CA2131794A1 - Drug delivery devices - Google Patents
Drug delivery devicesInfo
- Publication number
- CA2131794A1 CA2131794A1 CA002131794A CA2131794A CA2131794A1 CA 2131794 A1 CA2131794 A1 CA 2131794A1 CA 002131794 A CA002131794 A CA 002131794A CA 2131794 A CA2131794 A CA 2131794A CA 2131794 A1 CA2131794 A1 CA 2131794A1
- Authority
- CA
- Canada
- Prior art keywords
- drug
- drug delivery
- tubular elements
- reservoir
- subject
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
- A61M5/14—Infusion devices, e.g. infusing by gravity; Blood infusion; Accessories therefor
- A61M5/142—Pressure infusion, e.g. using pumps
- A61M5/14244—Pressure infusion, e.g. using pumps adapted to be carried by the patient, e.g. portable on the body
- A61M5/14248—Pressure infusion, e.g. using pumps adapted to be carried by the patient, e.g. portable on the body of the skin patch type
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N1/00—Electrotherapy; Circuits therefor
- A61N1/18—Applying electric currents by contact electrodes
- A61N1/20—Applying electric currents by contact electrodes continuous direct currents
- A61N1/30—Apparatus for iontophoresis, i.e. transfer of media in ionic state by an electromotoric force into the body, or cataphoresis
- A61N1/303—Constructional details
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
Abstract
A drug delivery device includes a liquid reservoir (24) for a liquid drug to be delivered, and a drug delivery body which includes a plurality of tubular elements (26) or hollow needles extending through the body, each having an inlet end communicating with the liquid reservoir, and an outlet end projecting from the body and engageable with the subject's skin to conduct the liquid drug directly to the subject's skin.
Description
!
W093/177~ 21317 9 4 PCT~EP93/00562 .j DRUG DELIVERY ~EVICES
;l The present invention relates to transdermal or ~1 interdermal drug deli~ery devices for deli~ering a liquid drug to a su~ject ~ia the subject's skin. The invention is particularly useful with respect to the drug delivery device ~, described in our Patent No.5,156,S9~, and is therefor,e described below with respect to that device, but it will be ~: appreciated thiat the invention could advantageously be used in other types of drug delivery devices.
Our Patent No~5,156,591 describes a transdermal drug delivery device which deli~ers a drug to the subject by ~ means of an electrically-induced mass transfer phenomenon f called iontophoresi$. This process for drug delivery has recently become of great interest, and many such transdermal ~! ~ 15 delivery devices have been described in the patent literaturer including US Patents 4,164,226, 4,640,689, 4,7~8,716, 4,752,285, 4,693,711, 5,057,072, US Statutory ~.
Invention Registration H516, and European Patent Applica~ion Publication 0299631. Other methods of electrically-aided or .~ 20 electrically-controlled transdermal drug delivery devices are described in US Patent 4,886,513, as well as in our prior US Patents 5,062,834 and 5,090,963.
:: According to the present invention, there is provided a drug deli~ery device for delivering a ~iquid drug to a subject ~ia the subject's skin, comprising: a housing;
a liquid reserYoir in the housing for a liquid drug to be i.`: ~: delivered; and a drug delivery body carried by the housing .. :~ and having one side~commu~icating with one side of the ~J~., ; ~ liquid reservoir, and the opposite side exposed to engage : 30 the skin of the subject to receive the drug; characterized in that the drug delivery body includes a plurality of stiff tubular elements extending through the body, each having an ` ~ inlet end co~miunicating with the liquid reservoir, and an outlet end at said opposite side of the drug delivery body . 35 to conduct the liquid drug directly to said opposite side.
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The plurality of stiff tubular elements may be in the orm of hollow needles having inner diameters of less than 1 mm and projecting at least 0.1 mm from the face of the dru~ delivery body. Preferably, the drug deiivery body includes at least fif~y of such stiff tubular elements or ,;. hollow needles. Their tips may be cut at a bias to pierce the outer layer of dead cells on the skin and thereby to enhance the penetrat~on of the drug.
,i In the use of the device, the plurality of tubular .~ 10 elements are pressed firmly against the subject's skin, and ,~ thereby provide a better delivery of the drug to the subjectls skin, as compared to the use of microporous or matrix-type drug deli~ery bodies as in the prior art. The device also permits better control of the drug delivery rate. ~Whën~the delivery is effected by iontophoresis, the better delivery of the drug enables lower electrical currents to be used, thereby decreasing the danger.of burning or irritating the subject's skin.
Fig. 1 is a top plan view illustrating one form of transdermal drug deli~ery de~ice constructed in accordance ~; with the present in~ention;
Fig. 2 is a bottom plan view of the deYice of Fig. 1;
Fig. 3 is an enlarged sectional view along ~ine III-III of Fig. 2;
Figs. 4, S and 6 are ~iews similar to that of ~, Fig. 3 but illustrating three further forms of drug delivery devices constructed i~ accordance with the present invention;
~, 30 and Figs. 7a-7e illustrate ~arious t~p constructions of the stiff tubular elements extendin~
through the dsug delivery body-The transdermal drug delivery deYice illustrated in Figs. 1-3 of the drawings, and genera~ly desi~nated 2, is applied by a ~and 3 to the arm or leg of the subject, with one side of the device (that side illustrated in Fig. 2) G~'.'' firmly pressed against the subject's skin. The device 2 is SU8S'rITUTE SHEE~
~i W093/l7754 2 1 3 1 7 9 4 PCT/EW3/0~62 ~ - 3 - ._.
