HYDRAULICALLY ACTUATED PUMP FOR LONG DURATION MEDICAMENT ADMINISTRATION The present application is a divisional application of Australian Application No. 2012201924, which is incorporated in its entirety herein by reference. 5 BACKGROUND OF THE INVENTION Any discussion of the prior art throughout the specification should in no way be considered as an admission that such prior art is widely known or forms part of common general knowledge in the field. The systems and methods described herein relate to a hydraulic pump system 10 that can be used in medicament pumps for injectibles, specifically to low-cost, miniature, single-use pump systems. Various people, such as diabetics, people require continuous or near continuous infusion of certain drugs or medicines (broadly referred to herein as medicaments). 15 Many attempts have been made to provide continuous or near continuous dosing of medicaments, such as insulin, using pump systems. For example, one known pumping technique uses gas generated by various means to advance a plunger in a syringe, thereby injecting the medicament through an infusion set. The infusion sets is a means for conveying medicament through the patient skin and may 20 comprise a standard needle, a microneedle, a microneedle array, and a catheter and cannula system. Although these systems can work quite well, patients using these systems, particularly in continuous dose mode, need to monitor closely or deactivate these devices under circumstances where the ambient air pressure may vary greatly, such 25 as in an airplane. In particular, patients need to be careful that the infusion pump does not deliver a dangerously increased dosage in airplanes at high altitudes, where the ambient pressure is significantly reduced. What is needed is a simple, inexpensive, single-use only medicament pump system. Such a system must have the capacity to provide variable dosing under 30 patient control as well as safety and consistency in the metered dose at any range of ambient pressures or operating conditions. -1 - SU1MARY I an exemplary enmbodinment, the systems described h ercin include, inter aka, a piup device, whih may he single use andI that that provides for sustained low volume fpreferably high potency) medicamnent application, such as for use by insu in-dependent diab ethics and other patients, The pump may i ploy as actuator a spring-compressed bellows crank, hinged plate, p airedrolr set or other peistaltic echanisms to fbrce a volume of hydraulic ffild through a Dow restrictor such as an aperture, thereby expanding one chamber of a two chamber hydraulic cylinder, The second, fluid storage chamber, containing a nedicament, is 10 vented through a conventional orifice as the hydraulic chamber is expanded by introduction of additional hydraulic fhid The medicament thus expelled may then be injected or infused into a patient via any suitable Injection and/or innsion mechanism The restrictor, in one enbodinent, may he a hydraulic fluid aperture and may 15 be a fixed micro-aperture of approximately 0 I10 un in diameter, or about 1-5 gim in diameter, and one tenthousandths of an inch (0 0(0 1", or about 2.5 um) in diameter, In another cibodiment, the hydrauhi thid aperture may be an adjustable aperture providing either continuous or step-wise diameter variations of approximately 0.1 10 inp in diameter, or about 1-5 p in diameterpreferably one 20 tenthousandths of an inch (00001" or about 2.5 sm) in diameter. Combined with a hydraulic fluid of appropriate viscosity, the micro-aperture provides precise pressure regulation that is insensitive to ambient pressure or other environmental conditions, This insensitivity in turns, allows for highly accurate dosing and dose regulation under a wider range of conditions than previously seen in the arts 25 Thaus one aspect of the invention provides a hydraulically actuated fluid delivery system for sustained delivery of a liquid component, comprising: a pump chamber, and a fluid storage chamber having an orifice and being fuctionally connected to said punp chapter by a movecable barrier; a hydraulic fluid reservoir for storing a high viscosity fluidA said reservoir being connected to said pump 30 chanter via a restrictor, such as an aperture, which may be less than 10 pm in -2diameter, and the largest insoluble particle, if anyin said hydrauic fluid nmay optionally be no more than the size of said aperture; and, an actuator functionally connected to said hydraulic fluid reservoir to cause said hydraulic fluid to flow into said pup chamber through said aperturethery expanding the volume of said 5 pump chanter, displacing said moveable harrier and causing a quantity of said liquid component stored in said fluid storage chanter to be delivered at a sustained rates In one enibodiment, the pump chamber and the fluid storage chamber are both within a compartment 10 In one embodiment, the moveable barrier is a piston or plunger plae, In one embodiment, the movement of the piston or plunger plate is guided such that the piston or plunger plate does not flip or generate leakage when moving In one embodiment, the moveable barier is one or more defonnable membrane separating the pump and the fluid storage chambers, 15 In one embodiment, the liquid component is a rnedicament and the wall of the fluid storage chanter is composed of bio-inert materials, In one embodiment, the aperture has a fixed size. In one embodiment, the aperture is adjustable in size to allow variable hydraulic pressure. 