AU2015207890B2 - Hydraulically actuated pump for long duration medicament administration - Google Patents

Abstract

Presently disclosed is a hydraulic pump device and its use thereof, especially in a fluid delivery system. In one embodiment, the fluid delivery system is an inexpensive, single-use device for slow dosing medicament applications. The fluid delivery system may employ a spring-compressed bellows crank or other combination of simple mechanisms operating according to the well-known peristaltic principle to force a volume of ultrapure bio-inert hydraulic fluid through an aperture, thereby expanding one chamber of a two chamber hydraulic cylinder. The second, fluid storage chamber, containing the medicament, is emptied through a conventional orifice in response to the expansion of the pump chamber. The medicament may thence flow through any suitable infusion set into a patient removeably attached thereto.

Description

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.

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 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).

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 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 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 patient control as well as safety and consistency in the metered dose at any range of ambient pressures or operating conditions.

SUMMARY

According to a first aspect, the present invention provides a fluid delivery device comprising: a hydraulic housing having a piston configured to sealingly slide along an inner wall of the hydraulic housing and separate the hydraulic housing into a hydraulic pump chamber and a fluid reservoir, the hydraulic pump chamber having a viscous hydraulic fluid and configured to urge the piston along the inner wall to deliver a fluid in the fluid reservoir to a patient, a viscosity of the hydraulic fluid being at least about ISO VG 1000 or more; a first actuator; a first hydraulic reservoir chamber having the hydraulic fluid and coupled between the first actuator and the hydraulic pump chamber, the first actuator being configured to urge the hydraulic fluid in the first hydraulic reservoir chamber into the hydraulic pump chamber; a flow restrictor fluidly coupling the first hydraulic reservoir chamber and the hydraulic pump chamber; a second hydraulic reservoir chamber having the hydraulic fluid and fluidly coupled with the hydraulic pump chamber; and a second actuator configured to urge the hydraulic fluid from the second hydraulic reservoir chamber into the hydraulic pump chamber, independent of the first actuator.

According to a second aspect, the present invention provides a fluid delivery device comprising: a hydraulic housing having a piston configured to sealingly slide along an inner wall of the hydraulic housing and separate the hydraulic housing into a hydraulic pump chamber and a fluid reservoir, the hydraulic pump chamber having a hydraulic fluid, a viscosity of the hydraulic fluid being at least about ISO VG 1000 or more, the hydraulic pump chamber being configured to urge the piston along the inner wall to deliver a fluid in the fluid reservoir to a patient; a first hydraulic reservoir chamber having the hydraulic fluid; a fixed aperture flow restrictor fluidly coupling the first hydraulic reservoir chamber and the hydraulic pump chamber, the fixed aperture flow restrictor configured to control the rate the hydraulic fluid flows between the first hydraulic reservoir chamber and the hydraulic pump chamber; a first actuator coupled to the first hydraulic reservoir chamber and configured to continuously deliver the hydraulic fluid from the first hydraulic reservoir chamber to the hydraulic pump chamber for a period of time; a second hydraulic reservoir chamber fluidly coupled to the hydraulic pump chamber, independent of the first hydraulic reservoir chamber; and a second actuator coupled to the second hydraulic reservoir chamber and operable independent of the first actuator and at discrete intervals during the period of time to periodically deliver the hydraulic fluid from the second hydraulic reservoir chamber to the hydraulic pump chamber independent of and in addition to the continuous delivery of the hydraulic fluid from the first hydraulic reservoir chamber.

According to a third aspect, the present invention provides a fluid delivery device comprising: a hydraulic housing having a piston configured to sealingly slide along an inner wall of the hydraulic housing and separate the hydraulic housing into a hydraulic pump chamber and a fluid reservoir, the hydraulic pump chamber having a hydraulic fluid and configured to urge the piston along the inner wall to deliver a fluid in the fluid reservoir to a patient; a first hydraulic reservoir chamber having the hydraulic fluid; a fixed aperture flow restrictor fluidly coupling the first hydraulic reservoir chamber and the hydraulic pump chamber, the fixed aperture flow restrictor configured to control the rate the hydraulic fluid flows between the first hydraulic reservoir chamber and the hydraulic pump chamber; a first actuator coupled to the first hydraulic reservoir chamber and configured to continuously deliver the hydraulic fluid from the first hydraulic reservoir chamber to the hydraulic pump chamber for a period of time; a second hydraulic reservoir chamber fluidly coupled to the hydraulic pump chamber, independent of the first hydraulic reservoir chamber; and a second actuator coupled to the second hydraulic reservoir chamber and operable independent of the first actuator and at discrete intervals during the period of time to periodically deliver the hydraulic fluid from the second hydraulic reservoir chamber to the hydraulic pump chamber independent of and in addition to the continuous delivery of the hydraulic fluid from the first hydraulic reservoir chamber.

Unless the context clearly requires otherwise, throughout the description and the claims, the words “comprise”, “comprising”, and the like are to be construed in an inclusive sense as opposed to an exclusive or exhaustive sense; that is to say, in the sense of “including, but not limited to”.

In an exemplary embodiment, the systems described herein include, inter alia, a pump device, which may be single use, and that that provides for sustained low volume (preferably high potency) medicament application, such as for use by insulin-dependent diabetics and other patients. The pump may employ as an actuator a spring-compressed bellows crank, hinged plate, paired roller set, or other peristaltic mechanisms to force a volume of hydraulic fluid through a flow restrictor, such as an aperture, thereby expanding one chamber of a two chamber hydraulic cylinder. The second, fluid storage chamber, containing a medicament, is vented through a conventional orifice as the hydraulic chamber is expanded by introduction of additional hydraulic fluid. The medicament thus expelled may then be injected or infused into a patient via any suitable injection and/or infusion mechanism.