,;1 ;~ a self-contained unit which ~ncludes a reservoir for the uid drug to be delivered, as well as electrodes for deliv~ring the dsug by means of the iontophoresis electrically-induced mass transfer phenomenon. De~ice 2 s 5 ~urther includes an electrolytic cell which, together with the iontophoresis electrodes, controls the rate of feed of the drug to the subject, and an electrical battery for powering both the iontophoresis electrodes and the electrolytic cell.
.1 10 The internal stucture of the transdermal drug ~ delivery de~ice 2 is more particularly illustrated in .j Fig. 3. It includes a housing 4 of plastic material and of :: circular configuration. Housing 4 is made of an inner section 4a, an outer section 4b, and an intermediate section 15 4c threadedly joining sections 4a.and 4b together. The inner section 4a is formed with a large circular opening 6, and the outer section 4b is formed with a smaller circular opening 8.
~ An inner membrane 10 is clamped between housing ;~ 20 sections ~a ~nd 4c, and an outer membrane 12 is clamped between housing sections 4b and 4c. Both membranes 10 and ~ : 12 are of elastome~ic ma~erial and include annular flexible ;. sections 1Oa, 1~a, to make them displaceable in response to.
:`:j,4 pressure. Membrane 10 is aligned with the center opening 6 25 in housing section 4a and is clamped between that housing ; section and the intermediate section 4c via a ring 14.
...
Membrane 12 is clamped between the i~termediate housing .. section 4c and the outer housi~g seGtion 4b ~ia a disc 16 ; ha~ing a central opening 18 in alignment with opening 8 in 30 the outer housing section 4b. A third membrane 20 is clamped between disc 16 asd the outer housing section 4b to l,i , close opening 8.
, Membrane 10 is displaceable outwardly of housing 4 i~ by its ~nnular fIexible section 1Oa, but is restrained ~ ~ 35 againSt inward displacement by a r~gid annular disc 22 .- integrally formed with the intermediate housing seGtion 4c.
: Mem~rane 12, however, is displaceable in both directions by ~;;i S U ~TIT U TE S H EE~r ~ W093/17754 2131~ 9 ~ PCT/EP93/0056~"
? ._ -- 4 its annular flexible section 12a. Membrane 20 is simila~ly , displaceable in both directions with respect to openings 8 ~''?i and 18 in housing section 4b and disc 16, respectively.
,. The two me~branes 10, 12 de~ine, between the~ a 5 chamber 24 sesYing as a liguid reser~oir for the liquid drug to be deli~ered by the device 2. Mem~ra~e 10 serves as a ~ ' drug deli~ery body through which the drug is delivered. For ??5,~ this purpose, membrane 10 includes a plurality of tubular elements 26 extending through it, with each tubular element ,~ 10 ha~ing an inlet end 26a communicating with the liquid reservoir 24, and an outlet end 26b engageable with the subject's skin.
A second chamber 28 is defined between membrane 12 and disc 16 and its membrane 20. Chamber 28 ser~es as a 15 pressure-control chamber for cont~olling the pressure applied to the drug chamber 24 for controlling the rat~ of feed of the liquid drug via tubular elements ~6 through the drug delivery ~embrane 10. For this purpose, chamber ~8 includes an electro}ytic cell, generally designated 30, 20 comprising a pair of electrodes 30a, 30b and an eIectrolyte 30c which generates a gas in accordance with the current passing through it. Such electrolytic cells are well known and are capable of:generating a gas (e.g., oxygen and/or hydrogen) when an electrical current is applied.
: 25 Electrolyti~ cell 30 is located in one side of a ~: ca~ity formed in membrane 12. The other side of the cavity serves as a compartment for a button-type battery 32 powering the electrolytic cell 30. Electrode 30a of the electrolytic cell is connected to one side of the battery via sprin~ clips-34a and 34b electrically connected together : by lead 34c, all carried by disc t6. Electrode 30b of the : electrolytic cell is extended so as to engage the other side of the battery 32.
Battery 32 also supplies electrical current to a pair of iontophoresis electrodes 36, 38, to induce the transfer of the drug within compartment 24 ~ia the tubular elements 26 i~ membrane 10 to the subject's skin. Electrode SUB~:~'ITUTE ~:HEFr ,- ~ 7 '' '~ :'1;
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- ~ W093t17754 2 I 31 794 PCI/EP93/0056~
. ! -- 5 36 is of annular shape and encloses membrane 10 so as to come into contact with the subject's skin when the de~ice 2 is applied to the subject. Electrode 38 is a conductive layer applied to membrane 12 facing the drug compartment 24 so as to come into direct contact with the drug therein~
~!~'''' The drug is introduced into the drug compartment 24 ~.ia an injection port 40 received in an opening on one side of the intermediate housing section 4c. A nipple 42 is ., threadely applied in alignment with an opening in the opposite side of the intermediate housing section 4c and is closed by a hydrophobic filter 44. The liquid drug is .1 introduced into drug compartment 24 ~ia an injection syringe .j piercing plug 40. Nipple 42 serves as a vent for purging .~ the air ~rom compartment 24 until the vent is closed by . 15 contact of the liquid drug with the hydrophobic filter 44 when the compartment is filled with the drug.