20 In one embodinent, the size of the aperture is adjusted by a ihulmbwheel control /dial. In one embodiment, the thumbwheel control activates a miniamned valve or iris device. i one embodiment, the quantity of said liquid component is expelled at a 25 rate selected kom: about 100 n 1 ptl per minute, about 1-plOul per minute, or about 10100 i per minute.
i one embodiment, the actuator is a miniaturized bellows crank, paired rollers, one or more piezoelectric elements, a ratchet or stepper motor driven unit, a two-plate hinged peristaltic mechanism, an lectically driven or piezoelectric mechanism. 5 In one embodiment, the actuator employs one or more extermal springs having a constant spring coefficient over its Pl range of motion In one embodient, the fluid delivery system further comprises a connective passage linking the hydraulic fluid reservoir to the pump chamber through the aperture. 10 in one embodiment, the liquid component is a solution of a medicament. in one embodiment, the medicament is insulin, an opiate, a hormone, a psychotropic therapeutic composition. In one emibodiment, the orifice of the fluid storage chamnbter is connected to an infusion set for delivering the liquid component to a patient 15 In one embodiment, the patient is a matmalian patient selected from hmnan or non-human animal, In one embodiment, fie infusion set is a needlea hnmen and needle set, a catheter-cannula set, or a nicroneedie or microneedle array attached by means of one or more lumens. 20 I one embodiment, the pump is manufactured with inexpensive material for singie-nse. In one embodiment, the inexpensive material is late-free and is suitable for use in latex-intolerant patient, In one embodiment, the inexpensive material is disposable or recyclable. 25 In one embodiment, the inexpensive material is glass or medical grade PVC, 4- In one embodiment, the fluid delivery system further comprises a second hydraulic reservoir. hi one embodiment, the second hydraulic reservoir is separately and independently controlled by a second actuator.. 5 In one embodiment, the second hydraulic resrvoir and the original reservoir are both connected via a common connective passage and through the aperture to the pump chamber. In one embodinent the second hydraulic reservoir is connected to the pump chanter through a second aperture. 10 In one embodiment, one of the two hydraulic reservoirs is used for sustained delivery of the liquid component, and the other of the two hydraulic reservoir is used for a bolus delivery of the liquid conip-nent at predetermined intervals In one eumbodiment both apertures are independently adjustable. In one embodiment one of the two apertures are adjustable, 15 In one embodiment, the sustained delivery is over a period ofnore &han 5 hours, more than 24 hours, more than 3 days, or more than one week. In one enmbodirment, the viscosity of the hydraulic fuid is at least about ISO VG 20, or at least about ISO VG 32, or at least about ISO VG 50, or at least about ISO VG 150, or at least about ISO VG 450, or at least about ISO VG 1000, or at 20 least about ISO VY 1500 or more, Another aspect of the invention provides a hydraulically actuated pump system comprising: ai pump chamber functionally connected to a moveable barrier; a hydraulic luid reservoifor storing a high viscosity fluid, said reservoir being connected to said pump chamber via an aperture of less than 10 and in some 25 embodiments less than 3 gon in diameter, and the Largest insoluble particle, if any in said hydraulic fluid is no more than the size of said aperture; and, an actuator 5R functionally connected to said hydnulic fluid reservoir to cause said hydraulic fluid to flow into said pump chamber through said aperture, thereby expanding the volume of said pump chamber, displacing said moveable barrier Another aspect of the invention provides a method ofMadiriiteringa 5 iedicament, comprising:compressing a hydraulic fuid reservoir to force said hydraulic flhid through a connection means; passing said hydraulic fluid through an adjustable aperture into a pump chambt, wherein said pump chamber is separated n an adjacent fuid storage chamber by a moveable barrier and wherein said fluid storage chamber is filled with a medicament. displacing said moveable barrier into 10 said fluid storage chamber by filling said pump chamber with said hydraulic fluid, wherein said displacing causes a quantity of said niedicament to be expelled from said fluid storage chamber through an output orifice, In one embodiment, the passing isreglated by the adjustable apertre varying the flow of the hydraulic fluid and