The restrictor, in one embodiment, may be a hydraulic fluid aperture and may be a fixed micro-aperture of approximately 0.1 - 10 pm in diameter, or about 1-5 pm in diameter, and one ten-thousandths of an inch (0.0001”, or about 2.5 pm) in diameter. In another embodiment, the hydraulic fluid aperture may be an adjustable aperture providing either continuous or step-wise diameter variations of approximately 0.1 - 10 pm in diameter, or about 1 -5 pm in diameter, preferably one ten-thousandths of an inch (0.0001”, or about 2.5 pm) 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.

Another 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 functionally connected to said pump chamber by a moveable barrier; a hydraulic fluid reservoir for storing a high viscosity fluid, said reservoir being connected to said pump chamber via a restrictor, such as an aperture, which may be less than 10 pm in dimneter, and the largest insoluble particle, if any^ in said hydraitim Said may optionally be »0 more man the siae of said aperture* and. an actuator tbnctiosally connected to said hyPraitiic Sttiti reservoir to cause said: hydraulic Surd to Sow into said pump chamber through said aperture, thereby espgpdiug the volume of said pump chamber, dlsplaemg md rnoveable harrier and causing a quantity of said liquid C€p|ronmt::^t^m:s^::Spd:abtage chamber to be delivered at a suslamed rate.

In one embodiment, the pump chamber and the Surd storage chamber are both within a oornparhuent,

In one embodiment, the moveable barri er is a piston of plunger plate, hr one embodiment, the movement of tire piston or plunger plate is guided such that the piston or plunger plate does not Sip or generate leakage when moving.

In one enrbodimmib the moveable harrier is one or more dsfomiable membrane separating the pump and the Said storage chambers. the liquid component is a medicament, and the wall of the SuM storap chamber is composed :of bin-inert materials. hr one embodiment* ihe aperture has a fixed size.

In one endmdirmnp the apertnre is adjustable in sfee to allow variable hydraulic pressure.

In one emboduierd, the sme of tbs aperbire is adjusted by a thumbwheel control / dial.

In one embodiment, lire t§umhw%epl control activates a mmiahaieed valve or Ms device, fir one embodiment, the paniity of said S^4'<mmp<mPiai:::isi«^peUed at-a rate selected from: about lOOpl -l piper minute, about ISO piper minute, or about 10-100 pi per minute.,· Μ op# is a miai&amp;tfei^ bellows etardg paired rollers, one or srere p .ieimelecloe eletfeetJtSj, a mlcbet or stepper motor drives: sslt, a tevo-plate Isagod pemtaltic meehankio, an electrically driven orpleaoeleetric mechanism.

Is ose esibodisients Ae acsiator employs Pirn or mote external springs hayisg a constant apring eoeffimest over its fell range of mottos.

Is one enfeodmiesf tire field ddivety system forte' comprises: a eoimeetive passagerilskisg fee hydrapiio;llpid'reservoir to fee pnm.p; chamber ifeoegft fee aperture.

Is one etelbodlxnestj fee liquid component is a solution of a Predicament

Mdse embodiment, fee mefecarneoi is inafes, an opiate, a komione,, a psyefeotppie tfesrapefeio eomposiilos.

Is ose esfeodirnem, fee orifice of ite llmd storage ehamber is connected to an infusion set for delivering the ligaid convposent to a patient

Is ose esd^isiem, feep^tlent is a. mammalian paths! selected from human, pr xKfedsssan^mnteaL

In one enfeodiment, fire mfeshm set is a needle, a Imnes and needle seg a e&amp;feeten-easssla set, or a mieroseedle or mieroseedle array attached by means of Ose or more lumens.

Is ose emhoditnsm, fee pomp is manufacteed ' single-use, fit one embodiment, fire inexpensive 'material is latex-fiee asdis suitable fer use in latevrintolerastpatimt

In ose embodiment, fee inexpensive:material is disposable or recyclable.

Is One embodiment fire intensive material is glass or medical grade Ffe

Mime miMdteesit, the fluid hydraulic reservoir.

In one embodiment, the second hydraulic reservoir is separately and

In ops embodiment, flis second hydmdic msseyvoir and the original teeesyoir ate both connected via a common connective passage and feoagh tfte aperture to the pump chamber. fit one embodiment, dm second hydraulic reservoir is connected to the pump chamber ihrongli a second aperture.

In ope embtxiimeni, one of tie two bydmuBc reservoirs la used for sustained delivery of fts liquid component, and the other of fte two hydraulic reservoir is used for a bolus delivery of tire liquid eomponent at predeiemnned intervals. la one embodiment, both -apertures are independently adjustable.

In one embodimeirt one of the tw o apertures are adjustable.

In one embodiment the sustained delivery is over a period of more than 5 hours, more than 24 hours* more than 3 dap, or more than· one week.

In one embodiment the viscosity of the hydraulic fluid is at least about ISd YG 20, or at least about ISO YG 32, or at least about ISO VG 50, or at least about ISO: YG 150, or at least about ISO YG 450, or at least about ISO VG 1000, or at least about ISO YG 1 SOD or more.

Another aspect of the Invention provides a hydraulically actuated pump system comprising: a pump chamber iundionaliy connected to a moveable barrier; a hydraulic fluid reservoir Ibr storing ft high viscosity fluid, said reservoir being··' cohneefcid to said pump chamber via an. aperture of less than 10 and jn some embodiments less than 3 pm in diameter, and the largest insoluble particle, if any, in Said hydraulic fluid is no more than the siae of said aperture; and, an actuator functionally comrecied to said hydxaulio fluid reservoir to· cause said hydrardie fluid to flow into said pua^c^bmber'lboi^ said aperture, thereby expanding the vplnme of said pump chamber* displaoing said ntoyoahfe barrier.

Another aspect of the invention provides a method of administering a medicament comprising: eompmssfeg a ky^5p|ip;S«id::iC^voif to force said hydraulic fluid through a cormection means; passing said hydraoho fluid through m adjustable aperture sow a pomp chamber, wherein stod pump chamber Is separated; fern an adjacent fluid storage dfenibe* by a moveable barrier and wherein said fluid storage chamber in filled with a medicament; displacing said moveable barrier into said fluid storage chamber by filling said pump chamber with said hydmutie fluid, wherein said dispkcmg cau ses a quan tity of said medicament to be gelled fiost said fluid stmafe ebambct throuiflr ah out^ fir one embodiment, the passing 1$ regulated by the adjustable aperture varying the flow nf ihe;bydmuBe fluid and tons the quantity of the medicament

In one Anther comprises injecting a quantity of the medieatoeM into sot connected to the orifice.

