CN105833395B

CN105833395B - Medicament delivery device

Info

Publication number: CN105833395B
Application number: CN201610178516.4A
Authority: CN
Inventors: R·桑德埃格; L·韦德林; C·宾厄姆; B·彼得森
Original assignee: Becton Dickinson and Co
Current assignee: Becton Dickinson and Co
Priority date: 2009-12-16
Filing date: 2009-12-16
Publication date: 2020-04-03
Anticipated expiration: 2029-12-16
Also published as: CN105833395A

Abstract

A medicament delivery device (100) comprising: a body (104, 116) having a reservoir (164, 176) disposed therein for containing a medicament; and an injection needle (152) for penetrating the skin of the patient, the needle (152) providing a path for the medicament between the reservoir (164, 176) and the patient. The apparatus (100) further comprises: a needle cover (114) for selectively covering the injection needle (152), an adhesive portion (264) for selectively attaching the device to a patient, a release liner (500) for selectively covering a patient side of the adhesive portion (264), and a connection means (112, 520, 512, 508, 524) for connecting the needle cover (114) with the release liner (500) such that removal of one of the needle cover (114) and the release liner (500) from the device (100) removes the other of the needle cover (114) and the release liner (500).

Description

Medicament delivery device

The divisional application is based on the chinese invention patent application No. 200980163434.0 (international application No. PCT/US2009/006573), the name "self-injection device", and the application date 2009, 12 month, 16 day.

Technical Field

The present invention generally relates to a substance delivery device having improved patient convenience, ease of use, and efficiency. The present invention also relates generally to a patch-like, self-contained substance infusion or self-injection device that can be used to deliver a variety of substances or drugs to a patient. More particularly, the present invention relates to patch-like infusion or self-injection devices having integral removal of a needle cover and an adhesive release liner.

Background

A large number of people (e.g., people suffering from conditions such as diabetes) use some form of infusion therapy, such as daily insulin infusion, to maintain tight control over their blood glucose levels. Currently, in the insulin infusion therapy example, there are two main modes of daily insulin therapy. The first mode includes a syringe and an insulin pen. These devices are simple to use and are relatively low cost, but they require a needle stick at each injection, typically three to four times per day. The second mode involves infusion pump therapy, which requires the purchase of expensive pumps for approximately three years. The high cost of the pump (approximately 8 to 10 times the daily cost of syringe therapy) and the limited lifetime are high barriers to such therapy. Insulin pumps also represent an older technology and are cumbersome to use. Furthermore, from a lifestyle perspective, it is inconvenient to couple the pump to tubing located on a delivery site on the abdomen of the patient (referred to as an "infusion set"), and the pump is heavy making carrying the pump a burden. However, from a patient perspective, the vast majority of patients who have used pumps prefer to have the pump remain in the rest of their lives. This is because infusion pumps, although more complex than syringes and pens, offer the advantages of continuous infusion of insulin, accurate dosing and programmable delivery schedules. This results in closer glycemic control and improved feeling of well-being.

Interest in better treatment is increasing, considering the observed increase in pump therapy and the increasing number of daily injections. In this and similar infusion examples, all that is needed to fully satisfy this increased interest is the following form of insulin delivery or infusion: it combines the best features of daily injection therapy (low cost and ease of use) with those of insulin pumps (continuous infusion and precise dosing) and also avoids the respective disadvantages.

Several attempts have been made to provide non-stationary or "wearable" drug infusion devices that are low cost and convenient to use. Some of these devices are intended to be partially or fully disposable. In theory, this type of device can provide many of the advantages of an infusion pump without the attendant cost and inconvenience. Unfortunately, however, many of these devices suffer from the following disadvantages: including patient discomfort (due to the gauge and/or length of the injection needle used), compatibility and interaction between the delivered substance and the materials used in the construction of the infusion device, and possible failure if not properly activated by the patient (e.g., a "wet" injection due to premature activation of the device). Difficulties in manufacturing and in controlling the depth of penetration of the needle have also been encountered, particularly when using short and/or fine gauge needles. The possibility of needle stick injuries to persons in contact with the devices used has also been a problem.

Accordingly, there is a need for an alternative to current infusion devices (e.g., infusion pumps for insulin) that further provides simplicity of manufacture and improved use for insulin and non-insulin applications.

Disclosure of Invention

It is an aspect of the present invention to provide a patch-like infusion or self-injection device that can be conveniently worn against the skin while providing for the infusion of a desired substance and providing minimal discomfort through the use of one or more microneedles. It is another aspect of the present invention to provide such an infusion or self-injection device wherein removal of the needle cover and adhesive release liner of such an infusion or self-injection device can be integrated into a single operation.

The foregoing and/or other aspects of the present invention are achieved by providing a medicament delivery device including: a body having a reservoir disposed therein for containing a medicament; and an injection needle for penetrating the skin of the patient, the needle providing a path for the medicament between the reservoir and the patient. The device further comprises: a needle cover for selectively covering the injection needle; an adhesive portion for selectively attaching the device to a patient; a release liner for selectively covering a patient side of the adhesive; and a connection means for connecting the needle cover with the release liner such that removal of one of the needle cover and the release liner from the device removes the other of the needle cover and the release liner from the device.

The foregoing and/or other aspects of the present invention are also achieved by providing a medicament delivery device including: an injection needle for penetrating the skin of a patient; an adhesive portion for selectively attaching the device to a patient; a release liner for selectively covering a patient side of the adhesive, the release liner having an opening therein; and a needle cover for selectively covering the injection needle. The needle cover includes: a needle-covering portion having a flange larger than the opening of the release liner; a middle portion positioned adjacent to the flange and smaller than the opening of the release liner; and a retaining portion positioned adjacent to the intermediate portion and having a portion larger than the opening of the release liner for retaining the release liner on the intermediate portion.

Additional and/or other aspects and advantages of the invention will be set forth in part in the description which follows and, in part, will be obvious from the description, or may be learned by practice of the invention.

Drawings

The foregoing and/or other aspects and advantages of embodiments of the present invention will be more readily understood from the following detailed description, taken with reference to the accompanying drawings, in which:

fig. 1 illustrates a perspective view of an embodiment of a patch-like infusion or self-injection device in a pre-activation state prior to activation;

FIG. 2 illustrates a partially exploded view of the infusion device of FIG. 1 in a pre-activated state;

FIG. 3 illustrates a partially exploded view of the infusion device of FIG. 1 in a pre-activated state with the activator button unscrewed to show more detail;

FIG. 4 illustrates a more fully exploded view of the infusion device of FIG. 1 in a pre-activated state;

FIG. 5 illustrates a cross-sectional view of the infusion device of FIG. 1 in a pre-activated state;

FIG. 6 illustrates a cross-sectional view of the infusion device of FIG. 1 in a pre-activated state with the activator button unscrewed;

FIG. 7 illustrates a partially exploded view of the infusion device of FIG. 1 during installation of the safety mechanism;

FIG. 8 illustrates a partially exploded view of the infusion device of FIG. 1 after activation;

FIG. 9 illustrates a more fully exploded view of the infusion device of FIG. 1 after activation;

FIG. 10 illustrates a cross-sectional view of the infusion device of FIG. 1 after activation;

fig. 11 illustrates a partially exploded view of the infusion device of fig. 1 after deployment of the safety mechanism;

fig. 12 illustrates a cross-sectional view of the infusion device of fig. 1 after deployment of the safety mechanism;

FIG. 13 illustrates a bottom surface of the safety mechanism;

FIG. 14 further illustrates the structure of the safety mechanism;

15A-15D illustrate an end-of-dose indicator and its operation in the infusion device of FIG. 1;

FIG. 16 illustrates an embodiment of an infusion device having an injection port;

FIG. 17 illustrates an embodiment of an adhesive pad and an adhesive release liner in the infusion device of FIG. 1;

FIG. 18 illustrates a needle-covering portion of a needle cover located in the infusion device of FIG. 1;

FIG. 19 illustrates an embodiment of a needle cover including the needle-covering portion of FIG. 18;

20A-20C illustrate an embodiment of a needle cover including the needle-covering portion of FIG. 18 in the infusion device of FIG. 1;

21A and 21B illustrate an embodiment of a needle cover including the needle-covering portion of FIG. 18 in the infusion device of FIG. 1;

22A-22D illustrate an embodiment of a needle cover located in the infusion device of FIG. 1;

23A and 23B illustrate an embodiment of a needle cover located in the infusion device of FIG. 1;

FIG. 24 illustrates an embodiment of a needle cover located in the infusion device of FIG. 1;

fig. 25A and 25B illustrate an embodiment of a needle cover located in the infusion device of fig. 1.

Detailed Description

Reference will now be made in detail to embodiments of the present invention, examples of which are illustrated in the accompanying drawings, wherein like reference numerals refer to the like elements throughout. The embodiments exemplify the present invention by referring to the drawings.