thus the quantity of the medicament 15 expelled through the orifice. in one embodiment fhe method further comprises hijecting a quantity of the nedicament into a patient through an infusion set connected to the orifice, In one embodiment, the compressing employs peristaic compaction of the reservoir at a constant rate. 20 In one embodiment, the compressing employs peristahtic compaction of the reservoir at a variable rate. in one embodiment, the method further comprises rapidly compressing a second hydraulic reservoir fluidly comected to the pump chamber to displace the moveable barrder and thus cause a bolus of the medicament to be expelled through 25 the orifice, Ione embodiment the method fuither composes passing the hydraulic fluid from the second hydraulic reservoir through a second apertue into the pump chamber, 6 It should be understood that the individual embodiments described above are meant to be freelv combined with one another, such that any particular combination may simultaneously contain two or more features described in different embodiments whenever appropriate i addition, all embodiments described for one 5 aspect of the invention (such as device) also applies to other aspects of the invention (e. method) whenever appropriate. BRIEF DESRWIN OF E RDP&% NGS The present disclosure may be better understood and its numerous features and advantages nade apparent to those skied in the art by referencing the 10 accompanying drawings" Figure I is a high-level fintional schematic drawing of a hydraulic pump system, according to one embodiment of the invention. Figure 2 is a highlevel functional schematic drawing of a fluid delivery system comprising the hydradic pumsysystem, according to one embodiment of the 15 invention. Figure 3 is a schematic drawing illustrating one of the advantages of the fluid delivery system comprising the hydraulic pump system. Figure 4 is a highlevel functional schematic drawing of several fluid delivery system with various barriers. 20 Figure 5 is a highdevel fUnctional schematic drawing of alterative fluid delivery system, according to one embodiment of the inventionThe alterative fluid delivery system in this embodiment features arrayed microneedles on an transdenmal patch, Figure 6 isa higheve functional schematic drmwing of several actuator 25 mechanisms that can be used with the fluid delivery system employing the hydraulic pump, according to one embodiment of the invention.
Figure 7 is a high-level functional schematic drawing of the adjustabe control for aperture opening size. Figure 8 is a high-level functional schematic drawing of several fluid delivery system with multiple actators, according to one embodiment of the 5 invention. The use of the same reference symbols in different dawings indicates similar or identical items. DETAILED DESCRIPTION OF THE INVENTION Described herein is a drug delivery system, uses thereof and methods for 10 making the same. In one embodiment the systems described herein provide pump devices for delivering a nedicant,. agent, fluid or some other material to a patient typically through the sin. To is endd, the system includes an actuator that operates on a reservoir of viscous fluid, The actuator causes the viscous fluid to apply pressure to Iedicant to the medicant being delivered, The viscous fuid is controled 15 by a res rictor that, in one practice, controls the rate of flow of the fltid so that an aneven application of pressure to the reservoir is mediated, and a controlled rate of fluid movement is achieved. This controlled rate of fluid movement is employed to cause a medicant to be delivered at a selected rate. In one embodiment the systems and methods described herein include a 20 hydraulic pump system that may include a chamber (the "pump chamber"') that can be filled with high viscosity fluid, which, when forced by pressure,enters the pump chamber though a restrictor, for example an opening / aperture, which is dimensionally adapted to control the rate of fluid flow therethrough In one embodiment, the aperture is about the size of a 1-100 rn diameter circle (but not 25 necessarily circular in shape). However, those of skill in the art will understandthat any suitable restrictor may be employed, and that the size and the shape of the restrtor can vary to achieve the desired flow rate of the fluid being mediated under the expected conditions, including temperamture and ambient pressure.