In one emlx)dintout, fce camptossing employ's peristaltic compac tion of the reser voir at a constant rate.

In one embodiment the compressing employs peristaltic compaction of the reservoir at a variable rate.

In one embodiment, the method further comprises rapidly compressing a second hydraulic reservoir fluidly connectedto the pump chamber to displace the moveable harrier and thus cause a bolns of toe msdtcameto :io be expelled through the orifice. hr one embodiment, the method further comprises passing the hydraulic fluid from the secosuS bydraalio toservoir through a second aperture intolhe pump chamber. it should be understood that the mdividual embodiments described above ate meant to be freely 'combined'wi th one another, such that any particular mmhimikm may sibmlM^bbsiy contain two of store features desenbed m difiment emlmdimeats whenever apfurspriate. &amp; additieOj all embodiments described for one aspect of the invention (suoh as detd.ce) also applies to other aspects of the invention (e.g. method) Whenever appropriate.

BRIEF DESCRIPTION OF THE DRAWINGS

Xhe pfesent diselesnre may he better understood: and its numerous features ami advantages made apparent to those skilled in the art by referencing the aecompaiiying drawings.

Figure 1 is a high-level #notional schematic drawing of a hyckaidie primp sy stem , according to one embodiment of the mvention.

Figure 2 is a high-level functional schematic dmving of a fluid delivery system comprising -am-'i^i^^li6:'p^p:^st!et»^ according to one embodiment of the invention.

Figure 3 is a schematic drawing illustrating one of the ad vantages of the luM delivery system composing the hydraulic pump system.

Figure 4 is a high-level funetional schematic drawing of several fluid delivery system with various harriers.

Figure d is a schemahe drawing of an altmuative fhdd delivery system, according to oneembodiment of the htveation. The alternative thud delivery system in this an ttansdermal patch.

Figure 6 2t$ lti^4syet'ftiEt!itidml schematic drawing of several actuator mechanisms thafean he used Wi&amp;the fluid delivery system employing the hydraulic pump, according;!© one emhodimeni of the invention.

Fi|fere Tis a hjgfc*level functional schematic drawing of fee adjustable cdjii^I^f^e^are opening sine.

Figure § is a Mghricvel iunefibnal sehfenatie drawing of Several fifed delivery system with multiple actuate, according to one embodiment of fee invention.

The nse of fee same reference symbols m different drawings indicates 'similar or identical items,

^TAILED iMCMMMlfflTSOM

Described herein is: a drag dfelveiy system, uses thereof and meilmdsior making the same, &amp; one embodiment, fee systems described herein provide pomp fievipps a feedicauij agent, fifed or some other maferiai fe apa&amp;pi; typically: tferoagh the skin. To this sud, fee system includes an afeuafer feat ogemtes on. a ieserooir of viscoosfifed. The actuator oanses fee viscous fifed fe apply prfe®^;^tfi^|(^at to fee feedicanf being delivered. The viscous fifed is eoferolled by: a restrictor feat, in one practice,fidw of the fifed so that an uneven application of pressure to the'ne8@r^if:ki^^tp4;a^ a controlled rate of fifed movement is achieved. This confeoied}i^''df:iteii4^o«ement Is employedto oafeea medicant to be: delivered at a selected fale, fe :fefe: :em'tedifeent'fee systems and me thods described herein· include a hydrafele pump system, feat may include a chamber (the “pump chamber’) feat can be filled wife high viscosi ty fluid, which, when forced by pressure, enters fee pump chamber feronip a restricto-g for example an .opening / aperture, which is dimensionally ; adapted to coferol tbeiate of fifed fiow feereferongh. In one embodiment fee aperiup is about the sign of a l -10fi ptn diameter circle {but not rtessariJy circular in shape), However those of shill in fits art will nndsrstatid find any suitable reefnetor may be employed, and feat the sfese and fee shape of the: festrietor nan vary to achieve fee desired Sow rate of the fluid being mediated under fee expected condlfiona,. inokding: tempemfere and; ambient pressure. 1½ increase in volume of chamber triggers &amp;e movement of a barrier meehmnsm, Which can be coupled is other dariees, such as a second, fluid storage chamber, 0m advan tage of fee instant hydraulic pump system resides with the restrictor through which the high viscosity working fluid flows, For example, when tire restoietdr is an apcmno, when subjected to Yaxying pressme, tim worlring fluid enters thetpririber thronpi the aperture at a slowf yet relatively constant rate, thus mostly eliminating the potentially large variations in the force generating the pressure, wfefe ensuring a substantially less variable expanrion m volume of the working fluid in the chamber. This in ten leads to a relatively smooth and constant movement of (he coupled barrier mechanism.

An additional advantage of the hydraulic pump system is that its relatively low reepipmeut for a constant pressure source, or its high ability to tolerate relatively large variations in force generated This is especially useful in manufacturing simple and hmxpeirsive devkes, such as single·' use, disposable devices for medical rise,

Badly because of the over-pressure employed ιη.^'.^^^0:|»ίηφ:'^^Βΐη^ a fmifeer advantage is that the hydraulic pump is relatively insensitive to environmental changes, such as ambient temperature, altitude, or mtemalpmssure.