The embodiments of the invention described below can be used as a convenient, patch-like infusion or self-injection device 100 to deliver a predicted dose of a substance, such as a liquid drug or medicament, to a patient over a period of time or all at once. The device is preferably provided to the end user in a pre-filled state (i.e. the drug or medicament is already located in the reservoir of the device). Although the patch-like infusion or self-injection device 100 (shown, for example, in fig. 1) described herein can be employed by a patient and/or caregiver, for convenience, the user of the device is hereinafter referred to as a "patient". In addition, for convenience, terms such as "vertical" and "horizontal" and "top" and "bottom" are used to denote relative orientation with respect to the infusion device 100 disposed on a horizontal surface. However, it should be understood that the infusion device 100 is not limited to this orientation and that the infusion device 100 may be used in any orientation. Additionally, the alternative use of the terms "infusion device" and "self-injection device" to describe devices that practice the present invention is not intended to be limiting. Infusion devices without self-injection capability fall within the scope of the invention, as do self-injection devices that do not perform continuous infusion. For convenience, but not by way of limitation, the term "infusion device" is used in the following description.

The patch-like infusion device 100 of fig. 1 is self-contained and is attached to the skin surface of the patient by an adhesive disposed on the bottom surface of the infusion device 100 (as will be described in more detail below). Once properly positioned and activated by the patient, the pressure of the release spring acting on the flexible reservoir within the device can be used to empty the contents of the reservoir through one or more patient needles (e.g., microneedles) via the needle manifold. The substance located within the reservoir is then delivered through the skin of the patient by the microneedles which are driven into the skin. It should be understood that other embodiments are possible in which the spring is replaced by a different type of energy storage device, which may be mechanical, electronic and/or chemical in nature.

As will be appreciated by those skilled in the art, there are a variety of ways to construct and use the patch-like infusion device 100 disclosed herein. While reference will be made to the embodiments depicted in the drawings and the following description, the embodiments disclosed herein are not intended to be exhaustive of the various alternative designs and embodiments encompassed by the disclosed invention. In each disclosed embodiment, the device is referred to as an infusion device, but the device is also capable of injecting a substance at a rate much faster (large dose) than is typically achieved by typical infusion devices. For example, the contents can be delivered over a period as short as a few seconds or as long as a few days.

In the embodiment of the device shown in fig. 1-12, a push button design of a patch-like infusion device 100 is shown, wherein activation and actuation of the device is achieved in a single multi-function/step process. Fig. 1 illustrates an assembled embodiment of an infusion device 100 in a pre-activated state. Fig. 2-6 illustrate a partially exploded view and a cross-sectional view of the infusion device 100 in a pre-activated state, fig. 7 illustrates a partially exploded view of the infusion device 100 during installation of the safety mechanism, fig. 8-10 illustrate an exploded view and a cross-sectional view of the infusion device 100 after activation, and fig. 11 and 12 illustrate an exploded view and a cross-sectional view of the infusion device 100 after deployment of the safety mechanism. The infusion device 100 is configured to operate between a pre-activated state (e.g., as shown in fig. 1, 2, and 5), an activated or fired state (e.g., as shown in fig. 8-10), and a retracted or safe state (e.g., as shown in fig. 11 and 12).

As shown in fig. 1, an embodiment of the patch-like infusion device 100 includes a bottom housing 104, a safety mechanism 108, a flexible needle-covering portion 112 of a needle cover 114, a top housing 116, a reservoir subassembly 120, an end-of-dose indicator (EDI)124, and an activator button 128, the activator button 128 including a patient interface surface 132. In addition, as shown in fig. 2-6, the infusion device 100 also includes a rotor or activation ring 136, a pressurization spring 140, an arcuate metal plunger 144, and a drive spring 148.

The flexible needle-covering portion 112 provides patient and device safety by protecting at least one needle 152 (described in more detail below) and providing a sterile barrier. The needle-covering portion 112 protects the needle 152 during device manufacture, protects the patient prior to use, and provides a sterile barrier at any time prior to removal. According to one embodiment, the needle-covering portion 112 is attached to a needle manifold via a press fit, within which at least one needle 152 is disposed. Additionally, according to one embodiment, a needle opening 156 (described in more detail below) of the safety mechanism 108 is shaped to closely correspond to the circumference of the needle-covering portion 112.

For example, as shown in fig. 2, 3, 5, 6, 8, 10, and 12, the reservoir subassembly 120 includes a reservoir 160, a reservoir dome seal 164, a valve 168, at least one needle 152, and at least one channel 172 (see, e.g., fig. 8) disposed between the valve 168 and the needle 152 and creating a flow path therebetween. The reservoir 160 includes a dome 176. Additionally, the reservoir subassembly 120 includes a removable needle-covering portion 112 to selectively cover the at least one needle 152. According to one embodiment, the reservoir subassembly 120 further includes a reservoir arm seal 180, covering the channel 172. Preferably, the needle 152 includes a needle manifold and a plurality of microneedles 152.

For example, as shown in fig. 5, the reservoir dome seal (flexible membrane) 164 of the reservoir subassembly 120 is disposed between the plunger 144 and the dome 176. Reservoir contents (e.g., medicinal material) for the infusion device 100 are disposed in the space between the reservoir dome seal 164 and the dome 176. The combination of the reservoir dome seal 164, the dome 176, and the space therebetween defines the reservoir 160. The dome 176 is preferably transparent to enable viewing of the reservoir contents. The reservoir dome seal 164 can be made of a non-expandable material or a laminate material (e.g., a metal coating or other similar substance). For example, one possible flexible laminate film that can be used in the reservoir dome seal 164 includes a first polyethylene layer, a second chemical layer as known to those skilled in the art to provide an attachment mechanism for a third metal layer chosen based on barrier characteristics, and a fourth layer comprising polyester fibers and/or nylon. By using a metallized or metallized film in combination with a rigid portion (e.g., dome 176), the barrier properties of the reservoir 160 are improved, thereby increasing or improving the shelf life of the contents contained therein. For example, when the reservoir contents include insulin, the primary contact materials in the reservoir 160 include Linear Low Density Polyethylene (LLDPE), Low Density Polyethylene (LDPE), Cyclic Olefin Copolymer (COC), and teflon. As described in more detail below, the primary contact materials in the remaining flow path of the reservoir contents may also include COC and LLDPE, as well as thermoplastic elastomers (TPE), medical grade acrylic, stainless steel, and needle adhesives (e.g., UV cured adhesives). Such materials that remain in extended contact with the contents of the reservoir 160 preferably pass ISO 10-993 and other applicable biocompatibility tests.

The reservoir subassembly 120 is also preferably capable of being stored within a specified shelf life of the reservoir contents in an implementable controlled environment without adversely affecting the contents, and is capable of being applied under a variety of environmental conditions. In addition, the barrier provided by the components of the reservoir subassembly 120 does not allow for the transport of gas, liquid, and/or solid materials into or out of the contents at a rate greater than that permitted to meet the desired shelf life. In the embodiments shown above, the reservoir material is capable of being stored and operated at a temperature range of about 34 degrees fahrenheit to 120 degrees fahrenheit, and can have a shelf life of two or more years.

In addition to meeting stability requirements, the reservoir subassembly 120 can also ensure operation with success through any number of leak tests (e.g., holding a 30psi sample for 20 minutes without leaks). As described in more detail below, other fill, storage, and delivery benefits that result from the configuration of the reservoir include adaptability and reduced head space.

In one embodiment, the reservoir 160 is emptied prior to filling. By emptying the reservoir 160 prior to filling and having only a slight recess in the dome 176, excess waste and head space within the reservoir 160 can be minimized. Additionally, the shape of the reservoir can be configured to suit the type of activation mechanism used (e.g., pressurization spring 140 and plunger 144). In addition, the evacuated flexible reservoir 160 is used during filling to reduce any air or air bubbles located within the filled reservoir 160. The use of the flexible reservoir 160 is also particularly beneficial when the infusion device 100 is subjected to changes in external pressure or temperature, which can result in increased reservoir internal pressure. In this case, the flexible reservoir 160 expands and contracts with the reservoir contents, thereby preventing possible leakage due to the expansion and contraction forces.

Yet another feature of the reservoir 160 includes the ability to allow for automatic particle inspection at the time of filling or particle inspection by the patient at the time of use. One or more reservoir barriers (e.g., domes 176) can be molded from a clear plastic material that enables inspection of the contents of the reservoir. The clear plastic material is preferably a cyclic olefin copolymer characterized by high clarity and clarity, low extractables (low extractables), and biocompatibility with the substance contained in the reservoir 160. One suitable material is available from Zeon chemical company, louisiville, kentucky under the name "BD CCP resin" and is registered by the U.S. food and drug administration as DMF No. 16368. In such applications, the reservoir 160 includes minimal features that may impede inspection (i.e., allow rotation during inspection).