The increase in volume of the working uithd inside the pump chamber triggers the movement of a harder mechanism, which can be coupled to otter devices, such as a second, fluid storage chamber, One advantage ofthe instanthydraulic pump system resides with the 5 restrictor through which the high viscosity working fluid flows. For example, when the restrictor is an apetu, when subjected to varying pressure the working fluid enters the chamber through the aperture at a slow, yet relatively constant rate, thus mostly eliminating the potentially large variations in the force generating the pressum while ensuring a substantially less variable expansion in volume of the 10 working fluid in the chamber This in tur leadsto a relatively smooth and constant movement of the coupled barrier nechanism An additional advantage of the hydraulic pump system is that its relatively low requirements for a constant pressure soue, or its high ability to tolerate relatively large variations in force generated by the pressure soure. This is 15 especially useful in manufacturing simple and inexpensive devices such as single use, disposable devices for medical use, Partly because ofthe over-pressure employed in the hydraulic pump system, a further advantage is that the hydraulic pump is relatively insensitive to environmental changes, such as ambient temperature, altitude, or extermal pressure. 20 An illustrative embodiment of the hydraulic fluid system described herein is shown in the high-level functional drawing of Figure 1. The pump chamber 110 may be shaped like, but is not limited to, a cylinder, The hatched lines represent a moveable batter 130, which may (but need not to) be at the distal end of aperture 152, Hydraulic thid 112 enters aperture 152 on pump chamber wall 150 into pump 25 chamber 110, optionally via a connective passage 116, As used herein, the term "ultrapure"is understood to encompass, although not be limited to, a fluid wherein the largest insoluble impurity particle in the working fluid is smaller than the aperture size (which may be for example about 2-3 um in diameter, but could be smaller or larger, and may be adjustable); h those embodiments wherein the restrictor is an aperture, the aperture need not be circular in shape, and could be an oval a square, a rectangle, a triangle, a polygon, or irregular in shape. In those enmbodients wherein the restrictor is a tube, valve, sieve, or other mechanism or combination of mechanisms, the size and shape of the 5 restrictor may be determined enpirically by testing the fluid flow of selected fluids at conditions of interest. In one particular embodiment the largest impurity particle is no more han I nun in diameter, or no more than 500 nm in diameter, or no more than 100 nm in diameter. in addition, the total amount of insoluble impurity particle is less than 01%, or 1 or 0001% in volume, 10 Viscosity is ordinarily expressed in terms of the time required for a standard quantity of the fluid at a certain temperature to flow through a standard orifice. The higher the value, the more viscous the fluid Since viscosity varies inversely with temperature, its value is less meaningful unless accompanied by the temperature at which it is determined. As used herein, Thigh viscosiy" means the working fluid has 15 a viscosity grade of at least about ISO VG 20, or at least about ISO VG 32 or at least about ISO VG 50, or at least about ISO VG 150, or at least about ISO VG 450, or at least about ISO VG 1000, or at least about ISO VG 1500: See www.superiodlubricants~com/classtable-html. The hydraulic pump system can be employed in a fluid delivery system tiat 20 can be manufactured inexpensively and could take advantage of the slow, yet relatively constant delivery rate associated with the hydraulic pump system. Partly due to the slow rate of delivery the fluid delivery system can be used to continuously deliver a fluid over a long period of time, e,g 6 bra, 12 hrs, i day, 3 days, 5 days, 10 days, one month, etc The fluid delivery system comprises the 25 hydraulic pump, coupled to a separate chamber for storing fluid to be delivered (the tuid storage chamber" or "flid chamber" i short .There could be various mechanisms coupling the movement of the barrier mechanisn in the hydraulic pump to the fluid chamber, such that a small amount of fluid (ideally equal to, or at least proportional to the amount of the working fluid entering he hydraulic pump -10chamber) is expelled froi the fluid chamber, though one or more orifice, in response to the movement ofthe barrier One embodiment of the luid delivery system is illustrated in a highievel schematic drawing in Figure 2 (see detailed description below). This type of fluid 5 delivery system device can be used for a broad range of applications, inchiding but are not limited to biomedical research (eg icroinjection into cells, nuclear or organelle transplantationisolation of single cells or hybridomas, etc,), and clinical application (administration of medicaments, etc For example, to provided low level or variable dose of medicine over a long TO period of time (e g, homs or even days), the fluid delivery system may fomi a portion of a single-use dispenser for a medicament to be applied through any of the standard infusions sets avail able on the market today or likely to be available in the future. The fluid delivery system, formed in some eibodiments as low-cost plastic parts anay comprise a hydraulic cylinder containing two chambersone fUnction as 15 the pump chamber described above, the other the fluid chamber for storing medicamesIn those embodiments the hydraulic cylinder may be configured similarly to most conventional hydraulic cylinders, and