An iilesriarive umbedinjent of the hydraulic fluid system described herein is shown in the high-level functional drawing of Figure 1- The pump chamber HO may be to, a cylinder. The hatched lines feprassnf a moveable harrier 130, wfeiefe may (hut need not to) fee at tfradistal end of aperture 152, ISydmulic flnid 112 enters aperture 152 on pump chamber wall I SO into pump chamber 110, optionally via ai connective passage TI&amp;

As used herein, tfiife fend '^l&amp;apure** % understood to encompass* although not fee limited to, a fluid wherein the largest insoluble impurity particle in the working fluid is smaller than the aperture size (which may fee for example about. 2-3 μηΐ in diameter, hut could fee smaller or larger, and may fee adjustable), hvtiiose embodiments wherein tlteresirieter Is an aperture, ttoapMnre need not %dtetear m shape, a»d could be ah oval, a square, a pctaBgief afriaagte, a polygon, or kregalar ip shape. Ik those embodiments wfeeminihe restrictor is a tube, valve,, sieve, pnoflter mechanism or combination of mechanisms,the sfee and shape of the restrictor may todstetmined empirically by ISs^;^,tii&amp;flow''0£^leeted fluids at conditions of interest Ik one particular embodiment, the largest impurity particle is no more than 1 am in diameter, or no more than 500 nm in diameter, or no mote than 100 nm in diameter» In addition, the total amount of insoluble impurity particle is less than §,!%, or 0ΤΕ54 or 0,001% iu volume.

Viscosity is ordinarily expressed in terms of the time m<|Uired lor a standard quantity of the fluid at a cemrin temperature to flow through a standard orifice. The Mghet tbe value, the more viscous the fluid. Since viscosity varies inversely wife temperature, its value is less mesningM unless accompanied by the temperature at wMebtiis determined. As used herein, <shigh viscosity” means: the working fluid has 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 VO 150, or at least steout KO VG 456, or at least about ISO VG 1000, or at least about BO VG 1500. See www.superioriabricante»coMtetessteble»btml»

The hydraulic pump system can be employed in a fluid delivery system Bat can be tnanu^ctered''ht^mmvely,:':|tnd could take advantege Of the slow, yet telatively constant delivery rate associated with the hydmuhe pump system. Partly due to the slow rate of delivery, the fltdd dMivery system can be usedl» continuously deliver a -fluid over a long period of time, e,g. 6 hrs, 12 Ins, I day, 3 days, 5 days, 10 days, one month, etc. T&amp;o hydraulic pump, emailed to a separate chamber far storing fluid to be deliveted (tee sifluid storage chamber^ or ‘“fluid chamber* in short). There could be various mechanisms coupling the movement of the barrier mechanism in the hydraulic pump to the fluid chamber, such that a small amount of fluklfideally equal to, or at least proporhoaai to the amount of the workmg fluid entering the hydraulic pump ctombei} is expelled from the fluid chamber, through one or more orifice, in response to fhn movement of the harrier, :Qne embodiment of the fluid delivery system is sifestested in a irighrievel sclmmatle dewing in Figure 2 (see detailed deseriptiembeiow), This typo of fluid deliyesy syvtem / device cap be used fora broad range of appiieatk>»s> including but are not limited to biomedical research (e,g. orieromjection into ceils, mieiear or organelle temsplautorion, isolation of single cells or hyfe,ridoaias>: etc,), and dinica! applications (administration of medicaments, etc.).

For example* to provide a low level or variable dose of medicine over a long period of rime (mg,, borne oreve» days), foe fluid delivery system may form a portion of a single-nse dispenser for a medimimeni to be applied through any of the startditrd, infusions sets available on the market today or likely to be available in the future, Ifoe fluid delivery system, formed in some eaibodimon.ts m low-cost plastic parts, may comprise a hydraulic cylindef confalpmg fimorion as the pomp obamber d€^bad.-sib&amp;v^.^:6rib#^;lstd;'#smber'f0r storing metbeaments. In those emhodiments, the hydraulic cyliinler may be oouflgjjtoti rimilariy to most conventional bydraulie cylinders, and the wall, especially the inner wall of at least the chamber for storing a fiqtrid medicament to be delivered, maybe composed of Mo-duett and inev^pensive materials.

The folfowtrsg description is for principal Sbfbe construed as limiting in any respect ¥ariousMusrisfo^^t8^^ are.·: described forfoer below.

Hydraulic cylinder 100, as described in Figure 2, consists of two chambers, no and 12,0. Chamber 110 (corresponding to foe pomp chamber) is rilled by hyriraulic working fluid 112 fern a hydraulic msemur 114. Filling is accomplished by means of a eonnecrive passage 116, suchas (butnot limited to) a fobs or lumen either flexibly or rigidly connecting liyriratriiciresemoir 114 and hydraulic cylinder 100,. As hydmulle fluid 112 is forced out of reservoir 114 by Abator 135 (consisting, in an exemplary embodiment, of peristalric compression plates 13$A and 13 SB sad hinge 135¾ chamber 110 fills with itolvamandfhus forcing piston element 130 elmfofe 120 (coraespoMing to foe fluid chamber), Ifoe Poifed -Ikes in the actuator and the piston in Figure 2 reptesenlthe lafoMmMme positioa of a plate-hinge actuating mechanism, and foe lateMnflime position of the harder / piston,

Figure 3 is a »d5SS|^jbt(i|igmth. ·»*» advantage of the IMiii delivery system; e,g.s its ability to tolerate relatively large variations ift force generating the over-pressures, to create a ; telatively constant fluid delfoery rate over time or distance traveled by foe barrier pistoft, It is apparent that without the hydraullppamp system, any direct useof force foexpel fluid in the fluid chamber svilt.be hard to control, and will be subjected .to a large variation in delivery rate of the fluid (Figures 3 A). In contrast, with .the hydraulte pump, foe delivery rate is much mom constant {Figure :333),.

Chambers 110 and 120: can be, bat are: not necessarily separate, physics! chambers, since both chambers can exist within the confines of a hydraulic cylinder such m. the one in Figure 2 (hydraulic cylinder 100), The chambers am separated, fey a movesble bamer, such as thepiston elcntent 130 in Figure 2, where pisfou 130 may fee a flniddigfet fcatTier that prevents .hydraulic fluid 112 from entering foe second medicament fluid storage chamber 120, However» the Invention is not limited in foe type offeydraulic cylmder 100 or foe contours, dimensions or-fonfoes of the interior surfaces of cylinder 100, chamber 110, or chamber 120, Furthermore, foe im^ention is not lunited to particular configurations of piston element 130, The following description illnsirates several of many possible alternative embodiments that can he employed in the subject fluid delivery system.