The channel arm 172 is provided in the form of at least one flexible arcuate arm extending from the valve 168 to the needle manifold or microneedles 152. The arcuate arm has a groove 174 (see, e.g., fig. 2) formed therein. To provide a fluid path between the valve 168 and the needle manifold or microneedles 152, the reservoir arm seal 180 covers the channel 174. The fluid path (disposed in the channel arm 172-e.g., shown in fig. 8) between the reservoir 160 and the microneedles 152 is constructed of a material similar to or the same as the material used for the reservoir 160 above. For example, the channel arm 172 may be constructed of the same material as the dome 160, while the reservoir arm seal 180 may be constructed of the same material as the reservoir dome seal 164. According to one embodiment, both channel arms 172 serve as a fluid path between the valve 168 and the needle manifold or microneedles 152. According to another embodiment, only one of the channel arms 172 serves as a fluid path, while the remaining channel arms 172 provide structural support. In such an embodiment, the channel 174 extends completely from the valve 168 to the needle manifold or microneedles 152 only in the channel arm 172 that will be used as the fluid path.

The channel arms 172 must be flexible enough to withstand the activation force. Comparing the position of the channel arm 172 in fig. 2 and 8, the channel arm 172 (covered by reservoir arm seal 180 in fig. 2, with reservoir arm seal 180 removed in fig. 8 for clarity) elastically deforms as the microneedles 152 are driven into the patient's skin (described in more detail below). During this deformation, the channel arms 172 must maintain the integrity of the fluid path between the valve 168 and the needle manifold or microneedles 152. In addition, the material used for channel arm 172 meets various biocompatibility and storage tests. For example, as shown in table 1 below, when the infusion set contents include insulin, the primary contact materials in the reservoir 160 include linear low density polyethylene, cyclic olefin copolymer, and teflon, and can also include clear, transparent plastic. The primary contact materials in the remaining flow paths (channels 62) between the reservoir 160 and the microneedles 152 of the needle manifold include COC and/or medical grade acrylic, LLDPE, TPE and stainless steel, and needle adhesives.

TABLE 1

More specifically, the microneedles 152 can be constructed of stainless steel, while the needle manifold can be constructed of polyethylene and/or medical grade acrylic. Such a material preferably passes the ISO 10-993 biocompatibility test when in extended contact with the contents of the reservoir.

A valve 168 disposed between the reservoir 160 and the passage 172 selectively permits and restricts fluid flow between the reservoir 160 and the passage 172. The valve 168 moves between a pre-activated position (shown, for example, in fig. 2, 3, and 6) and an activated position (shown, for example, in fig. 8-10). When in the activated position, the valve permits fluid flow between the reservoir 160 and the channel 172 and thereby fluid flow to the needle manifold and microneedles 152.

In use, the valve 168 will eventually be pushed into the activated position by movement of the activator button 128, as best illustrated by movement of the valve 168 between fig. 5 and 10. As shown in fig. 10, movement of the valve 168 advances the enlarged distal end of the valve 168, allowing the drug to flow from the reservoir 160 into the channel 172 and down the fluid path to the needle manifold.

The above-described embodiment includes at least one needle 152 or microneedle 152, but may include several (e.g., two) illustrated microneedles 152. Each microneedle 152 is preferably at least 31 gauge (gauge) or smaller, e.g., 34 gauge, and is anchored within a patient needle manifold that can be placed in fluid communication with the reservoir 160. The microneedles 152 can also have different lengths or gauges, or a combination of different lengths and gauges, when more than one is included in the infusion device 100, and can contain one or more ports along the length of the body, preferably disposed near the tips of the microneedles 152 or near the tip bevel (if any microneedle 152 has one).

According to one embodiment, the gauge of the microneedles 152 controls the delivery rate of the reservoir contents of the infusion device 100. The use of multiple 34 gauge needles 152 to deliver reservoir contents is practical when the infusion is performed over a longer period of time than is typically associated with an intermediate syringe injection (requiring a larger needle sheath or needle). In the disclosed embodiment, any microneedle 152 targeted at the intradermal or subcutaneous space can be used, but the illustrated embodiment includes an intradermal microneedle 152 having a length between 1mm and 7mm (e.g., 4 mm). The arrangement of microneedles 152 can be a linear or non-linear array, and can include any number of microneedles 152 as desired by a particular application.

As described above, the microneedles 152 are positioned in the needle manifold. In the needle manifold, each microneedle 152 is provided with at least one fluid communication pathway, or channel 172. The manifold may have only a single path for one or more microneedles 152, or may provide multiple fluid paths or channels that route the reservoir contents separately to each microneedle 152. These paths or channels may also include tortuous paths for the contents to travel, thereby affecting fluid pressure and delivery rate, and acting as flow restrictors. The path or channel within the needle manifold can be set to a range of widths, depths, and configurations depending on the application, with the channel width typically between 0.015 inches and 0.04 inches, preferably 0.02 inches, and configured to reduce dead space within the manifold.

According to one embodiment, the reservoir subassembly 120 has a pair of

apertures

184 and 188 to assist in positioning the reservoir subassembly 120 with respect to the bottom housing 104. First post 192 and second post 196 (described in more detail below) of bottom housing 104 are inserted through

respective apertures

184 and 188.

In an exploded view with the reservoir subassembly 120 removed, fig. 4, 7, and 9 illustrate that the bottom housing 104 includes a substantially cylindrical housing 200 with the pressurization spring 140 and the plunger 144 disposed in the cylindrical housing 200. According to one embodiment, the cylindrical housing 200 includes a plurality of recessed channels 204 to guide a corresponding plurality of legs 208 and feet 212 of the plunger 144 as the plunger moves within the housing 200. The legs 208 and feet 212 together form a plunger protrusion 214. For example, as shown in fig. 4, 7, and 9, the recessed channel 204 extends along only a portion of the path of the cylindrical housing 200 downward from the top of the cylindrical housing 200. An opening 216 is provided below the recessed channel 204, and the foot 212 of the plunger 144 can extend through the opening 216 to the outside of the cylindrical housing 200. The opening 216 is substantially L-shaped having a horizontal portion at the base of the cylindrical housing 200 and a vertical portion substantially aligned with the recessed channel 204.

When the infusion device 100 is in the pre-activated state, the pressurization spring 140 is compressed by the plunger 144 (e.g., as shown in fig. 4-6), and the feet 212 of the plunger 144 are disposed substantially in the horizontal portion of the opening 216. The force of the pressurization spring 140 biases the foot 212 of the plunger 144 against the top of the horizontal portion of the opening 216 (e.g., the ledge of the cylindrical housing 200). As described in more detail below, the pressurization spring 140 and the plunger 144 together form a pressurization system to pressurize the reservoir 160 when the infusion device 100 is activated.

As described in more detail below, the rotor 136 rotates about the base of the cylindrical housing 200 between a pre-activated position (e.g., illustrated in fig. 2-4) and an activated position (e.g., illustrated in fig. 8-10). As the rotor 136 is rotated from the pre-activated position to the activated position, at least one foot engaged with a surface 220 (shown, for example, in fig. 4) of the rotor 136 engages at least one of the feet 212 of the plunger 144 and rotates the plunger 144 such that the feet 212 are aligned with the vertical portions of the openings 216 and the recessed channel 204. At this point, the pressurization spring 140 moves the plunger 144 upward while the foot 212 is guided by the riser channel 204.

A pressurization spring 140 is included in the infusion device 100 to apply a substantially uniform force to the reservoir 160 to force the contents from the reservoir 160. The compression spring 140 serves to store energy which, in use, compresses the reservoir 160 at the moment of release. The pressurizing spring 140 is held in a compressed state by the engagement between the leg 212 of the plunger 144 and the cylindrical housing 200. This engagement prevents the pressurization spring 140 from applying stress to the membrane (described below) of the reservoir 160 or any remaining device components (other than the bottom housing 104 and the plunger 144) during storage. The plunger 144 is sufficiently rigid to resist spring tension and deformation, and should not fail under normal loads.

As described above, when the rotor 136 is rotated from the pre-activated position to the activated position, the rotor 136 engages at least one of the feet 212 of the plunger 144 and rotates the plunger 144 to align the feet 212 with the vertical portions of the opening 216 and the recessed channel 204. The compressed pressurization spring 140 then moves the plunger 144 upwardly and applies a force to the membrane of the reservoir 160 for this purpose. The pressurization spring 140 can be configured to preferably create a pressure within the reservoir 116 of from about 1psi to about 50psi, and more preferably from about 2psi to about 25psi, for intradermal delivery of the reservoir contents. For transdermal injection or infusion, a range of about 2psi to about 5psi may be sufficient.

According to one embodiment, the activator button 128 includes a patient interface surface 132, which the patient presses 132 to activate the infusion device 100. The activator button 128 also includes a hinge arm 224 and an activation arm 228 (e.g., both shown in fig. 3). The hinge arm 224 of the activator button 128 includes a cylindrical portion having an opening. Activation arm 228 includes a protrusion 230 (see, e.g., fig. 3). According to one embodiment, the projection 230 includes a bearing surface 232 and a locking surface 234 disposed adjacent a cantilevered end of the bearing surface 232. According to one embodiment, the protrusion 230 forms an acute angle with the main portion of the activation arm 228.

A first post 192 disposed on the bottom housing 104 extends upwardly from the bottom housing 104. According to one embodiment (e.g., as shown in fig. 4 and 7), the base of the first post 192 includes a pair of flat sides 236 and a pair of rounded sides 240. Additionally, for example, as shown in fig. 4 and 7, a second post 196 and first and second

drive spring bases

244 and 248 extend upwardly from the bottom housing 104. As will be described in greater detail below, the first and second

drive spring bases

244 and 248 anchor corresponding ends of the drive spring 148. A first drive spring base 244 is disposed adjacent the second post 196 with a space therebetween.

