollow needle 212, having a central channel 214 and a tip 216, and a drug delivery device 218 which includes a reservoir for receiving a volume of a liquid drug to be released over a period of time. Drug delivery device 218 is small relative to the overall dimensions of system 200 and is initially deployed within central channel 214 of hollow needle 212.
One distinguishing feature of system 200 is that sequential deployment and filling of drug delivery device 218 are effected by a single continuous motion of a manually operated actuator 220, thereby simplifying operation of the system, as will now be detailed.
As seen in
Prior to use, system 200 is prepared by introduction of the liquid drug to a storage volume defined within syringe body 234 between pistons 230 and 232. A non-limiting exemplary implementation of this preparatory process is illustrated in
For deployment of the drug delivery device through a biological membrane, a manually operated actuator 220, shown here in a preferred embodiment in the form of a plunger, is attached to second piston 232, as illustrated in
Manual pressure is then applied to plunger 220 to advance it along the body of syringe 234. Pressure applied by the plunger to piston 232 applies pressure to the liquid drug which in turn applies pressure to piston 230. This pressure advances piston 230, which presses against spacer 224, thereby advancing spacer 224, seal 228 and drug delivery device 218 along hollow needle 212 until drug delivery device 218 is deployed in the desired position beyond the tip of the deployment system (
It should be noted that system 200 has been shown here schematically, and has only been detailed to an extent necessary to appreciate the distinctive features of this embodiment, while numerous other features that are similar to features of the embodiment described above have not been detailed here. For example, drug delivery device 218 preferably features one or more radially expandable retention elements, such as is described above with reference to
Turning now to
Turning now to
In use, needle 402 is introduced into the drug delivery device via the refilling port while resilient wire 404 is in its straightened state. Wire 404 is then advanced within the device, forming its hooked or otherwise curled form within the device, preferably so as to become anchored on or tangled around internal features of the drug delivery device. The retrieval device can then be removed, drawing after it the drug delivery device.
It will now be appreciated that various embodiments of the present invention provides a number of significant advantages over existing options in the field of implantable devices for delivering liquid medications. hi particular, certain embodiments of the present invention provide one or more of the following functions:
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- Insertion of the drug delivery device through at least part of at least one layer of a biological barrier and anchoring of the drug delivery device within a layer, or between layers, of the biological barrier, where both the inserting and anchoring are performed sequentially by use of a single deployment system.
- Insertion of the drug delivery device through t least part of at least one layer of a biological barrier and subsequent filling of the drug delivery device with a quantity of liquid drug, wherein both the inserting and filling are performed sequentially by use of a single deployment system.
- Introduction of the drug delivery device by a straightforward injection technique via a needle of diameter smaller than the dimensions of the liquid reservoir after filling.
- Introduction of the drug delivery device by a deployment device which predefines the depth of insertion, thereby facilitating consistent results without requiring unusual skill in the deployment process.
It will be appreciated that the above descriptions are intended only to serve as examples, and that many other embodiments are possible within the scope of the present invention as defined in the appended claims.
Claims
1. A method for introducing a drug delivery device, the method comprising the steps of:
- (a) inserting the drug delivery device via a channel of a hollow needle through at least part of at least one layer of a biological barrier; and
- (b) subsequent to said inserting, filling the drug delivery device with a quantity of liquid drug via a filling needle extending within the channel of the hollow needle.
2. The method of claim 1, wherein the drug delivery device comprises a reservoir and a proximal filling port deployed to allow introduction of a volume of a liquid drug into said reservoir to be released over a period of time, and wherein said inserting and filling are performed using a system comprising:
- (a) a hollow needle having a central channel and a tip, the drug delivery device being deployed within said central channel of said hollow needle;
- (b) a plunger displaceable so as to push the drug delivery device along said central channel and beyond said tip of said hollow needle; and
- (c) a liquid injection device including a filling needle extending within said central channel of said hollow needle for engaging said filling port so as to allow filling of said reservoir after at least part of said reservoir has been advanced beyond said hollow needle.
3. The method of claim 2, wherein said reservoir is an inflatable reservoir sized for deployment within said central channel when substantially empty and inflatable by filling with a liquid drug to assume a deployed size greater than dimensions of said central channel.
4. The method of claim 2, wherein said filling needle extends through at least part of said plunger such that said filling needle engages said filling port prior to said inserting of said drug delivery device.
5. The method of claim 2, wherein said drug delivery device deployed within said hollow needle, said plunger, said filling needle and said liquid injection device pre-filled with a quantity of a liquid drug, are preassembled into a single integrated delivery system for implanting and filling said drug delivery device within the body.
6. The method of claim 2, wherein said tip of said hollow needle is a beveled tip terminating at a point for introducing said drug delivery device into the biological barrier without formation of a prior incision.
7. The method of claim 2, further comprising an abutment surface surrounding at least part of said hollow needle so as to define a depth of penetration, and wherein said plunger has a predefined fully-advanced position, such that, after penetration of said tip into or through the biological barrier and advancing of said plunger, said drug delivery device extends to a predefined depth into the body.
8. The method of claim 2, wherein said drug delivery device includes a radially expandable retention configuration configured to anchor said drug delivery device relative to a layer or layers of the biological barrier.
9. The method of claim 2, wherein said drug delivery device includes a resiliently compressible retention configuration configured to anchor said drug delivery device relative to a layer or layers of the biological barrier.
10. The method of claim 1, wherein the biological barrier includes the ocular sclera.
11. A system for filling an implanted drug delivery device with a liquid, the system comprising: wherein said processing system is configured to process said fluid pressure measurements to monitor for at least one alarm criteria.
- (a) a syringe comprising a syringe body for receiving a quantity of the liquid, a filling needle and a plunger;
- (b) a pressure measurement arrangement associated with the syringe for measuring a pressure of the liquid within the syringe; and
- (c) a processing system comprising a processor, the processing system being associated with said pressure measurement arrangement so as to receive fluid pressure measurements,
12. The system of claim 11, wherein said at least one alarm criteria includes the measured pressure dropping below a threshold minimum value.
13. The system of claim 11, wherein said at least one alarm criteria includes the measured pressure exceeding a threshold maximum allowed value.
14. The system of claim 11, wherein said processing system is configured to generate a warning under conditions of said alarm criteria.
15. The system of claim 11, further comprising a display associated with said processor, and wherein said processing system is configured to determine from the measured pressure a quantity of the liquid within the drug delivery device, and to display on said display an indication of the quantity of the liquid within the drug delivery device.
16. A method for filling an implanted drug delivery device with a liquid, the method comprising:
- (a) providing the system of claim 11 containing a quantity of the liquid;
- (b) inserting the filling needle into the drug delivery device and advancing the plunger of the syringe; and
- (c) monitoring an output of the processing system for an indication of the at least one alarm condition.
17. The method of claim 16, further comprising interrupting advancing of the plunger to allow measurement of the liquid pressure under zero-flow conditions.
Type: Application
Filed: Mar 25, 2015
Publication Date: Jul 23, 2015
Inventor: Avraham SHEKALIM (Nesher)
Application Number: 14/667,704