the wail, especially the inner wal of at least the chamber for storing a liquid medicament to be delivered, may be composed of bio-inert and inexpensive materials 20 The following description is for principal illustration only, and should not be construed as limiting in any respect Various illustrative alternative embodiments are described father below. Hydraulic cylinder 100, as described in Figure 2, consists of two chambers, 110 and 120. Chamber 110 (conesponding to the pump chamber) is filled by 25 hydraulic working fluid 112 FTom a hydraulic reservoir 11 4, Filling is accomplished by means of a comective passage 116, such as (but not limited to) a tube or lumen either flexibly or rigidlv connecting hydraulic reservoir i14 and hydraulic cylinder 110 As hydraulic fhuid 112 is forced out of reservoir 114 by actuator 135 (consisting, in an exemplary embodiment, of peristaltic compression plates 13$A .1and 135B and hinge 135Q, chamber 110 fills with hydraulic fluid expanding its volune and thus forcing piston element 130 (barrier rneehanism) into chamber 120 (corresponding to the fluid chanber) The dotted lines in the actuator and the piston in Figure 2 represent the laterin-time position of a plate-hinge actuating mechanism, S and the later-in-time position of the barrier / piston, Figure 3 is a schematic diagram illustrating one advantage of the fluid delivery system, eg, its ability to tolerate relatively large variations in force generating the over-pre sureto create a relatively constant fluid delivery rate over tire or distance traveled by the barrier piston, It is apparent that without the 10 hydraulic pump systeany direct use of force to expeI fuid in the fluid chamber will be hard to control., and will be subjected to a large variation in delivery rate of the fluid (Figures 3A), In contrast, with the hydraulic pump, the delivery rate is much more constant (Figure 3B), Chambers 110 and 120 can he, but are not necessarily separate, physical 15 chambers, since both chambers can exist within the confines of a hydraulic cylinder such as the one in Figure 2 (hydratilic cylinder 100), The chambers am separated by a moveable barier, such as tire piston element 130 in Figure 2, where piston 130 may be a fluid-tight barrier that prevents hydraulic fluid 112 from. entering the second medicament fluid storage chamber 120. However, the invention is not 20 limited in the type of hydraulic cylinder 100 or the contours, dienesions or fiislhes of the interior surfaces of cylinder 100, chamber 110, or chamber 120h Furthenmore, the invention is not limited to particular configurations of piston clement 130. The following description illustrates several ofinany possible alternative embodiments that can be employed in the subject fluid delivery system, 25 In one embodiment, as shown in Figure 4A, the piston element 130 in Figure 2 is replaced by a flexible inembrne 132 separating the pump chamber 110 and the fluid chamber 120, The flexible membrane can expand in response to the increased pressure oim the pump chamber 110, due to the increase in volume of the working fluid entering the pump chamber 110 through aperture 152, This in turn expels fluid 30 Thorn the fluid chamber 120 via orifice 140.
hi another embodiment, as shown in Figure 4, chambers 110 and 120 nay each has a separate wail unit 134 and 136, respectively (such as expandable bags made from flexible materials), By virtue of being within the limited confinement of cylinder 100, the expansion in volume of chamber 110 necessarily leads to the 5 decrease in volume of chamber 120, creating a force to expelliquidfom chamber 120 via orifice 140, In yet another embodiment, as shown in Figure 4(the pump chamber 110 and the fhid chamber 120 may be sepamted fom each other but are mechanically coupled through a barrier mechanism 138 that transmits movements in pump 10 chamber 110 to that in the fuid chamber 120. The coupling mechanism 138 can either augment or diminish the magnitude of the initial movement in the pump chamber 110, such that the corresponding movement in the fuid chamber 120 is increased, or decreased, respectively; resulting in expelling a larger or smaller amount ofmedicament luid from the fluid chamber 120. For example, the coupling 15 mechanism 138 can be two pistons linked by a shaft, as shown in Figure 4C in one embodiment, the fluid chanter 120 may be detached from the pump chamber 110, so that a new fluid chamber (120', not shown) may be reattached. As noted above, chanber 120 is to be initially filled with a quantity of liquid component to be delivered, such as a medicament.In the case of a niedicament, the 20 quantity would typically be determined by a medical professional in order to provide the necessary dosing over a pre-determined period of time, The volune of the fluid chamber may be about 100 pi, 500 pt i mai 3 Q 5 rW, 10 md 30 m 50 m, 100 ml or more The depicted hydraulic cylinder 100 in Figure 2 can be further connected to 25 an infusion set 160 through orifice 140 at the distal end of chamber 120 (distal here