Fig. 3 and 6 illustrate the position of the activator button 128 relative to the bottom housing 104 for assembly of the activator button 128, according to one embodiment. In this position, the opening of the cylindrical portion of the hinge arm 224 enables the activator button 128 to slide horizontally (past the flat side 236) and engage the first post 192. The hinge arm 224 (and thus the activator button 128) can then rotate about the first post 192. As the activation arm 228 moves into the space between the second post 196 and the first drive spring base 244, at least one of the projection 230 and the activation arm 228 elastically deforms until the cantilevered end of the bearing surface 232 of the projection 230 passes the retaining surface 252 of the second post 196. The movement of the cantilevered end of the bearing surface 232 of the protrusion 230 past the retaining surface 252 of the second post 196 (see, e.g., fig. 4) and the engagement of the locking surface 234 of the protrusion 230 with the retaining surface 252 provides an audible click and tactile feedback that the activator button 128 is in the pre-activated position.

Referring back to fig. 2-4, and 7-9, the rotor 136 additionally includes an activation tab 256 and a drive spring retainer 260. When the patient depresses the activator button 128, the activation arm 228 of the activator button 128 engages the activation tab 256, thereby rotating the rotor 136 from the pre-activated position to the activated position.

The drive spring retainer 260 retains the drive spring 148 in the pre-activated position when the rotor 136 is in the pre-activated position. As previously discussed, the first and second

drive spring bases

244 and 248 anchor opposite ends of the drive spring 148. At about the midpoint of the drive spring 148, a substantially U-shaped projection is provided as shown, for example, in fig. 2 and 3 for engaging the drive spring retainer 260 of the rotor 136. Thus, when the rotor 136 is in the pre-activated position and the drive spring 148 is engaged with the drive spring retainer 260, the drive spring 148 is maintained in a stretched state. And when the drive spring retainer 260 releases the drive spring 148 (i.e., when the rotor is rotated from the pre-activated position to the activated position as illustrated, for example, in fig. 8-10), the drive spring 148 drives the microneedles 152 to extend outside of the infusion device 100 through the openings 300 in the bottom housing 104 (and through openings in the safety mechanism 108, described in more detail below).

Thus, as will be described in greater detail below, activation and stimulation of the infusion device 100 in a single multi-function/step process includes the activation of the activator button 128 by the patient, and the rotation of the rotor 136 due to the engagement between the activation arm 228 of the activator button 128 and the activation tab 256 of the rotor 136. As described above, rotation of the rotor 136 rotates the plunger 144 and releases the plunger 144 to pressurize fluid located within the reservoir 160. Additionally, rotation of the rotor 136 releases the drive spring 148 from the drive spring retainer 260, thereby driving the microneedles 152 to extend outside of the infusion device 100. The single multi-function/step process also includes movement of the valve 168 from the pre-activated position to the activated position as a result of the activation button 128 engaging and moving the valve 168 when the activation button 128 is depressed, thereby initiating fluid flow between the reservoir and the microneedles 152 via the channels 172.

As described above, the patch-like infusion device 100 also includes a safety mechanism 108. To prevent inadvertent or accidental needle sticks, to prevent intentional reuse of the device, and to shield exposed needles, a locking needle safety mechanism 108 is provided. The safety mechanism 108 is automatically activated immediately upon removal of the infusion device 100 from the patient's skin surface. According to one embodiment, described in more detail below, a flexible adhesive pad 264 is attached to a bottom portion of the bottom housing 104 and a bottom portion of the safety mechanism 108. Adhesive pad 264 contacts the patient's skin and holds infusion device 100 in place on the skin surface during use. For example, as shown in fig. 11 and 12, when the infusion device 100 is removed from the skin surface, the safety mechanism 108 extends to a position to shield the microneedles 152. When fully extended, the safety mechanism 108 locks into place and prevents accidental injury or exposure of the patient needle 152.

Generally, passive security systems are most desirable. This enables the device to be self-safeguarded in the event of accidental removal or in the event that the patient forgets to provide a safety step. Since one typical use of such an infusion device 100 is to provide a supply of human growth hormone that is typically supplied overnight, it can be desirable that the patient (e.g., a child) wearing the device can wear them virtually overnight, even though the intended delivery can be completed in less than 10 minutes. Without a passive system, the microneedles 152 can re-penetrate into the patient or caregiver if the infusion device 100 is dropped. Solutions are to limit activity during use or to include passive safety systems.

With respect to security systems, there are typically three options. The first option is to retract the needle 152 into the device. The second option is to shield the needle 152 to eliminate access, while the third option is to destroy the needle 152 to prevent needle stick injury. Other systems, such as active systems, utilize manual shielding and/or vandalism, or manually release the security feature using another button press or similar action. A detailed description of the passive safety embodiment of the present invention is provided below.

One safety embodiment of the present invention is a passive, fully enclosed pull-out design embodiment, such as safety mechanism 108. Fig. 5, 10, and 12 are perspective cross-sectional views of the infusion device 100 illustrating the safety mechanism 108 before activation, after activation, and after deployment of the safety mechanism 108, respectively.

When the infusion device 100 is removed from the skin, the flexible adhesive pad 264 (attached to the bottom surface of the bottom housing 104 and the bottom surface of the safety mechanism 108) will pull the safety mechanism 108 out and lock the safety mechanism 108 in place before the adhesive pad 264 releases the skin surface. In other words, the force required to remove the adhesive pad from the skin surface is greater than the force required to deploy the safety mechanism 108. According to one embodiment, for example, as shown in fig. 13, the safety mechanism 108 includes a flat surface portion 268 that contacts the patient's skin. The flat surface 268 is in the following positions: wherein a portion of the adhesive pad 264 (shown in phantom in fig. 13) is attached to the safety mechanism 108 such that when the infusion device 100 is removed from the skin by the patient, the adhesive pad 264 will act to deploy the safety mechanism 108 from the infusion device 100, thereby shielding the microneedles 152 that would otherwise be exposed when the infusion device 100 is removed from the patient. When the safety mechanism 108 is fully extended, the safety mechanism 108 locks into place and prevents accidental injury or exposure of the microneedles 152.

According to one embodiment, the adhesive pad 264 is provided in substantially two portions, one on a majority of the bottom surface of the bottom enclosure 104 and one on the bottom surface of the safety mechanism 108. When the infusion device 100 is removed, the two patches move independently and the safety mechanism 108 can rotate relative to the bottom housing 104. According to another embodiment, two portions are formed as a single piece of flexible adhesive pad 264, one portion disposed on a majority of the bottom surface of the bottom enclosure 104 and one portion disposed on the bottom surface of the safety mechanism 108.

According to one embodiment, the safety mechanism 108 is a metal stamping. According to another embodiment, the safety mechanism 108 is made of substantially the same material as the bottom housing 104. As shown in fig. 14, the safety mechanism 108 includes a front shield 272, a pair of insertion projections 276 disposed at a rear portion of the safety mechanism 108, a pair of pivot projections 280 disposed at upper rear ends of edge portions 284 of the safety mechanism 108, respectively, a guide post 288 extending upwardly from a substantially flat bottom inner surface of the safety mechanism 108, and a locking post 292 also extending upwardly from the bottom inner surface of the safety mechanism 108. The front shield 272 extends over the rim portion 284 to shield the patient from the microneedles 152 when the safety mechanism 108 is deployed. The guide post 288 includes a notch therein to engage a safety retention tab 296 (shown, for example, in fig. 7 and 9) of the rotor 136 when the rotor 136 is in the pre-activation position to prevent the safety mechanism 108 from deploying prior to activation of the infusion device 100.

Additionally, as described above, the safety mechanism 108 includes a needle opening 156. Prior to deployment of the safety mechanism 108, the needle opening 156 at least partially overlaps the opening 300 in the bottom housing 104 to provide space for movement of the microneedles 152. The locking posts 292 are respectively disposed adjacent the forward side edges of the needle openings 156. The bottom housing 104 includes a guide post opening 304 (shown, for example, in fig. 7 and 9), a pair of insertion boss openings 308 (one of which is shown, for example, in fig. 4) disposed adjacent to opposite side edges of the bottom housing 104, and a pair of pivot abutments 312 (shown, for example, in fig. 7 and 9) disposed on opposite sides of the bottom housing 104.

Referring again to fig. 14, the insertion projections 276 each include a connection portion 316 and an extension portion 320. According to one embodiment, the connection portion 316 extends from a bottom interior surface of the safety mechanism 108 toward the rear of the infusion device 100 at a non-perpendicular angle with respect to the bottom interior surface of the safety mechanism 108. The extensions 320 each extend substantially perpendicularly from the extension 320 toward a respective outer side of the safety mechanism 108. To assemble the safety mechanism 108 to the bottom housing 104, the safety mechanism 108 is held at an angle of approximately 45 ° with respect to the bottom housing 104 and the insertion protrusion 276 is inserted through the insertion protrusion opening 308. The safety mechanism 108 is then rotated to a position such that the guide post 288 is inserted through the guide post opening 304 and the bottom inner surface of the safety mechanism 108 is substantially parallel to and in contact with the bottom surface of the bottom housing 104.