In one embodiment as shown in Figure 4A, the piston element 130 in Figure 2 is replaced by a flexible ntenterane 132 separating foe pump chamber 110 and the fluid chamber 120. The flexible membrane can expand in response to foe increased pressure::fi:om tlse pump chamber 110, da© to the increase in volume offoe working fluid entering foe pump chamber 110 through apeffom 1$2, This in turn expels fluid fiom foe finid chamber 120 via orifice 140, '.fia another emhodiBient, as shown in. Figure 4B, chambers 110 and 120 may each, lias a separate:ψall «Bit: 134 and; 136, respectively (such as expandable bags: made from SexiMe matmal^. By virtue of being vdthin die limited confinement of cylinder 100, the expansion; in volume of chamber 110 necessarily leads to the decrease in volume of chamber 120, emattng a force· Id expelfiquid from chamber 120 via orifice 140. 1« yet another embodiment,: as shown In Figure 4Q, die pump chamber 110 and the Said chamber 120 may be separated from each other, but am mechanically etmpled. through a barrier mechanism 138 that trsasmifr movements in pump ehamber 1 10 to that in the fluid chamber 120. The coupling mechanism 138 can either a ugment or dimmish the magnitude of the initial movement in the pump chamber 11% snob that the cormaponding movement in the Said chamber 120 is increased, or decreased, in expelling a larger o* smaller ameexit 120. For example, the coupling mechanism 138 can be twd pistons United by a shaft, as shown in Figure 4€. ha one embodiment, the fluid chamber 120 may be detached from the pump chamber 110, so that a new fluid chamber (120’, not shown) may be m-attecheii

As noted above., chamber 120 is to be inifialiy filled wifta a quantity of liquid edrnponent to be delivered, such as ahmdi<amenfr In fiteease of a medicament, the qnaMity would typically be determined by a medical jan&amp;ssienal in order to provide the necessary dpfing over a prehteterntined period offinte. The volume of the fluid chamber May be about 100 μΐ, S0G pi, 1 ml, 3 mi,fi ml*. 1¾ ^30¾¾. 50 mi» 100 ml or more.

The depleted hydraulic, cylinder 100 in Figure 2 can be iMfitm· iteamected ha an infusion set 1.60 through orifice 140 at the distal end of chamber120{distal here meaning the end of chamber 120 distant from piston 130), In other words, the output orifice 140 of hydraulic cylinder 100 is on the opposite end of the cylinder from hydraulic fluid input aperture 132-, 08 one would commonly expect lit» hydraulic system*However, this is merely one of the preferred designs. The Output orifice 140 could be located on tie wall of cylinder 100 at fee chamber 120 potion If desired (see Figure 5 below).

Attached to orifice 140, in. some embodiments, is aa Infusion device or *se£*: 100 selected from -say of the infesion mesas conventionally known axel used in the medical arts,/Examples of infeskm devices melnde: g needle, such as depicted in Figure 1* a lumen and needle set; a catheter-cannula set; or a microneedle or mlcroneedle array attached fey means of one or more lumens. One of ordinary/ skill in fee art will readily appreciate that many devices exist to convey medicaments into a body. Accordingly, fee invention is not limited in the types .of infusion or injection devices used fefefevife.

In an lllnsteative embodiment, as shown here In a high-level schematic: drawing in Figure 5,the fluid delivery system is affixed to a delivery area of a patient, e.g. skin 200, by an adhesive means, such as a trausdepnal patch. TheilnM chamfeer 120 Is connected to a mlcmneedle or an array of mieroneedles IdO, such as fepse deaettfeed in IJ.S, Fat Ho, €,503,231 (fecotpofeted herein by reference^ ffelilce what is shown in Figure 5, fee mlcroneedle(s) need not completely enter fee skin layer 200, To achieve a low profile, both fee pump chamber 110 and fee fend Chamber 120 may be fiatm shape (rather than shaped like a cylinder), and fee outer· surfaces may hug fee contour of fee attached sfen layer300. Ibe orifiee(s) (not shewn) connecting fee fetid chamber and the mime^eedle(s) psefer#ly opens on a side-wall of fee fluid chamber 120. Alternatively, a epmeehve passage may link fee orifice on fl uid chamber 120 to fee mlereneedle or nderoneedlefe) array. Barrier 130 and aperture 152 are as described above. Also shown Is one embodiment of fee actuator, where plates 135 actuated by spring mechanism squeeze the hydmulic fluid reservoir 114 to inject hydraulic working fend Into fee pimp obafeber 110, Ofter actuators, such as feese descrihedin ether parts of fee specification,^maybe adapted fer use In this embodiment

As exemplified in Pigure 2, in operation, is adnfimsfered by compressing hyfeeulle fluid reservoir 114 in a eontmled manner with actuator 135. Figures 2 shows an exemplary peristaltic mechanism actuator 135. Ifowsvsr, ties aclnator may be alfemativdy aefeoM ffom any ofnfofor&amp;brof squeeze deuces that apply a force on foensservpifosueh as a mmiMuriged bellows crank or palter! rollers bearing on tessrvok 114 (see Figure 6 below), Moreover, Is other embodnnehts, foe reservoir can be acted on by aii expaading gas volume,:: thermal energy or any other device or process that will be capable of causing foe field to apply a pfessute,, either directly or indlfocfely,: to foe xnedicaut befog delivered. ϊη the enibodioient shown foKgnte plates 13SA and 13 5B are atteched by hinge 135C and forced together bynispriag'foj in mm embodiments, one or more pj<^oelec^bi#tneat^'|#h:p^;fgiibfo (&amp;g., elastomeric) hydraulic fluid reservoir 114 is squeezed betweenfopm, Sq^ieed[ng;ie|i:btoomericreservbiaf forces foe contents of the veasmir out forougi whatever aperture exists in foe reservoir. hi sortie :enfoodImgn!x} an aperture 153 is provided by the coupling tube lib and: foe adfosfofefe aperture 150, forther described below.