. Membrane 10 is made of a reslient~ deformable . material. The tubular elements 26 passing through membrane 10 are preferably made of a stiff, i.e., rigid or emi-rigid, plastic material ha~ing an inner diameter of less than 1.0 mm, and projecting at least 0.1 mm from *he . : outer face of membrane 10. As examples, these tubular elements 26 may be ~ade of Teflon (Reg. TM), or of a - polycarbona~e resin,:have an outer diameter of 1.0 mm, an inner diameter of ~.S mm, and projecting about 0.3 mm from the surface of the drug deli~ery membrane 10 in contact with .~ the subject's s~in. Preferably, they are in the form of hollow metal needles, such as of steel or aluminum coated on heir outer suraces with a c~ating of insulation, e.g., by ~ 30 oxidation, ~hemical deposition, etc.
t~ A drug delivery device would usually include at least SQ of such tubular elements, with the outlet ends 26b of each such ele~ent fi~mly engaging the subject's s~in so . as to effectively seal their inner channels to the subject's skin. These tubular elements thus deliver the drug from compartment 24 directly to a multitude of spaced discrete ~reas on the subject's skin, and at a rate determined by the ~,jQ gt IF~TIT~ ITE ~ HEET
W093/177~ PCT/EP93/005~?~
,:~ 213179~S
~ pressure applied to the drug chamber 24 by the displacement i:~ of membrane 12.
As one example, memb~anes 10, 12 and 20 may be of a silicone rubber. Electrically-conductive layer 38 ap~lied S to membrane 12, and/or eléctrode 36 applied to the subject's skin, may also be of a silicone rubber, but with an electrically-conductiye ~iller such as silver, carbon or aluminum particles.
The device illustrated in Figs. 1-3 may be applied 10 to the arm or leg of the subject to recei~e the drug by the use of the bands 3 such that the inner face of the device, trated in Fig. 2, firmly engages the subject's skin.
When the de~ice is so applied, the outer ends 26b of the st~f tubular elements 26 passing through the drug-delivery '~ 15 membrane 10 project slightly ~rom the mem~rane and firmly ~, engage the su~ject's skin.
Battery 32 supplies electrical current via an electrical switch or other control circuitry (not shown) to both the electsolytio cell electrodes 30a, 30b and to the iontophoresis electrodes 36, 38.
The electrolytic cell 30 generates a gas in accordance with the magnitude of the electrical current applied to its electrolyte 30c. This gas increases the pressure within chamber 28 to displace membrane 12 towards 25 membrane 10, thereby increasing the pressure within the drug chamber 24. Me~rane ~0, ha~ing one side exposed to the pressure within chamber~28 and the other si~e exposed to the osphere, tends to regulate the pressure within cha~ber 28.
The displacement of membrane 12 towards the drug delivery membrane 10 forces the liquid drug from compartment 24 through the tubular elements 26 in accordance with the . pres~re in ch ~ er 24. The pressure in chamber 24 also tends to displzce membrane 10 outwardly, thereby mo~e firmly 35 pressing the outlet ends 26b of the tubular elements 26 into contact with the subject's skin. It will thus be seen that the rate of feeding of the drug from chamber 24 ~ia tubular :
~:~ IR~:TITI ITF ~lEET
` ~ 21317~4 ~WO93/177~ - PCT/EP93/00~62 ~ _ 7 -.~J elements 26 to the subject's skin will be controlled by the.
rate of generation of gas by the electrQlytic cell 30.
The transfer of the dxug from compartment 24 to the subject's skin is electrically-induced by the voltage ,i 5 applied between the two iontophoresis electrodes 36 and 38.
Electrode 36 directly contacts the subject's skin, and electrode 38 directly contacts the drug within compartment 24 delivered to the subject's skin via the tubular elements 26.
. 10 It will thus be seen that the delivery of the drug ~ from compartment 24 to the subject's skin is effected in a !,j manner which is both efficient and controllable by .. controlling the electrical current supplied to the electrolyic cell 30 and also the voltage applied between the tw~ iontophoresis electrodes 36, 38.
f Fig. 4 illustrates another device which is `J~.,h generally similar to that of Fig. 3 but includes a nu~ber of changes. To faciiita~e understanding, the elements in the - device of Fig. 4 which are generally s~milar to those in , : 20 Fig. 3 are correspondingly numbered.
',!" One important difference in the de~ice of Fig. 4 :;1 over that of ~i~. 3 is that ~he housing 4 is a two-section ~l housing (rather than a three-section housing), including the A two sections 4 and 4b threadedly secured ~ogether. The ~ 25 injection port 40 for introducing the drug into the drug ~ '3 reser~oir in compartment 24 is located within an ope~ing in housing section 4a.
: Another difference in the construction of the device of Fig. 4 over that of Fig. 3 is that the drug 30 deli~ery body for delivering the drug from the drug compartmen~ ~4 is constituted, not by a displaceable ,i ~ membrane 10, but rather by the rigid wall S0 of housing section 4a, which rigid wall carries the stiff tubular elements 26 communicating with the drug compartment 24.
3_ Thus, the de~ice of Fig. 4 does not include a membrane ,.~ corresponding to membrane 10 in Fig. 3.
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.~ The device of Fig. 4, however, does include membranes 12 and 20 defining between them the compartment for the electrolytic cell 30 and battery 32. The latter ~ elements, instead of being received within a socket formed s~ 5 in membrane 12, are rathex received within a socket formed in a rigid holder 52 secured between the two housing sections 4a and 4b. $he electrolytic cell 3~ communicates with chamber 28 between the two membranes ~2 and 20, such that the pressure produced in chamber 28 by the gas generated from the electrolytic cell 30, deforms membrane 12 to control the rate of delivery of the drug ~ia the stiff tubular elements 26.
Membrane 20, in the construction of Fig. 4, is secured between housing section 4b and the rigid holder 50 and carries electrical contact 34c on its inner face engageable with electrical contacts 34a and 34b connecting battery 32 to the electrolytic cell 30 to regulate the pressure of the gas within chzmber 28. Thus, if an excessi~e pressure is developed within chamber 28, this will displace the center of membrane 20 outwardly, to cause its ~: contact 34c to disengage from contacts 34a and 34b, thereby de-energizing the elect~olytic cell 30 until the excessive pressure within chamber ~8 drops to the point where contact 34c again engages contacts 34b and 34a to restart the : 25 generation of the gas from the electrolytic cell.