Referring again to fig. 7 and 9, although these views illustrate the rotor 136 in the activated position, the exploded nature of fig. 7 and 9 facilitates illustrating this stage of assembly of the safety mechanism 108 to the bottom housing 104. However, it should be understood that the safety mechanism 108 should be assembled to the bottom housing prior to activation. As shown in fig. 4, after the safety mechanism 108 is rotated upward, the safety mechanism 108 moves rearward relative to the bottom housing 104 such that the pivot bosses 280 clear respective front edges of the pivot abutments 312 and are disposed above the pivot abutments 312, the locking posts 292 are disposed adjacent the side edges of the opening 300 of the bottom housing 104, and the safety retention tabs 296 of the rotor 136 engage the guide posts 288.

Returning to fig. 14, each of the locking posts 292 includes a cylindrical extension 324 extending substantially perpendicular from the flat bottom interior surface of the safety mechanism 108, and a wedge portion 328 disposed at an end of the cylindrical extension 324. As the height of the wedge portion 328 increases relative to the bottom inner surface of the safety mechanism 108, the width of the wedge portion 328 increases.

When the safety mechanism 108 is deployed and rotated downward relative to the bottom housing 104, the wedge portions 328 abut against corresponding side edges of the opening 180 of the bottom housing 104, causing the locking posts 192 to elastically deform toward each other. When the safety mechanism 108 is fully deployed, the protrusion 280 becomes seated in the pivot seat 312. In addition, the top edge of the wedge portion 328 passes the bottom edge of the opening 300 and the locking post 292 snaps back to its substantially undeformed state, providing an audible click and tactile feedback to indicate that the safety mechanism 108 is fully deployed and thus that the microneedles 152 are covered. Returning to fig. 11 and 12, once the safety mechanism 108 is fully deployed and the locking post 292 has tripped back to its substantially undeformed state, the top edge of the wedge portion 328 engages the bottom surface of the bottom housing 104 adjacent the opening 300, thereby preventing the safety mechanism 108 from rotating upward relative to the bottom housing 104 and exposing the microneedles 152. As described above, the front shield 272 shields the patient from the microneedles 152.

Thus, the safety mechanism 108 is a passive safety embodiment provided as a single piece and provides a good lock that will not break under human loads. With this passive safety mechanism, no additional force is applied to the skin during injection and the microneedles 152 are safely retained within the infusion device 100 after use.

After use of the infusion device 100, the patient can again check the device to ensure that the entire dose is delivered. In this regard, as shown in fig. 15A-15D, the infusion device 100 includes an end-of-dose indicator (EDI) 124. The EDI 124 includes a body 332 and first and

second arms

336 and 340 extending substantially horizontally relative to a top of the body 332.

EDI 124 also includes a spring arm 344 that curves upward from the top of the body 332. According to one embodiment, the spring arm 344 pushes against the bottom side of the reservoir subassembly 120, thereby resiliently biasing the EDI 124 toward the bottom housing 104 to ensure that the EDI 124 does not freely move out of the infusion device 100, for example, during shipping and handling of the infusion device 100.

Returning to fig. 4, the body 332 is disposed in the EDI channel 348 and moves substantially vertically therein. The EDI channel is adjacent one of the recessed channels 204 of the leg 208 and foot 212 of the pilot plunger 144. A first arm 336 extends across the top of the recessed channel 204.

Returning to fig. 15A, a vertical presser 352 extends upward from the end of the second arm 340. When the reservoir contents have been output, the vertical extrusion extends through the EDI opening 356 in the top housing 116 (see, e.g., fig. 15C) to signify that the end of dose has been reached. According to one embodiment, the EDI 124 is formed as a one-piece construction.

As shown in fig. 15B, when the plunger 144 travels upward in the cylindrical housing 200 due to the pressurization spring 140 after activation, one of the feet 212 of the plunger 144 contacts the first arm of the EDI 124. During reservoir content delivery, the feet 212 lift the EDI 124 upward, overcoming the bias of the spring arms 344 and causing the vertical extrusion 352 to gradually extend through the EDI opening 356. Referring back to fig. 10, a vertical extrusion 352 partially extends from the infusion device 100. Once the delivery of the reservoir contents is complete and the plunger has achieved its full stroke, the vertical extrusion 352 is fully extended as shown in fig. 15D. Thus, the EDI 124 employs linear movement of the plunger 144 to produce linear movement of the EDI 124, which linear movement of the EDI 124 can be seen on the outside of the infusion device 100, thereby expressing delivery of the reservoir contents.

Fig. 16 illustrates an embodiment of an infusion device 400 having an injection port 404. The injection port provides access to an empty or partially filled reservoir 408 so that the patient can inject a substance or combination of substances into the reservoir prior to activation. Alternatively, a drug manufacturer or pharmacist can employ the injection port 404 to fill the infusion device 400 with a substance or combination of substances prior to sale. In almost all other respects, the infusion device 400 is similar to the infusion device 100 described previously.

The operation of the infusion device 100 will now be described. The above-described embodiments of the present invention preferably include a push button (activator button 128) design in which the infusion device 100 can be positioned and attached to a skin surface and activated and/or activated by pressing the activator button 128. More specifically, in a first step, the patient removes the device from the sterile packaging (not shown) and removes the release liner of the adhesive pad 264 (discussed in more detail below). The patient also removes the needle cover 114 (also discussed in more detail below). When the infusion device 100 is removed from the packaging and prior to use (see, e.g., fig. 1, 2, 4, and 5), the infusion device 100 in the pre-activated state enables a patient to check the device and contents therein, including checking for missing or damaged parts, expiration dates, aerosolized or color-shifted medicaments, and so forth.

The next step is to position and apply the infusion device 100 to the skin surface of the patient. As with the drug patch, the patient firmly presses the infusion device 100 against the skin. One side of the adhesive pad 264 is attached to the bottom surface of the bottom housing 104 and the bottom surface of the safety mechanism 108, while the opposite side of the adhesive pad 264 secures the infusion device 100 to the patient's skin. In an alternative embodiment, the adhesive pad 264 may be replaced by an adhesive applied directly to the bottom surface of the bottom housing 104 and the bottom surface of the safety mechanism 108. Such an adhesive would be covered by a release liner prior to use of the infusion device 100. These bottom surfaces (of the bottom housing 104 and safety mechanism 108) can be flat, curved, or shaped in any suitable manner, and the adhesive pads 264 are secured to these bottom surfaces. As discussed in more detail below, according to one embodiment, a release liner (e.g., a film) is applied to the patient side of the adhesive pad 264 prior to shipping to protect the adhesive during shipping. As described above, prior to use, the patient peels the release liner, thereby exposing the adhesive pad 264 (or adhesive portion) for placement against the skin.

After removal of the release liner, the patient can place the infusion device 100 against the skin and press to ensure proper adhesion. As described above, once properly positioned, the device is activated by depressing the activator button 128. This activation step releases the plunger 144 and pressurization spring 140, thereby enabling the plunger 144 to be urged against the flexible membrane of the reservoir 160 (reservoir dome seal 164), thereby pressurizing the reservoir. This activation step also serves to release the drive spring 148 from the drive spring retainer 260 of the rotor 136, thereby driving the microneedles 152 to extend (through the openings 300 in the bottom housing 104 and the needle openings 156 of the safety mechanism 108) outside of the infusion device 100 and seat the microneedles 152 in the patient. In addition, the activation step opens the valve 168, thereby establishing a fluid communication path between the reservoir 160 and the microneedles 152 via the channels 172 (see, e.g., fig. 8-10). Significant benefits stem from the ability to accomplish each of these actions with a single button operation. Additionally, another significant benefit includes the use of a continuous fluid communication path that is entirely contained within the reservoir subassembly 120.

Once activated, the patient typically leaves the infusion device 100 in place or wears the device for a period of time (e.g., ten minutes to seventy-two hours) for complete delivery of the reservoir contents. The patient then removes and discards the device without having to damage the underlying skin or tissue. Upon intentional or accidental removal, one or more security features deploy to shield the exposed microneedles 152. More specifically, when the infusion device 100 is removed from the skin by the patient, the adhesive pad 264 deploys the safety mechanism 108 from the infusion device 100, thereby shielding the microneedles 152 that would otherwise be exposed when the infusion device 100 is removed from the patient. When the safety mechanism 108 is fully extended, the safety mechanism 108 locks into place and prevents accidental injury or exposure of the microneedles 152. However, the safety feature can be configured to not deploy if the activator button 128 has not been depressed and the microneedles 152 have not been extended, thereby preventing deployment of the safety mechanism prior to use. After use, the patient can again check the device to ensure that the entire dose is delivered. For example, the patient can view the interior of the reservoir through the transparent dome 176 and/or inspect the EDI 124.