Acfoator 1 '35 may also take on. others forms. Hatchet or striper motor driven units that compress plates or ofoef sfoic|ano,s bearing on hydraulic reservoir 114 that move hydraulic; be need wlfoout departing .fo>m foe present invenriou.

Additionally, for a two-plate hinged: peristaltic mechanism snob as that represented by reference designator 13 5 hr Figure % springs mounted internally or externally to foe plates (not shown) play be used to force the plates together, Electrically driven or piezoelectric mechanisms, sneb as those described in the prior art, may also be

In one embodiment, as shown in Figure 6 A, one or mom external springfo) 13513 having a constant: Spring: coefficient dyer bs MI range of motion is (are) employed, (For fee sake of simplicity, a single spring conrigmadon is described. But multiple springs may b® used to adjust forces.) ’this spring is disposed so as to connect portions ofplates 135A and 135B distant tom hinge 135C aud io draw dfem fopfoer (Inwari^ when the system Is initially prepared for use, foe spring ls extended (i.e.:i placed in tension) by forcing plates 135Ά and 13 SB apart The plates are then held in place with a removable 'biace or other dmdee (not shown) to keep tet from compxossfeg h^rahlic reservoir 114. Qnee fee pump is in place arrd cooseote4 ilm>uglr hrfosios jaeo-os 1.60 (see Figure 2, butiroi shown here) to inject feemedfea,ment into thepairenf, the brace may be removed. lire constant spring tenrionplaced on plates 135A and 1.35B of actuator 135 wiil hren slowly feme -aasd- $quee52sef:-I^^T«cdffie 112 oat of reservoir 114 In a pexisiaM$4ike aebou.

In anofeer embodknexrt,, asIllustrated in Figure 6B, a compressed firing or set of springs 260 may he used to push a piston element 250 through a guided-palh to compress the hydraulic Sold reservoir 114, Adthe end of the reservoir, distal hi the piston element 250, is an aperture 1 S2:''1^':i^6^.&amp;c'hyd^lic fifed 112 to tarter the adjacen t pump chamber .110, so that barrier 130 maymmmaccordingly. In a more simplified version. the spring mechanism 250 and 260 may be replaced by thumb feme 301¾ just like in a traditional syringe (Fignm 6C), In both Figures 6B and 6C, them is no connective passage separating the fluid reservoir 114 from the pump chamber 110,

The adjustable aperture provides regulation of fire hferaoliepressure and flow rate in fire pump chamber 110, TMs regulation may he effected by allowing the aperture 152 (in Figure 2) to be adjusted to exfesmeiy for example, to a diameter of one4en thousandths of an inch (0.0901 inches, or about 2.5 tu.m) ox less.

In one embodiment, the aperture 152 has feed size, 1 does not have to be: round / circular in shape. For example, it could be roughly a square, a triangle, an oval, an irregular shape, or a polygon. Bthatever the Shape, the area of the opening will be sized to achieve the flow rate desired, fe example, dm opening may he about one-tenth thousandths of an inch (or 2-3 pm.) in diameter. Depending on use, the ©pemug size cmt he anj'fhmg rachjdmg an opening between 200 mn - 500 nnt, or 500 urn --- 1000 nm, or 1-2 pm, or 540 pm. Other sizes and dimensions can be selected and the size and dimension selected will depend upon tire application at hand. M as shown In Flgm® tSe aferimt^e 152 may ho afoustahle m riws, as by means of a conventional Ms Figure 7), miniature valve, or paired gating slits (for example and not by way of limitation) currently feiown in foe arts, For example, the adjustable aperture 15:2 may he adj«sfod hy meansof asirupls fo«m.h xvheel I Stl that activates foe conventional^ foifoatfoized valve or iris device foscnssed above, Sr an Mtemafo fonbodhnent, ah electrical motor or piegmlectrie device may he used to open or dose foe aperture, thus affecting foe rate at whichhydraulic fluid 112; Slows into chamber 110 and moves hairier 130.

Regardless of whether foe: aperture is adjustable or not, foe flow rate of the hydraulic fond can he «xintmfledfo>i!fo,.d|f^ie8at need$'i» certain embodiments, foe quantity of the fond in foe fluid chamber is expelled at a rate selected frinm abont 100 nl ~l μΐ per minute, about Ki d pi per minute, or about Id-100 μ! per minute. hi other eufoodhnents, foe fluid rate is mediated and controlled to be from .00.1 μ! per hour to 1(30 milliters per hour. The rate selected will depend upon the application at hand, and those of skill in the art will he ahle to determine foe proper dosage rate for a given application.

One feature rfapurture 1S2, whether afonstaMe Qruoh Mfoat itcan bemade extremely small so that hydraulic Snid 112 atfers chamber 110 at very lev/ rates, such as hnt not limited fo rates as low as ones or tens MmdcaxMifers per minute. When used wife abyfemdio .Sold of appropriate viscosity (ferfoer discussed below), foe configuration of aperture 152 enables preei# ptessure mptlafion that is insensitive to anfoisfo pressure or other This insensitivity, in Uuns, allovvs for lughiy accurate do$mg'a^^d^'^άl^te:'npdor a wider range of conditions than previously seen in the arts.

Jdyfoaufie ifoid 112 is, in some embodiments, an nitrapure, high viscosity, bioforerf materM, Yiscosity is limited at its upper bound by foe amount offeree developed1by theaotnaifo. In certain embodiments, foe force generated hy the actuator is about lO fo, 5fo,3 lb, 21b, 1 lb, 0,5 Μ, 0.1!Ρ? ,001. lb or less, At its lower bound, the fluid must be fosoons enough so that foe Sow can J5sm«fo;ldj^f':*egulatel' fey tiie cpnfiunatlon of actuate pressure.: and. aperture diameter in all eimroument conditions, especially In the presence of low atmospheric pressure and/or high auifeieni temperature (¾¾¾¾ viscosity tends to decrease). A simple test,may fee performed 1® roughly determine fete awage flow; mte of tfeefeymmdicilaid, fey fixing an aperture size ted fie futshihg the fluid reservoir, and detemifeiing the amount of hydraulic fluid. remaining jft the reservoir (and thus the amount exited) after a period of time. Ctememive periods of hydraulic Said loss (e.g. fluid loss in eonseoutive S-mimste periods, etc.} may fee measured to determine i f the rate of hydraulic fluidloss fern tfee resenmix is constant owfirae underihc condition used.

Medicaments suitable for use with the system presently disclosed include: insulin, opiates and/or other palliaduesj feornioneSj. psychotropic therapeutic composition, or any other drug or chemical whose continuous low vedmae dosing is desirable Of efficacious for use in weating patients. Mote mo that Mpaticnts?5 can be humaa or noh^mau animal; the use of continuous dosing pumps is not confined solely to human medicine, but can equally applied to veterinarian medicines,

In an. atteraate turn or more hydraulic ruscruons and actuators are piovided (Figure M an illustrative SA, the first reservoir 400 and actuate 235 are the same as or similar to items 114 and 135 in Figure2. The second reservoir 500 and actuate 235, which may use the same peristaltic actuate 135 as shown in idgure 2 or any oilier conventional alternative, such as those described above, are provided with a separate control In other words, the second actuate mey be cphtrolled independendy of the first Both fluid reservoirs me connected: to fim pmhp chamber wall 150,:;ttrdugfe apertures 154 and 156, mspeelively. The connection may optionally go Armagh 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 widr confinuor^ly supplied insulin during the day. The. second actuator control may thus be operated independently of the fimt actuator control mechanism to deliver the botes.

In an tetemarive embodiment, fewninfignre SB, faydmaKe fcid 112 fern botfe reservoirs 400 and 500 may pass tegeteer through a common lumen 1¾ and thence tfereagh adjustable aperture 152 0Sgaxe SB), Alternatively, as described above, the twoteservnim may lead into hydrateic chamber 110 by way of separate lumens aud separately adjustable apertures 154 and 150 (Eigure SA). te this tetter configuration, the rate of dosing aBeeted by either resenmir may be independently controlled through their respective adjustable apertures,

In a further alternative, ope Of fie ps^vpirs may lead to a fixed aperture while the other leads to an sdjaslatee aperterei I» this embodiment, aseM in eases such as die insulin-dependent diabetic described above, the tixed-apemne-eomieeted hydraulic reservoir can be actuated to provide botes dosing at discrete intervals, while the adjustable-aperlnre-connected hydraulic reservoir can be nsed to provide continuous slow dosing.

EXEMPLARY EMBODIMENT USING THE FLUID DELIVERY SYSTEM te one exemplary embodiment, there is provided a. method of adraimstering a medieame»| eomprlsteg: compressing a hydraulic fluid reservoir to fomesaid hydrahlie flidd through a eoeneciioh means; passing said hydraulic fluid ihrongh an adjustable aperture into a first, pump chamber, wherein said pump chamber |s seppated from an adjacent fitnd storage chamber for barrier, and wherein, said: fluid storage chamber ts filled vvite a medicament; displacing said moveable barrier into said fluid storage chamber by filling said pump chamber with said hydraulic fluid, wherein said displacing censes a quantity of said medicament to he expelled from said fluid storage chamber through an orifice.

Said passing may be aperture varying the flow of said hydraulic fluid and thus the quantity of said medicament expelled through said, orifice. Burteermote, the method may furfirer eomprixe injecting a quantity of said medicament into a patient through an infusion set connected to smd orifice.

In some mlmdimenf% the step of eompmssing may employ peristaltic companion of said reservoir at a constant fete, Alfematm^ tbs eompMssffig step muy employ pmisteibe compaction of said h«tery»lfaPa 'variable rate.

In yM atioftier atiersafe embodmreBi, dip: method may foteher compose rapidly compressing a second byiteaElie reservoir Siddly connected to said pomp chamber to displace said moveable barrier and thus causa a bolus o f said naedioamenf to he expelled through said orifice, This <fedxnfiBieni may bather comprise passing said hydraulie dmd from said seecmd hydraalie reservoir firmugfa a second aperture into smd primp chamber.

The order in which the stepsof the present mefimd ate perforatedis-purely illnstratiye in nature, and may not need to he performed in the exact sequence they am described. In feet, the steps can he performed ixi any suitable order or in parallel, «Mess otherwise indicated as inappropriate by tire present disclosure.

While several ilhtstmfiye embodiments of hydraulic pump system and its «so i« the Snid delivery system haver been shown and described, it wBl he apparent to those skilled in the art that changes and modifications may be made without depardirg itons this invention in us broader aspect and. therefore, the appended claims are to encompass within their scope all such changes aid modifications as fell within the true spirit of this invention.

Claims (24)

1. THE CLAIMS DEFINING THE INVENTION ARE AS FOLLOWS:-

   1. A fluid delivery device comprising: a hydraulic housing having a piston configured to sealingly slide along an inner wall of the hydraulic housing and separate the hydraulic housing into a hydraulic pump chamber and a fluid reservoir, the hydraulic pump chamber having a viscous hydraulic fluid and configured to urge the piston along the inner wall to deliver a fluid in the fluid reservoir to a patient, a viscosity of the hydraulic fluid being at least about ISO VG 1000 or more; a first actuator; a first hydraulic reservoir chamber having the hydraulic fluid and coupled between the first actuator and the hydraulic pump chamber, the first actuator being configured to urge the hydraulic fluid in the first hydraulic reservoir chamber into the hydraulic pump chamber; a flow restrictor fluidly coupling the first hydraulic reservoir chamber and the hydraulic pump chamber; a second hydraulic reservoir chamber having the hydraulic fluid and fluidly coupled with the hydraulic pump chamber; and a second actuator configured to urge the hydraulic fluid from the second hydraulic reservoir chamber into the hydraulic pump chamber, independent of the first actuator.
2. 2. The fluid delivery device of claim 1, wherein any insoluble impurity particles in the hydraulic fluid have a maximum diameter of 1 mm or less.
3. 3. The fluid delivery device of claim 1 or claim 2, wherein any insoluble impurity particles in the hydraulic fluid have a maximum diameter of 500 nm or less.
4. 4. The fluid delivery device of any one of claims 1 to 3, wherein any insoluble impurity particles in the hydraulic fluid have a maximum diameter of 100 nm or less.
5. 5. The fluid delivery device of any one of claims 1 to 4, wherein any insoluble impurity particles in the hydraulic fluid comprise less than 0.1% of a total volume of the hydraulic fluid.
6. 6. The fluid delivery device of any one of claims 1 to 5, wherein any insoluble impurity particles in the hydraulic fluid comprise less than 0.01% of a total volume of the hydraulic fluid.
7. 7. The fluid delivery device of any one of claims 1 to 6, wherein any insoluble impurity particles in the hydraulic fluid comprise less than 0.001% of a total volume of the hydraulic fluid.
8. 8. The fluid delivery device of any one of claims 1 to 7, wherein the flow restrictor and the first actuator are configured to transfer the hydraulic fluid from the first hydraulic reservoir chamber to the hydraulic pump chamber to deliver the fluid from the fluid reservoir at a sustained basal rate.
9. 9. The fluid delivery device of any one of claims 1 to 8, wherein the first actuator includes one or more springs.
10. 10. The fluid delivery device of any one of claims 1 to 9, further comprising the fluid in the fluid reservoir, wherein the fluid comprises insulin.
11. 11. The fluid delivery device of claim 8, wherein the sustained basal rate is constant.
12. 12. The fluid delivery device of claim 8, wherein the sustained basal rate is over a period of more than 5 hours.
13. 13. The fluid delivery device of claim 8, wherein the sustained basal rate is over a period of approximately 24 hours.
14. 14. The fluid delivery device of any one of claims 1 to 13, wherein the hydraulic fluid has a viscosity of approximately ISO VG 1500 or more when in use.
15. 15. The fluid delivery device of any one of claims 1 to 14, further comprising a moveable piston separating the hydraulic pump chamber and the second actuator.
16. 16. The fluid delivery device of any one of claims 1 to 15, wherein the hydraulic pump chamber and the fluid reservoir are comprised of a polymer.
17. 17. The fluid delivery device of any one of claims 1 to 16, wherein any insoluble impurity particles in the hydraulic fluid each have a maximum diameter that is smaller than a diameter of the flow restrictor.
18. 18. The fluid delivery device of any one of claims 1 to 17, wherein the first actuator is purely mechanical.
19. 19. The fluid delivery device of claim 18, wherein the first actuator includes two springs.
20. 20. The fluid delivery device of any one of claims 1 to 19, wherein the second hydraulic reservoir is positioned between the second actuator and the hydraulic pump chamber.
21. 21. The fluid delivery device of any one of claims 1 to 20, wherein the flow restrictor is a fixed aperture.
22. 22. The fluid delivery device of any one of claims 1 to 21, wherein the piston is a single piston that contacts the fluid in the fluid reservoir on one side and the hydraulic fluid on another side.
23. 23. A fluid delivery device comprising: a hydraulic housing having a piston configured to sealingly slide along an inner wall of the hydraulic housing and separate the hydraulic housing into a hydraulic pump chamber and a fluid reservoir, the hydraulic pump chamber having a hydraulic fluid, a viscosity of the hydraulic fluid being at least about ISO VG 1000 or more, the hydraulic pump chamber being configured to urge the piston along the inner wall to deliver a fluid in the fluid reservoir to a patient; a first hydraulic reservoir chamber having the hydraulic fluid; a fixed aperture flow restrictor fluidly coupling the first hydraulic reservoir chamber and the hydraulic pump chamber, the fixed aperture flow restrictor configured to control the rate the hydraulic fluid flows between the first hydraulic reservoir chamber and the hydraulic pump chamber; a first actuator coupled to the first hydraulic reservoir chamber and configured to continuously deliver the hydraulic fluid from the first hydraulic reservoir chamber to the hydraulic pump chamber for a period of time; a second hydraulic reservoir chamber fluidly coupled to the hydraulic pump chamber, independent of the first hydraulic reservoir chamber; and a second actuator coupled to the second hydraulic reservoir chamber and operable independent of the first actuator and at discrete intervals during the period of time to periodically deliver the hydraulic fluid from the second hydraulic reservoir chamber to the hydraulic pump chamber independent of and in addition to the continuous delivery of the hydraulic fluid from the first hydraulic reservoir chamber.
24. 24. A fluid delivery device comprising: a hydraulic housing having a piston configured to sealingly slide along an inner wall of the hydraulic housing and separate the hydraulic housing into a hydraulic pump chamber and a fluid reservoir, the hydraulic pump chamber having a hydraulic fluid and configured to urge the piston along the inner wall to deliver a fluid in the fluid reservoir to a patient; a first hydraulic reservoir chamber having the hydraulic fluid; a fixed aperture flow restrictor fluidly coupling the first hydraulic reservoir chamber and the hydraulic pump chamber, the fixed aperture flow restrictor configured to control the rate the hydraulic fluid flows between the first hydraulic reservoir chamber and the hydraulic pump chamber; a first actuator coupled to the first hydraulic reservoir chamber and configured to continuously deliver the hydraulic fluid from the first hydraulic reservoir chamber to the hydraulic pump chamber for a period of time; a second hydraulic reservoir chamber fluidly coupled to the hydraulic pump chamber, independent of the first hydraulic reservoir chamber; and a second actuator coupled to the second hydraulic reservoir chamber and operable independent of the first actuator and at discrete intervals during the period of time to periodically deliver the hydraulic fluid from the second hydraulic reservoir chamber to the hydraulic pump chamber independent of and in addition to the continuous delivery of the hydraulic fluid from the first hydraulic reservoir chamber.