A still further difference in the construction of .~ Fig. 4 over that of Fig. 3 is that in Fig. 4 the iontophoresis electrodes 36 and 38 are omitted. Thus, in the construction of Fig. 4, the deli~ery of the drug from ~: 30 compartme~t 24 ~ia the stiff tubular elements 26 i5 ~,: controlled by the rate of generation of gas by electrolytic ~ cell 30. In substantially all other respects, the device of ;, Fig. 4 is constructed, and operates, in substantially the same manner as described above with respect to Fig~ 3.
Fig. S illustrates another device similar ta that ~i of Fi~s. 3 and 4 but further simplified in construction. To facilitate understanding, those parts which are ~enerally SUBST~TUTE ~:HEEr ~ . WO93/17754 21 31 7 9 4 PCT/EP93/00562 g -- _ .
similar to those in Figs. 3 and 4 are correspondingly numbered.
Thus, the de~ice in Fig. 5 also includes a two-: section housing 4a, 4b, as in Fig. 4, with the stiff tubular elements 28 ~arried by the rigid end wall 50 of housingsection 4a. In Fig. 5, however, the drug reservoir compartment 24 is defined by a displaceable membrane 62, generally sim~lar to membrane 20 in Figs. 3 and 4, secured . between the two housing sections 4a, 4b, and a partition wall 60 within the housing and formed with a metering or~fice 64 for metering the flow of the drug from compartment 24 to the stiff tubular e7ements 28. Partition 60 is formed wîth an annular rib 66, or other rib formation, in order to space it from the ends of the stiff tubular elements 28 and to permit the drug to flow thereto from the reservo~r in co~partment 24 via the metering orifice 64.
Thus, in the construction illustrated in Fig. 5, the control of the rate of delivery of the drug via the stiff tubular elements 28 is effected by the metering orifice 64 of partition 60. Therefore, whenever it is desired to change the drug deli~ery rate, a partition 60 with the appropriate-size metering orifice 64 would be inserted into the housing 4.
Fig. 6 illustrates another construction, similar to that of Fig. 5, but even further si~plified. trhose elements in Fig. 6 which generally correspond to those in Fig. 5 are correspo~dingly numbered to facilitate understarlding .
In the construction illustrated in Fig. 6, the partition 60, including its metering orifice 64, is omitte~, and instead the rate of delivery of the drug is controlled by the pressure withi~ the drug reservoir chamber 24. The drug is introduced into cha~ber 24, at the appropriate ` pressure, via iniection port 40, and membrane 62 is 3s displaced outwardly so as to apply a continuous pressure tending to ur~e the drug to flow from chamber 24 through the stiff tubular elements 28. If the pressure within chamber ' SUBSTITUTE SHEET
s .~. WO93/177~ PCT/EP93/00562>
W093/177~ 21317 9 4 PCT~EP93/00562 .j DRUG DELIVERY ~EVICES
;l The present invention relates to transdermal or ~1 interdermal drug deli~ery devices for deli~ering a liquid drug to a su~ject ~ia the subject's skin. The invention is particularly useful with respect to the drug delivery device ~, described in our Patent No.5,156,S9~, and is therefor,e described below with respect to that device, but it will be ~: appreciated thiat the invention could advantageously be used in other types of drug delivery devices.
Our Patent No~5,156,591 describes a transdermal drug delivery device which deli~ers a drug to the subject by ~ means of an electrically-induced mass transfer phenomenon f called iontophoresi$. This process for drug delivery has recently become of great interest, and many such transdermal ~! ~ 15 delivery devices have been described in the patent literaturer including US Patents 4,164,226, 4,640,689, 4,7~8,716, 4,752,285, 4,693,711, 5,057,072, US Statutory ~.
Invention Registration H516, and European Patent Applica~ion Publication 0299631. Other methods of electrically-aided or .~ 20 electrically-controlled transdermal drug delivery devices are described in US Patent 4,886,513, as well as in our prior US Patents 5,062,834 and 5,090,963.
:: According to the present invention, there is provided a drug deli~ery device for delivering a ~iquid drug to a subject ~ia the subject's skin, comprising: a housing;
a liquid reserYoir in the housing for a liquid drug to be i.`: ~: delivered; and a drug delivery body carried by the housing .. :~ and having one side~commu~icating with one side of the ~J~., ; ~ liquid reservoir, and the opposite side exposed to engage : 30 the skin of the subject to receive the drug; characterized in that the drug delivery body includes a plurality of stiff tubular elements extending through the body, each having an ` ~ inlet end co~miunicating with the liquid reservoir, and an outlet end at said opposite side of the drug delivery body . 35 to conduct the liquid drug directly to said opposite side.
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The plurality of stiff tubular elements may be in the orm of hollow needles having inner diameters of less than 1 mm and projecting at least 0.1 mm from the face of the dru~ delivery body. Preferably, the drug deiivery body includes at least fif~y of such stiff tubular elements or ,;. hollow needles. Their tips may be cut at a bias to pierce the outer layer of dead cells on the skin and thereby to enhance the penetrat~on of the drug.
,i In the use of the device, the plurality of tubular .~ 10 elements are pressed firmly against the subject's skin, and ,~ thereby provide a better delivery of the drug to the subjectls skin, as compared to the use of microporous or matrix-type drug deli~ery bodies as in the prior art. The device also permits better control of the drug delivery rate. ~Whën~the delivery is effected by iontophoresis, the better delivery of the drug enables lower electrical currents to be used, thereby decreasing the danger.of burning or irritating the subject's skin.