The examples are suitable for administering to a patient, and especially a human patient, a variety of substances including drugs and pharmaceutical agents as used herein, pharmaceutical agents including substances having biological activity capable of being delivered across membranes and surfaces, and especially the skin, examples listed in more detail below include antibiotics, antivirals, analgesics, anesthetics, anorectics, antiasthmatics, antidepressants, antihistamines, anti-inflammatory agents, antineoplastics, vaccines (including DNA vaccines) and the like, other substances capable of being delivered intradermally or subcutaneously to a patient include human growth hormone, insulin, proteins, polypeptides and fragments thereof, proteins and polypeptides can be naturally occurring, synthetically or recombinantly produced, blocking agents which can be used in cell therapy, such as during intradermal infusion of dendritic cells, other substances capable of being delivered according to the methods of the invention can be selected from the group consisting of drugs, vaccines and vaccines used in the prevention, diagnosis, alleviation, treatment or cure of diseases, including α -1 antitrypsin, antiandrogenic drugs, anti-angiectasia, anti-inflammatory hormone, anti-nociceptin, anti-inflammatory hormone receptor, anti-inflammatory hormone, anti-inflammatory drugs, anti-rat-inflammatory drugs, anti-nociceptin, anti-inflammatory drugs, anti-nociceptin, anti-inflammatory drugs, anti-nociceptin, anti-inflammatory drugs, anti-nociceptin, anti-inflammatory drugs, anti-rat-nociceptin, anti-inflammatory drugs, anti-hormone-inflammatory drugs, anti-rat-inflammatory drugs, anti-rat-inflammatory drugs, anti-hormone-rat-inflammatory drugs, anti-nociceps, anti-inflammatory drugs, anti-hormone-inflammatory drugs, anti-rat-inflammatory drugs, anti-hormone-inflammatory drugs, anti-rat-inflammatory drugs, anti-hormone-rat-hormone-inflammatory drugs, anti-nociceptin, anti-nociceps, anti-inflammatory drugs, anti-rat-hormone-rat-hormone-inflammatory drugs, anti-rat-nociceptin, anti-rat-nociceps, anti-inflammatory drugs, anti-rat-hormone-rat-hormone-inflammatory drugs, anti-hormone-rat-hormone, anti-hormone, anti-hormone.

The vaccine formulations which can be delivered according to the systems and methods of the invention can be selected from the group consisting of antigens or antigenic components capable of abolishing an immune response to a human pathogen, derived from HIV-1 (e.g., tetanus antitoxin, nef, gp120 or gp160), human herpes virus (HSV) (e.g., gD or derivatives thereof, or immediate early proteins such as ICP27 derived from HSV1 or HSV 2), cytomegalovirus (CMV (especially human) (e.g., gB or derivatives thereof), rotaviruses (including active attenuated viruses), EB virus (e.g., gp350 or derivatives thereof), varicella zoster virus (VZV, e.g., gpIII, and 63) or from hepatitis viruses (e.g., hepatitis B virus (e.g., hepatitis B surface antigen IE or derivatives thereof), Hepatitis A Virus (HAV), hepatitis C virus, and hepatitis E virus), or from other viral pathogens such as hepatitis syncytial virus (respiratory syncytial virus) (RSV) E.g., F and G proteins or derivatives thereof), parainfluenza virus, measles virus, mumps virus, human papilloma virus (HPV, e.g., HPV6, HPV11, HPV16, HPV18), flavivirus (e.g., yellow fever virus, dengue virus, tick-borne encephalitis virus, japanese encephalitis virus), or influenza virus (whole or inactivated virus, split influenza virus (grown in egg cells or MDCK cells), or whole influenza virus particles or purified or recombinant proteins thereof (e.g., HA, NP, NA, or M proteins or combinations thereof)); or from bacterial pathogens, such as neisseria, including neisseria gonorrhoeae and neisseria meningitidis (e.g. capsular polysaccharides and conjugates thereof, transferrin binding proteins, lactoferrin binding proteins, pilcs, bacterial cell surface ligands); streptococcus pyogenes (e.g. M protein or fragments thereof, C5A protease, lipoteichoic acid), streptococcus agalactiae, streptococcus mutans; haemophilus ducreyi; moraxella, including Moraxella catarrhalis, also known as Branhamella catarrhalis (e.g., high and low molecular weight bacterial cell surface ligands and invasins); bordetella, including pertussis (e.g., pertactin, pertussis toxin or derivatives thereof, filamentous hemagglutinin, adenylate cyclase, pili), bordetella parapertussis, and bordetella bronchiseptica; mycobacterium species, including Mycobacterium tuberculosis (e.g., ESAT6, antigen 85A, 85B or 85C), Mycobacterium bovis, Mycobacterium leprae, Mycobacterium smegmatis, Mycobacterium paratuberculosis, Mycobacterium smegmatis; legionella, including legionella pneumophila; escherichia including escherichia coli (e.g., colonization factor, thermit or derivative thereof, heat stable toxin or derivative thereof), enterohemorrhagic escherichia coli, enteropathogenic escherichia coli (e.g., a congrotoxin or derivative thereof); vibrio species, including Vibrio cholerae (e.g., cholera toxin or a derivative thereof); shigella species, including shigella sojae, shigella dysenteriae, shigella flexneri; yersinia species, including yersinia enterocolitica (e.g., photoproteins), yersinia pestis, yersinia pseudotuberculosis; campylobacter, including campylobacter jejuni (e.g., toxins, bacterial cell surface ligands, and invasins) and campylobacter coli; salmonella including Salmonella typhi, Salmonella paratyphi A, Salmonella choleraesuis, and Salmonella enteritidis; listeria, including listeria monocytogenes; helicobacter species, including helicobacter pylori (e.g., urease, catalase, vacuolar toxin); pseudomonas, including pseudomonas aeruginosa; staphylococci, including staphylococcus aureus, staphylococcus epidermidis; enterococcus including enterococcus faecalis, enterococcus faecium; clostridia including tetanus (e.g., tetanus toxin and derivatives thereof), clostridium botulinum (e.g., botulinum toxin and derivatives thereof), clostridium difficile (e.g., clostridium toxin a or B and derivatives thereof); bacillus, including Bacillus anthracis (e.g., botulinum toxin and derivatives thereof); corynebacterium species, including diphtheria (e.g., diphtheria toxin and derivatives thereof); borrelia genus, including Borrelia burgdorferi (e.g., OspA, OspC, DbpA, DbpB), Borrelia afzelii (e.g., OspA, OspC, DbpA, DbpB), Borrelia andersoni (e.g., OspA, OspC, DbpA, DbpB), Borrelia hernalis; agents of the ehrlichia genus, including ehrlichia marmorata and human granulocytic ehrlichiosis; rickettsiae, including rickettsiae; chlamydia, including Chlamydia trachomatis (e.g., MOMP, heparin binding protein), Chlamydia pneumoniae (e.g., MOMP, heparin binding protein), Chlamydia psittaci; leptospira, including renal leptospira; treponema, including Treponema pallidum (e.g., rare outer membrane proteins), Treponema denticola, Treponema hyodysenteriae; or from parasites, such as plasmodium species, including plasmodium falciparum; toxoplasma, including Toxoplasma gondii (e.g., SAG2, SAG3, Tg 34); entamoeba, including entamoeba histolytica; babesia, including Babesia fruticosa; trypanosomes, including trypanosoma cruzi; giardia, including giardia lamblia; leishmania, including leishmania major; pneumocystis, including pneumocystis pneumoniae; trichomonas, including Trichomonas vaginalis; schistosomes, including Schistosoma mansoni; or from yeasts, such as candida species, including candida albicans; cryptococcus, including cryptococcus; as described in PCT patent application publication No. wo 02/083214 entitled "vaccine delivery system," the entire contents of which are incorporated herein by reference.

These also include other preferred specific antigens for tuberculosis, such as Tb Ral2, Tb H9, Tb Ra35, Tb38-1, Erd14, DPV, MT1, MSL, mTTC2, and hTCC 1. Proteins for tuberculosis also include fusion proteins and variants thereof, wherein at least two, preferably three polypeptides of tuberculosis are fused into a larger protein. Preferred fusions include Ra12-TbH9-Ra35, Erd14-DPV-MT1, DPV-MT1-MSL, Erdl4-DPV-MT1-MSL-mTCC2, Erd14-DPV-MT1-MSL, DPV-MT1-MSL-mTCC2, TbH9-DPV-MT 1. Most preferred antigens for chlamydia include, for example, high molecular weight proteins (HWMP), ORF3, and putative membrane proteins (Pmps). Preferred bacterial vaccines include antigens derived from Streptococcus species including Streptococcus pneumoniae (e.g.capsular polysaccharide antigens and conjugates thereof, PsaA, PspA, streptolysin, choline binding protein) and the protein antigens pneumolysin (Biochem Biophys Acta,1989,67, 1007; Rubins et al, microbiological Pathenogeni, 25,337-342 (biochemical and biophysical literature, 1989,67, 1007; Rubin et al, Microbial pathogenesis, p. 25, 337-342)), and mutant detoxified derivatives thereof. Other preferred bacterial vaccines include antigens derived from haemophilus including haemophilus influenzae type B ("Hib", e.g. PRP and conjugates thereof), non-haemophilus influenzae type (e.g. OMP26, high molecular weight bacterial cell surface ligands, P5, P6, protein D and L lipoprotein), and plastin derivative peptides or multiple copy variants or fusion proteins thereof. Derivatives of hepatitis B surface antigen are well known in the art and include PreS1, PreS2S antigen, and the like. In a preferred aspect, the vaccine formulation of the invention comprises an HIV-1 antigen, gp120, particularly when expressed in CHO cells. In further embodiments, the vaccine formulation of the invention comprises gD2t as defined above.