meaning the end of chamber 120 distant fom piston 130), In other words, the output orifice 140 of hydraulic cylinder 100 is on the opposite end of the cylinder from hydraulic fuid input aperture 52 as one would commonly expect in a hydraulic system However, this is merely one of tie pebrred designs The output orifie 140 could be located on the wall of cylinder 100 at the chamber 120 portion if desired (see Figure 5 below), Attached to orifice 140, in some embodiments, is an infusion. device or "set" 160 selected from any of the infusion means conventionally known and used in the 5 medical arts Examples of infusion devices include: a needle, such as depicted in Figure 1, a lumen and needle set; a catheterlcanula set; or a microneedle or microneedle array attached by means of one or more lumens One of ordinary skill in the art will readily appreciate tat many devices exist to convey Medicamnents into a body. Accordingly, the invention is not limited in the types of infusion or injection 10 devices used therewith, In an illustrative embodiment, as shown here in a high-level schematic drawing in Figure 5, the fluid delivery system is affixed to a delivery area ofta patient, e.g. skin. 200, by an adhesive means, such as a transdennal patch. The fluid chamber 120 is connected to a microneedle or an array of microneedles 180, such as 1$ those described in US, Pat. No, 6,503,231 (incorporated herein by reference). Unlike what is shown in Figure 5, the microneedle(s) need not completely enter the skin layer 200. To achieve a low profile, both the pump chamber 110 and the fuid chamber 120 may he fat in shape (rather than shaped like a cylinder) and the outer surfaces may bug the contour of the attached skin layer 200. The orifice(s) (not 20 shown) connecting the fluid chamber and the micraneedle(s) preferably opens on a side-wall of the fluid chaner 120, Altenatively, a comective passage may link the orifice on fluid chamber 120 to the microneedle or micronoeedle(s) array. Barrier 130 and aperture 152 are as described above. Also shown is one embodiment of the actator, where plates 135 actuated by spring mechanism squeeze the hydraulic fluid 25 reservoir 114 to inect hydraulic working fhud into the pump chamber 110Other actuators, such as those described in other parts of the specification, maybe adapted for use in this embodiment As exemplified in Figure 2, in operation, the fluid (e g medicament) is administered by compressing ydraulie fluid, reservoir 114 in a controlled manner 30 wih actuator 135. Figures 2 shows an exemplary peristaltic mechanism actuator 14 135 However; the actuator may be alternatively selected fronm any of a number of squeeze devices that apply a fre on the reservoir, such as a miniaindzed bellows crank or paired rcliers bearing on reservoir 114 (see Figure 6 below) Moreover, in other emubodihnent the reservoir can be acted on by an expanding gas volume, 5 thermal energy or any other device or process that will be capable of causing the fluid to apply a pressure, either directly or indirectely, to the medicant being delivered In the embodiment shown in Figure 2, plates 135A and 135B are attached by hinge 135C aid forced together by means of a spring or in some embodiments, one 10 or more piezoelectric elements such that. flexible (eg.. elastomeric) hydraulic fluid reservoir 114 is squeezed between them, Squeezing an elastomeric reservoir forces the contents of the reservoir out through whatever aperture exists in the reservoir. In some embodiments. an aperiure 152 is provided by the coupling tube 116 and the adjustable aperture 150, further described below, 15 Actuator 135 may also take on others forms Ratchet or stepper motor driven units that compress plates or other strutures beating on hydraulic reservoir 114 that move hydraulic fluid may also be used without departing from the present invention. Additionally, for a two-plate hinged peristaitic mechanism such as that represented by refernce designator 135 in Figure 2, springs mounted internally or externally to 20 the plates (not shown) may be used to force the plates together. Electrically driven or piezoelectric mechanisms, such as those described in the prior art, may also be employed. In one embodiment, as shown in Figure 6A, one or more extrnal springs) 135D having a constant spring coefficient over its full range of notion is (are) 25 employed. (For the sake of simplicity, a single spring configuration is described But multiple springs may be used to adjust forces.) This spring is disposed so as to connect portions of plates 135A and 135B3 distant from hinge 1 3502 and to draw them together (inwardly), thus bearing on reservoir 114, Thus, when the system is initially prepared for use the spring is extended (ie, laced in tension) by forcing 30 plates 13 5A and 135B apart The plates are then held in place 'with a removable 15brace or other device (not shown) to keep them from compressing hydraulic reservoir 114, Once the pump is in place and connected through inifsion means 160 (see Figure 2, but not shown here) to