Fig. 1 is a top plan view illustrating one form of transdermal drug deli~ery de~ice constructed in accordance ~; with the present in~ention;
Fig. 2 is a bottom plan view of the deYice of Fig. 1;
Fig. 3 is an enlarged sectional view along ~ine III-III of Fig. 2;
Figs. 4, S and 6 are ~iews similar to that of ~, Fig. 3 but illustrating three further forms of drug delivery devices constructed i~ accordance with the present invention;
~, 30 and Figs. 7a-7e illustrate ~arious t~p constructions of the stiff tubular elements extendin~
through the dsug delivery body-The transdermal drug delivery deYice illustrated in Figs. 1-3 of the drawings, and genera~ly desi~nated 2, is applied by a ~and 3 to the arm or leg of the subject, with one side of the device (that side illustrated in Fig. 2) G~'.'' firmly pressed against the subject's skin. The device 2 is SU8S'rITUTE SHEE~
~i W093/l7754 2 1 3 1 7 9 4 PCT/EW3/0~62 ~ - 3 - ._.
,;1 ;~ a self-contained unit which ~ncludes a reservoir for the uid drug to be delivered, as well as electrodes for deliv~ring the dsug by means of the iontophoresis electrically-induced mass transfer phenomenon. De~ice 2 s 5 ~urther includes an electrolytic cell which, together with the iontophoresis electrodes, controls the rate of feed of the drug to the subject, and an electrical battery for powering both the iontophoresis electrodes and the electrolytic cell.
.1 10 The internal stucture of the transdermal drug ~ delivery de~ice 2 is more particularly illustrated in .j Fig. 3. It includes a housing 4 of plastic material and of :: circular configuration. Housing 4 is made of an inner section 4a, an outer section 4b, and an intermediate section 15 4c threadedly joining sections 4a.and 4b together. The inner section 4a is formed with a large circular opening 6, and the outer section 4b is formed with a smaller circular opening 8.
~ An inner membrane 10 is clamped between housing ;~ 20 sections ~a ~nd 4c, and an outer membrane 12 is clamped between housing sections 4b and 4c. Both membranes 10 and ~ : 12 are of elastome~ic ma~erial and include annular flexible ;. sections 1Oa, 1~a, to make them displaceable in response to.
:`:j,4 pressure. Membrane 10 is aligned with the center opening 6 25 in housing section 4a and is clamped between that housing ; section and the intermediate section 4c via a ring 14.
...
Membrane 12 is clamped between the i~termediate housing .. section 4c and the outer housi~g seGtion 4b ~ia a disc 16 ; ha~ing a central opening 18 in alignment with opening 8 in 30 the outer housing section 4b. A third membrane 20 is clamped between disc 16 asd the outer housing section 4b to l,i , close opening 8.
, Membrane 10 is displaceable outwardly of housing 4 i~ by its ~nnular fIexible section 1Oa, but is restrained ~ ~ 35 againSt inward displacement by a r~gid annular disc 22 .- integrally formed with the intermediate housing seGtion 4c.
: Mem~rane 12, however, is displaceable in both directions by ~;;i S U ~TIT U TE S H EE~r ~ W093/17754 2131~ 9 ~ PCT/EP93/0056~"
? ._ -- 4 its annular flexible section 12a. Membrane 20 is simila~ly , displaceable in both directions with respect to openings 8 ~''?i and 18 in housing section 4b and disc 16, respectively.
,. The two me~branes 10, 12 de~ine, between the~ a 5 chamber 24 sesYing as a liguid reser~oir for the liquid drug to be deli~ered by the device 2. Mem~ra~e 10 serves as a ~ ' drug deli~ery body through which the drug is delivered. For ??5,~ this purpose, membrane 10 includes a plurality of tubular elements 26 extending through it, with each tubular element ,~ 10 ha~ing an inlet end 26a communicating with the liquid reservoir 24, and an outlet end 26b engageable with the subject's skin.
A second chamber 28 is defined between membrane 12 and disc 16 and its membrane 20. Chamber 28 ser~es as a 15 pressure-control chamber for cont~olling the pressure applied to the drug chamber 24 for controlling the rat~ of feed of the liquid drug via tubular elements ~6 through the drug delivery ~embrane 10. For this purpose, chamber ~8 includes an electro}ytic cell, generally designated 30, 20 comprising a pair of electrodes 30a, 30b and an eIectrolyte 30c which generates a gas in accordance with the current passing through it. Such electrolytic cells are well known and are capable of:generating a gas (e.g., oxygen and/or hydrogen) when an electrical current is applied.
: 25 Electrolyti~ cell 30 is located in one side of a ~: ca~ity formed in membrane 12. The other side of the cavity serves as a compartment for a button-type battery 32 powering the electrolytic cell 30. Electrode 30a of the electrolytic cell is connected to one side of the battery via sprin~ clips-34a and 34b electrically connected together : by lead 34c, all carried by disc t6. Electrode 30b of the : electrolytic cell is extended so as to engage the other side of the battery 32.