In addition to delivering the substances listed above, the infusion device 100 can also be used to withdraw substances from a patient or to monitor the level of a substance in a patient. Examples of substances that can be monitored or extracted include blood, interstitial fluid or plasma. The extracted substances may then be analyzed for analytes, glucose, drugs, etc.

As described above, according to one embodiment, the infusion device 100 includes a needle cover 114 and a release liner for the adhesive pad 264. The needle cover 114 and release liner are removed prior to use of the infusion device 100. Additionally, the needle cover 114 and release liner are discarded after removal from the infusion device 100. One solution is to combine the needle cover and release liner such that removal of the needle cover also removes the release liner. Another solution is to combine the needle cover and the release liner such that removal of the release liner also removes the needle cover. Optionally, the needle cover and release liner can also be discarded at the same time.

Fig. 17 illustrates an embodiment of the adhesive pad 264 and adhesive release liner 500 of the infusion device 100, while fig. 18 illustrates the needle-covering portion 112 of the needle cover 114. Additionally, fig. 19 illustrates an embodiment of a needle cover 114A (including a needle-covering portion 112) and a release liner 500. As shown in fig. 17, the adhesive pad 164 includes a needle cover opening 504 and the release liner 500 includes a liner opening 508. Fig. 18 illustrates that the needle-covering portion 112 includes an aperture 512 having an aperture opening 516, and a shoulder or flange 520. As previously described, according to one embodiment, the needle-covering portion 112 is attached to the needle manifold via a press fit. Although fig. 17 and 18 are not to the same scale, liner opening 508 is larger than aperture 512 and smaller than flange 520, and thus aperture 512 can be inserted through liner opening 508 such that flange 520 is in contact with release liner 500. In addition, the needle cover opening 504 is larger than the cross-section of the needle-covering portion 112, such that the entire needle-covering portion 112 can be inserted through the needle cover opening 504.

As shown in fig. 19, needle cover 114A includes needle-covering portion 112 and a retaining portion or pull tab portion 524. The pull tab portion 524 includes a pull tab arm 528 that can be inserted into the eyelet opening 516. Fig. 19 illustrates the pull tab portion 524 retaining the release liner 500 on the needle cover 114A once the pull tab arm 528 is inserted into the eyelet opening 516 after the eyelet 512 has been inserted through the liner opening 508. According to one embodiment, at least one of the eyelet 512 and the pull tab 524 is sufficiently flexible such that after insertion of the pull tab arm 528 within the eyelet opening 516, the pull tab 524 can be rotated approximately 90 ° from the position illustrated in fig. 19, for example, to reduce the outer dimension or profile of the infusion device 100 for packaging. Additionally, although the pull tab 524 is able to rotate forward or backward, rotation of the pull tab 524 toward the activator button 128 (similar to the embodiment illustrated in fig. 20B) more effectively reduces the outer profile of the infusion device 100.

To install the embodiment illustrated in fig. 19, the needle-covering portion 112 is inserted through the needle opening 156 and attached to the needle manifold via a press-fit such that the eyelet 512 extends outside of the infusion device 100. Subsequently, the adhesive pad 264 is attached to the bottom housing 104 and the safety mechanism 108 such that the needle cover opening 504 of the adhesive pad 264 substantially corresponds to the needle opening 156. Additionally, the release liner 500 is attached to the adhesive pad 264 such that the eyelet 512 is inserted through the liner opening 508 and the release liner 500 is in contact with the flange 520. It should be understood that the adhesive pad 264 and release liner 500 may be applied in a single operation. Next, the pull tab arm 528 is inserted through the eyelet opening 516, thereby securing the release liner 500 and combining the release liner 500 with the needle cover 114A.

To remove the release liner 500 and needle cover 114A, the patient grasps and pulls on the pull tab 524. Because the release liner 500 is held between the pull tab 524 and the flange 520, not only is the needle cover 114 removed from the needle manifold, but the release liner 500 is also removed from the adhesive pad 264 by this single action of the patient. In addition, because the release liner 500 remains between the pull tab 524 and the flange 520 after removal from the infusion set 100, the patient can easily discard the combined release liner 500 and needle cover 114A.

Similar to the embodiment of fig. 19, fig. 20A-20C illustrate an embodiment of a needle cover 114B. In this embodiment, as shown in fig. 20A, the pull tab portion 532 has a pull tab arm 536, the pull tab arm 536 being inserted into the eyelet opening 516 of the eyelet 512 after the adhesive pad 264 and release liner 500 are installed. However, in contrast to the embodiment of FIG. 19, the pull tab portion 532 is substantially flat. As shown in fig. 20B, this flat configuration provides a smaller profile than the embodiment of fig. 19, requiring a smaller envelope for the package. Additionally, during assembly, the configuration of the pull tab portion 532 as shown in fig. 20B may reduce side stresses to the needle cover 114B, which may be advantageous to ensure a seal between the needle-covering portion 112 and the needle manifold.

Additionally, according to one embodiment, the pull tab arm 536 includes a scale to help align the pull tab portion 532 in a first position substantially aligned with the needle-covering portion 112 and a second position substantially parallel to the bottom surface of the bottom housing 104. Fig. 20C illustrates the combined release liner 500 and needle cover 114B after removal from the infusion device 100 and ready for disposal.

Fig. 21A and 21B illustrate another embodiment of a needle cover 114C and release liner 560. The release liner 560 includes a pull tab 564. In addition, needle cover 114C includes a needle-covering portion 112 and a clip portion 568. The clip portion 568 includes a pair of cantilevered clip wings 572. Each of the clip wings 572 is elastically deformable and has an inclined surface such that when the clip portion 568 is inserted into the eyelet opening 516, the inclined surfaces engage the eyelet 512 and contact therebetween gradually deforms the clip wings 572. After the trailing edge of the angled face moves past the eyelet opening 516, the clip wings 572 return to their respective undeformed positions, thereby locking the clip portion 568 in the eyelet 512 and retaining the release liner 560 between the clip portion 568 and the flange 520.

To remove the combined release liner 560 and needle cover 114C, the patient grasps and pulls the pull tab 564 of the release liner 560. This single action removes the release liner 560 and needle cover 114C from the infusion set 100 as the release liner 560 is retained between the clip portion 568 and the flange 520. Fig. 21B illustrates the combined release liner 560 and needle cover 114C after removal from the infusion device 100 and ready for disposal.

In contrast to fig. 18, 19, 20A-20C, 21A and 21B, in each of the needle covers illustrated in fig. 22A-22D, 23A, 23B, 24, 25A and 25B, the needle covering portion and the pulling projection portion are integrally formed as a single structure. For example, fig. 22A-22D illustrate a needle cover 114D including a needle-covering portion 112D and a pull tab portion 580, the needle-covering portion 112D and the pull tab portion 580 being connected by a living hinge and thus integrally formed as a unitary structure. The living hinge can be provided as a thin flexible plastic portion that joins two more rigid plastic parts together, thereby enabling the more rigid portions to rotate relative to each other such that the living hinge is an axis of rotation. In other words, the thin plate (web) of the living hinge provides for rotation between the components connected by the living hinge. For example, as shown in fig. 22B and 22C, the living hinge enables the pull tab portion 580 to move between a first position (fig. 22B) substantially aligned with the needle-covering portion 112D and a second position (fig. 22C) approximately 90 ° from the first position. In the second position, the needle cover 114D provides a smaller profile and allows for a smaller envelope for the package. Additionally, due to the smaller profile and configuration in the second position, the needle cover 114D is less likely to receive accidental impacts during assembly, and thus side stresses to the needle cover 114D are reduced, which may facilitate sealing between the needle-covering portion 112D and the needle manifold.

As shown in fig. 22A, the pull tab portion 580 includes a pair of cantilevered pull tab wings 584. Each of the pulling convex wings 584 is elastically deformable and has an inclined surface such that, upon insertion of the pulling convex portion 580 into the liner opening 508, the inclined surface engages the release liner 500 and contact therebetween gradually deforms the pulling convex wings 584. After the trailing edge of the inclined surface moves past the liner opening 508, the pull tab 584 returns to substantially its respective undeformed position, thereby locking the release liner to the needle cover 114D and retaining the release liner 500 between the pull tab 584 and the flange 520D (see, e.g., fig. 22A and 22D).