inject the medicanent into the patient, the brace may be removed The constant spring tension placed on plates 135A and 135B 5 of actuator 135 will then slowly force the plates together and squeeze hydraulic fluid 112 out of reservoir 114 in a peristalsisdike action, In another embodiment, as illustrated in Figure 6B, a compressed springor set of springs 260 may be used to push a piston element 250 through a guided-path to compress the hydraulic fluid reservoir 114, At the end of the reservoir, distal to 10 the piston element 250, is an aperture 152 that allows the hydraulic fluid 112 to enter the adjacent pump chanter 110, so that barrier 130 may move accordingly in a more simplined version, the spring miechani 250 and260 may be replaced by thunb force 300,ast like in a traditional syringe (Figure 6C) In both Figures 6B and 6C, there is no connective passage sep rating the fluid reservoir 114 froM the 15 pump chanber 110. The adjustable aperture provides regulation of the hydraulic pressure And flow rate in the pam chamber 110. This regulation may be effected by allowing the aperture 152 (in Figure 2) to be adjusted to extremely small diensions, for exainple, to a diameter of oneAten thousandths of an inch (0.0001 inches, or about 20 25 pin) or less. in one embodiment, the aperture 152 has a fixed size it does not have to be roundhirculr in shape. For example, it could be roughly a square, a triangle an oval, an irregular shape, or a polygon, Whatever the shape, the area of the opening will be sized to achieve the flow rate desired, In example, the opening may be about 25 one-tenth thousandths of an inch (or 2-3 pm) in diameter, Depending on use, the opening size can be anything including an opening between 200 n - 500 m, or 500 nm -1000 nm, or I-2 pm.. or 5-10 pam. Other sizes and dimensions can be selected and the size and dimension selected will depend upon the application at hand -16- In other cmbodiments, as shown in Figure 7, the aperture 152 may be adjustable in size, as by mians of a convotional iris mechanism (see Figure 7), miniature valve, or paired gating slits (for example and not by way of limitation) currently known in the arts, For example, the adjustable aperture 152 may be 5 adjusted by means of a simple thumb Wheel 150 that activates the conventional, miniaturized valve or iris device discussed above i an alternate embodiment, an electrical motor or piezoelectric device may be used to open or close the aperture, thus affecting the rate at vhich hydraulic fluid 112 flows into chamber 110 and moves barrier 130 10 Regardless of whether the aperture is adjustable or not, the flow rate of the hydraulic thid can be controlled to sit different needs. In certain embodiments, the quantity o the fluid in the fluid chamber is expelled at a rate selected fr about 100 ii p. ,a per minute, about i-O pl per minute, or about 10-100 pL per minute. bi other embodiments, the fluid rate is mediated and controlled to be from .001pl per 1$ hour to 100 nilliters per hour. The rate selected will depend upon the application at hand, and those of skill in the art will be able to determine the proper dosage rate -for a given application One feature of aperture 152, whether adjustable or not, is that it can be inade extremely smal so that hydraulic fluid 112 enters chamber 110 at very low rates, 20 such as but not limited to rates as low as ones or tens of microliters per minute, When used with a hydraulic fluid of appropriate viscosity (further discussed below), the configuration of aperture 152 enables precise pressure regulation that is insensitive to ambient pressure or other environmental conditions This insensitivity, in turns, allows -for highly accurate dosing and dose regulation under a wider range 25 of conditions than previously seen inthe arts, Flydraulic fluid 12 is in son embodiments, an ultrapure, high viscosity, bioinert material Viscosity is limited at its upper bound by the amount of force developed by the actuator. hi certain embodiments, the force generated by the actuator is about 10 lb, lb, 3 lb,21b, I Ib, 0.5 lb, 01 lb, .001 lb or less. At its lower 30 bound, the fluid must be viscous enough so that the flow can remain highly regulated 17 by the combination of actuator pressure and aperture diameter in all environment conditions, especially in the presence of low atmospheric pressure and/or high ambient temperature (where viscosity tends to decrease)-A simple test may be performed to rougtly determine the avege flow rate of the hydraulic fluid, by 5 fixing an aperture size ard the pushing force exerted an the fluid reservoir, and determining the amount of hydraulic fluid remaining in the reservoir (and thus the amomt exited) after a period of time. Consecutive periods of hydraulic fluid loss (e-g. fluid loss in consecutive 5-minute periods ete) nay be measured to determine if the rate of hydraulic fluid loss from the reservoir is constant over time under the 10 condition used. Medic agents suitable fbr use with the system presently disclosed include: insuin, opiates and/or other