Battery 32 also supplies electrical current to a pair of iontophoresis electrodes 36, 38, to induce the transfer of the drug within compartment 24 ~ia the tubular elements 26 i~ membrane 10 to the subject's skin. Electrode SUB~:~'ITUTE ~:HEFr ,- ~ 7 '' '~ :'1;
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- ~ W093t17754 2 I 31 794 PCI/EP93/0056~
. ! -- 5 36 is of annular shape and encloses membrane 10 so as to come into contact with the subject's skin when the de~ice 2 is applied to the subject. Electrode 38 is a conductive layer applied to membrane 12 facing the drug compartment 24 so as to come into direct contact with the drug therein~
~!~'''' The drug is introduced into the drug compartment 24 ~.ia an injection port 40 received in an opening on one side of the intermediate housing section 4c. A nipple 42 is ., threadely applied in alignment with an opening in the opposite side of the intermediate housing section 4c and is closed by a hydrophobic filter 44. The liquid drug is .1 introduced into drug compartment 24 ~ia an injection syringe .j piercing plug 40. Nipple 42 serves as a vent for purging .~ the air ~rom compartment 24 until the vent is closed by . 15 contact of the liquid drug with the hydrophobic filter 44 when the compartment is filled with the drug.
. Membrane 10 is made of a reslient~ deformable . material. The tubular elements 26 passing through membrane 10 are preferably made of a stiff, i.e., rigid or emi-rigid, plastic material ha~ing an inner diameter of less than 1.0 mm, and projecting at least 0.1 mm from *he . : outer face of membrane 10. As examples, these tubular elements 26 may be ~ade of Teflon (Reg. TM), or of a - polycarbona~e resin,:have an outer diameter of 1.0 mm, an inner diameter of ~.S mm, and projecting about 0.3 mm from the surface of the drug deli~ery membrane 10 in contact with .~ the subject's s~in. Preferably, they are in the form of hollow metal needles, such as of steel or aluminum coated on heir outer suraces with a c~ating of insulation, e.g., by ~ 30 oxidation, ~hemical deposition, etc.
t~ A drug delivery device would usually include at least SQ of such tubular elements, with the outlet ends 26b of each such ele~ent fi~mly engaging the subject's s~in so . as to effectively seal their inner channels to the subject's skin. These tubular elements thus deliver the drug from compartment 24 directly to a multitude of spaced discrete ~reas on the subject's skin, and at a rate determined by the ~,jQ gt IF~TIT~ ITE ~ HEET
W093/177~ PCT/EP93/005~?~
,:~ 213179~S
~ pressure applied to the drug chamber 24 by the displacement i:~ of membrane 12.
As one example, memb~anes 10, 12 and 20 may be of a silicone rubber. Electrically-conductive layer 38 ap~lied S to membrane 12, and/or eléctrode 36 applied to the subject's skin, may also be of a silicone rubber, but with an electrically-conductiye ~iller such as silver, carbon or aluminum particles.
The device illustrated in Figs. 1-3 may be applied 10 to the arm or leg of the subject to recei~e the drug by the use of the bands 3 such that the inner face of the device, trated in Fig. 2, firmly engages the subject's skin.
When the de~ice is so applied, the outer ends 26b of the st~f tubular elements 26 passing through the drug-delivery '~ 15 membrane 10 project slightly ~rom the mem~rane and firmly ~, engage the su~ject's skin.
Battery 32 supplies electrical current via an electrical switch or other control circuitry (not shown) to both the electsolytio cell electrodes 30a, 30b and to the iontophoresis electrodes 36, 38.
The electrolytic cell 30 generates a gas in accordance with the magnitude of the electrical current applied to its electrolyte 30c. This gas increases the pressure within chamber 28 to displace membrane 12 towards 25 membrane 10, thereby increasing the pressure within the drug chamber 24. Me~rane ~0, ha~ing one side exposed to the pressure within chamber~28 and the other si~e exposed to the osphere, tends to regulate the pressure within cha~ber 28.
The displacement of membrane 12 towards the drug delivery membrane 10 forces the liquid drug from compartment 24 through the tubular elements 26 in accordance with the . pres~re in ch ~ er 24. The pressure in chamber 24 also tends to displzce membrane 10 outwardly, thereby mo~e firmly 35 pressing the outlet ends 26b of the tubular elements 26 into contact with the subject's skin. It will thus be seen that the rate of feeding of the drug from chamber 24 ~ia tubular :
~:~ IR~:TITI ITF ~lEET
` ~ 21317~4 ~WO93/177~ - PCT/EP93/00~62 ~ _ 7 -.~J elements 26 to the subject's skin will be controlled by the.
rate of generation of gas by the electrQlytic cell 30.
The transfer of the dxug from compartment 24 to the subject's skin is electrically-induced by the voltage ,i 5 applied between the two iontophoresis electrodes 36 and 38.
Electrode 36 directly contacts the subject's skin, and electrode 38 directly contacts the drug within compartment 24 delivered to the subject's skin via the tubular elements 26.
. 10 It will thus be seen that the delivery of the drug ~ from compartment 24 to the subject's skin is effected in a !,j manner which is both efficient and controllable by .. controlling the electrical current supplied to the electrolyic cell 30 and also the voltage applied between the tw~ iontophoresis electrodes 36, 38.
f Fig. 4 illustrates another device which is `J~.,h generally similar to that of Fig. 3 but includes a nu~ber of changes. To faciiita~e understanding, the elements in the - device of Fig. 4 which are generally s~milar to those in , : 20 Fig. 3 are correspondingly numbered.
',!" One important difference in the de~ice of Fig. 4 :;1 over that of ~i~. 3 is that ~he housing 4 is a two-section ~l housing (rather than a three-section housing), including the A two sections 4 and 4b threadedly secured ~ogether. The ~ 25 injection port 40 for introducing the drug into the drug ~ '3 reser~oir in compartment 24 is located within an ope~ing in housing section 4a.
: Another difference in the construction of the device of Fig. 4 over that of Fig. 3 is that the drug 30 deli~ery body for delivering the drug from the drug compartmen~ ~4 is constituted, not by a displaceable ,i ~ membrane 10, but rather by the rigid wall S0 of housing section 4a, which rigid wall carries the stiff tubular elements 26 communicating with the drug compartment 24.