To remove the combined release liner 500 and needle cover 114D, the patient rotates the pull tab portion 580 from the second position to the first position such that the pull tab portion 580 is substantially aligned with the needle-covering portion 112D. Subsequently, the patient grasps and pulls on the pull tab portion 580. This single action removes the release liner 500 and the needle cover 114D from the infusion set 100 as the release liner 500 is held between the pull tab 584 and the flange 520D. Fig. 22A illustrates the combined release liner 500 and needle cover 114D during removal from the infusion device 100. The combined release liner 500 and needle cover 114D is then ready to be discarded.

Fig. 23A and 23B illustrate yet another embodiment of a needle cover 114E that can be combined with a release liner 500. The needle cover 114E includes a needle covering portion 112E and a pull tab portion 588, the pull tab portion 588 including a pair of pull tab hooks 592. At least one of the release liner 500 and the pair of pull tab hooks 592 can be sufficiently elastically deformed such that the pull tab hooks 592 can be inserted through the liner opening 508. After such insertion, the release liner 500 is retained on the needle cover 114E between the flange 520E and the pull tab hooks 592.

As shown in fig. 23A, in addition to the flange 520E, the needle-covering portion 112E includes a post 596 extending therefrom, the post 596 having a post hook 600. Corresponding to the post 596, the pull tab 588 includes a slot 604. According to one embodiment, the needle cover 114E is integrally formed as a unitary structure, while the pull tab portion 588 is connected to the needle-covering portion 112E by a living hinge.

When the pull tab portion 588 is rotated from a first position (fig. 23A) substantially aligned with the major axis or longitudinal axis of the needle-covering portion 112E to a second position (fig. 23B) approximately 90 ° from the first position, the post hook 600 engages an edge of the slot 600 for maintaining or locking the pull tab portion 588 in the second position. When mounted on the infusion device 100, the pull tab portion 588 of the needle cover 114E configured in the second position provides a low profile and thereby allows for a small envelope for packaging the infusion device 100. Additionally, during assembly, the needle cover 114E configured in the second position may reduce side stresses to the needle cover 114E, which may be advantageous to ensure a seal between the needle-covering portion 112E and the needle manifold.

To remove the combined release liner 500 and needle cover 114E from the infusion set 100, the patient first applies sufficient force to disengage the edges of the slot 604 from the post hook 600 and rotate the pull tab portion 588 from the second position to the first position such that the pull tab portion 588 is substantially aligned with the needle-covering portion 112E. Subsequently, the patient grasps and pulls on the pull projection 588. This single action removes the release liner 500 and the needle cover 114E from the infusion set 100 because the release liner 500 is held between the pull tab hooks 592 and the flange 520E. The combined release liner 500 and needle cover 114E are then ready to be discarded.

Fig. 24 illustrates yet another embodiment of a needle cover 114F that can be combined with a release liner 500. The needle cover 114F includes a needle covering portion 112F and a pull tab portion 608, the pull tab portion 608 including a pair of pull tab hooks 612. At least one of the release liner 500 and the pair of pull tab hooks 612 can be sufficiently elastically deformed such that the pull tab hooks 612 can be inserted through the liner opening 508. After such insertion, the release liner 500 is retained on the needle cover 114F between the flange 520 and the pull tab hook 612.

According to one embodiment, the needle cover 114F is integrally formed as a unitary structure. As shown in fig. 24, the major axis or longitudinal axis of the pull tab portion 608 forms an angle of approximately 90 ° with respect to the major axis or longitudinal axis of the needle-covering portion 112F.

The needle cover 114F with the pull tab 608 provides a low profile when mounted on the infusion device 100 and thereby allows for a small envelope for packaging the infusion device 100. Additionally, the configuration of needle cover 114F may reduce side stresses to needle cover 114F during assembly, which may be advantageous to ensure a seal between needle-covering portion 112F and the needle manifold.

To remove the combined release liner 500 and needle cover 114F from the infusion set 100, the patient grasps and pulls on the pull tab 608. This single action removes the release liner 500 and the needle cover 114F from the infusion set 100 because the release liner 500 is held between the pull tab hook 612 and the flange 520F. The combined release liner 500 and needle cover 114F are then ready to be discarded.

Fig. 25A and 25B illustrate another embodiment of a needle cover 114G that can be combined with a release liner 500. As shown in fig. 25A and 25B, the needle cover 114G includes a needle covering portion 112G and a pull projection portion 616, and the pull projection portion 616 includes a pair of pull projection hooks 620. At least one of the release liner 500 and the pair of pull tab hooks 620 can be sufficiently elastically deformed such that the pull tab hooks 612 can be inserted through the liner opening 508. After such insertion, the release liner 500 is retained on the needle cover 114G between the flange 520G of the needle-covering portion 112G and the pull tab hook 620.

According to one embodiment, the needle cover 114G is integrally formed as a unitary structure and the pull tab portion 588 is connected to the needle-covering portion 112G by a living hinge, which is incorporated into a bi-stable hinge. A bistable hinge, which can be found on caps for shampoo or cosmetics bottles for example, remains stable in two positions. For example, two stable positions of the needle cover 114G are: a first position (fig. 25A) substantially aligned with the major or longitudinal axis of the needle-covering portion 112G and a second position (fig. 25B) approximately 90 ° from the first position. In the bi-stable hinge of needle cover 114G, a thin strip of material acts like a spring to bias pull tab 616 toward the first and second positions. For example, during rotation from the first position toward the second position, the bi-stable hinge will pull raised portion 616 toward the first position until a flipping point (tipping point) is reached, at which point the bi-stable hinge will pull raised portion 616 toward the second position.

When mounted on the infusion device 100, the pull tab portion 616 of the needle cover 114G configured in the second position provides a low profile and thereby allows for a small envelope for packaging the infusion device 100. Additionally, the configuration of needle cover 114G in the second position may reduce side stresses to needle cover 114G during assembly, which may be advantageous to ensure a seal between needle-covering portion 112G and the needle manifold.

To remove the combined release liner 500 and needle cover 114G from the infusion set 100, the patient first rotates the pull tab portion 616 from the second position to the first position such that the pull tab portion 616 is substantially aligned with the needle-covering portion 112G. Subsequently, the patient grasps and pulls on the pull tab portion 616. This single action removes the release liner 500 and needle cover 114G from the infusion set 100 because the release liner 600 is held between the pull tab hooks 620 and the flange 520G. The combined release liner 500 and needle cover 114G is then ready to be discarded.

According to one embodiment, needle cover 114 (e.g.,

needle cover

114D, 114E, 114F, or 114G) is injection molded as a single component, such as a thermoplastic elastomer (TPE). According to another embodiment, needle cover 114 (e.g.,

needle cover

114D, 114E, 114F, or 114G) is injection molded in a two-shot process. For example, the pull tab 580 of the needle cover 114D may be molded from polypropylene, while the needle-covering portion 112D of the needle cover 114D may be molded from TPE, and thus flexible or elastically deformable to accommodate a press fit with the needle manifold.

Additionally, according to one embodiment, when the needle cover 114 is installed on the infusion device 100 (e.g., press fit with the needle manifold), the needle cover 114 interlocks with the rotor 136 to prevent rotation of the rotor 136 prior to removal of the needle cover 114.

As described above, the needle cover 114 and release liner (e.g., 500) are removed prior to use of the infusion device 100. Thus, these removal actions can be integrated into a single action by employing the described embodiments, thereby increasing patient convenience, ease of use, and efficiency. In addition, by optionally maintaining a connection between the needle cover 114 and the release liner after removal from the infusion device 100, the embodiments can further increase patient convenience, ease of use, and efficiency by simplifying its disposal.

Although a few exemplary embodiments of this invention have been described in detail above, those skilled in the art will readily appreciate that many modifications are possible in the exemplary embodiments without materially departing from the novel teachings and advantages of this invention. Accordingly, all such modifications are intended to be included within the scope of the appended claims and their equivalents.

Claims

1. A medicament delivery device comprising:

a device body;

a reservoir for containing a medicament, the reservoir being disposed in the device body;

an injection needle for penetrating the skin of a patient, the injection needle being selectively movable from a first position within the device body to a second position in which at least a portion of the injection needle is disposed outside of the device body;

a pressurizing system that pressurizes the reservoir when the medicament delivery device is activated;

a needle cover that selectively covers at least a patient end of the injection needle and prevents activation of the medicament delivery device when covering the patient end of the injection needle;

an adhesive liner connected with the needle cover for removal therewith, wherein the adhesive liner and the needle cover are removed prior to use of the medicament delivery device; and

an activator button, wherein activation of the medicament delivery device pressurizes the reservoir, establishes fluid communication between the reservoir and the injection needle, and moves the injection needle from the first position to the second position;

wherein the needle cover comprises a needle-covering portion and a pull tab, and the pull tab is rotatable from a pull position substantially aligned with a longitudinal axis of the needle-covering portion to a packaging position approximately 90 ° from the pull position;

wherein the needle-covering portion includes a post extending therefrom, the post having a hook;

the pull tab has a slot therein through which the post passes when rotated between the pull position and the package position; and

the hook engages the pull tab to maintain the pull tab in the packaging position as the pull tab is rotated to the packaging position.

2. The medicament delivery device of claim 1, wherein the adhesive liner and the needle cover are directly connected.