palliatives, hormones, psychotropic therapeutic composition, or any other drag or chemical Whose continuous low volume dosing is desirable or efficacious for use in treating patients Note too that "patients" can be 15 human or non-human. animal; the use of continuous dosing pumps is not confined solely to human medicine, but can equally applied to veterinarian medicines 1I an, altermate embodiment of the system, two or more hydraulic reservoirs and actaators are provided (Figure 8), In an illustrative embodiment shown in Figure SA. the first reservoir 400 and actuator 235 are the same as or similar to items 114 20 and 135 in Figure 2 The second reservoir 500 and actuator 235,whidh may use the same peristaltic actuator 135 as shown in Figure 2 or any other conventional alternativesuch as those described above are provided with a separate contro-l in other words, the second actuator may be controlled independently of the first Bh fluid reservoirs are connected to the pump chamber wall 150, through apertures 1 54 25 and 156, respectively The connection. may optionally go through connective passages 116, Such a configuration is useful in situations where special, discrete doses of the medicament may be necessary For example, an insulin-dependent diabetic may often find it necessary to receive an additional booster dose or bolus of insulin immediately after meals, in addition to and along with continuously supplied -18 insulin during the day The second actuator control may thus be operated independently of the first actuator control mechanism to deliver the bolus in an alternative embodiment, shown in Figure 8B, hydraulic fluid 112 from both reservoirs 400 and 500 may pass together through a common lumen 116 and 5 thence through adjustable aperture 5 ure 8B). Alternatively as described above, the two reservoirs may lead into hydraulic chanter 110 by way of separate lunens and separately adjustable apertures 154 and 156 (Figure 84) in this latter configuration, the rate of dosing affected by either reservoir may be independently controlled through their respective adjustable apertures,. 10 in a further alternative, one of the reervoirs may lead to a fixed aperture while the other leads to an adjustable aperture in this embodiment; useful in cases such as the insulin-dependent diabetic described above, the flxed-aperture-connected hydraulic reservoir can be actuated to provide bolus dosing at discrete intervals, while the adjustabie-aperture-connected hydraulic reservoir can be used to provide 15 continuous slow dosing EXEMPLARY FM DME U TI-UEiFLUDXVF SYSTEM In one exemplary embodiment, there is provided a method of administering a medicament, comprising: compressing a hydraulic fluid reservoir to force said hydraulic fluid through a connection means; passing said hydraulic fluid through an 20 adjustable aperture into a first, pump chamber, wherein said pump chamber is separated from an adjacent fluid storage chamber, for example, by a moveable barrier, and wherein said fluid storage chamber is filed with a niedicarent; displacing said moveable barrier into said fliid storage chamber by filling said pump chamber with said hydraulic fluid, wherein said displacing causes a quantity of said 25 medicanent to be expelled front said fluid storage chamber through an orifice, Said passing may be regulated by said adjustable aperture varying the fow of said hydraulic fluid and thus the quantity of said medicament expelled through said orifice. Furthermore, the method may further comprise injecting a quantity of said medicament into a patient through an infusion set comected to said ouince. -19- In some embodiments, the step of compressing may employ peristaltic companion of said reservoir at a constant rate. Altermatively, the eompressig step may employ peristalie compaction of said reservoir at a variable rate. in yet another alternate embodiment, the method may further comprise 5 rapidly comprssing a second hydrauli reservoir fluidly connected to said pump chamber to displace said moveable barrier and thus cause a bohIs of said medicament to be expelled dhmugh said orifice. This embodiment may further comprise passing said hydraulic fluid from said second hydraulic reservoir through a second aperture into said pump chamber. 10 Alternt . odings The order in which the steps of the present method are performed is pumly illustrative in nature and may not need to be performed in the exact sequence they are described. In fact, the steps can be performed in any suitable order or in parallel, unless otherwise indicated as inappropriate by the present disclosure 15 While several illustrative embodiments of the hydraulic pump system and its use in the fluid delivery system have been shown and. described, it will be apparent to those skilled in the art that changes and modifications may be made without departing from this invention in its broader aspect and therefore, the appended ieahns are to encompass within their scope all such changes and modifications as 20 fal within the true spirit of this invention -20-