3_ Thus, the de~ice of Fig. 4 does not include a membrane ,.~ corresponding to membrane 10 in Fig. 3.
~, ;.
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~ WO93/17754 PCT/EP93/0056~.~
~ 213~ 8 -~
.~ The device of Fig. 4, however, does include membranes 12 and 20 defining between them the compartment for the electrolytic cell 30 and battery 32. The latter ~ elements, instead of being received within a socket formed s~ 5 in membrane 12, are rathex received within a socket formed in a rigid holder 52 secured between the two housing sections 4a and 4b. $he electrolytic cell 3~ communicates with chamber 28 between the two membranes ~2 and 20, such that the pressure produced in chamber 28 by the gas generated from the electrolytic cell 30, deforms membrane 12 to control the rate of delivery of the drug ~ia the stiff tubular elements 26.
Membrane 20, in the construction of Fig. 4, is secured between housing section 4b and the rigid holder 50 and carries electrical contact 34c on its inner face engageable with electrical contacts 34a and 34b connecting battery 32 to the electrolytic cell 30 to regulate the pressure of the gas within chzmber 28. Thus, if an excessi~e pressure is developed within chamber 28, this will displace the center of membrane 20 outwardly, to cause its ~: contact 34c to disengage from contacts 34a and 34b, thereby de-energizing the elect~olytic cell 30 until the excessive pressure within chamber ~8 drops to the point where contact 34c again engages contacts 34b and 34a to restart the : 25 generation of the gas from the electrolytic cell.
A still further difference in the construction of .~ Fig. 4 over that of Fig. 3 is that in Fig. 4 the iontophoresis electrodes 36 and 38 are omitted. Thus, in the construction of Fig. 4, the deli~ery of the drug from ~: 30 compartme~t 24 ~ia the stiff tubular elements 26 i5 ~,: controlled by the rate of generation of gas by electrolytic ~ cell 30. In substantially all other respects, the device of ;, Fig. 4 is constructed, and operates, in substantially the same manner as described above with respect to Fig~ 3.
Fig. S illustrates another device similar ta that ~i of Fi~s. 3 and 4 but further simplified in construction. To facilitate understanding, those parts which are ~enerally SUBST~TUTE ~:HEEr ~ . WO93/17754 21 31 7 9 4 PCT/EP93/00562 g -- _ .
similar to those in Figs. 3 and 4 are correspondingly numbered.
Thus, the de~ice in Fig. 5 also includes a two-: section housing 4a, 4b, as in Fig. 4, with the stiff tubular elements 28 ~arried by the rigid end wall 50 of housingsection 4a. In Fig. 5, however, the drug reservoir compartment 24 is defined by a displaceable membrane 62, generally sim~lar to membrane 20 in Figs. 3 and 4, secured . between the two housing sections 4a, 4b, and a partition wall 60 within the housing and formed with a metering or~fice 64 for metering the flow of the drug from compartment 24 to the stiff tubular e7ements 28. Partition 60 is formed wîth an annular rib 66, or other rib formation, in order to space it from the ends of the stiff tubular elements 28 and to permit the drug to flow thereto from the reservo~r in co~partment 24 via the metering orifice 64.
Thus, in the construction illustrated in Fig. 5, the control of the rate of delivery of the drug via the stiff tubular elements 28 is effected by the metering orifice 64 of partition 60. Therefore, whenever it is desired to change the drug deli~ery rate, a partition 60 with the appropriate-size metering orifice 64 would be inserted into the housing 4.
Fig. 6 illustrates another construction, similar to that of Fig. 5, but even further si~plified. trhose elements in Fig. 6 which generally correspond to those in Fig. 5 are correspo~dingly numbered to facilitate understarlding .
In the construction illustrated in Fig. 6, the partition 60, including its metering orifice 64, is omitte~, and instead the rate of delivery of the drug is controlled by the pressure withi~ the drug reservoir chamber 24. The drug is introduced into cha~ber 24, at the appropriate ` pressure, via iniection port 40, and membrane 62 is 3s displaced outwardly so as to apply a continuous pressure tending to ur~e the drug to flow from chamber 24 through the stiff tubular elements 28. If the pressure within chamber ' SUBSTITUTE SHEET
s .~. WO93/177~ PCT/EP93/00562>
2 13 17 9 ~ - 10 -24 drops below tha~ needed for deli~ering the drug at the .
desired rate, an additional quantity of the drug may be troduced into compart~ent 24 via injection port 40.
The outer tips of the stiff tubu~ar elements; -! 5 therein ~esignated t26, may be cut at a bias, or ~ade ~'''''"'!' conical, to pierce the layer of dead cells on the skin and thereby to enhance the penetration of the drug. Figs. 7a-7e illustrate various configurations of tip constructio~s.
Thus, Fig. 7a illustrates a tip construction 126a of conical 10 configurat~on; Fig. 7b illustrates the tip 126b ha~ing an rdly-tapered cut; Fig. 7c illustrates the tip 126c as cut at a ~ias; Fig. 7d illustrates the tip of a flat figuration (similar to that illustrated in Figs. 3-6);
and Fig. 7e illustrates the tip 126e as being of frusto-lS conical configuration.
Whe~e technical features mentioned in any claim are followed by ference signs, those reference signs have been incluted for the sole purpose of increzsing the intellisibility of the claims and acc~rdingly~ such re;ereoce signs do not have any ~imiting efrect on the scope of e~ch elemen. identified by way of example , :~ by such reference~s~gns.
~ :
: : :
:
~ :
~ SUE~STITUTE SHEEr
desired rate, an additional quantity of the drug may be troduced into compart~ent 24 via injection port 40.
The outer tips of the stiff tubu~ar elements; -! 5 therein ~esignated t26, may be cut at a bias, or ~ade ~'''''"'!' conical, to pierce the layer of dead cells on the skin and thereby to enhance the penetration of the drug. Figs. 7a-7e illustrate various configurations of tip constructio~s.
Thus, Fig. 7a illustrates a tip construction 126a of conical 10 configurat~on; Fig. 7b illustrates the tip 126b ha~ing an rdly-tapered cut; Fig. 7c illustrates the tip 126c as cut at a ~ias; Fig. 7d illustrates the tip of a flat figuration (similar to that illustrated in Figs. 3-6);
and Fig. 7e illustrates the tip 126e as being of frusto-lS conical configuration.
Whe~e technical features mentioned in any claim are followed by ference signs, those reference signs have been incluted for the sole purpose of increzsing the intellisibility of the claims and acc~rdingly~ such re;ereoce signs do not have any ~imiting efrect on the scope of e~ch elemen. identified by way of example , :~ by such reference~s~gns.
~ :
: : :
:
~ :
~ SUE~STITUTE SHEEr
Claims (10)
1. A drug delivery device for delivering a liquid drug to a subject via the subject's skin, comprising:
a housing;
a liquid reservoir in said housing for a liquid drug to be delivered;
and a drug delivery body carried by said housing and having one side communicating with one side of the liquid reservoir, and the opposite side exposed to engage the skin of the subject to receive the drug;
characterized in that said drug delivery body includes a plurality of hollow, stiff tubular elements extending through the body, each having an inlet end communicating with said liquid reservoir, and an outlet end at said opposite side of the drug delivery body to conduct the liquid drug directly to said opposite side.
a housing;
a liquid reservoir in said housing for a liquid drug to be delivered;
and a drug delivery body carried by said housing and having one side communicating with one side of the liquid reservoir, and the opposite side exposed to engage the skin of the subject to receive the drug;
characterized in that said drug delivery body includes a plurality of hollow, stiff tubular elements extending through the body, each having an inlet end communicating with said liquid reservoir, and an outlet end at said opposite side of the drug delivery body to conduct the liquid drug directly to said opposite side.
2. The device according to Claim 1, further including control means for controlling the rate of delivery of the drug from said reservoir via said plurality of stiff tubular elements extending through the drug delivery body.
3. The device according to Claim 2, wherein said control means includes a displaceable membrane for controlling the pressure in said reservoir in order to control the rate of feed of the liquid from the reservoir via said tubular elements to the subject's skin.
4. The device according to Claim 3, wherein said drug delivery body is in the form of a second displaceable membrane through which said plurality of stiff tubular elements extend and displaceable by the pressure in said reservoir.
5. The device according to Claim 4, wherein said control means further includes an electrolytic cell capable of generating a gas to displace said first-mentioned membrane corresponding to the electrical current applied to the electrolytic cell.
6. The device according to Claim 2, wherein said control means includes a partition between the liquid reservoir and the drug delivery body and formed with a metering orifice for metering the flow of the drug from the reservoir to said drug delivery body.
7. The device according to Claim 1, wherein said housing further includes a first electrode exposed for contact with the skin of a subject, and a second electrode in contact with the liquid drug in said reservoir.
8. The device according to Claim 1, wherein said plurality of stiff tubular elements have inner diameters of less than 1 mm.
9. The device according to Claim 1, wherein said plurality of stiff tubular elements are hollow needles of metal coated externally with insulation.
10. The device according to Claim 1, wherein said drug delivery body includes at least 50 of said stiff tubular elements.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US85059592A | 1992-03-13 | 1992-03-13 | |
| US850,595 | 1992-03-13 | ||
| US07/981,652 US5279544A (en) | 1990-12-13 | 1992-11-25 | Transdermal or interdermal drug delivery devices |
| US981,652 | 1992-11-25 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2131794A1 true CA2131794A1 (en) | 1993-09-16 |
Family
ID=27126940
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002131794A Abandoned CA2131794A1 (en) | 1992-03-13 | 1993-03-11 | Drug delivery devices |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US5279544A (en) |
| EP (1) | EP0630276B1 (en) |
| JP (1) | JPH07508427A (en) |
| AT (1) | ATE156375T1 (en) |
| AU (1) | AU3632593A (en) |
| CA (1) | CA2131794A1 (en) |
| DE (1) | DE69312916T2 (en) |
| TW (1) | TW286286B (en) |
| WO (1) | WO1993017754A1 (en) |
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| CN114028718A (en) * | 2021-12-06 | 2022-02-11 | 湖南省万卓医疗器械有限公司 | Magnetic transmission composite treatment device based on data analysis |
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| CN114028718A (en) * | 2021-12-06 | 2022-02-11 | 湖南省万卓医疗器械有限公司 | Magnetic transmission composite treatment device based on data analysis |
| CN114028718B (en) * | 2021-12-06 | 2022-05-17 | 湖南省万卓医疗器械有限公司 | Magnetic transmission composite treatment device based on data analysis |
Also Published As
| Publication number | Publication date |
|---|---|
| EP0630276A1 (en) | 1994-12-28 |
| WO1993017754A1 (en) | 1993-09-16 |
| DE69312916T2 (en) | 1998-01-08 |
| AU3632593A (en) | 1993-10-05 |
| JPH07508427A (en) | 1995-09-21 |
| ATE156375T1 (en) | 1997-08-15 |
| EP0630276B1 (en) | 1997-08-06 |
| TW286286B (en) | 1996-09-21 |
| DE69312916D1 (en) | 1997-09-11 |
| US5279544A (en) | 1994-01-18 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |